Ischemia and reperfusion injury of the rat liver: the role of nimodipine.
The protective effect of the calcium channel blocker nimodipine on liver ischemia and reperfusion was studied in the rat. The homeostasis of intracellular calcium ions seems to be a determinant factor in the cell 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 and reperfusion injury. The experimental procedure consisted of the temporary interruption of blood flow to the left lateral and medial lobes of the rat liver and subsequent reperfusion after a period of 45 min of ischemia. Nimodipine (10 micrograms/kg body wt) was administered either before 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 group, 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 the respective untreated controls of flow (32.8%) and reflectance (70.5%). In the group that received nimodipine after ischemia, the recovery of the blood flow and the postreperfusion liver reflectance were not significantly better than those in the untreated control group. ALT levels (P < 0.05), galactose elimination capacity (P < 0.001), and histological studies also showed a protective effect of calcium antagonist nimodipine when administered before ischemia.
Chávez-Cartaya
R E
RE
University of Cambridge Clinical School, Addenbrookes Hospital, Department of Surgery, United Kingdom.
Pino DeSola
G
G
Ramirez-Romero
P
P
Calne
R Y
RY
Jamieson
N V
NV
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D006454:Hemoglobins / Q000378:metabolism; D007511:Ischemia / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D008099:Liver / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D008102:Liver Circulation / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009553:Nimodipine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000473:pathology / Q000503:physiopathology*
D002121:Calcium Channel Blockers; D006454:Hemoglobins; D009553:Nimodipine