The cardioprotective effect and mechanism of lumbrokinase

AimTo investigate the protective effect of lumbrokinase against myocardial ischemia and to further explore its underlying mechanisms. MethodsThe effect of lumbrokinase on myocardial ischemia was observed by a model of acute myocardial infarction due to permanent ligation of the left anterior descending coronary artery in rats. Patch-clamp technique and laser scanning confocal microscopy were utilized to study the action of lumbrokinase on L-type calcium current (I_Ca-L) and intracellular calcium concentration (［Ca²⁺］_i). ResultsLumbrokinase decreased the infarct size of myocardium in a dose-dependent manner. The inhibitory rate of lumbrokinase at the dose of 20, 40 and 80 mg·kg^-1 was 7.7%, 34.6% and 46.2%, respectively. The electrophysiological studies displayed that, at +10 mV, the I_Ca-L was markedly reduced from (-14.42±1.53) pA/pF to (-11.33±1.40) pA/pF (decreased by 21.4%, P<0.01) and (-9.92±1.31) pA/pF (decreased by 36.5%, P<0.01) by lumbrokinase (10 and 50 μmol·L^-1), respectively. Confocal experiments showed that 10 μmol·L^-1 lumbrokinase showed no obvious effects on ［Ca²⁺］_i at resting states (P>0.05). However, the increase of ［Ca²⁺］_i induced by 60 mmol·L^-1 KCl was distinctly limited by 10 μmol·L^-1 lumbrokinase (P<0.01). Within 240 s, the no obvious peak value of fluorescent intensity (FI) was shown. ConclusionLumbrokinase showed protective action against myocardial infarction in rats. The possible mechanisms of anti-ischemia could be attributed to decreasing I_Ca-L and ［Ca²⁺］_i of ventricular myocytes in rats.