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Bartley P Griffith - One of the best experts on this subject based on the ideXlab platform.
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neutrophil dysfunction due to continuous mechanical shear exposure in mechanically Assisted Circulation in vitro
Artificial Organs, 2021Co-Authors: Wenji Sun, Jiafeng Zhang, Aakash Shah, Katherin Arias, Zachary B Berk, Bartley P GriffithAbstract:Objective Leukocytes play an important role in the body's immune system. The aim of this study was to assess alterations in neutrophil phenotype and function in pump-Assisted Circulation in-vitro. Methods Human blood was circulated for four hours in three circulatory flow loops with a CentriMag blood pump operated at a flow of 4.5 L/min at three rotational speeds (2100, 2800, and 4000 rpm), against three pressure heads (75 mmHg, 150 mmHg, and 350 mmHg), respectively. Blood samples were collected hourly for analyses of neutrophil activation state (Mac-1, CD62L, CD162), neutrophil reactive oxygen species (ROS) production, apoptosis, and neutrophil phagocytosis. Results Activated neutrophils indicated by both Mac-1 expression and decreased surface expression of CD62L and CD162 receptors increased with time in three loops. The highest level of neutrophil activation was observed in the loop with the highest rotational speed. Platelet-neutrophil aggregates (PNAs) progressively increased in two loops with lower rotational speeds. PNAs peaked at one hour after Circulation and decreased subsequently in the loop with the highest rotational speed. Neutrophil ROS production dramatically increased at one hour after Circulation and decreased subsequently in all three loops with similar levels and trends. Apoptotic neutrophils increased with time in all three loops. Neutrophil phagocytosis capacity in three loops initially elevated at one hour after Circulation and decreased subsequently. Apoptosis and altered phagocytosis were dependent on rotational speed. Conclusions Our study revealed that the pump-Assisted Circulation induced neutrophil activation, apoptosis, and functional impairment. The alterations were strongly associated with pump operating condition and duration.
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device induced hemostatic disorders in mechanically Assisted Circulation
Clinical and Applied Thrombosis-Hemostasis, 2021Co-Authors: Shigang Wang, Bartley P GriffithAbstract:Mechanically Assisted Circulation (MAC) sustains the blood Circulation in the body of a patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) or on ventricular assistance with a ventricular assist device (VAD) or on extracorporeal membrane oxygenation (ECMO) with a pump-oxygenator system. While MAC provides short-term (days to weeks) support and long-term (months to years) for the heart and/or lungs, the blood is inevitably exposed to non-physiological shear stress (NPSS) due to mechanical pumping action and in contact with artificial surfaces. NPSS is well known to cause blood damage and functional alterations of blood cells. In this review, we discussed shear-induced platelet adhesion, platelet aggregation, platelet receptor shedding, and platelet apoptosis, shear-induced acquired von Willebrand syndrome (AVWS), shear-induced hemolysis and microparticle formation during MAC. These alterations are associated with perioperative bleeding and thrombotic events, morbidity and mortality, and quality of life in MCS patients. Understanding the mechanism of shear-induce hemostatic disorders will help us develop low-shear-stress devices and select more effective treatments for better clinical outcomes.
