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Wouter Wieling - One of the best experts on this subject based on the ideXlab platform.
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The pathophysiology of the Vasovagal Response
Heart Rhythm, 2017Co-Authors: David L. Jardine, Wouter Wieling, Michele Brignole, Richard Sutton, Jacques W.m. Lenders, Julian M. StewartAbstract:In part I of this study, we found that the classical studies on Vasovagal syncope, conducted in fit young subjects, overstated vasodilatation as the dominant hypotensive mechanism. Since 1980, blood pressure and cardiac output have been measured continuously using noninvasive methods during tilt, mainly in patients with recurrent syncope, including women and the elderly. This has allowed us to analyze in more detail the complex sequence of hemodynamic changes leading up to syncope in the laboratory. All tilt-sensitive patients appear to progress through 4 phases: (1) early stabilization, (2) circulatory instability, (3) terminal hypotension, and (4) recovery. The physiology responsible for each phase is discussed. Although the order of phases is consistent, the time spent in each phase may vary. In teenagers and young adults, progressive hypotension during phases 2 and 3 can be driven by vasodilatation or falling cardiac output. The fall in cardiac output is secondary to a progressive decrease in stroke volume because blood is pooled in the splanchnic veins. In adults a fall in cardiac output is the dominant hypotensive mechanism because systemic vascular resistance always remains above baseline levels.
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Cardiac output and vasodilation in the Vasovagal Response: An analysis of the classic papers
Heart Rhythm, 2015Co-Authors: Wouter Wieling, David L. Jardine, Frederik J. De Lange, Michele Brignole, Henning B. Nielsen, Julian M. Stewart, Richard SuttonAbstract:The simple faint is secondary to hypotension and bradycardia resulting in transient loss of consciousness. According to Ohm's law applied to the circulation, BP = SVR × CO, hypotension can result from a decrease in systemic vascular resistance (SVR), cardiac output (CO), or both. It is important to understand that when blood pressure (BP) is falling, SVR and CO do not change reciprocally as they do in the steady state. In 1932, Lewis, assuming that decreased SVR alone accounted for hypotension, defined "the Vasovagal Response" along pathophysiologic lines to denote the association of vasodilation with vagal-induced bradycardia in simple faint. Studies performed by Barcroft and Sharpey-Schafer between 1940 and 1950 used volume-based plethysmography to demonstrate major forearm vasodilation during extreme hypotension and concluded that the main mechanism for hypotension was vasodilation. Plethysmographic measurements were intermittent and not frequent enough to capture rapid changes in blood flow during progressive hypotension. However, later investigations by Weissler, Murray, and Stevens performed between 1950 and 1970 used invasive beat-to-beat BP measurements and more frequent measurements of CO using the Fick principle. They demonstrated that CO significantly fell before syncope, and little vasodilation occurred until very late in the Vasovagal reaction Thus, since the 1970s, decreasing cardiac output rather than vasodilation has been regarded as the principal mechanism for the hypotension of Vasovagal syncope.
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steep fall in cardiac output is main determinant of hypotension during drug free and nitroglycerine induced orthostatic Vasovagal syncope
Heart Rhythm, 2008Co-Authors: Bart Verheyden, Nynke Van Dijk, Berend E Westerhof, Tony Reybrouck, Andre Aubert, Wouter WielingAbstract:Background How much of the hypotension occurring during postural syncope is cardiac output-mediated and how much can be ascribed to a fall in systemic vascular resistance are unknown. The contribution of both determinants may be influenced by the use of vasoactive drugs. Objective The purpose of this study was to assess the determinants of hypotension during drug-free and nitroglycerine (NTG)-induced Vasovagal presyncope in routine tilt table testing. Methods In this retrospective study, a total of 56 patients (37 female; age 36 ± 19 years) with suspected Vasovagal syncope and a positive tilt test at two clinical centers were selected. In 29 patients, presyncope was provoked by 0.4 mg sublingual NTG, administered in the 60° head-up tilt position. In the other 27 patients, presyncope was provoked by passive tilt alone. Finger arterial pressure was monitored continuously, and left ventricular stroke volume was computed from pressure pulsations. Results After NTG administration, heart rate rose, and peak heart rate was similar in all patients. Use of NTG did not affect circulatory patterns precipitating a Vasovagal Response. On average in all patients, marked hypotension was mediated by an approximately 50% fall in cardiac output, whereas systemic vascular resistance was well maintained until presyncope. Conclusion Hypotension during routine tilt testing is cardiac output-mediated, and the mechanism appears independent of the use of 0.4 mg sublingual NTG. The study data challenge the conventional idea of systemic vasodilation as the overriding cause of hypotension during postural syncope.
