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Organ arrest, Protection and Preservation: Natural Hibernation to Cardiac Surgery

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Organ Arrest, Protection and Preservation: Natural Hibernation to Cardiac Surgery

 

Geoffrey P Dobson PhD
Dept Physiology and Pharmacology
Molecular Science Building
School of Biomedical Sciences
James Cook University, Townsville
Queensland, Australia, 4811

 

 

Key Words: hibernation, torpor, cardioplegia, organ preservation, xenotransplantation, heart, adenosine, lidocaine, hibernating myocardium, opioids

 

Abstract:

 

Cardiac surgery continues to be limited by an inability to achieve complete myocardial protection. This paper considers the following questions: 1) what lessons can be learned from mammalian hibernators to improve current methods of human myocardial arrest, protection and preservation? and 2)  can the human heart be pharmacologically manipulated during acute global ischemia to act more like the heart of a hibernating mammal?  After reviewing the major entropy-slowing strategies of hibernation, a major player identified in the armortarium is maintenance of the membrane potential. The resting membrane potential of the hibernator’s heart  appears to be maintained close to its pre-torpid state of around –85 mV.   In the clinical setting, 99% of all surgical cardioplegia and preservation solutions employ high potassium (16 to 125 mM) which depolarises the membrane voltage from –85 to around –50 mV.  In the last decade, depolarisng potassium cardioplegia has been increasingly linked to myocyte and microvascular damage leading to functional loss during reperfusion.  Our recent work has borrowed from hibernation biology and focused on a very different cardioplegia which ‘clamps’ the membrane near its resting potential and thereby depresses O₂ consumption by about 90%.  The new ‘polarising’ cardioplegia incorporates adenosine and lidocaine as the arresting combination, not high potassium.  Early  studies in the isolated rat heart show that AL cardioplegia delivered at 37°C can arrest the heart for up to 4 hours with 70-80% recovery of the cardiac output, 85-100% recovery of heart rate, systolic pressure and rate-pressure product and 70-80% of baseline coronary flows.  Only 14% of hearts arrested with a gold-standard cardioplegia St. Thomas' solution No 2 survived after 4 hours.  In conclusion, maintenance of the myocardial membrane potential near or close to its resting state appears to be an important feature of the hibernator’s heart that may find great utility in  surgical arrest and cellular preservation strategies.  Identifying and safely turning ‘off’ and ‘on’ the entropy-slowing genes to downregulate the hibernator’s heart and applying this to human organs and tissues remains a major challenge for future genomics and proteomics.