Effects of nifedipine on diastolic abnormalities in low-flow and pacing-induced ischemia in isolated rat hearts.
An animal experimental model which stimulates human effort angina, especially in terms of diastolic abnormalities, was developed using isovolumically beating perfused rat hearts. Using this model, we studied the effects of nifedipine, a Ca2+ channel blocker, on diastolic properties during pacing-induced ischemia. When the preload of the left ventricle was set at a low level, low-flow ischemia (coronary perfusion pressure of 40 mmHg) plus tachycardia (480 beats/min for 4 min) did not induce an increase in left ventricular end-diastolic pressure (LVEDP). However, with a high preload, low-flow ischemia plus pacing tachycardia induced an increase in LVEDP of 8.4 +/- 5.4 mmHg (p less than 0.01) and a prolongation of the time constant of ventricular pressure decline (6.8 +/- 4.6 msec, p less than 0.05) immediately after pacing tachycardia. Pretreatment with nifedipine (3 x 10(-8) M) prevented the rise in LVEDP induced by pacing tachycardia. Thus, in isolated perfused hearts, diastolic abnormalities similar to those seen in angina pectoris were obtained by low-flow ischemia plus pacing tachycardia. The response to nifedipine suggested that an alteration of Ca2+ movement may play an important role in the increase in left ventricular stiffness under these conditions.
Momomura
S
S
Second Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Serizawa
T
T
Ikenouchi
H
H
Sugimoto
T
T
Iizuka
M
M
D000787:Angina Pectoris / Q000503:physiopathology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D003326:Coronary Circulation; D003327:Coronary Disease / Q000503:physiopathology*; D003971:Diastole / Q000187:drug effects*; D004195:Disease Models, Animal; D006339:Heart Rate; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016277:Ventricular Function, Left / Q000187:drug effects
D009543:Nifedipine