Effects of intrinsic sympathomimetic activity on cardiac function during variations in preload

The effect of intrinsic sympathomimetic activity (ISA) on ventricular function during wide variations in preload was investigated in 10 healthy men. Hemodynamic and ventricular performance responses were measured during minute 90 of 5° head-down tilt (TILT) and -40 Torr lower body negative pressure (LBNP) after bolus injections of either saline, pindolol (0.01 mg/kg) or propranolol (0.1 mg/kg). Differences in response between drugs were attributed to ISA effects. Heart rate, chamber volumes, ejection fraction, mean velocity of circumferential fiber shortening (V(cf)) and diastolic and systolic wall stress were determined by M-mode echocardiographic and electrocardiographic measurements. Propranolol decreased V(cf) and heart rate (p < 0.05) relative to both saline and pindolol during all preload conditions, whereas the responses during pindolol treatment were not different from those during saline. Systolic and diastolic wall stress were increased (p < 0.05) by propranolol treatment regardless of preload. Both systolic and diastolic wall stress increased > 12% during TILT with propranolol while no changes were observed with saline (-1%) or pindolol (+2%). These data indicate that the noncardiodepressive effects of β-blockade with ISA persist regardless of variations in preload. In addition, increases in wall stress by β-blockade (propranolol), particularly during increases in preload (TILT), are prevented by blockade with ISA (pindolol). Thus, under certain conditions, pindolol does not elicit the wall-stressrelated increases in myocardial oxygen demand that occur with propranolol treatment.