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Sample records for isolated rat ventricular

  1. Calcium current in isolated neonatal rat ventricular myocytes.

    PubMed Central

    Cohen, N M; Lederer, W J

    1987-01-01

    1. Calcium currents (ICa) from neonatal rat ventricular heart muscle cells grown in primary culture were examined using the 'whole-cell' voltage-clamp technique (Hamill, Marty, Neher, Sakmann & Sigworth, 1981). Examination of ICa was limited to one calcium channel type, 'L' type (Nilius, Hess, Lansman & Tsien, 1985), by appropriate voltage protocols. 2. We measured transient and steady-state components of ICa, and could generally describe ICa in terms of the steady-state activation (d infinity) and inactivation (f infinity) parameters. 3. We observed that the reduction of ICa by the calcium channel antagonist D600 can be explained by both a shift of d infinity to more positive potentials as well as a slight reduction of ICa conductance. D600 did not significantly alter either the rate of inactivation of ICa or the voltage dependence of f infinity. 4. The calcium channel modulator BAY K8644 shifted both d infinity and f infinity to more negative potentials. Additionally, BAY K8644 increased the rate of inactivation at potentials between +5 and +55 mV. Furthermore, BAY K8644 also increased ICa conductance, a change consistent with a promotion of 'mode 2' calcium channel activity (Hess, Lansman & Tsien, 1984). 5. We conclude that, as predicted by d infinity and f infinity, there is a significant steady-state component of ICa ('window current') at plateau potentials in neonatal rat heart cells. Modulation of the steady-state and transient components of ICa by various agents can be attributed both to specific alterations in d infinity and f infinity and to more complicated alterations in the mode of calcium channel activity. PMID:2451004

  2. Isolated ventricular noncompaction.

    PubMed

    Okçün Baniş; Tekin, Abdullah; Oz, Büge; Küçükoğlu, M Serdar

    2004-04-01

    Isolated ventricular noncompaction of myocardium is a rare congenital disease due to an arrest of myocardial morphogenesis during foetal development. It is characterized by a thin compacted epicardial and an extremely thickened endocardial layer with prominent trabeculations and deep intertrabecular recesses. The persistence of myocardial noncompaction is usually an associated anomaly in patients with congenital left or right ventricular outflow tract obstruction. However, isolated noncompaction of myocardium is not associated with any factors that would explain it apart from the foetal arrest of compaction of the ventricular myocardium. The disease results in systolic and diastolic ventricular dysfunction, systemic embolism and ventricular arrhythmias. We describe a case of isolated noncompaction of the ventricular myocardium in a 20-year-old man who presented initially with ventricular tachycardia.

  3. A novel anionic conductance affects action potential duration in isolated rat ventricular myocytes.

    PubMed

    Spencer, C I; Uchida, W; Kozlowski, R Z

    2000-01-01

    Effects of extracellular anions were studied in electrophysiological experiments on freshly isolated rat ventricular myocytes. Under current-clamp, action potential duration (APD) was prolonged by reducing the extracellular Cl(-) concentration and shortened by replacement of extracellular Cl(-) with I(-). Under voltage-clamp, membrane potential steps or ramps evoked an anionic background current (I(AB)) carried by either Cl(-), Br(-), I(-) or NO(3)(-). Activation of I(AB) was Ca(2+)- and cyclic AMP-independent, and was unaffected by cell shrinkage. I(AB) was insensitive to stilbene and fenamate anion transport blockers at concentrations that inhibit Ca(2+)-, cyclic AMP- and swelling-activated Cl(-) currents in ventricular cells of other mammals. These results suggest that I(AB) may be carried by a novel class of Cl(-) channel. Correlation of anion substitution experiments on membrane current and action potentials revealed that I(AB) could play a major role in controlling rat ventricular APD. These findings have important implications for those studying cardiac Cl(-) channels as potential targets for novel antiarrythmic agents.

  4. Characterization of two distinct depolarization-activated K+ currents in isolated adult rat ventricular myocytes

    PubMed Central

    1991-01-01

    Depolarization-activated outward K+ currents in isolated adult rat ventricular myocytes were characterized using the whole-cell variation of the patch-clamp recording technique. During brief depolarizations to potentials positive to -40 mV, Ca(2+)-independent outward K+ currents in these cells rise to a transient peak, followed by a slower decay to an apparent plateau. The analyses completed here reveal that the observed outward current waveforms result from the activation of two kinetically distinct voltage-dependent K+ currents: one that activates and inactivates rapidly, and one that activates and inactivates slowly, on membrane depolarization. These currents are referred to here as Ito (transient outward) and IK (delayed rectifier), respectively, because their properties are similar (although not identical) to these K+ current types in other cells. Although the voltage dependences of Ito and IK activation are similar, Ito activates approximately 10-fold and inactivates approximately 30-fold more rapidly than IK at all test potentials. In the composite current waveforms measured during brief depolarizations, therefore, the peak current predominantly reflects Ito, whereas IK is the primary determinant of the plateau. There are also marked differences in the voltage dependences of steady-state inactivation of these two K+ currents: IK undergoes steady-state inactivation at all potentials positive to -120 mV, and is 50% inactivated at -69 mV; Ito, in contrast, is insensitive to steady-state inactivation at membrane potentials negative to -50 mV. In addition, Ito recovers from steady-state inactivation faster than IK: at -90 mV, for example, approximately 70% recovery from the inactivation produced at -20 mV is observed within 20 ms for Ito; IK recovers approximately 25-fold more slowly. The pharmacological properties of Ito and IK are also distinct: 4-aminopyridine preferentially attenuates Ito, and tetraethylammonium suppresses predominantly IK. The voltage- and

  5. Electrical properties of individual cells isolated from adult rat ventricular myocardium.

    PubMed

    Powell, T; Terrar, D A; Twist, V W

    1980-05-01

    1. Individual cells were isolated from adult rats ventricular myocardium by a collagenase digestion procedure. 2. Steady membrane potentials recorded with conventional intracellular glass micro-electrodes from cells in a modified Krebs solution containing 3 . 8 mM-KCl and 0 . 5 mM-CaCl2 were less negative than -40 mV in most cells (-25 . 3 +/- 10 . 9 mV, mean +/- S.D., 211 cells). 3. After addition of the potassium selective ionophore valinomycin (60 nM) to the bathing solution all recorded membrane potentials were more negative than -60 mV (-74 . 8 +/- 7 . 0 mV, sixty-three cells). 4. The internal concentration of potassium in the cells was determined as 120 . 8 +/- 1 . 7 mM (+/- S.E., n = 24) by flame emission spectrometry after centrifugation through silicone oil, using tritiated water and D-[1-14C] mannitol to estimate total and extracellular water in the pellet. 5. In the majority of cells in the standard solution the membrane potential recorded within a few msec of penetration was more negative than -70 mV (-78 . 4 +/- 9 . 7 mV, seventy-three cells). In sixty-six cells penetration initiated an action potential which overshot zero by 31 . 3 +/- 7 . 1 mV. This overshoot was abolished by reducing the external sodium to 0 . 1 of the normal value, and reduced or abolished by addition of tetrodotoxin (30 microM). 6. Modifications of the standard bathing solution which increased the number of cells with steady recorded membrane potentials more negative than -60 mV were: isosmotic substitution of sucrose for NaCl; replacement of NaCl and KCl by sodium isethionate and potassium methyl sulphate; addition of 5 or 10 mM-CaCl2; addition of 10 mM-MnCl2. 7. For cells in solution containing 2 . 5 or 5 . 5 mM-CaCl2, input resistances estimated from the amplitude of hyperpolarizations evoked by 200 msec current pulses were approximately 40 M omega at a resting potential close to -80 mV and became much greater as cells were depolarized. Time constants measured at the resting

  6. Melatonin, given at the time of reperfusion, prevents ventricular arrhythmias in isolated hearts from fructose-fed rats and spontaneously hypertensive rats.

    PubMed

    Diez, Emiliano Raúl; Renna, Nicolás Federico; Prado, Natalia Jorgelina; Lembo, Carina; Ponce Zumino, Amira Zulma; Vazquez-Prieto, Marcela; Miatello, Roberto Miguel

    2013-09-01

    Melatonin reduces reperfusion arrhythmias when administered before coronary occlusion, but in the clinical context of acute coronary syndromes, most of the therapies are administered at the time of reperfusion. Patients frequently have physiological modifications that can reduce the response to therapeutic interventions. This work determined whether acute melatonin administration starting at the moment of reperfusion protects against ventricular arrhythmias in Langendorff-perfused hearts isolated from fructose-fed rats (FFR), a dietary model of metabolic syndrome, and from spontaneous hypertensive rats (SHR). In both experimental models, we confirmed metabolic alterations, a reduction in myocardial total antioxidant capacity and an increase in arterial pressure and NADPH oxidase activity, and in FFR, we also found a decrease in eNOS activity. Melatonin (50 μm) initiated at reperfusion after 15-min regional ischemia reduced the incidence of ventricular fibrillation from 83% to 33% for the WKY strain, from 92% to 25% in FFR, and from 100% to 33% in SHR (P = 0.0361, P = 0.0028, P = 0.0013, respectively, by Fisher's exact test, n = 12 each). Although, ventricular tachycardia incidence was high at the beginning of reperfusion, the severity of the arrhythmias progressively declined in melatonin-treated hearts. Melatonin induced a shortening of the action potential duration at the beginning of reperfusion and in the SHR group also a faster recovery of action potential amplitude. We conclude that melatonin protects against ventricular fibrillation when administered at reperfusion, and these effects are maintained in hearts from rats exposed to major cardiovascular risk factors. These results further support the ongoing translation to clinical trials of this agent.

  7. Characterization of the hyperpolarization-activated current, I(f), in ventricular myocytes isolated from hypertensive rats.

    PubMed Central

    Cerbai, E; Barbieri, M; Mugelli, A

    1994-01-01

    1. Left ventricular myocytes isolated from the heart of young (2-month-old) and old (18- to 20-month-old) spontaneously hypertensive rats (SHRs) were studied in the whole-cell configuration. Since multicellular preparations from old SHRs show a diastolic depolarization phase, we performed experiments to test whether it was associated with the presence of a hyperpolarization-activated If-like current. 2. In control Tyrode solution, a time-dependent increasing inward current activated by hyperpolarization was recorded in myocytes from old SHRs showing a diastolic depolarization phase. A barium-insensitive, caesium-sensitive, time-dependent inward current was recorded in a minority (4 of 33) of cells from young SHRs (membrane capacitance, 160 +/- 7 pF) but in 93% (25 of 27, P < 0.01) of myocytes from old SHRs (membrane capacitance, 355 +/- 19 pF, P < 0.01). 3. The current was fully activated at -120 mV and voltage of half-maximal activation was -88.1 +/- 1.5 mV; it was blocked by extracellular CsCl (4 mM) in a voltage-dependent manner. Reducing [K+]o from 25 to 5.4 mM caused a shift of the reversal potential from -17.3 +/- 3.8 to -25.7 +/- 2.7 mV and a 60% decrease of current conductance. 4. These findings suggest that an If-like current is present in rat ventricular myocytes from old SHRs, where it might favour the occurrence of spontaneous action potentials. PMID:7707227

  8. H-89 inhibits transient outward and inward rectifier potassium currents in isolated rat ventricular myocytes

    PubMed Central

    Pearman, Charles; Kent, William; Bracken, Nicolas; Hussain, Munir

    2006-01-01

    Voltage clamp was used to investigate the effects of N-[2-p-bromo-cinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), a potent inhibitor of PKA, on transient outward K+ current (Ito) and inward rectifying K+ current (IK1) in rat cardiac muscle. Initial experiments, performed using descending voltage ramps, showed that H-89 inhibited both the outward and inward ramp currents in a concentration-dependent manner at concentrations between 5 and 60 μmol l−1. A similar degree of inhibition was observed when Ito and IK1 were recorded using square wave depolarising and hyperpolarising voltage steps, respectively. The IC50 was 35.8 μmol l−1 for Ito and 27.8 μmol l−1 for IK1 compared to 5.4 μmol l−1 for L-type Ca2+ current (ICa). The Hill coefficients for Ito, IK1 and ICa were −1.97, −1.60 and −1.21, respectively. In addition to inhibiting Ito amplitude, H-89 also accelerated the time to peak and the rate of voltage-dependent inactivation so that the time course of Ito was abbreviated. Paired-pulse protocols were performed to study the effects of H-89 on steady-state activation and inactivation as well as recovery from voltage-dependent inactivation. H-89 produced a concentration-dependent rightward shift in voltage-dependent activation but had no significant effect on steady-state inactivation. Recovery from voltage-dependent inactivation was delayed, although this was only visible at the highest concentration (60 μmol l−1) used. In experiments investigating the effects of elevated cyclic AMP, the β-adrenergic agonist isoprenaline and the phosphatase inhibitor calyculin A had no major effects on Ito or IK1. Data suggest that the effects of H-89 on K+ currents are more complex than simple inhibition of PKA-mediated phosphorylation. PMID:16799649

  9. Role of the T-type calcium channel CaV3.2 in the chronotropic action of corticosteroids in isolated rat ventricular myocytes.

    PubMed

    Maturana, Andrés; Lenglet, Sébastien; Python, Magaly; Kuroda, Shun'ichi; Rossier, Michel F

    2009-08-01

    The mineralocorticoid receptor is involved in the development of several cardiac dysfunctions, including lethal ventricular arrhythmias associated with heart failure or hyperaldosteronism, but the molecular mechanisms responsible for these effects remain to be clarified. Reexpression of low voltage-activated T-type calcium channels in ventricular myocytes together with other fetal genes during cardiac pathologies could confer automaticity to these cells and would represent a pro-arrhythmogenic condition if occurring in vivo. In the present study, we demonstrated that in isolated neonatal rat ventricular myocytes, corticosteroids selectively induced the expression of a particular isoform of T channel, Ca(V)3.2/alpha1H. This response was accompanied by an increase of the Ca(V)3.2 T-type current, identified with the patch clamp technique by its sensitivity to nickel, and a concomitant acceleration of the myocyte spontaneous contractions. Silencing Ca(V)3.2 expression markedly reduced the chronotropic response to steroids. Moreover, modulation of the frequency of cell contractions by different redox agents was independent of channel expression but involved a direct regulation of channel activity. Although oxidants increased both Ca(V)3.2 current amplitude and beating frequency, they decreased L-type channel activity. Reducing agents had the opposite effect on these parameters. In conclusion, the acceleration of ventricular myocyte spontaneous contractions induced by corticosteroids in vitro appears dependent on the expression of the Ca(V)3.2 T channel isoform and modulated by the redox potential of the cells. These results provide a molecular model that could explain the high incidence of arrhythmias observed in patients upon combination of inappropriate activation of the mineralocorticoid receptor and oxidative stress.

  10. Isolated right ventricular noncompaction in a newborn.

    PubMed

    Sert, Ahmet; Aypar, Ebru; Aslan, Eyup; Odabas, Dursun

    2013-01-01

    Noncompaction of the ventricular myocardium is a rare cardiomyopathy characterized by a pattern of prominent trabecular meshwork and deep intertrabecular recesses. The prevalence of left ventricular noncompaction is 0.01% in adults and 0.14% in pediatric patients. Although the usual site of involvement is the left ventricle, the right ventricle and septum can be affected as well. Previously, right ventricular noncompaction has been described only in a few cases of newborns with congenital heart defects and in adult patients. This report presents a newborn with isolated right ventricular noncompaction. To the authors' knowledge, this is the first newborn patient with isolated right ventricular noncompaction but no congenital heart defect involving only the right ventricle.

  11. Verapamil-sensitive fascicular ventricular tachycardia in a patient with isolated left ventricular noncompaction.

    PubMed

    Ying, Zhi-Qiang; Chen, Miao-Yan

    2014-01-01

    Isolated left ventricular noncompaction (IVNC) is a rare congenital form of cardiomyopathy. Verapamil-sensitive fascicular ventricular tachycardia is a rare arrhythmogenic condition characterized by a right bundle-branch block pattern and left-axis deviation with a relatively narrow QRS complex. We herein present the case of a patient with IVNC who presented with verapamil-sensitive fascicular ventricular tachycardia.

  12. Effects of the Selective Stretch-Activated Channel Blocker GsMtx4 on Stretch-Induced Changes in Refractoriness in Isolated Rat Hearts and on Ventricular Premature Beats and Arrhythmias after Coronary Occlusion in Swine

    PubMed Central

    Barrabés, José A.; Inserte, Javier; Agulló, Luis; Rodríguez-Sinovas, Antonio; Alburquerque-Béjar, Juan J.; Garcia-Dorado, David

    2015-01-01

    Mechanical factors may contribute to ischemic ventricular arrhythmias. GsMtx4 peptide, a selective stretch-activated channel blocker, inhibits stretch-induced atrial arrhythmias. We aimed to assess whether GsMtx4 protects against ventricular ectopy and arrhythmias following coronary occlusion in swine. First, the effects of 170-nM GsMtx4 on the changes in the effective refractory period (ERP) induced by left ventricular (LV) dilatation were assessed in 8 isolated rat hearts. Then, 44 anesthetized, open-chest pigs subjected to 50-min left anterior descending artery occlusion and 2-h reperfusion were blindly allocated to GsMtx4 (57 μg/kg iv. bolus and 3.8 μg/kg/min infusion, calculated to attain the above concentration in plasma) or saline, starting 5-min before occlusion and continuing until after reflow. In rat hearts, LV distension induced progressive reductions in ERP (35±2, 32±2, and 29±2 ms at 0, 20, and 40 mmHg of LV end-diastolic pressure, respectively, P<0.001) that were prevented by GsMTx4 (33±2, 33±2, and 32±2 ms, respectively, P=0.002 for the interaction with LV end-diastolic pressure). Pigs receiving GsMtx4 had similar number of ventricular premature beats during the ischemic period as control pigs (110±28 vs. 103±21, respectively, P=0.842). There were not significant differences among treated and untreated animals in the incidence of ventricular fibrillation (13.6 vs. 22.7%, respectively, P=0.696) or tachycardia (36.4 vs. 50.0%, P=0.361) or in the number of ventricular tachycardia episodes during the occlusion period (1.8±0.7 vs. 5.5±2.6, P=0.323). Thus, GsMtx4 administered under these conditions does not suppress ventricular ectopy following coronary occlusion in swine. Whether it might protect against malignant arrhythmias should be tested in studies powered for these outcomes. PMID:25938516

  13. Effects of the Selective Stretch-Activated Channel Blocker GsMtx4 on Stretch-Induced Changes in Refractoriness in Isolated Rat Hearts and on Ventricular Premature Beats and Arrhythmias after Coronary Occlusion in Swine.

