Reduced cardiovascular responsiveness to exercise-induced sympathoadrenergic stimulation in patients with cirrhosis

Cardiovascular responsiveness to sympathoadrenergic activation obtained by muscle exercise in the supine position was evaluated in 22 patients with cirrhosis (11 alcoholic, 11 postnecrotic/cryptogenic; 14 with ascites) and 10 controls of comparable age. Plasma norepinephrine, heart rate, diastolic arterial pressure and cardiac function, as evaluated by systolic time intervals, were monitored. At rest, cirrhotics had higher norepinephrine (154 +/- 19 S.E.M. ng/l) and heart rate (79 +/- 2 beats per min) than controls (71 +/- 3 ng/l, p less than 0.01; 67 +/- 2 beats per min, p less than 0.001), whereas diastolic arterial pressure was similar. Among systolic time intervals, electromechanical systole, pre-ejection period, electromechanical delay and pre-ejection period to left ventricular ejection time ratios were prolonged (p less than 0.05 or less). Exercise led to significant increases in plasma norepinephrine, heart rate and diastolic arterial pressure in both controls and patients. In the latter, however, whereas the increase in norepinephrine was greater (p less than 0.001), those in heart rate and diastolic arterial pressure were less (p less than 0.005). As expected, most systolic time intervals shortened, but the decrease in pre-ejection period (p less than 0.05), isometric contraction time (p less than 0.02) and pre-ejection period to left ventricular ejection time ratio (p = 0.06) was less in patients than in controls. Direct correlations between exercise-induced changes in norepinephrine and both diastolic arterial pressure (r = 0.81; p less than 0.005) and heart rate (r = 0.85; p less than 0.002) were observed in controls, while inverse correlations (r = -0.67, p less than 0.001 and r = -0.44; p less than 0.05) were found in cirrhotics. These results suggest that cardiovascular reactivity to the sympathetic drive is impaired in cirrhotics. The impairment of cardiac contractility may be due to altered electromechanical coupling.