Does dobutamine prevent the rise in left ventricular filling pressures observed during exercise after heart transplantation?

Abstract

The purpose of the study was to evaluate whether infusion of a beta-adrenergic agonist, prior to and during exercise, could compensate for reduced sympathetic stimulation and correct deficient acceleration of left ventricular relaxation, so preventing a rise in left ventricular filling pressures during exercise after cardiac transplantation. Abnormal left ventricular relaxation kinetics can contribute to exercise-induced diastolic dysfunction of the cardiac allograft. This was demonstrated in transplant recipients whose acceleration of left ventricular relaxation during exercise was almost negligible recently and whose elevation of left ventricular end-diastolic pressure was high. Decreased adrenergic tone due to denervation could be involved in deficient left ventricular lusitropic response to exercise, because acceleration of left ventricular relaxation during exercise depends on adequate sympathetic stimulation. Serial supine bicycle exercise was performed at an identical workload in eight transplant recipients while in the control state and during continuous infusion of dobutamine, titrated before exercise to achieve a heart rate matching the heart rate at peak exercise in the control state. During control exercise, heart rate rose from 87 +/- 8 to 104 +/- 12 beats.min-1 (P < 0.05), left ventricular end-diastolic pressure from 14 +/- 5 to 20 +/- 4 mmHg (P < 0.05), left ventricular dP/dtmax from 1374 +/- 172 to 1854 +/- 278 mmHg.s-1 (P < 0.05), and cardiac output from 5.8 +/- 0.9 to 8.5 +/- 1.1 l.min-1 P < 0.05). There was a small but significant decrease of the time constant of left ventricular pressure decay (T) from 42 +/- 6 to 38 +/- 6 ms (P < 0.05). During dobutamine infusion, exercise resulted in a further increase in heart rate from 108 +/- 11 to 122 +/- 17 mmHg (P < 0.05), in cardiac output from 7.4 +/- 0.9 to 10.3 +/- 2.5 l.min-1 (P < 0.05), and in left ventricular dP/dtmax from 2181 +/- 220 to 2620 +/- 214 mmHg.s-1 (P < 0.05). These values were higher than the measurements obtained at the end of the control exercise run (P < 0.05). T failed to change (29 +/- 4 vs 27 +/- 5 mmHg, P > 0.05) and left ventricular end-diastolic pressure increased from 5 +/- 3 to 11 +/- 5 mmHg (P < 0.05) but remained lower than at the end of the control exercise run (11 +/- 5 vs 20 +/- 4 mmHg, P < 0.05). Compensation for reduced sympathetic stimulation by administration of dobutamine improves exercise haemodynamics in cardiac transplant recipients, but cannot prevent the exercise-induced rise in left ventricular end-diastolic pressure and correct deficient acceleration of left ventricular relaxation. Abnormal exercise haemodynamics after heart transplantation are therefore only partly related to deficient sympathetic stimulation.