    PubMed

    Barrabés, José A; Inserte, Javier; Agulló, Luis; Rodríguez-Sinovas, Antonio; Alburquerque-Béjar, Juan J; Garcia-Dorado, David

    2015-01-01

    Mechanical factors may contribute to ischemic ventricular arrhythmias. GsMtx4 peptide, a selective stretch-activated channel blocker, inhibits stretch-induced atrial arrhythmias. We aimed to assess whether GsMtx4 protects against ventricular ectopy and arrhythmias following coronary occlusion in swine. First, the effects of 170-nM GsMtx4 on the changes in the effective refractory period (ERP) induced by left ventricular (LV) dilatation were assessed in 8 isolated rat hearts. Then, 44 anesthetized, open-chest pigs subjected to 50-min left anterior descending artery occlusion and 2-h reperfusion were blindly allocated to GsMtx4 (57 μg/kg iv. bolus and 3.8 μg/kg/min infusion, calculated to attain the above concentration in plasma) or saline, starting 5-min before occlusion and continuing until after reflow. In rat hearts, LV distension induced progressive reductions in ERP (35±2, 32±2, and 29±2 ms at 0, 20, and 40 mmHg of LV end-diastolic pressure, respectively, P<0.001) that were prevented by GsMTx4 (33±2, 33±2, and 32±2 ms, respectively, P=0.002 for the interaction with LV end-diastolic pressure). Pigs receiving GsMtx4 had similar number of ventricular premature beats during the ischemic period as control pigs (110±28 vs. 103±21, respectively, P=0.842). There were not significant differences among treated and untreated animals in the incidence of ventricular fibrillation (13.6 vs. 22.7%, respectively, P=0.696) or tachycardia (36.4 vs. 50.0%, P=0.361) or in the number of ventricular tachycardia episodes during the occlusion period (1.8±0.7 vs. 5.5±2.6, P=0.323). Thus, GsMtx4 administered under these conditions does not suppress ventricular ectopy following coronary occlusion in swine. Whether it might protect against malignant arrhythmias should be tested in studies powered for these outcomes.

  14. [Isolated left ventricular noncompaction causing refractory heart failure].

    PubMed

    Meneguz-Moreno, Rafael Alexandre; Rodrigues da Costa Teixeira, Felipe; Rossi Neto, João Manoel; Finger, Marco Aurélio; Casadei, Carolina; Castillo, Maria Teresa; Sanchez de Almeida, Antonio Flávio

    2016-03-01

    Left ventricular noncompaction is a rare congenital anomaly characterized by excessive left ventricular trabeculation, deep intertrabecular recesses and a thin compacted layer due to the arrest of compaction of myocardial fibers during embryonic development. We report the case of a young patient with isolated left ventricular noncompaction, leading to refractory heart failure that required extracorporeal membrane oxygenation followed by emergency heart transplantation. Copyright © 2015 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

  15. Left ventricular volumetric conductance catheter for rats.

    PubMed

    Ito, H; Takaki, M; Yamaguchi, H; Tachibana, H; Suga, H

    1996-04-01

    Left ventricular (LV) volume (V) is an essential parameter for assessment of the cardiac pump function. Measurement of LVV in situ by a conductance catheter method has been widely used in dogs and humans but not yet in small experimental animals such as rats. We instituted a miniaturized six-electrode conductance catheter (3-F) for rat LVV measurement and its signal processing apparatus. We compared stroke volumes (SVs) simultaneously measured with this conductance catheter introduced into the LV through the apex and an electromagnetic flow probe placed on the ascending aorta during gradual decreases in LVV by an inferior vena caval occlusion. A high and linear correlation (r = 0.982) was obtained between these differently measured by SVs pooled from six rats. In another group of three rats, LV pressure was simultaneously measured with a 3-F catheter-tip micromanometer introduced into the LV through the apex. We obtained the slope of the end-systolic pressure-volume (P-V) relationship (Emax) by a gradual ascending aortic occlusion. After administration of propranolol, Emax obviously decreased with no change in volume intercept of the P-V relationship. The conductance volumetry proved to be useful in rats.

  16. Isolated Ventricular Noncompaction Cardiomyopathy Presenting as Recurrent Syncope

    PubMed Central

    Ladia, Vatsal; Sitwala, Puja; AlBalbissi, Kais

    2016-01-01

    Isolated ventricular noncompaction (IVNC) occurs because of interruption of trabecular morphogenesis in the myocardium leading to ventricular noncompaction. Patients present with heart failure or with systemic complications secondary to thromboembolism or arrhythmias. High index of suspicion is necessary for early diagnosis. We present a case of 48-year-old male with unexplained recurrent syncope who was eventually diagnosed with IVNC. PMID:28105050

  17. Resveratrol reduces intracellular free calcium concentration in rat ventricular myocytes.

    PubMed

    Liu, Zheng; Zhang, Li-Ping; Ma, Hui-Jie; Wang, Chuan; Li, Ming; Wang, Qing-Shan

    2005-10-25

    Resveratrol (trans-3, 4', 5-trihydroxy stilbene), a phytoalexin found in grape skins and red wine, has been reported to have a wide range of biological and pharmacological properties. It has been speculated that resveratrol may have cardioprotective activity. The objective of our study was to investigate the effects of resveratrol on intracellular calcium concentration ([Ca(2+)](i)) in rat ventricular myocytes. [Ca(2+)](i) was detected by laser scanning confocal microscopy. The results showed that resveratrol (15~60 mumol/L) reduced [Ca(2+)](i) in normal and Ca(2+)-free Tyrode's solution in a concentration-dependent manner. The effects of resveratrol on [Ca(2+)](i) in normal Tyrode's solution was partially inhibited by pretreatment with sodium orthovanadate (Na3VO4, 1.0 mmol/L, P<0.01), an inhibitor of protein tyrosine phosphatase, or L-type Ca(2+) channel agonist Bay K8644 (10 mumol/L, P<0.05), but could not be antagonized by NO synthase inhibitor L-NAME (1.0 mmol/L). Resveratrol also markedly inhibited the ryanodine-induced [Ca(2+)](i) increase in Ca(2+)-free Tyrode's solution (P<0.01). When Ca(2+) waves were produced by increasing extracellular Ca(2+) concentration from 1 to 10 mmol/L, resveratrol (60 mumol/L) could reduce the velocity and duration of propagating waves, and block the propagating waves of elevated [Ca(2+)](i). These results suggest that resveratrol may reduce the [Ca(2+)](i) in isolated rat ventricular myocytes. The inhibition of voltage-dependent Ca(2+) channel and tyrosine kinase, and alleviation of Ca(2+) release from sarcoplasmic reticulum (SR) are possibly involved in the effects of resveratrol on rat ventricular myocytes. These findings could help explain the protective activity of resveratrol against cardiovascular disease.

  18. Xanthine oxidase contributes to preconditioning's preservation of left ventricular developed pressure in isolated rat heart: developed pressure may not be an appropriate end-point for studies of preconditioning.

    PubMed

    Gelpi, Ricardo J; Morales, Celina; Cohen, Michael V; Downey, James M

    2002-01-01

    Studies of preconditioning frequently use the isolated rat heart model in which recovery of post-ischemic function is the end-point. However, function following an episode of ischemia/reperfusion represents a composite of both stunning, which is related to free radical production and is not attenuated by preconditioning, and tissue salvage, the primary effect of preconditioning. Brief ischemia/reperfusion is also known to diminish adenosine release during subsequent ischemia by a mechanism independent of preconditioning's anti-infarct effect. Reduced purine release would diminish generation of free radicals by xanthine oxidase in rat heart and thus produce less stunning. In this paradigm preserved post-ischemic function in rat heart might look similar to salvage by preconditioning, but its mechanism would be quite different and not be relevant to the xanthine oxidase-deficient human heart. This hypothesis was tested in isolated rat hearts. Control or ischemically preconditioned hearts were subjected to 30 min of global ischemia and 60 min of reperfusion, either in the presence or absence of 25 micromol/l allopurinol, an inhibitor of xanthine oxidase. In non-preconditioned hearts allopurinol increased left ventricular developed pressure after 60 min of reperfusion from 26 +/- 5 mmHg in control hearts to 47 +/- 7 mmHg, whereas developed pressure in preconditioned hearts following reperfusion was 59 +/- 5 mmHg and was unaffected by allopurinol. Developed pressure in non-preconditioned hearts treated with allopurinol was midway between that for untreated control and preconditioned hearts suggesting that at least 50% of the recovery of developed pressure in preconditioned hearts may be related to free radical-induced stunning. In xanthine oxidase-deficient rabbit hearts, return of function was not different between non-preconditioned and preconditioned hearts. Therefore, post-ischemic developed pressure in the rat is significantly affected by purine-dependent stunning

  19. Isolated Right Ventricular Infarction after Modified Cabrol Operation

    PubMed Central

    Pappy, Reji M.; Hanna, Elias B.; Peyton, Marvin D.; Saucedo, Jorge F.

    2012-01-01

    We report the case of a 27-year-old woman with a rare presentation of right ventricular failure secondary to isolated right ventricular myocardial infarction, 3 weeks after an uncommon surgical procedure, the modified Cabrol operation. Her medical history also included a Ross procedure at the age of 12 years. On the basis of her subacute presentation and a consultation with cardiac surgeons, we decided on medical management. Follow-up echocardiography at 6 months revealed that the right ventricular systolic function remained severely impaired, but the patient was asymptomatic with excellent functional capacity. We review the surgical techniques of aortic graft replacement and their respective complications. We also discuss the impact of conservative and reperfusion strategies on prognosis and long-term outcomes in the setting of right ventricular infarction. PMID:22412249

  20. Isolated right ventricular infarction after modified Cabrol operation.

    PubMed

    Pappy, Reji M; Hanna, Elias B; Peyton, Marvin D; Saucedo, Jorge F

    2012-01-01

    We report the case of a 27-year-old woman with a rare presentation of right ventricular failure secondary to isolated right ventricular myocardial infarction, 3 weeks after an uncommon surgical procedure, the modified Cabrol operation. Her medical history also included a Ross procedure at the age of 12 years. On the basis of her subacute presentation and a consultation with cardiac surgeons, we decided on medical management. Follow-up echocardiography at 6 months revealed that the right ventricular systolic function remained severely impaired, but the patient was asymptomatic with excellent functional capacity.We review the surgical techniques of aortic graft replacement and their respective complications. We also discuss the impact of conservative and reperfusion strategies on prognosis and long-term outcomes in the setting of right ventricular infarction.

  1. Hydrostatic forces limit swelling of rat ventricular myocardium.

    PubMed

    Pine, M B; Brooks, W W; Nosta, J J; Abelmann, W H

    1981-11-01

    To study ventricular cellular volume regulation when cell membranes and ion pumps cannot prevent swelling, rat ventricular sections were incubated in modified Krebs-Henseleit solutions in which 1) potassium was substituted for sodium, ion for ion; or 2) sodium chloride was reduced to decrease osmolarity to 228, 171, or 114 mosM. Ventricular water, [3H]inulin and [3H]mannitol spaces, potassium, sodium, chloride, and protein contents, and resting transmembrane potentials were measured. Increases in ventricular cellular volume were less than 30% in potassium-substituted and extremely dilute media (114 mosM), in contrast to increases of over 100% in identically treated renal cortical slices. In potassium-substituted solution, the fluid gained by ventricular cells during incubation was hypertonic with respect to the bathing medium. In dilute solution (171 and 114 mosM), ventricular, cellular, and extracellular osmolarities equilibrated only after substantial losses of cellular ions had occurred. These findings support the existence of mechanical limitations to ventricular cellular swelling, which may be caused by a unique network of interstitial collagen present in ventricular myocardium.

  2. Increased susceptibility of spontaneously hypertensive rats to ventricular tachyarrhythmias in early hypertension

    PubMed Central

    Sovari, Ali A.; Pezhouman, Arash; Iyer, Shankar; Cao, Hong; Ko, Christopher Y.; Bapat, Aneesh; Vahdani, Nooshin; Ghanim, Mostafa; Fishbein, Michael C.

    2016-01-01

    Key points Hypertension is a risk factor for sudden cardiac death caused by ventricular tachycardia and fibrillation.Whether hypertension in its early stage is associated with an increased risk of ventricular tachyarrhythmias is not known.Based on experiments performed at the cellular and whole heart levels, we show that, even early in chronic hypertension, the hypertrophied and fibrotic ventricles of spontaneously hypertensive rats aged 5 to 6 months have already developed increased stress‐induced arrhythmogenicity, and this increased susceptibility to ventricular arrhythmias is primarily a result of tissue remodelling rather than cellular electrophysiological changes.Our findings highlight the need for early hypertension treatment to minimize myocardial fibrosis, ventricular hypertrophy, and arrhythmias. Abstract Hypertension is a risk factor for sudden cardiac death caused by ventricular tachycardia and fibrillation (VT/VF). We hypothesized that, in early hypertension, the susceptibility to stress‐induced VT/VF increases. We compared the susceptibility of 5‐ to 6‐month‐old male spontaneously hypertensive rats (SHR) and age/sex‐matched normotensive rats (NR) to VT/VF during challenge with oxidative stress (H2O2; 0.15 mmol l−1). We found that only SHR hearts exhibited left ventricular fibrosis and hypertrophy. H2O2 promoted VT in all 30 SHR but none of the NR hearts. In 33% of SHR cases, focal VT degenerated to VF within 3 s. Simultaneous voltage‐calcium optical mapping of Langendorff‐perfused SHR hearts revealed that H2O2‐induced VT/VF arose spontaneously from focal activations at the base and mid left ventricular epicardium. Microelectrode recording of SHR hearts showed that VT was initiated by early afterdepolarization (EAD)‐mediated triggered activity. However, despite the increased susceptibility of SHR hearts to VT/VF, patch clamped isolated SHR ventricular myocytes developed EADs and triggered activity to the same extent as NR

  3. Cellular engineering of ventricular adult rat cardiomyocytes.

    PubMed

    Weikert, Christian; Eppenberger-Eberhardt, Monika; Eppenberger, Hans M

    2003-10-01

    Preparation of viable cultured adult cardiomyocytes (vARCs) is a prerequisite for cell-based transplantation and tissue engineering. Ectopic gene expression is important in this context. Here, we present an in vitro cell replating strategy using Accutase for cultured vARCs, allowing ectopic gene expression. Cultured vARCs from 6- to 8-week-old rats were used. Transfections with EGFP (enhanced green fluorescent protein) constructs, Mlc-3f-EGFP or alpha-actinin-EGFP were performed using adenovirus-enhanced transferrin-mediated infection (AVET). Accutase (PAA Laboratories, Linz, Austria) was used for the detachment of cultured cells. Immunohistochemical analysis, together with confocal laser microscopy was used for structural analysis of the cells. Cultured vARCs could be detached with a high yield (40 to 60%) from primary cultures using Accutase. The cultivation period plays an important role in the yield of viable cells. Resultant replated vARCs (rep-vARCs) rapidly (1-2 h) acquired a rounded up shape without degradation of their contractile apparatus, which is in contrast to the rod-shaped freshly isolated vARCs (fi-vARCs). The detached cells survived passage through a narrow syringe needle. After seeding, detached cells rapidly attached to various substrates, increased their content of the contractile apparatus, and formed cell-cell contacts within 3 days after reseeding. The detached cells survived passage through a narrow syringe needle. The high recovery of cells after replating enabled the use of the AVET system for gene delivery. AVET is free of infectious particles and does not lead to expression of viral proteins. Transfection of vARCs prior to detachment had a small effect on cell recovery and ectopically synthesized proteins were properly localized after replating. Detachment of cultured vARCs using Accutase is well compatible with ectopic gene expression and yields a viable transgenic population of vARCs that eventually may be suitable as transgenic

  4. [Acute cerebral ischemia: an unusual clinical presentation of isolated left ventricular noncompaction in an adult patient].

    PubMed

    Fiorencis, Andrea; Quadretti, Laura; Bacich, Daniela; Chiodi, Elisabetta; Mele, Donato; Fiorencis, Roberto

    2013-01-01

    Isolated left ventricular noncompaction in adults is uncommon. The most frequent clinical manifestations are heart failure due to left ventricular systolic dysfunction and supraventricular and ventricular arrhythmias, which may be sustained and associated with sudden death. Thromboembolic complications are also possible. We report the case of an adult patient with isolated left ventricular noncompaction who came to our observation because of acute cerebral ischemia, an initial presentation of the disease only rarely described.

