In Vitro Effects of Dantrolene on Rat Myocardium

1997 ◽  
Vol 86 (1) ◽  
pp. 205-215 ◽  
Author(s):  
Sylvia Fratea ◽  
Olivier Langeron ◽  
Yves Lecarpentier ◽  
Pierre Coriat ◽  
Bruno Riou
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Calcium Concentration ◽  
Calcium Release ◽  
Negative Inotropic Effect ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Rat Myocardium ◽  
High Calcium ◽  
Low Load

Background Dantrolene is the only known effective treatment for malignant hyperthermia. However, its effects on myocardial contraction and relaxation remain debatable. Methods The effects of dantrolene (10(-5)-10(-3) M) on the contractility of rat left ventricular papillary muscles were investigated in vitro (Krebs-Henseleit solution, 29 degrees C, pH 7.40, 2.5 and 0.5 mM Ca2+, stimulation frequency 12 pulses/min). The authors studied contraction, relaxation, contraction-relaxation coupling under high and low load, energetics, and postrest potentiation. The effects of dantrolene after depletion of catecholamine stores with reserpine also were studied. Results Dantrolene induced a moderate concentration-dependent negative inotropic effect at a low calcium concentration (active force at 10(-4) M: 86 +/- 14% of control values, P < 0.05), but not at a high calcium concentration. Dantrolene did not significantly modify the curvature of the force-velocity relation, suggesting that it did not modify myocardial energetics. Dantrolene induced no significant lusitropic effect under low load, suggesting that it did not modify calcium uptake by the sarcoplasmic reticulum. Dantrolene did not significantly modify postrest potentiation and postrest potentiation recovery, suggesting that it did not modify maximum capacity of calcium release by the sarcoplasmic reticulum nor its postrest resetting capacity. Reserpine did not modify the myocardial effects of dantrolene. Conclusions In rat myocardium, dantrolene did not modify any of the sarcoplasmic reticulum functions tested (uptake, release, postrest recovery). Dantrolene induced a moderate negative inotropic effect, probably mediated by a decrease in transarcolemmal calcium entry, and this negative inotropic effect was blunted by an increase in calcium concentration.

In Vitro Effects of Eltanolone on Rat Myocardium

1995 ◽  
Vol 83 (4) ◽  
pp. 792-798. ◽  
Author(s):  
Bruno Riou ◽  
Patrick Ruel ◽  
Jean-Luc Hanouz ◽  
Olivier Langeron ◽  
Yves Lecarpentier ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Calcium Release ◽  
Isometric Force ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Induction Agent ◽  
Dependent Manner ◽  
Rat Myocardium ◽  
Shortening Velocity

Background Eltanolone is a new short-acting intravenous induction agent. However, its effects on intrinsic myocardial contractility remain unknown. Methods The effects of eltanolone and its solvent (soya bean emulsion) on the intrinsic contractility of rat left ventricular papillary muscles were investigated in vitro (Krebs-Henseleit solution, 29 degrees C, pH 7.40, Ca2+ 0.5 mM, stimulation frequency 12 pulses/min). We studied contraction; relaxation; contraction-relaxation coupling under high and low loads; and postrest potentiation. Results Eltanolone (0.1, 0.3, 1, 3, and 10 micrograms.ml-1) induced no significant inotropic effect, as shown by the lack of changes in maximum unloaded shortening velocity and active isometric force. Eltanolone did not significantly modify the contraction-relaxation coupling under low load, suggesting that it did not modify calcium uptake by the sarcoplasmic reticulum. Eltanolone did not significantly modify the contraction-relaxation coupling under high load, suggesting that it did not modify calcium myofilament sensitivity. Eltanolone decreased the postrest potentiation in a concentration-dependent manner (from 150 +/- 14% to 118 +/- 9% at 10 micrograms.ml-1, P < 0.001), suggesting a decrease in the maximum capacity of calcium release by the sarcoplasmic reticulum, whereas its solvent did not. However, eltanolone did not slow postrest potentiation recovery, as shown by the absence of significant changes in the recovery slope, tau (4.5 +/- 1.4 vs. 3.8 +/- 1.0 beats; difference not statistically significant). Conclusions Eltanolone induced no significant inotropic effect on rat myocardium. It induced a decrease in the calcium release function of the sarcoplasmic reticulum, but this effect was not sufficiently important to modify the inotropic properties.

