scholarly journals Energy expenditure by Ba2+contracture in rat ventricular slices derives from cross-bridge cycling

1999 ◽  
Vol 277 (1) ◽  
pp. H74-H79 ◽  
Author(s):  
Hisaharu Kohzuki ◽  
Hiromi Misawa ◽  
Susumu Sakata ◽  
Yoshimi Ohga ◽  
Hiroyuki Suga ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Energy Expenditure ◽  
Cyclopiazonic Acid ◽  
Left Ventricular ◽  
Basal Metabolism ◽  
Dependent Manner ◽  
Tyrode Solution ◽  
Cross Bridge ◽  
Butanedione Monoxime ◽  
Dose Dependent

To clarify the energy-expenditure mechanism during Ba2+ contracture of mechanically unloaded rat left ventricular (LV) slices, we measured myocardial O2 consumption (V˙o 2) of quiescent slices in Ca2+-free Tyrode solution andV˙o 2 during Ba2+ contracture by substituting Ca2+ with Ba2+. We then investigated the effects of cyclopiazonic acid (CPA) and 2,3-butanedione monoxime (BDM) on the Ba2+ contractureV˙o 2. The Ca2+-freeV˙o 2 corresponds to that of basal metabolism (2.32 ± 0.53 ml O2 ⋅ min−1 ⋅ 100 g LV−1). Ba2+ increased theV˙o 2 in a dose-dependent manner (from 0.3 to 3.0 mmol/l) from 110 to 150% of basal metabolic V˙o 2. Blockade of the sarcoplasmic reticulum (SR) Ca2+ pump by CPA (10 μmol/l) did not at all decrease the Ba2+-activatedV˙o 2. BDM (5 mmol/l), which specifically inhibits cross-bridge cycling, reduced the Ba2+activatedV˙o 2 almost to basal metabolic V˙o 2. These energetic results revealed that the Ba2+-activatedV˙o 2 was used for the cross-bridge cycling but not for the Ca2+ handling by the SR Ca2+ pump.

O2 consumption of mechanically unloaded contractions of mouse left ventricular myocardial slices

2004 ◽  
Vol 287 (1) ◽  
pp. H54-H62 ◽  
Author(s):  
Daisuke Yamashita ◽  
Hisaharu Kohzuki ◽  
Yutaka Kitagawa ◽  
Tamiji Nakashima ◽  
Akio Kikuta ◽  
...  
Keyword(s):  
Cyclopiazonic Acid ◽  
Left Ventricular ◽  
Dependent Manner ◽  
O2 Consumption ◽  
Tyrode Solution ◽  
Independent Manner ◽  
Contraction Coupling ◽  
Butanedione Monoxime ◽  
Dose Dependent ◽  
Normal Tyrode Solution

Left ventricular (LV) myocardial slices were isolated from murine hearts (300 μm thick) and were stimulated at 1 Hz without external load. Mean myocardial slice O2 consumption (MVo2) per minute (mMVo2) without stimulation was 0.97 ± 0.14 ml O2·min−1·100 g LV−1 and mean mMVo2 with stimulation increased to 1.80 ± 0.17 ml O2·min−1·100 g LV−1 in normal Tyrode solution. Mean ΔmVo2 (the mMVo2 with stimulation − the mMVo2 without stimulation) was 0.83 ± 0.12 ml O2·min−1·100 g LV−1. There were no differences between mean mMVo2 with and without stimulation in Ca2+-free solution. The increases in extracellular Ca2+ concentrations up to 14.4 mM did not affect the mMVo2 without stimulation but significantly increased the mMVo2 with stimulation up to 140% of control. The ΔmMVo2 significantly increased up to 190% of the control in a dose-dependent manner. In contrast, the shortening did not increase in a dose-dependent manner. Cyclopiazonic acid (CPA; 30 μM) significantly reduced the ΔmMVo2 to 0.27 ± 0.06 ml O2·min−1·100 g LV−1 (35% of control). The combination of 5 mM 2,3-butanedione monoxime (BDM) and 30 μM CPA did not further decrease ΔmMVo2. Although BDM (3–5 mM) decreased the ΔmMVo2 by 28–30% of control in a dose-independent manner, 3–5 mM BDM decreased shortening in a dose-dependent manner. Our results indicate that the ΔmMVo2 of mouse LV slices during shortening under mechanically unloaded conditions consists of energy expenditure for total Ca2+ handling during excitation-contraction coupling, basal metabolism, but no residual cross-bridge cycling.

