Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Possible changes in Ca2+ currents (ICa), which might contribute to Ca2+ overload in young (70- to 100-day-old) cardiomyopathic (CM) hamster hearts, were determined in isolated ventricular myocytes with conventional recording and discontinuous single-electrode voltage-clamp techniques. Action potential duration at 90% repolarization (APD90) was significantly longer in CM myocytes compared with normal cells (APD90 = 120.3 +/- 4.5 vs. 98.2 +/- 5.9 ms, P < 0.01). Input resistance, membrane time constant, and membrane capacitance were similar in normal and CM myocytes. Current-voltage (I-V) relations for peak ICa were depressed in CM cells compared with normal cells; this difference was statistically significant at the peak of the I-V curve. Activation and inactivation relations for ICa and recovery from inactivation were similar in myocytes from normal and CM hearts. These changes occurred in myocytes from young CM animals before development of heart failure. Results indicate that increased Ca2+ influx through L-type Ca2+ channels does not account for the longer APD in cardiomyopathy and is not involved in the development of Ca2+ overload in cardiomyopathy.
 ...
PMID:Calcium currents in ventricular myocytes of prehypertrophic cardiomyopathic hamsters. 790 Aug 97

Patients with severe heart failure are at high risk of sudden cardiac death. In the majority of these patients, sudden cardiac death is thought to be due to ventricular tachyarrhythmias. Alterations of the electric properties of single myocytes in heart failure may favor the occurrence of ventricular arrhythmias in these patients by inducing early or delayed afterdepolarizations. Mathematical models of the cellular action potential and its underlying ionic currents could help to elucidate possible arrhythmogenic mechanisms on a cellular level. In the present study, selected ionic currents based on human data are incorporated into a model of the ventricular action potential for the purpose of studying the cellular electrophysiological consequences of heart failure. Ionic currents that are not yet sufficiently characterized in human ventricular myocytes are adopted from the action potential model developed by Luo and Rudy (LR model). The main results obtained from this model are as follows: The action potential in ventricular myocytes from failing hearts is longer than in nonfailing control hearts. The major underlying mechanisms for this prolongation are the enhanced activity of the Na+-Ca2+ exchanger, the slowed diastolic decay of the [Ca2+]i transient, and the reduction of the inwardly rectifying K+ current and the Na+-K+ pump current in myocytes of failing hearts. Furthermore, the fast and slow components of the delayed rectifier K+ current (I(Kr) and I(Ks), respectively) are of utmost importance in determining repolarization of the human ventricular action potential. In contrast, the influence of the transient outward K+ current on APD is only small in both cell groups. Inhibition of I(Kr) promotes the development of early afterdepolarizations in failing, but not nonfailing, myocytes. Furthermore, spontaneous Ca2+ release from the sarcoplasmic reticulum triggers a premature action potential only in failing myocytes. This model of the ventricular action potential and its alterations in heart failure is intended to serve as a tool for investigating the effects of therapeutic interventions on the electric excitability of the human ventricular myocardium.
 ...
PMID:Simulation study of cellular electric properties in heart failure. 963 20

Survival and causes of death in children dialyzed in a single center were analyzed. During the last 12 years a chronic dialysis program was introduced in 146 children in our center and 125 of them, eligible for observation, were included in this analysis; 58 patients were on hemodialysis (HD) and 67 on peritoneal dialysis [continuous ambulatory peritoneal dialysis/automated peritoneal dialysis (CAPD/APD)]. Mean age at the start of dialysis was 13.1 years in HD and 9.8 years in CAPD/APD patients. Overall, 16 patients died (12.5%); 6 (10.3%) on HD and 10 (14.9%) on CAPD/APD; 4 HD patients died of hemorrhagic stroke and 2 were killed in road traffic accidents. Of 10 CAPD/APD patients, 7 died of heart failure, ischemic stroke, and/or disseminated thromboembolic disease. Another was killed in a road traffic accident and 2 died during the course of severe infections. The 1-year patient survival rate was 96.6% in HD patients and 95% in CAPD/APD patients, 2-year survival 94% and 93% and 5-year survival 91% and 78%, respectively (P=0.2, NS). In conclusion, the survival rate for HD and CAPD patients is similar, although after 2 years of therapy, it is lower in CAPD patients. The main causes of death are cardiovascular. However, in CAPD/APD patients, heart failure with low cardiac output and thromboembolic complications are major causes of death, and in HD patients the main cause is hemorrhagic stroke.
 ...
PMID:Patient survival and causes of death on hemodialysis and peritoneal dialysis--single-center study. 1179 88

