INFLUENCE OF RESERPINE, HEART FAILURE, AND IMMUNOSYMPATHECTOMY ON THE CARDIAC EFFECTS OF OUABAIN

1967 ◽  
Vol 45 (4) ◽  
pp. 643-654 ◽  
Author(s):  
S. Wendlandt ◽  
D. R. Varma
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Positive Inotropic Effect ◽  
Lethal Dose ◽  
Inotropic Effect ◽  
Pulmonary Artery Stenosis ◽  
Papillary Muscles ◽  
Normal Amount ◽  
Release Of Noradrenaline ◽  
Cardiac Effects

A possible relationship between myocardial noradrenaline and the cardiac effects of ouabain has been investigated. Pretreatment with reserpine, with or without acute adrenalectomy, failed to reduce the positive inotropic effect of ouabain in cats. Similarly, reserpine did not reduce the positive inotropic effect of ouabain in cats which had developed congestive heart failure from chronic pulmonary artery stenosis and which had approximately 40% of the normal amount of myocardial noradrenaline. The positive inotropic effect of ouabain on isolated papillary muscles from reserpine-treated rabbits and on the isolated left atria from reserpine-treated rats or rats with immunosympathectomy was also normal. Depletion of myocardial noradrenaline did not influence the toxicity of ouabain except in cats with congestive heart failure. In these cats, pretreatment with reserpine increased the arrhythmic and the lethal dose of ouabain. Reserpine or immunosympathectomy produced a marked depletion of myocardial noradrenaline stores. It is concluded that the positive inotropic effect of ouabain is not due to a release of noradrenaline from the heart. The mechanism by which pretreatment with reserpine reduces the toxicity of ouabain in cats with congestive heart failure is not clear. It may or may not be due to a depletion of myocardial noradrenaline.

Alpha 1-adrenoceptor subtypes mediating inotropic and electrophysiological effects in mammalian myocardium

1996 ◽  
Vol 271 (4) ◽  
pp. H1423-H1432
Author(s):  
M. Nagashima ◽  
Y. Hattori ◽  
Y. Akaishi ◽  
N. Tohse ◽  
I. Sakuma ◽  
...  
Keyword(s):  
Positive Inotropic Effect ◽  
Outward Current ◽  
Ventricular Myocardium ◽  
Inotropic Effect ◽  
Transient Outward Current ◽  
Papillary Muscles ◽  
Binding Studies ◽  
Positive Inotropism ◽  
Wb 4101 ◽  
Rabbit Ventricular Myocardium

Stimulation of alpha 1-adrenoceptors produces a positive inotropic effect in rat and rabbit ventricular myocardium via different mechanisms, the prolongation of action potential duration (APD) exclusively in the former and an increase in myofibrillar Ca2+ sensitivity in large part in the latter. This study was designed to determine whether the two inotropic mechanisms are mediated by different alpha 1-adrenoceptor subtypes. In rat papillary muscles, the positive inotropic effect and APD prolongation induced by phenylephrine (in the presence of propranolol) were inhibited by WB-4101, but not affected by chlorethylclonidine (CEC). WB-4101, but not CEC, blocked the phenylephrine-induced inhibition of the transient outward current (Ito) in rat ventricular cells. On the other hand, WB-4101 and CEC each antagonized the positive inotropic effect of phenylephrine in rabbit papillary muscles. However, the phenylephrine-induced APD prolongation observed in rabbit papillary muscles was blocked only by WB-4101. These results indicate that the WB-4101 sensitive alpha 1-adrenoceptor subtype mediates the positive inotropism that is correlated with the APD prolongation resulting from Ito reduction, whereas the CEC-sensitive subtype mediates the positive inotropism that is probably associated with increased myofibrillar Ca2+ sensitivity. Radioligand binding studies with [3H] prazosin showed a similar ratio of alpha 1A-to alpha 1B-adrenoceptor subtypes in rat and rabbit ventricular myocardium, implying that the different degree of contribution of each action mechanism to the overall inotropic effect in the two species cannot be explained by distribution of the alpha 1-adrenoceptor subtypes.

scholarly journals EVALUATION OF BENEFICIAL EFFECTS OF LINUM USITATISSIMUM IN CONGESTIVE HEART FAILURE

2017 ◽  
Vol 9 (10) ◽  
pp. 62
Author(s):  
Pravin Tirgar ◽  
Limbasiya Kalpesh
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Linum Usitatissimum ◽  
Positive Inotropic Effect ◽  
Methanolic Extract ◽  
In Vitro Study ◽  
Control Group ◽  
Force Of Contraction ◽  
Beneficial Effects