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impact of age on the Vasovagal Response provoked by sublingual nitroglycerine in routine tilt testing
Clinical Science, 2007Co-Authors: Bart Verheyden, Andre Aubert, John M. Karemaker, Janneke Gisolf, Karel H. Wesseling, Frank Beckers, Wouter WielingAbstract:NTG (nitroglycerine) is used in routine tilt testing to elicit a Vasovagal Response. In the present study we hypothesized that with increasing age NTG triggers a more gradual BP (blood pressure) decline due to a diminished baroreflex-buffering capacity. The purpose of the present study was to examine the effect of NTG on baroreflex control of BP in patients with distinct age-related Vasovagal collapse patterns. The study groups consisted of 29 patients (16-71 years old, 17 females) with clinically suspected VVS (Vasovagal syncope) and a positive tilt test. Mean FAP (finger arterial pressure) was monitored continuously (Finapres). Left ventricular SV (stroke volume), CO (cardiac output) and SVR (systemic vascular resistance) were computed from the pressure pulsations (Modelflow). BRS (baroreflex sensitivity) was estimated in the time domain. In the first 3 min after NTG administration, BP was well-maintained in all patients. This implied an adequate arterial resistance Response to compensate for steeper reductions in SV and CO with increasing age. HR (heart rate) increased and the BRS decreased after NTG administration. The rate of mean FAP fall leading to presyncope was; inversely related to age (r = 0.51, P = 0.005). Accordingly, patients with a mean FAP fall > 1.44 mmHg/s (median) were generally younger compared with patients with a slower mean FAP-fall (30 +/- 10 years compared with 51 +/- 17 years; P = 0.001). The main determinant of the rate of BP fall on approach of presyncope was the rate of fall in HR (r = 0.75, P <0.001). It was concluded that, in older patients, sublingual NTG provokes a more gradual BP decline compared with younger patients. This gradual decline cannot be ascribed to failure of the baroreflex-buffering capacity with increasing age. Age-related differences in the laboratory presentation of a Vasovagal episode depend on the magnitude of the underlying bradycardic Response
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Impact of age on the Vasovagal Response provoked by sublingual nitroglycerine in routine tilt testing
Clinical Science, 2007Co-Authors: Bart Verheyden, John M. Karemaker, Janneke Gisolf, Karel H. Wesseling, Frank Beckers, Andre E Aubert, Wouter WielingAbstract:Nitroglycerine (NTG) is used in routine tilt testing to elicit a Vasovagal Response. We hypothesized that with increasing age NTG triggers a more gradual blood pressure decline due to a diminished baroreflex buffering capacity. The purpose was to examine the effect of NTG on baroreflex control of blood pressure in patients with distinct age-related Vasovagal collapse patterns. The study groups consisted of 29 patients (16-71 yrs, 17 females) with clinically suspected VVS and a positive tilt test. Mean finger arterial pressure (MAP) was monitored continuously (Finapres). Left ventricular stroke volume (SV), cardiac output (CO) and systemic vascular resistance (SVR) were computed from the pressure pulsations (Modelflow). Spontaneous baroreflex control of heart rate (BRS) was estimated in the time domain. In the first 3 minutes after NTG, blood pressure was well maintained in all patients. This implies an adequate arterial resistance Response to compensate for steeper reductions in SV and CO with increasing age. Heart rate (HR) increased and the BRS decreased after NTG. The rate of MAP-fall leading to presyncope was inversely related to age (r = 0.51, p = 0.005). Accordingly, patients with a MAP-fall > 1.44 mmHg/s (median) were generally younger compared to patients with a slower MAP-fall (30 ± 10 yrs vs. 51 ± 17 yrs; p = 0.001). The main determinant of the rate blood pressure drop on approach of presyncope was the rate of fall in HR (r = 0.75, p < 0.001). It is concluded that, in the older patients, sublingual NTG provokes a more gradual blood pressure decline compared to the younger. This gradual decline cannot be ascribed to failure of the baroreflex buffering capacity with increasing age. Age-related differences in the laboratory presentation of a Vasovagal episode depend on the magnitude of the underlying bradycardic Response.
Sergei B. Yakushin - One of the best experts on this subject based on the ideXlab platform.
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Vestibular Activation Habituates the Vasovagal Response in the Rat.
