Abstract

The University of Wisconsin solution modified with 2,3-butanedione monoxime and calcium experimentally extends the limits of ischemic preservation of the heart. This study evaluates other characteristics of this modified solution that may further enhance preservation: osmolarity, Mg 2+ concentration ([Mg 2+]), and pH. Rabbit hearts were flushed with the modified University of Wisconsin solution and stored for 40 hours at 4 °C. Maximal left ventricular developed pressure (LVDP), left ventricular end-diastolic volume (LVEDV), maximum rate of increase of left ventricular pressure (dP/dt), heart rate, and coronary flow were measured during 60 minutes of isolated crystalloid reperfusion with an isovolumic left ventricular balloon at constant end-diastolic pressure. Creatine kinase release and myocardial adenine nucleotide content were measured at completion of reperfusion. Solution osmolarity was tested at 357, 327, 297, and 277 mOsm/L by reducing K +, Na +, and lactobionate concentrations. [Mg 2+]was assessed at 5 and 16 mmol/L. Solution pH was studied at 7.0, 7.4, and 7.8. A control group of hearts was flushed and immediately reperfused to establish baseline function. Hearts stored in either hypertonic (357 mOsm/L) or hypotonic (277 mOsm/L) solutions functioned poorly, reaching 58% and 50% of control LVDP ( p < 0.001), 49% ( p < 0.01), and 58% ( p = not significant) of LVEDV, 56% and 49% of +dP/dt ( p < 0.001), respectively, and released substantially more creatine kinase ( p < 0.001 versus control). Hearts stored in near-isotonic solutions (327 and 297 mOsm/L) functioned better, attaining 79% and 72% of control LVDP ( p < 0.05), 94% and 110% of LVEDV ( p = not significant), 89% and 85% of +dP/dt ( p = not significant), respectively, and released less creatine kinase ( p = not significant versus control). An increase in [Mg 2+]to 16 mmol/L further improved LVDP to 84% ( p < 0.05), and dP/dt to 91% of control ( p = not significant). Adenosine triphosphatase regeneration also returned to control levels. Raising or lowering the solution pH resulted in significantly worsened ventricular function and a greater creatine kinase release ( p < 0.001). We conclude that hearts preserved in this modified University of Wisconsin solution regain substantial ventricular function, even after 40 hours of cold ischemia, when the solution osmolarity is kept between 297 and 327 mOsm/L, [Mg 2+]is elevated to 16 mmol/L, and pH is maintained at 7.4.

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