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Markus Wallner - One of the best experts on this subject based on the ideXlab platform.

  • hdac inhibition improves Cardiopulmonary Function in a feline model of diastolic dysFunction
    Science Translational Medicine, 2020
    Co-Authors: Markus Wallner, Deborah M Eaton, Remus M Berretta, Laura Liesinger, Matthias Schittmayer, Juergen Gindlhuber, Mark Y Jeong, Jichuan Wu, Giulia Borghetti
    Abstract:

    Heart failure with preserved ejection fraction (HFpEF) is a major health problem without effective therapies. This study assessed the effects of histone deacetylase (HDAC) inhibition on Cardiopulmonary structure, Function, and metabolism in a large mammalian model of pressure overload recapitulating features of diastolic dysFunction common to human HFpEF. Male domestic short-hair felines (n = 31, aged 2 months) underwent a sham procedure (n = 10) or loose aortic banding (n = 21), resulting in slow-progressive pressure overload. Two months after banding, animals were treated daily with suberoylanilide hydroxamic acid (b + SAHA, 10 mg/kg, n = 8), a Food and Drug Administration–approved pan-HDAC inhibitor, or vehicle (b + veh, n = 8) for 2 months. Echocardiography at 4 months after banding revealed that b + SAHA animals had significantly reduced left ventricular hypertrophy (LVH) (P

  • hdac inhibition improves Cardiopulmonary Function in a feline model of diastolic dysFunction
    Science Translational Medicine, 2020
    Co-Authors: Markus Wallner, Deborah M Eaton, Remus M Berretta, Laura Liesinger, Matthias Schittmayer, Juergen Gindlhuber, Mark Y Jeong, Ying H Lin, Giulia Borghetti
    Abstract:

    Heart failure with preserved ejection fraction (HFpEF) is a major health problem without effective therapies. This study assessed the effects of histone deacetylase (HDAC) inhibition on Cardiopulmonary structure, Function, and metabolism in a large mammalian model of pressure overload recapitulating features of diastolic dysFunction common to human HFpEF. Male domestic short-hair felines (n = 31, aged 2 months) underwent a sham procedure (n = 10) or loose aortic banding (n = 21), resulting in slow-progressive pressure overload. Two months after banding, animals were treated daily with suberoylanilide hydroxamic acid (b + SAHA, 10 mg/kg, n = 8), a Food and Drug Administration-approved pan-HDAC inhibitor, or vehicle (b + veh, n = 8) for 2 months. Echocardiography at 4 months after banding revealed that b + SAHA animals had significantly reduced left ventricular hypertrophy (LVH) (P < 0.0001) and left atrium size (P < 0.0001) versus b + veh animals. Left ventricular (LV) end-diastolic pressure and mean pulmonary arterial pressure were significantly reduced in b + SAHA (P < 0.01) versus b + veh. SAHA increased myofibril relaxation ex vivo, which correlated with in vivo improvements of LV relaxation. Furthermore, SAHA treatment preserved lung structure, compliance, blood oxygenation, and reduced perivascular fluid cuffs around extra-alveolar vessels, suggesting attenuated alveolar capillary stress failure. Acetylation proteomics revealed that SAHA altered lysine acetylation of mitochondrial metabolic enzymes. These results suggest that acetylation defects in hypertrophic stress can be reversed by HDAC inhibitors, with implications for improving cardiac structure and Function in patients.

Giulia Borghetti - One of the best experts on this subject based on the ideXlab platform.

