Adriamycin cardiomyopathy in the rabbit: an animal model of low output cardiac failure with activation of vasoconstrictor mechanisms.
Chronic administration of intravenous adriamycin (1 mg . kg-1 twice weekly for 8 weeks) to rabbits resulted in a cardiomyopathy which was similar to that occurring in patients with adriamycin cardiotoxicity. We studied systemic and renal haemodynamics and the activation of vasoconstrictor mechanisms reflected by changes in plasma renin activity (PRA), noradrenaline (NA) and vasopressin (AVP) levels during the development of heart failure in this animal model. By 8 weeks cardiac failure was clearly established. At postmortem all animals had dilated hearts, pleural and pericardial effusions, ascites and hepatic congestion. Heart weights were increased (8.1 +/- 0.7 g in treated animals n = 9 vs 6.0 +/- 0.2 g in controls n = 9 p less than 0.05). Cardiac output (measured by thermodilution) fell at 8 weeks from 799 +/- 61 ml . min-1 to 624 +/- 44 ml . min-1 (n = 6 p less than 0.05) with a parallel fall in mean blood pressure from 85 +/- 2 mmHg to 75 +/- 4 mmHg. Total peripheral resistance rose in four of the six rabbits. Renal blood flow fell from 108 +/- 4 ml . min-1 to 61 +/- 6 ml . min-1 (p less than 0.05) by 8 weeks. Renal vascular resistance increased in all animals. PRA increased from 5.1 +/- 0.5 ng AI . ml-1 . h-1 to 11.6 +/- 2.6 ng AI . ml-1 . h-1 by 4 weeks (p less than 0.05) and remained elevated thereafter.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002311:Cardiomyopathy, Dilated / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity*; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000473:pathology; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects
D004317:Doxorubicin