Effects of R 56,865, a preventer of cellular calcium overload, on left ventricular diastolic properties during pacing-induced ischemia in dogs.
The effects of R 56,865, a compound with unusual calcium antagonistic properties, on altered left ventricular (LV) diastolic properties were studied during pacing-induced ischemia in dogs with coronary stenosis. Severe coronary artery stenosis was produced on both the left anterior descending (LAD) and circumflex (Cx) coronary arteries in anesthetized beta-blocked dogs. The right atrium was paced at 200 beats/min for 3 min. In the post-pacing period and before drug intervention, the most characteristic observation was a significant increase in LV end-diastolic pressure (LVEDP) and in the time constant of (tau) LV pressure decrease; after return of LV hemodynamics to baseline values (15 min), R 56,865 (0.16 mg.kg-1) or solvent (control) was injected and four subsequent pacing runs were performed at 30-min intervals. In the postpacing period of these four subsequent runs, there was a steep increase in LVEDP and tau-values while HR returned more slowly to baseline values. After R 56,865 infusion, the increase in LVEDP and tau-values was significantly lower than in the pretreatment run and all LVEDP values were significantly lower than in the control group. We conclude that R 56,865 effectively attenuates ischemia-induced changes in LV diastolic stiffness.
Vandeplassche
G
G
Department of Cardiovascular Pharmacology, Janssen Research Foundation, Beerse, Belgium.
Hermans
C
C
Wouters
L
L
Borgers
M
M
D000818:Animals; D052160:Benzothiazoles; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000502:physiology; D003971:Diastole; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects*
D052160:Benzothiazoles; D010880:Piperidines; D013844:Thiazoles; C054551:R 56865; D011433:Propranolol