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the impact of shear stress on device induced platelet hemostatic dysfunction relevant to thrombosis and bleeding in mechanically Assisted Circulation
Artificial Organs, 2020Co-Authors: Zengsheng Chen, Jiafeng Zhang, Douglas Tran, Bartley P GriffithAbstract:The aim of this study was to examine the impact of the nonphysiological shear stress (NPSS) on platelet hemostatic function relevant to thrombosis and bleeding in mechanically Assisted Circulation. Fresh human blood was circulated for four hours in in vitro circulatory flow loops with a CentriMag blood pump operated under a flow rate of 4.5 L/min against three pressure heads (70 mm Hg, 150 mm Hg, and 350 mm Hg) at 2100, 2800, and 4000 rpm, respectively. Hourly blood samples from the CentriMag pump-Assisted Circulation loops were collected and analyzed for glycoprotein (GP) IIb/IIIa activation and receptor shedding of GPVI and GPIbα on the platelet surface with flow cytometry. Adhesion of platelets to fibrinogen, collagen, and von Willebrand factor (VWF) of the collected blood samples was quantified with fluorescent microscopy. In parallel, mechanical shear stress fields within the CentriMag pump operated under the three conditions were assessed by computational fluid dynamics (CFD) analysis. The experimental results showed that levels of platelet GPIIb/IIIa activation and platelet receptor shedding (GPVI and GPIbα) in the blood increased with increasing the Circulation time. The levels of platelet activation and loss of platelet receptors GPVI and GPIbα were consistently higher with higher pressure heads at each increasing hour in the CentriMag pump-Assisted Circulation. The platelet adhesion on fibrinogen increased with increasing the Circulation time for all three CentriMag operating conditions and was correlated well with the level of platelet activation. In contrast, the platelet adhesion on collagen and VWF decreased with increasing the Circulation time under all the three conditions and was correlated well with the loss of the receptors GPVI and GPIbα on the platelet surface, respectively. The CFD results showed that levels of shear stresses inside the CentriMag pump under all three operating conditions exceeded the maximum level of shear stress in the normal physiological Circulation and were strongly dependent on the pump operating condition. The level of platelet activation and loss of key platelet adhesion receptors (GPVI and GPIbα) were correlated with the level of NPSS generated by the CentriMag pump, respectively. In summary, the level of NPSS associated with pump operating condition is a critical determinant of platelet dysfunction in mechanically Assisted Circulation.
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device induced platelet dysfunction in mechanically Assisted Circulation increases the risks of thrombosis and bleeding
Artificial Organs, 2019Co-Authors: Zengsheng Chen, Jiafeng Zhang, Douglas Tran, Katherin Arias, Kafayat Kareem, Robert G Conway, Bartley P GriffithAbstract:Thrombotic and bleeding complications are the major obstacles for expanding mechanical circulatory support (MCS) beyond the current use. While providing the needed hemodynamic support, those devices can induce damage to blood, particularly to platelets. In this study, we investigated device-induced alteration of three major platelet surface receptors, von Willebrand factor (VWF) and associated hemostatic functions relevant to thrombosis and bleeding. Fresh human whole blood was circulated in an extracorporeal circuit with a clinical rotary blood pump (CentriMag, Abbott, Chicago, IL, USA) under the clinically relevant operating condition for 4 hours. Blood samples were examined every hour for glycoprotein (GP) IIb/IIIa activation and receptor loss of GPVI and GPIbα on the platelet surface with flow cytometry. Soluble P-selectin in hourly collected blood samples was measured by enzyme linked immunosorbent assay to characterize platelet activation. Adhesion of device-injured platelets to fibrinogen, collagen, and VWF was quantified with fluorescent microscopy. Device-induced damage to VWF was characterized with western blotting. The CentriMag blood pump induced progressive platelet activation with blood circulating time. Particularly, GPIIb/IIIa activation increased from 1.1% (Base) to 11% (4 hours) and soluble P-selectin concentration increased from 14.1 ng/mL (Base) to 26.5 ng/mL (4 hours). Those device-activated platelets exhibited increased adhesion capacity to fibrinogen. Concurrently, the CentriMag blood pump caused progressive platelet receptor loss (GPVI and GPIbα) with blood circulating time. Specifically, MFI of the GPVI and GPIbα receptors decreased by 17.2% and 16.1% for the 4-hours sample compared to the baseline samples, respectively. The device-injured platelets exhibited reduced adhesion capacities to collagen and VWF. The high molecular weight multimers (HMWM) of VWF in the blood disappeared within the first hour of the Circulation. Thereafter the multimeric patterns of VWF were stable. The change in the VWF multimeric pattern was different from the progressive structural and functional changes of platelets with the Circulation time. This study suggested that the CentriMag blood pump could induce two opposite effects on platelets and associated hemostatic functions under a clinically relevant operating condition. The device-altered hemostatic function may contribute to thrombosis and bleeding simultaneously as occurring in patients supported by a rotary blood pump. Device-induced damage of platelets may be an important cause for bleeding in patients supported with rotary blood pump MCS systems relative to device-induced loss of HMWM-VWF.
