scholarly journals Physiological response of cardiac tissue to bisphenol a: alterations in ventricular pressure and contractility

2015 ◽  
Vol 309 (2) ◽  
pp. H267-H275 ◽  
Author(s):  
Nikki Gillum Posnack ◽  
Daina Brooks ◽  
Akhil Chandra ◽  
Rafael Jaimes ◽  
Narine Sarvazyan ◽  
...  
Keyword(s):  
Bisphenol A ◽  
Sinus Rhythm ◽  
Electrical Conduction ◽  
Left Ventricular ◽  
Dependent Manner ◽  
Cardiac Contractile ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Dose Dependent ◽  
Contractile Performance

Biomonitoring studies have indicated that humans are routinely exposed to bisphenol A (BPA), a chemical that is commonly used in the production of polycarbonate plastics and epoxy resins. Epidemiological studies have shown that BPA exposure in humans is associated with cardiovascular disease; however, the direct effects of BPA on cardiac physiology are largely unknown. Previously, we have shown that BPA exposure slows atrioventricular electrical conduction, decreases epicardial conduction velocity, and prolongs action potential duration in excised rat hearts. In the present study, we tested if BPA exposure also adversely affects cardiac contractile performance. We examined the impact of BPA exposure level, sex, and pacing rate on cardiac contractile function in excised rat hearts. Hearts were retrogradely perfused at constant pressure and exposed to 10−9-10−4 M BPA. Left ventricular developed pressure and contractility were measured during sinus rhythm and during pacing (5, 6.5, and 9 Hz). Ca2+ transients were imaged from whole hearts and from neonatal rat cardiomyocyte layers. During sinus rhythm in female hearts, BPA exposure decreased left ventricular developed pressure and inotropy in a dose-dependent manner. The reduced contractile performance was exacerbated at higher pacing rates. BPA-induced effects on contractile performance were also observed in male hearts, albeit to a lesser extent. Exposure to BPA altered Ca2+ handling within whole hearts (reduced diastolic and systolic Ca2+ transient potentiation) and neonatal cardiomyocytes (reduced Ca2+ transient amplitude and prolonged Ca2+ transient release time). In conclusion, BPA exposure significantly impaired cardiac performance in a dose-dependent manner, having a major negative impact upon electrical conduction, intracellular Ca2+ handing, and ventricular contractility.

Effect of perfusate Ca2+ on the relation between metabolism and mechanical performance in the rat heart

1980 ◽  
Vol 58 (5) ◽  
pp. 570-573 ◽  
Author(s):  
T. Russell Snow ◽  
Gabor Rubanyi ◽  
Tunde Dora ◽  
Eörs Dora ◽  
Arisztid G. B. Kovach
Keyword(s):  
Respiratory Chain ◽  
Mechanical Performance ◽  
Left Ventricular ◽  
Perfused Heart ◽  
Exogenous Substrate ◽  
Rat Hearts ◽  
Nadh Fluorescence ◽  
Perfused Rat Hearts ◽  
Developed Pressure ◽  
Contractile Performance

Langendorf perfused rat hearts (n = 25) were used to study the effects of changes in perfusate Ca2+ concentration ([Ca2+p]) on the relation between metabolism and mechanical performance with either glucose or pyruvate as the exogenous substrate. Increased [Ca2+p] (from 1.3 to 3.9 mM) produced an increase (243 ± 38%) in left ventricular developed pressure regardless of the substrate. With glucose as the substrate, the NADH fluorescence intensity increased by 11.8 ± 1.2% (n = 17) relative to control indicating a more reduced state of the respiratory chain. Increasing [Ca2+p] in the pyruvate perfused heart produced the expected NADH oxidation (−6.2 ± 1.1%; n = 8). Hence the change in NADH fluorescence associated with increased [Ca2+p] is substrate dependent. The data show that, with glucose as the substrate but not with pyruvate, increases in [Ca2+p] increase the availability of reducing equivalents to the respiratory chain above the level necessary to compensate for the increased demand resulting from the greater contractile performance.