Objective: Evaluation of beneficial effects of the seed of Linum usitatissimum in congestive heart failure.Methods: Methanolic extract of seeds of Linumusitatissimum (MELU) was prepared using soxhlet apparatus and oil of seed of Linumusitatissimum (OLU) was isolated using Clevenger apparatus. The positive inotropic action of methanolic extract of seeds of Linum usitatissimum was evaluated using Langendorff’s assembly (in vitro study). Beneficial effects of methanolic extract and oil of seeds of Linum usitatissimum were carried out by doxorubicin (1 mg/kg, i. p. within 3 w) to induce congestive heart failure (in vivo study). Parameters like electrocardiogram (ECG) recording and cytosolic Ca2+level and histopathology of the heart were carried out. In same study diuretic action was evaluated using Lipschitz model.Results: Methanolic extract of seeds of Linum usitatissimum showed significantly increased in positive inotropic effect (force of contraction 48.8±1.53 mm) as compared to control group (force of contraction 17.5±0.76 mm) on Langendorff”s study (in vitro study). In doxorubicin-induced congestive heart failure both MELU and OLU showed significant decreased QT (Note: In cardiology, the QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. There is no full form for this medical word) interval. The histopathologic study indicated the least damage to the architecture of myocardial membrane. MELU and OLU increased urine output (5.66±0.16 ml and 6.58±0.15 ml respectively) significantly in Lipschitz model as compared to disease control group (4.58±0.15 ml).Conclusion: Present research work emphasizes that the seeds of Linum usitatissimum is beneficial in the management of congestive heart failure because of having positive inotropic effect, diuretic activity and control of rhythmicity of heart.

scholarly journals Na+/Ca2+ exchanger overexpression impairs frequency- and ouabain-dependent cell shortening in adult rat cardiomyocytes

2004 ◽  
Vol 287 (4) ◽  
pp. H1435-H1445 ◽  
Author(s):  
Birgit Bölck ◽  
Götz Münch ◽  
Peter Mackenstein ◽  
Martin Hellmich ◽  
Ingo Hirsch ◽  
...  
Keyword(s):  
Heart Failure ◽  
Gene Transfer ◽  
Mode Of Action ◽  
Positive Inotropic Effect ◽  
Inotropic Effect ◽  
Adrenergic Stimulation ◽  
Human Heart Failure ◽  
Rat Cardiomyocytes ◽  
Cell Shortening ◽  
Reverse Mode

The Na+/Ca2+ exchanger (NCX) may influence cardiac function depending on its predominant mode of action, forward mode or reverse mode, during the contraction-relaxation cycle. The intracellular Na+ concentration ([Na+]i) and the duration of the action potential as well as the level of NCX protein expression regulate the mode of action of NCX. [Na+]i and NCX expression have been reported to be increased in human heart failure. Nevertheless, the consequences of altered NCX expression in heart failure are still a matter of discussion. We aimed to characterize the influence of NCX expression on intracellular Ca2+ transport in rat cardiomyocytes by adenoviral-mediated gene transfer. A five- to ninefold (dose dependent) overexpression of NCX protein was achieved after 48 h by somatic gene transfer (Ad.NCX.GFP) versus control (Ad.GFP). NCX activity, determined by Na+ gradient-dependent 45Ca2+-uptake, was significantly increased. The protein expressions of sarco(endo)plasmic reticulum Ca2+-ATPase, phospholamban, and calsequestrin were unaffected by NCX overexpression. Fractional shortening (FS) of isolated cardiomyocytes was significantly increased at low stimulation rates in Ad.NCX.GFP. After a step-wise enhancing frequency of stimulation to 3.0 Hz, FS remained unaffected in Ad.GFP cells but declined in Ad.NCX.GFP cells. The positive inotropic effect of the cardiac glycoside ouabain was less effective in Ad.NCX.GFP cells, whereas the positive inotropic effect of β-adrenergic stimulation remained unchanged. In conclusion, NCX overexpression results in a reduced cell shortening at higher stimulation frequencies as well as after inhibition of sarcolemmal Na+-K+-ATPase, i.e., in conditions with enhanced [Na+]i. At low stimulation rates, increased NCX expression enhances both intracellular systolic Ca2+ and contraction amplitude.

scholarly journals Cardiac involvement in children with community-acquired pneumonia and respiratory failure