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mechanisms of red blood cell trauma in Assisted Circulation rheologic similarities of red blood cell transformations due to natural aging and mechanical stress
Asaio Journal, 1995Co-Authors: Marina V Kameneva, Bartley P Griffith, James F Antaki, Harvey S Borovetz, Kenneth C Butler, Krishna K Yeleswarapu, Mary J Watach, Robert L KormosAbstract:Clinical experience with circulatory support devices has typically shown alteration of patient blood rheology exhibited through increasing blood viscosity and decreasing erythrocyte deformability. Our hemorheologic studies have additionally shown a remarkable increase in red blood cell (RBC) aggregation in the blood of artificial heart patients as compared to healthy donors. These hemorheologic changes may be caused by mechanical trauma to RBCs. The authors hypothesize that the mechanical trauma process, from a rheologic point of view, could be analogous to an "accelerated" RBC aging process. The hypothesis was examined through in vivo and in vitro experiments on RBCs, age-separated on the basis of density, specifically to identify the rheologic similarities between aged and mechanically traumatized RBCs. Older RBCs demonstrated an increased mechanical fragility, a decreased deformability, and a increased ability to aggregate as compared to younger RBCs. RBCs exposed to mechanical stress demonstrated similar alterations in the same rheologic parameters. Our experiments have also shown that mechanical stress decreases the negative surface charge of RBCs as is known to occur in aged RBCs. Similarities found between the processes of RBC mechanical trauma and senescence enhance our understanding of mechanisms of subhemolytic trauma incurred in Assisted Circulation. This may improve the design and evaluation of future heart assist devices through minimizing shear induced blood trauma.
Joseph G Rogers - One of the best experts on this subject based on the ideXlab platform.
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balancing bleeding and clotting the known unknowns of mechanically Assisted Circulation
Circulation-heart Failure, 2017Co-Authors: Joseph G RogersAbstract:Mechanically Assisted Circulation has established a firm footing in the management of patients with advanced heart failure. Relative to the high predicted mortality and poor quality of life associated with inotrope-dependent heart failure, clinical trials and registries have demonstrated a highly favorable impact of left ventricular assist devices (LVADs) on these important, patient-centric outcomes. More recently, LVADs were shown to improve survival and submaximal exercise performance in ambulatory heart failure patients not treated with inotropic support.1 Despite this growing and compelling literature, broader adoption by the heart failure and cardiovascular communities has been limited—an interesting paradox for one of the most impactful therapies ever developed to reduce cardiovascular mortality. Concerns over patient selection, device durability, postimplant quality and quantity of life, adverse events, therapeutic complexity, and cost likely fuel the uncertainty. See Article by Andreas et al Seventy percent of patients have a serious adverse event in the first year of LVAD therapy highlighting the need to refine the unique interplay between man, machine, and medicine required to achieve the potential of the therapy.2 Although some adverse events, such as driveline infections, are more directly attributable to human factors, others are linked to the interaction between blood components, the blood-contacting surfaces of the pump, shear stress, and the medications …
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Changing the Carburetor Without Changing the Plugs: The Intersection of Stock Car Racing With Mechanically Assisted Circulation.
