Phenothiazine protection in calcium overload-induced heart failure: a possible role for calmodulin

1983 ◽  
Vol 244 (3) ◽  
pp. H328-H334
Author(s):  
S. W. Schaffer ◽  
K. P. Burton ◽  
H. P. Jones ◽  
H. H. Oei
Keyword(s):  
Heart Failure ◽  
Creatine Phosphokinase ◽  
Potent Inhibitor ◽  
High Energy ◽  
Major Effect ◽  
Calcium Overload ◽  
Cellular Damage ◽  
Maximal Response ◽  
Membrane Changes ◽  
Calcium Permeability

The effect of several phenothiazines on the extent of cellular damage resulting from the calcium paradox was examined. Hearts treated with trifluoperazine, a potent calmodulin inhibitor, exhibited less cellular damage than untreated myocardium as reflected by light microscopy, high-energy phosphate content and the loss of protein and creatine phosphokinase into the perfusate. A dose response of this effect revealed a maximal response at about 1 microM trifluoperazine, a concentration which lies well within the range generally attributed to calmodulin inhibition. Several other lines of evidence were also obtained suggesting a possible role for calmodulin in calcium-overload induced necrosis. First, the phenothiazines had little influence on membrane changes believed responsible for altered calcium permeability. Second, trifluoperazine was without major effect unless included in the reperfusion buffer, indicating that the drug is only effective during the phase associated with calcium overload. Finally, less protection was afforded hearts exposed to phenothiazines such as chlorpromazine and promethazine, which are weaker inhibitors of calmodulin, than those treated with the potent inhibitor trifluoperazine. While other interpretations are possible, these studies are consistent with a role for calmodulin in calcium overload-induced heart failure.

scholarly journals Effect of defibrillation on the performance of an implantable vagus nerve stimulation system

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Imad Libbus ◽  
Scott R. Stubbs ◽  
Scott T. Mazar ◽  
Scott Mindrebo ◽  
Bruce H. KenKnight ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Function ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Pulse Generator ◽  
High Energy ◽  
Implantable Pulse Generator ◽  
Defibrillation Pulse ◽  
Stimulation System

Abstract Background Vagus Nerve Stimulation (VNS) delivers Autonomic Regulation Therapy (ART) for heart failure (HF), and has been associated with improvement in cardiac function and heart failure symptoms. VNS is delivered using an implantable pulse generator (IPG) and lead with electrodes placed around the cervical vagus nerve. Because HF patients may receive concomitant cardiac defibrillation therapy, testing was conducted to determine the effect of defibrillation (DF) on the VNS system. Methods DF testing was conducted on three ART IPGs (LivaNova USA, Inc.) according to international standard ISO14708-1, which evaluated whether DF had any permanent effects on the system. Each IPG was connected to a defibrillation pulse generator and subjected to a series of high-energy pulses. Results The specified series of pulses were successfully delivered to each of the three devices. All three IPGs passed factory electrical tests, and interrogation confirmed that software and data were unchanged from the pre-programmed values. No shifts in parameters or failures were observed. Conclusions Implantable VNS systems were tested for immunity to defibrillation, and were found to be unaffected by a series of high-energy defibrillation pulses. These results suggest that this VNS system can be used safely and continue to function after patients have been defibrillated.

scholarly journals The Ku Protein Complex Interacts with YY1, Is Up-Regulated in Human Heart Failure, and Represses α Myosin Heavy-Chain Gene Expression

2004 ◽  
Vol 24 (19) ◽  
pp. 8705-8715 ◽  
Author(s):  
Carmen C. Sucharov ◽  
Steve M. Helmke ◽  
Stephen J. Langer ◽  
M. Benjamin Perryman ◽  
Michael Bristow ◽  
...  
Keyword(s):  
Heart Failure ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Human Heart ◽  
Ventricular Myocytes ◽  
Major Effect ◽  
Neonatal Rat ◽  
Chain Gene ◽  
Human Heart Failure ◽  
Peptide Mass

