Cardiovascular effects of the novel potassium channel opener bimakalim in conscious pigs after myocardial infarction: a comparative study with nicorandil.
The benzopyran-derivative bimakalim is an ATP-dependent potassium channel activator that has been shown to be a potent arterial vasodilator in anesthetized pigs. In the present study we evaluated the cardiovascular profile of bimakalim in normal conscious animals and conscious animals with chronic left ventricular dysfunction and compared the results to those obtained with nicorandil. In normal conscious pigs, bimakalim (37.5-300 ng/kg/min, n = 6) and nicorandil (10-80 micrograms/kg/min, n = 8) increased cardiac output from 2.7 +/- 0.1 l/min to 3.8 +/- 0.2 l/min and from 2.7 +/- 0.1 l/min to 3.9 +/- 0.3 l/min (both p less than .05) due to increases in heart rate (up to 62 +/- 14% and 74 +/- 9%, respectively, both p less than .05). The mean arterial blood pressure decreased gradually from 104 +/- 4 mmHg to 91 +/- 5 mmHg with bimakalim and from 98 +/- 3 mmHg to 84 +/- 5 mmHg with nicorandil (both p less than .05), due to similar decreases in systemic vascular resistance. LVdP/dtmax also increased with both drugs (up to 48 +/- 11% and 69 +/- 7%, respectively, p less than .05), but left ventricular end-diastolic pressure remained unchanged with bimakalim, while it gradually decreased from 9 +/- 1 mmHg to 5 +/- 1 mmHg (p less than .05) with nicorandil. In pigs with a 3- to 4-week-old myocardial infarction, the vasodilator responses to bimakalim (n = 8) and nicorandil (n = 9) were not affected, but the increases in heart rate and LVdP/dtmax were attenuated compared to the effects in the normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)
van Woerkens
L J
LJ
Laboratory for Experimental Cardiology, Erasmus University Rotterdam, The Netherlands.
Baas
N R
NR
van der Giessen
W J
WJ
Verdouw
P D
PD
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001578:Benzopyrans / Q000494:pharmacology* / Q000627:therapeutic use; D004095:Dihydropyridines / Q000494:pharmacology* / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects*; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D020108:Nicorandil; D015221:Potassium Channels / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D013552:Swine; D014664:Vasodilation / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
D000959:Antihypertensive Agents; D001578:Benzopyrans; D004095:Dihydropyridines; D015221:Potassium Channels; D009536:Niacinamide; D020108:Nicorandil; C061050:bimakalim; D011433:Propranolol