Relaxation Abnormalities

11 October, 2012 (21:19) | Heart Diseases | By: Health news

Slowed relaxation was noted in early studies of experimental cardiac hypertrophy, but it was not until the past decade that the importance of lusitropic (relaxation) abnormalities was clearly demonstrated in patients with congestive heart failure. Although an impairment of the ion pumps that cause the myocardium to relax could be due in part to a chronic energy deficiency in the overloaded cells of the hypertrophied and failing heart (as described earlier), recent studies indicate that more complex molecular mechanisms contribute to the diastolic abnormalities. For example, relaxation is slowed in papillary muscles from cardiac-transplant recipients with dilated and hypertrophic cardiomyopathy, even after the tissue is isolated and studied in vitro.

Slowing of the active transport of calcium has been shown in several studies of sarcoplasmic-reticulum vesicles obtained from hypertrophied hearts. In keeping with the earlier emphasis on depressed contractility, this abnormality was initially interpreted as explaining the inotropic rather than the lusitropic abnormalities in heart failure. However, these observations have assumed new importance with the recognition of the clinical importance of relaxation abnormalities in the failing heart.

Impaired relaxation in the failing heart could be explained in part if the uptake of calcium by the sarcoplasmic reticulum was slowed by a chemical-energy deficit or altered membrane assembly. There are, however, other plausible explanations for this lusitropic abnormality; for example, diastolic stiffness may be increased by the spontaneous recycling of calcium in the sarcoplasmic reticulum during diastole. In addition, the energy-dependent reactions that cause the hypertrophied heart to relax appear to be abnormally sensitive to a fall in high-energy phosphate levels, such as occurs in hypoxia. This finding could be explained in part by the attenuation of an allosteric effect of ATP that accelerates the rate of the calcium pump of the sarcoplasmic reticulum. Reports that the calcium sensitivity of the sodium—calcium exchanger is reduced in hypertrophied rat hearts and that the activity of this important mechanism for the extrusion of calcium from the myocardial cell is depressed late in the course of heart failure in hamsters with cardiomyopathy suggest yet other causes for the lusitropic abnormalities in heart failure.