  • hdac inhibition improves Cardiopulmonary Function in a feline model of diastolic dysFunction
    Science Translational Medicine, 2020
    Co-Authors: Markus Wallner, Deborah M Eaton, Remus M Berretta, Laura Liesinger, Matthias Schittmayer, Juergen Gindlhuber, Mark Y Jeong, Jichuan Wu, Giulia Borghetti
    Abstract:

    Heart failure with preserved ejection fraction (HFpEF) is a major health problem without effective therapies. This study assessed the effects of histone deacetylase (HDAC) inhibition on Cardiopulmonary structure, Function, and metabolism in a large mammalian model of pressure overload recapitulating features of diastolic dysFunction common to human HFpEF. Male domestic short-hair felines (n = 31, aged 2 months) underwent a sham procedure (n = 10) or loose aortic banding (n = 21), resulting in slow-progressive pressure overload. Two months after banding, animals were treated daily with suberoylanilide hydroxamic acid (b + SAHA, 10 mg/kg, n = 8), a Food and Drug Administration–approved pan-HDAC inhibitor, or vehicle (b + veh, n = 8) for 2 months. Echocardiography at 4 months after banding revealed that b + SAHA animals had significantly reduced left ventricular hypertrophy (LVH) (P

  • hdac inhibition improves Cardiopulmonary Function in a feline model of diastolic dysFunction
    Science Translational Medicine, 2020
    Co-Authors: Markus Wallner, Deborah M Eaton, Remus M Berretta, Laura Liesinger, Matthias Schittmayer, Juergen Gindlhuber, Mark Y Jeong, Ying H Lin, Giulia Borghetti
    Abstract:

    Heart failure with preserved ejection fraction (HFpEF) is a major health problem without effective therapies. This study assessed the effects of histone deacetylase (HDAC) inhibition on Cardiopulmonary structure, Function, and metabolism in a large mammalian model of pressure overload recapitulating features of diastolic dysFunction common to human HFpEF. Male domestic short-hair felines (n = 31, aged 2 months) underwent a sham procedure (n = 10) or loose aortic banding (n = 21), resulting in slow-progressive pressure overload. Two months after banding, animals were treated daily with suberoylanilide hydroxamic acid (b + SAHA, 10 mg/kg, n = 8), a Food and Drug Administration-approved pan-HDAC inhibitor, or vehicle (b + veh, n = 8) for 2 months. Echocardiography at 4 months after banding revealed that b + SAHA animals had significantly reduced left ventricular hypertrophy (LVH) (P < 0.0001) and left atrium size (P < 0.0001) versus b + veh animals. Left ventricular (LV) end-diastolic pressure and mean pulmonary arterial pressure were significantly reduced in b + SAHA (P < 0.01) versus b + veh. SAHA increased myofibril relaxation ex vivo, which correlated with in vivo improvements of LV relaxation. Furthermore, SAHA treatment preserved lung structure, compliance, blood oxygenation, and reduced perivascular fluid cuffs around extra-alveolar vessels, suggesting attenuated alveolar capillary stress failure. Acetylation proteomics revealed that SAHA altered lysine acetylation of mitochondrial metabolic enzymes. These results suggest that acetylation defects in hypertrophic stress can be reversed by HDAC inhibitors, with implications for improving cardiac structure and Function in patients.

Xinbiao Guo - One of the best experts on this subject based on the ideXlab platform.

  • different health effects of indoor and outdoor originated pm2 5 on Cardiopulmonary Function in copd patients and healthy elderly adults
    Indoor Air, 2019
    Co-Authors: Rui Chi, Chen Chen, Lu Pan, Bin Zhao, Furong Deng, Xinbiao Guo
    Abstract:

    Numerous research has explored the associations of outdoor or indoor fine particulate matter (PM2.5 ) and health effects; however, few studies compared the effects of indoor PM2.5 originated from outdoor (PM2.5,os ) and indoor sources (PM2.5,is ). To assess the associations of PM2.5,os and PM2.5,is with Cardiopulmonary Function in patients with chronic obstructive pulmonary disease (COPD) and healthy elderly adults, blood pressure (BP) and pulmonary Function were repeatedly examined in 43 COPD patients and their 32 healthy spouses in Beijing, China. Iron was used as tracer element to separate PM2.5,os and PM2.5,is . Mixed-effects models were applied to assess the associations of PM2.5,os or PM2.5,is and health effects after controlling for potential confounders. There was a reduction in forced expiratory volume in first second (FEV1 ) in COPD patients associated with PM2.5,is during the heating season. PM2.5,os was positively associated with diastolic BP (DBP) in healthy elderly adults during the heating season. There was a reduction in peak expiratory flow (PEF) in healthy elderly adults associated with PM2.5,os during the non-heating season. Exposure to indoor- and outdoor-originated PM2.5 had different health effects on Cardiopulmonary Function in different populations. The results provide supporting evidence for improving indoor air quality to promote public health among susceptible population.

