Comparative effect of procainamide and lidocaine on myocardial contractility

1969 ◽  
Vol 47 (12) ◽  
pp. 1038-1042 ◽  
Author(s):  
M. Nahas ◽  
J. Lachapelle ◽  
G. M. Tremblay
Keyword(s):  
Myocardial Contractility ◽  
Positive Inotropic Effect ◽  
Negative Inotropic Effect ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Inotropic Effect ◽  
Comparative Effect ◽  
Heart Perfusion ◽  
Biphasic Effect ◽  
Therapeutic Doses

The effect of procainamide and lidocaine on myocardial contractility was studied in an isovolumic isolated rat heart perfusion preparation following the Langendorff technique. As a measure of myocardial contractility, the left ventricular intracavitary pressure and maximum dp/dt were determined and were found to be depressed proportionately to the dose of these agents. At the same concentration, lidocaine showed a more negative inotropic effect than procainamide (although the former seems clinically innocuous at therapeutic doses). In addition, procainamide produced in about one-half of the experiments a biphasic effect characterized by a slight transitory positive inotropic effect followed by a negative inotropic effect.

scholarly journals Molecular Mechanism of Palmitic Acid on Myocardial Contractility in Hypertensive Rats and Its Relationship with Neural Nitric Oxide Synthase Protein in Cardiomyocytes

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Haibo Tan ◽  
Weiwei Song ◽  
Sha Liu ◽  
Qing Song ◽  
Tiangang Zhou ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Myocardial Contractility ◽  
Sham Group ◽  
Positive Inotropic Effect ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Hypertensive Rats ◽  
Atp Level ◽  
Ventricular Cardiomyocytes ◽  
Oxide Synthase

Objective. It is aimed at investigating the mechanism of palmitic acid (PA) on myocardial contractility in hypertensive rats and its relationship with myocardial neural nitric oxide synthase (nNOS) protein. Methods. The rats were randomly divided into sham operation group and hypertensive group, with thirty rats in each group, to prepare angiotensin II-induced hypertensive model rats. The blood pressure of rats was measured by the multianimal multichannel tail cuff noninvasive blood pressure system of Kent Coda, USA. The Ionoptix single-cell contraction detection system was used to detect myocardial cells. ATP level of left ventricular cardiomyocytes was determined by luminescence method, and protein was measured by Western blot. Results. Compared with the sham group, systolic blood pressure and diastolic blood pressure were increased in the hypertensive group over 4 weeks; PA increased the contractility of left ventricular cardiomyocytes in normal rats, but not in hypertensive rats, and PA increased the intracellular ATP level of rats in the sham group but not in the hypertension group. In the hypertension group, the expression of nNOS in the cardiomyocytes was significantly increased, and specific nNOS inhibitor S-methyl-L-thiocitrulline (SMTC) was found to restore the positive inotropic effect of PA in the myocardium of the hypertension group. PA was supplemented after using CPT-1 inhibitor etomoxir (ETO); it was found that ETO inhibited the positive inotropic effect of PA on left ventricular cardiomyocytes in the sham group, and PA was supplemented after using SMTC and ETO, it was found that SMTC + ETO could inhibit the positive inotropic effect of PA on left ventricular cardiomyocytes in myocardium of hypertensive rats. Conclusion. PA could increase the contractility of healthy cardiomyocytes, but had no obvious positive effect on the cardiomyocytes of hypertensive rats, PA enhanced the contractility of cardiomyocytes by increasing ATP level in them, and the inhibitory effect of PA on myocardial contractility in hypertensive rats may be related to the increased nNOS and CPT-1 in cardiomyocytes.

Interaction of Halothane with α- and β-Adrenoceptor Stimulations in Rat Myocardium

1997 ◽  
Vol 86 (1) ◽  
pp. 147-159 ◽  
Author(s):  
Jean-Luc Hanouz ◽  
Bruno MD Riou ◽  
Laurent Massias ◽  
Yves Lecarpentier ◽  
Pierre Coriat
Keyword(s):  
Positive Inotropic Effect ◽  
Negative Inotropic Effect ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Papillary Muscles ◽  
Inotropic Effects ◽  
Beta Adrenoceptor ◽  
Low Load ◽  
Positive Inotropic Effects

