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-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)
Angus
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PW
Gastroenterology Unit, Austin Hospital, Heidelberg, Victoria, Australia.
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Ghabrial
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Morgan
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Smallwood
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RA
D000818:Animals; D002496:Central Venous Pressure / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D008099:Liver / Q000378:metabolism*; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000502:physiology; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013806:Theophylline / Q000493:pharmacokinetics*; D018487:Ventricular Dysfunction, Left / Q000378:metabolism* / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000502:physiology
D013806:Theophylline