Inhibition of the increase of intrahepatic Ca2+ by diltiazem in rats with liver ischemia.
The effects of a continuous infusion of a calcium entry blocker, 1, 5-benzothiazepine derivative (diltiazem), on ischemic liver cell damage were studied using quantitative 45Ca-autoradiographic and liquid scintillation techniques. The drug was administered to male Wistar rats as a continuous infusion for 3 h, beginning 30 min before ischemia. Autoradiographic studies showed that 45Ca accumulated in the liver lobuli after 1 h of liver ischemia and 3 h of reperfusion, but the level of 45Ca accumulation was significantly lower in drug-treated rats than in untreated animals. In addition, liquid scintillation studies showed significant differences in the intrahepatic 45Ca contents. These results suggest that diltiazem may inhibit the rise of intracellular Ca2+ due to the flow of extracellular Ca2+ into the cytosol, and may protect the ischemic liver from damage.
Kurita
K
K
First Department of Surgery, Kagoshima University, School of Medicine, Japan.
Tanabe
G
G
Aikou
T
T
Shimazu
H
H
D000818:Animals; D001345:Autoradiography; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D002132:Calcium Radioisotopes; D003600:Cytosol / Q000378:metabolism; D004110:Diltiazem / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D007511:Ischemia / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism; D008099:Liver / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D015220:Calcium Channels; D002132:Calcium Radioisotopes; D008054:Lipid Peroxides; D004110:Diltiazem; D002118:Calcium