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.

scholarly journals Hemidesmus indicusandHibiscus rosa-sinensisAffect Ischemia Reperfusion Injury in Isolated Rat Hearts

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Vinoth Kumar Megraj Khandelwal ◽  
R. Balaraman ◽  
Dezider Pancza ◽  
Táňa Ravingerová
Keyword(s):  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Moderate Increase ◽  
Dependent Manner ◽  
Hemidesmus Indicus ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Developed Pressure

Hemidesmus indicus(L.) R. Br. (HI) andHibiscus rosa-sinensisL. (HRS) are widely used traditional medicine. We investigated cardioprotective effects of these plants applied for 15 min at concentrations of 90, 180, and 360 μg/mL in Langendorff-perfused rat hearts prior to 25-min global ischemia/120-min reperfusion (I/R). Functional recovery (left ventricular developed pressure—LVDP, and rate of development of pressure), reperfusion arrhythmias, and infarct size (TTC staining) served as the endpoints. A transient increase in LVDP (32%–75%) occurred at all concentrations of HI, while coronary flow (CF) was significantly increased after HI 180 and 360. Only a moderate increase in LVDP (21% and 55%) and a tendency to increase CF was observed at HRS 180 and 360. HI and HRS at 180 and 360 significantly improved postischemic recovery of LVDP. Both the drugs dose-dependently reduced the numbers of ectopic beats and duration of ventricular tachycardia. The size of infarction was significantly decreased by HI 360, while HRS significantly reduced the infarct size at all concentrations in a dose-dependent manner. Thus, it can be concluded that HI might cause vasodilation, positive inotropic effect, and cardioprotection, while HRS might cause these effects at higher concentrations. However, further study is needed to elucidate the exact mechanism of their actions.

Testosterone-augmented contractile responses to α1- and β1-adrenoceptor stimulation are associated with increased activities of RyR, SERCA, and NCX in the heart

2009 ◽  
Vol 296 (4) ◽  
pp. C766-C782 ◽  
Author(s):  
Sharon Tsang ◽  
Stanley S. C. Wong ◽  
Song Wu ◽  
Gennadi M. Kravtsov ◽  
Tak-Ming Wong
Keyword(s):  
Ventricular Myocytes ◽  
Left Ventricular ◽  
Contractile Responses ◽  
Adrenoceptor Antagonist ◽  
Cardiac Contractile ◽  
Plasmic Reticulum ◽  
Adrenoceptor Agonist ◽  
Intracellular Ca ◽  
Developed Pressure ◽  
Stimulation Of

We hypothesized that testosterone at physiological levels enhances cardiac contractile responses to stimulation of both α1- and β1-adrenoceptors by increasing Ca2+ release from the sarcoplasmic reticulum (SR) and speedier removal of Ca2+ from cytosol via Ca2+-regulatory proteins. We first determined the left ventricular developed pressure, velocity of contraction and relaxation, and heart rate in perfused hearts isolated from control rats, orchiectomized rats, and orchiectomized rats without and with testosterone replacement (200 μg/100 g body wt) in the presence of norepinephrine (10−7 M), the α1-adrenoceptor agonist phenylephrine (10−6 M), or the nonselective β-adrenoceptor agonist isoprenaline (10−7 M) in the presence of 5 × 10−7 M ICI-118,551, a β2-adrenoceptor antagonist. Next, we determined the amplitudes of intracellular Ca2+ concentration transients induced by electrical stimulation or caffeine, which represent, respectively, Ca2+ release via the ryanodine receptor (RyR) or releasable Ca2+ in the SR, in ventricular myocytes isolated from the three groups of rats. We also measured 45Ca2+ release via the RyR. We then determined the time to 50% decay of both transients, which represents, respectively, Ca2+ reuptake by sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) and removal via the sarcolemmal Na+/Ca2+ exchanger (NCX). We correlated Ca2+ removal from the cytosol with activities of SERCA and its regulator phospholamban as well as NCX. The results showed that testosterone at physiological levels enhanced positive inotropic and lusitropic responses to stimulation of α1- and β1-adrenoceptors via the androgen receptor. The increased contractility and speedier relaxation were associated with increased Ca2+ release via the RyR and faster Ca2+ removal out of the cytosol via SERCA and NCX.

