ABSTRACT
AIM: To investigate the effects of heptanol preconditioning on the changes of structure, function and connexin 43 (Cx43) content in mitochondria in a rabbit model of myocardial isehemia-reperfusion (IR) injury. METHODS: In anesthetized open-chest rabbits, the left anterior descending artery (LAD) was occluded for 30 min and reperfused for 4 h. Sixty-four rabbits were randomly divided into 4 groups (n=16 in each group): sham operation group (sham group), ischemia-reperfusion group (IR group), ischemic preconditioning group (IP group) and heptanol preconditioning group (HT group). All rabbits in the 4 groups were killed 4 h after reperfusion. Myocardial infarct size was determined at the end of the experiment. Mitochondria was isolated by centrifugations. The ultrastructural changes of the mitochondria were observed under electronic microscope. The mitochondrial membrane potential, Ca~(2+) concentration, MDA content and SOD activity of myocardial mitochondria were also examined. The content of mitochondria Cx43 was detected by Western blotting. RESULTS: Compared to IR group, the myocardial infarct size was significantly reduced in IP (18.97%±2.80%) and HT (19.97%±3.80%) groups, the damage of mitoehondrial ultrastructure was milder (P<0.05), mitochondrial membrane potential was significantly higher and Ca~(2+) concentration was much lower (P<0.01) in IP group and HT group. No significant difference of MDA content and SOD activity in myocardial mitochondria between IR group and HT group was found. However, MDA content were much lower and SOD activity was significantly higher in IP group as compared to IR group (P<0.01). Compared to sham group, the mitochondria Cx43 expression was distinctly decreased compared to IR group (P<0.05) and no significant difference was found between IP group and HT group (P>0.05). CONCLUSION: Heptanol preconditioning protects myocardium from ischemia-reperfusion injury. The mechanism may be related to increasing in mitochondrial membrane potential, alleviating Ca~(2+) overload in myocardial mitochondria and attenuating the decrease in mitochondria Cx43 expression induced by isehemia-reperfusion.
ABSTRACT
Objective To investigate the effects of ischemic postconditioning on apoptosis, structural and functional changes of mitochondria induced by myocardial isehemia/reperfusion (I/R) injury of rabbits and potential mechanism. Methods Eighty healthy rabbits were divided randomly into five groups: sham operation group ( Group Sham) , ischemic reperfusion group (Group IR) , ischemic preconditioning group (Group IP) , ischemic postconditioning group (Group PC) and 5-HD plus ischemic postconditioning group (Group PC +5-HD). All rabbits in the five groups were killed 4 h after reperfusion. The hearts were quickly collected for microscopy by TUNEL. We observed ultrastructural changes of myocardium under electron microscope and examined mitochondrial membrane potential and Ca~(2+) concentration, MDA content and SOD activity of myocardial mitochondria. Results Compared with group IR, the damage of mitoehondrial ultrastrueture was milder, the apoptosis rate decreased and Ca concentration and MDA content were much lower in group IP and group PC ( P < 0. 05 ). Mitochondrial membrane potential and SOD activity of myocardial mitochondria in group IP and group PC was significantly higher than that in group IR(P<0.05). The protective effect of PC against I/R injury was partially counteracted by 5-HD .Conclusion Ischemic posteonditioning can protect the heart from I/R injury, this is supported by improvement mitochondrial ultrastructure and by decreasing apoptosis, increasing mitochondrial membrane potential and SOD activity, alleviating Ca~(2+) overload and decreasing MDA content in myocardial mitochondria. The cardio protective effects may be explained by mitochondrial ATP sensitive potassium channel.
ABSTRACT
Aim To investigate the roles of Cx43 in mitochondria and mitochondrial ATP sensitive potassium channe1(mitoK_(ATP)~+)participating in the protection for heptanol preconditioning on myocardial ischemia/reperfusion injury of rabbits.Methods In anesthetized open-chest rabbits,the left anterior descending artery(LAD)was occluded for 30 min and reperfused for 4 hrs.All rabbits were randomly divided into five groups(n=16 in each group):sham operation group(Group Sham),ischemic reperfusion group(Group IR),ischemic preconditioning group(Group IP),heptanol preconditioning group(Group HT)and 5-HD plus heptanol preconditioning group(Group HT+5-HD),All rabbits in the five groups were killed 4h after reperfusion.Myocardial infarct size was determined at the end of the experiment.The heart rate and the mean arterial pressure(MAP)were recorded and plasma CK-MB and cTnI activity were measured at baseline,the end of ischemia,and after 2 hrs and 4 hrs of reperfusion respectively.Mitochondria was isolated with different centrifugations.Ultrastructural changes of mitochondria were observed under electron microscope.The content of the mitochondria Cx43 was detected with Western blot.Results The plasma CK-MB,cTnI activity and myocardial infarct size were significantly reduced in IP(18.97±2.8)% and HT(19.97±3.8)% groups as compared to IR groups (35.67±5.8)%,(P<0.01).Compared to group IR,the damage of mitochondria in group IP and group HT were milder(P<0.01).No significant difference was found between Group IP and Group HT.Compared to sham group, the mitochondria Cx43 expression was distinctly decreased in group IR and group HT+5-HD(P<0.01)and no significant difference was found between Group IP and Group HT.Conclusions Heptanol preconditioning can protect the heart from I/R injury by improving mitochondrial ultrastructure and by attenuating the decrease of mitochondria Cx43 expression induced by I/R.The mitochondrial Cx43 expression may be concerned with depending on mito K_(ATP)~+.