Myocardial Effects of Halothane and Isoflurane in Hamsters with Hypertrophic Cardiomyopathy 

1997 ◽  
Vol 87 (6) ◽  
pp. 1406-1416 ◽  
Author(s):  
Benoit Vivien ◽  
Jean-Luc Hanouz ◽  
Pierre-Yves Gueugniaud ◽  
Yves Lecarpentier ◽  
Pierre Coriat ◽  
...  
Keyword(s):  
Isometric Force ◽  
Negative Inotropic Effect ◽  
Myocardial Contraction ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Inotropic Effects ◽  
Low Load ◽  
Cardiomyopathic Hamsters ◽  
Negative Inotropic Effects

Background The effects of halothane and isoflurane on myocardial contraction and relaxation in diseased myocardium are not completely understood. Methods The effects of equianesthetic concentrations of halothane and isoflurane on inotropy and lusitropy in left ventricular papillary muscles of healthy hamsters and those with genetically induced cardiomyopathy (strain BIO 14.6) were investigated in vitro (29 degrees C; pH 7.40; Ca2+ 2.5 mM; stimulation frequency, 3/min) in isotonic and isometric conditions. Results Halothane induced a negative inotropic effect that was greater in cardiomyopathic than in healthy hamsters (1.5 vol%, active isometric force (AF): 19 +/- 8% vs. 28 +/- 11% of control values; P < 0.05). Isoflurane induced a negative inotropic effect that was greater in cardiomyopathic than in healthy hamsters (2.0 vol%, AF: 64 +/- 13% vs. 75 +/- 11% of control values; P < 0.01). However, the negative inotropic effects of halothane and isoflurane were not different for cardiomyopathic or healthy hamsters when their concentrations were corrected for minimum alveolar concentration (MAC) values in each strain. Halothane induced a negative lusitropic effect under low load, which was more important in cardiomyopathic hamsters, suggesting a greater impairment in calcium uptake by the sarcoplasmic reticulum. In contrast, isoflurane induced a moderate positive lusitropic effect under low load in healthy but not in cardiomyopathic hamsters. Halothane and isoflurane induced no significant lusitropic effect under high load. Conclusions Halothane and isoflurane had greater negative inotropic effects in cardiomyopathic than in healthy hamsters. Nevertheless, no significant differences in their inotropic effects were noted when concentrations were correlated as a multiple of MAC in each strain.

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.

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.

Effects of Desflurane in Senescent Rat Myocardium

2006 ◽  
Vol 105 (5) ◽  
pp. 961-967 ◽  
Author(s):  
Sandrine Rozenberg ◽  
Sophie Besse ◽  
Julien Amour ◽  
Benoît Vivien ◽  
Benoît Tavernier ◽  
...  
Keyword(s):  
Negative Inotropic Effect ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Shortening Velocity ◽  
Adult Rats ◽  
Inotropic Effects ◽  
Beta Adrenoceptor ◽  
Low Load ◽  
Positive Effect ◽  
Negative Inotropic Effects

