Aims We investigated whether cooling instituted by total liquid ventilation (TLV) improves cardiac and mitochondrial functions in rabbits submitted to lethal myocardial ischemia. Methods Rabbits were instrumented with a coronary artery occluder and myocardial ultrasonic crystals for assessment of segment length shortening. Two weeks later they were reanesthetized and underwent either a normothermic 30-min coronary artery occlusion (CAO) (Control group, n=7) or a comparable CAO with cooling initiated after 5-min of occlusion. Cooling was initiated by a 10-min hypothermic TLV episode and then maintained by ice-filled cold blanket put over the skin (Hypo-TLV group, n=6). A last group underwent normothermic TLV during CAO (Normo-TLV group, n=6). Wall motion was measured in the conscious state over 3 days of reperfusion before infarct size evaluation and histology. Additional experiments were done in anesthetized rabbits for myocardial sampling at the end of the ischemic period (electron microscopy and mitochondrial studies). Results The cooling procedure induced a rapid decrease in heart temperature to a target 32–34°C. Post-ischemic contractile dysfunction and infarct sizes were significantly decreased in Hypo-TLV vs Control and Normo-TLV (e.g., 4±1, 39±2 and 42±5% of region at risk for infarct sizes, respectively). Mitochondrial function was improved by Hypo-TLV regarding ADP-stimulated respiration and calcium-induced opening of mitochondrial permeability transition pore (mPTP). Histology and electron microscopy revealed also better preservation of lung and cardiomyocyte ultrastructure in Hypo-TLV as compared to Control, respectively. Conclusion Institution of hypothermia by TLV during ischemia not only reduces infarct size but also abolishes most consequences of ischemia such as post-ischemic contractile dysfunction and calcium-induced opening of mPTP.

Background-In animal models of cardiac arrest, the benefit afforded by hypothermia is closely linked to the rapidity of the decrease in body temperature after resuscitation. Because total liquid ventilation (TLV) with temperature-controlled perfluorocarbons induces a very rapid and generalized cooling, we aimed to determine whether this could limit the post-cardiac arrest syndrome in a rabbit model. We especially focused on neurological, cardiac, pulmonary, liver and kidney dysfunctions. Methods and Results-Anesthetized rabbits were submitted to either 5 or 10 minutes of untreated ventricular fibrillation.After cardiopulmonary resuscitation and resumption of a spontaneous circulation, the animals underwent either normothermic life support (control) or therapeutic hypothermia induced by TLV. The latter procedure decreased esophageal and tympanic temperatures to 32°C to 33°C within only 10 minutes. After rewarming, the animals submitted to TLV exhibited an attenuated neurological dysfunction and decreased mortality 7 days later compared with control. The neuroprotective effect of TLV was confirmed by a significant reduction in brain histological damages. We also observed limitation of myocardial necrosis, along with a decrease in troponin I release and a reduced myocardial caspase 3 activity, with TLV. The beneficial effects of TLV were directly related to the rapidity of hypothermia induction because neither conventional cooling (cold saline infusion plus external cooling) nor normothermic TLV elicited a similar protection. Conclusions-Ultrafast cooling instituted by TLV exerts potent neurological and cardiac protection in an experimental model of cardiac arrest in rabbits. This could be a relevant approach to provide a global and protective hypothermia against the post-cardiac arrest syndrome. (Circulation. 2011;124:901-911.)Key Words: cardiopulmonary resuscitation Ⅲ fibrillation Ⅲ heart arrest Ⅲ ischemia Ⅲ ventilation I nstitution of mild therapeutic hypothermia (32°C to 34°C) during 24 to 36 hours after resuscitation is known to improve survival and neurological recovery in comatose survivors of cardiac arrest. 1,2 However, experimental studies in dogs, 3,4 pigs, 5,6 and rodents 7,8 demonstrated that the neuroprotection afforded by hypothermia was related to the rapidity of the decrease in body temperature after resuscitation. When achieved rapidly, hypothermia could also be beneficial for other organs because, for example, it can also be potently cardioprotective during myocardial ischemia. 9 -12 Accordingly, many strategies were proposed to afford such a rapid hypothermia, including intravenous infusion of cold fluid 13 and endovascular 14 or intranasal cooling. 15,16 Clinical Perspective on p 911Another strategy that can experimentally provide very rapid and generalized cooling is liquid ventilation of the lungs with temperature-controlled perfluorocarbons. 11,[17][18][19][20][21][22] These liquids can use the lungs as heat exchangers while maintaining normal gas exchanges. 18 -20 In addition, this ven...