Effects of epanolol, a selective beta1-blocker with intrinsic sympathomimetic activity, in patients with ischemic left ventricular dysfunction.
Recently, different beta-blockers have been shown to be effective in the treatment of chronic heart failure (CHF), but the importance of their ancillary properties is not clear. Epanolol is a selective beta1-blocker with intrinsic sympathomimetic activity, which has been shown useful in angina pectoris, but its value in patients with left ventricular (LV) dysfunction and CHF is unknown. We examined the effects of epanolol in patients with LV dysfunction (n = 8; mean LV ejection fraction, 0.33 +/- 0.08) and compared them with patients with normal LV function (n = 8; mean LV ejection fraction, 0.52 +/- 0.04). Measurement of invasive hemodynamics and neurohormones was performed at rest and during myocardial ischemia, which was induced by atrial pacing. All measurements were performed before and after epanolol. Before epanolol, pacing-induced ischemia led to a similar increase in norepinephrine and coronary sinus blood flow in both groups. After epanolol, the increase in neurohormones was more pronounced in the group with LV dysfunction (norepinephrine, 1,130 +/- 164 pg/ml for patients with LV dysfunction vs. 637 +/- 41 pg/ml for normal subjects; p < 0.05). A similar effect was observed for angiotensin II. Further, in the LV-dysfunction group, coronary sinus blood flow increased less, and coronary vascular resistance decreased less (both values, p < 0.05). Despite the fact that the increase in double product was decreased to a similar extent in both groups, ischemia was reduced only in normal LV function (p < 0.05). In ischemic LV dysfunction, neurohumoral activation after epanolol may impair adequate coronary flow response, and this may limit its antiischemic properties. Because of the small size of the study, no definitive inference on the clinical benefit of epanolol in patients with ischemic LV function can be made from this study.
Van Den Heuvel
A F
AF
Sticares Cardiovascular Research Foundation, Rotterdam, The Netherlands.
van der Ent
M
M
van Veldhuisen
D J
DJ
Kruijssen
D A
DA
Bartels
G L
GL
Remme
W J
WJ
D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000368:Aged; D000804:Angiotensin II / Q000097:blood; D044482:Benzeneacetamides; D002304:Cardiac Pacing, Artificial; D003326:Coronary Circulation / Q000187:drug effects; D004562:Electrocardiography / Q000187:drug effects; D004837:Epinephrine / Q000097:blood; D005260:Female; D006333:Heart Failure / Q000188:drug therapy; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism; D009638:Norepinephrine / Q000097:blood; D011412:Propanolamines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D013566:Sympathomimetics / Q000008:administration & dosage / Q000494:pharmacology*; D018487:Ventricular Dysfunction, Left / Q000188:drug therapy*
D000319:Adrenergic beta-Antagonists; D044482:Benzeneacetamides; D011412:Propanolamines; D013566:Sympathomimetics; D000804:Angiotensin II; C038616:epanolol; D009638:Norepinephrine; D004837:Epinephrine