Early Changes Induced in the Left Ventricle by Pressure Overload. An Experimental Study on Swine Heart

C. Nediani, L. Formigli, A. M. Perna, L. Ibba-Manneschi, S. Zecchi-Orlandini, C. Fiorillo, V. Ponziani, C. Cecchi, P. Liguori, G. Fratini and P. Nassi. Early Changes Induced in the Left Ventricle by Pressure Overload. An Experimental Study on Swine Heart. Journal of Molecular and Cellular Cardiology (2000) 32, 131–142. The purpose of this study was to evaluate the early changes in sarcoplasmic reticulum (SR) function and the parallel morphological and hemodynamic modifications occurring in the heart following pressure overload. As regards SR function, we also explored the levels of acylphosphatase, an enzyme which might have a regulatory effect on the SR Ca2+pump by hydrolyzing the phosphorylated intermediate of this transport system. Pigs subjected to pressure overload by aortic stenosis for 6, 12, 24, 48, 72, and 96 h were compared to sham-operated controls. At each of the considered times both SR Ca2+-ATPase activity and Ca2+uptake, as well as acylphosphatase activity, were significantly enhanced in the pressure overloaded compared to the control hearts, with a maximal increase at 6 h; moreover, a positive and significant correlation was found between these parameters. The modifications in the activities of Ca2+-ATPase and acylphosphatase reflected an increased expression of these proteins, while phospholamban did not show significant changes in its concentration nor in its phosphorylation status. As for hemodynamic parameters, rapid changes in the left ventricular function were observed and especially the early hours following the aortic stenosis appeared to be crucial for the adjustment of heart function. The most relevant morphological finding was a focal disarrangement of the myofibrillar pattern which was very evident at 6 h, and progressively attenuated at later times. Taken together our data suggest that an early adaptation to the increased hemodynamic working overload is a consistent activation of the contractile apparatus which reflects, at least in part, an enhanced SR function. Besides the changes in Ca2+pump protein expression, increased acylphosphatase levels might also contribute to this effect.