Frontiers in Neurology, 2017Co-Authors: Bernard Cohen, Giovanni Martinelli, Yongqing Xiang, Theodore Raphan, Sergei B. YakushinAbstract:Vasovagal syncope is a significant medical problem without effective therapy, postulated to be related to a collapse of baroreflex function. While some studies have shown that repeated static tilts can block Vasovagal syncope, this was not found in other studies. Using anesthetized, male Long-Evans rats that were highly susceptible to generation of Vasovagal Responses, we found that repeated activation of the vestibulosympathetic reflex with ±2 and ±3 mA, 0.025 Hz sinusoidal Galvanic Vestibular Stimulation (sGVS) caused incremental changes in blood pressure (BP) and heart rate (HR) that blocked further generation of Vasovagal Responses. Initially, BP and HR fell ≈20-50 mmHg and ≈20-50 beats/min (bpm) into a Vasovagal Response when stimulated with sGVS in susceptible rats. As the rats were continually stimulated, HR initially rose to counteract the fall in BP; then the increase in HR became more substantial and long lasting, effectively opposing the fall in BP. Finally, the vestibular stimuli simply caused an increase in BP, the normal sequence following activation of the VSR. Concurrently, habituation caused disappearance of the low frequency (0.025 and 0.05 Hz) oscillations in BP and HR that must be present when Vasovagal Responses are induced. Habituation also produced significant increases in baroreflex sensitivity (P
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vestibular activation habituates the Vasovagal Response in the rat
Frontiers in Neurology, 2017Co-Authors: Bernard Cohen, Giovanni Martinelli, Yongqing Xiang, Theodore Raphan, Sergei B. YakushinAbstract:Vasovagal syncope is a significant medical problem without effective therapy, postulated to be related to a collapse of baroreflex function. While some studies have shown that repeated static tilts can block Vasovagal syncope, this was not found in other studies. Using anesthetized, male Long-Evans rats that were highly susceptible to generation of Vasovagal Responses, we found that repeated activation of the vestibulosympathetic reflex with ±2 and ±3 mA, 0.025 Hz sinusoidal Galvanic Vestibular Stimulation (sGVS) caused incremental changes in blood pressure (BP) and heart rate (HR) that blocked further generation of Vasovagal Responses. Initially, BP and HR fell ≈20-50 mmHg and ≈20-50 beats/min (bpm) into a Vasovagal Response when stimulated with sGVS in susceptible rats. As the rats were continually stimulated, HR initially rose to counteract the fall in BP; then the increase in HR became more substantial and long lasting, effectively opposing the fall in BP. Finally, the vestibular stimuli simply caused an increase in BP, the normal sequence following activation of the VSR. Concurrently, habituation caused disappearance of the low frequency (0.025 and 0.05 Hz) oscillations in BP and HR that must be present when Vasovagal Responses are induced. Habituation also produced significant increases in baroreflex sensitivity (P<0.001). Thus, repeated low frequency activation of the VSR resulted in a reduction and loss of susceptibility to development of Vasovagal Responses in rats that were previously highly susceptible. We posit that reactivation of the baroreflex, which is depressed by anesthesia and the disappearance of low frequency oscillations in BP and HR are likely to be critically involved in producing resistance to the development of Vasovagal Responses. SGVS has been widely used to activate muscle sympathetic nerve activity in humans and is safe and well tolerated. Potentially, it could be used to produce similar habituation of Vasovagal syncope in humans.
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A model of blood pressure, heart rate, and vaso-vagal Responses produced by vestibulo-sympathetic activation
Frontiers Media S.A., 2016Co-Authors: Theodore Eraphan, Bernard Ecohen, Yongqing Exiang, Sergei B. YakushinAbstract:Blood Pressure (BP), comprised of recurrent systoles and diastoles, is controlled by central mechanisms to maintain blood flow. Periodic behavior of BP was modeled to study how peak amplitudes and frequencies of the systoles are modulated by vestibular activation. The model was implemented as a relaxation oscillator, driven by a central signal related to Desired BP. Relaxation oscillations were maintained by a second order system comprising two integrators and a threshold element in the feedback loop. The output signal related to BP was generated as a nonlinear function of the derivative of the first state variable, which is a summation of an input related to desired BP, feedback from the states, and an input from the vestibular system into one of one of the feedback loops. This nonlinear function was structured to best simulate the shapes of systoles and diastoles, the relationship between BP and Heart Rate (HR) as well as the amplitude modulations of BP and Pulse Pressure. Increases in threshold in one of the feedback loops produced lower frequencies of HR, but generated large pulse pressures to maintain orthostasis, without generating a Vasovagal Response (VVR). Pulse pressures were considerably smaller in the anesthetized rats than during the simulations, but simulated pulse pressures were lowered by including saturation in the feedback loop. Stochastic changes in Threshold maintained the compensatory Baroreflex Sensitivity. Sudden decreases in Desired BP elicited non-compensatory VVRs with smaller pulse pressures, consistent with experimental data. The model suggests that the Vestibular Sympathetic Reflex modulates BP and HR of an oscillating system by manipulating parameters of the baroreflex feedback and the signals that maintain the oscillations. It also shows that a VVR is generated when the vestibular input triggers a marked reduction in Desired BP
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The Vasovagal Response of the rat: its relation to the vestibulosympathetic reflex and to Mayer waves
The FASEB Journal, 2013Co-Authors: Bernard Cohen, Giovanni Martinelli, Yongqing Xiang, Theodore Raphan, Adam Schaffner, Sergei B. YakushinAbstract:Vasovagal Responses (VVRs) are characterized by transient drops in blood pressure (BP) and heart rate (HR) and increased amplitude of low-frequency oscillations in the Mayer wave frequency range. Typical VVRs were induced in anesthetized, male, Long-Evans rats by sinusoidal galvanic vestibular stimulation (sGVS). VVRs were also produced by single sinusoids that transiently increased BP and HR, by 70–90° nose-up tilts, and by 60° tilts of the gravitoinertial acceleration vector using translation while rotating (TWR). The average power of the BP signal in the Mayer wave range increased substantially when tilts were >70° (0.91 g), i.e., when linear accelerations in the x–z plane were ≥0.9–1.0 g. The standard deviations of the wavelet-filtered BP signals during tilt and TWR overlaid when they were normalized to 1 g. Thus, the amplitudes of the Mayer waves coded the magnitude of the linear acceleration ≥1 g acting on the head and body, and the average power in this frequency range was associated with the generation of VVRs. These data show that VVRs are a natural outcome of stimulation of the vestibulosympathetic reflex and are not a disease. The results also demonstrate the usefulness of the rat as a small animal model for studying human VVRs.—Cohen, B., Martinelli, G. P., Raphan, T., Schaffner, A., Xiang, Y., Holstein, G. R., Yakushin, S. B. The Vasovagal Response of the rat: its relation to the vestibulosympathetic reflex and to Mayer waves.