Myocardial VO2 of mechanically unloaded contraction of rat ventricular slices measured by a new approach

1996 ◽  
Vol 270 (3) ◽  
pp. H1063-H1070 ◽  
Author(s):  
S. Yasuhara ◽  
M. Takaki ◽  
A. Kikuta ◽  
H. Ito ◽  
H. Suga
Keyword(s):  
Electrical Field Stimulation ◽  
Left Ventricular ◽  
Tyrode Solution ◽  
Electrical Field ◽  
New Approach ◽  
Contraction Coupling ◽  
Cross Bridge ◽  
Butanedione Monoxime ◽  
Normal Inhibition ◽  
Normal Tyrode Solution

We instituted a new approach of measuring mechanically unloaded myocardial oxygen consumption (VO2) by using rat left ventricular (LV) slices in an air-tight chamber filled with oxygenated Tyrode solution. Myocardial slices (300 microns in thickness) freely shortened without external load by electrical field stimulation (St). VO2 without St (n = 6) was 1.69 +/- 0.41 ml O2.min-1.100 g LV-1. VO2 with St (n = 6) increased to 2.28 +/- 0.36 ml O2.min-1.100 g LV-1. VO2 in Ca(2+)-free Tyrode solution irrespective of St was nearly equal to VO2 without St in normal Tyrode solution, indicating that all these VO2 correspond to basal metabolic VO2. The increment in VO2 by St (delta VO2) increased up to twice normal with the extracellular Ca2+ concentration up to 4 times normal. Inhibition of cross-bridge cycling by 2,3-butanedione monoxime (5 and 10 mM) did not decrease delta VO2. These results suggest that delta VO2 consists of VO2 primarily for excitation-contraction coupling but not for cross-bridge cycling.

Effect of aminophylline on the contraction threshold of rat diaphragm fibers

1991 ◽  
Vol 71 (4) ◽  
pp. 1409-1414 ◽  
Author(s):  
A. S. Losavio ◽  
B. A. Kotsias
Keyword(s):  
Membrane Potential ◽  
Sarcoplasmic Reticulum ◽  
Resting Membrane Potential ◽  
Dependent Manner ◽  
Direct Visualization ◽  
Rat Diaphragm ◽  
Current Clamp ◽  
Cyclic Monophosphate ◽  
Dose Dependent

We studied the effect of aminophylline (0.1–1 mM) on the contraction threshold (CT) of rat diaphragm fibers (25 degrees C). The CT was measured by direct visualization (x200) of the fiber under current-clamp conditions. The main findings are the following: 1) Aminophylline lowers the CT, in a dose-dependent manner, toward more negative values of the resting membrane potential (Vm). 2) Dibutyryl adenosine 3′,5′-cyclic monophosphate (2 mM) shifts the CT, although this change is smaller than in the presence of xanthine. 3) Tetracaine (1 mM), a drug that diminishes Ca release from the sarcoplasmic reticulum, reduces the shift induced by 1 mM aminophylline; this is partially overcome by increasing aminophylline concentration to 5 mM. 4) Hyperpolarization of the fibers shifts the CT to more negative Vm. We suggest that the displacement in the CT to more negative Vm plays an important role in the potentiating effect of aminophylline. This could be the result of an enhancement of Ca release from the sarcoplasmic reticulum.

