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

TL;DR

A treatment combining isoprenaline and adenosine before heart surgery may reduce injury in pigs with recent heart attacks.

Contribution

This study demonstrates the safety and efficacy of ISO/ADE treatment in a porcine model of cardiac surgery after MI.

Findings

ISO/ADE treatment reduced circulating lactate levels and preserved oxygen efficiency.

ISO/ADE reduced tissue glycogen and protein carbonylation, indicating less cellular damage.

No postoperative low cardiac output or deaths occurred in the ISO/ADE group, unlike the control group.

Abstract

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.

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.

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.

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.

Globally, more than 64 million patients develop ischaemic heart failure following myocardial infarction (MI) [1].

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