Reductions of myocardial Na-K-ATPase activity and ouabain binding sites in heart failure: prevention by nadolol

1993 ◽  
Vol 265 (6) ◽  
pp. H2086-H2093 ◽  
Author(s):  
T. H. Fan ◽  
R. P. Frantz ◽  
H. Elam ◽  
S. Sakamoto ◽  
N. Imai ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atpase Activity ◽  
Binding Sites ◽  
Early Stage ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Adrenergic Stimulation ◽  
Ouabain Binding ◽  
Systemic Hemodynamic

To study the changes in myocardial digitalis binding sites in heart failure, we measured myocardial ouabain binding sites, Na-K-adenosinetriphosphatase (ATPase) activity, and ventricular muscle mechanical responses to acetylstrophanthidin in dogs with right-heart failure (RHF) produced by tricuspid avulsion and pulmonary artery constriction. Sham-operated dogs were studied as the control. RHF produced a significant decrease in ouabain binding sites in the right and left ventricular myocardium, which was accompanied by a proportional decrease in Na-K-ATPase activity. However, RHF and sham-operated dogs did not differ in systemic hemodynamic or right ventricular trabeculate muscle isometric contractile responses to acetylstrophanthidin. To determine whether chronic beta-adrenergic stimulation contributed to the development of Na-K-ATPase downregulation, we administered nadolol (40 mg/day) to a separate group of dogs during an early stage of RHF development. Nadolol effectively prevented the reduction of myocardial ouabain binding sites that occurred in RHF. Thus we conclude that myocardial ouabain binding sites and Na-K-ATPase activity are reduced in dogs with experimental heart failure and that these changes probably occur as a result of the attendant heightened sympathetic activity.

β-blockade abolishes the augmented cardiac tPA release induced by transactivation of heterodimerised bradykinin receptor-2 and β2-adrenergic receptor in vivo

2014 ◽  
Vol 112 (11) ◽  
pp. 951-959 ◽  
Author(s):  
Morten Eriksen ◽  
Arnfinn Ilebekk ◽  
Alessandro Cataliotti ◽  
Cathrine Rein Carlson ◽  
Torstein Lyberg ◽  
...  
Keyword(s):  
Adrenergic Receptor ◽  
Sympathetic Nerves ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Adrenergic Stimulation ◽  
Β2 Adrenergic Receptor ◽  
Β Blocker

SummaryBradykinin (BK) receptor-2 (B2R) and β2-adrenergic receptor (β2AR) have been shown to form heterodimers in vitro. However, in vivo proofs of the functional effects of B2R-β2AR heterodimerisation are missing. Both BK and adrenergic stimulation are known inducers of tPA release. Our goal was to demonstrate the existence of B2R-β2AR heterodimerisation in myocardium and to define its functional effect on cardiac release of tPA in vivo. We further investigated the effects of a non-selective β-blocker on this receptor interplay. To investigate functional effects of B2R-β2AR heterodimerisation (i. e. BK transactivation of β2AR) in vivo, we induced serial electrical stimulation of cardiac sympathetic nerves (SS) in normal pigs that underwent concomitant BK infusion. Both SS and BK alone induced increases in cardiac tPA release. Importantly, despite B2R desensitisation, simultaneous BK infusion and SS (BK+SS) was characterised by 2.3 ± 0.3-fold enhanced tPA release compared to SS alone. When β-blockade (propranolol) was introduced prior to BK+SS, tPA release was inhibited. A persistent B2R-β2AR heterodimer was confirmed in BK-stimulated and nonstimulated left ventricular myocardium by immunoprecipitation studies and under non-reducing gel conditions. All together, these results strongly suggest BK transactivation of β2AR leading to enhanced β2AR-mediated release of tPA. Importantly, non-selective β-blockade inhibits both SS-induced release of tPA and the functional effects of B2R-β2AR heterodimerisation in vivo, which may have important clinical implications.

scholarly journals Exertional dyspnea after myocardial infarction: thinking beyond the diagnosis of heart failure

