Age-dependent Changes in the Effects of Endocardial Endothelium on the Contractile Characteristics of its Adjacent Myocardium in Rats

Abstract

Cardiac contractility and the ability of myocardium to respond to various stimuli have been shown to be age-related. Endocardial endothelium has been shown to modulate the performance of its adjacent myocardium, and it has been proven that these changes are reversible by increasing extracellular calcium. This study was designed to evaluate whether the effects of endocardial endothelium and their modifications with changing extracellular calcium were age-dependent. Experiments were carried out on left ventricular papillary muscles isolated from male Wistar rats belonging to three different age groups: 7 weeks, 4 months, and 9 months old. Extracellular calcium concentration (0.7 to 5 mm) curves were conducted in papillary muscles with intact endocardial endothelium (+EE) and after its removal (−EE) with Triton X-100. At a low extracellular calcium concentration (0.7 mm), total tension (TT), maximum rate of tension development (+dT/dt), time to peak tension (TTPT), and time to half tension decline from maximum tension (RT) increased with increasing age (P<0.01). Increasing extracellular calcium concentration eliminated age-related differences in TT and RT did not affect TTPT and caused +dT/dtto increase to greater levels in 7-week-old as compared to 4-month-old myocardium. Endocardial endothelial removal (−EE) had a greater effect on contractile indices in younger rats. Increasing extracellular calcium concentration eliminated EE-mediated changes in contractile indices regardless of age. Thus, increasing extracellular calcium concentration had a greater effect in younger rats and after −EE. Increasing extracellular calcium from 0.7 to 2.5 mmincreased total tension in 7-week-olds, between 56% +EE and 131% −EE (P<0.01); in 4-month-olds, from 29% +EE to 57% −EE (P<0.01); and in 9-month-olds, from 13% +EE to 23% −EE (P=0.08). These results indicate that the contractile effects of endocardial endothelium are both age- and calcium-dependent, with responsiveness to endocardial endothelium decreasing with age. Myocardial contractile characteristics also vary with age and these differences are only partially reversible with increasing extracellular calcium concentration.