Abstract 323: Dronedarone Impairs Cardiac Mitochondrial Oxidative Phosphorylation in Dose-Dependent Manner

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Larisa Emelyanova ◽  
Sirisha Gudlawar ◽  
Farhan Rizvi ◽  
Ekhson Holmuhamedov ◽  
Monika Thakur ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Complex I ◽  
Consumption Rate ◽  
Inhibitory Effect ◽  
Left Ventricular ◽  
Dependent Manner ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Complex Ii ◽  
Dose Dependent ◽  
Energetic Reserves

Introduction: Dronedarone (DR), a new antiarrhythmic drug, was recently shown to worsen heart failure (HF) and mortality in patients with atrial fibrillation and left ventricular dysfunction. However, the mechanism underlying the adverse effect is not known. Since, myocardium depends on mitochondrial oxidative phosphorylation (OXPHOS), we hypothesized that DR impairs mitochondrial function, which could further compropmise energetic reserves predisposing to worsening of HF and death in patients with HF. Methods: Mitochondria isolated from rat heart (2 month old, SD) were treated with DR (1, 5, 10, 20, 50 μM), and the effect on oxygen consumption rate (OCR) in State 3 (St 3, ADP stimulated), State 4 (St 4o, oligomycin) and following FCCP addition were determined using Seahorse XF24 Analyzer in the presence of glutamate/malate (complex I substrates) and succinate/rotenone (complex II substrate). Results: DR dose dependently reduced St 3 respiration both in the presence of complex I (Fig). In the presence of glutamate/malate, DR inhibited OCR by 16%, 20%, 25%, 39% and 100% at 1, 5, 10, 20, 50 μM, respectively, when compared to untreated control. At 20 μM, DR uncoupled mitochondria and increased St 4o respiration. DR at 50 μM was toxic with complete inhibition of OCR and loss of membrane potential. Similar results were observed when succinate/rotenone were used to assess complex II activity. Conclusion: DR has dose-dependent inhibitory effect on mitochondrial respiration, inhibiting OXPHOS at low concentration (1-10 μM), uncoupling at higher (20 μM) and toxic effect at 50 μM. Impairment of mitochondrial energetics could explain DR results reported in HF patients in clinical trials.

Nordexfenfluramine causes more severe pulmonary vasoconstriction than dexfenfluramine

2004 ◽  
Vol 286 (3) ◽  
pp. L531-L538 ◽  
Author(s):  
Zhigang Hong ◽  
Andrea Olschewski ◽  
Helen L. Reeve ◽  
Daniel P. Nelson ◽  
Fangxiao Hong ◽  
...  
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Pulmonary Arteries ◽  
Cyclopiazonic Acid ◽  
Cytosolic Calcium ◽  
Ring Contraction ◽  
Pulmonary Vasoconstriction ◽  
Reduced Ring ◽  
Dose Dependent Decrease ◽  
Trisphosphate Receptor ◽  
Dose Dependent

The anorectic agent dexfenfluramine (dex) causes the development of primary pulmonary hypertension in susceptible patients by an unknown mechanism. We compared the effects of dex with those of its major metabolite, nordexfenfluamine (nordex), in the isolated perfused rat lung and in isolated rings of resistance pulmonary arteries. Nordex caused a dose-dependent and more intense vasoconstriction, which can be inhibited by the nonspecific 5-hydroxytryptamine type 2 (5-HT2) blocker ketanserin. Similarly a rise in cytosolic calcium concentration ([Ca2+]i) in dispersed pulmonary artery smooth muscle cells (PASMCs) induced by nordex could be prevented by ketanserin. Unlike prior observations with dex, nordex did not inhibit K+ current or cause depolarization in PASMCs. Removal of Ca2+ from the tissue bath or addition of nifedipine (1 μM) reduced ring contraction to nordex by 60 ± 9 and 63 ± 4%, respectively. The addition of 2-aminoethoxydiphenyl borate (2-APB), a blocker of store-operated channels and the inositol 1,4,5-trisphosphate receptor, caused a dose-dependent decrease in the ring contraction elicited by nordex. The combination of 2-APB (10 μM) and nifedipine (1 μM) completely ablated the nordex contraction. Likewise the release of Ca2+ from the sarcoplasmic reticulum by cyclopiazonic acid markedly reduced the nordex contraction while leaving the KCl contraction unchanged. We conclude that nordex may be responsible for much of the vasoconstriction stimulated by dex, through the activation of 5-HT2 receptors and that the [Ca2+]i increase in rat PASMCs caused by dex/nordex is due to both influx of extracellular Ca2+ and release of Ca2+ from the sarcoplasmic reticulum.

