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Organ arrest, protection and preservation: natural hibernation to cardiac surgery

https://doi.org/10.1016/j.cbpc.2004.06.002Get rights and content

Abstract

Cardiac surgery continues to be limited by an inability to achieve complete myocardial protection from ischemia-reperfusion injury. 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 open-heart surgery, 99% of all surgical heart arrest solutions (cardioplegia) employ high potassium (>16 mM) which depolarises the membrane voltage from −85 to around −50 mV. However, depolarising potassium cardioplegia has been increasingly linked to myocyte and microvascular damage leading to functional loss during reperfusion. Our recent work has been borrowed from hibernation biology and is focused on a very different arrest strategy which ‘clamps’ the membrane near its resting potential and depresses O2 consumption from baseline by about 90%. The new ‘polarising’ cardioplegia incorporates adenosine and lidocaine (AL) as the arresting combination, not high potassium. Studies in the isolated rat heart show that AL cardioplegia delivered at 37 °C can arrest the heart for up to 4 h 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 crystalloid St. Thomas' solution No. 2 cardioplegia survived after 4 h. 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 down-regulate the hibernator's heart and applying this to human organs and tissues remains a major challenge for future genomics and proteomics.

Section snippets

Foreword

Peter Hochachka was inspirational as a scientist and as a person. I will always cherish his infectious enthusiasm for science, his keen sense of humour, and his tireless search for the unifying concepts that underpin the spectacular diversity of life. Many of these concepts, and other ‘news and views’ stories in science, were topics of lively discussions with Peter during the lab's morning and afternoon walks to the University of British Columbia's (UBC) Faculty club for tea or coffee. It was

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    The papers in this volume are dedicated to the memory of our friend and mentor, Peter W. Hochachka, whose intelligence, curiosity, enthusiasm, and encouragement catalyzed research in diverse areas of comparative physiology and biochemistry and taught us that following one's curiosity in science can be both productive and fun.

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