Abstract 1712: The P2Y 12 Antagonist Cangrelor and the GP IIb/IIIa Blocker Abciximab Reduce Platelet-Mediated Myocardial Injury After Ischemia and Reperfusion

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Jose A Barrabes ◽  
Javier Inserte ◽  
Maribel Mirabet ◽  
Adoracion Quiroga ◽  
Victor Hernando ◽  
...  
Keyword(s):  
Myocardial Injury ◽  
Myocardial Damage ◽  
Left Ventricular ◽  
Myocardial Salvage ◽  
Ischemia And Reperfusion ◽  
Activated Platelets ◽  
Rat Hearts ◽  
Developed Pressure ◽  
Enddiastolic Pressure ◽  
Isolated Rat

Objective: Platelets activated during experimental acute myocardial infarction (AMI) contribute to myocardial injury. We aimed to investigate whether platelets from patients with AMI increase myocardial damage after transient ischemia in isolated rat hearts and the modification of this effect by the P2Y 12 receptor antagonist cangrelor and the GPIIb/IIIa receptor blocker abciximab. Methods: Platelets were obtained from 9 AMI patients (7 thrombolyzed, all on aspirin) within 24 h after symptom onset. Incubation with 100 μM cangrelor or 50 μg/ml abciximab resulted, respectively, in 78 ± 4 and 90 ± 2% inhibition of aggregation (optical aggregometry). Isolated rat hearts (four simultaneous experiments per patient) were subjected to 40 min of global ischemia and 60 min of reperfusion. Hearts received no additional intervention (Control) or were infused during the 5 min prior to ischemia with platelets (22.5x10 6 /min), either untreated or treated with cangrelor or abciximab. Results: P-selectin expression (flow cytometry) in isolated platelets before infusion was 31 ± 3% (P = NS between groups). Platelets augmented myocardial injury, as demonstrated by worse left ventricular developed pressure (LVDevP), higher left ventricular enddiastolic pressure (LVEDP) and coronary resistance, and greater LDH release and infarct size (TTC staining), and both cangrelor and abciximab greatly attenuated these effects (Table ). Conclusions: Activated platelets from patients with AMI increase myocardial injury after ischemia and reperfusion, and cangrelor and abciximab attenuate this effect. The results support the notion that very early antiplatelet treatment may increase myocardial salvage by direct effects on the microcirculation in these patients.

Correlation between myocardial contractile force and cytosolic inorganic phosphate during early ischemia

1997 ◽  
Vol 272 (3) ◽  
pp. H1333-H1341 ◽  
Author(s):  
M. X. He ◽  
S. Wang ◽  
H. F. Downey
Keyword(s):  
Inorganic Phosphate ◽  
Contractile Force ◽  
Left Ventricular ◽  
Resonance Spectroscopy ◽  
Rat Hearts ◽  
Initial Control ◽  
Myocardial Contractile Force ◽  
Myocardial Contractile ◽  
Developed Pressure

To test the role of inorganic phosphate (Pi) in downregulation of myocardial contractile force at the onset of ischemia, Pi of rat hearts was determined with 31P nuclear magnetic resonance spectroscopy. Forty cycles of brief hypoperfusion (30% of baseline flow for 33 s) were used to achieve a time resolution of 0.512 s for comparing dynamic changes in Pi and contractile force. Initial control values of left ventricular developed pressure (LVP), heart rate, and oxygen consumption were 136 +/- 11 mmHg, 236 +/- 4 beats/min, and 95 +/- 3 microl O2 x min(-1) x g(-1); these values were unchanged at the end of the experiment. During the first 10 s of hypoperfusion, Pi increased at a rate (percentage of the total observed change) faster than the decrease in LVP; Pi and LVP then changed at the same rate during the remainder of the hypoperfusion. ADP did not change in advance of LVP. Intracellular pH did not change. The results indicate that Pi plays an important role in initiating the downregulation of myocardial contractile force at the onset of ischemia. Perfusion pressure also declined faster than LVP at the onset of ischemia, indicating potential importance of vascular collapse in contractile downregulation during early ischemia.

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.

