Improved cardiac function following hormonal therapy in brain dead pigs: relevance to organ donation |
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| Authors: | D Novitzky W N Wicomb D K Cooper M A Tjaalgard |
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| Institution: | 1. Department of Medicine, MacKay Medical College, New Taipei City, Taiwan;2. Division of Cardiology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan;3. Ph.D. Program for Cancer Molecular Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University and Academia Sinica, Taipei, Taiwan;4. Department of Pharmacy, MacKay Memorial Hospital, Taipei, Taiwan;5. Health and Clinical Research Data Center, College of Public Health, Taipei Medical University, Taipei, Taiwan;6. School of Health Care Administration, College of Management, Taipei Medical University, Taipei, Taiwan;1. Institute of Biomedical Research of Salamanca (IBSAL), Salamanca, Spain;2. Fundación Instituto de Estudios de Ciencias de la Salud de Castilla y León (IECSCYL), Soria, Spain;3. Department of Physiology and Pharmacology, University of Salamanca (USAL), Salamanca, Spain;4. Departments of Applied Mathematics and Biology, and Schools of Computer Science and Pharmacology, University of Waterloo, Waterloo, Ontario, Canada;5. Group of Translational Research on Renal and Cardiovascular Diseases (TRECARD), Salamanca, Spain, National Network for Kidney Research REDINREN, RD016/0009/0025, Instituto de Salud Carlos III, Madrid, Spain;6. Group of Biomedical Research on Critical Care (BioCritic), Valladolid, Spain;7. Disease and Theranostic Modeling (DisMOD) International Consortium, Salamanca, Spain |
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| Abstract: | Deterioration of function in brain dead baboons is associated with depletion of both myocardial energy stores and certain circulating hormones, notably thyroxine, cortisol, and insulin. We have therefore investigated the effect of the administration of these three hormones to the brain dead pig; their value has been assessed on both the freshly excised and stored donor heart. Brain death was induced by ligation of the two arteries to the upper part of the body which arise from the aortic arch. Storage of selected hearts was by continuous hypothermic perfusion for 20 to 24 hr. Hearts were biopsied for estimation of adenosine triphosphate, creatine phosphate, lactate, and glycogen, and were subsequently functionally tested. Six groups of pigs were studied. Hearts were tested from control pigs which had not undergone brain death (A1), from brain dead pigs which had received intravenous fluid and inotropic support for 4 hr (B1), and from brain dead pigs which had in addition received 2 hr of hormonal therapy (thyroxine 2 micrograms cortisol 100 mg, and insulin 5-10 IU hourly) (C1). A further 3 groups (A2-C2) underwent management identical to A1-C1, but in addition the hearts were stored for 24 hr. Brain death in pigs was followed by a consumption of myocardial energy stores, despite anaerobic glycolysis; this was associated with reduced myocardial function. The administration of hormones to the brain dead pig led to some replenishment of myocardial energy and glycogen reserves and reduction in lactate, with associated improvement in hemodynamic function. A period of hypothermic perfusion storage appeared to reverse the anaerobic metabolism occurring in the heart in the nonhormonally treated brain dead animal, though not in the hormonally treated animal, and led to replenishment of glycogen reserves in nontreated animals. The observation that both better function and an increase in myocardial energy stores occurred in hormonally treated, stored hearts, even though perfusate lactate dehydrogenase rose to significantly higher levels during hypothermic perfusion storage, and tissue lactate levels remained high, suggests that thyroxine promotes both aerobic and anaerobic metabolism in brain dead animals. |
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