The effects of hyperosmolal coronary perfusion on the haemodynamic, metabolic and ultrastructural changes of myocardial anoxia

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Abstract
Recovery from anoxia has been evaluated in the isovolumic non-recirculating paced perfused rat heart. Seventy studies were performed consisting of 15 min of aerobic perfusion (AP); AP+15 min anoxic perfusion; and AP+15 min anoxic perfusion+15 min reoxygenation (recovery). Krebs-Ringer-bicarbonate+5 mmol glucose (KRB) (290 mmol) was compared to KRB+mannitol (350 mmol). Mannitol decreased myocardial water content. It improved recovery of haemodynamic function after reoxygenation. With KRB alone left ventricular systolic peak pressure (LVSP) decreased 32% and maximum dP/dt by 50%. With mannitol added LVSP decreased 18% and dP/dt 21% (P<0·01). KRB and mannitol did not differentially affect total coronary flow, lactate and glucose extraction, tissue glycogen, creatine phosphate or adenine nucleotide concentrations. No difference in submicroscopic appearance was noted with either perfusate during aerobic perfusion. Anoxic hearts perfused with isosmolal KRB demonstrated the most severe ultrastructural alterations including mitochondrial swelling with disruption of cristae and extraction of matrix components, myofibrillar fusion and contraction bands, and subsarcolemmal oedema and vacuolization. These changes were only partially reversed during reoxygenated perfusion. However, cellular changes were reversed or markedly improved during both the anoxic and reoxygenation perfusion periods with hyperosmolal solutions. When studied by silicone rubber injection of the microcirculation, only focal capillary endothelial cell swelling was noted and no difference in arteriolar or capillary filling was observed with either perfusate. Mannitol appears to improve LV function by direct myocardial osmotic action unrelated to enhanced energy production.