Exercise response of the denervated heart in long-term cardiac transplant recipients

Abstract

The left ventricular response to volume loading and graded supine bicycle exercise (3 minutes at 15, 45 and 90 watts) was assessed in nine long-term (more than 1 year) cardiac transplant recipients. Computer-aided fluoroscopy of radiopaque myocardial markers implanted in the left ventricle at the time of surgery was used to measure left ventricular dynamics. Pulmonary arterial and left ventricular pressures were monitored. Plasma norepinephrine was measured by radio-enzymatic assay at each level of exercise. Early in exercise mean end-diastolic volume (six patients) increased from a resting value of 125 to 138 ml (p < 0.02) at the 45 watt level, then decreased to 121 ml at the 90 watt level. End-systolic volume decreased from 68 to 63 ml and then to 49 ml (p < 0.01) at corresponding exercise levels. Stroke volume increased from 57 to 76 ml (p < 0.01) then declined slightly to 71 ml (p < 0.02 for increase relative to resting value). Heart rate increased gradually from 102 to 116 beats/min (p < 0.05) and then rapidly to 140 beats/min (p < 0.01). Thus cardiac output increased significantly at all levels of exercise from 5.7 liters/min at rest, to 6.5 at 15 watts (p < 0.02), to 8.7 at 45 watts (p < 0.01) and to 10.0 liters/min at 90 watts (p < 0.01). Plasma norepinephrine increased slowly from 233 pcg/ml at rest to 460 at 45 watts, then rapidly to 1,970 pcg/ml at 90 watts. Increases in velocity of circumferential fiber shortening (Vcf) and heart rate were correlated with increasing norepinephrine concentrations (r = 0.92 for Vcf; r = 0.79 for heart rate). A functioning Frank-Starling mechanism was demonstrated in seven patients with volume loading by leg elevation resulting in significant increases in end-diastolic volume, stroke volume and cardiac output in the absence of any increase in heart rate. Thus, cardiac output increases in the transplanted heart were brought about early in exercise by augmented preload and the Frank-Starling mechanism, and later in exercise by chronotropic and inotropic influences of increased circulating catecholamines.