Simultaneous study of metabolism and function following cardioplegic arrest: a novel method of evaluation of the transplanted heart in the rat

Abstract

Background: Limitations of the isolated perfused rat heart model for heart preservation studies include short study time due to the lack of stability of the preparation. We aimed to develop a new experimental model based on heterotopic heart transplantation in the rat to achieve simultaneous 31P magnetic resonance spectroscopy (MRS) and functional study of the transplanted heart during early and late blood reperfusion. Methods Twenty-five Lewis rats underwent heterotopic abdominal isograft heart transplantation and were randomized in two groups. Hearts were harvested after cardioplegic arrest induced with Centre de Résonance Magnétique Biologique et Médicale (CRMBM) solution and then stored at 4°C for a total ischemic time of 3 hours. Graft contractility measurement and simultaneous 31P MRS were performed after 1 hour and 24 hours of blood reperfusion, respectively, in groups I ( n = 12) and II ( n =13). Results Contractility improved during reperfusion. The mean rate pressure product plus or minus standard error of mean increased from 11,373 ± 1,377 mm Hg/min in group I to 24,363 ± 3,860 mm Hg/min in group II ( P = 0.003), while mean dP/dtmax increased from 1,642 ± 173 mm Hg/sec to 2,571 ± 333 mm Hg/sec, respectively ( p = 0.03). Simultaneously, both the phosphocreatine/adenosine triphosphate (ATP) and inorganic phosphate/ATP ratios decreased from group I to group II ( p = 0.025 and p = 0.015, respectively), suggesting regeneration of the intracellular pool of ATP in group II. Conclusions Simultaneous functional and metabolic studies of the transplanted heart are feasible in rats. Improvement in contractility during late reperfusion is contemporary with significant changes in energetic metabolism. Our model should be useful for the further improvement of heart preservation, which may result in significant clinical progress.