  5. Endothelin-B Receptors and Left Ventricular Dysfunction after Regional versus Global Ischaemia-Reperfusion in Rat Hearts.

    PubMed

    Bibli, Sofia-Iris; Toli, Eleni V; Vilaeti, Agapi D; Varnavas, Varnavas C; Baltogiannis, Giannis G; Papalois, Apostolos; Kyriakides, Zenon S; Kolettis, Theofilos M

    2012-01-01

    Background. Endothelin-1 (ET-1) is implicated in left ventricular dysfunction after ischaemia-reperfusion. ETA and ETB receptors mediate diverse actions, but it is unknown whether these actions depend on ischaemia type and duration. We investigated the role of ETB receptors after four ischaemia-reperfusion protocols in isolated rat hearts. Methods. Left ventricular haemodynamic variables were measured in the Langendorff-perfused model after 40- and 20-minute regional or global ischaemia, followed by 30-minute reperfusion. Wild-type (n = 39) and ETB-deficient (n = 41) rats were compared. Infarct size was measured using fluorescent microspheres after regional ischaemia-reperfusion. Results. Left ventricular dysfunction was more prominent in ETB-deficient rats, particularly after regional ischaemia. Infarct size was smaller (P = 0.006) in wild-type (31.5 ± 4.4%) than ETB-deficient (45.0 ± 7.3%) rats after 40 minutes of regional ischaemia-reperfusion. Although the recovery of left ventricular function was poorer after 40-minute ischaemia-reperfusion, end-diastolic pressure in ETB-deficient rats was higher after 20 than after 40 minutes of regional ischaemia-reperfusion. Conclusion. ETB receptors exert cytoprotective effects in the rat heart, mainly after regional ischaemia-reperfusion. Longer periods of ischaemia suppress the recovery of left ventricular function after reperfusion, but the role of ETB receptors may be more important during the early phases.

  6. Endothelin-B Receptors and Left Ventricular Dysfunction after Regional versus Global Ischaemia-Reperfusion in Rat Hearts

    PubMed Central

    Bibli, Sofia-Iris; Toli, Eleni V.; Vilaeti, Agapi D.; Varnavas, Varnavas C.; Baltogiannis, Giannis G.; Papalois, Apostolos; Kyriakides, Zenon S.; Kolettis, Theofilos M.

    2012-01-01

    Background. Endothelin-1 (ET-1) is implicated in left ventricular dysfunction after ischaemia-reperfusion. ETA and ETB receptors mediate diverse actions, but it is unknown whether these actions depend on ischaemia type and duration. We investigated the role of ETB receptors after four ischaemia-reperfusion protocols in isolated rat hearts. Methods. Left ventricular haemodynamic variables were measured in the Langendorff-perfused model after 40- and 20-minute regional or global ischaemia, followed by 30-minute reperfusion. Wild-type (n = 39) and ETB-deficient (n = 41) rats were compared. Infarct size was measured using fluorescent microspheres after regional ischaemia-reperfusion. Results. Left ventricular dysfunction was more prominent in ETB-deficient rats, particularly after regional ischaemia. Infarct size was smaller (P = 0.006) in wild-type (31.5 ± 4.4%) than ETB-deficient (45.0 ± 7.3%) rats after 40 minutes of regional ischaemia-reperfusion. Although the recovery of left ventricular function was poorer after 40-minute ischaemia-reperfusion, end-diastolic pressure in ETB-deficient rats was higher after 20 than after 40 minutes of regional ischaemia-reperfusion. Conclusion. ETB receptors exert cytoprotective effects in the rat heart, mainly after regional ischaemia-reperfusion. Longer periods of ischaemia suppress the recovery of left ventricular function after reperfusion, but the role of ETB receptors may be more important during the early phases. PMID:22844633

  7. Acquired Fontan paradox in isolated right ventricular cardiomyopathy

    PubMed Central

    Saran, Mahim; Sivasubramonian, Sivasankaran; Abhilash, Sreevilasam P; Tharakan, Jaganmohan A

    2016-01-01

    A 44-year-old woman presented with features of congestive heart failure. Echocardiography revealed severe right ventricular dysfunction along with passive minimally pulsatile pulmonary blood flow suggesting very high systemic venous pressures. This was confirmed with cardiac catheterization in which the pressures of superior vena cava and inferior vena cava (19 mmHg) were higher than the pulmonary artery pressures (17 mmHg). Elevation of systemic venous pressures above the pulmonary venous pressures, Fontan paradox, to drive the forward flow, is a specific feature of artificially created cavopulmonary shunts. Late stage of isolated right ventricular cardiomyopathy resulted in the spontaneous evolution of Fontan circulation with a nonfunctional right ventricle in this patient. PMID:27625525

  8. Dual Endothelin Receptor Blockade Abrogates Right Ventricular Remodeling and Biventricular Fibrosis in Isolated Elevated Right Ventricular Afterload

    PubMed Central

    Nielsen, Eva Amalie; Sun, Mei; Honjo, Osami; Hjortdal, Vibeke E.; Redington, Andrew N.; Friedberg, Mark K.

    2016-01-01

    Background Pulmonary arterial hypertension is usually fatal due to right ventricular failure and is frequently associated with co-existing left ventricular dysfunction. Endothelin-1 is a powerful pro-fibrotic mediator and vasoconstrictor that is elevated in pulmonary arterial hypertension. Endothelin receptor blockers are commonly used as pulmonary vasodilators, however their effect on biventricular injury, remodeling and function, despite elevated isolated right ventricular afterload is unknown. Methods Elevated right ventricular afterload was induced by progressive pulmonary artery banding. Seven rabbits underwent pulmonary artery banding without macitentan; 13 received pulmonary artery banding + macitentan; and 5 did not undergo inflation of the pulmonary artery band (sham-operated controls). Results: Right and left ventricular collagen content was increased with pulmonary artery banding compared to sham-operated controls and ameliorated by macitentan. Right ventricular fibrosis signaling (connective tissue growth factor and endothelin-1 protein levels); extra-cellular matrix remodeling (matrix-metalloproteinases 2 and 9), apoptosis and apoptosis-related peptides (caspases 3 and 8) were increased with pulmonary artery banding compared with sham-operated controls and decreased with macitentan. Conclusion Isolated right ventricular afterload causes biventricular fibrosis, right ventricular apoptosis and extra cellular matrix remodeling, mediated by up-regulation of endothelin-1 and connective tissue growth factor signaling. These pathological changes are ameliorated by dual endothelin receptor blockade despite persistent elevated right ventricular afterload. PMID:26765263

  9. Isorhamnetin protects rat ventricular myocytes from ischemia and reperfusion injury.

    PubMed

    Zhang, Najuan; Pei, Fei; Wei, Huaying; Zhang, Tongtong; Yang, Chao; Ma, Gang; Yang, Chunlei

    2011-01-01

    Ischemia/reperfusion (I/R) has been known to cause damages to ventricular myocytes. Isorhamnetin, one member of flavonoid compounds, has cardioprotective effect, the effect that suggests a possible treatment for I/R damages. In the present investigation, we found that isorhamnetin could significantly promote the viability of neonatal rat ventricular myocytes that were exposed to ischemia/reperfusion (I/R) in vitro. Ventricular myocytes were obtained from neonatal SD rats, and then were divided randomly into three groups, namely I/R-/isor-, I/R+/isor- and I/R+/isor+ group. Before the whole experiment, the most appropriate concentration of isorhamnetin (4 μM) was determined by MTT assay. Our results showed that isorhamnetin could alleviate the damages of I/R to ventricular myocytes through inhibiting lactate dehydrogenase (LDH) activity, and repressing apoptosis. Compared with the counterpart of the I/R+/isor- group, LDH activity in the isorhamnetin-treated group weakened, halving from 24.1 ± 2.3 to 11.4 ± 1.2U/L. Additionally, flow cytometry showed the apparently increased apoptosis rate induced by I/R, the result that was further confirmed by transmission electron microscope. Administration of isorhamnetin, however, assuaged the apoptosis induced by I/R. Corresponding to the reduced apoptosis rate in the I/R+/isor+ group, western blotting assay showed increased amount of Bcl-2 and p53, decreased amount of Bax, and nuclear accumulation of NF-κB/p65.

  10. [Echocardiographic study of left ventricular geometry in spontaneously hypertensive rats].

    PubMed

    Escudero, Eduardo M; Pinilla, Oscar A; Carranza, Verónica B

    2009-01-01

    The purpose of this study was to analyze by echocardiogram left ventricular (LV) geometry in spontaneously hypertensive rats (SHR). Echocardiographic study, systolic blood pressure and heart rate were obtained in 114 male, 4-month old rats, 73 SHR and 41 Wistar (W). Left ventricular mass index (LVMI), relative wall thickness (RWT), stroke volume, and mid ventricular shortening were calculated with echocardiographic parameters. Normal LV was defined considering the mean plus 2 SD of LVMI and RWT in W. Patterns of abnormal LV geometry were: LV concentric remodeling, LVMI < 2.06 mg/g - RWT > 0.71; eccentric, left ventricular hypertrophy (LVH), LVMI > 2.06 mg/g - RWT < 0.71; and concentric LVH, LVMI > 2.06 mg/g - RWT > 0.71. Systolic blood pressure (SBP) and cardiac output (CO) were used to obtain total peripheral resistance (TPR). twelve % of SHR had normal LV geometry; 18% LV concentric remodeling; 33% concentric LVH and 37% eccentric LVH. LV concentric remodeling showed the smallest CO and highest TPR of any group. Eccentric LVH presented similar SBP as the other SHR groups and high CO with lower TPR. Our findings in SHR exhibit different patterns of LV geometry like in humans. These results strengthen the similarities between SHR and human essential hypertension.

  11. Isolated Right Ventricular Infarction Mimicking Anterior ST-Segment Elevation

    PubMed Central

    Oktay, Veysel; Coskun, Ugur; Yildiz, Ahmet; Gurmen, Tevfik

    2016-01-01

    Acute coronary syndromes in patients with presence of ST-segment elevation in the anterior precordial leads indicates left anterior descending coronary artery occlusion. However, anterior ST-segment elevation has also been described in right ventricular myocardial infarction and is thought to be due to right coronary artery (RCA) occlusion. We present a rare case of isolated RVMI presenting with anterior ST-segment elevation due to proximal occlusion of a right coronary artery that was treated by primary coronary angioplasty. Primary coronary angioplasty and stenting of this artery was performed resulting in resolution of the chest pain and ST- segment elevation. PMID:27190867

  12. Reduced mechanical efficiency in left‐ventricular trabeculae of the spontaneously hypertensive rat

    PubMed Central

    Han, June‐Chiew; Tran, Kenneth; Johnston, Callum M.; Nielsen, Poul M. F.; Barrett, Carolyn J.; Taberner, Andrew J.; Loiselle, Denis S.

    2014-01-01

    Abstract Long‐term systemic arterial hypertension, and its associated compensatory response of left‐ventricular hypertrophy, is fatal. This disease leads to cardiac failure and culminates in death. The spontaneously hypertensive rat (SHR) is an excellent animal model for studying this pathology, suffering from ventricular failure beginning at about 18 months of age. In this study, we isolated left‐ventricular trabeculae from SHR‐F hearts and contrasted their mechanoenergetic performance with those from nonfailing SHR (SHR‐NF) and normotensive Wistar rats. Our results show that, whereas the performance of the SHR‐F differed little from that of the SHR‐NF, both SHR groups performed less stress‐length work than that of Wistar trabeculae. Their lower work output arose from reduced ability to produce sufficient force and shortening. Neither their heat production nor their enthalpy output (the sum of work and heat), particularly the energy cost of Ca2+ cycling, differed from that of the Wistar controls. Consequently, mechanical efficiency (the ratio of work to change of enthalpy) of both SHR groups was lower than that of the Wistar trabeculae. Our data suggest that in hypertension‐induced left‐ventricular hypertrophy, the mechanical performance of the tissue is compromised such that myocardial efficiency is reduced. PMID:25413328

  13. Cardiac Muscle Studies with Rat Ventricular Strips

    ERIC Educational Resources Information Center

    Whitten, Bert K.; Faleschini, Richard J.

    1977-01-01

    Details undergraduate physiology laboratory experiments that demonstrate mechanical properties of cardiac muscle, using strips from the ventricle of a rat heart. Includes procedures for obtaining length-tension curves, demonstrating the role of calcium in excitation-contraction coupling, and showing effects of several cardiovascular drugs…

  14. Cardiac Muscle Studies with Rat Ventricular Strips

    ERIC Educational Resources Information Center

    Whitten, Bert K.; Faleschini, Richard J.

    1977-01-01

    Details undergraduate physiology laboratory experiments that demonstrate mechanical properties of cardiac muscle, using strips from the ventricle of a rat heart. Includes procedures for obtaining length-tension curves, demonstrating the role of calcium in excitation-contraction coupling, and showing effects of several cardiovascular drugs…

  15. Right ventricular hypertrophy causes impairment of left ventricular diastolic function in the rat.

    PubMed

    Lamberts, Regis R; Vaessen, Rob J; Westerhof, Nico; Stienen, Ger J M

    2007-01-01

    Right ventricular (RV) pressure overload causes right ventricular hypertrophy in several types of pulmonary and congenital heart diseases. The associated cardiac dysfunction has generally been attributed to alterations in RV function. However, due to global neurohormonal adaptations and mechanical ventricular interaction left ventricular (LV) function could be affected as well.Therefore,LV function, RV function and their interaction were studied in rats with monocrotaline (MCT)-induced RV hypertrophy and control rats. MCT (30 mg/kg) was used to induce pulmonary hypertension, which resulted, after 28 days, in marked RV hypertrophy (RV-weight: control 220 +/- 15,MCT 437 +/- 34mg,p < 0.05). In Langendorff-perfused hearts with balloons inserted in both the LV and the RV, the diastolic pressure-volume relations showed increased stiffness, and relaxation was prolonged in the LV and RV in the MCT group compared to controls. In the MCT group, developed pressures were increased only in the RV. An increase of LV volume increased RV diastolic pressure to a similar extent in both groups. However, an increase in RV volume did not affect LV diastolic pressure in controls, but significantly increased LV diastolic pressure in the MCT group. LV and RV developed pressure-volume relations were not affected. Calculated circumferential end-diastolic wall stresses (sigma) were larger in the MCT group (LV-sigma: 0.55 +/- 0.02, RV-sigma: 1.94 +/- 0.30 kN/m(2), both p< 0.05 to control) compared to controls (LV-sigma: 0.34 +/- 0.06,RV-sigma: 1.23 +/- 0.46 kN/m2). In the MCT group, collagen content was increased in the LV, septum and RV compared to controls. In conclusion, structural changes of the RV and LV result in depressed LV diastolic function during RV hypertrophy.

  16. l-Arginine currents in rat cardiac ventricular myocytes

    PubMed Central

    Peluffo, R Daniel

    2007-01-01

    l-Arginine (l-Arg) is a basic amino acid that plays a central role in the biosynthesis of nitric oxide, creatine, agmantine, polyamines, proline and glutamate. Most tissues, including myocardium, must import l-Arg from the circulation to ensure adequate intracellular levels of this amino acid. This study reports novel l-Arg-activated inward currents in whole-cell voltage-clamped rat ventricular cardiomyocytes. Ion-substitution experiments identified extracellular l-Arg as the charge-carrying cationic species responsible for these currents, which, thus, represent l-Arg import into cardiac myocytes. This result was independently confirmed by an increase in myocyte nitric oxide production upon extracellular application of l-Arg. The inward movement of Arg molecules was found to be passive and independent of Na2+, K2+, Ca2+ and Mg2+. The process displayed saturation and membrane potential (Vm)-dependent kinetics, with a K0.5 for l-Arg that increased from 5 mm at hyperpolarizing Vm to 20 mm at +40 mV. l-Lysine and l-ornithine but not d-Arg produced currents with characteristics similar to that activated by l-Arg indicating that the transport process is stereospecific for cationic l-amino acids. l-Arg current was fully blocked after brief incubation with 0.2 mmN-ethylmaleimide. These features suggest that the activity of the low-affinity, high-capacity CAT-2A member of the y2+ family of transporters is responsible for l-Arg currents in acutely isolated cardiomyocytes. Regardless of the mechanism, we hypothesize that a low-affinity arginine transport process in heart, by ensuring substrate availability for sustained NO production, might play a cardio-protective role during catabolic states known to increase Arg plasma levels severalfold. PMID:17303641

  17. Substrate Ablation of Ventricular Tachycardia: Late Potentials, Scar Dechanneling, Local Abnormal Ventricular Activities, Core Isolation, and Homogenization.

    PubMed

    Briceño, David F; Romero, Jorge; Gianni, Carola; Mohanty, Sanghamitra; Villablanca, Pedro A; Natale, Andrea; Di Biase, Luigi

    2017-03-01

    Ventricular arrhythmias are a frequent cause of mortality in patients with ischemic cardiomyopathy and nonischemic cardiomyopathy. Scar-related reentry represents the most common arrhythmia substrate in patients with recurrent episodes of sustained ventricular tachycardia (VT). Initial mapping of scar-related VT circuits is focused on identifying arrhythmogenic tissue. The substrate-based strategies include targeting late potentials, scar dechanneling, local abnormal ventricular activities, core isolation, and homogenization of the scar. Even though substrate-based strategies for VT ablation have shown promising outcomes for patients with structural heart disease related to ischemic cardiomyopathy, the data are scarce for patients with nonischemic substrates.

