The protective effect of hyperosmotic mannitol in myocardial ischemia and necrosis.

Abstract

Morphologic and hemodynamic changes that occur following coronary occlusion are examined. The effectiveness of hyperosmotic mannitol in lessening the extent of myocardial damage is assessed and mechanisms for its action discussed. Forty and 60 min of coronary vascular occlusion followed by 15 and 45 min of reflow were associated with a persistence of ischemia following reflow of blood, as established by infusions of silastic into the aortic root. Electron microscopic studies demonstrated myocardial and endothelial cell swelling at the end of the reflow period. The process of cell swelling appeared to be initiated during the period of arterial occlusion. This cell swelling was reduced by elevation of serum osmolality by 30-40 mOsm above control with the administration of mannitol during and following occlusion. There was an associated 40-50% reduction of vascular resistance following occlusion if mannitol was administered. In addition, the extent of necrosis, which was widespread in untreated hearts 12 hours after occlusion, was strikingly less in the hearts of dogs which received mannitol. Thus, in ischemic myocardium, elevation of osmolality by mannitol reduces myocardial necrosis, probably through its restoration of normal cell volume.

Myocardial reperfusion: a double-edged sword?

“…Thus, the finding that the administration of hypertonic mannitol (15) and of fluorocarbons (73) during reperfusion augment myocardial salvage is of great interest because potentially these agents could be infused directly into the infarct-related coronary artery when the latter is opened by the intracoronary administration of a thrombolytic agent or by means of transluminal angioplasty. The demonstration, in experimental animals, that the deleterious effects of reperfusion are related importantly to the action of oxygen-derived free radicals and that these effects can be reduced or even prevented with scavengers offree radicals is intriguing.…”

“…Similar considerations apply to patients in whom the subendocardium also Receivedfor publication 10 July 1985. is most susceptible to ischemic damage. It (15,16). However, in a recent study (17), we found that administration of a calcium channel antagonist at the time of coronary reperfusion did not limit infarct size, a finding which does not support the suggestion that reperfusion causes necrosis ofreversibly injured myocytes.…”

Localization of anti-mitochondrial antibody in experimental canine myocardial infarcts.

“…Myocardial ischemia produces alterations in cell membrane integrity that develop early during the course of experimental ischemic myocardial injury (1)(2)(3)(4)(5)(6)(7)(8). Such alterations in cell membrane permeability appear to precede the development of irreversible cellular injury (1,2,8); some investigators have even suggested that these alterations in membrane permeability play a causal role in the development of irreversible cellular injury (1,2,5,6,8).…”

“…Such alterations in cell membrane permeability appear to precede the development of irreversible cellular injury (1,2,8); some investigators have even suggested that these alterations in membrane permeability play a causal role in the development of irreversible cellular injury (1,2,5,6,8).…”

Spontaneous changes in left ventricular function over the first 24 hours of acute myocardial infarction: implications for evaluating early therapeutic interventions.

“…[1][2][3][4][5][6] However, such clear-cut therapeutic benefit in human myocardial infarction has not been demonstrated.7 -3 One reason for this may be limitations in the techniques suitable for objective documentation of myocardial salvage in man. Recently, radionuclide techniques such as multigated cardiac blood pool imaging have been proposed for noninvasive assessment of global cardiac performance at the patient's bedside, thereby providing functional estimates of myocardial salvage.…”