ENZYME-RELEASE INTO THE INTERSTITIAL SPACE OF THE ISOLATED RAT-HEART INDUCED BY CHANGES IN CONTRACTILE PERFORMANCE

Objective: The aim was to investigate changes in interstitial concentr ation and release of creatine kinase in isolated perfused rat hearts a fter an experimental inotropic stimulation or after recovery from a ne gative inotropic intervention (low Ca2+ or high K+ buffer). Methods: I nterstitial transudate emerging at the surface of the heart and venous effluent were analysed for creatine kinase. Results: The interstitial concentration of creatine kinase was always higher, by a factor of 25 to 100 (range from 10 to 580 mU.ml(-1)), than the concentration in th e venous effluent (close to or below the limit of detection: 0.4 mU.ml (-1)). Continuous stimulation with a submaximal effective concentratio n (8 nM) of isoprenaline for 30 min resulted in an initial transient i ncrease in the interstitial release of creatine kinase to about 160% o f the control (p < 0.05). Similarly, in a second series, three repeate d (5 min) periods of inotropic stimulation also caused a significant a nd transient increase in the interstitial release of creatine kinase t o a maximum of 180%. Change to a buffer containing 2.0 mM Ca2+ after a 60 min period of low Ca2+ perfusion (0.25 mM) led to restoration of c ontractile function and an immediate and transient increase in the int erstitial release of creatine kinase to about 900%. After a period of cardiac arrest (16 mM K+ for 60 min), perfusion with 4 mM K+ also imme diately restored cardiac function, and led to an increase in creatine kinase release of 2500%. In additional experiments dilatation of the l eft ventricle by inflating an intraventricular balloon during cardiopl egic perfusion induced a significant fivefold increase in the intersti tial release of creatine kinase, which was further enhanced 3.5-fold d uring the subsequent recovery period. Conclusions: The coincidence of an increase in or a restoration of cardiac contractile function and an increase in the interstitial enzyme release suggests that myocardial enzyme release may occur in response to physiological stimuli during d ifferent episodes of metabolic or mechanical stress, as well as under pathophysiological conditions.