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Sinusoidal galvanic vestibular stimulation (sGVS) induces a Vasovagal Response in the rat
Experimental Brain Research, 2011Co-Authors: Bernard Cohen, Yongqing Xiang, Theodore Raphan, Giorgio P. Martinelli, Dmitri Ogorodnikov, Gay R. Holstein, Sergei B. YakushinAbstract:Blood pressure (BP) and heart rate (HR) were studied in isoflurane-anesthetized Long-Evans rats during sinusoidal galvanic vestibular stimulation (sGVS) and sinusoidal oscillation in pitch to characterize vestibular influences on autonomic control of BP and HR. sGVS was delivered binaurally via Ag/AgCl needle electrodes inserted over the mastoids at stimulus frequencies 0.008–0.4 Hz. Two processes affecting BP and HR were induced by sGVS: 1) a transient drop in BP (≈15–20 mmHg) and HR (≈3 beat*s^−1), followed by a slow recovery over 1–6 min; and 2) inhibitory modulations in BP (≈4.5 mmHg/g) and HR (≈0.15 beats*s^−1/g) twice in each stimulus cycle. The BP and HR modulations were approximately in-phase with each other and were best evoked by low stimulus frequencies. A wavelet analysis indicated significant energies in BP and HR at scales related to twice and four times the stimulus frequency bands. BP and HR were also modulated by oscillation in pitch at frequencies 0.025–0.5 Hz. Sensitivities at 0.025 Hz were ≈4.5 mmHg/g (BP) and ≈0.17 beat*s^−1/g (HR) for pitches of 20–90°. The tilt-induced BP and HR modulations were out-of-phase, but the frequencies at which Responses were elicited by tilt and sGVS were the same. The results show that the sGVS-induced Responses, which likely originate in the otolith organs, can exert a powerful inhibitory effect on both BP and HR at low frequencies. These Responses have a striking resemblance to human Vasovagal Responses. Thus, sGVS-activated rats can potentially serve as a useful experimental model of the Vasovagal Response in humans.
Bart Verheyden - One of the best experts on this subject based on the ideXlab platform.
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steep fall in cardiac output is main determinant of hypotension during drug free and nitroglycerine induced orthostatic Vasovagal syncope
Heart Rhythm, 2008Co-Authors: Bart Verheyden, Nynke Van Dijk, Berend E Westerhof, Tony Reybrouck, Andre Aubert, Wouter WielingAbstract:Background How much of the hypotension occurring during postural syncope is cardiac output-mediated and how much can be ascribed to a fall in systemic vascular resistance are unknown. The contribution of both determinants may be influenced by the use of vasoactive drugs. Objective The purpose of this study was to assess the determinants of hypotension during drug-free and nitroglycerine (NTG)-induced Vasovagal presyncope in routine tilt table testing. Methods In this retrospective study, a total of 56 patients (37 female; age 36 ± 19 years) with suspected Vasovagal syncope and a positive tilt test at two clinical centers were selected. In 29 patients, presyncope was provoked by 0.4 mg sublingual NTG, administered in the 60° head-up tilt position. In the other 27 patients, presyncope was provoked by passive tilt alone. Finger arterial pressure was monitored continuously, and left ventricular stroke volume was computed from pressure pulsations. Results After NTG administration, heart rate rose, and peak heart rate was similar in all patients. Use of NTG did not affect circulatory patterns precipitating a Vasovagal Response. On average in all patients, marked hypotension was mediated by an approximately 50% fall in cardiac output, whereas systemic vascular resistance was well maintained until presyncope. Conclusion Hypotension during routine tilt testing is cardiac output-mediated, and the mechanism appears independent of the use of 0.4 mg sublingual NTG. The study data challenge the conventional idea of systemic vasodilation as the overriding cause of hypotension during postural syncope.
