RIGHT HEART-FAILURE IMPAIRS HEPATIC OXYGENATION AND THEOPHYLLINE CLEARANCE IN RATS

The effect of right heart failure on theophylline clearance was invest igated in rats in which right ventricular pressure overload was produc ed by pulmonary artery constriction (PAC). Fifteen wk after the surger y, compared to sham-operated controls (n = 9), PAC rats (n = 9) showed markedly elevated mean central venous pressure (11 +/- 3 vs. 1.44 +/- 0.88 mm Hg, P =.0001), and increased right ventricular weight (0.229 +/- 0.047 vs. 0.124 +/- 0.013 g/100 g body weight, P =.0001). Centrilo bular hepatic congestion was present in all PAC rats and total hepatic oxygen delivery was reduced significantly compared to controls (146 /- 58 mu mol/min vs. 206 +/- 28 mu mol/min; P =.025). In the PAC group , theophylline clearance was reduced (0.82 +/- 0.12 ml/min vs. 0.96 +/ - 0.13 ml/min in controls; P =.014), and there was a nonlinear correla tion between theophylline clearance and total hepatic oxygen delivery (r =.82). These results suggest that in animals with PAC, metabolism o f theophylline was impaired as a result of a reduction in total hepati c oxygen delivery. Therefore, in addition to the known effect of reduc ed hepatic blood flow on the hepatic clearance of ''flow limited'' dru gs, reduction of hepatic oxygen delivery may be another important mech anism that can lead to reduction in hepatic clearance of capacity-limi ted drugs in congestive heart failure.