Myocardial hydroxyproline and mechanical response to prolonged pressure loading followed by unloading in the cat.

Abstract

A B S T R A C T To determine the myocardial response to prolonged pressure-loading and unloading, kittens weighing 0.8-1.2 kg underwent pulmonary artery banding, which initially elevated right ventricular (RV) systolic pressure by 10-15 mmHg. 52 and 76 wk later; RV weight/body weight had increased by -80%. Total RV hydroxyproline had increased significantly, whereas hydroxyproline concentration was unchanged from that of nonbanded animals of comparable age. In isometrically contracting RV papillary muscles, peak active force was significantly less at 76 wk (3.3±0.8 [SD] g/ mm2 than at 52 wk (5.1±0.8 g/mm2) or in nonbanded animals (4.8±0.8 g/mm2). Velocity of muscle shortening at comparable loads was unchanged after 52 wk but was significantly less after 76 wk. In nonstimulated, slowly stretched muscles, passive stiffness constants, a and ,B, derived from a = a(eft -1), where a is instantaneous stress and e is Lagrangian strain, were unchanged by banding. The band was removed after 52 wk in additional animals that were studied 24 wk later.In those animals with normal RV pressures at death, hypertrophy had regressed and hydroxyproline 'concentration was humans (1, 2) and experimental animals (3, 4) after removal of the hypertrophic stimulus. Unfortunately, this is not a universal occurrence and myocardial dysfunction may persist (1, 2, 5). The reasons for these therapeutic failures are unclear but myocardial fibrosis from prolonged overload often is incriminated as a major factor in the persistent dysfunction (6, 7). However, several studies have observed no increase in myocardial collagen or connective tissue concentration in patients dying with long-standing myocardial hypertrophy (8-10). An unanswered question and one that might contribute to these conflicting results regarding myocardial fibrosis is whether increased connective tissue that accompanies the hypertrophic process regresses when the stimulus for hypertrophy is removed. For example, connective tissue may increase proportionately to other myocardial constituents during hypertrophy but not regress or even continue to increase after removal of the stimulus, resulting in an increase in connective tissue concentration as muscle mass declines.Experimental studies of the hydroxyproline response to the development and regression of hypertrophy have produced conflicting data that may be due in part to differences in methods for producing hypertrophy. Baratosova (11) Engineering, Pennsauken, NJ). The compliance of the system without muscle but including the suture was 2 um/g and the equivalent mass of the lever system was 150 mg. Micrometers located above the lever permitted us to obtain isometric contractions (while varying muscle length by known amounts) or isotonic contractions under various afterloads (while maintaining initial muscle length constant).The muscle was stimulated at a frequency of 12/min and initially allowed to contract isotonically under a 0.5-g preload for 45-60 min at which time extent and rate of shortening were constant. Thereafte...