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impact of age on the Vasovagal Response provoked by sublingual nitroglycerine in routine tilt testing
Clinical Science, 2007Co-Authors: Bart Verheyden, Andre Aubert, John M. Karemaker, Janneke Gisolf, Karel H. Wesseling, Frank Beckers, Wouter WielingAbstract:NTG (nitroglycerine) is used in routine tilt testing to elicit a Vasovagal Response. In the present study we hypothesized that with increasing age NTG triggers a more gradual BP (blood pressure) decline due to a diminished baroreflex-buffering capacity. The purpose of the present study was to examine the effect of NTG on baroreflex control of BP in patients with distinct age-related Vasovagal collapse patterns. The study groups consisted of 29 patients (16-71 years old, 17 females) with clinically suspected VVS (Vasovagal syncope) and a positive tilt test. Mean FAP (finger arterial pressure) was monitored continuously (Finapres). Left ventricular SV (stroke volume), CO (cardiac output) and SVR (systemic vascular resistance) were computed from the pressure pulsations (Modelflow). BRS (baroreflex sensitivity) was estimated in the time domain. In the first 3 min after NTG administration, BP was well-maintained in all patients. This implied an adequate arterial resistance Response to compensate for steeper reductions in SV and CO with increasing age. HR (heart rate) increased and the BRS decreased after NTG administration. The rate of mean FAP fall leading to presyncope was; inversely related to age (r = 0.51, P = 0.005). Accordingly, patients with a mean FAP fall > 1.44 mmHg/s (median) were generally younger compared with patients with a slower mean FAP-fall (30 +/- 10 years compared with 51 +/- 17 years; P = 0.001). The main determinant of the rate of BP fall on approach of presyncope was the rate of fall in HR (r = 0.75, P <0.001). It was concluded that, in older patients, sublingual NTG provokes a more gradual BP decline compared with younger patients. This gradual decline cannot be ascribed to failure of the baroreflex-buffering capacity with increasing age. Age-related differences in the laboratory presentation of a Vasovagal episode depend on the magnitude of the underlying bradycardic Response
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Impact of age on the Vasovagal Response provoked by sublingual nitroglycerine in routine tilt testing
Clinical Science, 2007Co-Authors: Bart Verheyden, John M. Karemaker, Janneke Gisolf, Karel H. Wesseling, Frank Beckers, Andre E Aubert, Wouter WielingAbstract:Nitroglycerine (NTG) is used in routine tilt testing to elicit a Vasovagal Response. We hypothesized that with increasing age NTG triggers a more gradual blood pressure decline due to a diminished baroreflex buffering capacity. The purpose was to examine the effect of NTG on baroreflex control of blood pressure in patients with distinct age-related Vasovagal collapse patterns. The study groups consisted of 29 patients (16-71 yrs, 17 females) with clinically suspected VVS and a positive tilt test. Mean finger arterial pressure (MAP) was monitored continuously (Finapres). Left ventricular stroke volume (SV), cardiac output (CO) and systemic vascular resistance (SVR) were computed from the pressure pulsations (Modelflow). Spontaneous baroreflex control of heart rate (BRS) was estimated in the time domain. In the first 3 minutes after NTG, blood pressure was well maintained in all patients. This implies an adequate arterial resistance Response to compensate for steeper reductions in SV and CO with increasing age. Heart rate (HR) increased and the BRS decreased after NTG. The rate of MAP-fall leading to presyncope was inversely related to age (r = 0.51, p = 0.005). Accordingly, patients with a MAP-fall > 1.44 mmHg/s (median) were generally younger compared to patients with a slower MAP-fall (30 ± 10 yrs vs. 51 ± 17 yrs; p = 0.001). The main determinant of the rate blood pressure drop on approach of presyncope was the rate of fall in HR (r = 0.75, p < 0.001). It is concluded that, in the older patients, sublingual NTG provokes a more gradual blood pressure decline compared to the younger. This gradual decline cannot be ascribed to failure of the baroreflex buffering capacity with increasing age. Age-related differences in the laboratory presentation of a Vasovagal episode depend on the magnitude of the underlying bradycardic Response.
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Impact of age on the Vasovagal Response provoked by sublingual nitroglycerine in routine tilt testing
Clinical Science, 2007Co-Authors: Bart Verheyden, Andre Aubert, John M. Karemaker, Janneke Gisolf, Karel H. Wesseling, Frank Beckers, Wouter WielingAbstract:NTG (nitroglycerine) is used in routine tilt testing to elicit a Vasovagal Response. In the present study we hypothesized that with increasing age NTG triggers a more gradual BP (blood pressure) decline due to a diminished baroreflex-buffering capacity. The purpose of the present study was to examine the effect of NTG on baroreflex control of BP in patients with distinct age-related Vasovagal collapse patterns. The study groups consisted of 29 patients (16-71 years old, 17 females) with clinically suspected VVS (Vasovagal syncope) and a positive tilt test. Mean FAP (finger arterial pressure) was monitored continuously (Finapres). Left ventricular SV (stroke volume), CO (cardiac output) and SVR (systemic vascular resistance) were computed from the pressure pulsations (Modelflow). BRS (baroreflex sensitivity) was estimated in the time domain. In the first 3 min after NTG administration, BP was well-maintained in all patients. This implied an adequate arterial resistance Response to compensate for steeper reductions in SV and CO with increasing age. HR (heart rate) increased and the BRS decreased after NTG administration. The rate of mean FAP fall leading to presyncope was; inversely related to age (r = 0.51, P = 0.005). Accordingly, patients with a mean FAP fall > 1.44 mmHg/s (median) were generally younger compared with patients with a slower mean FAP-fall (30 +/- 10 years compared with 51 +/- 17 years; P = 0.001). The main determinant of the rate of BP fall on approach of presyncope was the rate of fall in HR (r = 0.75, P
John M. Karemaker - One of the best experts on this subject based on the ideXlab platform.
