Protective effects of hemodilution and ischemic preconditioning against reperfusion injury in pig heart

Objective

We investigated the protective effects of isovolumetric hemodilution and ischemia preconditioning against myocardial injury due to reperfusion through a pig myocardial ischemia reperfusion model.

Methods

Eighteen mini-pigs were used in an acute myocardial ischemia model. They were randomly divided into three groups, with six pigs in each group: the control (group I, n = 6), ischemia pre-treatment (group II, n = 6), ischemia pretreatment plus blood dilution (group III, n = 6). Cardiac output (CO), saturation of mixed venous blood oxygen (SvO₂) and blood flow of coronary artery were measured, and then the oxygen supply to the myocardium and the oxygen consumption were calculated. The amount of malondialdehyde (MDA), the superoxide dismutase (SOD) activity, the creatine phosphokinase (CPK) and creatine phosphokinase isoenzyme (CK-MB) were also determined 20 min and 60 min, respectively, before and after the forceps clamping. A sample was taken from the left atrial appendage to determine the rate of expression of heat shock proteins Hsp70 mRNA.

Results

When ischemia lasted for 20 min, the heart rate (HR) of group I and group II slowed down dramatically while that of group III accelerated slightly. The MAP, CI and SVR of all three groups significantly decreased from control values (P < 0.01), but the magnitude of decrease in groups II and III were lower than those of group I (P < 0.05). Also the SVR of group III was significantly lower than group II (P < 0.05). After reperfusion at 20 min and 60 min, the HR of groups I and II was significantly lower than that of the controls (P < 0.01). The HR of group III was significantly higher than that of groups I and II (P < 0.05), but was not significantly higher than the control value (P > 0.05). The decreased MAP and CI of groups II and III were significantly lower than those of group I (P < 0.05). In addition the SVR of group III was lower than groups I or II (P < 0.05). The values of CPK, CPK-MB of all three groups were significantly higher than the controls after reperfusion at 20 min and 60 min (P < 0.05–0.01, respectively). However, groups II and III increased less than those of group I. The values of CPK and CPK-MB in group III were lower than that of group II (P < 0.05). The MDA value of group I was dramatically higher than that of groups II and III after reperfusion at 20 min and 60 min (P < 0.05), while the value of group III was lower than that of group II after reperfusion at 60 min (P < 0.05). The expression of Hsp70 mRNA in group II and group III was higher than that of group I (P < 0.05), and Hsp70 mRNA in group III was higher than group II (P < 0.05) after reperfusion at 20 min and 60 min.

Conclusion

Isovolumetric hemodilution can increase the protection of preconditioning against ischemic myocardial injury caused by reperfusion.