  18. Isolated Left Ventricular Apical Hypoplasia with Right Ventricular Outflow Tract Obstruction: A Rare Combination.

    PubMed

    Zhao, Yonghui; Zhang, Jiaying; Zhang, Jing

    2015-09-01

    Isolated left ventricular (LV) apical hypoplasia is a unusual and recently recognized congenital cardiac anomaly. A 19-year-old man was found to have an abnormal ECG and cardiac murmur identified during a routine health check since joining work. His ECG revealed normal sinus rhythm, right-axis deviation, poor R wave progression, and T wave abnormalities. On physical examination, a 2/6~3/6 systolic murmur was heard at the second intercostal space along the left sternal border. Subsequent echocardiography and cardiac magnetic resonance imaging confirmed the LV apical hypoplasia. Of note, we first found that LV apical hypoplasia was accompanied by RV outflow tract obstruction due to exaggerated rightward bulging of the basal-anterior septum during systole. A close follow-up was performed for the development of heart failure, pulmonary hypertension, and potentially tachyarrhythmia.

  19. Isolated right ventricular infarct presenting as ventricular fibrillation arrest and confirmed by delayed-enhancement cardiac MRI.

    PubMed

    Cavalcante, João L; Al-Mallah, Mouaz; Hudson, Michael

    2010-10-01

    Malignant ventricular arrhythmias resulting from isolated right ventricular myocardial infarction (RVMI) without left ventricular myocardial ischaemia or infarction occur rarely. We present a case of a 61 year-old male with acute onset of chest pain and ventricular fibrillation cardiac arrest requiring prompt defibrillation. Subsequent 15-lead EKG, showed ST-segment elevation in the anterior and right precordial leads without ST-segment elevation in the inferior leads. Angiography documented occlusion of a large RV marginal branch. Delayed enhancement cardiac magnetic resonance imaging (DE-CMR) with gadolinium performed two days post-infarct showed isolated RVMI. Patient remained symptom free and haemodynamically stable throughout his hospital stay. The clinical presentation of isolated RV infarct can be misleading and diagnosis difficult. EKG findings can resemble acute anterior wall myocardial infarction, while its course can be accompanied by life-threatening ventricular arrhythmias. This case uniquely combines this rare clinical sequence with DE-CMR images using gadolinium to confirm isolated RVMI. A brief review of RVMI presentation and associated EKG patterns is also discussed. Published by Elsevier B.V.

  20. The superoxide dismutase mimetic, tempol, blunts right ventricular hypertrophy in chronic hypoxic rats

    PubMed Central

    Elmedal, Britt; de Dam, Mette Y; Mulvany, Michael John; Simonsen, Ulf

    2003-01-01

    The purpose of this study was to investigate whether a membrane-permeable superoxide dismutase mimetic, tempol, added either alone or in combination with the nitric oxide (NO) donor molsidomine, prevents the development of pulmonary hypertension (PH) in chronic hypoxic rats.Chronic hypobaric hypoxia (10% oxygen) for 2 weeks increased the right ventricular systolic pressure (RVSP), right ventricle and lung wet weight. Relaxations evoked by acetylcholine (ACh) and the molsidomine metabolite SIN-1 were impaired in isolated proximal, but not distal pulmonary arteries, from chronic hypoxic rats.Treatment with tempol (86 mg kg−1 day−1 in drinking water) normalized RVSP and reduced right ventricular hypertrophy, while systemic blood pressure, lung and liver weights, and blunted ACh relaxation of pulmonary arteries were unchanged.Treatment with molsidomine (15 mg kg−1 day−1 in drinking water) had the same effects as tempol, except that liver weight was reduced, and potassium and U46619-evoked vasoconstrictions in pulmonary arteries were increased. Combining tempol and molsidomine did not have additional effects compared to tempol alone. ACh relaxation in pulmonary arteries was not normalized by these treatments.The media to lumen diameter ratio of the pulmonary arteries was greater for the hypoxic rats compared to the normoxic rats, and was not reversed by treatment with tempol, molsidomine, or the combination of tempol and molsidomine.We conclude that tempol, like molsidomine, is able to correct RVSP and reduce right ventricular weight in the rat hypoxic model. Functional and structural properties of pulmonary small arteries were little affected. The results support the possibility that superoxide dismutase mimetics may be a useful means for the treatment of PH. PMID:14656807

  1. Albumin resuscitation improves ventricular contractility and myocardial tissue oxygenation in rat endotoxemia.

    PubMed

    Tokunaga, Chiho; Bateman, Ryon M; Boyd, John; Wang, Yingjin; Russell, James A; Walley, Keith R

    2007-05-01

    Fluid resuscitation to improve delivery of oxygen to vital organs is a principal clinical intervention for septic patients. We previously reported that albumin resuscitation in rat endotoxemia improved contractility in isolated cardiomyocytes, but whether this effect occurs in vivo is unknown. We hypothesized that albumin resuscitation would improve decreased ventricular contractility and myocardial tissue oxygenation in vivo. Randomized, controlled, prospective animal study. University animal laboratory. Male Sprague-Dawley rats (250-350 g). Rats were randomized into three groups: control with no lipopolysaccharide (n = 8), lipopolysaccharide (10 mg/kg) without albumin resuscitation (n = 8), and lipopolysaccharide with albumin resuscitation (n = 6). Five hours after lipopolysaccharide injection, animals were resuscitated with 10 mL/kg 5% rat albumin in 0.9% saline. Six hours after 10 mL/kg lipopolysaccharide, a pressure-volume conductance catheter (MIKRO-Tip 2.0-Fr, Millar Instruments, Houston, TX) was inserted into the left ventricle to quantify maximum elastance as an index of contractility. Myocardial tissue Po2 was measured using a fiberoptic oxygen probe. Maximum elastance decreased after lipopolysaccharide relative to control (47%, from 5.9 +/- 0.8 to 3.1 +/- 0.4 mm Hg/microL, p < .05). Albumin resuscitation prevented the lipopolysaccharide-induced decrease in maximum elastance (7.0 +/- 1.2 mm Hg/microL, p < .05 vs. lipopolysaccharide). Myocardial tissue Po2 was reduced in endotoxemia compared with control (53%, from 10.1 +/- 0.9 to 4.7 +/- 0.6 mm Hg, p < .05), and albumin resuscitation improved the lipopolysaccharide-induced tissue hypoxia toward the control value (9.0 +/- 1.4 mm Hg, p < .05). Albumin resuscitation improved decreased ventricular contractility and myocardial oxygenation in endotoxemic rats. This result suggests that albumin resuscitation may improve ventricular dysfunction by improving myocardial hypoxia.

  2. Isolation of rat adrenocortical mitochondria

    SciTech Connect

    Solinas, Paola; Fujioka, Hisashi; Tandler, Bernard; Hoppel, Charles L.

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer A method for isolation of adrenocortical mitochondria from the adrenal gland of rats is described. Black-Right-Pointing-Pointer The purified isolated mitochondria show excellent morphological integrity. Black-Right-Pointing-Pointer The properties of oxidative phosphorylation are excellent. Black-Right-Pointing-Pointer The method increases the opportunity of direct analysis of adrenal mitochondria from small animals. -- Abstract: This report describes a relatively simple and reliable method for isolating adrenocortical mitochondria from rats in good, reasonably pure yield. These organelles, which heretofore have been unobtainable in isolated form from small laboratory animals, are now readily accessible. A high degree of mitochondrial purity is shown by the electron micrographs, as well as the structural integrity of each mitochondrion. That these organelles have retained their functional integrity is shown by their high respiratory control ratios. In general, the biochemical performance of these adrenal cortical mitochondria closely mirrors that of typical hepatic or cardiac mitochondria.

  3. Effect of resveratrol on L-type calcium current in rat ventricular myocytes.

    PubMed

    Zhang, Li-ping; Yin, Jing-xiang; Liu, Zheng; Zhang, Yi; Wang, Qing-shan; Zhao, Juan

    2006-02-01

    To study the effect of resveratrol on L-type calcium current (I(Ca-L)) in isolated rat ventricular myocytes and the mechanisms underlying these effects. I(Ca-L) was examined in isolated single rat ventricular myocytes by using the whole cell patch-clamp recording technique. Resveratrol (10-40 micromol/L) reduced the peak amplitude of I(Ca-L) and shifted the current-voltage (I-V) curve upwards in a concentration-dependent manner. Resveratrol (10, 20, 40 micromol/L) decreased the peak amplitude of I(Ca-L) from -14.2+/-1.5 pA/pF to -10.5+/-1.5 pA/pF (P<0.05), -7.5+/-2.4 pA/pF (P<0.01), and -5.2+/-1.2 pA/pF (P<0.01), respectively. Resveratrol (40 micromol/L) shifted the steady-state activation curve of I(Ca-L) to the right and changed the half-activation potential (V0.5) from -19.4+/-0.4 mV to -15.4+/-1.9 mV (P<0.05). Resveratrol at a concentration of 40 micromol/L did not affect the steady-state inactivation curve of I(Ca-L), but did markedly shift the time-dependent recovery curve of I(Ca-L) to the right, and slow down the recovery of I(Ca-L) from inactivation. Sodium orthovanadate (Na(3)VO(4); 1 mmol/L), a potent inhibitor of tyrosine phosphatase, significantly inhibited the effects of resveratrol (P<0.01). Resveratrol inhibited I(Ca-L) mainly by inhibiting the activation of L-type calcium channels and slowing down the recovery of L-type calcium channels from inactivation. This inhibitory effect of resveratrol was mediated by the inhibition of protein tyrosine kinase in rat ventricular myocytes.

  4. Modeling CICR in rat ventricular myocytes: voltage clamp studies

    PubMed Central

    2010-01-01

    Background The past thirty-five years have seen an intense search for the molecular mechanisms underlying calcium-induced calcium-release (CICR) in cardiac myocytes, with voltage clamp (VC) studies being the leading tool employed. Several VC protocols including lowering of extracellular calcium to affect Ca2+ loading of the sarcoplasmic reticulum (SR), and administration of blockers caffeine and thapsigargin have been utilized to probe the phenomena surrounding SR Ca2+ release. Here, we develop a deterministic mathematical model of a rat ventricular myocyte under VC conditions, to better understand mechanisms underlying the response of an isolated cell to calcium perturbation. Motivation for the study was to pinpoint key control variables influencing CICR and examine the role of CICR in the context of a physiological control system regulating cytosolic Ca2+ concentration ([Ca2+]myo). Methods The cell model consists of an electrical-equivalent model for the cell membrane and a fluid-compartment model describing the flux of ionic species between the extracellular and several intracellular compartments (cell cytosol, SR and the dyadic coupling unit (DCU), in which resides the mechanistic basis of CICR). The DCU is described as a controller-actuator mechanism, internally stabilized by negative feedback control of the unit's two diametrically-opposed Ca2+ channels (trigger-channel and release-channel). It releases Ca2+ flux into the cyto-plasm and is in turn enclosed within a negative feedback loop involving the SERCA pump, regulating[Ca2+]myo. Results Our model reproduces measured VC data published by several laboratories, and generates graded Ca2+ release at high Ca2+ gain in a homeostatically-controlled environment where [Ca2+]myo is precisely regulated. We elucidate the importance of the DCU elements in this process, particularly the role of the ryanodine receptor in controlling SR Ca2+ release, its activation by trigger Ca2+, and its refractory characteristics

  5. Soybean oil increases SERCA2a expression and left ventricular contractility in rats without change in arterial blood pressure

    PubMed Central

    2010-01-01

    Background Our aim was to evaluate the effects of soybean oil treatment for 15 days on arterial and ventricular pressure, myocardial mechanics and proteins involved in calcium handling. Methods Wistar rats were divided in two groups receiving 100 μL of soybean oil (SB) or saline (CT) i.m. for 15 days. Ventricular performance was analyzed in male 12-weeks old Wistar rats by measuring left ventricle diastolic and systolic pressure in isolated perfused hearts according to the Langendorff technique. Protein expression was measured by Western blot analysis. Results Systolic and diastolic arterial pressures did not differ between CT and SB rats. However, heart rate was reduced in the SB group. In the perfused hearts, left ventricular isovolumetric systolic pressure was higher in the SB hearts. The inotropic response to extracellular Ca2+ and isoproterenol was higher in the soybean-treated animals than in the control group. Myosin ATPase and Na+-K+ATPase activities, the expression of sarcoplasmic reticulum calcium pump (SERCA2a) and sodium calcium exchanger (NCX) were increased in the SB group. Although the phosfolamban (PLB) expression did not change, its phosphorylation at Ser16 was reduced while the SERCA2a/PLB ratio was increased. Conclusions In summary, soybean treatment for 15 days in rats increases the left ventricular performance without affecting arterial blood pressure. These changes might be associated with an increase in the myosin ATPase activity and SERCA2a expression. PMID:20504316

  6. Anesthetic experience of patient with isolated left ventricular noncompaction: a case report

    PubMed Central

    Kim, Doyeon; Kim, Eunhee; Lee, Jong-Hwan; Lee, Sangmin Maria; Lee, Jung Eun

    2016-01-01

    Isolated left ventricular noncompaction (LVNC) is a rare primary genetic cardiomyopathy characterized by prominent trabeculation of the left ventricular wall and intertrabecular recesses. Perioperative management of the patient with LVNC might be challenging due to the clinical symptoms of heart failure, systemic thromboembolic events, and fatal left ventricular arrhythmias. We conducted real time intraoperative transesophageal echocardiography in a patient with LVNC undergoing general anesthesia for ovarian cystectomy. PMID:27274374

  7. Characterization of nifedipine-resistant calcium current in neonatal rat ventricular cardiomyocytes.

    PubMed

    Pignier, C; Potreau, D

    2000-11-01

    Calcium current was recorded from ventricular cardiomyocytes of rats at various stages of postnatal development using the whole cell patch-clamp technique. In cultured 3-day-old neonatal cells, the current carried by Ca(2+) or Ba(2+) (5 mM) was not completely inhibited by 2 microM nifedipine. A residual current was activated in the same voltage range as the L-type, nifedipine-sensitive Ca(2+) current, but its steady-state inactivation was negatively shifted by 16 mV. This nifedipine-resistant calcium current was not further inhibited by other organic calcium current antagonists such as PN200-110, verapamil, and diltiazem nor by nickel, omega-conotoxin, or tetrodotoxin. It was completely blocked by cadmium and increased by isoproterenol and forskolin. This current was >20% of total calcium current in ventricular myocytes freshly isolated from neonatal rats, and it decreased during postnatal maturation, disappearing at the adult stage. This suggests that this current could be caused by an isoform of the L-type calcium channel expressed in a way that reflects the developmental stage of the rat heart.

  8. Modulation of ventricular fibrillation in isolated perfused heart by dofetilide.

    PubMed

    Amitzur, Giora; Shenkar, Nitza; Leor, Jonathan; Novikov, Ilia; Eldar, Michael

    2003-06-01

    The authors studied the involvement of IKr potassium current in ventricular fibrillation during perfusion. Electrophysiologic parameters were measured before and after dofetilide administration (2.5, 7.5, and 12.5 x 10-7 M, n = 8) in isolated perfused feline hearts. During pacing, these parameters included epicardial conduction time, refractoriness, and the fastest rate for 1:1 pacing/response capture. During 8 minutes of electrically induced tachyarrhythmias, they included heart rate and normalized entropy reflecting the degree of organization. In all groups, arrhythmia rate was slower in the right ventricle than in the left ventricle. Dofetilide decreased the arrhythmia rate more than it increased organization, reduced its maintenance, or increased difficulty in initiation. Refractoriness was prolonged in a reverse use-dependent way which was less than 1:1 pacing/response capture. Unexpectedly, a moderate prolongation of conduction time was observed. Inverse correlation was found between the arrhythmia rate and changes in refractoriness and conduction time and between the degree of organization and refractoriness (both ventricles) and conduction time (right ventricle). Dofetilide, which intensively blocks IKr current and unexpectedly suppressed conduction, has different quantitative effects on fibrillation features. These changes in fibrillation suggest that these effects are mainly associated with refractoriness prolongation and do not seem to be attenuated by conduction suppression.

  9. Ventricular arrhythmia incidence in the rat is reduced by naloxone.

    PubMed

    Pugsley, M K; Hayes, E S; Wang, W Q; Walker, M J A

    2015-07-01

    This study characterized the antiarrhythmic effects of the opioid receptor antagonist naloxone in rats subject to electrically induced and ischemic arrhythmias. Naloxone (2, 8 and 32 μmol/kg/min) was examined on heart rate, blood pressure, and the electrocardiogram (EKG) as well as for effectiveness against arrhythmias produced by occlusion of the left anterior descending coronary artery or electrical stimulation of the left ventricle. Naloxone reduced blood pressure at the highest dose tested while heart rate was dose-dependently reduced. Naloxone dose-dependently prolonged the P-R and QRS intervals and increased the RSh amplitude indicative of effects on cardiac sodium (Na) channels. Naloxone prolonged the Q-T interval suggesting a delay in repolarization. Naloxone effects were comparable to the comparator quinidine. Naloxone (32 μmol/kg/min) reduced ventricular fibrillation (VF) incidence to 38% (from 100% in controls). This same dose significantly increased the threshold for induction of ventricular fibrillation (VFt), prolonged the effective refractory period (ERP) and reduced the maximal following frequency (MFF). The patterns of ECG changes, reduction in ischemic arrhythmia (VF) incidence and changes in electrically induced arrhythmia parameters at high doses of naloxone suggest that it directly blocks cardiac Na and potassium (K) ion channels.