  • short term effects of various ozone metrics on Cardiopulmonary Function in chronic obstructive pulmonary disease patients results from a panel study in beijing china
    Environmental Pollution, 2018
    Co-Authors: Lu Pan, Furong Deng, Jiao Shan, Xuan Yang, Wei Dong, Yahong Chen, Masayuki Shima, Xinbiao Guo
    Abstract:

    Abstract Background Short-term exposure to ambient air pollution has been associated with lower pulmonary Function and higher blood pressure (BP). However, controversy remains regarding the relationship between ambient multiple daily ozone (O3) metrics and Cardiopulmonary health outcomes, especially in the developing countries. Objectives To investigate and compare the short-term effects of various O3 metrics on pulmonary Function, fractional exhaled nitric oxide (FeNO) and BP in a panel study of COPD patients. Methods We measured pulmonary Function, FeNO and BP repeatedly in a total of 43 patients with COPD for 215 home visits. Daily hourly ambient O3 concentrations were obtained from central-monitoring stations close to subject residences. We calculated various O3 metrics [daily 1-h maximum (O3-1 h max), maximum 8-h average (O3-8 h max) and 24-h average (O3-24 h avg)] based on the hourly data. Daily indoor O3 concentrations were estimated based on estimated indoor/outdoor O3 ratios. Linear mixed-effects models were used to estimate associations of various O3 metrics with Cardiopulmonary Function variables. Results An interquartile range (IQR) increase in ambient O3-8 h max (80.5 μg/m3, 5-d) was associated with a 5.9% (95%CI: −11.0%, −0.7%) reduction in forced expiratory volume in 1 s (FEV1) and a 6.2% (95%CI: −10.9%, −1.5%) reduction in peak expiratory flow (PEF). However, there were no significant negative associations between ambient O3-1 h max, O3-24 h avg and FEV1, PEF. An IQR increase in ambient O3-1 h max (85.3 μg/m3, 6-d) was associated with a 6.7 mmHg (95%CI: 0.7, 12.7) increase in systolic BP. The estimated indoor O3 were still significantly associated with reduction of FEV1 and PEF. No significant associations were found between various O3 metrics and FeNO. Conclusions Our results provide clues for the adverse Cardiopulmonary effects associated with various O3 metrics in COPD patients and highlight that O3-8 h max was more closely associated with respiratory health variables.

Christopher West - One of the best experts on this subject based on the ideXlab platform.

  • respiratory muscle training in athletes with cervical spinal cord injury effects on Cardiopulmonary Function and exercise capacity
    The Journal of Physiology, 2019
    Co-Authors: Cameron M Gee, Alexandra M Williams, William A Sheel, Neil D Eves, Christopher West
    Abstract:

