CARDIAC-HYPERTROPHY AND FAILURE - A DISEASE OF ADAPTATION - MODIFICATIONS IN MEMBRANE-PROTEINS PROVIDE A MOLECULAR-BASIS FOR ARRHYTHMOGENICITY

Cardiac hypertrophy is the physiological adaptation of the heart to ch ronic mechanical overload. Cardiac failure indicates the limits of the process. Cardiac hypertrophy is only one example of biological adapta tion and results from the induction of several changes in gene express ion, mostly of the fetal type, including those coding for the myosin h eavy chain or the alpha-subunit of the Na+,K+-ATPase. From a thermodyn amic point of view, the decrease in V(max) allows the heart to produce a normal tension at a lower cost. This process results from changes b oth in the sarcomere and in the expression of certain membrane protein s. The decrease in calcium transient is determined by several changes in membrane proteins that result in a rather fragile equilibrium in te rms of calcium homeostasis. Any abnormal input in calcium will have ex aggerated detrimental consequences on a hypertrophied myocyte and may cause automaticity and arrhythmias or an exaggerated response to anoxi a in terms of compliance.