Background Halothane induces negative inotropic and lusitropic effects in myocardium. It has been suggested that halothane potentiates beta-adrenoceptor stimulation. However, its effects on the inotropic response to alpha-adrenoceptor stimulation and its effects on the lusitropic effects of alpha- and beta-adrenoceptor stimulation are unknown. Methods The effects of halothane (0.5 and 1 minimum alveolar concentration [MAC]) on the inotropic responses induced by phenylephrine (10(-8) to 10(-4) M) and isoproterenol (10(-8) to 10(-4) M) were studied in rat left ventricular papillary muscles in vitro (in Krebs-Henseleit solution at 29 degrees C, pH 7.40, with 0.5 mM calcium and stimulation frequency at 12 pulses/min). The lusitropic effects were studied in isotonic (R1) and isometric (R2) conditions. Results One MAC halothane induced a negative inotropic effect (54 +/- 3%, P < 0.05), increased R1 (109 +/- 3%, P < 0.05), and decreased R2 (88 +/- 2%, P < 0.05). In control groups, phenylephrine (137 +/- 7%, P > 0.05) and isoproterenol (162 +/- 6%, P < 0.05) induced a positive inotropic effect. Halothane did not significantly modify the positive inotropic effect of calcium, suggesting that it did not modify the inotropic reserve of papillary muscles. In contrast, 1 MAC halothane enhanced the positive inotropic effects of phenylephrine (237 +/- 19%, P < 0.05) and isoproterenol (205 +/- 11%, P < 0.05). Halothane did not modify the lusitropic effect of phenylephrine under high or low load. In contrast, 1 MAC halothane impaired the positive lusitropic effect of isoproterenol under low load (P < 0.05), whereas it did not modify the positive lusitropic effect of isoproterenol under high load. Conclusions At clinically relevant concentrations, halothane potentiated the positive inotropic effects of both alpha- and beta-adrenoceptor stimulation. Furthermore, halothane alters the positive lusitropic-effect of beta-adrenoceptor stimulation under low load.

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.

Calcium channels and excitation–contraction coupling in cardiac cells. II. A pharmacological study of the biphasic contraction in guinea-pig papillary muscle

1987 ◽  
Vol 65 (9) ◽  
pp. 1832-1839 ◽  
Author(s):  
E. Honoré ◽  
M. M. Adamantidis ◽  
B. A. Dupuis ◽  
C. E. Challice ◽  
P. Guilbault
Keyword(s):  
Guinea Pig ◽  
Papillary Muscle ◽  
Positive Inotropic Effect ◽  
Pharmacological Study ◽  
Negative Inotropic Effect ◽  
Cardiac Cells ◽  
Inotropic Effect ◽  
Free Solution ◽  
Contraction Coupling ◽  
Rich Solution

Biphasic contractions were obtained in guinea-pig papillary muscle by inducing partial depolarization in K+-rich solution (17 mM) in the presence of 0.3 μM isoproterenol. Mn2+ ions inhibited the two components of contraction in a similar way. Nifedipine and particularly Cd2+ ions specifically inhibited the second component of contraction. Isoproterenol and BAY K 8644 markedly increased the amplitude of the second component (P2) of contraction. Nevertheless, a moderate positive inotropic effect of isoproterenol was found on the first component (P1) of contraction when excitability was restored by 0.2 mM Ba instead of isoproterenol. Acetylcholine and hypoxia decreased the amplitude of the second component of contraction to a greater extent. In the presence of digoxin or Na+-free solution, P1was strongly increased. When sarcoplasmic reticular function was hindered by 1 mM caffeine or in the presence of Ca2+-free Sr2+ solution, digoxin always induced a negative inotropic effect on P2. Inversely in these conditions the transient positive inotropic effect of Na+-free solution was strongly reduced. These results are consistent with the hypothesis that the late component of contraction is triggered by the slow inward Ca2+ current and that the early component is due to Ca2+ release from the sarcoplasmic reticulum.

Positive inotropic effects of low concentrations of leukotrienes C4 and D4 in rat heart

1990 ◽  
Vol 259 (4) ◽  
pp. H1239-H1246 ◽  
Author(s):  
M. Karmazyn ◽  
M. P. Moffat
Keyword(s):  
Calcium Channel ◽  
Positive Inotropic Effect ◽  
Negative Inotropic Effect ◽  
Bay K 8644 ◽  
Inotropic Effect ◽  
Receptor Interaction ◽  
Inotropic Effects ◽  
Coronary Pressure ◽  
Low Concentrations ◽  
Rat Hearts