JACC. Heart failure, 2015Co-Authors: Joseph G RogersAbstract:This Editorial Comment is dedicated to those “who think the last four words of the national anthem are ‘Gentlemen, start your engines'” (Jeff Foxworthy) [(1)][1]. Summer in the South is filled with sweltering heat, the sweet smell of magnolias, lazy summer weekends, and afternoons at the
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risk assessment and comparative effectiveness of left ventricular assist device and medical management in ambulatory heart failure patients design and rationale of the roadmap clinical trial
American Heart Journal, 2015Co-Authors: Joseph G Rogers, Andrew J Boyle, John B Oconnell, D A Horstmanshof, Donald C Haas, Mark S Slaughter, Soon J Park, David J Farrar, Randall C StarlingAbstract:Background Mechanical circulatory support is now a proven therapy for the treatment of patients with advanced heart failure and cardiogenic shock. The role for this therapy in patients with less severe heart failure is unknown. Objective The objective of this study is to examine the impact of mechanically Assisted Circulation using the HeartMate II left ventricular assist device in patients who meet current US Food and Drug Administration–defined criteria for treatment but are not yet receiving intravenous inotropic therapy. Methods This is a prospective, nonrandomized clinical trial of 200 patients treated with either optimal medical management or a mechanical circulatory support device. Clinical context This trial will be the first prospective clinical evaluation comparing outcomes of patients with advanced ambulatory heart failure treated with either ongoing medical therapy or a left ventricular assist device. It is anticipated to provide novel insights regarding relative outcomes with each treatment and an understanding of patient and provider acceptance of the ventricular assist device therapy. This trial will also provide information regarding the risk of events in "stable" patients with advanced heart failure and guidance for the optimal timing of left ventricular assist device therapy.
Peter Safar - One of the best experts on this subject based on the ideXlab platform.
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fructose 1 6 bisphosphate and mk 801 by aortic arch flush for cerebral preservation during exsanguination cardiac arrest of 20 min in dogs an exploratory study
Resuscitation, 2001Co-Authors: Wilhelm Behringer, Rainer Kentner, Samuel A Tisherman, Ann Radovsky, William Stezoski, Jeremy Henchir, Stephan Prueckner, Edwin K Jackson, Peter SafarAbstract:Abstract In our exsanguination cardiac arrest (CA) outcome model in dogs we are systematically exploring suspended animation (SA), i.e. preservation of brain and heart immediately after the onset of CA to enable transport and resuscitative surgery during CA, followed by delayed resuscitation. We have shown in dogs that inducing moderate cerebral hypothermia with an aortic arch flush of 500 ml normal saline solution at 4°C, at start of CA 20 min no-flow, leads to normal functional outcome. We hypothesized that, using the same model, but with the saline flush at 24°C inducing minimal cerebral hypothermia (which would be more readily available in the field), adding either fructose-1,6-bisphosphate (FBP, a more efficient energy substrate) or MK-801 (an N -methyl- d -aspartate (NMDA) receptor blocker) would also achieve normal functional outcome. Dogs (range 19–30 kg) were exsanguinated over 5 min to CA of 20 min no-flow, and resuscitated by closed-chest cardiopulmonary bypass (CPB). They received Assisted Circulation to 2 h, mild systemic hypothermia (34°C) post-CA to 12 h, controlled ventilation to 20 h, and intensive care to 72 h. At CA 2 min, the dogs received an aortic arch flush of 500 ml saline at 24°C by a balloon-tipped catheter, inserted through the femoral artery (control group, n =6). In the FBP group ( n =5), FBP (total 1440 or 4090 mg/kg) was given by flush and with reperfusion. In the MK-801 group ( n =5), MK-801 (2, 4, or 8 mg/kg) was given by flush and with reperfusion. Outcome was assessed in terms of overall performance categories (OPC 1, normal; 2, moderate disability; 3, severe disability; 4, coma; 5, brain death or death), neurologic deficit scores (NDS 0–10%, normal; 100%, brain death), and brain histologic damage scores (HDS, total HDS 0, no damage; >100, extensive damage; 1064, maximal damage). In the control group, one dog achieved OPC 2, one OPC 3, and four OPC 4; in the FBP group, two dogs achieved OPC 3, and three OPC 4; in the MK-801 group, two dogs achieved OPC 3, and three OPC 4 ( P =1.0). Median NDS were 62% (range 8–67) in the control group; 55% (range 34–66) in the FBP group; and 50% (range 26–59) in the MK-801 group ( P =0.2). Median total HDS were 130 (range 56–140) in the control group; 96 (range 64–104) in the FBP group; and 80 (range 34–122) in the MK-801 group ( P =0.2). There was no difference in regional HDS between groups. We conclude that neither FBP nor MK-801 by aortic arch flush at the start of CA, plus an additional i.v. infusion of the same drug during reperfusion, can provide cerebral preservation during CA 20 min no-flow. Other drugs and drug-combinations should be tested with this model in search for a breakthrough effect.
