Perfluorochemical Reperfusion Limits Myocardial Reperfusion Injury After Prolonged Hypothermic Global Ischemia

The ability of an oxygenated perfluorochemical (Fluosol®) to limit myocardial reperfusion injury following global hypothermia ischemic insult was investigated. Neonatal piglet hearts were arrested with cold crystalloid cardioplegia and stored for 12 hours in 2° C saline. Reperfusion was carried out using an isolated, blood-perfused, working heart preparation. Hearts were initially reperfused (10 minutes) with either whole blood (WB, n=6), unmodified perfluorochemical (PFC, n=8), or aspartate/glutamate-enriched perfluorochemical cardioplegia (PFC+, n=6), prior to institution of whole blood perfusion, functional evaluation and left ventricular biopsy. A control group (C, n=7) was evaluated without an intervening period of ischemia. At a left ventricular diastolic pressure of 9 mm Hg WB hearts developed a left-ventricular stroke work index (SWI) of 3.8±2.3 × 103 erg/g (mean±standard error of the mean). Under similar conditions, PFC-reperfused hearts achieved a SWI of 14.6±1.3 × 103, significantly greater than that of WB (p < 0.001). SWI for PFC+ hearts was 19.8±1.6 × 103, significantly increased over that of PFC (p < 0.01), and not different from values obtained for C (19.2±0.8 × 103). In addition, PFC-reperfused hearts demonstrated superior maintenance (p < 0.05) of ATP (2.08±0.16 umole/g), compared to WB (1.50±0.19), while preservation of ATP in PFC+ hearts (2.9910.12), was significantly increased over that of PFC (p < 0.001), and not significantly different from that for C (2.68±0.17). Electron microscopy revealed notably improved preservation of ultrastructural architecture in perfluorochemical-treated hearts (PFC and PFC+) compared to WB. We conclude that oxygenated perfluorochemical reperfusion ameliorates the myocardial injury seen upon whole blood reperfusion, as demonstrated by its comparative ability to improve functional recovery, maintain high-energy phosphates, and preserve ultrastructural integrity. Further, amino acid enrichment and chemical cardioplegia enhance this effect and allow for complete functional recovery of the myocardium after 12 hours of hypothermia ischemia.