Circulation Research, Vol 53, 332-341, Copyright © 1983 by American Heart Association

ARTICLES

Contractile function, myosin ATPase activity and isozymes in the hypertrophied pig left ventricle after a chronic progressive pressure overload

T Wisenbaugh, P Allen, G Cooper 4th, H Holzgrefe, G Beller and B Carabello

Experimental right ventricular pressure-overload hypertrophy in small mammals is associated with early muscle dysfunction, even before the onset of overt pump failure. Experimental results are quite heterogeneous regarding muscle function of the pressure hypertrophied left ventricle. Muscle dysfunction of the right or left ventricle, when found, may be causally related to alterations of myosin ATPase activity and isozyme type. However, the effect of a gradual pressure overload, analogous to that which occurs in human aortic stenosis, on myocardial contractile function and myosin ATPase activity has not been studied in a large animal whose normal myosin isozyme pattern resembles that of man. We therefore studied pump performance, myocardial contractile function, and myosin ATPase activity and isozyme pattern in pigs with severe, gradually applied left ventricular pressure overload. Thirteen weeks after supravalvular aortic banding, 10 pigs grew more than 7-fold in body weight and were found to have an aortic stenosis area of 0.5 +/- 0.1 cm2 with a gradient of 93 +/- 12 mm Hg. Compared with nine control animals, the banded animals had a 67% increase in left ventricular mass relative to body weight without overt pump failure as measured by cardiac index and pulmonary artery wedge pressure. Left ventricular ejection performance, measured as shortening fraction, was maintained except in three animals with extreme hypertrophy, in which depressed ejection performance may have been due to an afterload mismatch, myocardial dysfunction, or both. Myocardial contractile function, determined from the end-systolic stress-diameter relationship, was normal except in two pigs in which ejection performance was depressed and left ventricular mass was more than doubled. Only the slow V3 isozyme of myosin ATPase was found in both normal and hypertrophied pig myocardium, and the ATPase activity was normal in pigs with all degrees of hypertrophy. Thus, in a large animal model of severe, gradual left ventricular pressure overload, in which myosin isozyme pattern remains apparently unaltered, moderate hypertrophy can be associated with normal myosin ATPase activity and contractile function that is normal by current methods of evaluation.

This article has been cited by other articles:

				Y. Ishibashi, M. Takahashi, Y. Isomatsu, F. Qiao, Y. Iijima, H. Shiraishi, J. M. Simsic, C. F. Baicu, J. Robbins, M. R. Zile, et al. Role of microtubules versus myosin heavy chain isoforms in contractile dysfunction of hypertrophied murine cardiocytes Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1270 - H1285. [Abstract] [Full Text] [PDF]

				A. Banerjee, A. M. Mendelsohn, T. K. Knilans, R. A. Meyer, and D. C. Schwartz Effect of myocardial hypertrophy on systolic and diastolic function in children: insights from the force-frequency and relaxation-frequency relationships J. Am. Coll. Cardiol., October 1, 1998; 32(4): 1088 - 1095. [Abstract] [Full Text] [PDF]

				M. Koide, M. Nagatsu, M. R. Zile, M. Hamawaki, M. M. Swindle, G. Keech, G. DeFreyte, H. Tagawa, G. Cooper IV, and B. A. Carabello Premorbid Determinants of Left Ventricular Dysfunction in a Novel Model of Gradually Induced Pressure Overload in the Adult Canine Circulation, March 18, 1997; 95(6): 1601 - 1610. [Abstract] [Full Text]

				B. D. Hoit, Y. Shao, M. Gabel, and R. A. Walsh Disparate Effects of Early Pressure Overload Hypertrophy on Velocity-Dependent and Force-Dependent Indices of Ventricular Performance in the Conscious Baboon Circulation, February 15, 1995; 91(4): 1213 - 1220. [Abstract] [Full Text]