EFFECT OF ACUTE INCREASE OF INTERSTITIAL MYOCARDIAL FLUID ON VENTRICULAR-FUNCTION IN ISOLATED WORKING RAT HEARTS

An acute increase of myocardial interstitial fluid may affect ventricu lar function. In the present study we evaluated the effects of acute c hanges of myocardial tissue fluid on cardiac function and ultrastructu ral morphometry. Isolated rat hearts were perfused for 100 min in the working heart mode. Hearts were distributed into 5 groups: controls [p erfused with Krebs-Henseleit (KH) isotonic buffer to rat plasma, KH, 2 87 mOsm], moderate hyposmotic perfusion (75% Hyposm: perfusion with 75 % diluted KH, 216 mOsm), highly hyposmotic perfusion (60% Hyposm: perf usion with 60% diluted KH, 170 mOsm), afterload increase (Pre-over: is otonic perfused hearts subjected to an increase of afterload from 72 t o 145 cm H2O) and ion dilution (Ion-dil: hearts perfused with a 60% KH with 115 mM sucrose, isotonic, 287 mOsm). We evaluated functional cha nges, markers of cellular necrosis or damage (CPK, LDH and purine rele ase in coronary effluent), heart weight changes (weight gain and ww/dw ratio) and ultrastructural morphometry (analysis of cell damage, inte rstitial area, and mitochondrial alterations by a computerized image a nalysis system). The ww/dw ratio increased significantly only in 60% H yposm (+140%, p < 0.001) and Pre-over (+63%, p < 0.001 vs control) gro ups. An impaired myocardial function in 60% Hyposm, Pre-over and Ion-d il groups was observed with cardiac failure at 50, 60 and 60 min, resp ectively. Enzyme release was significant higher in 60% Hyposm and Pre- over groups and was related to heart weight gain (r = 0.85, p < 0.001) . Ultrastructural analysis confirmed a significant increase of interst itial space area (ISA) and mitochondrial damage in 60% Hyposm and Pre- over groups (p < 0.001); a significant (p < 0.05) increase was observe d in the Ion-dil group; in 75% Hyposm group, a significant increase of mitochondrial damage was detected (p < 0.05). In brief, a higher func tional and morphological deterioration was observed in hearts in which a more evident interstitial edema was detected (60% Hyposm and Pre-ov er groups). We conclude that, in the experimental condition, an acute increase of myocardial interstitial tissue fluid directly compromises left ventricular function and contributes to the ultrastructural damag e to the myocardium.