ABSTRACT Human heart failure is accompanied by repression of genes such as α myosin heavy chain (αMyHC) and SERCA2A and the induction of fetal genes such as βMyHC and atrial natriuretic factor. It seems likely that changes in MyHC isoforms contribute to the poor contractility seen in heart failure, because small changes in isoform composition can have a major effect on the contractility of cardiac myocytes and the heart. Our laboratory has recently shown that YY1 protein levels are increased in human heart failure and that YY1 represses the activity of the human αMyHC promoter. We have now identified a region of the αMyHC promoter that binds a factor whose expression is increased sixfold in failing human hearts. Through peptide mass spectrometry, we identified this binding activity to be a heterodimer of Ku70 and Ku80. Expression of Ku represses the human αMyHC promoter in neonatal rat ventricular myocytes. Moreover, overexpression of Ku70/80 decreases αMyHC mRNA expression and increases skeletal α-actin. Interestingly, YY1 interacts with Ku70 and Ku80 in HeLa cells. Together, YY1, Ku70, and Ku80 repress the αMyHC promoter to an extent that is greater than that with YY1 or Ku70/80 alone. Our results suggest that Ku is an important factor in the repression of the human αMyHC promoter during heart failure.

Fresh State Behaviour of Cement Paste Containing Nano Kaolin

2014 ◽  
Vol 925 ◽  
pp. 28-32 ◽  
Author(s):  
Muhd Sidek Muhd Norhasri ◽  
M.S. Hamidah ◽  
A. Mohd Fadzil ◽  
A.G. Abd Halim ◽  
M.R. Zaidi
Keyword(s):  
Surface Area ◽  
Cement Paste ◽  
Setting Time ◽  
High Energy ◽  
Major Effect ◽  
Cement Replacement ◽  
High Energy Milling ◽  
Replacement Method ◽  
Fresh State ◽  
State Behaviour

The application of nanomaterials in cement by replacement method in concrete is becoming a trend in cement research. The utilisation of nanosilica, nanoalumina, titanium oxide and others are proven to enhance properties of concrete. The major effect of nanomaterials is its size in which it contributes to the packing theory due to increase in the surface area. nanokaolin which comes from kaolin, was tansformed to the nanoform by using high energy milling. The process of developing nanokaolin by using high energy milling is referred to process top to bottom approach in nanoprocessing technique. In this research, the nanokaolin will be used as an additive in cement by 7% weight of cement. Four (4) cement replacement materials catered by using metakaolin on weight basis from 0, 10%, 20% and 30% will also be adopted. To determine the fresh state, cement paste contains nanokaolin and metakaolin are tested its standard consistency and setting time. The effect of the inclusion of the nanokaolin as additive in cement paste that also contains metakaolin as cement replacement material will be investigated. It was found the inclusion of 7% nanokaolin increases the water demand of the cement paste level of metakaolin replacement. In addition to that, the setting time namely initial and final set was been delayed as compared to that of plain OPC. The nanoparticles of nanokaolin and also finer particles of metakaolin increase the surface area and refining the internal structure of cement paste which reduce the flow capabilities of cement paste containing nanokaolin and metakaolin.

Abstract 565: The Activation of AMP-Activated Protein Kinase Ameliorates the Severity of Heart Failure in Dogs

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Hideyuki Sasaki ◽  
Hiroshi Asanuma ◽  
Masashi Fujita ◽  
Hiroyuki Takahama ◽  
Masakatsu Wakeno ◽  
...  
Keyword(s):  
Heart Failure ◽  
Protein Kinase ◽  
Cardiac Myocytes ◽  
Left Ventricular ◽  
Neonatal Rat ◽  
Cellular Damage ◽  
Control Group ◽  
Compound C ◽  
Rapid Pacing ◽  
Amp Activated Protein Kinase