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.

scholarly journals Rutin trihydrate attenuated cisplatin- induced cardiac toxicity in isolated perfused rat’s hearts

2020 ◽  
Author(s):  
Ishfaq Bukhari ◽  
Osama Yousif Mohamed ◽  
Rahmathunnisa Lateef ◽  
Sabiha Fatima ◽  
Fahim Vohra ◽  
...  
Keyword(s):  
Mechanical Performance ◽  
Left Ventricular ◽  
Dependent Manner ◽  
Protective Effects ◽  
Time Index ◽  
Pressure Time ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Dose Dependent ◽  
Isolated Perfused Rat Hearts

Abstract Background The present study aims to investigate the protective effect of rutin against cisplatin induced toxic effects on the mechanical performance of the myocardium, histopathology, and oxidative stress in isolated perfused rat hearts. Methods Cardiotoxicity of cisplatin was assessed at three dosage levels (1, 7, and 14 mg/l) in the isolated perfused rat hearts. The toxic effect of cisplarin was assessed on left ventricular pressure (LVP), heart rate (HR), dp/dt(max), dp/dt (min), perfusion pressure, pressure-time index, contractility index and duration of diastole. Measurements were carried out one minute before perfusion of cisplatin and 60 minutes after perfusion. Results Cisplatin reduced significantly (p < 0.05) in a dose-dependent manner LVP, dp/dt(max), dp/dt(min) and pressure- time index. Perfusion of rutin trihydrate (1 µM/l), 10 minutes before administration of cisplatin and throughout the experiment significantly (p < 0.05) attenuated the detrimental effects of cisplatin on cardiac parameters. Cisplatin caused degeneration and necrosis of cardiac muscle cells, while rutin reduced these changes and restored normal heart histology. Moreover, cisplatin reduced the myocardium concentration of reduced glutathione and increased the level of malondialdehyde, whereas rutin almost reversed these changes. Conclusion Cisplatin-induced dose-dependent impairment of several parameters of cardiac function and produced histopathological alterations in isolated rat hearts. These harmful effects of cisplatin were ameliorated by rutin trihydrate. These findings suggest the potential protective effects of rutin trihydrate against cisplatin-induced cardiotoxicity.

Role of Intracellular Ca2+Stores in the Inhibitory Effect of Halothane on Airway Smooth Muscle Contraction 

1998 ◽  
Vol 89 (1) ◽  
pp. 165-173 ◽  
Author(s):  
Michiaki Yamakage ◽  
Shinji Kohro ◽  
Takashi Matsuzaki ◽  
Hideaki Tsuchida ◽  
Akoyoshi Namiki
Keyword(s):  
Smooth Muscle ◽  
Sarcoplasmic Reticulum ◽  
Airway Smooth Muscle ◽  
Muscle Tension ◽  
Inhibitory Effect ◽  
Intracellular Concentration ◽  
Dependent Manner ◽  
Release Channel ◽  
Dose Dependent