Background The myocardial negative inotropic effects of desflurane are less pronounced than those of other halogenated anesthetics, partly because of intramyocardial catecholamine store release. However, the effects of desflurane on aging myocardium are unknown, whereas aging is known to be associated with an attenuation of catecholamine responsiveness. Methods The effects of desflurane (1.9-9.3 vol%) were studied in left ventricular papillary muscle of adult and senescent rats (29 degrees C; 0.5 mm Ca; stimulation frequency 12 pulses/min). The inotropic effects were compared under low and high loads, using the maximum unloaded shortening velocity and maximum isometric active force, and without or with alpha- and beta-adrenoceptor blockade. Results Desflurane induced a moderate positive inotropic effect in adult rats but a negative inotropic effect in senescent rats. After alpha- and beta-adrenoceptor blockade, desflurane induced a comparable negative inotropic effect in adult and senescent rats. No lusitropic effect under low load was observed, whereas desflurane induced a slight but significant positive lusitropic effect under high load similar between the two groups of rats. This positive effect was abolished by adrenoceptor blockade. Conclusion The authors' study suggests that desflurane does not induce significant intramyocardial catecholamine release in senescent myocardium, a result that should be integrated in the well-known alteration in the catecholamine response during aging.

Effects of Desflurane in Rat Myocardium

1997 ◽  
Vol 87 (3) ◽  
pp. 599-609 ◽  
Author(s):  
Pierre-Yves Gueugniaud ◽  
Jean-Luc Hanouz ◽  
Benoit Vivien ◽  
Yves Lecarpentier ◽  
Pierre Coriat ◽  
...  
Keyword(s):  
Negative Inotropic Effect ◽  
Cardiovascular Effects ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Papillary Muscles ◽  
Shortening Velocity ◽  
Inotropic Effects ◽  
Beta Adrenoceptor ◽  
Low Load

Background The cardiovascular effects of desflurane have been investigated in several in vivo animal and human studies. To determine the possible contributions of myocardial depression, the effects of desflurane on various contractile parameters in isolated cardiac papillary muscles were compared with those of isoflurane and halothane. Methods The effects of desflurane, isoflurane, and halothane (0.5-2.5 minimum alveolar concentration [MAC]) were studied in rat left ventricular papillary muscles (29 degrees C; pH 7.40; stimulation frequency, 12 pulses/min). The inotropic effects were compared under low (isotony) and high (isometry) loads, using the maximum unloaded shortening velocity (Vmax) and maximum isometric active force (AF). The lusitropic effects were compared in isotonic and isometric conditions. Results Desflurane has no significant inotropic effect (AF at 2.5 MAC: 95 +/- 11% of control values; NS) in contrast with halothane and isoflurane (AF at 2.5 MAC: 37 +/- 14 vs. 65 +/- 10%, respectively; P < 0.05). After alpha- and beta-adrenoceptor blockade or pretreatment with reserpine, desflurane induced a negative inotropic effect (AF at 2.5 MAC: 83 +/- 11 vs. 89 +/- 8%, respectively) that was not significantly different from that of isoflurane (AF at 2.5 MAC: 80 +/- 12%). Halothane induced a negative lusitropic effect under low load, which was significantly greater than those of isoflurane and desflurane. In contrast to halothane, isoflurane and desflurane induced no significant lusitropic effect under high load and did not modify postrest potentiation. These results suggest that desflurane did not impair sarcoplasmic reticulum function. Conclusions When compared with isoflurane, desflurane induced a moderate positive inotropic effect related to intramyocardial catecholamine release. After adrenoceptor blockade, desflurane induced a negative inotropic effect comparable with that induced by isoflurane.

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.

scholarly journals Intraventricular and interventricular cellular heterogeneity of inotropic responses to α1-adrenergic stimulation

2013 ◽  
Vol 304 (7) ◽  
pp. H946-H953 ◽  
Author(s):  
Charles Chu ◽  
Kevin Thai ◽  
Ki Wan Park ◽  
Paul Wang ◽  
Om Makwana ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Negative Inotropic Effect ◽  
Left Ventricular ◽  
Cellular Heterogeneity ◽  
Inotropic Effect ◽  
Adrenergic Stimulation ◽  
Regulation Of Contraction ◽  
Inotropic Responses ◽  
Subtype Selective ◽  
Stimulation Of

