Enzyme release into the interstitial space of the isolated rat heart induced by changes in contractile performance

Abstract

The aim was to investigate changes in interstitial concentration and release of creatine kinase in isolated perfused rat hearts after an experimental inotropic stimulation or after recovery from a negative inotropic intervention (low Ca2+ or high K+ buffer). Interstitial transudate emerging at the surface of the heart and venous effluent were analysed for creatine kinase. 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 the venous effluent (close to or below the limit of detection: 0.4 mU.ml-1). Continuous stimulation with a submaximal effective concentration (8 nM) of isoprenaline for 30 min resulted in an initial transient increase in the interstitial release of creatine kinase to about 160% of the control (p < 0.05). Similarly, in a second series, three repeated (5 min) periods of inotropic stimulation also caused a significant and transient increase in the interstitial release of creatine kinase to 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 contractile function and an immediate and transient increase in the interstitial 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 immediately restored cardiac function, and led to an increase in creatine kinase release of 2500%. In additional experiments dilatation of the left ventricle by inflating an intraventricular balloon during cardioplegic perfusion induced a significant fivefold increase in the interstitial release of creatine kinase, which was further enhanced 3.5-fold during the subsequent recovery period. 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 different episodes of metabolic or mechanical stress, as well as under pathophysiological conditions.