Effects of uremic serum on isolated cardiac myocyte calcium cycling and contractile function.

Abstract

These data show that one or more substances are present in uremic sera that acutely cause increased force of contraction and impaired recovery of cardiac myocyte calcium concentration as well as impaired relaxation. As these effects are similar to that seen with ouabain and can be prevented by co-incubation with an antibody fragment to digitalis, which also attenuates the sodium pump inhibitory effect, we suggest that this (these) substance(s) circulating in uremic sera and inhibiting the sodium pump also causes the acute diastolic dysfunction seen in our system.

Effect of Chronic Renal Failure on Cardiac Contractile Function, Calcium Cycling, and Gene Expression of Proteins Important for Calcium Homeostasis in the Rat

“…Details of the method of isolation and culture of calcium-tolerant adult myocytes may be found in several recent reports from our laboratory (9,10,12). This method of isolation produced a good yield of rod-shaped (70 to 80%) myocytes in each of the experimental groups presented here.…”

“…Recent work suggests that echocardiographically demonstrable diastolic dysfunction is extremely common in ESRD patients treated with hemodialysis (30). As discussed briefly in the introduction, we have observed that sodium pump inhibition, which appears to accompany the chronic renal failure state, may acutely cause or contribute to both diastolic dysfunction and cardiac hypertrophy (7,10). To gain further insights into this issue we conducted the current study.…”

“…The simultaneous observation of both indo-1 fluorescence and edge detection was accomplished by continuous illumination of the cells during field stimulation with a red light and splitting of the emission light based on wavelength to either a video imaging system or the spectrofluorometer. Again, details of this methodology may be found in recent reports from our laboratory (9,10,12). Calculations of cytosolic calcium concentration ([Ca 2ϩ ] I ) were made using the following formula:…”

“…The time constant, , for recovery of length and calcium after electrical stimulation was performed by fitting a least square regression line to the log transformation of the edge detection and fluorescence data, respectively, as described by Bers et al (13,14) and also reported previously by our group (10).…”

“…We have observed that sodium pump inhibition initiates a signal cascade that can cause alterations in gene transcription and ultimately produce hypertrophy in cardiomyocytes grown in culture (7)(8)(9). We have also observed that sodium pump inhibitors, including those circulating in the serum of uremic patients, can acutely cause altered calcium cycling and cardiomyocyte relaxation through sodium pump inhibition (10). The following studies were performed to further examine how cardiac growth and function are chronically modified by the uremic milieu.…”