  10. Isolated left ventricular noncompaction diagnosed by transthoracic threedimensional echocardiography.

    PubMed

    Wang, X X; Song, Z Z

    2009-05-01

    A 55-year-old man was admitted to our hospital because of chest distress, associated with activity. Two-dimensional echocardiography (2DE) demonstrated a suspected trabeculation versus false tendon of the left ventricular apex cordis but not meeting the diagnostic criteria of noncompaction of the ventricular myocardium (NVM). Threedimensional echocardiography (3DE) revealed more prominent trabeculations and deeper intertrabecular recesses of the left ventricular apex, which were consistent with the diagnostic criteria of NVM. In contrast to 2DE, 3DE provides wide, pyramid-shaped datasets that encompass the entire left ventricle. (Neth Heart J 2009;17:208-10.).

  11. Intracellular calibration of the fluorescent Mg2+ indicator furaptra in rat ventricular myocytes.

    PubMed

    Watanabe, M; Konishi, M

    2001-04-01

    Single ventricular myocytes enzymatically isolated from rat hearts were loaded with the Mg2+ indicator furaptra, and the relationship between the fluorescence ratio signal (R) and the intracellular free concentration of Mg2+ ([Mg2+]i) was studied in situ at 25 degrees C. After the application of ionophores (ionomycin, monensin, nigericin and valinomycin), an immediate change in furaptra R was noted, followed by a slow change in R that reached a steady level in 2-4 h. The direction of the early change in R that accompanied rigor contraction was independent of the extracellular Mg2+ concentration ([Mg2+]o), and was consistent with the breakdown of ATP and release of bound Mg2+. The intracellular calibration curve was constructed from the steady levels of R obtained at various [Mg2+]o between 0 and 47 mM. The dissociation constant of intracellular furaptra was estimated to be 5.3 mM, which was 44% higher than that determined in salt solutions (3.7 mM). The basal [Mg2+]i of rat ventricular myocytes calculated with the intracellular curve averaged 0.91 mM.

  12. Current-Voltage Relationship for Late Na(+) Current in Adult Rat Ventricular Myocytes.

    PubMed

    Clark, R B; Giles, W R

    2016-01-01

    It is now well established that the slowly inactivating component of the Na(+) current (INa-L) in the mammalian heart is a significant regulator of the action potential waveform. This insight has led to detailed studies of the role of INa-L in a number of important and challenging pathophysiological settings. These include genetically based ventricular arrhythmias (LQT 1, 2, and 3), ventricular arrhythmias arising from progressive cardiomyopathies (including diabetic), and proarrhythmic abnormalities that develop during local or global ventricular ischemia. Inhibition of INa-L may also be a useful strategy for management of atrial flutter and fibrillation. Many important biophysical parameters that characterize INa-L have been identified; and INa-L as an antiarrhythmia drug target has been studied extensively. However, relatively little information is available regarding (1) the ion transfer or current-voltage relationship for INa-L or (2) the time course of its reactivation at membrane potentials similar to the resting or diastolic membrane potential in mammalian ventricle. This chapter is based on our preliminary findings concerning these two very important physiological/biophysical descriptors for INa-L. Our results were obtained using whole-cell voltage clamp methods applied to enzymatically isolated rat ventricular myocytes. A chemical agent, BDF 9148, which was once considered to be a drug candidate in the Na(+)-dependent inotropic agent category has been used to markedly enhance INa-L current. BDF acts in a potent, selective, and reversible fashion. These BDF 9148 effects are compared and contrasted with the prototypical activator of INa-L, a sea anemone toxin, ATX II.

  13. Regulatory Effect of Connexin 43 on Basal Ca2+ Signaling in Rat Ventricular Myocytes

    PubMed Central

    Li, Chen; Yu, Xinfeng; Jing, Xian; Xu, Pingxiang; Luo, Dali

    2012-01-01

    Background It has been found that gap junction-associated intracellular Ca2+ [Ca2+]i disturbance contributes to the arrhythmogenesis and hyperconstriction in diseased heart. However, whether functional gaps are also involved in the regulation of normal Ca2+ signaling, in particular the basal [Ca2+]i activities, is unclear. Methods and Results Global and local Ca2+ signaling and gap permeability were monitored in cultured neonatal rat ventricular myocytes (NRVMs) and freshly isolated mouse ventricular myocytes by Fluo4/AM and Lucifer yellow (LY), respectively. The results showed that inhibition of gap communication by heptanol, Gap 27 and flufenamic acid or interference of connexin 43 (Cx43) with siRNA led to a significant suppression of LY uptake and, importantly, attenuations of global Ca2+ transients and local Ca2+ sparks in monolayer NRVMs and Ca2+ sparks in adult ventricular myocytes. In contrast, overexpression of rat-Cx43 in NRVMs induced enhancements in the above measurements, and so did in HEK293 cells expressing rat Cx43. Additionally, membrane-permeable inositol 1,4,5-trisphosphate (IP3 butyryloxymethyl ester) and phenylephrine, an agonist of adrenergic receptor, could relieve the inhibited Ca2+ signal and LY uptake by gap uncouplers, whereas blockade of IP3 receptor with xestospongin C or 2-aminoethoxydiphenylborate mimicked the effects of gap inhibitors. More importantly, all these gap-associated effects on Ca2+ signaling were also found in single NRVMs that only have hemichannels instead of gap junctions. Further immunostaining/immunoblotting single myocytes with antibody against Cx43 demonstrated apparent increases in membrane labeling of Cx43 and non-junctional Cx43 in overexpressed cells, suggesting functional hemichannels exist and also contribute to the Ca2+ signaling regulation in cardiomyocytes. Conclusions These data demonstrate that Cx43-associated gap coupling plays a role in the regulation of resting Ca2+ signaling in normal ventricular

  14. Aspirate from human stented saphenous vein grafts induces epicardial coronary vasoconstriction and impairs perfusion and left ventricular function in rat bioassay hearts with pharmacologically induced endothelial dysfunction.

    PubMed

    Lieder, Helmut R; Baars, Theodor; Kahlert, Philipp; Kleinbongard, Petra

    2016-08-01

    Stent implantation into aortocoronary saphenous vein grafts (SVG) releases particulate debris and soluble vasoactive mediators, for example, serotonin. We now analyzed effects of the soluble mediators released into the coronary arterial blood during stent implantation on vasomotion of isolated rat epicardial coronary artery segments and on coronary flow and left ventricular developed pressure in isolated perfused rat hearts. Coronary blood was retrieved during percutaneous SVG intervention using a distal occlusion/aspiration protection device in nine symptomatic patients with stable angina pectoris and a flow-limiting SVG stenosis. The blood was separated into particulate debris and plasma. Responses to coronary plasma were determined in isolated rat epicardial coronary arteries and in isolated, constant pressure-perfused rat hearts (±nitric oxide synthase [NOS] inhibition and ±serotonin receptor blockade, respectively). Coronary aspirate plasma taken after stent implantation induced a stronger vasoconstriction of rat epicardial coronary arteries (52 ± 8% of maximal potassium chloride induced vasoconstriction [% KClmax = 100%]) than plasma taken before stent implantation (12 ± 8% of KClmax); NOS inhibition augmented this vasoconstrictor response (to 110 ± 15% and 24 ± 9% of KClmax). Coronary aspirate plasma taken after stent implantation reduced in isolated perfused rat hearts only under NOS inhibition coronary flow by 17 ± 3% and left ventricular developed pressure by 25 ± 4%. Blockade of serotonin receptors abrogated these effects. Coronary aspirate plasma taken after stent implantation induces vasoconstriction in isolated rat epicardial coronary arteries and reduces coronary flow and left ventricular developed pressure in isolated perfused rat hearts with pharmacologically induced endothelial dysfunction. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The

  15. Rutaecarpine attenuates hypoxia-induced right ventricular remodeling in rats.

    PubMed

    Li, Wen-Qun; Li, Xiao-Hui; Du, Jie; Zhang, Wang; Li, Dai; Xiong, Xiao-Ming; Li, Yuan-Jian

    2016-07-01

    Rutaecarpine has been shown to exhibit wide pharmacological effects in the cardiovascular system via stimulation of calcitonin gene-related peptide (CGRP) release. In the present study, the effect of rutaecarpine on hypoxia-induced right ventricular (RV) remodeling and the underlying mechanisms were evaluated. RV remodeling was induced by hypoxia (10 % O2, 3 weeks) in rats. Rats were treated with rutaecarpine (20 or 40 mg/kg) by intragastric administration. Proliferation of cardiac fibroblasts was induced by TGF-β1 (5 ng/mL) and determined by MTS and EdU incorporation method. Cardiac fibroblasts were treated with exogenous CGRP (10 or 100 nM). The concentrations of CGRP and TGF-β1 in plasma were measured by ELISA. The expression of eIF3a, p27, α-SMA, collagen-I/III, ANP, and BNP were measured by real-time PCR or western blot. Hypoxia induced an increase of right ventricle systolic pressure (RVSP), ration of RV/LV+S, and RV/tibial length in rats, while cardiac hypertrophy, apoptosis, and fibrosis were detected. The expression of ANP, BNP, α-SMA, collagen-I, collagen-III, eIF3a, and TGF-β1 was up-regulated, and the expression of p27 was down-regulated in the right ventricle of hypoxia-treated rats. The plasma concentration of CGRP was decreased and TGF-β1 was increased in hypoxia-treated rats. All of these effects induced by hypoxia were attenuated by rutaecarpine in a dose-dependent manner. In cultured cardiac fibroblasts, TGF-β1 significantly promoted the proliferation and up-regulated the expression of α-SMA and collagen-I/III, while the expression of eIF3a was up-regulated and the expression of p27 was down-regulated. The effects of TGF-β1 were attenuated by CGRP. CGRP8-37, a selective CGRP receptor antagonist, abolished the effects of CGRP. Rutaecarpine attenuates hypoxia-induced RV remodeling via stimulation of CGRP release, and the effects of rutaecarpine involve the eIF3a/p27 pathway.

  16. Isolated right ventricular cardiomyopathy with autoimmune hypothyroidism: a rare association in an adolescent

    PubMed Central

    Yelve, Kavita; Panandikar, Gajanan Ashok; Pazare, Amar; Bajpai, Smrati

    2015-01-01

    A 13-year-old girl presented with progressive dyspnoea and palpitation, diagnosed on echocardiography as primary right ventricular cardiomyopathy with atrial fibrillation. Her thyroid profile was positive for antithyroid microsomal antibody, and antithyroid peroxidase antibodies were suggestive of autoimmune hypothyroidism. She was managed with furosemide, digoxin, acenocoumarol and thyroxine following which she showed significant improvement. This is a rare case of isolated right ventricular cardiomyopathy and its association with autoimmune hypothyroidism presenting at the age of 13. PMID:25795745

  17. [Effects of neuroendocrine obesity induction on systemic hemodynamics and left ventricular function of normotensive rats].

    PubMed

    Voltera, Alina F; Cesaretti, Mário L R; Ginoza, Milton; Kohlmann, Osvaldo

    2008-02-01

    The aim of this study was to evaluate the effects of obesity induced by neonatal Monosodium Glutamate (MSG) administration upon body weight, tail blood pressure, systemic hemodynamics and left ventricular function of Wistar rats. Two groups of Wistar rats were prepared: a) 18 animals made obese through the administration of 2 mg/Kg/SC of MSG during the first 11 days of the neonatal period and b)16 control animals (vehicle treated for the same period). Adults animals were followed from the 3rd up the 6th month of life with blood pressure and body weight being measured twice a week. At the end of this period, in part of animals from both groups, we evaluated the left ventricular function through the Langendorff isolated heart preparation whereas the remainders were used to evaluate the systemic hemodynamics through a termodilution method. MSG animals showed significant increases in heart rate (WST=235.0+/-35.1; MSG=312.0+/-90.8 bpm), total peripheral resistance (WST=0.312+/-0.100; MSG=0.535+/-0.195 mmHg.ml(-1).min) and in relative epididymal adipose tissue content (WST=2.076+/-0.622; MSG=2.731+/-0.722 g/100 g) and a reduction of systolic volume (WST=1.020+/-0.364; MSG=0.748+/-0.455 microl/bat). An increase in mean arterial pressure was also detected in obese animals during the hemodynamic evaluation. The increases in HR and TPR and the reduction in SV suggest an augmentation in the sympathetic activation of those obese normotensive rats associated with an increased visceral fat deposition.

  18. Arrhythmogenic substrate in hearts of rats with monocrotaline-induced pulmonary hypertension and right ventricular hypertrophy

    PubMed Central

    Benoist, David; Stones, Rachel; Drinkhill, Mark; Bernus, Olivier

    2011-01-01

    Mechanisms associated with right ventricular (RV) hypertension and arrhythmias are less understood than those in the left ventricle (LV). The aim of our study was to investigate whether and by what mechanisms a proarrhythmic substrate exists in a rat model of RV hypertension and hypertrophy. Rats were injected with monocrotaline (MCT; 60 mg/kg) to induce pulmonary artery hypertension or with saline (CON). Myocardial levels of mRNA for genes expressing ion channels were measured by real-time RT-PCR. Monophasic action potential duration (MAPD) was recorded in isolated Langendorff-perfused hearts. MAPD restitution was measured, and arrhythmias were induced by burst stimulation. Twenty-two to twenty-six days after treatment, MCT animals had RV hypertension, hypertrophy, and decreased ejection fractions compared with CON. A greater proportion of MCT hearts developed sustained ventricular tachycardias/fibrillation (0.83 MCT vs. 0.14 CON). MAPD was prolonged in RV and less so in the LV of MCT hearts. There were decreased levels of mRNA for K+ channels. Restitution curves of MCT RV were steeper than CON RV or either LV. Dispersion of MAPD was greater in MCT hearts and was dependent on stimulation frequency. Computer simulations based on ion channel gene expression closely predicted experimental changes in MAPD and restitution. We have identified a proarrhythmic substrate in the hearts of MCT-treated rats. We conclude that steeper RV electrical restitution and rate-dependant RV-LV action potential duration dispersion may be contributing mechanisms and be implicated in the generation of arrhythmias associated with in RV hypertension and hypertrophy. PMID:21398591

  19. Left ventricular remodeling after experimental myocardial cryoinjury in rats.

    PubMed

    Ciulla, Michele M; Paliotti, Roberta; Ferrero, Stefano; Braidotti, Paola; Esposito, Arturo; Gianelli, Umberto; Busca, Giuseppe; Cioffi, Ugo; Bulfamante, Gaetano; Magrini, Fabio

    2004-01-01

    The standard coronary ligation, the most studied model of experimental myocardial infarction in rats, is limited by high mortality and produces unpredictable areas of necrosis. To standardize the location and size of the infarct and to elucidate the mechanisms of myocardial remodeling and its progression to heart failure, we studied the functional, structural, and ultrastructural changes of myocardial infarction produced by experimental myocardial cryoinjury. The cryoinjury was successful in 24 (80%) of 30 male adult CD rats. A subepicardial infarct was documented on echocardiograms, with an average size of about 21%. Macroscopic examination reflected closely the stamp of the instrument used, without transition zones to viable myocardium. Histological examination, during the acute setting, revealed an extensive area of coagulation necrosis and hemorrhage in the subepicardium. An inflammatory infiltrate was evident since the 7th hour, whereas the reparative phase started within the first week, with proliferation of fibroblasts, endothelial cells, and myocytes. From the 7th day, deposition of collagen fibers was reported with a reparative scar completed at the 30th day. Ultrastructural study revealed vascular capillary damage and irreversible alterations of the myocytes in the acute setting and confirmed the histological findings of the later phases. The damage was associated with a progressive left ventricular (LV) remodeling, including thinning of the infarcted area, hypertrophy of the noninfarcted myocardium, and significant LV dilation. This process started from the 60th day and progressed over the subsequent 120 days period; at 180 days, a significant increase in LV filling pressure, indicative of heart failure, was found. In conclusion, myocardial cryodamage, although different in respect to ischemic damage, causes a standardized injury reproducing the cellular patterns of coagulation necrosis, early microvascular reperfusion, hemorrhage, inflammation

  20. [The rat ventricular myocardium in chronic hypercapnia. Electron microscopic study].

    PubMed

    Reichart, E; Moravec, J; Moravec, M; Marotte, F; Hatt, P Y

    1975-11-01

    An electron microscope study of the left ventricular myocardium from rat acclimatized to chronic hypercapnia was done in order to complete the preceding work concerning general effects of respiratory acidosis. After 15 and 30 days of the acclimatation to 8% CO2 no lesions of the myocardium could be found. The results of the morphometric analysis indicated, however, discrete modifications of heart ultrastructure similar to those found before in hypoxic and failing hearts: namely a decrease of mitochondrial mean diameter and a non significant decrease of mitochondrial fractional volume. The latter was accompanied by a significant decrease of myofibrillar mass. The presence of cellular oedema seems to be suggested by an increase of fractional volume of the cytosol. The mechanism of these changes is not easy to explain. Further work will be necessary to make a choice between two possibilities: (1) depressed contractility related to some direct effect of high pCO2 and (2) tissue hypoxia secondary to local effects of the former.

