An improved isolated, left ventricular ejecting, murine heart model - Functional and metabolic evaluation

An improved, isolated, left ventricular-ejecting, murine heart model is des cribed and evaluated. Special attention was paid to the design and impedanc e characteristics of the artificial aortic outflow tract and perfusate comp osition, which contained glucose (10 mM plus insulin) and pyruvate (1.5 mM) as substrates. Temperature of the isolated perfused hearts was maintained at 38.5 degrees C. During antegrade perfusion (preload 10 mm Hg, afterload 50 mm Hg, 2.5 mM Ca2+) proper design of the aortic outflow tract provided b aseline values for cardiac output (CO), left ventricular developed pressure (LVDP) and the maximum first derivative of left ventricular pressure (LV d P/dt(max)) of 11.1 +/- 1.7 ml min(-1), 83 +/- 5 mm Hg and 6283 +/- 552 mm H g s(-1), respectively, resembling findings in the intact mouse. During 100 min normoxic antegrade perfusion CO declined non-significantly by less than 10%. Varying pre- and afterloads resulted in typical Frank-Starling relati onships with maximal CO values of 18.6 +/- 1.8 ml min(-1) at pre- and after load pressures of 25 and 50 mm Hg, respectively Left ventricular function c urves were constructed at free [Ca2+] of 1.5 and 2.5 mM in the perfusion me dium. Significantly higher values for CO, LVDP and LV dP/dt(max) and LV dP/ dt(max) were obtained at 2.5 mM Ca2+ at all loading conditions investigated . Phosphocreatine and creatine levels remained stable throughout the perfus ion period. Despite a small but significant decline in tissue ATP content, the sum of adenine nucleotides did not change during the normoxic perfusion period. The tissue content of glycogen increased significantly.