Myocardial Damage Induced by Uncontrolled Reoxygenation

Abstract

To evaluate myocardial impairment induced by uncontrolled reoxygenation, the effects of hypoxia-reoxygenation were compared with ischemia-reperfusion in isolated rat hearts. After stabilization, 2 groups (n = 8) of Langendorff-perfused rat hearts were exposed to 40 minutes of ischemia (10% of baseline flow) or hypoxia (10% of baseline oxygen content) followed by a sudden return to baseline conditions (reperfusion or reoxygenation). The O 2 content was identical for the two groups during baseline conditions, O 2 shortage, and O 2 readmission. Metabolic (lactate production) and functional parameters (heart rate, peak systolic pressure, left ventricular developed pressure, maximal contraction and relaxation rates, end-diastolic pressure, coronary perfusion pressure) were recorded at the end of stabilization, after O 2 deficiency, and after 2 minutes of reoxygenation. Systolic function was significantly depressed after ischemia (p < 0.0001) but completely recovered to baseline values after 2 minutes of reperfusion. In contrast, systolic function was less severely depressed after hypoxia but failed to return to baseline after 2 minutes of reoxygenation. Diastolic function, unchanged during ischemiareperfusion, remained significantly impaired during hypoxia-reoxygenation.

Chronic hypoxia: A model for cyanotic congenital heart defects

“…Possibly the decreased ventricular compliance and impaired contractility are due to the hypoxia-induced calcium load, which is further increased by the sudden reoxygenation. In this regard, we demonstrated, in previous studies, the occurrence of reoxygenation injury within the first few minutes of full oxygen readmission, 15 as well as the possibility of reducing the reoxygenation injury by reducing the rate of reoxygenation, 14 as routinely performed in our clinical practice. 24 Reduced coronary vascular resistance in hypoxic hearts during the hypoxic perfusion, as well as during the reoxygenation, shows that chronic hypoxia induces coronary vasodilation.…”

“…Children with cardiac malformations are often cyanotic, and the surgical intervention for cyanotic congenital heart defects is hindered by greater mortality and morbidity than in the corresponding treatment in noncyanotic hearts. 4,17 This feature may arise from the injury induced by acute reoxygenation at the onset of cardiopulmonary bypass, [13][14][15][16]19 with free radicals as a major mediator in the hypoxiareoxygenation injury. 13,16 Despite the fact that the vast majority of experimental studies, including ours, [5][6][7] have evaluated the effects of acute hypoxia on the cardiovascular system, within the last few years, an increasing number of studies concerned chronic hypoxia, 8,9,11,12,20 and it is now evident that hypoxia produces long-term effects that could profoundly influence the myocardial metabolism and function.…”

“…In this context, however, there are at least 2 instances in which the hearts may be suddenly reoxygenated prematurely, thereby undergoing reoxygenation injury. [13][14][15][16] First, the classic design of the hypoxic or hypobaric chamber usually does not allow for daily maintenance, and therefore during feeding, as well as during cleaning, the animals are exposed to room air, with subsequent intermittent reoxygenation. Second, the hearts are generally perfused with oxygenated media to obtain baseline values; this operation implies that reoxygenation injury occurs before the baseline hypoxic values are taken.…”