  1. Temporal evaluation of left ventricular remodeling and function in rats with chronic volume overload.

    PubMed

    Brower, G L; Henegar, J R; Janicki, J S

    1996-11-01

    The left ventricle (LV) significantly dilates and hypertrophies in response to chronic volume overload. However, the temporal responses in LV mass, volume, and systolic/diastolic function secondary to chronic volume overload induced by an infrarenal arteriovenous (A-V) fistula in rats have not been well characterized. To this end, LV end-diastolic pressure, size, and function (i.e., isovolumetric pressure-volume relationships in the blood-perfused isolated heart) were assessed at 1, 2, 3, 5, and 8 wk post-A-V fistula and compared with age-matched control animals. Progressive hypertrophy (192% at 8 wk), ventricular dilatation (172% at 8 wk), and a decrease in ventricular stiffness (257% at 8 wk) occurred in the fistula groups. LV end-diastolic pressure increased from a control value of 4.2 +/- 3.1 mmHg to a peak value of 15.7 +/- 3.6 mmHg after 3 wk of volume overload. A subsequent decline in LVEDP to 11.0 +/- 6.0 mmHg together with further LV dilation (169%) corresponded to a significant decrease in LV stiffness (222%) at 5 wk post-A-V fistula. Myocardial contractility, as assessed by the isovolumetric pressure-volume relationship, was significantly reduced in all A-V fistula groups; however, the compensatory remodeling induced by 8 wk of chronic biventricular volume overload tended to preserve systolic function.

  2. The Effects of Puerarin on Rat Ventricular Myocytes and the Potential Mechanism

    PubMed Central

    Xu, Hao; Zhao, Manxi; Liang, Shenghui; Huang, Quanshu; Xiao, Yunchuan; Ye, Liang; Wang, Qinyi; He, Longmei; Ma, Lanxiang; Zhang, Hua; Zhang, Li; Jiang, Hui; Ke, Xiao; Gu, Yuchun

    2016-01-01

    Puerarin, a known isoflavone, is commonly found as a Chinese herb medicine. It is widely used in China to treat cardiac diseases such as angina, cardiac infarction and arrhythmia. However, its cardioprotective mechanism remains unclear. In this study, puerarin significantly prolonged ventricular action potential duration (APD) with a dosage dependent manner in the micromolar range on isolated rat ventricular myocytes. However, submicromolar puerarin had no effect on resting membrane potential (RMP), action potential amplitude (APA) and maximal velocity of depolarization (Vmax) of action potential. Only above the concentration of 10 mM, puerarin exhibited more aggressive effect on action potential, and shifted RMP to the positive direction. Millimolar concentrations of puerarin significantly inhibited inward rectified K+ channels in a dosage dependent manner, and exhibited bigger effects upon Kir2.1 vs Kir2.3 in transfected HEK293 cells. As low as micromolar range concentrations of puerarin significantly inhibited Kv7.1 and IKs. These inhibitory effects may due to the direct inhibition of puerarin upon channels not via the PKA-dependent pathway. These results provided direct preclinical evidence that puerarin prolonged APD via its inhibitory effect upon Kv7.1 and IKs, contributing to a better understanding the mechanism of puerarin cardioprotection in the treatment of cardiovascular diseases. PMID:27762288

  3. The effect of sildenafil on right ventricular remodeling in a rat model of monocrotaline-induced right ventricular failure

    PubMed Central

    Bae, Hyun Kyung; Lee, Hyeryon; Kim, Kwan Chang

    2016-01-01

    Purpose Pulmonary arterial hypertension (PAH) leads to right ventricular failure (RVF) as well as an increase in pulmonary vascular resistance. Our purpose was to study the effect of sildenafil on right ventricular remodeling in a rat model of monocrotaline (MCT)-induced RVF. Methods The rats were distributed randomly into 3 groups. The control (C) group, the monocrotaline (M) group (MCT 60 mg/kg) and the sildenafil (S) group (MCT 60 mg/kg+ sildenafil 30 mg/kg/day for 28 days). Masson Trichrome staining was used for heart tissues. Western blot analysis and immunohistochemical staining were performed. Results The mean right ventricular pressure (RVP) was significantly lower in the S group at weeks 1, 2, and 4. The number of intra-acinar arteries and the medial wall thickness of the pulmonary arterioles significantly lessened in the S group at week 4. The collagen content also decreased in heart tissues in the S group at week 4. Protein expression levels of B-cell lymphoma-2 (Bcl-2)-associated X, caspase-3, Bcl-2, interleukin (IL)-6, matrix metalloproteinase (MMP)-2, endothelial nitric oxide synthase (eNOS), endothelin (ET)-1 and ET receptor A (ERA) in lung tissues greatly decreased in the S group at week 4 according to immunohistochemical staining. According to Western blotting, protein expression levels of troponin I, brain natriuretic peptide, caspase-3, Bcl-2, tumor necrosis factor-α, IL-6, MMP-2, eNOS, ET-1, and ERA in heart tissues greatly diminished in the S group at week 4. Conclusion Sildenafil alleviated right ventricular hypertrophy and mean RVP. These data suggest that sildenafil improves right ventricular function. PMID:27462355

  4. Contractile force measured in unskinned isolated adult rat heart fibres.

    PubMed

    Brady, A J; Tan, S T; Ricchiuti, N V

    1979-12-13

    A number of investigators have succeeded in preparing isolated cardiac cells by enzymatic digestion which tolerate external [Ca2+] in the millimolar range. However, a persistent problem with these preparations is that, unlike in situ adult ventricular fibres, the isolated fibres usually beat spontaneously. This spontaneity suggests persistent ionic leakage not present in situ. A preferable preparation for mechanical and electrical studies would be one which is quiescent but excitable in response to electrical stimulation and which does not undergo contracture with repeated stimulation. We report here a modified method of cardiac fibre isolation and perfusion which leaves the fibre membrane electrically excitable and moderately resistant to mechanical stress so that the attachment of suction micropipettes to the fibre is possible for force measurement and length control. Force generation in single isolated adult rat heart fibres is consistent with in situ contractile force. The negative staircase effect (treppe) characteristic of adult not heart tissue is present with increased frequency of stimulation. Isometric developed tension increases with fibre length as in in situ ventricular tissue.

  5. Alpha 1-adrenergic agonists selectively suppress voltage-dependent K+ current in rat ventricular myocytes.

    PubMed Central

    Apkon, M; Nerbonne, J M

    1988-01-01

    The effects of alpha 1-adrenergic agonists on the waveforms of action potentials and voltage-gated ionic currents were examined in isolated adult rat ventricular myocytes by the whole-cell patch-clamp recording technique. After "puffer" applications of either of two alpha 1 agonists, phenylephrine and methoxamine, action-potential durations were increased. In voltage-clamped cells, phenylephrine (5-20 microM) or methoxamine (5-10 microM) reduced the amplitudes of Ca2+-independent voltage-activated outward K+ currents (Iout); neither the kinetics nor the voltage-dependent properties of Iout were significantly affected. The effects of phenylephrine or methoxamine on Iout were larger and longer-lasting at higher concentrations and after prolonged or repeated exposures; in all experiments, however, Iout recovered completely when puffer applications were discontinued. The suppression of Iout is attributed to the activation of alpha 1-adrenergic receptors, as neither beta- nor alpha 2-adrenergic agonists had measurable effects on Iout; in addition, the effect of phenylephrine was attenuated in the presence of the alpha antagonist phentolamine (10 microM), but not in the presence of the beta antagonist propranolol (10 microM). Voltage-gated Ca2+ currents, in contrast, were not altered measurably by phenylephrine or methoxamine and no currents were activated directly by these agents. Suppression of Iout was also observed during puffer applications of either of two protein kinase C activators, phorbol 12-myristate 13-acetate (10 nM-1 microM) and 1-oleoyl-2-acetylglycerol (60 microM). We conclude that the activation of alpha 1-adrenergic receptors in adult rat ventricular myocytes leads to action-potential prolongation as a result of the specific suppression of Iout and that this effect may be mediated by activation of protein kinase C. PMID:2903506

  6. Post-translational modifications of tubulin and microtubule stability in adult rat ventricular myocytes and immortalized HL-1 cardiomyocytes.

    PubMed

    Belmadani, Souad; Poüs, Christian; Fischmeister, Rodolphe; Méry, Pierre-François

    2004-03-01

    Little is known about the subcellular distribution and the dynamics of tubulins in adult cardiac myocytes although both are modified during cardiac hypertrophy and heart failure. Using confocal microscopy, we examined post-translational modifications of tubulin in fully differentiated ventricular myocytes isolated from adult rat hearts, as well as in immortalized and dividing HL-1 cardiomyocytes. Detyrosinated Glu-alpha-tubulin was the most abundant post-translationally modified tubulin found in ventricular myocytes, while acetylated- and delta2-alpha-tubulins were found in lower amounts or absent. In contrast, dividing HL-1 cardiomyocytes exhibited high levels of tyrosinated or acetylated alpha-tubulins. A mild nocodazole treatment (0.1 microM, 1 h) disrupted microtubules in HL-1 myocytes, but not in adult ventricular myocytes. A stronger treatment (10 microM, 2 h) was required to disassemble tubulins in adult myocytes. Glu-alpha-tubulin containing microtubules were more resistant to nocodazole treatment in HL-1 cardiomyocytes than in ventricular myocytes. Endogenous activation of the cAMP pathway with the forskolin analog L858051 (20 microM) or the beta-adrenergic agonist isoprenaline (10 microM) disrupted the most labile microtubules in HL-1 cardiomyocytes. In contrast, isoprenaline (10 microM), cholera toxin (200 ng/ml, a G(S)-protein activator), L858051 (20 microM) or forskolin (10 microM) had no effect on the microtubule network in ventricular myocytes. In addition, intracellular Ca2+ accumulation induced either by thapsigargin (2 microM) or caffeine (10 mM) did not modify microtubule stability in ventricular myocytes. Our data demonstrate the unique stability of the microtubule network in adult cardiac myocytes. We speculate that microtubule stability is required to support cellular integrity during cardiac contraction.

  7. Isolated right ventricular infiltrating tumour: metastatic hepatocellular carcinoma.

    PubMed

    Lee, Wei-Chieh; Fu, Morgan; Liu, Wen-Hao

    2015-10-01

    Hepatocellular carcinoma (HCC) with intracavitary metastasis to the heart is rare. The incidence of HCC with right atrial metastasis is less than 6% at autopsy. Reports of HCC with right ventricular metastasis without inferior vena cava and right atrial metastasis are rarer. The diagnosis of metastasis of HCC into the cardiac cavity might be overlooked because the symptoms are neither apparent nor specific. Here, we report a patient with metastasis of HCC into the right ventricle cavity. The patient was in a disease-free status and experienced lower limbs oedema and gradual shortness of breath.

  8. Resveratrol treatment reduces cardiac progenitor cell dysfunction and prevents morpho-functional ventricular remodeling in type-1 diabetic rats.

    PubMed

    Delucchi, Francesca; Berni, Roberta; Frati, Caterina; Cavalli, Stefano; Graiani, Gallia; Sala, Roberto; Chaponnier, Christine; Gabbiani, Giulio; Calani, Luca; Del Rio, Daniele; Bocchi, Leonardo; Lagrasta, Costanza; Quaini, Federico; Stilli, Donatella

    2012-01-01

    Emerging evidence suggests that both adult cardiac cell and the cardiac stem/progenitor cell (CSPC) compartments are involved in the patho-physiology of diabetic cardiomyopathy (DCM). We evaluated whether early administration of Resveratrol, a natural antioxidant polyphenolic compound, in addition to improving cardiomyocyte function, exerts a protective role on (i) the progenitor cell pool, and (ii) the myocardial environment and its impact on CSPCs, positively interfering with the onset of DCM phenotype. Adult Wistar rats (n = 128) with streptozotocin-induced type-1 diabetes were either untreated (D group; n = 54) or subjected to administration of trans-Resveratrol (i.p. injection: 2.5 mg/Kg/day; DR group; n = 64). Twenty-five rats constituted the control group (C). After 1, 3 or 8 weeks of hyperglycemia, we evaluated cardiac hemodynamic performance, and cardiomyocyte contractile properties and intracellular calcium dynamics. Myocardial remodeling and tissue inflammation were also assessed by morphometry, immunohistochemistry and immunoblotting. Eventually, the impact of the diabetic "milieu" on CSPC turnover was analyzed in co-cultures of healthy CSPCs and cardiomyocytes isolated from D and DR diabetic hearts. In untreated animals, cardiac function was maintained during the first 3 weeks of hyperglycemia, although a definite ventricular remodeling was already present, mainly characterized by a marked loss of CSPCs and adult cardiac cells. Relevant signs of ventricular dysfunction appeared after 8 weeks of diabetes, and included: 1) a significant reduction in ±dP/dt in comparison with C group, 2) a prolongation of isovolumic contraction/relaxation times, 3) an impaired contraction of isolated cardiomyocytes associated with altered intracellular calcium dynamics. Resveratrol administration reduced atrial CSPC loss, succeeded in preserving the functional abilities of CSPCs and mature cardiac cells, improved cardiac environment by reducing inflammatory

  9. The effect of Ligustrum delavayanum on isolated perfused rat heart

    PubMed Central

    Stankovičová, Tatiana; Frýdl, Miroslav; Kubicová, Mária; Baróniková, Slávka; Nagy, Milan; Grančai, Daniel; Švec, Pavel

    2001-01-01

    BACKGROUND: Extract of ligustrum leaves (Ligustrum delavayanum Hariot [Oleaceae]) is well known in traditional Chinese medicine. One of the active components, oleuropein, displays vasodilating and hypotensive effects. OBJECTIVE: To analyze the effect of 0.008% lyophilized extract of ligustrum dissolved in 0.5% ethanol on heart function. ANIMALS AND METHODS: Experiments were done on isolated rat hearts perfused by the Langendorff method in control conditions and during ischemic-reperfusion injury. RESULTS: Application of ligustrum induced positive inotropic and vasodilating effects in spontaneously beating hearts. Pretreatment of the hearts with ligustrum reduced left ventricular diastolic pressure measured during reperfusion and improved left ventricular contraction compared with hearts without any pretreatment. Ligustrum significantly suppressed the incidence and duration of cardiac reperfusion arrhythmias, expressed as G-score, from 7.40±0.58 in nontreated rats to 1.97±0.50. DISCUSSION: Application of ligustrum or ethanol alone induced changes in coordination between atria and ventricles during ischemia-reperfusion injury. The ‘g-score’, a new parameter summing the incidence and duration of atrioventricular blocks, atrioventricular dissociation and cardiac arrest, is introduced. The g-scores with ligustrum pretreatment were higher during ischemia than during reperfusion. Ethanol significantly depressed myocardial contractility and coronary flow, and nonsignificantly decreased heart rate of isolated rat hearts. Electrical changes observed during coronary reperfusion in the presence of ethanol were accompanied by deterioration of contractile function. CONCLUSIONS: Ligustrum had a significant protective effect on rat myocardium against ischemic-reperfusion injury. Ethanol partially attenuated the protective effect of ligustrum. PMID:20428448

  10. [Effect of berberine on left ventricular remodeling in renovascular hypertensive rats].

    PubMed

    Zhao, Hai-Ping; Hong, Ying; Xie, Jun-Da; Xie, Xin-Ran; Wang, Jing; Fan, Jiang-Bo

    2007-03-01

    The purpose of this study is to evaluate the effects and the underline mechanisms of berberine on the cardiac function and left ventricular remodeling in rats with renovascular hypertension. The renovascular hypertensive model was established by the two-kidney, two-clip (2K2C) method in Sprague-Dawley (SD) rats. Two weeks after surgery, all the operated SD rats were randomly assigned into four groups: (1) renovascular hypertensive model group; (2) berberine 5 mg x kg(-1) group; (3) berberine 10 mg x kg(-1) group; (4) captopril 45 mg x kg(-1) group; and the sham operated rats were used as control. Four weeks after the drugs were administered, the cardiac function was assessed. The ratios of heart weight to body weight (HW/BW), left ventricular weight to body weight (LVW/BW) and right ventricular weight to body weight (RVW/BW) were compared between groups. Coronal sections of the left ventricular tissue (LV) were prepared for paraffin sections, picrosirius red and HE staining was performed. The left ventricular wall thickness (LVWT), interventricular septal thickness (IVST), the parameters of myocardial fibrosis indicated by interstitial collagen volume fraction (ICVF) and perivascular collagen area (PVCA) were assessed. Nitric oxide (NO), adenosine cyclophosphate (cAMP) and guanosine cyclophosphate (cGMP) concentrations of left ventricular tissue were measured. Berberine 5 mg x kg(-1) and 10 mg x kg(-1) increased the left ventricular +/- dp/dt(max) and HR. Berberine 10 mg x kg(-1) decreased HW/BW and LVW/BW. The image analysis showed that both 5 and 10 mg x kg(-1) of berberine decreased LVWT, ICVF and PVCA, while increased the NO and cAMP contents in left ventricular tissue. Berberine could improve cardiac contractility of 2K2C model rats, and inhibit left ventricular remodeling especially myocardial fibrosis in renovascular hypertension rats. And such effects may partially associate with the increased NO and cAMP content in left ventricular tissue.

