The interaction of MCI-154, a calcium sensitizer, and isoflurane on systemic and coronary hemodynamics in chronically instrumented dogs.
We conducted this study to determine the interaction of MCI-154, 6-[4-(4'-pyridylamino)phenyl]-4,5-dihydro-3(2H)-pyridazinone hydrochloride, a calcium sensitizer, and isoflurane on myocardial contractility as well as systemic and coronary hemodynamics in chronically instrumented dogs after pharmacological autonomic nervous system activity blockade. MCI-154 increased heart rate and left ventricular function with no change in rate pressure product, pressure work index, and coronary blood flow, with a decrease in coronary vascular resistance (CVR) in the conscious state. Isoflurane decreased heart rate and left ventricular function, with a decrease in rate pressure product and pressure work index. Isoflurane also decreased CVR, but not coronary blood flow. The cardiovascular actions of MCI-154 during isoflurane anesthesia were qualitatively similar to those observed in the conscious state. In contrast to the finding in the conscious state, MCI-154 reversed the decrease in cardiac output and preload recruitable stroke work caused by isoflurane, but these are not significantly different from the effects of isoflurane alone. These results indicate that MCI-154 increases myocardial contractility and decreases CVR without changing calculated myocardial oxygen consumption during both the conscious state and isoflurane anesthesia.


CONCLUSIONS
MCI-154, a calcium sensitizer, restores the myocardial contractility depressed by isoflurane and enhances the coronary vasodilating effect of isoflurane in chronically instrumented dogs.
Takahashi
Shunji
S
Department of Anesthesiology, Nagasaki University School of Medicine, Nagasaki, Japan.
Cho
Sungsam
S
Hara
Tetsuya
T
Ureshino
Hiroyuki
H
Tomiyasu
Shiro
S
Sumikawa
Koji
K
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects; D001794:Blood Pressure / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects*; D004285:Dogs; D005260:Female; D006321:Heart / Q000294:innervation; D006439:Hemodynamics / Q000187:drug effects*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011724:Pyridazines / Q000494:pharmacology*; D013318:Stroke Volume / Q000502:physiology; D016277:Ventricular Function, Left / Q000502:physiology
D018685:Anesthetics, Inhalation; D002316:Cardiotonic Agents; D011724:Pyridazines; C052228:MCI 154; D007530:Isoflurane; D002118:Calcium