Experiments were performed to investigate the effects of long-term treatment with adrenergic receptor antagonist on electrical remodeling of the left ventricle with chronic pressure-overload. New Zealand rabbits underwent subtotal banding of superrenal abdominal aorta. At 10 weeks after surgery, echocardiography examination was performed, then action potential (AP), inward rectifier potassium current (I(Ki)), delayed rectifier potassium current (I(K)) and Na(+)/Ca(2+) exchanger current (I(Na(+)/Ca(2+))) were recorded in midmyocardial cells isolated from left ventricle of abdominal aorta banded group (banded group), abdominal aorta banding plus Carvedilol intervention group (Carvedilol group), and normal control group rabbits by using the whole-cell patch-clamp techniques. The results showed that left ventricular mass index in control, banded, and Carvedilol groups were 1.78+/-0.06 (n=7), 2.33+/-0.11 (n=7), and 1.87+/-0.08 (n=7), respectively (banded vs control and Carvedilol, P<0.01). At basic cycle length of 2 s, AP duration (measured at 90% repolarization, APD(90), ms) in control, banded, and Carvedilol groups were 522.0+/-19.5 (n=6), 664.7+/-46.2 (n=7), 567.8+/-14.3 (n=8) respectively (banded vs control, P<0.01; Carvedilol vs banded, P<0.05). At test potential of -100 mV, inward I(Ki) density (pA/pF) in control, banded, and Carvedilol groups were -11.8+/-0.50 (n=8), -8.07+/-0.28 (n=8), -10.69+/-0.35 (n=8) respectively (banded vs control and Carvedilol, P<0.01). At test potential of +50 mV, I(K) tail current density (pA/pF) in control, banded, and Carvedilol groups were 0.59+/-0.04 (n=8), 0.40+/-0.02 (n=9), 0.51+/-0.02 (n=8) respectively (banded vs control, P<0.01; Carvedilol vs banded, P<0.05). At test potential of +60 mV, outward I(Na(+)/Ca(2+)) density (pA/pF) in control, banded, and Carvedilol groups were 1.06+/-0.11 (n=8), 1.54+/-0.10 (n=9), 1.24+/-0.07 (n=8), respectively (banded vs control and Carvedilol, P<0.01). At test potential of -120 mV, inward I(Na(+)/Ca(2+)) density (pA/pF) in control, banded, and Carvedilol groups were -0.54+/-0.06 (n =8), -0.75+/-0.04 (n=9), -0.60+/-0.03 (n=8), respectively (banded vs control, P<0.01; Carvedilol vs banded, P<0.05). It is shown that long-term treatment with Carvedilol not only prevents development of cardiac hypertrophy, but also improves the electrophysiological alterations in rabbit hearts with chronic pressure-overload. This finding may add new electrophysiological evidence for the treatment of heart failure and hypertension with adrenergic receptor antagonist.
 ...
PMID:Adrenergic receptor antagonist prevents the left ventricle with chronic pressure-overload from electrical remodeling. 1532 84

Ageing related stiffening of the vascular system is believed to be in part responsible for a number of clinical outcomes including hypertension and heart failure. In the present study, we sought to determine whether there are alterations in cardiac excitation contraction coupling that may help compensate for the increased vessel stiffness. Experiments were performed on single cardiac myocytes isolated from young (18 months) and aged (>8 years) sheep. Intracellular Ca(2+) concentration, action potentials, L-type Ca(2+) currents and SR Ca(2+) content were measured at 23 degrees C. With ageing, cell capacitance increased by 26% indicating cellular hypertrophy. Action potential duration (APD90) (590 +/- 21 vs. 726 +/- 36 ms), Ca(2+) transient amplitude (112 +/- 15 vs. 202 +/- 25 nmol l(-1)) and fractional cell shortening (by 37%) also increased in the aged hearts (all values P < 0.05). The larger Ca(2+) transient amplitude observed under current clamp conditions was maintained under voltage clamp control; however, SR Ca(2+) content was identical. Both the peak L-type Ca(2+) current (2.8 +/- 0.3 vs. 4.9 +/- 0.5 pA pF(-1)) and integrated Ca(2+) entry (5.1 +/- 0.7 vs. 7.9 +/- 0.8 micromol l(-1), all P < 0.01) were greater in aged cells. In this study we show that in the ageing ovine myocardium, the amplitude of the systolic Ca(2+) transient is increased. The larger Ca(2+) transients cannot simply be explained by changes in APD and we suggest that the greater inward L-type Ca(2+) current provides a more effective trigger for calcium-induced-calcium release from the SR whilst maintaining a stable SR Ca(2+) content. These changes in cardiac excitation contraction coupling may help maintain cardiac output in the face of increased great vessel stiffness.
 ...
PMID:Mechanisms underlying enhanced cardiac excitation contraction coupling observed in the senescent sheep myocardium. 1557 47

