Cardiovascular Research Advance Access first published online on February 5, 2009
This version [Corrected Proof] published online on February 24, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp046
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Rapid cooling preserves the ischaemic myocardium against mitochondrial damage and left ventricular dysfunction
1 INSERM U955, Equipe 3, 94010 Créteil cedex, France
2 Université Paris 12, Faculté de Médecine, Créteil F-94010, France
3 Ecole Nationale Vétérinaire d'Alfort, Maisons-Alfort F-94704, France
4 INSERM UMRs872, Institut des Cordeliers, Paris F-75005, France
5 Department of Physiology, University of South Alabama, College of Medicine, Mobile, AL 36688, USA
6 Department of Medicine, University of South Alabama, College of Medicine, Mobile, AL36688, USA
* Corresponding author. Tel: +33 1 49 81 36 51; fax: +33 1 48 98 17 77. E-mail address: alain.berdeaux{at}inserm.fr
Aims: We investigated whether rapid cooling instituted by total liquid ventilation (TLV) improves cardiac and mitochondrial function in rabbits submitted to ischaemia-reperfusion.
Methods and results: 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.
Conclusion: 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.
KEYWORDS Cooling; Contractile function; Mitochondria; Infarction; Total liquid ventilation
Time of primary review: 25 days
Both the authors contributed equally to this work.