2018 ◽  
Vol 46 (11) ◽  
pp. 4769-4774
Author(s):  
Konstantinos Koutsampasopoulos ◽  
Savvas Grigoriadis ◽  
Ioannis Vogiatzis
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Aneurysm ◽  
Left Ventricular Myocardium ◽  
Inferior Wall ◽  
Delayed Presentation ◽  
Exertional Dyspnea ◽  
St Elevation

Introduction We herein present an unusual case of a pseudoaneurysm of the left ventricular myocardium, which is a rare and fatal complication of myocardial infarction. Case report A 64-year-old man with a history of bipolar disorder and arterial hypertension was hospitalized for delayed presentation ST-elevation myocardial infarction. He was admitted to our hospital 24 hours after symptom onset. Diagnostic coronary angiography revealed 95% stenosis at the distal third of the right coronary artery, and he underwent a primary percutaneous coronary intervention to the culprit lesion. Despite administration of a diuretic and optimization of other pharmaceutical treatment, his heart failure deteriorated. Electrocardiography showed a sinus rhythm with Q-wave formation in the inferior wall leads (II, III, aVF), T-wave inversion in the same leads, and borderline QT prolongation (QTc of 490 ms). No ST elevation suggestive of left ventricular aneurysm formation was noticed. Forty days later, cardiac ultrasound revealed a dyskinetic cavity (pseudoaneurysm) in continuity with the posterior–inferior wall of the myocardium, resulting in severe mitral valve regurgitation. Unfortunately, the patient died while awaiting surgical treatment. Conclusion Although most patients with left ventricular pseudoaneurysm have a relatively benign outcome, those with symptoms of heart failure must be urgently diagnosed and treated.

Deloading of the Left Ventricle by Ventricular Assist Device Normalizes Increased Expression of Endothelin ET A Receptors But Not Endothelin-Converting Enzyme-1 in Patients With End-Stage Heart Failure

Circulation ◽  
2000 ◽  
Vol 102 (suppl_3) ◽  
Author(s):  
Henning Morawietz ◽  
Marten Szibor ◽  
Winfried Goettsch ◽  
Babett Bartling ◽  
Matthias Barton ◽  
...  
Keyword(s):  
Heart Failure ◽  
Heart Transplantation ◽  
Ace Inhibitor ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Converting Enzyme ◽  
Ventricular Assist ◽  
End Stage Heart Failure ◽  
End Stage

Background —Ventricular assist devices (VAD) are implanted in patients with end-stage heart failure for bridging the time until heart transplantation, resulting in hemodynamic unloading of the failing heart, improved cardiac contractile and mitochondrial function, and reversal of cardiac hypertrophy. It is unknown whether VAD unloading may affect the cardiac endothelin (ET) system, which has been proposed as one of the putative pathomechanisms of heart failure. Methods and Results —With the use of standard-calibrated, competitive reverse-transcription–polymerase chain reaction mRNA expression of components of the ET system was analyzed in left ventricular myocardium from nonfailing donor hearts, from failing hearts without and with ACE inhibitor therapy, and from patients with end-stage heart failure at the time of VAD implantation and 103±15 days after VAD implantation during removal with subsequent heart transplantation. ET receptor A (ET A ) was markedly upregulated in failing human myocardium. This increased ET A expression was not affected by ACE inhibitor treatment but was normalized by VAD unloading. ET A expression before or after VAD implantation did not correlate with duration of VAD implantation or suppression of Pro-ANP mRNA. ET B mRNA expression was unaffected by heart failure or VAD. In contrast, increased ET-converting enzyme-1 mRNA and ET-1 peptide levels in failing myocardium were partially normalized by ACE inhibition but not by VAD unloading. Conclusions —We conclude that VAD implantation normalizes ET A expression in failing human left ventricular myocardium, probably as the result of the beneficial effects of VAD unloading.