  11. Detection of cardiac variability in the isolated rat heart.

    PubMed

    Schumacher, Autumn M; Zbilut, Joseph P; Webber, Charles L; Schwertz, Dorie W; Piano, Mariann R

    2006-07-01

    Cardiac variability can be assessed from two perspectives: beat-to-beat performance and continuous performance during the cardiac cycle. Linear analysis techniques assess cardiac variability by measuring the physical attributes of a signal, whereas nonlinear techniques evaluate signal dynamics. This study sought to determine if recurrence quantification analysis (RQA), a nonlinear technique, could detect pharmacologically induced autonomic changes in the continuous left ventricular pressure (LVP) and electrographic (EC) signals from an isolated rat heart-a model that theoretically contains no inherent variability. LVP and EC signal data were acquired simultaneously during Langendorff perfusion of isolated rat hearts before and after the addition of acetylcholine (n = 11), norepinephrine (n = 12), or no drug (n = 12). Two-minute segments of the continuous LVP and EC signal data were analyzed by RQA. Findings showed that%recurrence,%determinism, entropy, maxline, and trend from the continuous LVP signal significantly increased in the presence of both acetylcholine and norepinephrine, although systolic LVP significantly increased only with norepinephrine. In the continuous EC signal, the RQA trend variable significantly increased in the presence of norepinephrine. These results suggest that when either the sympathetic or parasympathetic division of the autonomic nervous system overwhelms the other, the dynamics underlying cardiac variability become stationary. This study also shows that information concerning inherent variability in the isolated rat heart can be gained via RQA of the continuous cardiac signal. Although speculative, RQA may be a tool for detecting alterations in cardiac variability and evaluating signal dynamics as a nonlinear indicator of cardiac pathology.

  12. Effects of acute intravenous iloprost on right ventricular hemodynamics in rats with chronic pulmonary hypertension

    PubMed Central

    Bachman, Timothy N.; El-Haddad, Hazim; Champion, Hunter C.

    2014-01-01

    Abstract The inotropic effects of prostacyclins in chronic pulmonary arterial hypertension (PAH) are unclear and may be important in directing patient management in the acute setting. We sought to study the effects of an acute intravenous (IV) infusion of iloprost on right ventricular (RV) contractility in a rat model of chronic PAH. Rats were treated with monocrotaline, 60 mg/kg intraperitoneally, to induce PAH. Six weeks later, baseline hemodynamic assessment was performed with pressure-volume and Doppler flow measurements. In one group of animals, measurements were repeated 10–15 minutes after IV infusion of a fixed dose of iloprost (20 μg/kg). A separate group of rats underwent dose-response assessment. RV contractility and RV–pulmonary artery coupling were assessed by the end-systolic pressure-volume relationship (ESPVR) and end-systolic elastance/effective arterial elastance (Ees/Ea). RV cardiomyocytes were isolated, and intracellular cAMP (cyclic adenosine monophosphate) concentration was measured with a cAMP-specific enzyme immunoassay kit. Animals had evidence of PAH and RV hypertrophy. Right ventricle/(left ventricle + septum) weight was 0.40 ± 0.03. RV systolic pressure (RVSP) was 39.83 ± 1.62 mmHg. Administration of iloprost demonstrated an increase in the slope of the ESPVR from 0.29 ± 0.02 to 0.42 ± 0.05 (P < .05). Ees/Ea increased from 0.63 ± 0.07 to 0.82 ± 0.06 (P < .05). The RV contractility index (max dP/dt normalized for instantaneous pressure) increased from 94.11 to 114.5/s (P < .05), as did the RV ejection fraction, from 48.0% to 52.5% (P < .05). This study suggests a positive inotropic effect of iloprost on a rat model of chronic PAH. PMID:25610597

  13. Effects of mercury on myosin ATPase in the ventricular myocardium of the rat.

    PubMed

    Moreira, C M; Oliveira, E M; Bonan, C D; Sarkis, J J F; Vassallo, D V

    2003-07-01

    Mercury reduces twitch and tetanic force development in isolated rat papillary muscles, and a putative toxic effect on the contractile machinery has been suggested. Based on that, the actions of HgCl2 on the myosin ATPase activity of the left ventricular myocardium were investigated. Samples for assay of myosin ATPase activity were obtained from rats' left ventricles. Increasing concentrations of HgCl2 reduced dose-dependently the activity of the myosin ATPase. This reduction was observed even at very small concentrations, 50 nM HgCl2. This effect was dependent on the presence of SH groups in the myosin molecule since DTT and glutathione protected the myosin ATPase against toxic effects of mercury; full activity being restored by using 500 nM DTT or 500 nM glutathione. Results also suggested that the metal acts as an uncompetitive inhibitor with a Ki of 200 nM HgCl2. Our results suggest that mercury reduces the activity of the myosin ATPase by an uncompetitive mechanism at a very low dose that does not depress force. DTT and glutathione are effective for protection against the actions of mercury suggesting that SH groups might be the sites of action of the metal on the myosin molecule.

  14. Action potential conduction between a ventricular cell model and an isolated ventricular cell.

    PubMed Central

    Wilders, R; Kumar, R; Joyner, R W; Jongsma, H J; Verheijck, E E; Golod, D; van Ginneken, A C; Goolsby, W N

    1996-01-01

    We used the Luo and Rudy (LR) mathematical model of the guinea pig ventricular cell coupled to experimentally recorded guinea pig ventricular cells to investigate the effects of geometrical asymmetry on action potential propagation. The overall correspondence of the LR cell model with the recorded real cell action potentials was quite good, and the strength-duration curves for the real cells and for the LR model cell were in general correspondence. The experimental protocol allowed us to modify the effective size of either the simulation model or the real cell. 1) When we normalized real cell size to LR model cell size, required conductance for propagation between model cell and real cell was greater than that found for conduction between two LR model cells (5.4 nS), with a greater disparity when we stimulated the LR model cell (8.3 +/- 0.6 nS) than when we stimulated the real cell (7.0 +/- 0.2 nS). 2) Electrical loading of the action potential waveform was greater for real cell than for LR model cell even when real cell size was normalized to be equal to that of LR model cell. 3) When the size of the follower cell was doubled, required conductance for propagation was dramatically increased; but this increase was greatest for conduction from real cell to LR model cell, less for conduction from LR model cell to real cell, and least for conduction from LR model cell to LR model cell. The introduction of this "model clamp" technique allows testing of proposed membrane models of cardiac cells in terms of their source-sink behavior under conditions of extreme coupling by examining the symmetry of conduction of a cell pair composed of a model cell and a real cardiac cell. We have focused our experimental work with this technique on situations of extreme uncoupling that can lead to conduction block. In addition, the analysis of the geometrical factors that determine success or failure of conduction is important in the understanding of the process of discontinuous

  15. Cardiac Body Surface Potentials in Rats with Experimental Pulmonary Hypertension during Ventricular Depolarization.

    PubMed

    Suslonova, O V; Smirnova, S L; Roshchevskaya, I M

    2016-11-01

    The spatial and the amplitude-temporal parameters of cardiac body surface potentials were examined in female Wistar rats with experimental pulmonary hypertension during ventricular depolarization. The cardiac body surface potentials have been led from 64 subcutaneous electrodes evenly distributed across the chest surface prior to and 4 weeks after subcutaneous injection of a single dose of monocrotaline (60 mg/kg). Right ventricular hypertrophy and electrophysiological remodeling of the heart developed in rats with experimental pulmonary hypertension in 4 weeks after monocrotaline injection; these changes led to a significant increase in amplitude and temporal characteristics of the cardioelectric field on the body surface in comparison with the initial state.

  16. Prognostic impact of isolated right ventricular dysfunction in sepsis and septic shock: an 8-year historical cohort study.

    PubMed

    Vallabhajosyula, Saraschandra; Kumar, Mukesh; Pandompatam, Govind; Sakhuja, Ankit; Kashyap, Rahul; Kashani, Kianoush; Gajic, Ognjen; Geske, Jeffrey B; Jentzer, Jacob C

    2017-09-07

    Echocardiographic myocardial dysfunction is reported commonly in sepsis and septic shock, but there are limited data on sepsis-related right ventricular dysfunction. This study sought to evaluate the association of right ventricular dysfunction with clinical outcomes in patients with severe sepsis and septic shock. Historical cohort study of adult patients admitted to all intensive care units at the Mayo Clinic from January 1, 2007 through December 31, 2014 for severe sepsis and septic shock, who had an echocardiogram performed within 72 h of admission. Patients with prior heart failure, cor-pulmonale, pulmonary hypertension and valvular disease were excluded. Right ventricular dysfunction was defined by the American Society of Echocardiography criteria. Outcomes included 1-year survival, in-hospital mortality and length of stay. Right ventricular dysfunction was present in 214 (55%) of 388 patients who met the inclusion criteria-isolated right ventricular dysfunction was seen in 100 (47%) and combined right and left ventricular dysfunction in 114 (53%). The baseline characteristics were similar between cohorts except for the higher mechanical ventilation use in patients with isolated right ventricular dysfunction. Echocardiographic findings demonstrated lower right ventricular and tricuspid valve velocities in patients with right ventricular dysfunction and lower left ventricular ejection fraction and increased mitral E/e' ratios in patients with combined right and left ventricular dysfunction. After adjustment for age, comorbidity, illness severity, septic shock and use of mechanical ventilation, isolated right ventricular dysfunction was independently associated with worse 1-year survival-hazard ratio 1.6 [95% confidence interval 1.2-2.1; p = 0.002) in patients with sepsis and septic shock. Isolated right ventricular dysfunction is seen commonly in sepsis and septic shock and is associated with worse long-term survival.

  17. Spontaneous closure of isolated ventricular septal defect in the pika (Ochotona rufescens rufescens).

    PubMed

    Shinohara, H; Nishimura, H

    1986-04-01

    The incidence of spontaneously occurring ventricular septal defects (VSD) in PIKA neonates and its fate during development are investigated. A total of 160 PIKAs were used in the present study. They consisted of three groups; first, 56 live neonates, second, 37 3-week-old live animals and third, 68 animals which had died during the first two weeks after birth from unknown causes. As high as 8.9% (5 cases out of 56) of the live neonates revealed isolated ventricular septal defects of membranous type. Decreased incidence (2.7%) was seen in 3-week-old PIKAs. Its implication and significance are evaluated in the discussion.

  18. Cardiac pathology in the hypertensive diabetic rat. Biventricular damage with right ventricular predominance.

    PubMed Central

    Fein, F. S.; Cho, S.; Zola, B. E.; Miller, B.; Factor, S. M.

    1989-01-01

    The hypertensive-diabetic rat is a new small animal model of cardiomyopathy characterized by ventricular damage. To determine the extent of pathology in this model, quantitation of light microscopic changes in hearts from 15 hypertensive-diabetic rats and 15 age-matched controls was performed. The fraction of myocardium involved by interstitial fibrosis, myocyte necrosis, replacement fibrosis, vascular sclerosis and perivascular fibrosis was computed separately for right and left ventricles. Spontaneously dying as well as deliberately killed hypertensive-diabetic rats were studied. Spontaneously dying animals had higher systolic blood pressures compared with rats killed deliberately. Body weights were lower and lung weights higher in the former group. Left and right ventricular necrosis and fibrosis were increased in spontaneously dying compared with deliberately killed rats. The degree of right ventricular necrosis and fibrosis paralleled that in the left ventricle, but was, unexpectedly, several times greater in magnitude. Thus, quantitative histology in the hypertensive-diabetic rat reveals more cardiac necrosis and fibrosis, in either ventricle, from spontaneously dying animals compared with deliberately killed rats. This damage, coupled with major functional alterations in the viable myocardium, may lead to congestive heart failure or arrhythmia. Images Figure 1 Figure 2 PMID:2719080

  19. Sustained vortex-like waves in normal isolated ventricular muscle.

    PubMed Central

    Davidenko, J M; Kent, P F; Chialvo, D R; Michaels, D C; Jalife, J

    1990-01-01

    Sustained reentrant excitation may be initiated in small (20 x 20 x less than 0.6 mm) preparations of normal ventricular muscle. A single appropriately timed premature electrical stimulus applied perpendicularly to the wake of a propagating quasiplanar wavefront gives rise to circulation of self-sustaining excitation waves, which pivot at high frequency (5-7 Hz) around a relatively small "phaseless" region. Such a region develops only very low amplitude depolarizations. Once initiated, most episodes of reentrant activity last indefinitely but can be interrupted by the application of an appropriately timed electrical stimulus. The entire course of the electrical activity is visualized with high temporal and spatial resolution, as well as high signal-to-noise ratio, using voltage-sensitive dyes and optical mapping. Two- and three-dimensional graphics of the fluorescence changes recorded by a 10 x 10 photodiode array from a surface of 12 x 12 mm provide sequential images (every msec) of voltage distribution during a reentrant vortex. The results suggest that two-dimensional vortex-like reentry in cardiac muscle is analogous to spiral waves in other biological and chemical excitable media. Images PMID:2247448

  20. Cardiac spinal deafferentation reduces the susceptibility to sustained ventricular tachycardia in conscious rats

    PubMed Central

    Lujan, Heidi L.; Krishnan, Sandhya

    2011-01-01

    The response to myocardial ischemia is complex and involves the cardio-cardiac sympathetic reflex. Specifically, cardiac spinal (sympathetic) afferents are excited by ischemic metabolites and elicit an excitatory sympathetic reflex, which plays a major role in the genesis of ventricular arrhythmias. For example, brief myocardial ischemia leads to ATP release, which activates cardiac spinal afferents through stimulation of P2 receptors. Clinical work with patients and preclinical work with animals document that disruption of this reflex protects against ischemia-induced ventricular arrhythmias. However, the role of afferent signals in the initiation of sustained ventricular tachycardia has not been investigated. Therefore, we tested the hypothesis that cardiac spinal deafferentation reduces the susceptibility to sustained ventricular tachycardia in adult (12–15 wk of age), conscious, male Sprague-Dawley rats. To test this hypothesis, the susceptibility to ventricular tachyarrhythmias produced by occlusion of the left main coronary artery was determined in two groups of conscious rats: 1) deafferentation (bilateral excision of the T1-T5 dorsal root ganglia) and 2) control (sham deafferentation). The ventricular arrhythmia threshold (VAT) was defined as the time from coronary occlusion to sustained ventricular tachycardia resulting in a reduction in arterial pressure. Results document a significantly higher VAT in the deafferentation group (7.0 ± 0.7 min) relative to control (4.3 ± 0.3 min) rats. The decreased susceptibility to tachyarrhythmias with deafferentation was associated with a reduced cardiac metabolic demand (lower rate-pressure product and ST segment elevation) during ischemia. PMID:21677267

  1. [Serial assessment of left ventricular function after valve replacement for isolated aortic regurgitation].

    PubMed

    Misawa, Y; Hasegawa, T; Kato, M; Horimi, H; Yamaguchi, T

    1991-04-01

    Between 1978 and 1990, serial echocardiographic studies were performed on consecutive twenty-five patients of isolated aortic regurgitation (AR) before and after aortic valve replacement (AVR). The mean follow up period was 55 +/- 30 months. The serial changes in left ventricular end-diastolic dimension (LVDd), left ventricular end-systolic dimension (LVDs), fractional shortening (FS), and ejection fraction (EF) were assessed. According to preoperative echocardiographic studies, 25 patients were divided into two groups: Group I with LVDs greater than 50 mm and FS less than 25%, Group II with LVDs less than or equal to 50 mm and/or FS greater than or equal to 25%. One year after AVR, echocardiographic studies revealed normalization of LVDd and LVDs in Group II, and persistent left ventricular enlargement with lower FS and EF levels in Group I. However three years after AVR, LVDd, LVDs, and FS and EF of Group I returned to normal levels. It was concluded that in order to normalize the left ventricular function in isolated AR patients, those who had LVDs greater than 50 mm and FS less than 25% required three years after AVR, those patients who had LVDs less than or equal to 50 mm and/or FS greater than or equal to 25%, required only one year after AVR.

  2. Cardioprotective effect of polydatin on ventricular remodeling after myocardial infarction in coronary artery ligation rats.

    PubMed

    Gao, Yan; Gao, Jianping; Chen, Changxun; Wang, Huilin; Guo, Juan; Wu, Rong

    2015-05-01

    The purpose of this study was to explore the effect of polydatin on ventricular remodeling after myocardial infarction in coronary artery ligation rats and to elucidate the underlying mechanisms. A rat model of ventricular remodeling after myocardial infarction was established by left coronary artery ligation. Rats with coronary artery ligation were randomly divided into five groups: control, plus 40 mg/kg captopril, plus 25 mg/kg polydatin, plus 50 mg/kg polydatin, and plus 100 mg/kg polydatin. The sham-operated group was used as a negative control. Rats were administered intragastrically with the corresponding drugs or drinking water for seven weeks. At the end of the treatment, the left ventricular weight index and heart weight index were assessed. The cross-sectional size of cardiomyocytes was measured by staining myocardium tissue with hematoxylin and eosin. Collagen content was counted by Sirius red in aqueous saturated picric acid. The concentrations of angiotensin I, angiotensin II, aldosterone, and endothelin 1 in myocardium or serum were determined by radioimmunoassay. Hydroxyproline and nitric oxide concentrations and glutathione peroxidase and catalase activities in serum were measured by ultraviolet spectrophotometry. Our results showed that seven weeks of polydatin treatment resulted in a significantly reduced left ventricular weight index, heart weight index, serum concentrations of hydroxyproline and aldosterone, an increased concentration of nitric oxide as well as enhanced activities of glutathione peroxidase and catalase. Myocardial angiotensin I, angiotensin II, and endothelin 1 levels were also reduced. The cardiomyocyte cross-sectional area and collagen deposition diminished. This study suggests that polydatin may attenuate ventricular remodeling after myocardial infarction in coronary artery ligation rats through restricting the excessive activation of the renin-angiotensin-aldosterone system and inhibiting peroxidation. Georg Thieme

  3. [Hypervolemic redistribution mechanism in pulmonary edema in patients with isolated left ventricular failure].