We examined the effects of leukotrienes (LT) B4, C4, D4, and E4 (0.010-2.5 ng/ml) on contractile and coronary function in isolated rat hearts. Concentration-dependent effects were examined either by the cumulative addition of LTs or by addition of specific concentrations to individual preparations. Neither LTB4 nor LTE4 produced myocardial or coronary effects at any concentration, irrespective of addition protocol. At 0.010 ng/ml, both LTC4 and LTD4 produced an increase in force that was associated with a 30% elevation in coronary pressure. Further cumulative addition of either leukotriene resulted in a negative inotropic effect and a further increase in coronary pressure. In contrast, following single additions of LTC4 or LTD4 (0.01-0.50 ng/ml) a positive inotropic effect and an increased coronary pressure were observed. LTC4 or LTD4 at 0.5 ng/ml produced a negative inotropic effect in hearts pretreated with 0.01 ng/ml of LTD4 or LTC4, respectively. Reversal of this addition protocol resulted in a negative inotropic effect of either 0.01 ng/ml LTD4 or LTC4. Verapamil and nifedipine significantly attenuated the positive inotropic and coronary constricting effect of 0.5 ng/ml LTC4 and LTD4. The addition of either LT following BAY K 8644 resulted in a negative inotropic effect, in contrast to the positive inotropic influence seen with leukotriene alone. Our results demonstrate a positive inotropic effect of low concentrations of LTC4 and LTD4 concomitant with coronary artery constriction, a phenomenon determined by leukotriene addition protocols and suggestive of LTC4/LTD4 receptor interaction. The effects of calcium channel antagonists and BAY K 8644 on the inotropic response suggest a leukotriene-mediated activation of the calcium channel resulting in increased intracellular calcium concentrations.

Some Effects of Caffeine and Quinidine on Sarcoplasmic Reticulum of Skeletal and Cardiac Muscle

1973 ◽  
Vol 51 (7) ◽  
pp. 499-503 ◽  
Author(s):  
William R. Thorpe
Keyword(s):  
Skeletal Muscle ◽  
Sarcoplasmic Reticulum ◽  
Cardiac Muscle ◽  
Myocardial Contractility ◽  
Gastrocnemius Muscle ◽  
Negative Inotropic Effect ◽  
Inotropic Effect ◽  
Experimental Conditions

Sarcoplasmic reticulum (SR) was prepared from the gastrocnemius muscle and the heart of freshly killed rabbits. It was found that the skeletal SR actively bound significantly more calcium than did the cardiac SR under the same experimental conditions. The effect of caffeine and quinidine on the release of calcium actively bound by both cardiac and skeletal SR was studied. Quinidine (10−3 M) released 4.1% of the calcium bound by skeletal SR and 27.7% of that bound by cardiac SR. Similarly, caffeine (20 mM) released 10.5% and 34.3% of the calcium bound by skeletal and cardiac SR, respectively. It is suggested that both caffeine and quinidine could produce contracture of skeletal muscle by acting on the SR and that caffeine could stimulate myocardial contractility through its action on the cardiac SR. However, it is unlikely that quinidine exerts its negative inotropic effect on the heart through its calcium releasing action on the cardiac SR.

Interaction of Halogenated Anesthetics with α- and β-Adrenoceptor Stimulations in Diabetic Rat Myocardium

2004 ◽  
Vol 101 (5) ◽  
pp. 1145-1152 ◽  
Author(s):  
Julien Amour ◽  
Jean-Stéphane David ◽  
Benoît Vivien ◽  
Pierre Coriat ◽  
Bruno Riou
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Positive Inotropic Effect ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Diabetic Rat ◽  
Inotropic Effects ◽  
Beta Adrenoceptor ◽  
Alpha Adrenoceptor ◽  
Positive Inotropic Effects

Background Halogenated anesthetics potentiate the positive inotropic effects of alpha- and beta-adrenoceptor stimulations. Although diabetes mellitus induces significant myocardial abnormalities, the interaction of halogenated anesthetics and adrenoceptor stimulation in diabetic myocardium remains unknown. Methods Left ventricular papillary muscles were provided from healthy and streptozotocin-induced diabetic rats. Effects of 1 minimum alveolar concentration halothane, isoflurane, and sevoflurane on the inotropic and lusitropic responses of alpha (phenylephrine)- and beta (isoproterenol)-adrenoceptor stimulations were studied at 29 degrees C with 12 pulses/min. Data shown are mean percentage of baseline active force +/- SD. Results Phenylephrine induced comparable positive inotropic effects in healthy and diabetic rats (143 +/- 8 vs. 136 +/- 18%; not significant), but the potentiation by halogenated anesthetics was abolished in the diabetic rats (121 +/- 20, 130 +/- 20, and 123 +/- 20% for halothane, isoflurane, and sevoflurane, respectively; not significant). In diabetic rats, the positive inotropic effect of isoproterenol was markedly diminished (109 +/- 9 vs. 190 +/- 18%; P < 0.05), but its potentiation was preserved with isoflurane (148 +/- 21%; P < 0.05) and sevoflurane (161 +/- 40%; P < 0.05) but not with halothane (126 +/- 16%; not significant). Halothane induced a deleterious effect on the sarcoplasmic reticulum, as shown by its impairment in the lusitropic effect of isoproterenol, compared with isoflurane and sevoflurane. Conclusion Potentiation of the positive inotropic effect of alpha-adrenoceptor stimulation by halogenated anesthetics is abolished in diabetic rats. In contrast, potentiation of beta-adrenoceptor stimulation is preserved with isoflurane and sevoflurane but not with halothane, probably because of its deleterious effects on sarcoplasmic reticulum.