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thiopental and phenytoin by aortic arch flush for cerebral preservation during exsanguination cardiac arrest of 20 minutes in dogs an exploratory study
Resuscitation, 2001Co-Authors: Wilhelm Behringer, Rainer Kentner, Samuel A Tisherman, Ann Radovsky, William Stezoski, Jeremy Henchir, Stephan Prueckner, Peter SafarAbstract:Abstract We are systematically exploring in our exsanguination cardiac arrest (CA) outcome model in dogs suspended animation (SA), i.e. immediate preservation of brain and heart for resuscitative surgery during CA, with delayed resuscitation. We have shown in dogs that inducing moderate cerebral hypothermia with an aortic arch flush of 500 ml normal saline solution of 4°C, at start of CA 20 min no-flow, leads to normal functional outcome. We hypothesized that, using the same model, adding thiopental (or even better thiopental plus phenytoin) to the flush at ambient temperature (24°C), which would be more readily available in the field, will also achieve normal functional outcome. Thirty dogs (20–28 kg) were exsanguinated over 5 min to CA of 20 min no-flow, and resuscitated by closed-chest cardiopulmonary bypass. They received Assisted Circulation to 2 h, 34°C post-CA to 12 h, controlled ventilation to 20 h, and intensive care to 72 h. At CA 2 min, the dogs received an aortic arch flush of 500 ml saline at 24°C by a balloon-tipped catheter, inserted through the femoral artery (control group 1, n =14). In group 2 ( n =9), thiopental (variable total doses of 15–120 mg/kg) was added to the flush and given with reperfusion. In group 3 ( n =7), thiopental (15 or 45 mg/kg) plus phenytoin (10, 20, or 30 mg/kg) was given by flush and with reperfusion. Outcome was assessed in terms of overall performance categories (OPC 1, normal; 2, moderate disability; 3, severe disability; 4, coma; 5, brain death), neurologic deficit scores (NDS 0–10%, normal; 100%, brain death), and histologic deficit scores (HDS, total and regional). The flush reduced tympanic temperature to about 36°C in all groups. In control group 1, one dog achieved OPC 1, three OPC 2, six OPC 3, and four OPC 4. In thiopental group 2, two dogs achieved OPC 1, two OPC 3, and five OPC 4. In thiopental/phenytoin group 3, one dog achieved OPC 1, two OPC 3, and four OPC 4 ( p =0.5). Median NDS were 36% (IQR 22–62%) in group 1; 51% (IQR 22–56%) in group 2; and 55% (IQR 38–59%) in group 3 ( p =0.7). Median total HDS were 67 (IQR 56–127) in group 1; 60 (IQR 52–138) in group 2; and 76 (IQR 48–132) in group 3 ( p =1.0). Thiopental and thiopental/phenytoin dogs achieved significantly lower HDS only in the putamen. Thiopental in large doses caused side effects. We conclude that neither thiopental alone nor thiopental plus phenytoin by flush, with or without additional intravenous infusion, can consistently provide ‘clinically significant' cerebral preservation for 20 min no-flow. Other drugs and drug-combinations should be tested with this model in search for a breakthrough effect.
Charles W Acher - One of the best experts on this subject based on the ideXlab platform.
