title: Remodeling of the heart in chronic pressure overload.
abstract: Cardiac hypertrophy resulting from a chronic mechanical overload is the physiological adaptation of the heart to a disease. From a physiological point of view it is characterized by a slowing of the maximum unloaded shortening velocity and an increased duration of the action potential. This slowing allows the heart to maintain a normal maximum tension at a slower rate. In addition, the heart produced per gram of tension is normalized and the efficiency returns to normal. From a biological point of view the expression of two protooncogenes and of two heat-shock proteins genes is enhanced at the beginning of the overload. The biological determinants of the changed shortening velocity are species-specific. An isomyosin shift plays a major role in some species, e.g., rat, while in others, e.g., man, changes in membrane proteins are determinant. The density in Ca2+ channels remains unmodified, with a significant drop in the density of Ca2+ ATPase of SR, adrenergic and muscarinic receptors, and a slowing of the Na+/Ca2+ exchange. More complex changes occur at the level of the Na+, K+ ATPase. One of the principal consequences of these findings is that most of the usual targets of inotropes are modified and that new drugs have to be conceptualized accordingly.
authors.affiliation: U 127 INSERM, Hopital Lariboisière, France.
authors.forename: B
authors.initials: B
authors.lastname: Swynghedauw
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000188:drug therapy / Q000209:etiology* / Q000503:physiopathology; D015870:Gene Expression; D006333:Heart Failure / Q000150:complications / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000503:physiopathology; D009200:Myocardial Contraction / Q000502:physiology; D009218:Myosins / Q000378:metabolism; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
chemical_list: D009218:Myosins; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium