Prolonging myocardial preservation with a modified University of Wisconsin solution containing 2,3-butanedione monoxime and calcium

Abstract

The University of Wisconsin solution is an effective preservative for cold storage of the cardiac allograft. In an earlier study we showed that addition of calcium and 2,3-butanedione monoxime, a reversible inhibitor of myocardial contracture, further improved preservation of the rabbit heart. In this study we investigated the following: (1) the effects of different concentrations of 2,3-butanedione monoxime and calcium on function of the preserved rabbit heart, (2) how heart preservation is affected when 2,3-butanedione monoxime and calcium are added to the St. Thomas’ Hospital and Stanford solutions, and (3) how 2,3-butanedione monoxime and calcium, at optimal concentrations in University of Wisconsin solution, affect hearts preserved up to 48 hours. Rabbit hearts were flushed with preservative and stored at 4° C for 24, 30, 40, or 48 hours. Myocardial function was assessed during 60 minutes of isolated reperfusion, and myocardial adenine nucleotide content was measured after completion of reperfusion. Three concentrations of 2,3-butanedione monoxime (15, 30, and 60 mmol/ L) in the University of Wisconsin solution were studied in hearts preserved for 30 hours. Storage with 2,3-butanedione monoxime at 30 mmol/L resulted in significantly better left ventricular developed pressure ( p < 0.01), left ventricular end-diastolic volume ( p < 0.01), rate of left ventricular pressure rise ( p < 0.01), coronary flow ( p < 0.05), rate-pressure product ( p < 0.001), and adenine nucleotide regeneration ( p < 0.05) than with 60 mmol/L, although function was not significantly different when the osmolarity of the solutions was equalized. There was significant reduction in end-diastolic volume ( p < 0.05) and adenine nucleotide recovery ( p < 0.01) when 2,3-butanedione monoxime was lowered to 15 mmol/L. Decreasing the calcium concentration from 1.0 to 0.1 mmol/L also had a deleterious effect on myocardial function ( p < 0.05). The addition of 30 mmol/L 2,3-butanedione monoxime and 1.0 mmol/L calcium to the St. Thomas’ or Stanford solutions improved preservation of the heart when compared with the unmodified solutions, but to a lesser degree than with the modified University of Wisconsin solution. After 24 to 48 hours of storage in University of Wisconsin solution containing 30 mmol/L 2,3-butanedione monoxime and 1.0 mmol/L calcium, there was substantial improvement in developed pressure ( p < 0.001), end-diastolic volume ( p < 0.05), and rate pressure product ( p < 0.001), although there was little effect on heart rate and coronary flow, when compared with the unmodified University of Wisconsin solution. We conclude that modification of the University of Wisconsin solution with 30 mmol/L 2,3-butanedione monoxime and 1.0 mmol/L calcium significantly improves long-term preservation of the rabbit heart. Further extension in preservation might be accomplished by optimizing the osmolarity of this modified solution. (J THORAC CARDIOVASC SURG 1994;107:764-75)