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the effect of intercostal artery reimplantation on spinal cord injury in thoracoabdominal aortic aneurysm surgery
Journal of Vascular Surgery, 2015Co-Authors: Martha M Wynn, Charles W Acher, Erich Marks, C W AcherAbstract:Objective Intercostal artery (ICA) reimplantation (ICAR) is thought to decrease spinal cord injury (SCI) in thoracic aortic aneurysm and thoracoabdominal aortic aneurysm (TAAA) surgery. Patients treated from 1989 to 2005 without ICAR were compared with those treated from 2005 to 2013 with ICAR to determine whether ICAR reduced SCI. We hypothesized that ICAR would reduce SCI, especially in the highest-risk patients. Methods This was a retrospective analysis using a prospectively maintained Investigational Review Board-approved database from a university tertiary referral center. The analysis included all patients (n = 805) undergoing thoracic aortic aneurysm and TAAA surgery from 1989 to 2013. The main outcome measure was any transient or permanent paraplegia or paraparesis (SCI). From 1989 to 2004, ICAR was not performed in patients, and open ICAs were ligated; from 2005 to 2013, open ICAs at T7 to L2 were reimplanted in patients with Crawford type I, II, and III TAAAs. Surgical technique was cross clamp without Assisted Circulation. Anesthetic management was the same from 1989 to 2013. Demographic, intraoperative, and outcome variables were assessed by univariate and multivariate analysis. Observed/expected ratios for paralysis were calculated. Results A total of 540 patients had surgery before 2005, and 265 had surgery after 2005, when ICAR was begun. There were 275 type I, II, and III TAAAs before 2005 and 164 after 2005. Aneurysm extent, acuity, SCI, mortality, renal failure, and pulmonary failure were the same in patients treated before and after 2005. Multivariate modeling of all patients showed type II TAAA ( P = .0001), dissection ( P = .00015), and age as a continuous variable ( P = .0085) were significant for SCI. Comparing only type I, II, and III TAAAs, there was no difference in SCI between those with ICAR after 2005 and those without ICAR before 2005 (5.1% vs 8.8%; P = .152). In a subanalysis of the highest-risk patients (type II, dissection, acute), ICAR was not significant ( P = .27). Observed/expected ratios ratios were 0.23 before 2005 and 0.16 after 2005 ( χ 2 = .796; P = .37). Conclusions Although there was a small decrease in SCI with ICAR, reattaching ICAs did not produce a statistically significant reduction in SCI, even in the highest-risk patients.
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paraplegia after thoracoabdominal aortic surgery not just Assisted Circulation hypothermic arrest clamp and sew or tevar
Annals of cardiothoracic surgery, 2012Co-Authors: Charles W Acher, Martha M WynnAbstract:Spinal cord ischemia in thoracoabdominal aortic surgery is caused by the imbalance of oxygen demand and oxygen delivery produced by aortic occlusion. Ischemia and reperfusion initiate neurochemical cellular responses that can exacerbate ischemia, which may in turn progress to infarction (Figure 1). The most important factors in protecting the spinal cord during and after thoracic and thoracoabdominal aortic replacement are perfusion, metabolism, and oxygen delivery to the spinal cord during the vulnerable period of aortic occlusion, when spinal cord blood flow is significantly reduced (1,2) as well as after aortic replacement while the co-axial collateral network is recruited to return resting blood flow to near-normal levels (3). Assisted Circulation and intercostal re-implantation have by themselves failed to reduce paraplegia risk both experimentally and clinically. This failure has been a source of frustration for surgeons as it runs counterintuitive to the anatomic paradigm for spinal cord preservation established by Adams and adopted by most surgeons for much of the last 60 years (4-8). However, reducing the vulnerability of the spinal cord during aortic replacement has always centered upon collateral Circulation, increasing ischemic tolerance and protecting the spinal cord while collateral blood flow accommodates. To reduce paraplegia risk in our patients we use the experimental literature to implement strategies validated as effective. In order to analyze our and others’ results we developed a predictive paraplegia model to calculate O/E ratios because percent paralysis is misleading by not accounting for patient mix (9). This model accounted for 99% of the variability in clinical reports of more than 5,000 patients. This analysis demonstrated that Crawford’s technique of repair, Assisted Circulation (AC), and now thoracic and thoracoabdominal endografts (TEVAR) have similar O/E ratios of approximately one if no protective adjuncts are used (Figure 2). This observation of parity implies the most important factor in paraplegia is interruption of intercostal blood flow, which lowers perfusion pressure in the axial collateral network reducing spinal cord blood flow and oxygen delivery regardless of technique of repair. This perfusion vulnerability is time dependent and influenced by other variables that positively or negatively affect blood flow, such as cardiac function (the strength of the pump) and arterial perfusion pressure (recruiting collateral flow); oxygen delivery (cardiac index, hemoglobin and pulmonary function); factors that increase ischemic tolerance of the spinal cord while perfusion is low, such as hypothermia and drugs that mitigate ischemic injury (steroids, excitatory neurotransmitters inhibitors and free radical scavengers).