Endothelin-1 (ET-1) is elevated in patients with atrial fibrillation (AF) and heart failure. We investigated effects of ET-1 on human atrial cellular electrophysiological measurements expected to influence the genesis and maintenance of AF. Action potential characteristics and L-type Ca(2+) current (I(CaL)) were recorded by whole cell patch clamp, in atrial isolated myocytes obtained from patients in sinus rhythm. Isoproterenol (ISO) at 0.05 muM prolonged the action potential duration at 50% repolarisation (APD(50): 54 +/- 10 vs. 28 +/- 5 ms; P < 0.05, N = 15 cells, 10 patients), but neither late repolarisation nor cellular effective refractory period (ERP) were affected. ET-1 (10 nM) reversed the effect of ISO on APD(50), and had no basal effect (in the absence of ISO) on repolarisation or ERP. During repetitive stimulation, ISO (0.05 microM) produced arrhythmic depolarisations (P < 0.05). Each was abolished by ET-1 at 10 nM (P < 0.05). ISO (0.05 microM) increased peak I(CaL) from -5.5 +/- 0.4 to -14.6 +/- 0.9 pA/pF (P < 0.05; N = 79 cells, 34 patients). ET-1 (10 nM) reversed this effect by 98 +/- 10% (P < 0.05), with no effect on basal I(CaL). Chronic treatment of patients with a beta-blocker did not significantly alter basal APD(50) or I(CaL), the increase in APD(50) or I(CaL) by 0.05 microM ISO, nor the subsequent reversal of this effect on APD(50) by 10 nM ET-1. The marked anti-adrenergic effects of ET-1 on human atrial cellular action potential plateau, arrhythmic depolarisations and I(CaL), without affecting ERP and independently of beta-blocker treatment, may be expected to contribute a potentially anti-arrhythmic influence in the atria of patients with AF and heart failure.
 ...
PMID:Anti-adrenergic effects of endothelin on human atrial action potentials are potentially anti-arrhythmic. 1660 81

In the first section of this short review the change of the cardiac action potential (APD) with the rate of stimulation under physiological conditions is described and mechanistically analyzed. A fast phase of adaptation is mainly caused by changes in gating characteristics of ionic currents, and rapid modulation of the Na(+)/Ca(2+) exchanger. The slower phase is largely conditioned by incomplete recovery from inactivation of the late Na(+) current (late I(Na)) and changes in ion concentrations of [K(+)](e), [Na(+)](i), and [Ca(2+)](i), which cause secondary changes in the permeation and the gating of ion channels and flux through transporters. In a second section, an analysis is presented of the rate dependence of APD in pathological conditions and its importance in the genesis of arrhythmias in hypertrophy, heart failure, congenital, and acquired LQT syndromes is summarized. The role of the late I(Na), Na(+), and Ca(2+) overload is emphasized. Special attention is given to the paradoxical transient lengthening of APD in LQT3 syndrome for the sudden increase in rate in this setting. The third section consists of a short commentary on Na(+) and Ca(2+) overload and drugs which block the late I(Na).
 ...
PMID:Action potential duration, rate of stimulation, and intracellular sodium. 1668 77