2020 ◽  
Vol 14 (3) ◽  
pp. 119-124
Author(s):  
Kachaporn Nimdet ◽  
Win Techakehakij
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Respiratory Failure ◽  
Cardiac Arrhythmia ◽  
Community Acquired Pneumonia ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Valvular Regurgitation ◽  
Healthy Children ◽  
Cardiac Effects

AbstractBackgroundPneumonia causes significant incidence in children younger than 5 years. Most fatalities are resulted from complications. High rates of cardiac events were detected in adult studies but usually related to underlying diseases.ObjectiveTo study the cardiac effects of community-acquired pneumonia (CAP) with respiratory failure (RF) in healthy children.MethodsThe prospective cohort study was conducted in children aged 2–59 months with CAP and RF. Cardiac enzyme assessments, chest radiography, electrocardiography, and echocardiography were performed at the admission date and 2 weeks after admission. t-test and chi-square test were used for comparison between first and second investigations, and the statistically significance level was a P <0.05.ResultsOf the 135 patients, pericardial effusion occurred in 80 (59%), valvular regurgitation in 30 (22%), ST/T changes in 66 (49%), cardiac arrhythmia in 7 (5%), and myocardial injury in 83 (62%). Significant improvement of cardiothoracic-ratio, heart rate, ST/T changes, cardiac arrhythmia, troponin T, myocardial performance, and left-ventricular ejection fraction was demonstrated at second investigations. Three mortality cases exhibited evidence of congestive heart failure (CHF).ConclusionChildren with CAP and RF had several cardiac effects even in healthy children. Most cardiac effects were mild and transient. Mortality cases were revealed evidence of congestive heart failure (CHF). Future research should be designed to find out the characteristics and predictors of CHF for early recognition and therapeutic strategy.

P5440Systolic/diastolic effects of chronic treatment with omecamtiv mecarbil in minipigs with post-myocardial infarction Heart Failure with reduced Ejection Fraction (HFrEF)

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
D Caillaud ◽  
X Baudot ◽  
L Gouraud ◽  
L Lucats ◽  
M P Pruniaux ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Ejection Fraction ◽  
Healthy Volunteers ◽  
Chronic Treatment ◽  
Positive Inotropic Effect ◽  
Post Myocardial Infarction ◽  
Inotropic Effect ◽  
Reduced Ejection Fraction ◽  
Omecamtiv Mecarbil

Abstract Background Omecamtiv mecarbil (OM), a novel myosin ATPase activator, is currently developed for the treatment of Heart Failure with reduced Ejection Fraction (HFrEF). Phase I in healthy volunteers and patients showed that the positive inotropic effect of OM was associated with an impairment of diastolic function as assessed by change in E peak, e' wave and E/e' ratio. Purpose The diastolic impact of chronic treatment with OM has not been described yet. This study investigates the balance between positive inotropic effect and the diastolic impairment after chronic treatment with OM in a post-myocardial infarction (Post-MI) swine model of HFrEF. Methods HFrEF was induced in minipigs after myocardial infarction caused by a 150-min left anterior descending (LAD) artery occlusion performed under angiography. HFrEF minipigs were treated with OM at 3 mg/kg PO BID for 15 days (n=4), a dose known to increase systolic ejection time (SET) by ∼50 ms as achieved in healthy volunteers and patients at plasma levels between 200–300 ng/ml. Echocardiogram was performed before and after 15 days of treatment with OM. An additional echocardiogram was conducted 7 days after the last administration. Results One year after MI, minipigs displayed increased left ventricular end-diastolic volume index (LVEDVi 151±3.7ml/m2 vs 100±8.9ml/m2 before infarction) and decreased LVEF (42±2.5% vs 68±4.4% before infarction) associated with a pseudo-normal mitral pattern. A two-week treatment with OM increased SET by 64ms (p<0.0001 vs before treatment) and EF to 49±3.8% (p=0.07 vs before treatment) as well as it improved SVi by 13%. This inotropic effect was associated with a decrease of mitral E peak (p=0.01 vs before treatment) and e' waves, and with the prolongation of deceleration time (p<0.05 vs before treatment). OM treatment was associated with marked reduction of LVEDVi to 117±13.2ml/m2 (p<0.05 vs before treatment) concomitant with a ∼20% increase in diastolic septum and posterior wall thicknesses. None of these systolic or diastolic effects remained 7 days post OM treatment completion. Conclusion Similarly to clinical description, OM treatment increased LVEF and SVi principally through extension of SET. It provides positive inotropic effects associated with diastolic impairment resulting in impaired ventricular filling as assessed by LVEDVi decrease and the thickening of ventricular wall in diastole. Whether this profile will allow a beneficial reverse remodeling, needs to be investigated in a longer chronic study. Acknowledgement/Funding Sanofi sponsored study