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it is not just Assisted Circulation hypothermic arrest or clamp and sew
The Journal of Thoracic and Cardiovascular Surgery, 2010Co-Authors: Charles W AcherAbstract:We have surgically treated 771 patients for thoracic and thoracoabdominal aortic aneurysms since 1983. Our primary effort has been to develop experimentally validated strategies to reduce paraplegia, renal failure, and mortality in these high-risk patients. This approach has led to a spinal cord protection protocol that has reduced paraplegia risk by 80% (observed/expected ratio = 0.19) with the use of cerebral spinal fluid drainage, moderate hypothermia (31°C–33°C), endorphin receptor antagonist (naloxone), and thiopental burst suppression while optimizing mean arterial pressure (>90 mm Hg) and cardiac index. The elective mortality rate is 2.80% (17% for acute patients), and with rapid renal cooling for renal protection, only 0.88% required permanent dialysis. These results were achieved without the use of Assisted Circulation. We have reattached intercostal arteries since 2005 using preoperative magnetic resonance angiographic localization, but it remains unclear whether intercostal reimplantation reduces paraplegia risk, as we had initially proposed. We strongly believe that a consistent anesthetic and postoperative care protocol uniformly built and applied around these principles greatly enhances our surgical outcomes. We also show that improved outcomes with Assisted Circulation and hypothermic arrest in treatment of thoracoabdominal aortic disease follow similar principles of spinal cord and end-organ protection.
Wilhelm Behringer - One of the best experts on this subject based on the ideXlab platform.
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fructose 1 6 bisphosphate and mk 801 by aortic arch flush for cerebral preservation during exsanguination cardiac arrest of 20 min in dogs an exploratory study
Resuscitation, 2001Co-Authors: Wilhelm Behringer, Rainer Kentner, Samuel A Tisherman, Ann Radovsky, William Stezoski, Jeremy Henchir, Stephan Prueckner, Edwin K Jackson, Peter SafarAbstract:Abstract In our exsanguination cardiac arrest (CA) outcome model in dogs we are systematically exploring suspended animation (SA), i.e. preservation of brain and heart immediately after the onset of CA to enable transport and resuscitative surgery during CA, followed by delayed resuscitation. We have shown in dogs that inducing moderate cerebral hypothermia with an aortic arch flush of 500 ml normal saline solution at 4°C, at start of CA 20 min no-flow, leads to normal functional outcome. We hypothesized that, using the same model, but with the saline flush at 24°C inducing minimal cerebral hypothermia (which would be more readily available in the field), adding either fructose-1,6-bisphosphate (FBP, a more efficient energy substrate) or MK-801 (an N -methyl- d -aspartate (NMDA) receptor blocker) would also achieve normal functional outcome. Dogs (range 19–30 kg) were exsanguinated over 5 min to CA of 20 min no-flow, and resuscitated by closed-chest cardiopulmonary bypass (CPB). They received Assisted Circulation to 2 h, mild systemic hypothermia (34°C) post-CA to 12 h, controlled ventilation to 20 h, and intensive care to 72 h. At CA 2 min, the dogs received an aortic arch flush of 500 ml saline at 24°C by a balloon-tipped catheter, inserted through the femoral artery (control group, n =6). In the FBP group ( n =5), FBP (total 1440 or 4090 mg/kg) was given by flush and with reperfusion. In the MK-801 group ( n =5), MK-801 (2, 4, or 8 mg/kg) was given by flush and with reperfusion. Outcome was assessed in terms of overall performance categories (OPC 1, normal; 2, moderate disability; 3, severe disability; 4, coma; 5, brain death or death), neurologic deficit scores (NDS 0–10%, normal; 100%, brain death), and brain histologic damage scores (HDS, total HDS 0, no damage; >100, extensive damage; 1064, maximal damage). In the control group, one dog achieved OPC 2, one OPC 3, and four OPC 4; in the FBP group, two dogs achieved OPC 3, and three OPC 4; in the MK-801 group, two dogs achieved OPC 3, and three OPC 4 ( P =1.0). Median NDS were 62% (range 8–67) in the control group; 55% (range 34–66) in the FBP group; and 50% (range 26–59) in the MK-801 group ( P =0.2). Median total HDS were 130 (range 56–140) in the control group; 96 (range 64–104) in the FBP group; and 80 (range 34–122) in the MK-801 group ( P =0.2). There was no difference in regional HDS between groups. We conclude that neither FBP nor MK-801 by aortic arch flush at the start of CA, plus an additional i.v. infusion of the same drug during reperfusion, can provide cerebral preservation during CA 20 min no-flow. Other drugs and drug-combinations should be tested with this model in search for a breakthrough effect.
