Adenosine protects cardiomyocytes from hypoxia/reoxygenation injury / 生理学报

The aim of this study was to investigate the protective effect of adenosine (ADO) on cardiomyocytes following hypoxia/reoxygenation (H/R) and its molecular mechanism. Primary cultured cardiomyocytes of neonatal rats were divided into two groups, namely H/R (control) and ADO (1.0 micromol/L) groups. The morphologic changes in cardiomyocytes were observed under an inverted phase-contrast microscope. The following parameters of the two groups were determined: lactate dehydrogenase (LDH) activity, intracellular calcium concentration and malondialdehyde (MDA) content. Tumor necrotic factor (TNF-alpha) assay was performed using an ELISA kit and NF-kappaB in the nucleus was analyzed by electrophoretic mobility shift assay (EMSA). The results are as follows: (1) after H/R injury, cardiomyocytes contracted, tending to get round in shape and its pseudopods decreased, while marked morphological changes were not observed in ADO group; (2) LDH leakage maintained at a lower level in ADO group than that in the control group during H/R (both P<0.01); (3) ADO significantly reduced the concentration of calcium in cells and prevented calcium overload during H/R (both P<0.01); (4) ADO markedly reduced the content of MDA during H/R (both P<0.01); (5) ADO inhibited the production of TNF-alpha during H/R (both P<0.01); and (6) ADO down-regulated NF-kappaB binding activity of cardiomyocytes during H/R (both P<0.01) The results suggest that (1) exogenous ADO attenuates H/R injury of cultured cardiomyocytes; (2) exogenous ADO inhibits the production of TNF-alpha after H/R injury; (3) exogenous ADO prevents the activation of NF-kappaB, which may be the molecular mechanism of down-regulation of TNF-alpha expression.

Dependence of ventricular wallstress-induced refractoriness changes on pacing cycle lengths and its mechanism / 生理学报

The aim of this article was to investigate the dependence of ventricular wallstress-induced refractoriness changes on pacing cycle lengths and its mechanism in anaesthetized rabbits. The rabbit heart preparation was used. The left ventricular afterload was increased by partially clipping the root of the ascending aorta. The changes in effective refractory periods (ERP) induced by the left ventricular afterload rising were examined at different pacing cycle lengths (1000, 500, 300 and 200 ms). In addition, the effect of streptomycin on these changes was also observed. The results are as follows: (1) The rising of left ventricular afterload led to marked changes in ERP at rapidly pacing cycle lengths (300 ms, 21+/-5 ms, 17.0%; 200 ms, 19+/-3 ms, 18.8%. P<0.01) than at slow ones (1000 ms, 3+/-2 ms, 1.5%; 500 ms, 7+/-3 ms, 4.0%. P>0.05); (2) Streptomycin inhibited the changes caused by the left ventricular afterload rising at pacing cycle lengths 300 ms and 200 ms (P>0.05). It is suggested that ventricular wallstress-induced refractoriness changes are pacing cycle length-dependent, and the effect of streptomycin appears to be consistent with the inhibition of stretch-activated ion channels.

Effect of tetradrine on electrophysilogic changes caused by rising of left ventricular preload in guinea pigs / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the changes of guinea pig heart electrophysiological properties caused by increasing left ventricular preload, and to assess the effects of tetradrine on these changes.</p><p><b>METHOD</b>Working model preparation of guinea pig hearts in vitro was used, and the preload of left ventricle was increased by adjusting the prefusion pressure of left atria. The changes of heart electrophysiologic parameters including monophasic action potential duration (MAPD90), monophasic action potential amplitude (MAPA), effective refractory period (ERP) and ventricular fibrillation threshold (VFT) were observed before and after altering the preload of left ventricle, and compared in the absence and presence of tetradrine, streptomycin or verapamil.</p><p><b>RESULT</b>The rising of left ventricular preload led to shortening of MAPD90, ERP, and to descent of MAPA, VFT (all P<0.01). Both Tetradrine and streptomycin inhibited these changes of heart electrophysiologic parameters caused by elevation of left ventricular afterload (all P<0.01). In contrast, verapamil had no effects on the preload-related electrophysiological changes (all P>0.05).</p><p><b>CONCLUSION</b>Electrophysiologic changes caused by increasing left ventricular preload may be inhibited by tetrandrine, through inhibition of stretch-activated ion channels.</p>