Metabolic and hemodynamic consequences of mannitol following myocardial anoxia.

The mechanism of action of hyperosmolal mannitol was evaluated by hemodynamic and metabolic studies in 79 isovolumic nonrecirculating paced perfused rat hearts during sequential 15-min periods of aerobic, anoxic, and reoxygenated perfusion. Hyperosmolality induced by addition of mannitol significantly decreased myocardial water content (wet/dry wt ratio). It improved recovery of hemodynamic function during reoxygenation. With isomolal perfusion (290 mosmol/kg) left ventricular systolic peak pressure (LVSP) decreased 32% (127 +/- 5 to 86 +/- 6 mmHg) and maximum dP/dt fell 50% (3,513 +/- 328 to 1,758 +/- 172 mmHg/s) during the postanoxic recovery period. With hyperosmolal perfusion (350 mosmol/kg), LVSP decreased 23% (132 +/- 5 to 102 +/- 7 mmHg) and dP/dt fell 21% (3,817 +/- 215 to 2,998 +/- 234 mmHg/s) (P less than .01). Hyperosmolal perfusion did not affect postanoxic total coronary flow, lactate and glucose metabolism, tissue glycogen, creatine phsophate, or adenine nucleotide concentrations. Coronary perfusion with hypersmolal solution aided recovery, enhanced postanoxic myocardial performance, and minimized tissue swelling. The most tenable explanation for the locus of action of hyperosmolal mannitol during anoxia under our experimental conditions is its direct effect on myocardial water content.