scholarly journals Evidence for a negative inotropic effect of obesity in human myocardium?☆

2009 ◽  
Vol 36 (2) ◽  
pp. 300-305 ◽  
Author(s):  
Katja Denk ◽  
Jörg Albers ◽  
Nalan Kayhan ◽  
Dilek Ister ◽  
Andreas Bonz ◽  
...  
Keyword(s):  
Negative Inotropic Effect ◽  
Human Myocardium ◽  
Inotropic Effect

Halothane Restores the Altered Force-Frequency Relationship in Failing Human Myocardium

1995 ◽  
Vol 82 (6) ◽  
pp. 1456-1462. ◽  
Author(s):  
Ulrich Schmidt ◽  
Robert H. G. Schwinger ◽  
Michael Bohm
Keyword(s):  
Cardiac Surgery ◽  
Human Heart ◽  
Positive Inotropic Effect ◽  
Negative Inotropic Effect ◽  
Human Myocardium ◽  
Inotropic Effect ◽  
Force Frequency ◽  
Beta Adrenoceptors ◽  
Frequency Relationship

Background The terminally failing human myocardium exerts a negative force-frequency relationship (FFR), whereas a positive FFR occurs in nonfailing myocardium. To study the possibility of pharmacologically influencing this defect of the failing human heart, the effect of halothane on the basal FFR and the FFR in the presence of isoproterenol and ouabain was investigated. Methods Experiments were performed on isolated, electrically driven (0.5-2 Hz, 37 degrees C, Ca2+ 1.8 mmol/l) ventricular preparations. Myocardium from human failing and nonfailing hearts was obtained at cardiac surgery. To further characterize the studied myocardium, the positive inotropic effect of isoproterenol and the density of beta-adrenoceptors were measured using the radioligand 125I-CYP. Results Halothane produced a negative inotropic effect. The anesthetic (0.38 mmol/l) reversed the negative FFR in failing myocardium, antagonized the effect of isoproterenol (0.1 mumol/l) on FFR, and restored the FFR in the presence of ouabain. Conclusions Halothane restores the FFR in human failing myocardium possibly by influencing the intracellular Ca2+ homeostasis. These findings provide evidence that pharmacologic interventions, e.g., during anesthesia, may influence contractility also as a result of a depressed or enhanced FFR.

Abstract 1469: Diastolic dysfunction induced by Flecainide but not Amiodarone

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Egbert Bisping ◽  
Christian Pagel ◽  
Andre Wilken ◽  
Karl Toischer ◽  
Burkert Pieske
Keyword(s):  
Atrial Fibrillation ◽  
Diastolic Dysfunction ◽  
Diastolic Function ◽  
Negative Inotropic Effect ◽  
Human Myocardium ◽  
Inotropic Effect ◽  
Force Frequency ◽  
Inotropic Effects ◽  
Rabbit Myocardium ◽  
Negative Inotropic Effects

Diastolic dysfunction is a significant risk factor for the development and progression of atrial fibrillation. Flecainide (Flec) and Amiodarone (AM) are frequently used in patients with atrial fibrillation but their impact on diastolic function has not been evaluated yet. We tested the effect of Flec and AM on systolic and diastolic performance in isolated muscle strips from failing human and nonfailing rabbit myocardium. Isolated ventricular trabeculae contracted isometrically at 1 Hz, Ca2+ 2.5 mmol/L, 37°C. Flec (0.01 – 100 μmol/L, dissolved in water) showed a concentration dependent negative inotropic effect in human myocardium (13 ± 2 vs. 3 ± 0.5 mN/mm 2 at base vs. 100 μmol/L; p< 0.05). This was associated with a significant prolongation of the relaxation time RT95 and an increase of diastolic tension (Dias) by 35 ± 9 % (at 100 μmol/L; p< 0.05). Water alone had no effect. Calcium transients measured by Aequorin technique declined proportionally to developed force after Flec. In contrast, AM (0.01 – 100 μmol/L, dissolved in 2% benzyl alcohol and 10% polsorbate) showed identical negative inotropic effects to solvent alone (maximally by 16 ± 8 %), and neither AM nor its solvent affected diastolic tension or relaxation times. Flec (3 μmol/L) resulted in a significant impairment of the Force frequency relationship (FFR) at 0.5–3.0 Hz in human myocardium. This was related to a decline in systolic force and a rise in Dias at high frequencies (at 3 Hz by 32 ± 12 % in control and 87 ± 25 % after Flec, p < 0.05 vs. control). In nonfailing rabbit myocardium (1.0–5.0 Hz) Dias decreased by 11 ± 10 % (n.s.) in control but raised by 65 ± 25 % after Flec, p < 0.05). AM (100 μmol/L) had no significant effect on FFR, whereas its solvent tended to impair the FFR by a decline in systolic performance. Conclusion: Flec exerts calcium dependent negative inotropic effects in human myocardium and significantly impairs diastolic function. The latter is observable not only in human failing myocardium with preexisting diastolic dysfunction but also in nonfailing animal myocardium. In contrast AM shows no compound specific negative inotropic effect and no change in diastolic function. In patients treated with Flec attention should be turned to the potential of the drug to deteriorate diastolic function.

