[The cardioprotective effect and mechanism of lumbrokinase].
OBJECTIVE
To investigate the protective effect of lumbrokinase against myocardial ischemia and to further explore its underlying mechanisms.


METHODS
The 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 (ICa-L) and intracellular calcium concentration ([Ca2+]i).


RESULTS
Lumbrokinase 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 x kg(-1) was 7.7%, 34.6% and 46.2%, respectively. The electrophysiological studies displayed that, at + 10 mV, the ICa-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 micromol x L(-1)), respectively. Confocal experiments showed that 10 micromol x 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 x L(-1) KCl was distinctly limited by 10 micromol x L(-1) lumbrokinase (P <0.01). Within 240 s, the no obvious peak value of fluorescent intensity (FI) was shown.


CONCLUSIONS
Lumbrokinase showed protective action against myocardial infarction in rats. The possible mechanisms of anti-ischemia could be attributed to decreasing ICa-L and [Ca2+] of ventricular myocytes in rats.
Sun
Hong-li
HL
Department of Pharmacology, Harbin Medical University, China.
Jiao
Jun-dong
JD
Pan
Zhen-wei
ZW
Dong
De-li
DL
Yang
Bao-feng
BF
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D010450:Endopeptidases / Q000494:pharmacology*; D005260:Female; D006352:Heart Ventricles; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D020746:Calcium Channels, L-Type; D002316:Cardiotonic Agents; D010450:Endopeptidases; C083421:lumbrokinase; D002118:Calcium