Impaired metabolism interferes with the active extrusion of intracellular
sodium and results in intracellular
edema. In the brain and regionally in the kidney, elevation of extracellular osmolality is accompanied by a reduction of ischemic cell swelling and improvement of reflow of blood after
arterial occlusion. Studies were therefore performed to examine the effect of elevation of extracellular osmolality on ischemic myocardial physiology and by morphologic examination on the extent of acute injury and subsequent
necrosis. Under conditions of controlled hemodynamics, administration of hyperosmotic
mannitol resulted in improvement of function of the canine heart with regional
ischemia, a lessening of the extent of ischemic injury assessed by electrocardiographic ST segment mapping, and improved total and collateral blood flow. Metabolic studies under conditions of controlled hemodynamics revealed that hyperosmotic
mannitol reduced the myocardial
oxygen requirement of the ischemic heart.
Mannitol dilated large collateral conductance vessels in addition to improving blood flow through the region of
myocardial ischemia. Under conditions of
ischemia induced by a prolonged reduction in coronary perfusion, hyperosmotic
mannitol attenuated the progressive rise in vascular resistance. Direct morphologic examination of areas of myocardium subjected to total interruption of blood flow followed by reflow of blood revealed swelling of both myocardial and capillary endothelial cells early during the reflow period. The extent of swelling was substantially reduced with elevation of the extracellular osmolality with
mannitol. Simarilty, osmolality elevation strikingly reduced the extent of eventual myocardial
necrosis following prolonged periods of reflow of blood.