Evidence against a role of nitric oxide in the indirect negative inotropic-effect of M-cholinoceptor stimulation in human ventricular myocardium

1995 ◽  
Vol 352 (3) ◽  
pp. 308-312 ◽  
Author(s):  
Heiko Kilter ◽  
Olaf Lenz ◽  
Karl La Rosée ◽  
Markus Flesch ◽  
Robert H. G. Schwinger ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Negative Inotropic Effect ◽  
Ventricular Myocardium ◽  
Inotropic Effect ◽  
Human Ventricular Myocardium

Mechanism of the Negative Inotropic Effect of Thiopental in Isolated Ferret Ventricular Myocardium 

1995 ◽  
Vol 82 (2) ◽  
pp. 436-450 ◽  
Author(s):  
Philippe R. Housmans ◽  
Turkan S. Kudsioglu ◽  
Jonathan Bingham
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Negative Inotropic Effect ◽  
Ventricular Myocardium ◽  
Underlying Mechanism ◽  
Inotropic Effect ◽  
Inotropic Effects ◽  
Beta Adrenoceptor ◽  
Force Peak ◽  
Human Ventricular Myocardium ◽  
Negative Inotropic Effects

Background Thiopental's myocardial depressant effects are well known and most likely involve some alteration in intracellular Ca2+ homeostasis. The aim of this study was to investigate the mechanisms of thiopental's negative inotropic effects and its underlying mechanism in isolated ferret ventricular myocardium (which shows physiologic characteristics similar to human ventricular myocardium), and in frog ventricular myocardium, in which Ca2+ ions for myofibrillar activation are derived almost entirely from transsarcolemmal influx. Methods The authors analyzed the effects of thiopental after beta-adrenoceptor blockade on variables of contractility and relaxation, and on the free intracellular Ca2+ transient detected with the Ca(2+)-regulated photoprotein aequorin. Thiopental's effects also were evaluated in ferret right ventricular papillary muscles in which the sarcoplasmic reticulum (SR) function was impaired by ryanodine and in frog ventricular strips with little or no SR function. Results At concentration > or = 10(-4) M, which is in the high range of the clinically encountered free plasma thiopental concentrations, thiopental decreased contractility and the amplitude of the intracellular Ca2+ transient. At equal peak force, peak aequorin luminescence in 10(-4) M thiopental and [Ca2+]0 > 2.25 mM was slightly smaller than that in control conditions at [Ca2+]o = 2.25 mM. This indicates that thiopental causes a small increase in myofibrillar Ca2+ sensitivity. After inactivation of sarcoplasmic reticulum Ca2+ release with 10(-6) M ryanodine, a condition in which myofibrillar activation depends almost exclusively on transsarcolemmal Ca2+ influx, thiopental caused a further decrease in contractility and in the amplitude of the intracellular Ca2+ transient, and thiopental's relative negative inotropic effect was not different from that in control muscles not exposed to ryanodine. Thiopental, > or = 10(-4) M, decreased contractility in frog ventricular myocardium. Conclusions These findings indicate that the direct negative inotropic effect of thiopental results from a decrease in intracellular Ca2+ availability. At least part of thiopental's action is caused by inhibition of transsarcolemmal Ca2+ influx. These effects become apparent at concentrations routinely present during intravenous induction with thiopental.

Effect of Volatile Anesthetics on the Force–Frequency Relation in Human Ventricular Myocardium

2001 ◽  
Vol 95 (5) ◽  
pp. 1160-1168 ◽  
Author(s):  
Ulrich Schotten ◽  
Maura Greiser ◽  
Volker Braun ◽  
Christian Karlein ◽  
Friedrich Schoendube ◽  
...  
Keyword(s):  
Calcium Release ◽  
Negative Inotropic Effect ◽  
Volatile Anesthetics ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Force Frequency ◽  
Calcium Release Channel ◽  
Frequency Relation ◽  
Human Ventricular Myocardium

Background In human ventricular myocardium, contractile force increases at higher stimulation frequencies (positive force-frequency relation). In failing hearts, the force-frequency relation (FFR) is negative. Data on the effect of volatile anesthetics on FFR are very limited. Methods The authors obtained left ventricular tissue from 18 explanted hearts from patients undergoing cardiac transplantation and tissue of 8 organ donors. The negative inotropic effect of halothane, isoflurane, and sevoflurane on isometric force of contraction of isolated muscle preparations at a stimulation frequency of 1 and 3 Hz and the effect of each anesthetic on the FFR were studied. Ryanodine and verapamil were studied for comparison. In addition, the effect of the anesthetics on Ca(2+)-dependent (3)H-ryanodine binding was investigated. Results In nonfailing myocardium, halothane was the strongest negative inotropic compound, and the positive FFR was not affected by either drug. In failing myocardium, halothane also showed the strongest negative inotropic effect, but the positive shape of FFR was restored by halothane and ryanodine. In contrast, isoflurane, sevoflurane, and verapamil did not change FFR. Only halothane shifted the Ca(2+)-dependent (3)H-ryanodine binding curve toward lower Ca(2+) concentrations. Conclusion In nonfailing human myocardium, none of the anesthetics affect FFR, but halothane is the strongest negative inotropic compound. In failing myocardium, halothane, but not isoflurane or sevoflurane, restores the positive shape of FFR. Both the more pronounced negative inotropic effect of halothane and the restoration of the positive shape of FFR in failing myocardium in the presence of halothane can be explained by its interaction with the myocardial sarcoplasmic reticulum calcium-release channel.

Negative inotropic effect of bradykinin in porcine isolated atrial trabeculae: role of nitric oxide

2001 ◽  
Vol 19 (7) ◽  
pp. 1289-1293 ◽  
Author(s):  
Beril Tom ◽  
René de Vries ◽  
Pramod R. Saxena ◽  
A. H. Jan Danser
Keyword(s):  
Nitric Oxide ◽  
Negative Inotropic Effect ◽  
Inotropic Effect

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.

Crucial role of cytoskeleton reorganization in the negative inotropic effect of chromogranin A-derived peptides in eel and frog hearts

2007 ◽  
Vol 138 (2-3) ◽  
pp. 145-151 ◽  
Author(s):  
Rosa Mazza ◽  
Cinzia Mannarino ◽  
Sandra Imbrogno ◽  
Sandra Francesca Barbieri ◽  
Cristina Adamo ◽  
...  
Keyword(s):  
Crucial Role ◽  
Chromogranin A ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Cytoskeleton Reorganization
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