HYPOVENTILATION PRIOR TO ISCHEMIA PRECONDITIONS RAT MYOCARDIUM

Repetitive episodes of brief regional ischemia have been shown to reduce the severity of life-threatening ventricular anhythrnias and infarct size that occur during prolonged occlusion of the coronary artery. This phenomenon is known as ischemic preconditioning. During studies in anesthetized, open chest Wistar rats, we accidentally observed that poorly ventilated animals had a reduced severity of ischemic arrhythmias. Therefore, we wished to (1) find out whether acute hypoventilation prior to coronary ligation affords protection to the ischemic rat hearts, and (2) to evaluate the effect of recovery period of normoventilation between hypoventilation and prolonged ischemia on the degree of protection. Male Wistar rats were anesthetized and prepared for left coronary artery ligation. Following a left thoracotomy, artificial respiration was immediately started with room air of 1.5 mLll00g and 54 strokes/min. Analysis of ventricular anhythrnias during 30 min occlusion was performed. In some experiments 30 min. sustained ischemia followed by 2 hours reperfusion and then the percentage of infarct size was measured. The reduction of volume of ventilation to 1.1 and 0.7 mL/l00g only for 10 min immediately prior to coronary artery occlusion resulted in a marked decrease (p<0.01) in the total number of ventricular ectopic beats from 1336±100 in control to 485 ±75 and 328±51, respectively, mainly by reduction of beats occurring as ventricular tachycardia (VT). Also, the time spent in VT and in reversible ventricular fibrillation was reduced significantly (p<0.01 and p<O.OOI, respectively). There was no mortality in animals subjected to hypoventilation, while 33% of control rats died due to irreversible VF. Hypoventilation also limited the infarct size very considerably (p<0.0 1) from 43.4 ±2.9% in control animals to 12.1 ± 1 % and 9.1 ±2.9% in hypoventilated rats. The presence of an intervening period of normoventilation between hypoventilation and prolonged ischemia did not affect the antianhythrnic effect of hypoventilation but abolished the protective effects of hypoventilated preconditioning against the infarction. These results may suggest that the heart can be preconditioned by hypoventilation prior to prolonged ischemia despite the lack of an intervening period of normoventilation.