This laboratory and others have shown that
methylprednisolone sodium succinate and
betahistine hydrochloride can each reduce the size of experimental
myocardial infarct in dogs at six hours. In light of the fact that these two agents probably act via different mechanisms, a study was carried out to determine if there would be cumulative effects of using these two agents together. Using a left anterior descending coronary artery
ligation model to create an experimental
myocardial infarction and an intracellular lactic
dehydrogenase (LDH)
stain to measure the
infarct size, 66 dogs were studied. Nineteen dogs served as controls with no
therapy; 20 received a continuous
intravenous infusion of
betahistine hydrochloride (0.24 mg/kg/min) for six hours following
ligation; 10 dogs received
methylprednisolone sodium succinate intravenously 30 mg/kg at one hour postligation; and 17 other dogs received
betahistine hydrochloride intravenously (0.24 mg/kg/min) over six hours following
ligation, plus
methylprednisolone sodium succinate intravenously (30 mg/kg) at one hour postligation. At six hours, the combined treatment demonstrated no significant improvement over
betahistine HCl alone (control, 16.0%;
betahistine HCl, 11.4%; combined, 11.2% P less than 0.05). At 24 hours, only the combined treatment group demonstrated a significant
infarct size reduction (control, 15.5%;
methylprednisolone, 13.1%;
betahistine--HCl, 14.2%; combined, 9.7%; P less than 0.0025). Other parameters that were evaluated and analyzed include mean aortic pressure, left atrial pressure, cardiac index, total peripheral resistance, arterial and coronary sinus pH, pCO2, pO2, hematocrit, O2 consumption, O2 content difference, and coronary sinus
lactate and
creatine phosphokinase (CPK). These results suggest a significant cumulative effect in reducing
infarct size over that achieved with one agent alone; however, further studies are needed to determine the appropriate dosage and temporal factors.