Tissue osmolality, cell swelling, and reperfusion in acute regional myocardial ischemia in the isolated porcine heart.

Abstract

SUMMARY We divised a method to determine tissue osmolality in intact beating hearts. After occlusion of the left anterior descending coronary artery (LAD) of isolated porcine hearts, tissue osmolality in the ischemic myocardium increased within 50 minutes by about 40 mOsm/kg. This rise in osmolality could be accounted for by metabolic processes, notably the conversion of glycogen into lactate, and the hydrolysis of high energy phosphates. Concomitant with the rise in osmolality, the ischemic myocardium during the 1-hour period of LAD occlusion took up fluid and increased tistue water volume by an average of 16.5%. We demonstrated that the osmolality of fixatives used for morphological studies markedly influences ischemic cell morphology. Thus, normotonic fixation of the ischemic myocardium accentuates cell swelling, whereas nearly normal cell volumes result from hypertonic fixation, adjusted according to the rise hi ischemic tissue osmolality. Normotonic reperfusion of the ischemic area after 1 hour of LAD occlusion resulted in the "no-refiow" phenomenon in the mldmural and subendocardial regions. Epicardial and intramural DC-electrograms showed persistent ischemic changes, i.e., T-Q depression, S-T elevation, and monophasic potentials. Tissue resistivity, which during ischemia had risen twofold, remained high. Lacate levels remained high, creatinephosphate (CP) and adenosinetriphosphate (ATP) levels remained low. Selective hypertonic reperfusion of the LAD, followed by a gradual return to normotonic perfnsion, resulted in a normalization of DC extracellular elcctrograms, restoration of electrical resistivity to near normal, low levels of lactate, and higher levels of CP and ATP although control values were not reached. Cell morphology was correspondingly normalized following this procedure. We conclude that ischemic cells become hyperosmotic and consequently take up additional fluid when exposed to normotonic blood. This increased cell swelling compresses capillaries, prevents reperfusion, and may be a major factor in causing reperfusion damage. This damage can be prevented to a large extent by selective hypertonic reperfusion. Circ Res 49: 364-381, 1881

Mannitol enhances delivery of marrow stromal cells to the brain after experimental intracerebral hemorrhage

“…In our study, mannitol alone increased new cell formation around the ICH. Mannitol can prevent the swelling of cells and alleviate the subsequent cell damage at the vicinity of the injured site (Tranum-Jensen et al, 1981). It is therefore a possibility that mannitol may enhance tissue tolerance to acute stress after injury and that mannitol may salvage more viable cells at the vicinity of the injury site (Lizasoain et al, 2006).…”

Role of oxygen-derived free radicals in myocardial edema and ischemia in coronary microvascular embolization.

“…[23][24][25] During postischemic reflow, an increment of the tissue water content can be detected as early as 30 seconds after reperfusion.14 However, reflow is not essential for cellular swelling in the ischemic heart because myocardial edema was also observed in the ischemic model of diminished coronary perfusion without abrupt reflow.23 In the latter model, cellular water content was increased by 10.9% during 45 minutes of low perfusion, whereas the extracellular volume was unchanged.23 Even during coronary occlusion without reflow, intracellular swelling can occur accompanying a decrease in the extracellular space with total tissue water content unchanged.26 In the present histological study, we fixed the tissue with high osmolar glutaraldehyde buffer (350 mosmol/l) to avoid artificial increases in extracellular tissue water content in the ischemic myocardium.24 Thus, existence of edema both in extracellular and intracellular spaces in our model ( Figure 6) indicates that the water supply from the nonischemic surrounding area augments the edema formation both in the extracellular and intracellular spaces.…”

Myocardial reperfusion: a double-edged sword?

“…Ischemic cell swelling An impairment of cell volume regulation is characteristic of ischemic tissue injury (19). Severe persistent ischemia, in the absence of reperfusion, may cause cell swelling and a net gain in tissue water; the mechanism of the latter has not been identified with certainty but it might be secondary to ischemiainduced depression ofthe sodium-potassium exchange pump in the sarcolemma, to the development of increased cell membrane permeability, and/or the formation of osmotically active intracellular particles (20). Regardless of the specific mechanism(s) responsible for the impairment of cell-volume regulation, the finding of a correlation between increases in myocardial water and reductions in myocardial blood flow (21) suggests that swelling of myocytes may contribute to vascular compression.…”