Differential cardioprotective properties of the l- and d- enantiomers of bucindolol in a canine model of heart failure.
In previous studies racemic bucindolol was found to reverse the effects of pentobarbital-induced heart failure in anesthetized dogs. Reductions of right ventricular contractile force (RVCF), left ventricular (LV) dp/dt, and aortic blood flow (ABF) serve as indicators of depressed cardiac function in this model. In this study, racemic bucindolol (0.25 mumol/kg +0.25 mumol/kg/hr) again evoked pronounced and sustained stimulant effects on these depressed parameters. l-Bucindolol (0.125 mumol/kg +0.125 mumol/kg/hr) was a more effective stimulator of cardiac function than d-bucindolol in this model. l-Bucindolol elicited maximal increases in RVCF, ABF, LV dp/dt and heart rate of 66, 19, 30 and 11%, respectively. In comparison, d-bucindolol maximally increased these parameters only 20, 14, 12 and 4%, respectively. Total peripheral resistance was reduced 29% by l-bucindolol and 19% by d-bucindolol. The responses to l-bucindolol and racemic bucindolol were essentially the same. The myocardial stimulation and vasodilation profile derived from l-bucindolol (at one-half the molar dose of bucindolol) suggests the possible preference for its use in clinical management of congestive heart failure over bucindolol, the racemic compound. The results further suggest that l-bucindolol could also be used to treat hypertensive patients with depressed cardiac function.
Weyl
J D
JD
Snyder
R W
RW
Hanson
R C
RC
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D006321:Heart / Q000503:physiopathology; D006333:Heart Failure / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D010424:Pentobarbital / Q000494:pharmacology; D011412:Propanolamines / Q000627:therapeutic use*; D013237:Stereoisomerism; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; C024307:bucindolol; D010424:Pentobarbital