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Impaired left ventricular relaxation and filling is an important pathophysiologic mechanism in hypertrophic cardiomyopathy. To determine whether isoproterenol, known to improve relaxation in isolated cardiac muscle, could favorably modify this effect, we assessed simultaneous left ventricular volume and regional systolic asynchrony (by radionuclide angiography), left ventricular pressure (by micromanometer catheters), and lactate metabolism in 12 patients with hypertrophic cardiomyopathy. Pressure-volume relations were studied during atrial pacing stress to induce myocardial ischemia and during isoproterenol infusion to similar heart rates. Angina occurred in 10 patients with pacing and in 11 patients during isoproterenol infusion; lactate consumption was reduced in nine patients during isoproterenol compared with pacing, including five patients who produced lactate with isoproterenol. During isoproterenol compared with pacing, peak left ventricular pressure was higher (205 +/- 33 vs. 142 +/- 21 mm Hg, p less than 0.001), ejection fraction was higher (77 +/- 10% vs. 71 +/- 12%, p less than 0.02), and regional systolic nonuniformity was diminished. Despite ischemia, these changes in load and nonuniformity during isoproterenol were associated with enhanced diastolic function compared with pacing tachycardia: isoproterenol reduced T 1/2, the half-time of pressure decline after peak negative dP/dt (from 46 +/- 10 to 33 +/- 6 msec, p less than 0.001), shifted the diastolic pressure-volume curve downward and rightward in 10 of 12 patients, and increased end-diastolic volume (from 77 +/- 18% to 100 +/- 11% of control values, p less than 0.001) with no change in end-diastolic pressure (19 +/- 7 to 19 +/- 5 mm Hg, p = NS). Thus, despite ischemia, isoproterenol improved left ventricular relaxation and filling compared with tachycardia in the absence of beta-adrenergic stimulation. Although isoproterenol is detrimental in hypertrophic cardiomyopathy by provoking ischemia, these data suggest that the adverse effects of ischemia on ventricular relaxation and distensibility may be alleviated by beta-adrenergic stimulation, possibly as a result of enhanced inactivation and restored load sensitivity.

circulation

Beta-adrenergic stimulation with isoproterenol enhances left ventricular diastolic performance in hypertrophic cardiomyopathy despite potentiation of myocardial ischemia. Comparison to rapid atrial pacing.