FROM OVERLOAD TO FAILURE - WHAT HAPPENS INSIDE THE MYOCYTE

To determine whether there is a defect in the surviving muscle cells o f the failing human heart, studies have been performed on individual m yocytes isolated from normal and failing human myocardium. Myocytes fr om the failing ventricle contract and relax more slowly, and have a re duced contraction amplitude at physiological (but not low) stimulation frequencies. Slow relaxation is seen irrespective of the aetiology of the heart disease studied, and is more pronounced in myocytes from hy pertrophied ventricles. Myocytes from hypertrophied ventricles are lar ger than normal, but the relaxation deficit is independent of cell siz e. beta-adrenoceptor desensitization is evident in myocytes and it var ies according to the severity of disease and with the age of the patie nt. Action potentials are longer in myocytes from failing human heart, probably because of an alteration in K+ current density. Many of the functional changes identified in failing human myocardium are seen at the level of the single cardiac myocyte, which implies that pharmacolo gical or genetic manipulation of surviving cells is a logical therapeu tic strategy.