EFFECTS OF CHRONIC LEFT-VENTRICULAR FAILURE ON HEPATIC OXYGENATION AND THEOPHYLLINE ELIMINATION IN THE RAT

The effect of heart failure on the hepatic elimination of low-clearanc e drugs has not been clearly defined. We investigated the effect of le ft ventricular failure on theophylline clearance in rats. Cardiovascul ar function and theophylline pharmacokinetics were studied in consciou s rats 6-8 weeks after left anterior descending coronary artery ligati on. Rats with infarcts involving >35% of the left ventricle (N = 9) ha d severe left ventricular failure, and, compared with control rats (N = 9), had reduced cardiac output (97.3 +/- 18.2 vs. 132 +/- 26 ml/min; p < 0.05), reduced mean arterial blood pressure (86 +/- 20 vs. 109 +/ - 16 mm Hg; p < 0.05), markedly elevated left ventricular end-diastoli c pressure (25.9 +/- 13.6 vs. 10.6 +/- 3.9 mm Hg; p < 0.01), and incre ased lung weight. There was also an increase in central venous pressur e (6.44 +/- 2.60 vs. 3.67 +/- 2.60 mm Hg; p < 0.05), but no evidence o f hepatic congestion, as judged by liver weights (14.7 +/- 1.5 vs. 15. 3 +/- 1.3 g) and liver histology. However, total hepatic blood flow, t otal hepatic oxygen delivery, and theophylline clearance were found to be similar in both groups (1.66 +/- 0.30 vs. 1.75 +/- 0.38 ml/min/g l iver weight; 12.4 +/- 1.8 vs. 13.3 +/- 3.7 mu mol/min/g liver weight a nd 0.451 +/- 0.097 vs. 0.438 +/- 0.079 ml/min/100 g body weight), resp ectively Taking the infarct group as a whole, total hepatic oxygen del ivery was linearly correlated to theophylline clearance (r = 0.66, p < 0.02). We conclude that severe left ventricular failure has little im pact on theophylline clearance, because hepatic perfusion and thus oxy genation are largely maintained in the face of systemic circulatory ch anges.