Verapamil improves rat hepatic preservation with UW solution.
Verapamil, a calcium channel blocker, improves myocardial preservation during cold cardioplegia and protects against renal damage during periods of warm and cold ischemia. To determine if verapamil could prevent ischemic damage to livers during and after cold storage, harvested rat livers were flushed with either University of Wisconsin (UW) solution or UW solution with 25 mg/liter verapamil. Twenty rats were used in each group. After 24 hr of storage at 4 degrees C, livers were perfused with oxygenated blood through the portal veins for 2 hr at 37 degrees C and pH 7.4. Liver enzymes, electrolytes, and perfusate flow rate were determined at 30-min intervals. At 90 min of perfusion, the verapamil group of livers had less elevation of AST (110 +/- 17 IU/liter vs 172 +/- 25 IU/liter, P less than 0.05), ALT (115 +/- 21 IU/liter vs 210 +/- 34 IU/liter, P less than 0.05), and LDH (962 +/- 170 IU/liter vs 1452 +/- 253 IU/liter, NS). Verapamil livers produced more bile than controls (6.9 +/- 1.9 microliters/g vs 2.3 +/- 1.7 microliter/g, P less than 0.05) and maintained a higher portal flow rate throughout the perfusion. Both groups showed similar reduction in liver weights after storage (3.9 +/- 0.9% vs 2.8 +/- 0.7%) and required the same amount of bicarbonate for correction of acidosis during perfusion (2.6 +/- 0.2 mM vs 2.8 +/- 0.2 mM). Light microscopic exam after perfusion showed hepatocyte damage in 30% of control livers, but 0% of verapamil livers. We conclude that verapamil-treated rat livers showed less damage and better function upon reperfusion after 24 hr of cold storage. This agent may be clinically useful as an additive to the UW preservation solution for livers.
Cheng
S
S
Department of Surgery, Oregon Health Sciences University, Portland 97201.
Ragsdale
J R
JR
Sasaki
A W
AW
Lee
R G
RG
Deveney
C W
CW
Pinson
C W
CW
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D005978:Glutathione; D007328:Insulin; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008102:Liver Circulation; D008297:Male; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D011887:Raffinose; D051381:Rats; D011919:Rats, Inbred Strains; D012996:Solutions; D014021:Tissue Preservation; D014700:Verapamil / Q000494:pharmacology*
D007328:Insulin; D019188:Organ Preservation Solutions; D012996:Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D014700:Verapamil; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose