Cardiac alterations at the myofibrillar level: is a redistribution of the myosin isoenzyme pattern decisive for cardiac failure in haemodynamic overload?

Cardiac muscle physiology, cardiac dynamics and energetics of normotensive and hypertensive rats [Goldblatt II, spontaneously hypertensive rats (SHR)] are analyzed in the light of the question of whether a shift in the isoenzyme pattern of myosin in favour of the isoenzyme VM-3--i.e., transformation towards a slower muscle--is the essential factor for manifestation of cardiac insufficiency under chronic haemodynamic overload. Earlier investigations on chemically skinned myocardial preparations with homogeneous VM-3 and VM-1 patterns revealed that the decrease in unloaded shortening velocity attributable to extreme redistribution of the isoenzyme pattern can amount to approx. 40% whereas isometric tension development at the myofibrillar level is not significantly reduced. Findings from old normotensive and spontaneously hypertensive rates show that even substantial prevalence of VM-3 permits adequate ventricular pumping function. The decrease in the systolic parameters observed in later stages of chronic pressure overload may be attributed primarily to regressive alterations (fibrosis, structural dilatation). Under chronic haemodynamic overload, experimentally imposed isoenzyme redistribution towards a faster myocardium (small thyroxine doses) as well as transformation towards a slower muscle (thyrostatic treatment) affects the time parameters of contraction and oxygen consumption more than left ventricular work capacity. Signs of congestive heart failure are absent. It is concluded that mere transformation of myocardium towards a more slowly functioning muscle should not be considered the cause of cardiac failure in the rat model although this adaptive process may have detrimental consequences under certain conditions.