BACKGROUND: The effectiveness of beta-blocker therapy for dilated cardiomyopathy (DCM) may be attributed to the inhibition of detrimental effects on the failing heart of sympathetic stimulation during exertion. However, the harmful effects of activity as well as the protective effects of beta-blockers have not been demonstrated. Diastolic ventricular function is known to be sensitive to transient myocardial metabolic insult. In this study, we investigated the effect of modest exercise with or without beta-blockade on the diastolic left ventricular pressure-volume (P-V) relation in patients with DCM. METHODS AND RESULTS: The diastolic left ventricular P-V relation was obtained by high-fidelity pressure measurements and digital subtraction left ventriculography at rest and immediately after modest supine bicycle exercise in 12 patients with DCM. The effects of intravenous administration of 0.1 mg/kg propranolol on resting and exercise P-V relations were studied. The end-diastolic and lowest left ventricular pressures were significantly elevated by exercise (20 +/- 9 to 32 +/- 13 mm Hg, P < .01, and 12 +/- 6 to 21 +/- 11 mm Hg, P < .01, respectively) despite insignificant changes in left ventricular volumes. The administration of propranolol did not alter the resting diastolic P-V relation. However, propranolol significantly attenuated the exercise-induced upward shift of the diastolic P-V relation despite a significant increase in end-diastolic volume. The significant upward shift and attenuation by propranolol were also observed even when the left ventricular pressure was corrected by the subtraction of right atrial pressure. CONCLUSIONS: These results indicate that even modest exercise exerts detrimental effects on diastolic left ventricular function of the failing heart through beta-adrenergic stimulation. The clinical effectiveness of beta-blocker therapy in patients with DCM can be attributed in part to the inhibition of detrimental myocardial effects of sympathetic stimulation during daily activity.
BACKGROUND: The effectiveness of beta-blocker therapy for dilated cardiomyopathy (DCM) may be attributed to the inhibition of detrimental effects on the failing heart of sympathetic stimulation during exertion. However, the harmful effects of activity as well as the protective effects of beta-blockers have not been demonstrated. Diastolic ventricular function is known to be sensitive to transient myocardial metabolic insult. In this study, we investigated the effect of modest exercise with or without beta-blockade on the diastolic left ventricular pressure-volume (P-V) relation in patients with DCM. METHODS AND RESULTS: The diastolic left ventricular P-V relation was obtained by high-fidelity pressure measurements and digital subtraction left ventriculography at rest and immediately after modest supine bicycle exercise in 12 patients with DCM. The effects of intravenous administration of 0.1 mg/kg propranolol on resting and exercise P-V relations were studied. The end-diastolic and lowest left ventricular pressures were significantly elevated by exercise (20 +/- 9 to 32 +/- 13 mm Hg, P < .01, and 12 +/- 6 to 21 +/- 11 mm Hg, P < .01, respectively) despite insignificant changes in left ventricular volumes. The administration of propranolol did not alter the resting diastolic P-V relation. However, propranolol significantly attenuated the exercise-induced upward shift of the diastolic P-V relation despite a significant increase in end-diastolic volume. The significant upward shift and attenuation by propranolol were also observed even when the left ventricular pressure was corrected by the subtraction of right atrial pressure. CONCLUSIONS: These results indicate that even modest exercise exerts detrimental effects on diastolic left ventricular function of the failing heart through beta-adrenergic stimulation. The clinical effectiveness of beta-blocker therapy in patients with DCM can be attributed in part to the inhibition of detrimental myocardial effects of sympathetic stimulation during daily activity.
Authors: M Karita; H Sato; Y Koretsune; K Imai; H Ozaki; H Yokoyama; M Hori; H Takeda; M Inoue; T Kamada Journal: Eur J Clin Pharmacol Date: 1995 Impact factor: 2.953