Backgrounds; Since AMP-activated protein kinase (AMPK) is activated in the pressure-overloaded hypertrophic hearts, we investigated whether the activation of AMPK caused by metformin attenuates the progression of heart failure induced by rapid pacing in dogs and decreases cellular damage caused by oxidative stress in neonatal rat cardiac myocytes. Methods and Results; Heart failure was induced by right ventricular (RV) pacing at 230 bpm for 4 weeks in dogs. Treatment of dogs with metformin (100mg/kg/day, orally, n=8, Met group) for 4 weeks prevented significantly the progression of pacing-induced heart failure evaluated by echocardiographical and hemodynamic measurement compared with the control group (n=8). Left ventricular (LV) diastolic and systolic dimension (LVDd and LVDs) were smaller (32.8±0.4 and 26.7±0.9 mm, respectively) and fractional shortening (FS) and ejection fraction (EF) were preserved in Met group (18.6±1.8 and 45.5±3.5 %, respectively) compared with the control group (LVDd and LVDs; 36.5±1.0 and 33.0±1.0 mm, FS and EF; 9.6±0.7 and 27.0±1.9 %, p<0.05 vs. Met group each). Furthermore, both pulmonary capillary wedge pressure (PCWP) and mean pulmonary arterial pressure (mPA) were significantly lower in Met group (11.1±0.9 and 18.1±1.4 mmHg, respectively) compared with the control group (21.0±2.2 and 26.8±2.8 mmHg, respectively). Treatment of cultured cardiac myocytes with a maximal physiological concentration of metformin (10μmol/L) attenuated the cellular damage against H 2 O 2 exposure (50μmol/L). These effects were blunted by an AMPK inhibitor, compound-C (20μmol/L), suggesting that the activation of AMPK increased the cellular viability during H 2 O 2 exposure. Conclusions; Metformin that activates AMPK prevented the progression of heart failure induced by rapid pacing in dogs and attenuated the cellular damage against H 2 O 2 exposure in cardiac myocytes. AMPK may be one of new targets for preventing heart failure in clinical settings.

Creatine Phosphokinase Activity in Myocardial Infarction, Heart Failure, and Following Various Diagnostic and Therapeutic Procedures

1968 ◽  
Vol 14 (12) ◽  
pp. 1185-1196 ◽  
Author(s):  
Leonard V Crowley
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Electroconvulsive Therapy ◽  
Cardiac Failure ◽  
Creatine Phosphokinase ◽  
Coronary Arteriography ◽  
Surgical Operation ◽  
Patients With Heart Failure ◽  
Therapeutic Procedures ◽  
Infarction Heart

Abstract The creatine phosphokinase(CPK) test based on the method of Okinaka et al. (1) was compared with the glutamic oxalacetic transaminase (GOT) test of Reitman and Frankel (2) in patients with myocardial infarction, cardiac failure, and following various diagnostic and therapeutic procedures. The CPK method used was somewhat less discriminatory than the GOT method in detecting myocardial infarction. The CPK test possessed greater specificity, since it was not elevated in congestive cardiac failure, while the GOT test was elevated in 25% of the patients with heart failure. Therefore, the CPK test offered a real advantage when evaluating suspected infarction in the presence of cardiac failure. CPK activity may be elevated when the GOT test is normal, indicating the advantage of performing more than one enzyme procedure in suspected myocardial infarction. Both GOT and CPK were elevated in many patients following surgical operation and cardiac catheterization. No CPK elevations were encountered after electroconvulsive therapy, and CPK was only occasionally elevated following coronary arteriography.

scholarly journals Epigenetic-sensitive liquid biomarkers and personalised therapy in advanced heart failure: a focus on cell-free DNA and microRNAs

2020 ◽  
Vol 73 (9) ◽  
pp. 535-543 ◽  
Author(s):  
Gelsomina Mansueto ◽  
Giuditta Benincasa ◽  
Nunzia Della Mura ◽  
Giovanni Francesco Nicoletti ◽  
Claudio Napoli
Keyword(s):  
Heart Failure ◽  
Cellular Damage ◽  
Molecular Networks ◽  
Acute Injury ◽  
Cell Free Dna ◽  
Reduced Ejection Fraction ◽  
Free Dna ◽  
Frequent Mutations ◽  
Patients At Risk ◽  
Personalised Therapy

