Cardiac storage with University of Wisconsin solution and a nucleoside-transport blocker.
Findings from previous investigations conducted at this institution and others have suggested that University of Wisconsin solution (UWS) is preferable for the prolonged hypothermic storage of hearts before transplantation. The benefit seen with UWS may in part be related to the inclusion of adenosine (5 mmol/L) in the UWS. To investigate whether further manipulations of adenosine metabolism might enhance myocardial protection, studies were initially conducted using cultured myocytes, followed by confirmatory experiments using isolated rat hearts. Cultured human ventricular myocytes (7 to 8 dishes/group) were stored for 12 hours at 0 degrees C in unmodified UWS or UWS supplemented with increasing concentrations (1 to 100 mumol/L) of the nucleoside-transport blocker p-nitrobenzylthioinosine. The adenosine triphosphate concentrations were found to be enhanced with nucleoside-transport inhibition, with the best results achieved with the 1- and 3-mumol/L groups (control, 3.37 +/- 0.41 nmol/micrograms DNA; UWS, 2.89 +/- 1.31 nmol/micrograms DNA; 1 mumol/L, 5.91 +/- 3.23 nmol/micrograms DNA; 3 mumol/L, 7.86 +/- 3.45 nmol/micrograms DNA; p < 0.05 versus control or UWS group). Isolated rodent hearts from Sprague-Dawley rats were prepared on a Langendorff apparatus with an intraventricular balloon and subsequently stored for 8 hours at 0 degrees C in unmodified UWS (13 hearts/group) or UWS supplemented with 1 or 3 mumol/L of p-nitrobenzylthioinosine (9 to 10 hearts/group).(ABSTRACT TRUNCATED AT 250 WORDS)
Fremes
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SE
Division of Cardiovascular Surgery, University of Toronto, Ontario, Canada.
Furukawa
R D
RD
Zhang
J
J
Li
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RK
Tumiati
L C
LC
Weisel
R D
RD
Mickle
D A
DA
D000227:Adenine Nucleotides / Q000378:metabolism; D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D002478:Cells, Cultured; D003326:Coronary Circulation; D003402:Creatine Kinase / Q000378:metabolism; D004247:DNA / Q000378:metabolism; D005978:Glutathione; D016027:Heart Transplantation; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D033703:Nucleoside Transport Proteins; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D011684:Purine Nucleosides / Q000378:metabolism; D011887:Raffinose; D051381:Rats; D017207:Rats, Sprague-Dawley; D013868:Thioinosine / Q000031:analogs & derivatives* / Q000494:pharmacology
D000227:Adenine Nucleotides; D002352:Carrier Proteins; D007328:Insulin; D008565:Membrane Proteins; D033703:Nucleoside Transport Proteins; D019188:Organ Preservation Solutions; D011684:Purine Nucleosides; C055206:University of Wisconsin-lactobionate solution; D013868:Thioinosine; D000493:Allopurinol; D004247:DNA; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D005978:Glutathione; C001789:4-nitrobenzylthioinosine; D000241:Adenosine; D011887:Raffinose