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impact of age on the Vasovagal Response provoked by sublingual nitroglycerine in routine tilt testing
Clinical Science, 2007Co-Authors: Bart Verheyden, Andre Aubert, John M. Karemaker, Janneke Gisolf, Karel H. Wesseling, Frank Beckers, Wouter WielingAbstract:NTG (nitroglycerine) is used in routine tilt testing to elicit a Vasovagal Response. In the present study we hypothesized that with increasing age NTG triggers a more gradual BP (blood pressure) decline due to a diminished baroreflex-buffering capacity. The purpose of the present study was to examine the effect of NTG on baroreflex control of BP in patients with distinct age-related Vasovagal collapse patterns. The study groups consisted of 29 patients (16-71 years old, 17 females) with clinically suspected VVS (Vasovagal syncope) and a positive tilt test. Mean FAP (finger arterial pressure) was monitored continuously (Finapres). Left ventricular SV (stroke volume), CO (cardiac output) and SVR (systemic vascular resistance) were computed from the pressure pulsations (Modelflow). BRS (baroreflex sensitivity) was estimated in the time domain. In the first 3 min after NTG administration, BP was well-maintained in all patients. This implied an adequate arterial resistance Response to compensate for steeper reductions in SV and CO with increasing age. HR (heart rate) increased and the BRS decreased after NTG administration. The rate of mean FAP fall leading to presyncope was; inversely related to age (r = 0.51, P = 0.005). Accordingly, patients with a mean FAP fall > 1.44 mmHg/s (median) were generally younger compared with patients with a slower mean FAP-fall (30 +/- 10 years compared with 51 +/- 17 years; P = 0.001). The main determinant of the rate of BP fall on approach of presyncope was the rate of fall in HR (r = 0.75, P <0.001). It was concluded that, in older patients, sublingual NTG provokes a more gradual BP decline compared with younger patients. This gradual decline cannot be ascribed to failure of the baroreflex-buffering capacity with increasing age. Age-related differences in the laboratory presentation of a Vasovagal episode depend on the magnitude of the underlying bradycardic Response
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Impact of age on the Vasovagal Response provoked by sublingual nitroglycerine in routine tilt testing
Clinical Science, 2007Co-Authors: Bart Verheyden, John M. Karemaker, Janneke Gisolf, Karel H. Wesseling, Frank Beckers, Andre E Aubert, Wouter WielingAbstract:Nitroglycerine (NTG) is used in routine tilt testing to elicit a Vasovagal Response. We hypothesized that with increasing age NTG triggers a more gradual blood pressure decline due to a diminished baroreflex buffering capacity. The purpose was to examine the effect of NTG on baroreflex control of blood pressure in patients with distinct age-related Vasovagal collapse patterns. The study groups consisted of 29 patients (16-71 yrs, 17 females) with clinically suspected VVS and a positive tilt test. Mean finger arterial pressure (MAP) was monitored continuously (Finapres). Left ventricular stroke volume (SV), cardiac output (CO) and systemic vascular resistance (SVR) were computed from the pressure pulsations (Modelflow). Spontaneous baroreflex control of heart rate (BRS) was estimated in the time domain. In the first 3 minutes after NTG, blood pressure was well maintained in all patients. This implies an adequate arterial resistance Response to compensate for steeper reductions in SV and CO with increasing age. Heart rate (HR) increased and the BRS decreased after NTG. The rate of MAP-fall leading to presyncope was inversely related to age (r = 0.51, p = 0.005). Accordingly, patients with a MAP-fall > 1.44 mmHg/s (median) were generally younger compared to patients with a slower MAP-fall (30 ± 10 yrs vs. 51 ± 17 yrs; p = 0.001). The main determinant of the rate blood pressure drop on approach of presyncope was the rate of fall in HR (r = 0.75, p < 0.001). It is concluded that, in the older patients, sublingual NTG provokes a more gradual blood pressure decline compared to the younger. This gradual decline cannot be ascribed to failure of the baroreflex buffering capacity with increasing age. Age-related differences in the laboratory presentation of a Vasovagal episode depend on the magnitude of the underlying bradycardic Response.
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Impact of age on the Vasovagal Response provoked by sublingual nitroglycerine in routine tilt testing
Clinical Science, 2007Co-Authors: Bart Verheyden, Andre Aubert, John M. Karemaker, Janneke Gisolf, Karel H. Wesseling, Frank Beckers, Wouter WielingAbstract:NTG (nitroglycerine) is used in routine tilt testing to elicit a Vasovagal Response. In the present study we hypothesized that with increasing age NTG triggers a more gradual BP (blood pressure) decline due to a diminished baroreflex-buffering capacity. The purpose of the present study was to examine the effect of NTG on baroreflex control of BP in patients with distinct age-related Vasovagal collapse patterns. The study groups consisted of 29 patients (16-71 years old, 17 females) with clinically suspected VVS (Vasovagal syncope) and a positive tilt test. Mean FAP (finger arterial pressure) was monitored continuously (Finapres). Left ventricular SV (stroke volume), CO (cardiac output) and SVR (systemic vascular resistance) were computed from the pressure pulsations (Modelflow). BRS (baroreflex sensitivity) was estimated in the time domain. In the first 3 min after NTG administration, BP was well-maintained in all patients. This implied an adequate arterial resistance Response to compensate for steeper reductions in SV and CO with increasing age. HR (heart rate) increased and the BRS decreased after NTG administration. The rate of mean FAP fall leading to presyncope was; inversely related to age (r = 0.51, P = 0.005). Accordingly, patients with a mean FAP fall > 1.44 mmHg/s (median) were generally younger compared with patients with a slower mean FAP-fall (30 +/- 10 years compared with 51 +/- 17 years; P = 0.001). The main determinant of the rate of BP fall on approach of presyncope was the rate of fall in HR (r = 0.75, P
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Sublingual nitroglycerin used in routine tilt testing provokes a cardiac output-mediated Vasovagal Response.