    KEY POINTS The effect of combined inspiratory and expiratory muscle training on resting and reflexive cardiac Function, as well as exercise capacity, in individuals with cervical spinal cord injury (SCI) is presently unknown. Six weeks of combined inspiratory and expiratory muscle training enhances both inspiratory and expiratory muscle strength in highly-trained athletes with cervical SCI with no significant effect on lung Function. There was a significant decrease in left-ventricular filling and stroke volume at rest in response to 45° head-up tilt, which is irreversible by respiratory muscle training. Combined inspiratory and expiratory muscle training increased peak aerobic work rate and reduced end-expiratory lung volumes during exercise, which may have implications for left-ventricular filling during exercise. ABSTRACT To investigate the pulmonary, cardiovascular and exercise responses to combined inspiratory and expiratory respiratory muscle training (RMT) in athletes with tetraplegia, six wheelchair rugby athletes (five males and one female, aged 33 ± 5 years) completed 6 weeks of pressure threshold RMT, 2 sessions day-1 on 5 days week-1 . Resting pulmonary and cardiac Function, exercise capacity, exercising lung volumes and field-based exercise performance were assessed at pre-RMT, post-RMT and after a 6-week no RMT period. RMT enhanced maximal inspiratory (pre- vs. post-RMT: -76 ± 15 to -106 ± 23 cmH2 O, P = 0.002) and expiratory (59 ± 26 to 73 ± 32 cmH2 O, P = 0.007) mouth pressures, as well as peak expiratory flow (6.74 ± 1.51 vs. 7.32 ± 1.60 L/s, P < 0.04). Compared to pre-RMT, peak work rate was higher at post-RMT (60 ± 23 to 68 ± 22 W, P = 0.003), whereas exercising end-expiratory lung volumes were reduced (P < 0.017). Peak oxygen uptake increased in all athletes at post-RMT (1.24 ± 0.40 vs. 1.40 ± 0.50 l min-1 , P = 0.12). After 6 weeks of no RMT all indices returned towards baseline, with peak work rate (P = 0.037), peak oxygen uptake (P = 0.041) and end-expiratory lung volume (P < 0.034) being significantly lower at follow-up than at post-RMT. There was a significant decrease in left-ventricular end-diastolic volume and stroke volume in response to 45° head-up tilt (P = 0.030 and 0.021, respectively); however, all cardiac indices in both supine and tilted positions were unchanged by RMT. Our findings demonstrate the efficacy of RMT with respect to enhancing respiratory muscle strength, lowering exercising lung volumes and increasing exercise capacity. Although the precise mechanisms by which RMT may enhance exercise capacity remain unclear, our data suggest that it is probably not the result of a direct cardiac adaptation associated with RMT.

  • Resting Cardiopulmonary Function in paralympic athletes with cervical spinal cord injury
    Medicine and science in sports and exercise, 2012
    Co-Authors: Christopher West, Ian G. Campbell, Rob Shave, Lee M. Romer
    Abstract:

    WEST, C. R., I. G. CAMPBELL, R. E. SHAVE, and L. M. ROMER. Resting Cardiopulmonary Function in Paralympic Athletes with Cervical Spinal Cord Injury. Med. Sci. Sports Exerc., Vol. 44, No. 2, pp. 323–329, 2012. Purpose: The purposes of this study were to describe resting Cardiopulmonary Function in highly trained athletes with cervical spinal cord injury (SCI) and to compare the data with able-bodied (AB) control subjects. Methods: Twelve Paralympic wheelchair rugby players with cervical SCI (injury level = C5–C7) and 12 AB controls matched for age, stature, and body mass were assessed for pulmonary Function using spirometry, body plethysmography, and maximal inspiratory and expiratory mouth pressures; diaphragm Function using magnetic stimulation of the phrenic nerves; and cardiac Function using transthoracic echocardiography. Results: Total lung capacity, vital capacity, inspiratory reserve volume, and expiratory reserve volume were lower in SCI compared with AB (P G 0.01), whereas residual volume was elevated in SCI (P = 0.022). Airway resistance and maximal inspiratory mouth pressure were not different between groups (P 9 0.41), whereas maximal expiratory mouth pressure, maximal transdiaphragmatic pressure, and twitch transdiaphragmatic pressure were lower in SCI (P G 0.01). Percent predicted total lung capacity was significantly correlated with maximal transdiaphragmatic pressure in SCI (r = 0.74), suggesting that the pulmonary restriction was a result of diaphragm weakness. Left ventricular mass, ejection fraction, stroke volume, and cardiac output were lower in SCI (P G 0.04), but early and late filling velocities during diastole were not different between groups (P 9 0.05). Conclusions: Highly trained athletes with cervical SCI exhibit a restrictive pulmonary defect, weakness of the expiratory and diaphragm muscles, atrophy of the heart, and reduced systolic cardiac Function. Key Words: CARDIAC, DIAPHRAGM, PHRENIC NERVE, PULMONARY, TETRAPLEGIA, ULTRASONOGRAPHY

Frank Gasthuys - One of the best experts on this subject based on the ideXlab platform.

