The mechanism of mannitol in reducing ischemic injury: hyperosmolarity or hydroxyl scavenger?

The effectiveness of postischemic reperfusion with mannitol has been well documented in previous studies. Mannitol, a hyperosmolar agent, is also an effective scavenger of the cytotoxic hydroxyl radical. If mannitol acts solely as a hyperosmolar agent, hyperosmolar reperfusion with its isomer, glucose, should be equally effective. To elucidate the beneficial effect of mannitol, 24 isolated rabbit heart preparations were subjected to 60 min of hypothermic (27 degrees C) cardioplegic arrest and normothermic reperfusion. There were three study groups with eight hearts in each. Group I hearts were reperfused with an unmodified isosmolar solution. Group II hearts were reperfused with a hyperosmolar (350 mOsm/liter) solution containing glucose, and group III hearts had hyperosmolar (350 mOsm/liter) reperfusion with mannitol. Left ventricular function (developed pressure and maximum positive dP/dt) was measured isovolumically before and after ischemia. Coronary flow was measured volumetrically during reperfusion, and myocardial edema formation was determined after 45 min of reperfusion. Reperfusion with mannitol resulted in significant improvement in recovery of developed pressure (77.3 +/- 2.8% of control vs 65.5 +/- 2.9% in group I and 62.6 +/- 2.2% in group II; p less than .05). Mannitol-treated hearts also had significantly greater coronary flow throughout the reperfusion period and significantly less marked myocardial edema formation compared with hearts treated with isosmolar and hyperosmolar glucose. These data confirm the particular usefulness of mannitol in improving postischemic ventricular function, maintaining coronary blood flow during early reflow, and reducing myocardial edema formation.(ABSTRACT TRUNCATED AT 250 WORDS)