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The efficacy of calcium channel blockers in reducing the effects of ischemia/reperfusion (I/R) injury in animals subjected to cigarette smoke was examined. In this study, 40 rats were divided into 4 groups. Groups A, B, and C received a controlled cigarette smoke exposure for 14 days, following which all animals underwent a standardized sciatic nerve I/R procedure. One sciatic nerve was isolated, and the femoral artery was occluded for 3 hours followed by reperfusion. Group B received verapamil (20 mg/kg/d). Group C received nifedipine (10 mg/kg/d). Mean sciatic function index (SFI) was significantly higher in nonsmoking than smoking animals, and the sciatic function index of group B (verapamil) and group C (nifedipine) was significantly greater than group A (smoking). Mean malondialdehyde at day 28 in group A was 0.96 ± 0.14 compared with 0.74 ± 0.11 in the nonsmoking group (P = 0.03), and the mean malondialdehyde in the nifedipine group was significantly greater than in group A (P = 0.05). Histologic injury scores were not significantly different among groups exposed to smoke. Smoking was associated with slower recovery following peripheral nerve I/R injury, but calcium channel blockers were shown to ameliorate these effects.