Abstract

The effect of heart failure on the hepatic elimination of low-clearance drugs has not been clearly defined. We investigated the effect of left ventricular failure on theophylline clearance in rats. Cardiovascular function and theophylline pharmacokinetics were studied in conscious rats 6-8 weeks after left anterior descending coronary artery ligation. Rats with infarcts involving > 35% of the left ventricle (N = 9) had 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-diastolic pressure (25.9 +/- 13.6 vs. 10.6 +/- 3.9 mm Hg; p < 0.01), and increased lung weight. There was also an increase in central venous pressure (6.44 +/- 2.60 vs. 3.67 +/- 2.60 mm Hg; p < 0.05), but no evidence of 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, total 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 liver weight; 12.4 +/- 1.8 vs. 13.3 +/- 3.7 mumol/min/g liver weight and 0.451 +/- 0.097 vs. 0.438 +/- 0.079 ml/min/100 g body weight), respectively. Taking the infarct group as a whole, total hepatic oxygen delivery was linearly correlated to theophylline clearance (r = 0.66, p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)