Effects And Mechanisms Of MaFGF On Anoxia-reoxygenation In Isolated Rat Hearts

OBJECTIVES: To observe the effect of modified acidic fibroblast growth factor (maFGF) on cardiac function, the myocardial enzymology and myocardial apoptosis in anoxia-reoxygenation (A/R) isolated rat heart. The effects of maFGF and aFGF were compared to approach the protection of maFGF against myocardial ischemia-reperfusion (I/R) injury and its mechanism. METHODS:1. Using Langendorff perfusion apparatus, we established the model of anoxia-reoxygenation of isolated rat heart to mimic the I/R of myocardium, the role of aFGF and maFGF on cardiac function was investigated. 32 SD rats were divided into 4 groups randomly: (1) control group; (2) A/R group; (3) aFGF treatment group; (4) maFGF treatment group. The changes of left ventricular systolic pressure (LVSP), left ventricular developed pressure ( LVDP), maximum upstroke velocity of left ventricular systolic pressure (dp/dtnmx) and left ventricular diastolic pressure (dp/dtmax), coronary flow (CF) were measured in every group.2. The coronary effluent at different time points was collected respectively and the concentration of lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA) was detected.3. The myocardial A/R model with primary cultured cardiomyocytes from neonatal SD rat hearts was established. These cardiomyocytes were divided into 12 groups: (1) control group; (2) A/R group; (3) 0.5 ng/mL aFGF group; (4) 5 ng/mL aFGF group; (5) 50 ng/mL aFGF group; (6) 500 ng/mL aFGF group; (7) 5 μg/mL aFGF group; (8) 0.5 ng/mL maFGF group; (9) 5 ng/mL maFGF group; (10) 50 ng/mL maFGF group; (11) 500 ng/mL maFGF group; (12) 5 μg/mL maFGF group. The apoptosis rate induced by anoxia-reoxygenation was detected by flow cytometry.RESULTS:(1) The LVSP, LVDP, dp/dtmax and dp/dtmtn ,CF in every group after A/R at everytime point were lower than those of before anoxia, the every index in A/R group was lower than that in control group at different time points (P<0.01) after reoxygenation, although LVSP, LVDP, dp/dtmax and dp/dtmm, CF in aFGF and maFGF treatment group were not able to recover to the level of control group, they were all significant higher than those of A/R group (P<0.05).(2) The SOD activity in aFGF and maFGF treatment group was significant higher than that in A/R group (P<0.05), but the LDH level and MDA level in both aFGF and maFGF treatment group were significant lower than those in A/R group (P<0.01).(3)The apoptosis rate of cardiomyocytes after A/R was significant lower than that of control group (P<0.01). Treatment with aFGF and maFGF decreased the apoptosis rate in A/R cardiomyocytes, the effect showed dose-dependent relationship.CONCLUSIONS:(1) maFGF attenuated myocardial anoxia-reoxygenation injury in the isolated rat heart, improved systolic and diastolic function of anoxia-reoxygenation myocardium, and played a protective role in A/R heart.(2) maFGF holded back the decrease of coronary flow after reoxygenation, attenuated the leakage of LDH from the cardiomyocytes, protected cellular membrane.(3) maFGF and aFGF reversed the decrease of SOD activity and the increase of MDA level induced by anoxia-reoxygenation, suppressed lipid peroxidation and played a protective role in the myocardium of anoxia-reoxygenation.(4) maFGF holded back the apoptosis of cardiomyocytes, the effect showed dose-dependent relationship.(5) The myocardial protective effect and mechanism of maFGF was similar to aFGF. The protection of aFGF was not dependent on it's mitogenetic activity.