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thiopental and phenytoin by aortic arch flush for cerebral preservation during exsanguination cardiac arrest of 20 minutes in dogs an exploratory study
Resuscitation, 2001Co-Authors: Wilhelm Behringer, Rainer Kentner, Samuel A Tisherman, Ann Radovsky, William Stezoski, Jeremy Henchir, Stephan Prueckner, Peter SafarAbstract:Abstract We are systematically exploring in our exsanguination cardiac arrest (CA) outcome model in dogs suspended animation (SA), i.e. immediate preservation of brain and heart for resuscitative surgery during CA, with delayed resuscitation. We have shown in dogs that inducing moderate cerebral hypothermia with an aortic arch flush of 500 ml normal saline solution of 4°C, at start of CA 20 min no-flow, leads to normal functional outcome. We hypothesized that, using the same model, adding thiopental (or even better thiopental plus phenytoin) to the flush at ambient temperature (24°C), which would be more readily available in the field, will also achieve normal functional outcome. Thirty dogs (20–28 kg) were exsanguinated over 5 min to CA of 20 min no-flow, and resuscitated by closed-chest cardiopulmonary bypass. They received Assisted Circulation to 2 h, 34°C post-CA to 12 h, controlled ventilation to 20 h, and intensive care to 72 h. At CA 2 min, the dogs received an aortic arch flush of 500 ml saline at 24°C by a balloon-tipped catheter, inserted through the femoral artery (control group 1, n =14). In group 2 ( n =9), thiopental (variable total doses of 15–120 mg/kg) was added to the flush and given with reperfusion. In group 3 ( n =7), thiopental (15 or 45 mg/kg) plus phenytoin (10, 20, or 30 mg/kg) was given by flush and with reperfusion. Outcome was assessed in terms of overall performance categories (OPC 1, normal; 2, moderate disability; 3, severe disability; 4, coma; 5, brain death), neurologic deficit scores (NDS 0–10%, normal; 100%, brain death), and histologic deficit scores (HDS, total and regional). The flush reduced tympanic temperature to about 36°C in all groups. In control group 1, one dog achieved OPC 1, three OPC 2, six OPC 3, and four OPC 4. In thiopental group 2, two dogs achieved OPC 1, two OPC 3, and five OPC 4. In thiopental/phenytoin group 3, one dog achieved OPC 1, two OPC 3, and four OPC 4 ( p =0.5). Median NDS were 36% (IQR 22–62%) in group 1; 51% (IQR 22–56%) in group 2; and 55% (IQR 38–59%) in group 3 ( p =0.7). Median total HDS were 67 (IQR 56–127) in group 1; 60 (IQR 52–138) in group 2; and 76 (IQR 48–132) in group 3 ( p =1.0). Thiopental and thiopental/phenytoin dogs achieved significantly lower HDS only in the putamen. Thiopental in large doses caused side effects. We conclude that neither thiopental alone nor thiopental plus phenytoin by flush, with or without additional intravenous infusion, can consistently provide ‘clinically significant' cerebral preservation for 20 min no-flow. Other drugs and drug-combinations should be tested with this model in search for a breakthrough effect.
