ISCHEMIA AND REPERFUSION INJURY OF THE RAT-LIVER - THE ROLE OF NIMODIPINE

The protective effect of the calcium channel blocker nimodipine on liv er ischemia and reperfusion was studied in the rat. The homeostasis of intracellular calcium ions seems to be a determinant factor in the ce ll injury that appears after ischemia and reperfusion. Nimodipine was used to downregulate the calcium levels in the cytosol of the ischemic cell, the hypothetical role of Ca2+ in the pathogenesis of ischemia a nd reperfusion injury. The experimental procedure consisted of the tem porary interruption of blood how to the left lateral and medial lobes of the rat liver and subsequent reperfusion after a period of 45 min o f ischemia. Nimodipine (10 mu g/kg body wt) was administered either be fore or after the onset of ischemia. The postischemic liver blood flow and liver oxyhemoglobin saturation were recorded using a He-Ne laser Doppler flowmeter and photometer, which showed, in the pretreated grou p, a recovery of reperfusion blood flow (58.1%) and liver reflectance (85.5%) significantly better (P < 0.01 and P < 0.001) than those in th e respective untreated controls of how (32.8%) and reflectance (70.5%) . In the group that received nimodipine after ischemia, the recovery o f the blood flow and the postreperfusion liver reflectance were not si gnificantly better than those in the untreated control group. ALT leve ls (P < 0.05), galactose elimination capacity (P < 0.001), and histolo gical studies also showed a protective effect of calcium antagonist ni modipine when administered before ischemia. (C) 1996 Academic Press, I nc.