Isoproterenol-Induced Cardiac Failure in the Spontaneously Hypertensive Rat

Abstract

Abstract

Thirty-one age-matched, conscious, virgin, male Sprague-Dawley rats and spontaneously hypertensive rats (SHRs) were individually injected with a single subcutaneous dose of 85 mg/kg dl-isoproterenol to determine the degree and time course of druginduced cardiac failure and functional recovery. At 24 hr and 1 week postisoproterenol, rats were anesthetized and prepared for the recording of cardiac output and arterial pressure. Calculated cardiac index was used to determine normal cardiac function. Following that measurement, a 2-min, 15.3 ml/min infusion of Tyrode's solution was performed via a right jugular vein cannula. Volume-loaded peak cardiac outputs and peak stroke volumes were also used as indices of cardiac function. Twenty-four hours after the injection of isoproterenol to the normotensive Sprague-Dawley rats, cardiac failure was evident only during the stress of volume loading. Normal cardiac index was unaffected, but peak cardiac output and peak stroke volume were depressed. By 1 week after isoproterenol, the volume loaded measures of cardiac function had returned to normal. Interestingly, by 1 week postisoproterenol, total peripheral resistance was reduced. This reduced vascular resistance may have aided myocardial repair. At 24 hr postisoproterenol, the volume loaded peak cardiac outputs and peak stroke volumes in the SHRs were reduced to the same degree as in the Sprague-Dawley rats. Here, also, no change in normal cardiac index occurred. In the SHRs, however, total peripheral resistances were elevated at both 24 hr and 1 week. These increases in resistance appeared to impair the myocardial healing process, as both normal cardiac index and volume-loaded peak cardiac output and peak stroke volume were depressed at 1 week postisoproterenol. In normotensive and hypertensive rats, different vascular responses to isoproterenol or its initial cardiac effects may determine the duration and eventual degree of cardiac failure.