PRECONDITIONING WITH CROMAKALIM IMPROVES LONG-TERM MYOCARDIAL PRESERVATION FOR HEART-TRANSPLANTATION

Background. Myocardial preservation for heart transplantation relies o n hyperkalemic cardiac arrest and hypothermic storage. Our study inves tigated whether pretreatment with a potassium-channel opener (cromakal im) before prolonged storage in an extracellular fluid improves left v entricular recovery. Methods. Rabbit hearts were submitted to 6-hours' cold storage and assessed on a blood-perfused isolated heart preparat ion. Hemodynamic recovery, enzyme release (creatine kinase and lactate dehydrogenase), and adenine nucleotide content were determined. Five groups were tested: control (n = 6), no ischemia; UW group (n = 7), he arts arrested with and stored in University of Wisconsin solution; STH group (n = 5), hearts arrested with and stored in St. Thomas' Hospita l solution; cromakalim group (n = 6), hearts pretreated with cromakali m (30 mu g/kg) before arrest with and storage in St. Thomas' Hospital solution; and glibenclamide group (n = 5), hearts pretreated with crom akalim followed by glibenclamide (a potassium-channel blocker) before arrest with and storage in St. Thomas' Hospital solution. Results. Hem odynamic recovery was improved and enzyme release was lower in the UW group than in the STH group. Compared with the STH group, the group pr etreated with cromakalim had significantly decreased left ventricular end-diastolic pressures, increased left ventricular developed pressure s, increased maximal values of positive and negative rates of rise of left ventricular pressure, and increased time constant of isovolumetri c relaxation. Hemodynamic recovery was similar in the UW group and cro makalim groups. Glibenclamide did not abolish the effects of cromakali m. None of the protocols affected myocardial energy stores. Conclusion s. Pretreatment with cromakalim affords additional protection to that provided by cardioplegic arrest and prolonged cold storage using an ex tracellular solution. The intracellular mechanisms involved remain to be determined. (C) 1998 by The Society of Thoracic Surgeons.