Loss of mitochondrial respiratory function and its suppression during cold ischemic preservation of rat livers with University of Wisconsin solution.
Preservation of the liver involves a period of cold (0 degrees to 4 degrees C) ischemia; the longer the ischemic period, the greater the injury to the liver. The mechanisms for cold-induced ischemic injury are not known, but it is clear that after preservation the liver has a reduced capacity to regenerate high-energy phosphate compounds (ATP). One cause for the delayed rate of ATP synthesis could be injury to the mitochondria. The effects of long-term (more than 24 hr) preservation on liver mitochondrial function have not been previously studied. In this study, rat livers were preserved in University of Wisconsin solution at 4 degrees C for up to 96 hr. After preservation, mitochondrial respiratory function was assayed in a homogenate and in isolated mitochondria. We saw a progressive increase in oligomycin-sensitive respiration with time of preservation (from 1.2 +/- 0.09 mumol.min-1.gm tissue-1 at 0 hr to 3.8 +/- 0.2 mumol.min-1.gm tissue-1 after 96 hr). The increase after 24-hr preservation (2.1 +/- 0.2 mumol.min-1.gm tissue-1) was also significantly greater than 0 time values (p less than 0.05). No decrease was found in uncoupler-stimulated respiration for up to 48 hr of preservation; only a small decrease was seen after 72 hr of preservation (about 30%). The cause of the increase in oligomycin-sensitive respiration appeared to be related to free fatty acids (or another uncoupling factor) generated during preservation. This was suggested from the fact that bovine serum albumin prevented the increase in oligomycin-sensitive respiration after all periods of preservation.(ABSTRACT TRUNCATED AT 250 WORDS)
Kim
S K
SK
Department of Biomolecular Chemistry, University of Wisconsin, Madison 53792.
Belzer
F O
FO
Southard
J H
JH
D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology; D015925:Cryopreservation; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology; D005978:Glutathione; D007328:Insulin; D008099:Liver; D008297:Male; D008930:Mitochondria, Liver / Q000502:physiology*; D009840:Oligomycins / Q000494:pharmacology; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D010101:Oxygen Consumption / Q000187:drug effects; D011887:Raffinose; D051381:Rats; D011919:Rats, Inbred Strains; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D012996:Solutions; D013997:Time Factors; D014700:Verapamil / Q000494:pharmacology
D005230:Fatty Acids, Nonesterified; D007328:Insulin; D009840:Oligomycins; D019188:Organ Preservation Solutions; D012996:Solutions; C055206:University of Wisconsin-lactobionate solution; D012710:Serum Albumin, Bovine; D000493:Allopurinol; D014700:Verapamil; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose; D002746:Chlorpromazine