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.

Chronic verapamil treatment attenuates the negative inotropic effect of ethanol in diabetic rat myocardium

1994 ◽  
Vol 72 (9) ◽  
pp. 1013-1018 ◽  
Author(s):  
Ricardo A. Brown ◽  
Prashant Bhasin ◽  
Adedapo O. Savage ◽  
Joseph C. Dunbar
Keyword(s):  
Negative Inotropic Effect ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Diabetic Rat ◽  
Tension Development ◽  
Altered Expression ◽  
Peak Tension ◽  
Time To Peak ◽  
Diabetic Myocardium

It is well established that cardiomyopathy is a consistent feature of diabetic myocardium and that alcohol consumption increases the risk of cardiovascular disease among diabetic subjects. The objective of this investigation was to determine whether acute or chronic verapamil treatment attenuates the negative inotropic effect of ethanol (EtOH) in the diabetic rat heart. Wistar rats were made diabetic with streptozotocin (55 mg/kg, iv). Left-ventricular papillary muscles, from normal and diabetic (8 weeks) rats, were superfused with Tyrode's solution at 30 °C while driven at 0.5 Hz. A subgroup of diabetic and normal animals received daily injections of verapamil (8 mg/kg, ip; 8 weeks), whereas muscles from untreated animals were exposed to verapamil (2 μM) in vitro. Peak tension developed (PTD), time to peak tension (TPT), time to 90% relaxation (RT90), and the maximum velocities of tension development (+VT) and decay (−VT) were determined in the absence and presence of clinically relevant concentrations of EtOH (80–240 mg/dL, i.e., 17.4–52.1 mM). Ethanol at 80 mg/dL reduced PTD, + VT, and −VT only in preparations from diabetic animals. Higher concentrations of EtOH (120–240 mg/dL) decreased PTD, TPT, +VT, and −VT. The negative inotropic effect of EtOH (240 mg/dL) was attenuated only in diabetic myocardium chronically treated with verapamil, whereas acute verapamil treatment potentiated the negative inotropic effect of EtOH in both normal and diabetic myocardium. Thus, chronic verapamil therapy diminishes the negative inotropic effect of EtOH in diabetic myocardium and acute verapamil treatment exaggerates it. Altered expression of membrane-bound calcium channels may be involved in the negative inotropic response to EtOH in long-term diabetes.Key words: ethanol, papillary muscle, inotropism, myocardium, force of contraction, diabetes mellitus.

scholarly journals Cytochrome P-450 metabolite of arachidonic acid mediates bradykinin-induced negative inotropic effect

2001 ◽  
Vol 280 (6) ◽  
pp. H2823-H2832 ◽  
Author(s):  
R. Rastaldo ◽  
N. Paolocci ◽  
A. Chiribiri ◽  
C. Penna ◽  
D. Gattullo ◽  
...  
Keyword(s):  
Left Ventricular Pressure ◽  
Negative Inotropic Effect ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Cyclooxygenase Inhibitors ◽  
Epoxyeicosatrienoic Acid ◽  
Rat Hearts ◽  
Coronary Endothelium ◽  
Triton X ◽  
Cytochrome P 450

This study focused on the mechanisms of the negative inotropic response to bradykinin (BK) in isolated rat hearts perfused at constant flow. BK (100 nM) significantly reduced developed left ventricular pressure (LVP) and the maximal derivative of systolic LVP by 20–22%. The cytochrome P-450 (CYP) inhibitors 1-aminobenzotriazole (1 mM and 100 μM) or proadifen (5 μM) abolished the cardiodepression by BK, which was not affected by nitric oxide and cyclooxygenase inhibitors (35 μM N G-nitro-l-arginine methyl ester and 10 μM indomethacin, respectively). The CYP metabolite 14,15-epoxyeicosatrienoic acid (14,15-EET; 50 ng/ml) produced effects similar to those of BK in terms of the reduction in contractility. After the coronary endothelium was made dysfunctional by Triton X-100 (0.5 μl), the BK-induced negative inotropic effect was completely abolished, whereas the 14,15-EET-induced cardiodepression was not affected. In hearts with normal endothelium, after recovery from 14,15-EET effects, BK reduced developed LVP to a 35% greater extent than BK in the control. In conclusion, CYP inhibition or endothelial dysfunction prevents BK from causing cardiodepression, suggesting that, in the rat heart, endothelial CYP products mediate the negative inotropic effect of BK. One of these mediators appears to be 14,15-EET.

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