Dilated cardiomyopathy (DCM) represents a common genetic cause of mechanical and/or electrical dysfunction leading to heart failure (HF) onset for which truncating variants in titin (TTN) gene result in the most frequent mutations. Moreover, myocyte and endothelial cell apoptosis is a key endophenotype underlying cardiac remodelling. Therefore, a deeper knowledge about molecular networks leading to acute injury and apoptosis may reveal novel circulating biomarkers useful to better discriminate HF phenotypes, patients at risk of heart transplant as well as graft reject in order to improve personalised therapy. Remarkably, increased plasma levels of cell-free DNA (cfDNA) may reflect the extent of cellular damage, whereas circulating mitochondrial DNA (mtDNA) may be a promising biomarker of poor prognosis in patients with HF. Furthermore, some panels of circulating miRNAs may improve the stratification of natural history of disease. For example, a combination of miR-558, miR-122* and miR-520d-5p, as well as miR-125a-5p, miR-550a-5p, miR-638 and miR-190a, may aid to discriminate different phenotypes of HF ranging from preserved to reduced ejection fraction. We give update on the most relevant genetic determinants involved in DCM and discuss the putative role of non-invasive biomarkers to overcome current limitations of the reductionist approach in HF management.

Tachycardia heart failure alters rabbit aortic smooth muscle responsiveness to angiotensin II

1994 ◽  
Vol 266 (3) ◽  
pp. H1228-H1232
Author(s):  
E. Porsa ◽  
G. L. Freeman ◽  
J. T. Herlihy
Keyword(s):  
Heart Failure ◽  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Calcium Chloride ◽  
Maximal Response ◽  
Vasoactive Agents ◽  
Potassium Depolarization ◽  
Smooth Muscle Tissue ◽  
Aortic Smooth Muscle ◽  
And Control

The effects of heart failure on the responsiveness of aortic smooth muscle tissue to various vasoactive agents were examined. Heart failure was induced in rabbits by sustained rapid ventricular pacing (400 beats/min) for 6-7 wk. After the rabbits were killed, strips of thoracic aorta were prepared and mounted in tissue baths. Responsiveness of these aortic strips to potassium depolarization and cumulative additions of vasoactive agents was determined. Aortic strips from control and tachycardia heart failure (THF) rabbits developed similar maximum forces to stimulation by potassium depolarization (0.77 +/- 0.08 vs. 0.96 +/- 0.16 kg/cm2), calcium chloride (0.71 +/- 0.09 vs. 0.88 +/- 0.06 kg/cm2), and phenylephrine (0.90 +/- 0.08 vs. 1.14 +/- 0.09 kg/cm2). The maximum relaxation to isoproterenol was also unaffected by THF (0.08 +/- 0.02 vs. 0.07 +/- 0.01 kg/cm2). In contrast, the maximum response of aortic strips from THF rabbits to angiotensin II was significantly lower than control (0.37 +/- 0.07 vs. 0.069 +/- 0.09 kg/cm2). With regard to aortic smooth muscle sensitivity, no differences in the concentrations at which 50% of the maximal response is achieved (EC50) were observed between THF and control strips for calcium chloride (0.10 +/- 0.01 vs. 0.16 +/- 0.04 mM), isoproterenol (51.5 +/- 13.5 vs. 51.0 +/- 5.4 nM), and phenylephrine (65.2 +/- 12.3 vs. 92.5 +/- 18.0 nM). However, THF was associated with a significant increase in the EC50 value for angiotensin II response (2.03 +/- 0.25 vs. 0.58 +/- 0.05 nM). These results demonstrate that THF is associated with a specific and significant reduction in the sensitivity and maximal responsiveness of aortic smooth muscle to angiotensin II.(ABSTRACT TRUNCATED AT 250 WORDS)

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