Journal of the American College of Cardiology, 2004Co-Authors: Janneke Gisolf, Berend E Westerhof, Wouter Wieling, Nynke Van Dijk, Karel H. Wesseling, John M. KaremakerAbstract:Objectives We set out to determine the effect of sublingual nitroglycerin (NTG), as used during routine tilt testing in patients with unexplained syncope, on hemodynamic characteristics and baroreflex control of heart rate (HR) and systemic vascular resistance (SVR). Background Nitroglycerin is used in tilt testing to elicit a Vasovagal Response. It is known to induce venous dilation and enhance pooling. Also, NTG is lipophilic and readily passes cell membranes, and animal studies suggest a sympatho-inhibitory effect of NTG on circulatory control. Methods Routine tilt testing was conducted in 39 patients with suspected Vasovagal syncope (age 36 ± 16 years, 18 females). Patients were otherwise healthy and free of medication. Before a loss of consciousness set in, oncoming syncope was cut short by tilt-back or counter-maneuvers. Finger arterial pressure was monitored continuously (Finapres). Left ventricular stroke volume (SV) was computed from the pressure pulsations (Modelflow). Spontaneous baroreflex control of HR was estimated in the time and frequency domains. Results During tilt testing, 22 patients developed presyncope. After NTG administration but before presyncope, SV and cardiac output (CO) decreased (p < 0.001), whereas SVR and HR increased (p < 0.001) in all patients. Arterial pressure was initially maintained. Baroreflex sensitivity decreased after NTG. On Cox regression analysis, the occurrence of a Vasovagal Response was related to a drop in SV after NTG (hazard ratio 0.86, p = 0.005). Conclusions The cardiovascular Response to NTG is similar in Vasovagal and non-Vasovagal patients, but more pronounced in those with tilt-positive results. The NTG-facilitated presyncope appears to be CO-mediated, and there is no evidence of NTG-induced sympathetic inhibition.
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Neural Circulatory Control in Vasovagal Syncope
Pacing and Clinical Electrophysiology, 1997Co-Authors: J. J. Van Lieshout, Wouter Wieling, John M. KaremakerAbstract:The orthostatic volume displacement associated with the upright position necessitates effective neural cardiovascular modulation. Neural control of cardiac chronograpy and inotropy, and vasomotor tone aims at maintaining venous return, thus opposing gravitational pooling of blood in the lower part of the body. The present concept of the Vasovagal Response or “common faint” implicates the development of inappropriate cardiac slowing due to sudden augmentation of efferent vagal activity, and arteriolar dilatation by sudden reduction or cessation of sympathetic activity. The venous pooling associated with lasting orthostatic stress results in development of central hypovolemia. At a certain point during the ongoing reflex adaptation to the hypovolemia in progress, a depressor reflex is set in train. The depressor reflex input along this second “peripheral” afferent pathway is postulated to originate from various sites in the cardiovascular system but remains uncertain. The common faint in humans is of both vaso- and vagal origin; the pure vagal Response is less common than its vasodepressor variant. There is strong evidence for an early loss of vasomotor tone in the majority of fainting subjects. Blocking the vagus nerve or cardiac pacing is not of much help in preventing Vasovagal syncope; though atropine or pacing may prevent bradycardia in Vasovagal fainting, they have never been proven to prevent hypotension. Baroreflex modulation of autonomic outflow remains present during the presyncopal stages until it becomes offset by an opposing depressor reflex with relative bradycardia and relaxation of arterial resistance vessels. The nature of the vasodilatation associated with the Vasovagal Response has still not been settled.
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Respiratory and hemodynamic contributions to emotion-related pre-syncopal Vasovagal symptoms.
Biological Psychology, 2017Co-Authors: Johanna M. Harrison, Philippe T. Gilchrist, Simon L. Bacon, Tiana S. Corovic, Curtis Bogetti, Yuqing Song, Blaine DittoAbstract:Vasovagal reactions are conventionally understood as resulting from systemic changes in cardiovascular activity; however, there exists a complementary perspective focused on specific changes in cerebral vasoconstriction associated with hyperventilation-induced hypocapnia. The present study investigated the role of cardiovascular and respiratory activity in self-reported pre-syncopal Vasovagal reactions to a surgery video in a sample of 49 healthy women. Participants who indicated more previous real-life episodes of dizziness reported experiencing significantly more symptoms in the laboratory consistent with a Vasovagal Response. They also showed lower total peripheral resistance and higher pre-ejection period in general, suggesting lower sympathetic nervous system activity. Significant decreases in end-tidal carbon dioxide (PETCO2) occurred during the surgery video among susceptible participants, without significant increases in respiration rate. Further, participants who experienced reductions from the neutral video in PETCO2, systolic blood pressure, or both, reported Vasovagal symptoms during the surgery video. The results suggest that patterns of respiration associated with decreases in PETCO2 may contribute to Vasovagal symptoms reported in non-clinical groups as well as those with blood-injection-injury phobia and are associated with susceptibility to dizziness.
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Disgust stimuli reduce heart rate but do not contribute to Vasovagal symptoms.
