PROTECTIVE EFFECT OF ENDOGENOUS CATECHOLAMINE DEPLETION AGAINST HYPOXIC AND RE-OXYGENATION DAMAGE IN ISOLATED RAT-HEART - AN ULTRASTRUCTURAL-STUDY

Abstract

Using isolated, Langendorff-perfused rat hearts, left ventricular wall myocardial ultrastructural modifications appearing under conditions of severe hypoxia and subsequent reoxygenation were studied. Hypoxia was produced by gassing perfusate with N (aortic O2 partial pressure < 8 mmHg). Whether or not endogenous catecholamines might be involved in the development of hypoxia-induced tissue damage in the isolated heart and subsequent reoxygenation were studied using hearts isolated from normal untreated rats, and rats in which endogenous catecholamine levels were reduced to .apprx. 15% of control values by reserpine. Hearts were fixed by glutaraldehyde perfusion either after 10 min of control equilibration perfusion (with O2 and glucose), or after 100 min hypoxia (N, glucose-free, high K), or after hypoxia plus reoxygenation (O2, substrate-free, high K). After fixation, dehydration, embedding in araldite, 6-8 blocks/heart were sectioned. The sections were doubly stained and examined under the EM. Control hearts perfused for a 10 min equilibration period exhibited well preserved and normal ultrastructure. After severe hypoxia without substrate, untreated hearts exhibited ultrastructural alterations, the degree of which was consistently and severely increased by reoxygenation. In reserpine pretreated hearts with a marked increase in the number of glycogen granules hypoxia did not induce morphological alterations. Even after 100 min hypoxia, some glycogen granules were still visible. Myocardial ultrastructure was not altered by reoxygenation. In reserpine pretreated hearts, anaerobic metabolism of glycogen may be sufficient to sustain enough glycolytic ATP production during 100 min of O2 deprivation. Such a preservation of myocardial high-energy phosphates could help myocardial cells to maintain their structural integrity.