Effects of a bradycardic agent on postischemic cardiac recovery in rabbits.
Decreasing heart rate might be beneficial for improvement of myocardial energetics and could reduce the severity of myocardial ischemia. We examined the contribution of heart rate reduction by cilobradine (DK-AH 269), a direct sinus node inhibitor, on left ventricular function and peripheral vasomotion in anesthetized rabbits with experimental myocardial infarction. The rabbits were randomized to receive either placebo (n=10) or cilobradine (n=7). Cilobradine decreased significantly heart rate from 163 +/- 33 to 131 +/- 13 bpm, p< 0.05, without any inotopic or vascular effects. After 60 min coronary occlusion and 30 min reperfusion, both systolic and diastolic ventricular function were more reduced in the cilobradine group; i.e. maximal left ventricular pressure significantly decreased to 62 +/- 11 mmHg, p < 0.05 (placebo: 77 +/- 9 mmHg); dP/dt(min) significantly decreased to -904 +/- 247 mmHg, p < 0.05 (placebo: -1106 +/- 242 mmHg). However, infarct size in the cilobradine group was significantly smaller compared with the placebo group. In conclusion, cilobradine reduced heart rate without any negative inotropic effect and reduced infarct size. On that account, this bradycardic agent might open a promising therapeutical avenue to treat postischemic dysfunction.
Schmitz-Spanke
S
S
Research Group Experimental Surgery, Department of Surgery I, University Hospital Dusseldorf, Moorenstr. 5, Dusseldorf 40225, Germany. Schmitz-Spanke@med.uni-duesseldorf.de
Granetzny
A
A
Stoffels
B
B
Pomblum
V J
VJ
Gams
E
E
Schipke
J D
JD
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology / Q000627:therapeutic use*; D001919:Bradycardia / Q000139:chemically induced* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D011817:Rabbits
D001552:Benzazepines; D010880:Piperidines; C490484:cilobradine