α1-Adrenergic receptors (α1-ARs) elicit a negative inotropic effect (NIE) in the mouse right ventricular (RV) myocardium but a positive inotropic effect (PIE) in the left ventricular (LV) myocardium. Effects on myofilament Ca2+ sensitivity play a role, but effects on Ca2+ handling could also contribute. We monitored the effects of α1-AR stimulation on contraction and Ca2+ transients using single myocytes isolated from the RV or LV. Interestingly, for both the RV and LV, we found heterogeneous myocyte inotropic responses. α1-ARs mediated either a PIE or NIE, although RV myocytes had a greater proportion of cells manifesting a NIE (68%) compared with LV myocytes (36%). Stimulation of a single α1-AR subtype (α1A-ARs) with a subtype-selective agonist also elicited heterogeneous inotropic responses, suggesting that the heterogeneity arose from events downstream of the α1A-AR subtype. For RV and LV myocytes, an α1-AR-mediated PIE was associated with an increased Ca2+ transient and a NIE was associated with a decreased Ca2+ transient, suggesting a key role for Ca2+ handling. For RV and LV myocytes, α1-AR-mediated decreases in the Ca2+ transient were associated with increased Ca2+ export from the cell and decreased Ca2+ content of the sarcoplasmic reticulum. In contrast, for myocytes with α1-AR-induced increased Ca2+ transients, sarcoplasmic reticulum Ca2+ content was not increased, suggesting that other mechanisms contributed to the increased Ca2+ transients. This study demonstrates the marked heterogeneity of LV and RV cellular inotropic responses to stimulation of α1-ARs and reveals a new aspect of biological heterogeneity among myocytes in the regulation of contraction.

Myocardial Effects of Desflurane in Hamsters with Hypertrophic Cardiomyopathy 

1998 ◽  
Vol 89 (5) ◽  
pp. 1191-1198 ◽  
Author(s):  
Benoit Vivien ◽  
Jean-Luc Hanouz ◽  
Pierre-Yves Gueugniaud ◽  
Yves Lecarpentier ◽  
MD Pierre ◽  
...  
Keyword(s):  
Negative Inotropic Effect ◽  
Myocardial Contraction ◽  
Left Ventricular ◽  
High Load ◽  
Catecholamine Release ◽  
Inotropic Effect ◽  
Active Force ◽  
Shortening Velocity ◽  
Contraction And Relaxation

Background The effects of desflurane on myocardial contraction and relaxation in diseased myocardium have not been completely understood. Methods The effects of desflurane (1.8 to 9.4 vol%) in left ventricular papillary muscles of healthy hamsters and those with genetically induced cardiomyopathy (strain BIO 14.6) were investigated in vitro (29 degrees C, pH 7.40, Ca2+ 2.5 mM; stimulation frequency, 3/min) under low (isotony) and high (isometry) load. Data are mean percentages of baseline +/- SD. Results Desflurane induced no significant inotropic effect in healthy muscles (maximum unloaded shortening velocity and isometric active force at 9.4 vol%: 97 +/- 9% and 92 +/- 20%, respectively). In contrast, in cardiomyopathic muscles, desflurane induced a moderate negative inotropic effect (maximum unloaded shortening velocity and active force at 9.4 vol%: 84 +/- 19% and 75 +/- 25%, respectively). The negative inotropic effect was more pronounced than that in healthy muscles under low (P < 0.05) but not high load, and even when concentrations were corrected for minimum alveolar concentrations in each strain. Adrenoceptor blockade or pretreatment with reserpine did not modify the inotropic effect of desflurane, suggesting the absence of intramyocardial catecholamine release. However, tyramine also did not induce any significant catecholamine release in hamster myocardium. In both strains, desflurane induced no significant lusitropic effect under low or high load. Conclusions Desflurane had no inotropic effect in healthy muscles and a moderate negative inotropic effect in cardiomyopathic muscles. The absence of desflurane-induced intramyocardial catecholamine release was related to hamster myocardium characteristics.

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