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°C in unmodified UWS or UWS supplemented with increasing concentrations (1 to 100 μmol/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-μmol/L groups (control, 3.37 ± 0.41 nmol/μg DNA; UWS, 2.89 ± 1.31 nmol/μg DNA; 1 μmol/L, 5.91 ± 3.23 nmol/μg DNA; 3 μmol/L, 7.86 ± 3.45 nmol/μg 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°C in unmodified UWS (13 hearts/group) or UWS supplemented with 1 or 3 μmol/L of p-nitrobenzylthioinosine (9 to 10 hearts/group). In separate experiments (5 to 6 hearts/group), the tissue levels of purine metabolites were monitored. The addition of the nucleoside-transport blocker was associated with an increased postischemic developed pressure (UWS, 66.2% ± 11.1%; 1 μmol/L, 75.8% ± 6.4%; 3 μmol/L, 78.3% ± 10.7%; p < 0.05 UWS versus 1- or 3-μmol/L group) while diastolic compliance was reduced after storage in all groups (p = 0.01). Coronary flow was increased in association with the nucleoside-transport blocker (UWS, 71.3% ± 16.7%; 1 μmol/L, 78.5% ± 11.0%; 3 μmol/L, 86.6% ± 13.3%; p < 0.05 UWS versus 3 μmol/L). The p-nitrobenzylthioinosine did seem to block nucleoside transport, as the hypoxanthine content was unmeasurable after perfusion in the treated groups compared with the findings in the group receiving unmodified UWS (p < 0.01).