Abstract
OBJECTIVES: The goal of this study was to assess the feasibility, safety and efficacy of consecutive treatment with isoprenaline/adenosine (ISO/ADE) in a pig model of myocardial infarction and cardiac surgery. METHODS: The final ISO/ADE dose was selected from a pilot study (n = 8). In the subsequent randomized trial, 16 pigs underwent cardiac magnetic resonance imaging 4 weeks after a myocardial infarction, then were randomized to either the ISO/ADE (n = 8) or the control (n = 8) group before undergoing cardiac surgery with 1 h recovery. Feasibility and safety end points included the method of ISO/ADE delivery, serial blood pressure, heart rate, pH, HCO3-, circulating lactate levels, troponin levels and arrhythmias. Biomarkers of efficacy included serial lactate levels and serial pO2 mean arterial-to-venous functional ratio along with histologic levels of glycogen, protein carbonyls, O2, CO2, HCO3- and fibrosis. Postoperative rates of low cardiac output and death were also recorded. RESULTS: Cardiac magnetic resonance measures of myocardial infarction did not differ between the groups. The selected method of ISO/ADE delivery was feasible. At no time were all safety outcomes measured in the ISO/ADE group worse than those in the control group. ISO/ADE reduced circulating lactate levels, preserved the serial pO2 mean arterial-to-venous functional ratio and reduced tissue-based glycogen and protein carbonylation. No other differences were observed. Low cardiac output and death occurred in 3/8 (37.5%) and 2/8 (25%) control animals versus 0% in the ISO/ADE group. CONCLUSIONS: The therapy was feasible and safe and improved biomarkers of efficacy. ISO/ADE was not associated with any postoperative low cardiac output and deaths versus 37.5% and 25%, respectively, in the control group. A pilot human study is warranted.