  • comparison of the influence of two different constant rate infusions dexmedetomidine versus morphine on anaesthetic requirements Cardiopulmonary Function and recovery quality in isoflurane anaesthetized horses
    Research in Veterinary Science, 2013
    Co-Authors: Miguel Gozalomarcilla, Barbara Steblaj, Stijn Schauvliege, Luc Duchateau, Frank Gasthuys
    Abstract:

    Abstract Twenty adult healthy horses undergoing elective surgery were involved in this prospective, blinded, clinical study. Horses were randomly allocated to receive a constant rate infusion (CRI) of morphine or dexmedetomidine. After induction, anaesthesia was maintained with isoflurane in oxygen/air and mechanical ventilation applied. The end-tidal isoflurane concentration (F E ISO) was initially set at 0.9% and adjusted by the anaesthetist, to maintain a light surgical plane of anaesthesia, according to an objective flow-chart. The Cardiopulmonary Function was only minimally different between groups and maintained within clinically normal ranges. Less ketamine was required, F E ISO was lower after 1 h and fewer alterations in the anaesthetic depth were needed in horses receiving dexmedetomidine, with better recoveries. One horse receiving morphine developed post-operative colic and pulmonary oedema and two showed box-walking behaviour. This study showed that a dexmedetomidine CRI produced a more stable anaesthetic depth, reduced isoflurane requirements and better recoveries, without post-operative complications compared with a morphine CRI.

  • influence of a constant rate infusion of dexmedetomidine on Cardiopulmonary Function and recovery quality in isoflurane anaesthetized horses
    Veterinary Anaesthesia and Analgesia, 2012
    Co-Authors: Miguel Gozalo Marcilla, Stijn Schauvliege, Luc Duchateau, Stefanie Segaert, Frank Gasthuys
    Abstract:

    Abstract Objective To investigate the influence of a dexmedetomidine constant rate infusion (CRI) in horses anaesthetized with isoflurane. Study design Prospective, randomized, blinded, clinical study. Animals Forty adult healthy horses (weight mean 491 ± SD 102 kg) undergoing elective surgery. Methods After sedation [dexmedetomidine, 3.5 μg kg −1 intravenously (IV)] and induction IV (midazolam 0.06 mg kg −1 , ketamine 2.2 mg kg −1 ), anaesthesia was maintained with isoflurane in oxygen/air (FiO 2 55–60%). Horses were ventilated and dobutamine was administered when hypoventilation [arterial partial pressure of CO 2 > 8.00 kPa (60 mmHg)] and hypotension [arterial pressure 70 mmHg] occurred respectively. During anaesthesia, horses were randomly allocated to receive a CRI of dexmedetomidine (1.75 μg kg −1 hour −1 ) (D) or saline (S). Monitoring included end-tidal isoflurane concentration, Cardiopulmonary parameters, and need for dobutamine and additional ketamine. All horses received 0.875 μg kg −1 dexmedetomidine IV for the recovery period. Age and weight of the horses, duration of anaesthesia, additional ketamine and dobutamine, Cardiopulmonary data ( anova ), recovery scores (Wilcoxon Rank Sum Test), duration of recovery ( t -test) and attempts to stand (Mann–Whitney test) were compared between groups. Significance was set at p Results Heart rate and arterial partial pressure of oxygen were significantly lower in group D compared to group S. An interaction between treatment and time was present for cardiac index, oxygen delivery index and systemic vascular resistance. End-tidal isoflurane concentration and heart rate significantly increased over time. Packed cell volume, systolic, diastolic and mean arterial pressure, arterial oxygen content, stroke volume index and systemic vascular resistance significantly decreased over time. Recovery scores were significantly better in group D, with fewer attempts to stand and significantly longer times to sternal position and first attempt to stand. Conclusions and clinical relevance A dexmedetomidine CRI produced limited Cardiopulmonary effects, but significantly improved recovery quality.