title: Alteration of the cardiac effects of midazolam by hypothermia in rat isolated atria.
abstract: Hypothermia produces marked changes in cardiac activity and response to different anesthetic interventions. Isolated spontaneously beating right, or electrically stimulated left rat atria were examined while heart rate, sinus node recovery time, developed force, and effective refractory period were measured at 35 and 20 degrees C. Thus, we wanted to investigate the influence of low temperature on the cardiac effects of midazolam. The preparations were exposed to seven progressively increasing concentrations of midazolam. At 35 degrees C, midazolam produced a concentration-dependent positive inotropic effect and had a biphasic effect (shortening followed by lengthening) on the effective refractory period. These effects are best explained as due to a release of endogenous catecholamines, since the positive inotropy was completely blocked by propranolol. In reserpinized animals, there was no effect of midazolam. Midazolam, however, significantly decreased heart rate and increased the sinus node recovery time; these responses are believed to be direct effects. At 20 degrees C, midazolam had no effect on the developed force but, when a high concentration was administered, it significantly reduced the effective refractory period. Heart rate values were first increased and the reduced to control values. No effect on the sinus node recovery time was observed. Thus, hypothermia may reduce the catecholamine release and mask the effect of midazolam on cardiac tissue by mechanisms not yet fully understood.
authors.affiliation: Basic Cardiac Research Laboratory, Kirkenes Hospital, Norway.
authors.forename: A L
authors.initials: AL
authors.lastname: Melnikov
authors.forename: D A
authors.initials: DA
authors.lastname: Lathrop
authors.forename: K G
authors.initials: KG
authors.lastname: Helgesen
mesh_terms: D000759:Adjuvants, Anesthesia / Q000494:pharmacology*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003080:Cold Temperature; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006325:Heart Atria / Q000187:drug effects; D007036:Hypothermia, Induced; D066298:In Vitro Techniques; D008297:Male; D008874:Midazolam / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D011433:Propranolol; D051381:Rats; D012110:Reserpine; D013268:Stimulation, Chemical
chemical_list: D000759:Adjuvants, Anesthesia; D014151:Anti-Anxiety Agents; D012110:Reserpine; D011433:Propranolol; D008874:Midazolam