Actions of two new bradycardic agents, AQ-AH 208 and UL-FS 49, on ischemic myocardial perfusion and function.
The effects of continuous infusions (30 min) of two new bradycardic agents, AQ-AH 208 (3,4-dihydro-6,7-dimethoxy-2-(3-((2-(3,4 dimethoxyphenyl) ethyl)-amino methyl) propyl)-1(2H)-isochinolinon) (10 and 25 micrograms/kg/min) and UL-FS 49 (1,3,4,5-tetrahydro-7,8-dimethoxy-3(3((2-(3,4-dimethoxyphenyl) ethyl) methylimino) propyl)-2H-3-benzazepin-2 on) (1.0 and 2.5 micrograms/kg/min) on ischemic myocardial perfusion and function were studied in anesthetized open chest dogs. Coronary stenosis was induced by narrowing an extracorporeal shunt between the carotid and left anterior descending coronary artery. Regional perfusion was measured by use of radioactive microspheres and regional myocardial function (% segment shortening) was assessed by sonomicrometry. AQ-AH 208 and UL-FS 49 produced dose-dependent reductions in heart rate of 13 to 55 beats/min without prominent effects on left ventricular dP/dt, aortic blood pressure, and % segment shortening of the normally perfused area. In nonischemic myocardium, AQ-AH 208 did not change transmural blood flow in spite of the bradycardia, whereas UL-FS 49 decreased flow. At the high infusion rate, ischemic subendocardial perfusion increased from 0.43 to 0.58 ml/min/g following UL-FS 49 and from 0.57 to 0.84 ml/min/g after treatment with AQ-AH 208. Consequently, endo/epi rose from 0.52 to 0.80 and 0.62 to 0.96, respectively. Atrial pacing abolished the effects of UL-FS 49 on ischemic myocardium whereas the effects of AQ-AH 208 were only partially reduced. Ischemic myocardial function deteriorated less during treatment with UL-FS 49 and was significantly improved following AQ-AH 208 as compared with the control group.(ABSTRACT TRUNCATED AT 250 WORDS)
Dämmgen
J W
JW
Lamping
K A
KA
Gross
G J
GJ
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000503:physiopathology*; D003971:Diastole / Q000187:drug effects; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D054833:Isoindoles; D008297:Male; D010477:Perfusion; D010797:Phthalimides / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D001552:Benzazepines; D054833:Isoindoles; D010797:Phthalimides; C030532:falipamil; C043636:zatebradine