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 ventricular function. In the present study we evaluated the effects of acute changes of myocardial tissue fluid on cardiac function and ultrastructural morphometry. Isolated rat hearts were perfused for 100 min in the working heart mode. Hearts were distributed into 5 groups: controls [perfused with Krebs-Henseleit (KH) isotonic buffer to rat plasma, KH, 287 mOsm], moderate hyposmotic perfusion (75% Hyposm: perfusion with 75% diluted KH, 216 mOsm), highly hyposmotic perfusion (60% Hyposm: perfusion with 60% diluted KH, 170 mOsm), afterload increase (Pre-over: isotonic perfused hearts subjected to an increase of afterload from 72 to 145 cm H2O) and ion dilution (Ion-dil: hearts perfused with a 60% KH with 115 mM sucrose, isotonic, 287 mOsm). We evaluated functional changes, markers of cellular necrosis or damage (CPK, LDH and purine release in coronary effluent), heart weight changes (weight gain and ww/dw ratio) and ultrastructural morphometry (analysis of cell damage, interstitial area, and mitochondrial alterations by a computerized image analysis system). The ww/dw ratio increased significantly only in 60% Hyposm (+140%, p < 0.001) and Pre-over (+63%, p < 0.001 vs control) groups. An impaired myocardial function in 60% Hyposm, Pre-over and Ion-dil groups was observed with cardiac failure at 50, 60 and 60 min, respectively. 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 interstitial space area (ISA) and mitochondrial damage in 60% Hyposm and Pre-over groups (p < 0.001); a significant (p < 0.05) increase was observed in the Ion-dil group; in 75% Hyposm group, a significant increase of mitochondrial damage was detected (p < 0.05). In brief, a higher functional and morphological deterioration was observed in hearts in which a more evident interstitial edema was detected (60% Hyposm and Pre-over 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 damage to the myocardium.