Journal of Behavior Therapy and Experimental Psychiatry, 2016Co-Authors: Philippe T. Gilchrist, Simon L. Bacon, Tudor Vrinceanu, Sophie Béland, Blaine DittoAbstract:Abstract Background and objectives The Vasovagal Response demonstrates a unique form of stress Response, common in medical settings yet provoked by a variety of blood-injury-injection stimuli. This study aimed to better understand the psychophysiological mechanisms of the Vasovagal Response.. Methods 16 undergraduates with and 42 without a self-reported history of fainting watched five 3–5 min videos with different emotional content. One documentary clip (Neutral condition) described a campus environmental project while another (Blood/Injury) depicted portions of an open heart surgery. Three additional clips were also used, including Medical, Threat, and Contamination stimuli. Vasovagal symptoms and physiological variables were assessed during each video. Results As predicted, while the disgust-related stimuli (Blood/Injury, Medical, Contamination) were associated with generally lower heart rate, the Blood/Injury video produced the highest symptoms and the only significant difference between previous fainters and non-fainters. The physiological measures also revealed that participants with a fainting history experienced higher stroke volume and lower systolic blood pressure throughout, as well as several main effects of video. Limitations An additional decrease in systolic blood pressure and respiration produced by watching the Blood/Injury video may have been sufficient to trigger symptoms in some, though results also suggest that systemic variables do not entirely explain susceptibility to symptoms. More careful evaluation of regional blood flow may be required. Conclusions Participants who had previously experienced strong Vasovagal Responses displayed what appeared to be an anticipatory Response to the Blood/Injury video. Finally, disgust stimuli may reduce heart rate but do not appear to contribute to Vasovagal symptoms.
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the Vasovagal Response during confrontation with blood injury injection stimuli the role of perceived control
Journal of Anxiety Disorders, 2015Co-Authors: Philippe T. Gilchrist, Nadine Bekkouche, Simon L. Bacon, Gillian Mcgovern, Blaine DittoAbstract:The Vasovagal Response (VVR) is a common medical problem, complicating and deterring people from various procedures. It is an unusual stress Response given the widespread decreases in physiological activity. Nevertheless, VVR involves processes similar to those observed during episodes of strong emotions and pain. We hypothesized that heightened perceived control would reduce symptoms of VVR. Eighty-two young adults were randomly assigned to perceived control or no perceived control conditions during exposure to a stimulus video of a mitral valve surgery, known to trigger VVR in non-medical personnel. Perceived control was manipulated by allowing some participants to specify a break time, though all received equivalent breaks. Outcomes included subjective symptoms of VVR, anxiety, blood pressure, heart rate, and other measures derived from impedance cardiography. Compared to participants with perceived control, participants with no perceived control reported significantly more Vasovagal symptoms and anxiety, and experienced lower stroke volume, cardiac output, and diastolic blood pressure. Participants who were more fearful of blood were more likely to benefit from perceived control in several measures. Perceived control appears to reduce Vasovagal symptoms. Results are discussed in terms of cognition and emotion in VVR.
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The Vasovagal Response during confrontation with blood-injury-injection stimuli: The role of perceived control ☆
Journal of Anxiety Disorders, 2015Co-Authors: Philippe T. Gilchrist, Gillian E. Mcgovern, Nadine Bekkouche, Simon L. Bacon, Blaine DittoAbstract:The Vasovagal Response (VVR) is a common medical problem, complicating and deterring people from various procedures. It is an unusual stress Response given the widespread decreases in physiological activity. Nevertheless, VVR involves processes similar to those observed during episodes of strong emotions and pain. We hypothesized that heightened perceived control would reduce symptoms of VVR. Eighty-two young adults were randomly assigned to perceived control or no perceived control conditions during exposure to a stimulus video of a mitral valve surgery, known to trigger VVR in non-medical personnel. Perceived control was manipulated by allowing some participants to specify a break time, though all received equivalent breaks. Outcomes included subjective symptoms of VVR, anxiety, blood pressure, heart rate, and other measures derived from impedance cardiography. Compared to participants with perceived control, participants with no perceived control reported significantly more Vasovagal symptoms and anxiety, and experienced lower stroke volume, cardiac output, and diastolic blood pressure. Participants who were more fearful of blood were more likely to benefit from perceived control in several measures. Perceived control appears to reduce Vasovagal symptoms. Results are discussed in terms of cognition and emotion in VVR.
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the effects of blood draw and injection stimuli on the Vasovagal Response
Psychophysiology, 2012Co-Authors: Philippe T. Gilchrist, Blaine DittoAbstract:Vasovagal reactions (VVR) are common, complicating and deterring people from various medical procedures. A recent perspective (R. R. Diehl, ) suggests that VVR developed from the adaptive process of hemorrhagic fainting, perhaps as a means of preparing for anticipated blood loss. The primary goal of this study was to compare Vasovagal symptoms during intravenous-injection and blood-draw videos. Sixty-two young adults watched the videos. Vasovagal symptoms were assessed with self-report, blood pressure, and heart rate variability. As predicted, participants reported more Vasovagal symptoms and anxiety following the blood-draw video. Sympathetic nervous system activity (low- to high-frequency ratio) decreased during both videos but significantly more during the blood-draw video, although this could be reversed by the Applied Tension technique. Results are discussed in terms of the relevance of specific stimuli and emotions in VVR.