Objective: To compare the protective effect of different dose of penehyclidine hydrochloride (PHC) in rats with myocardial ischemia/reperfusion (I/R) injury.
Methods: Forty-eight healthy male Wistar rats were randomly divided into six groups (n = 8 each): sham group, sham + 1.0 mg/kg PHC group (sham + H-PHC group), I/R group, I/R + 0.1 mg/kg PHC preconditioning group (I/R + L-PHC group), I/R + 0.3 mg/kg PHC preconditioning group (I/R + M-PHC group), and I/R + 1.0 mg/kg PHC preconditioning group (/R + H-PHC group). 1/R injury model was reproduced by ligation followed by release of the coronary artery, and PHC in different dosages was given' at 30 minutes before model reproduction. At 3 hours after reperfusion, the left ventricular end-diastolic pressure (LVEDP), left ventricular end-systolic pressure (LVESP), ejection fraction (EF), and fractional shortening (FS) were recorded. The levels of aspertate aminotransferase (AST), MB isoenzyme of creatine kinase (CK-MB), and lactate dehydrogenase (LDH) were determined. The myocardial tissues were harvested for the determination of the area at risk (AAR) and the infarct area (AI), and the percentage of AI/AAR was calculated. The examination of myocardial fiber was performed with electron microscopy.
Results: Compared with sham and sham + H-PHC groups, LVEDP was increased in I/R groups, LVESP, EF and FS were decreased, and the levels of AST, CK-MB and LDH, as well as the AI/AAR were increased. Compared with I/R group, in pretreatment groups with different doses of PHC, LVEDP was decreased, LVESP, EF and FS were increased, the levels of AST, CK-MB, LDH, and AI/AAR were also decreased, especially in I/R+M-PHC and I/R+H-PHC groups [LVEDP (mmHg, 1 mmHg = 0.133 kPa): 11.33 ±1.17, 9.85 ± 1.09 vs. 15.82 ± 1.79, LVESP (mmHg): 98.9 ± 10.6, 112.8 ± 10.0 vs. 87.8 ± 9.2, EF: 0.681 ± 0.074, 0.741 ± 0.070 vs. 0.569 ± 0.072, FS: (42.4 ± 4.6)%, (46.0 ± 5.1 )% vs. (36.8 ± 3.9)%, AST (U/L): 386.97 ± 80.65, 298.31 ± 54.88 vs. 603.47 ± 173.66, CK-MB (U/L): 3.12 ± 0.84, 2.88 ± 0.72 vs. 7.14 ± 1.54, LDH (U/L): 1,784.23 ± 488.49, 1,629.37 ± 436.34 vs. 2,489.14 ± 460.80, AI/AAR: 0.284 ± 0.014, 0.223 ± 0.008 vs. 0.377 ± 0.011, all P < 0.05]. There was significant difference in LVEDP, LVESP, and AI/AAR between I/R + M-PHC group and I/R + H-PHC group (all P < 0.05), and no significant difference in other parameters (all P > 0.05). It was showed by electron microscopic examination that after I/R injury, the myocyte mitochondria membranes were broken, mitochondria were markedly swollen, mitochondrial cristae disappeared; however in I/R+M-PHC and I/R+H-PHC groups, mitochondrial swelling was mild, the capsule was more or less intact, mitochondrial cristae were partly visible, the structure was complete, especially in the group I/R+H-PHC, and the mitochondrial structure was close to normal.
Conclusions: PHC could protect myocardial from I/R injury. Mid dose of PHC (0.3 mg/kg) and high dose of PHC (1.0 mg/kg) could provide better protective effect than low dose of PHC (0.1 mg/kg), and high dose of PHC is better in effect than the middle dose.