REGRESSION OF VENTRICULAR HYPERTROPHY ABOLISHES CARDIOCYTE VULNERABILITY TO ACUTE-HYPOXIA

Left ventricular hypertrophy (LVH) secondary to a pressure overload commonly leads to perfusion abnormalities that may limit oxygen delivery to the myocardium and, therefore, result in cardiocyte intracellular damage. We initiated this study to test the hypothesis that the increased vulnerability of the hypertrophied left ventricle to acute hypoxia is minimized when LVH regresses and maximal coronary flow returns to normal. Six‐month‐old spontaneously hypertensive (SHR) and normotensive Wistar‐Kyoto (WKY) rats were divided into control or one of two antihypertensive treatment groups. A 3‐month treatment consisted of captopril (75‐100 mg/kg) or hydralazine (80‐160 mg/L) with hydrochlorothiazide (500 mg/L) added to each therapy. At the conclusion of the treatment period, the rats were administered a 7% O2‐93% N2 gas mixture for 20 minutes to induce acute hypoxic stress during which time hemodynamics, blood gases, and pH were monitored. The heart was then rapidly fixed by vascular perfusion and prepared for electron microscopy. Captopril and hydralazine were equally effective in lowering arterial pressure in both strains, but only captopril was efficacious in reducing heart mass. Hypoxia‐induced changes in hemodynamics, blood gases, and pH were similar in all of the groups; PO2 was decreased by about 70%. The electron micrographs revealed that the hypertrophied left ventricle consistently showed morphologic evidence of hypoxic damage (as indicated by T‐tubular swelling, intracellular edema, and mitochondrial alterations); in contrast hypoxia had little effect on the non‐hypertrophied ventricle. Captopril treatment resulted in a disappearance of the lability to hypoxic damage while hydralazine caused a small reduction in the frequency of hypoxic damage. In conclusion, reversal of hypertension alone had little effect on cardiocyte vulnerability to acute hypoxia, but reversal of hypertension in conjunction with regression of LVH prevented the intracellular damage characteristic of hypoxia. Thus, LVH and its associated maximal perfusion decrement, rather than hypertension per se, underlie cardiocyte vulnerability to hypoxic stress. Copyright © 1990 Wiley‐Liss, Inc.