Bradycardia induced by mivazerol, a selective alpha 2-adrenoceptor agonist, is amplified during mild hypothermia in the pentobarbital-anesthetized rat.
Mivazerol, 3-[1(H-imidazol-4-yl)methyl]-2-hydroxybenzamide hydrochloride, is a selective alpha 2-adrenoceptor agonist designed for the prevention of myocardial infarction in perioperative patients. Because unintended hypothermia occurs frequently during surgery, we were interested, in this study, to examine the relationship between body temperature and the bradycardic response induced by mivazerol. Experiments were carried out in pentobarbital-anesthetized and artificially ventilated rats. The femoral artery and vein were cannulated for the measurement of blood pressure and heart rate, and for intravenous infusion. Rectal temperature was maintained at 37.5 +/- 0.3 degrees C for normothermic groups or at 35.5 +/- 0.3 degrees C for hypothermic groups. Intravenous infusion of vehicle had no significant effect on mean arterial pressure and heart rate between the normothermic and hypothermic rats. Mivazerol dose-dependently produced a decrease in heart rate in normothermic rats, which became more pronounced in mildly hypothermic rats, but did not induce any significant change in mean arterial pressure in either thermic condition. These results show that the bradycardic effect of mivazerol, an alpha 2-adrenoceptor agonist, is amplified during mild hypothermia, a condition that occurs frequently in perioperative patients.
Kim
S Y
SY
Department of Pharmacology and Experimental Therapeutics, Loyola University Chicago Stritch School of Medicine, Maywood, IL 60153, USA.
Raikoff
K
K
Wülfert
E
E
Hanin
I
I
D000759:Adjuvants, Anesthesia; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D007035:Hypothermia / Q000503:physiopathology*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D010424:Pentobarbital; D051381:Rats; D017207:Rats, Sprague-Dawley
D000759:Adjuvants, Anesthesia; D058669:Adrenergic alpha-2 Receptor Antagonists; D000316:Adrenergic alpha-Agonists; D007093:Imidazoles; D010424:Pentobarbital; C087969:mivazerol