1.
Assist devices fail to reverse patterns of fetal gene expression despite beta-blockers.
Lowes, BD, Zolty, R, Shakar, SF, Brieke, A, Gray, N, Reed, M, Calalb, M, Minobe, W, Lindenfeld, J, Wolfel, EE, et al
The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation. 2007;(11):1170-6
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Abstract
BACKGROUND Heart failure is associated with reversal to a fetal gene expression pattern of contractile and metabolic genes. Substantial recovery of ventricular function with assist devices is rare. Our goal was to evaluate the effects of assist devices on fetal gene expression and hypoxia inducible factor-1 alpha (HIF-1 alpha), a transcriptional factor in hypoxic signaling. METHODS Human heart tissue was obtained from the left ventricular apex at the time of assist device implantation and again from the left ventricular free wall during cardiac transplantation. Non-failing tissue was obtained from unused hearts from human donors. Gene expression was measured with the Affymetrix 133 plus 2 Array. HIF-1 alpha was measured by Western blotting with commercially available antibodies. RESULTS Heart failure was associated with a decrease in alpha-myosin heavy chain and sarcoplasmic reticulum-Ca(2+) adenosine triphosphatase messenger RNA expression along with an increase in skeletal tropomyosin. This pattern persisted after assist device therapy. Heart failure was also associated with abnormalities in regulatory metabolic genes including glucose transporter 1 (GLUT1). These patterns also persisted after assist device therapy despite a reduction in atrial natriuretic peptide expression and normalization of HIF-1 alpha. CONCLUSIONS Failure of assist devices to produce sustained recovery of myocardial contractile function may be due in part to persistent fetal transcriptional patterns of contractile and metabolic genes.
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Low calcium dialysate increases cardiac relaxation in CAPD patients.
Tuncer, M, Ermiş, C, Süleymanlar, G, Yakupoglu, G, Ersoy, FF
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis. 2002;(6):714-8
Abstract
OBJECTIVE To establish whether changes in serum calcium affect left ventricular (LV) function in continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS This study was conducted on 28 clinically stable CAPD patients (11 females, 17 males). Left ventricular relaxation and systolic function were echocardiographically examined in all patients during standard dialysate (containing 1.75 mmol/L calcium) treatment. All patients were then changed to low calcium dialysate (1.25 mmol/L calcium) for 1 month and all patients were re-examined echocardiographically. Decrement in isovolumic relaxation time (IVRT) and deceleration time (DT), and increment in the ratio of peak early to peak late diastolic velocities (E/Amax) were admitted as indexes showing improvement in LV relaxation. 17 age- and sex-matched controls were also echocardiographically examined. RESULTS Deceleration time, interventricular septal thickness at systole (IVSTS) and diastole (IVSTD), and posterior wall thickness at systole (PWS) and diastole (PWD) were higher in CAPD patients using standard dialysate than in normal controls. With the use of low calcium dialysate, DTs were similar but IVSTS, IVSTD, PWS, and PWD values remained higher. In normal controls, E/Amax values were higher than those in CAPD patients using standard dialysate (p < 0.001) and low calcium dialysate (p = 0.009). Serum intact parathyroid hormone level, weight, clinical volume status, and blood pressure were similar throughout the study period. Serum ionized calcium levels were decreased significantly during low calcium dialysate treatment. The changes in IVRT, DT, and E/Amax suggest improvement in LV relaxation during low calcium dialysate treatment. CONCLUSION Left ventricular relaxation is increased with the use of low calcium dialysate compared with standard dialysate treatment. The idea of possible beneficial effects of increment in LV relaxation on cardiovascular morbidity and mortality deserves further studies.