Rapid cooling preserves the ischaemic myocardium against mitochondrial damage and left ventricular dysfunction
Open Access
- 5 February 2009
- journal article
- research article
- Published by Oxford University Press (OUP) in Cardiovascular Research
- Vol. 83 (2), 345-353
- https://doi.org/10.1093/cvr/cvp046
Abstract
We investigated whether rapid cooling instituted by total liquid ventilation (TLV) improves cardiac and mitochondrial function in rabbits submitted to ischaemia-reperfusion. Rabbits were chronically instrumented with a coronary artery occluder and myocardial ultrasonic crystals for assessment of segment length-shortening. Two weeks later they were re-anaesthetized and underwent either a normothermic 30-min coronary artery occlusion (CAO) (Control group, n = 7) or a comparable CAO with cooling initiated by a 10-min hypothermic TLV and maintained by a cold blanket placed on the skin. Cooling was initiated after 5 or 15 min of CAO (Hypo-TLV and Hypo-TLV15′ groups, n = 6 and 5, respectively). A last group underwent normothermic TLV during CAO (Normo-TLV group, n = 6). Wall motion was measured in the conscious state over three days of reperfusion before infarct size evaluation and histology. Additional experiments were done for myocardial sampling in anaesthetized rabbits for mitochondrial studies. The Hypo-TLV procedure induced a rapid decrease in myocardial temperature to 32–34°C. Throughout reperfusion, segment length-shortening was significantly increased in Hypo-TLV and Hypo-TLV15′ vs. Control and Normo-TLV (15.1 ± 3.3%, 16.4 ± 2.3%, 1.8 ± 0.6%, and 1.1 ± 0.8% at 72 h, respectively). Infarct sizes were also considerably attenuated in Hypo-TLV and Hypo-TLV15′ vs. Control and Normo-TLV (4 ± 1%, 11 ± 5%, 39 ± 2%, and 42 ± 5% infarction of risk zones, respectively). Mitochondrial function in myocardial samples obtained at the end of ischaemia or after 10 min of reperfusion was improved by Hypo-TLV with respect to ADP-stimulated respiration and calcium-induced opening of mitochondrial permeability transition pores (mPTP). Calcium concentration opening mPTP was, e.g., increased at the end of ischaemia in the risk zone in Hypo-TLV vs. Control (157 ± 12 vs. 86 ± 12 µM). Histology and electron microscopy also revealed better preservation of lungs and of cardiomyocyte ultrastructure in Hypo-TLV when compared with Control. Institution of rapid cooling by TLV during ischaemia reduces infarct size as well as other sequelae of ischaemia, such as post-ischaemic contractile and mitochondrial dysfunction.This publication has 32 references indexed in Scilit:
- Cardioprotective Effect of Morphine and a Blocker of Glycogen Synthase Kinase 3β, SB216763 [3-(2,4-Dichlorophenyl)-4(1-methyl-1H-indol-3-yl)-1H-pyrrole-2,5-dione], via Inhibition of the Mitochondrial Permeability Transition PoreThe Journal of pharmacology and experimental therapeutics, 2008
- Mitochondrial respiration and membrane potential after low-flow ischemia are not affected by ischemic preconditioningJournal of Molecular and Cellular Cardiology, 2007
- Prevention of the ischemia-induced decrease in mitochondrial Tom20 content by ischemic preconditioningJournal of Molecular and Cellular Cardiology, 2006
- Mitochondrial Ca2+ uptake during simulated ischemia does not affect permeability transition pore opening upon simulated reperfusion?Cardiovascular Research, 2006
- Effects of cold cardioplegia on pH, Na, and Ca in newborn rabbit heartsAmerican Journal of Physiology-Heart and Circulatory Physiology, 2006
- A pilot study: The Noninvasive Surface Cooling Thermoregulatory System for Mild Hypothermia Induction in Acute Myocardial Infarction (The NICAMI Study)American Heart Journal, 2005
- Preconditioning of salvaged myocardium in conscious rabbits with postinfarction dysfunctionAmerican Journal of Physiology-Heart and Circulatory Physiology, 2005
- Ischaemic Preconditioning Inhibits Opening of Mitochondrial Permeability Transition Pores in the Reperfused Rat HeartJournal Of Physiology-London, 2003
- Physiologic Characteristics of Cold Perfluorocarbon-Induced Hypothermia During Partial Liquid Ventilation in Normal RabbitsAnesthesia & Analgesia, 2002
- Prolonged studies of perfluorocarbon associated gas exchange and of the resumption of conventional mechanical ventilationCritical Care Medicine, 1995