Preoperative consecutive treatment with isoprenaline and adenosine is safe and reduces ischaemia-reperfusion injury in a porcine model of cardiac surgery with recent acute myocardial infarction

OBJECTIVES
To assess feasibility, safety and efficacy of consecutive isoprenaline/adenosine in a pig model of myocardial infarction and cardiac surgery.

METHODS
The final Isoprenaline/Adenosine dose was selected in a pilot study (n = 8). In the subsequent randomized trial, 16 pigs underwent cardiac magnetic resonance four weeks after myocardial infarction, then randomized to either Isoprenaline/Adenosine (n = 8) or Control (n = 8) before undergoing cardiac surgery with 1 h recovery. Feasibility and safety end-points included method of Isoprenaline/Adenosine delivery, serial blood pressure, heart rate, pH,
⁠, circulating lactate, troponin levels and arrhythmias. Biomarkers of efficacy included serial lactate levels and pO2 arterial-to-venous functional ratio (pO2a-v f-ratio) along with histological levels of glycogen, protein carbonyls, O2, CO2,
⁠, 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 groups. The selected method of Isoprenaline/Adenosine delivery was feasible. All safety outcomes measured in the Isoprenaline/Adenosine group were at no time worse than in the control group. Isoprenaline/Adenosine reduced circulating lactate levels, preserved pO2a-v f-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 vs 0% in the Isoprenaline/Adenosine group.

CONCLUSIONS
The therapy was feasible, safe and improved biomarkers of efficacy. Isoprenaline/Adenosine was associated with no postoperative low cardiac output and death vs 37.5% and 25% respectively in the control group. A pilot human study is warranted.