Evidence for physiological functions of protein phosphatases in the heart: evaluation with okadaic acid

1993 ◽  
Vol 265 (1) ◽  
pp. H257-H266 ◽  
Author(s):  
J. Neumann ◽  
P. Boknik ◽  
S. Herzig ◽  
W. Schmitz ◽  
H. Scholz ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Okadaic Acid ◽  
Guinea Pigs ◽  
Positive Inotropic Effect ◽  
Inotropic Effect ◽  
Papillary Muscles ◽  
Force Of Contraction ◽  
Phosphorylation State ◽  
Ventricular Cardiomyocytes ◽  
Channel Currents

Okadaic acid exerts a positive inotropic effect in cardiac preparations. We studied whether the positive inotropic effect of okadaic acid in cardiac preparations could be due to phosphatase inhibition and whether this inhibition affects the phosphorylation of cardiac proteins. In papillary muscles from guinea pigs, 30 microM okadaic acid increased force of contraction to 175% of predrug value. In isolated guinea pig ventricular cardiomyocytes, okadaic acid augmented single Ca(2+)-channel currents by enhancing channel availability. In homogenates from ventricles, 1 microM okadaic acid completely inhibited phosphorylase a phosphatase activity. In isolated 32P-labeled ventricular cardiomyocytes, 30 microM okadaic acid increased phosphorylation of phospholamban (PLB) and troponin inhibitor (TnI) to 325 and 284% of control, respectively. Furthermore, 30 microM okadaic acid increased phosphorylation of a hitherto unknown 23-kDa protein to 352% of control. It is concluded that the effects of okadaic acid could be mediated by increasing the phosphorylation state of several proteins including PLB, a 23-kDa protein, and TnI.

Dissociation between positive inotropic and alkalinizing effects of angiotensin II in feline myocardium

1997 ◽  
Vol 272 (3) ◽  
pp. H1131-H1136 ◽  
Author(s):  
A. Mattiazzi ◽  
N. G. Perez ◽  
M. G. Vila-Petroff ◽  
B. Alvarez ◽  
M. C. Camilion de Hurtado ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Simultaneous Measurement ◽  
Myocardial Contractility ◽  
Positive Inotropic Effect ◽  
Inotropic Effect ◽  
Papillary Muscles ◽  
Ang Ii ◽  
Acetoxymethyl Ester ◽  
Hepes Buffer ◽  
Ethanesulfonic Acid

The present study examines the intracellular pH (pHi) dependence of angiotensin (ANG) II-induced positive inotropic effect in cat papillary muscles contracting isometrically (0.2 Hz, 30 degrees C). Muscles were loaded with the fluorescent dye 2'-7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester for simultaneous measurement of pHi and contractility. In N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES) buffer (n = 4), there was a temporal dissociation between the positive inotropic and the alkalinizing effects of ANG II (0.5 microM). The positive inotropic effect of ANG II peaked at 9.7 +/- 0.8 min (240 +/- 57% above control) without significant changes in pHi. The increase in pHi became significant (0.05 +/- 0.01 pH units) only after 16 min of exposure to the drug, when the positive inotropic effect of ANG II was already fading. In HCO3- buffer (n = 7), the ANG II-induced positive inotropic effect occurred without significant pHi changes. In the presence of 5 microM ethyl isopropyl amiloride (EIPA, to specifically inhibit the Na+/H+ exchanger), the alkalinizing effect of ANG II was changed to a significant decrease in pHi, despite which ANG II still increased contractility by 87 +/- 16% (n = 6). The results indicate that in HEPES buffer only a fraction of the ANG II-induced positive inotropic effect can be attributed to a pHi change, whereas in a physiological CO2-HCO3- medium the positive inotropic effect of ANG II is independent of pHi changes. Furthermore, an ANG II-induced increase in myocardial contractility was observed even when ANG II administration elicited a decrease in pHi, as occurred after Na+/H+ exchanger blockade. The results show that in feline myocardium, the increase in contractility evoked by ANG II in a physiological CO2-HCO3- medium is not due to an increase in Ca2+ myofilament sensitivity secondary to an increase in myocardial pHi.

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