An experimental model of chronic cardiac failure using adriamycin in the rabbit: central haemodynamics and regional blood flow.
Central haemodynamics and regional blood flow were studied comprehensively in conscious New Zealand White rabbits before and during the development of chronic low output cardiac failure produced by administration of the anticancer agent adriamycin. After eight weeks of adriamycin treatment, cardiac index fell from 326(40 to 225(56) ml.min-1.kg-1. This was accompanied by an increase in heart rate and total peripheral resistance but no change in mean systemic blood pressure. Myocardial function was shown to be depressed by the measurement of Frank-Starling curves, the slopes of which were appreciably flatter in adriamycin treated rabbits. Regional blood flow (measured by the radioactive microsphere technique) was redistributed. There were decreases in renal, splenic, small gut, and skeletal muscle blood flow, whereas myocardial and cerebral blood flow were unchanged. There was an increase in total body exchangeable sodium, indicating some salt and water retention. Systemic toxic effects of adriamycin could be limited by treating the animals for eight weeks with adriamycin and then allowing a two week recovery period before haemodynamic study. This would appear to be the optimal dosage schedule.
Wanless
R B
RB
Department of Cardiac Medicine, Cardiothoracic Institute, London.
Anand
I S
IS
Poole-Wilson
P A
PA
Harris
P
P
D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000494:pharmacology*; D006333:Heart Failure / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D004317:Doxorubicin