Transmural electrical heterogeneity plays an important role in the normal dispersion of repolarizaion and propagation of excitation in the heart. The amplification of transmural electrical heterogeneity contributes to the genesis of arrhythmias in cardiac hypertrophy and failure. We established a mouse model with cardiac failure by aortic banding and investigated the possible contribution of L-type calcium current (I(Ca-L)) to transmural electrical heterogeneity in both normal and failing hearts. Single myocytes were enzymatically isolated from subendocardial and subepicardial myocardium of the free left ventricle wall. The recordings of action potential and I(Ca-L) were performed using the conventional whole-cell patch-clamp technique. The results showed that: (1) The action potential duration at 90% repolarization (APD(90)) of the subendocardial myocytes in normal control mice was (38.2 +/- 6.44) ms, which was significantly longer than that of the subepicardial myocytes [(15.672 +/- 5.31) ms]. The ratio of APD(90) for subendocardial/subepicardial myocytes was about 2.5:1. The peak I(Ca-L) density in subendocardial myocytes was (-2.7 +/- 0.49) pA/pF, which was not different from that in subepicardial myocytes [(-2.54 +/- 0.53) pA/pF]. (2) In failing hearts, both action potential duration at 50% repolarization (APD(50)) and APD(90) were remarkably prolonged either in subendocardial or subepicardial myocytes compared to that in sham hearts. The subendocardial myocytes had much longer APD. The ratio of APD(90) for subendocardial/subepicardial myocytes changed to about 4.2:1. (3) I(Ca-L) density in subendocardial myocytes was significantly decreased in failing hearts compared with that in sham hearts. At four test potentials from +10 mV to +40 mV, the density of I(Ca-L) from subendocardial myocytes in failing hearts was decreased by 20.2%, 21.4%, 21.6% and 25.7%, respectively (P<0.01). However, no significant difference was observed in I(Ca-L) density from subepicardial myocytes in failing hearts. There was no significant difference in the kinetic properties of I(Ca-L) in subendocardial and subepicardial myocytes between the band and sham groups. We conclude that I(Ca-L) may not contribute to the physiological transmural electrical heterogeneity in mouse hearts. The electrical heterogeneity is exaggerated and the density of I(Ca-L) is decreased in the subendocardial myocytes, but not in the subepicardial myocytes in failing hearts. The results obtained suggest that the decreased density of I(Ca-L) in subendocardial myocytes is possibly an adaptive response to the prolongation of action potential due to delayed depolarization and may reduce the transmural dispersion of repolarization in heart failure.
 ...
PMID:[Transmural L-type calcium current in a pressure-overloaded mouse model with heart failure]. 1729 38

Peritoneal dialysis (PD) is the first option for patients in end stage renal disease (ESRD). Several complications such as peritonitis, exit-site or tunnels infections are encountered during PD. Other complications such as pain, proteic malnutrition, hyperglycemia, hypertension, cardiac failure are described in patients on continuous ambulatory peritoneal dialysis (CAPD) or APD (automated peritoneal dialysis). Rare complications are incapsulated sclerosing peritonitis, hemoperitoneum or pneumoperitoneum. We present the case of a female patient, 66 years old, on cyclic continuous peritoneal dialysis (APD-CCPD) admitted for pneumoperitoneum developed during a dialysis change from a CCPD schedule, due to an error in the Tenckhoff catheter and peritoneal dialysis manipulation. The treatment consisted in extracting the air during manual peritoneal dialysis changes, with the patient in Trendelenburg position and pressing on the abdominal wall, without any other complications.
 ...
PMID:Pneumoperitoneum--rare complication in end stage renal disease patient on automated peritoneal dialysis. 1948 Mar 2

Much evidence indicates that increased persistent sodium current (I(Na.P)) is associated with cellular calcium overload and I(Na.P) is considered to be a potential target for therapeutic intervention in ischaemia and heart failure. By inhibiting type III phosphodiesterase, milrinone increases intracellular cyclic adenosine monophosphate (cAMP), with a positive inotropic effect. However, the effect of milrinone on increased I(Na.P) under pathological conditions remains unknown. Accordingly, we investigated the effect of milrinone on increased I(Na.P) induced by hypoxia or hydrogen dioxide in guinea pig ventricular myocytes. While milrinone (0.01 mM or 0.1mM) or cAMP (0.1 mM) decreased I(Na.P) respectively in control condition, application of 1 microM H-89, a selective cAMP-dependant protein kinase inhibitor, prevented the effect of 0.1mM milrinone in control condition. Milrinone (0.1 mM) reduced the increased I(Na.P) induced by hypoxia. Furthermore, 0.01 mM or 0.1mM milrinone reduced the enhanced I(Na.P) induced by 0.3 mM hydrogen peroxide. In addition, 0.01 mM or 0.1 mM milrinone shortened action potential duration at 90% repolarization (APD(90)). Bath application of 0.3 mM hydrogen dioxide markedly prolonged APD(90), while 2 microM tetrodotoxin (TTX) reversed the prolonged APD(90). In the other two groups, 0.01 mM or 0.1 mM milrinone shortened the prolonged APD(90) induced by 0.3 mM hydrogen peroxide, ultimately 2 microM TTX causing a further decurtation of APD(90). These findings demonstrate that milrinone inhibited I(Na.P) under normal condition, hypoxia or hydrogen dioxide-induced I(Na.P), and the APD(90) prolonged by hydrogen dioxide-induced I(Na.P) in ventricular myocytes, which is associated with the mechanism of milrinone increasing intracellular cAMP.
 ...
PMID:Milrinone inhibits hypoxia or hydrogen dioxide-induced persistent sodium current in ventricular myocytes. 1954 13


1 2 Next >>