Adenosine antagonism decreases metabolic but not functional recovery from ischemia

1991 ◽  
Vol 260 (1) ◽  
pp. H193-H200 ◽  
Author(s):  
D. A. Angello ◽  
J. P. Headrick ◽  
N. M. Coddington ◽  
R. M. Berne
Keyword(s):  
Functional Recovery ◽  
Left Ventricular ◽  
Low Flow ◽  
Ischemia And Reperfusion ◽  
Constant Flow ◽  
Hemodynamic Parameters ◽  
Isolated Hearts ◽  
Rat Hearts ◽  
Adenosine Antagonism ◽  
Developed Pressure

The effect of adenosine receptor antagonism on function and metabolism was examined in isolated hearts during low flow ischemia and reperfusion. Isovolumic rat hearts perfused at constant flow were subjected to 30 min of ischemia followed by 30 min of reperfusion. Infusion of vehicle or 10 microM 8-phenyltheophylline (8-PT) was initiated 10 min before ischemia and maintained throughout reperfusion. 8-PT infusion had no significant effects on hemodynamic parameters or metabolism preischemia. During ischemia, left ventricular developed pressure declined to approximately 15% of preischemic values in control and 8-PT hearts, and ATP and PCr decreased to approximately 73 and 60% of preischemic values. Inorganic phosphate (Pi) increased to 353 = 41 and 424 +/- 53% of preischemic values in control and 8-PT hearts, respectively. After reperfusion, function recovered to greater than 95% of preischemic levels in control and 8-PT hearts. Unlike control hearts, recovery of metabolites was significantly different during reperfusion in 8-PT hearts (P less than 0.05); ATP, phosphocreatine, and Pi recovered to 82 +/- 8, 71 +/- 8, and 281 +/- 27% of preischemic values, respectively. Venous purine washout was significantly greater (P less than 0.05) during reperfusion in 8-PT hearts (327 +/- 113 nmol) than in control hearts (127 +/- 28 nmol). Blockade of adenosine receptors appears to adversely affect metabolic but not functional recovery in the ischemic-reperfused myocardium.

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.

Heat stress protects aged hypertrophied and nonhypertrophied rat hearts against ischemic damage

1997 ◽  
Vol 273 (3) ◽  
pp. H1333-H1341 ◽  
Author(s):  
R. N. Cornelussen ◽  
A. V. Garnier ◽  
M. M. Vork ◽  
P. Geurten ◽  
R. S. Reneman ◽  
...  
Keyword(s):  
Heat Stress ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Control Treatment ◽  
Sham Operation ◽  
Hsp 70 ◽  
Rat Hearts ◽  
Developed Pressure ◽  
And Control ◽  
Postischemic Recovery

To explore the effects of heat stress (HS) in aged hypertrophied and nonhypertrophied rat hearts, postischemic recovery was investigated 15 mo after aortic constriction (AoB) or sham operation (Sham). Twenty-four hours after HS (42 degrees C; 15 min) or control treatment (normothermia), global ischemia was induced for 20 min in isolated AoB hearts and for 20 or 30 min in Sham hearts. After HS, postischemic recovery after 20-min ischemia in AoB hearts and 30-min ischemia in Sham hearts, respectively, was significantly better than in corresponding controls. In AoB hearts, cardiac output (CO), left ventricular developed pressure (LVDP), and the positive maximal first derivative of left ventricular pressure (+dP/dtmax) recovered to 33 +/- 26 (means +/- SD), 87 +/- 5, and 72 +/- 12%, respectively, after HS and to 5 +/- 8, 22 +/- 39, and 17 +/- 29% of preischemic values, respectively, in controls. Postischemic arrhythmias were significantly reduced in HS hypertrophied hearts, but creatine kinase (CK) loss was not reduced. In Sham hearts subjected to 30 min ischemia, CO, LVDP, and +dP/dtmax recovered to 20 +/- 20, 75 +/- 8, and 59 +/- 15%, respectively, after HS and to 3 +/- 8, 21 +/- 32, and 16 +/- 32% of preischemic values, respectively, in controls. Duration of arrhythmias and CK loss were not reduced in the heated hearts. When Sham hearts were subjected to only 20-min ischemia, functional recovery was not different in HS and control hearts, indicating that HS pretreatment extends the ischemic interval before irreversible injury occurs in the heart. In all HS Sham hearts, the myocardial 72-kDa HS protein (HSP 70) content was significantly increased. However, in HS AoB hearts, HSP 70 levels were not significantly different from the values in the control hearts. These results indicate that HS pretreatment induces cardioprotection in aged hypertrophied and nonhypertrophied rat hearts, which, however, cannot be unequivocally related to increased HSP 70 tissue contents.

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