Cellular basis of negative inotropic effect of 2,3-butanedione monoxime in human myocardium

1992 ◽  
Vol 263 (2) ◽  
pp. H503-H510 ◽  
Author(s):  
C. L. Perreault ◽  
L. A. Mulieri ◽  
N. R. Alpert ◽  
B. J. Ransil ◽  
P. D. Allen ◽  
...  
Keyword(s):  
Force Production ◽  
Negative Inotropic Effect ◽  
Hill Equation ◽  
Human Myocardium ◽  
Inotropic Effect ◽  
Transplant Recipients ◽  
Protective Actions ◽  
Maximal Activation ◽  
Butanedione Monoxime ◽  
Underlying Mechanisms

2,3-Butanedione monoxime (BDM) exerts a marked negative inotropic effect and has been shown to have protective actions on human myocardial force production that may be of clinical use. To determine the underlying mechanisms, we studied the effects of BDM on chemically skinned and aequorin-loaded myopathic human myocardium from transplant recipients. Eighteen muscles were chemically skinned with saponin (250 micrograms/ml) and then subjected to activation-relaxation cycles, with and without 5 mM BDM. Contracture force vs. Ca2+ data were fitted to a modified Hill equation, and values for 50% maximal activation (pCa50) and maximal Ca(2+)-activated force (Fmax) were obtained. pCa50 was decreased by 0.2 pCa units, indicating myofilament Ca2+ desensitization, and Fmax was reduced by 48% in 5 mM BDM. A second group of intact muscles (n = 8) was loaded with aequorin to monitor intracellular calcium (Cai2+) transients (peak light) and twitch force in the presence of BDM (1-30 mM). Over a range of 1-20 mM, BDM depressed peak light by 3-49% while force was depressed by 10-82%. This was accompanied by an abbreviation of the duration of the twitch but not of the Cai2+ transient. At a concentration of 30 mM, BDM completely inhibited force generation, but an Cai2+ transient was still present. We conclude that in human myocardium, 5 mM BDM predominantly affects cross-bridge force production and Ca2+ sensitivity and has a less pronounced effect on Cai2+.

Negative Inotropic Effect of Basic Fibroblast Growth Factor on Adult Rat Cardiac Myocyte

Circulation ◽  
1997 ◽  
Vol 96 (8) ◽  
pp. 2501-2504 ◽  
Author(s):  
Yuji Ishibashi ◽  
Yoshitoshi Urabe ◽  
Hiroyuki Tsutsui ◽  
Shintaro Kinugawa ◽  
Masaru Sugimachi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Fibroblast Growth Factor ◽  
Basic Fibroblast Growth Factor ◽  
Cardiac Myocyte ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Fibroblast Growth ◽  
Adult Rat

Functional and autoradiographic characterization of dopamine D2-like receptors in the guinea pig heart

2002 ◽  
Vol 80 (6) ◽  
pp. 578-587 ◽  
Author(s):  
María de Jesús Gómez ◽  
Guy Rousseau ◽  
Réginald Nadeau ◽  
Roberto Berra ◽  
Gonzalo Flores ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Western Blot ◽  
Dopamine Receptors ◽  
Negative Inotropic Effect ◽  
Cyclase Activity ◽  
Inotropic Effect ◽  
Receptor Subtypes ◽  
Guinea Pig Heart ◽  
Additional Information ◽  
The Right

