Beneficial effects of fenoldopam on systemic and regional hemodynamics in rabbits with congestive heart failure.
Fenoldopam (SKF 82526 J) is a selective DA-1 receptor agonist and thus of a potential benefit for promoting afterload reduction, renal vasodilatation, and diuresis in congestive heart failure. To examine the acute effects of fenoldopam in heart failure, studies were performed in control rabbits (n = 6) and in rabbits with chronic congestive heart failure (CHF, n = 6) induced by adriamycin treatment. Cardiovascular variables and regional blood flows were determined before and after an infusion of fenoldopam (150 micrograms/kg total dose). Resting hemodynamics differed in CHF and control groups. In the CHF group, mean arterial pressure (MAP), cardiac output (CO), and stroke volume (SV) were reduced and right atrial pressure (RAP), left ventricular end-diastolic pressure (LVEDP), and total peripheral resistance (TPR) were increased. Renal blood flow was much reduced in the CHF as compared with the control group (5.1 +/- 0.8 vs. 9.1 +/- 0.6 ml/min.g, p less than 0.05). Similar falls in MAP were noted after fenoldopam in CHF (-13 +/- 2%) and control rabbits (-12 +/- 3%) due to falls in TPR. An increase in CO was observed in both groups, the rise being more pronounced in the CHF group (22 vs. 12%). Heart rate was unchanged by fenoldopam in CHF rabbits but increased in controls. After fenoldopam, CHF rabbits exhibited significantly greater increases in blood flow to each of the three vascular beds studied: renal (113 +/- 27% vs. 7 +/- 13%), mesenteric (249 +/- 60% vs. 15 +/- 19%) and cerebral (145 +/- 13% vs. 12 +/- 12%). Plasma renin and norepinephrine (NE) levels increased after fenoldopam in both control and CHF rabbits. These results show that acute administration of fenoldopam produces favourable systemic and regional hemodynamic responses in rabbits with low output heart failure. However, long-term benefit remains to be demonstrated, particularly considering the hormonal responses.
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D002302:Cardiac Output / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D004317:Doxorubicin; D005260:Female; D018818:Fenoldopam; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D011817:Rabbits; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood; D013152:Splanchnic Circulation / Q000187:drug effects
D001552:Benzazepines; D002395:Catecholamines; D004317:Doxorubicin; D012083:Renin; D018818:Fenoldopam