SR Ca(2+)-ATPase activity and expression in ventricular myocardium of dogs with heart failure

1997 ◽  
Vol 273 (1) ◽  
pp. H12-H18 ◽  
Author(s):  
R. C. Gupta ◽  
H. Shimoyama ◽  
M. Tanimura ◽  
R. Nair ◽  
M. Lesch ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atpase Activity ◽  
Sodium Dodecyl ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Maximal Velocity ◽  
Protein Levels ◽  
Lv Dysfunction ◽  
Lv Ejection Fraction ◽  
Tissue Specimens

The purpose of this study was to examine the activity and expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase in left ventricular (LV) myocardium of dogs with chronic heart failure (HF). LV and right ventricular (RV) tissue specimens were obtained from six normal (NL) control dogs and six dogs with chronic HF (LV ejection fraction, 23 +/- 2%) produced by multiple sequential intracoronary microembolizations. Thapsigargin-sensitive Ca(2+)-ATPase activity was measured in isolated SR membrane fractions prepared from LV and RV myocardium. Ca(2+)-ATPase expression, using a specific dog myocardium monoclonal antibody, was measured in sodium dodecyl sulfate (SDS) extract prepared from LV and RV myocardium. Ca(2+)-ATPase activity in both ventricles of NL or HF dogs increased with increasing Ca2+ concentration and reached a plateau at 3 microM Ca2+. The maximal velocity (Vmax, mumol Pi released.min-1.mg-1) of Ca(2+)-ATPase activity was significantly lower in LV of HF dogs compared with NL (0.15 +/- 0.01 vs. 0.23 +/- 0.01, P < 0.05), whereas the affinity of the Ca2+ pump for Ca2+ was unchanged. LV tissue levels of Ca(2+)-ATPase (densitometric units/5 micrograms noncollagen protein) were also significantly lower in LV myocardium of HF dogs compared with NL (3.52 +/- 0.43 vs. 5.53 +/- 0.47, P < 0.05). No significant differences in Ca(2+)-ATPase activity or expression were observed in RV myocardium of HF dogs compared with NL. We conclude that SR Ca(2+)-ATPase activity and protein levels are reduced in LV myocardium of dogs with chronic HF. This abnormality of the SR Ca2+ pump of the failed LV can result in impaired Ca2+ uptake and ultimately to Ca2+ overload and global LV dysfunction.

scholarly journals Heart failure switches the RV α1-adrenergic inotropic response from negative to positive

2010 ◽  
Vol 298 (3) ◽  
pp. H913-H920 ◽  
Author(s):  
Guan-Ying Wang ◽  
Che-Chung Yeh ◽  
Brian C. Jensen ◽  
Michael J. Mann ◽  
Paul C. Simpson ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Problem ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Coronary Artery Ligation ◽  
Inotropic Response ◽  
Artery Ligation ◽  
Protein Levels ◽  
Inotropic Responses

Right ventricular (RV) failure is a serious common clinical problem that is poorly understood. Therefore, for failing and nonfailing hearts, we examined the distinctive inotropic responses induced in the RV myocardium after the stimulation of α1-adrenergic receptors (ARs). In RV trabeculae from nonfailing mouse hearts, α1-ARs induced a negative inotropic response, consistent with our previous study. In marked contrast, in RV trabeculae from failing hearts, 12 wk after coronary artery ligation, α1-ARs induced a positive inotropic response. Mechanistically, experiments with skinned trabeculae showed that α1-ARs decreased myofilament Ca2+ sensitivity in the nonfailing RV myocardium, whereas α1-ARs increased Ca2+ sensitivity in heart failure. This suggests that a switch in the Ca2+ sensitivity response to α1-AR stimulation explained the switch in the RV α1-AR inotropic response in heart failure. Myosin light chain kinase (MLCK) can increase myofilament Ca2+ sensitivity, and the smooth muscle isoform (smMLCK), which is also present in cardiomyocytes, was more abundant in the RV myocardium from failing versus nonfailing hearts. Moreover, the MLCK inhibitor ML-9 prevented the switch of the RV myocardium to a positive α1-AR inotropic response in heart failure. In the left ventricular myocardium, in contrast, α1-AR inotropic responses were not different in failing versus nonfailing hearts, and smMLCK abundance was not increased in heart failure. In relation to human disease, we found that smMLCK mRNA and protein levels were increased in RVs from failing human hearts. We conclude that the RV inotropic response to α1-ARs is switched from negative to positive in heart failure, through a pathway involving increased myofilament Ca2+ sensitivity. Since α1-AR agonist catecholamines are elevated in heart failure, increased α1-AR inotropic responses in the RV myocardium may be adaptive in heart failure by helping the failing RV respond to increased pulmonary pressures.

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