Dopamine receptors include the D1- (D1 and D5 subtypes) and D2-like (D2, D3, and D4 subtypes) families. D1-like receptors are positively and D2-like receptors negatively coupled to the adenylyl cyclase. Dopamine D2-like (D4 subtype) receptors have been identified in human and rat hearts. However the presence of D2 and D3 receptor subtypes is unclear. Furthermore, their role in cardiac functions is unknown. By autoradiographic studies of guinea pig hearts, we identified D3 and D4 receptors, using the selective radioligands [3H]-7-OH-DPAT and [3H]emonapride (YM-09151-2 plus raclopride). Western blot analysis confirmed D3 and D4 receptors in the right and left ventricle of the same species. Selective agonists of D3 and D4 receptors (±)-7-OH-DPAT and PD 168 077 (10–9 to 10–5 M, respectively) induced a significant negative chronotropic and inotropic effect in the isolated guinea pig heart preparation. Negative inotropic effect induced by PD 168 077 was associated with an inhibition in cyclase activity. No changes in cyclase activity were found with (±)-7-OH-DPAT. The aim of this study is to support the presence of D3 and D4 receptors in the heart. Although our results suggest that D3 and D4 receptors are functionally active in the heart, we need additional information with an antagonist and an agonist of improved potency and selectivity to understand the respective roles of D3 and D4 receptors in the cardiac functions.Key words: Dopamine receptors (D2, D3, D4 subtypes), autoradiography, Western blot, cAMP, heart.

Cholinergic stimulation modulates negative inotropic effect of cocaine on ferret ventricular myocardium

1996 ◽  
Vol 270 (2) ◽  
pp. H678-H684
Author(s):  
L. Miao ◽  
Z. Qiu ◽  
J. P. Morgan
Keyword(s):  
Response Curve ◽  
Negative Inotropic Effect ◽  
Ventricular Myocardium ◽  
Inotropic Effect ◽  
Dependent Manner ◽  
Cholinergic Stimulation ◽  
Concentration Dependent Manner ◽  
Cell Shortening ◽  
Inotropic State ◽  
Concentration Response Curve

We tested the hypothesis that the negative inotropic effect (NIE) of cocaine is mediated, at least in part, by cholinergic stimulation and can be correlated with the degree of adenosine 3',5'-cyclic monophosphate (cAMP) dependency of the inotropic state. Cardiac myocytes were isolated from left ventricles of ferrets and loaded with the fluorescent Ca2+ indicator indo 1. Cells were placed in physiological solution containing 2.0 mM Ca2+ and stimulated at 0.5 Hz and 30 degrees C. Cocaine decreased peak cell shortening and peak intracellular Ca2+ in a concentration-dependent manner (10(-8)-10(-4) M). The concentration-response curve of cocaine was shifted significantly downward compared with those of lidocaine and procaine in the same range of concentrations. Atropine (10(-6) M) shifted the concentration-response curve of cocaine, but not those of lidocaine and procaine, rightward, with a pA2 value (7.66) similar to that obtained with carbachol (7.99). With prior addition of isoproterenol (ISO, 10(-8) M) or increased Ca2+ (4.0 mM) to increase cell shortening to the same degree (approximately 60%), cocaine and carbachol decreased contractility to a significantly greater extent in ISO-stimulated myocytes. To clarify whether these treatments changed responsiveness of the contractile elements to Ca2+, the effect of 2,3-butanedione monoxime, an agent that interferes with the interaction of myosin and actin, was tested with previous addition of ISO or increased Ca2+, and no differential effect occurred. Therefore, we postulate that 1) the NIE of cocaine on myocytes is caused by decreased Ca2+ availability; 2) this effect is due to specific stimulation of cholinergic receptors in addition to other direct myocardial (probably local anesthetic) effects; and 3) the NIE correlates with the level of cAMP dependence of the inotropic state.

Gαi-biased apelin analog protects against isoproterenol-induced myocardial dysfunction in rats

2021 ◽  
Vol 320 (4) ◽  
pp. H1646-H1656
Author(s):  
David Coquerel ◽  
Eugénie Delile ◽  
Lauralyne Dumont ◽  
Frédéric Chagnon ◽  
Alexandre Murza ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Left Ventricular Hypertrophy ◽  
Ventricular Hypertrophy ◽  
Myocardial Dysfunction ◽  
Negative Inotropic Effect ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Camp Production ◽  
Data Point

By using more potent Gαi-biased APJ agonists that strongly inhibit cAMP production, these data point to the negative inotropic effect of APJ-mediated Gαi signaling in the heart and highlight the potential protective impact of APJ-dependent Gαi signaling in cardiovascular diseases associated with left ventricular hypertrophy.

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