Background Halothane directly inhibits contraction of airway smooth muscle, mainly by decreasing the intracellular concentration of free Ca2+ ([Ca2+]i). The role of intracellular Ca2+ stores, sarcoplasmic reticulum, is still unclear. We investigated the role of sarcoplasmic reticulum in the inhibitory effect of halothane on contraction of airway smooth muscle by measuring [Ca2+]i and intracellular concentration of inositol 1,4,5-triphosphate ([IP3]i), a second messenger for release of Ca2+ from sarcoplasmic reticulum. Methods [Ca2+]i was monitored by measuring the 500-nm light emission ratio (F340/F380) of a Ca2+ indicator fura-2 with isometric tension of canine tracheal smooth muscle strip. During Ca2+-free conditions, carbachol (10(-5) M) was introduced with pretreatment of halothane (0-3%). During Ca2+-free conditions, 20 mM caffeine, a Ca2+-induced Ca2+ release channel opener, was introduced with or without halothane. We measured [IP3]i during exposure to carbachol and halothane by radioimmunoassay technique. Results Pretreatment with halothane significantly diminished carbachol-induced increases in [Ca2+]i by 77% and muscle tension by 83% in a dose-dependent manner. Simultaneous administration of halothane significantly enhanced caffeine-induced transient increases in [Ca2+]i and muscle tension in a dose-dependent manner, by 97% and 69%, respectively. Pretreatment with halothane abolished these responses. Rapid increase in [IP3]i produced by carbachol was significantly inhibited by 32% by halothane in a dose-dependent manner. Conclusions Halothane, during Ca2+-free conditions, inhibits transient contraction of airway smooth muscle induced by muscarinic receptor stimulation, mainly by attenuating the increase in [Ca2+]i. Depletion of Ca2+ from sarcoplasmic reticulum via Ca2+-induced Ca2+ release channels also may contribute to the attenuation of the increase in [Ca2+]i by halothane.

Sodium modulates inotropic response to hyperosmolarity in isolated working rat heart

1992 ◽  
Vol 263 (4) ◽  
pp. H1154-H1160 ◽  
Author(s):  
S. A. Ben-Haim ◽  
Y. Edoute ◽  
G. Hayam ◽  
O. S. Better
Keyword(s):  
Rat Heart ◽  
Control Period ◽  
Time Derivative ◽  
Left Ventricular ◽  
Dependent Manner ◽  
Bicarbonate Buffer ◽  
Dependent Behavior ◽  
Acute Changes ◽  
Dose Dependent ◽  
Working Rat Heart

The present study was designed to examine the effects of acute changes in perfusate Na+ concentrations and osmolarities on left ventricular (LV) mechanics in the isolated working rat heart model. Specifically, we separated the effect of isosmotic perfusates with different Na+ concentrations on LV mechanics. After a control period during which the hearts were perfused in a working mode with a control solution of Krebs-Henseleit bicarbonate buffer (Na+ of 136 meq/l, Ca2+ of 2.6 mM, and osmolarity of 300 mosM), the hearts were subjected to different perfusates (Na+ of 96-156 meq/l and osmolarity of 240-380 mosM, using different mannitol concentrations) in a semirandom order. Peak LV pressure (PLVP), maximal time derivative of LV pressure (dP/dtmax), and cardiac output (CO) were recorded. Increasing Na+ concentrations from 96 to 156 meq/l, using isosmotic perfusates, decreased PLVP, dP/dtmax, and CO in a dose-dependent manner. The dose-dependent behavior was evident for tonicities of 240, 280, 320, and 360 but not for 380 mosM. Increasing Na+ concentration from 96 to 136 meq/l at constant perfusate tonicity (320 mosM) decreased dP/dtmax from 6,753 +/- 133 to 5,602 +/- 418 mmHg/s (P < 0.001). Rearranging the same results to examine the effect of perfusate tonicity with iso-Na+ concentration demonstrated that increasing perfusate osmolarity had a dose-dependent effect on PLVP, dP/dtmax, and CO. At a constant Na+ concentration of 116 meq/l, increasing perfusate osmolarity from 240 to 320 mosM increased dP/dtmax from 6,116 +/- 132 to 7,274 +/- 594 mmHg/s (P < 0.01). Further increase in perfusate tonicity to 380 mosM decreased dP/dtmax to 2,338 +/- 398 mmHg/s (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

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