    PubMed

    Shteĭngardt, Iu N; Inzel', T N

    1981-04-01

    The authors examined 90 patients with ischemic heart disease and isolated left-ventricular insufficiency by impedance plethysmography and determined the body total water content by means of tritium oxide in 32 of them. It was established that there is no essential increase in total body water and volumes of circulating blood and plasma at the peak of manifestations of isolated left-ventricular insufficiency. The redistribution of some of the blood from the periphery of systemic circulation to the center, mainly into the pulmonary circulation, possibly plays the principle role in the genesis of pulmonary circulation hypervolemia and pulmonary edema in approximately half of the cases. The same mechanism with its reverse direction occurs in successful treatment and correction of hypervolemia of pulmonary circulation and pulmonary edema.

  4. Halothane, isoflurane and enflurane potentiate the effect of noradrenaline on ventricular automaticity in the rat heart: evidence of the involvement of both alpha- and beta-adrenoceptors.

    PubMed

    Cárceles, M D; Laorden, M L; Hernandez, J; Miralles, F S; Campos, M

    1990-03-01

    Direct evidence has been sought as to what extent the sensitization of heart to the arrhythmogenic action of sympathomimetic drugs in the presence of the inhalatory anaesthetics, halothane, isoflurane and enflurane, is mediated by either alpha- or beta-adrenoceptors. For this purpose, the effects of isoprenaline, noradrenaline and phenylephrine on ventricular automaticity induced by local injury have been studied in the isolated right ventricle of the rat. Isoprenaline was more potent in increasing ventricular automaticity than either phenylephrine or noradrenaline. The anaesthetic potentiated the effects of noradrenaline, as well as that of higher concentrations of phenylephrine, but not those of isoprenaline. These results support the contention that increases in ventricular automaticity induced by sympathomimetic drugs are mainly mediated by adrenoceptors of the beta-type. However, the simultaneous activation of both alpha- and beta-adrenoceptors seems to be necessary for the effect of the anaesthetics in sensitizing the heart to sympathomimetic drugs.

  5. Toxic effects of palladium compounds on the isolated rat heart.

    PubMed

    Perić, Tanja; Jakovljević, Vladimir Lj; Zivkovic, Vladimir; Krkeljic, Jelena; Petrović, Zorica D; Simijonović, Dusica; Novokmet, Slobodan; Djuric, Dragan M; Janković, Slobodan M

    2012-01-01

    Taken into consideration limited data about effects of palladium on cardiovascular system, the aim of our study was to compare toxicity of inorganic and organic palladium compounds on the isolated rat heart. The hearts (total number n=30, 6 for each experimental group) excised from Wistar albino rats, male sex, age 8 weeks, and body mass 180-200 g, were retrogradely perfused according to the Langendorff technique at constant perfusion pressure (70 cm H2O). After the insertion of sensor in the left ventricle, the parameters of heart function: maximum rate of left ventricular pressure development (dP/dt max), systolic left ventricular pressure (SLVP), diastolic left ventricular pressure (DLVP), mean blood pressure (MBP) and heart rate (HR)), were continuously registered. The experiments were performed during control conditions, and in the presence of perfusion with incresing concentration of the following: (triethanolamine (TEA), triethanolamine acetate (TEAA), palladium(II)chloride (PdCl2), and trans-dichlorobis(triethanolamine-N)palladium(II) complex (trans-[PdCl2(TEA)2])) started every 30 minutes (30, 60, 90, 120 minute). dP/dt max was not affected significantly by either TEAA, TEA, PdCl2 or Pd complex. SLVP was, also, not affected significantly by either TEAA, TEA, PdCl2, or Pd complex. DLVP was significantly decreased by both TEAA and PdCl2, while TEA and Pd complex did not show significant effect. MBP was significantly decreased only by PdCl2, while TEAA, TEA and Pd complex did not show significant effect. HR was significantly decreased by all compounds- PdCl2, TEAA, TEA and Pd complex. In our study, inorganic palladium compound (PdCl2) induced clear depression of the isolated rat heart contractility, manifested as drop in diastolic and mean blood pressure , and as decrease of the heart rate. On the other hand, it seems that palladium, when bound in an organic compound (linked to TEA in Pd complex), does not contribute significantly to cardio-toxicity in our

  6. Congenital isolated cleft mitral valve leaflet and apical muscular ventricular septal defect in a Holstein calf.

    PubMed

    Depenbrock, Sarah M; Visser, Lance C; Kohnken, Rebecca A; Russell, Duncan S; Simpson, Katharine M; Bonagura, John D

    2015-09-01

    A 5-week-old Holstein heifer calf presented for emergency treatment of signs referable to gastrointestinal disease and hypovolemic shock. Fluid resuscitation uncovered clinical signs of primary cardiac disease and echocardiography revealed multiple congenital cardiac defects. Malformations included a cleft anterior mitral valve leaflet resembling an isolated cleft mitral valve and an apically-located muscular ventricular septal defect. The echocardiographic and postmortem findings associated with these defects are presented and discussed in this report.

  7. Dinitrophenol pretreatment of rat ventricular myocytes protects against damage by metabolic inhibition and reperfusion.

    PubMed

    Rodrigo, G C; Lawrence, C L; Standen, N B

    2002-05-01

    We have investigated the protective effects of pretreatment with the mitochondrial uncoupler 2,4-dinitrophenol on the cellular damage induced by metabolic inhibition (with cyanide and iodoacetic acid) and reperfusion in freshly isolated adult rat ventricular myocytes. Damage was assessed from changes in cell length and morphology measured using video microscopy. Intracellular Ca(2+), mitochondrial membrane potential, and NADH were measured using fura-2, tetramethylrhodamine ethyl ester and autofluorescence, respectively. During metabolic inhibition myocytes developed rigor, and on reperfusion 73.6+/-8.1% hypercontracted and 10.8+/-6.7% recovered contractile function in response to electrical stimulation. Intracellular Ca(2+) increased substantially, indicated by a rise in the fura-2 ratio (340/380 nm) on reperfusion from 0.86+/-0.04 to 1.93+/-0.18. Myocytes pretreated with substrate-free Tyrode containing 50 microm dinitrophenol showed reduced reperfusion injury: 29.0+/-7.4% of cells hypercontracted and 65.3+/-7.3% recovered contractile function (P<0.001 vs control). The fura-2 ratio on reperfusion was also lower at 1.01+/-0.08. Fluorescence measurements showed that dinitrophenol caused mitochondrial depolarisation, and decreased NADH. The presence of the substrates glucose and pyruvate reduced these effects, and abolished the protection against damage by metabolic inhibition and reperfusion. However protection was unaffected by block of ATP-sensitive potassium channels. Thus the protective effects of pretreatment with dinitrophenol may result from a reduction in NADH in response to mitochondrial depolarisation.

  8. Hyaluronate degradation affects ventricular function of the early postlooped embryonic rat heart in situ.

    PubMed

    Baldwin, H S; Lloyd, T R; Solursh, M

    1994-02-01

    Hyaluronic acid is the major glycosaminoglycan of the early cardiac extracellular matrix or "cardiac jelly," yet little is known about its role in the ontogeny of early ventricular performance. To investigate the in situ effect of hyaluronate degradation on ventricular function, whole rat embryos were cultured in rat serum alone (control embryos) or rat serum plus 20 TRU/mL of Streptomyces hyaluronidase (treatment embryos) from gestational day 9.5 (before formation of the heart tube) through initial looping of the heart. Cardiac function was measured before looping (24 hours in culture) and immediately after looping (36 hours in culture) by video motion analysis of the external wall motion of the bulbus cordis and primitive ventricle. Degradation of hyaluronic acid in the treated embryos was confirmed by Alcian blue staining at pH 2.5. Significant increases in heart rate, circumferential shortening fraction, maximum velocity of circumferential contraction, and maximum velocity of circumferential relaxation were observed with looping in both control and treatment embryos. Although there was minimal difference in ventricular performance between control and treatment embryos before looping, there was a significant increase in all parameters of ventricular performance in the hyaluronidase-treated embryos immediately after looping of the heart. Endocardial cushions were absent in hyaluronidase-treated embryos, and an additional group of embryos cultured in the presence of Streptomyces hyaluronidase for 48 to 72 hours failed to develop endocardial cushions. These experiments are the first to (1) document a quantifiable increase in ventricular performance during early cardiac looping and (2) demonstrate that hyaluronate degradation results in abnormal endocardial cushion formation and altered ventricular performance of the postlooped heart.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Itraconazole decreases left ventricular contractility in isolated rabbit heart: Mechanism of action

    SciTech Connect

    Qu, Yusheng; Fang, Mei; Gao, BaoXi; Amouzadeh, Hamid R.; Li, Nianyu; Narayanan, Padma; Acton, Paul; Lawrence, Jeff; Vargas, Hugo M.

    2013-04-15

    Itraconazole (ITZ) is an approved antifungal agent that carries a “black box warning” in its label regarding a risk of negative cardiac inotropy based on clinical findings. Since the mechanism of the negative inotropic effect is unknown, we performed a variety of preclinical and mechanistic studies to explore the pharmacological profile of ITZ and understand the negative inotropic mechanism. ITZ was evaluated in: (1) an isolated rabbit heart (IRH) preparation using Langendorff retrograde perfusion; (2) ion channel studies; (3) a rat heart mitochondrial function profiling screen; (4) a mitochondrial membrane potential (MMP) assay; (5) in vitro pharmacology profiling assays (148 receptors, ion channels, transporters, and enzymes); and (6) a kinase selectivity panel (451 kinases). In the IRH, ITZ decreased cardiac contractility (> 30%) at 0.3 μM, with increasing effect at higher concentrations, which indicated a direct negative inotropic effect upon the heart. It also decreased heart rate and coronary flow (≥ 1 μM) and prolonged PR/QRS intervals (3 μM). In mechanistic studies, ITZ inhibited the cardiac NaV channel (IC{sub 50}: 4.2 μM) and was devoid of any functional inhibitory effect at the remaining pharmacological targets. Lastly, ITZ did not affect MMP, nor interfere with mitochondrial enzymes or processes involved with fuel substrate utilization or energy formation. Overall, the cardiovascular and mechanistic data suggest that ITZ-induced negative inotropy is a direct effect on the heart, in addition, the potential involvement of mitochondria function and L-type Ca{sup 2+} channels are eliminated. The exact mechanism underlying the negative inotropy is uncertain, and requires further study. - Highlights: ► Effect of itraconazole (ITZ) was assessed in the isolated rabbit heart (IRH) assay. ► ITZ decreased ventricular contractility in IRH, indicating a direct effect. ► IC{sub 50} of ITZ on L-type I{sub Ca} was greater than 30 μM, on I{sub Na} was 4

  10. The Actions of Lyophilized Apple Peel on the Electrical Activity and Organization of the Ventricular Syncytium of the Hearts of Diabetic Rats

    PubMed Central

    Martínez-Ladrón de Guevara, Elideth; Pérez-Hernández, Nury; Villalobos-López, Miguel Ángel; Pérez-Ishiwara, David Guillermo; Salas-Benito, Juan Santiago; Martínez Martínez, Alejandro; Hernández-García, Vicente

    2016-01-01

    This study was designed to examine the effects of lyophilized red delicious apple peel (RDP) on the action potentials (APs) and the input resistance-threshold current relationship. The experiments were performed on isolated papillary heart muscles from healthy male rats, healthy male rats treated with RDP, diabetic male rats, and diabetic male rats treated with RDP. The preparation was superfused with oxygenated Tyrode's solution at 37°C. The stimulation and the recording of the APs, the input resistance, and the threshold current were made using conventional electrophysiological methods. The RDP presented no significant effect in normal rats. Equivalent doses in diabetic rats reduced the APD and ARP. The relationship between input resistance and threshold current established an inverse correlation. The results indicate the following: (1) The functional structure of the cardiac ventricular syncytium in healthy rats is heterogeneous, in terms of input resistance and threshold current. Diabetes further accentuates the heterogeneity. (2) As a consequence, conduction block occurs and increases the possibility of reentrant arrhythmias. (3) These modifications in the ventricular syncytium, coupled with the increase in the ARP, are the adequate substrate so that, with diabetes, the heart becomes more arrhythmogenic. (4) RDP decreases the APD, the ARP, and most syncytium irregularity caused by diabetes. PMID:26839897

  11. The Actions of Lyophilized Apple Peel on the Electrical Activity and Organization of the Ventricular Syncytium of the Hearts of Diabetic Rats.

    PubMed

    Martínez-Ladrón de Guevara, Elideth; Pérez-Hernández, Nury; Villalobos-López, Miguel Ángel; Pérez-Ishiwara, David Guillermo; Salas-Benito, Juan Santiago; Martínez Martínez, Alejandro; Hernández-García, Vicente

    2016-01-01

    This study was designed to examine the effects of lyophilized red delicious apple peel (RDP) on the action potentials (APs) and the input resistance-threshold current relationship. The experiments were performed on isolated papillary heart muscles from healthy male rats, healthy male rats treated with RDP, diabetic male rats, and diabetic male rats treated with RDP. The preparation was superfused with oxygenated Tyrode's solution at 37°C. The stimulation and the recording of the APs, the input resistance, and the threshold current were made using conventional electrophysiological methods. The RDP presented no significant effect in normal rats. Equivalent doses in diabetic rats reduced the APD and ARP. The relationship between input resistance and threshold current established an inverse correlation. The results indicate the following: (1) The functional structure of the cardiac ventricular syncytium in healthy rats is heterogeneous, in terms of input resistance and threshold current. Diabetes further accentuates the heterogeneity. (2) As a consequence, conduction block occurs and increases the possibility of reentrant arrhythmias. (3) These modifications in the ventricular syncytium, coupled with the increase in the ARP, are the adequate substrate so that, with diabetes, the heart becomes more arrhythmogenic. (4) RDP decreases the APD, the ARP, and most syncytium irregularity caused by diabetes.

  12. Isolated left ventricular noncompaction in a newborn with Pierre-Robin sequence.

    PubMed

    Aypar, Ebru; Sert, Ahmet; Gokmen, Zeynel; Aslan, Eyup; Odabas, Dursun

    2013-02-01

    Pierre-Robin sequence or syndrome (PRS) (OMIM #261800) is characterized by a small mandible (micrognathia), posterior displacement/retraction of the tongue (glossoptosis), and upper airway obstruction. It has an incidence varying from 1 in 8,500 to 1 in 30,000 births. Congenital heart defects (CHDs) occur in 20 % of the patients with PRS. Ventricular septal defect, patent ductus arteriosus, and atrial septal defects are the most common lesions. Noncompaction of the ventricular myocardium is a rare cardiomyopathy characterized by a pattern of prominent trabecular meshwork and deep intertrabecular recesses. It is thought to be caused by arrest of the normal endomyocardial morphogenesis. Isolated left ventricular noncompaction (LVNC) in patients with PRS has not been reported previously. This report describes a newborn with PRS and isolated LVNC. Previously, LVNC has been reported in association with mitochondrial disorders, Barth syndrome hypertrophic cardiomyopathy, zaspopathy, muscular dystrophy type 1, 1p36 deletion, Turner syndrome, Ohtahara syndrome, distal 5q deletion, mosaic trisomy 22, trisomy 13, DiGeorge syndrome, and 1q43 deletion with decreasing frequency. Karyotype analysis of the reported patient showed normal chromosomes (46, XX), and a fluorescent in situ hybridization study did not show chromosome 22q11.2 deletion. This is the first clinical report of a patient with isolated LVNC and PRS. Noncompaction of the ventricular myocardium is a rare and unique disorder with characteristic morphologic features that can be identified by echocardiography. Long-term follow-up evaluation for development of progressive LV dysfunction and cardiac arrhythmias is indicated for these patients.

  13. Sarcolemmal hydraulic conductivity of guinea-pig and rat ventricular myocytes.

    PubMed

    Ogura, Toshitsugu; Matsuda, Hiroyuki; Imanishi, Sunao; Shibamoto, Toshishige

    2002-06-01

    Osmotic gradient-induced volume change and sarcolemmal water permeability of cardiac myocytes were evaluated to characterize the mechanism of water flux across the plasma membranes. Cell surface dimensions were measured from isolated guinea-pig and rat ventricular myocytes by digital videomicroscopy, and membrane hydraulic conductivity (L(p)) was obtained by analyzing the time course of cell swelling and shrinkage in response to osmotic gradients. Superfusion with anisosmotic solution (0.5-4 times normal osmolality) caused a rapid (<3 min to steady states) and reversible myocyte swelling or shrinkage. L(p) was approximately 1.9 x 10(-10) l N(-1) s(-1) for guinea-pig myocytes and approximately 1.7 x 10(-10) l N(-1) s(-1) for rat myocytes at 35 degrees C. Arrhenius activation energy (E(a)), a measure of the energy barrier to water flux, was approximately 3.7 (guinea-pig) and approximately 3.6 kcal mol(-1) (rat) between 11 and 35 degrees C; these values are equivalent to E(a) of self-diffusion of water in bulk solution ( approximately 4 kcal mol(-1)). Treatment with 0.1 mM Hg(2+), a sulfhydryl-oxidizing reagent that blocks membrane water channels, reduced L(p) by approximately 80%, and the sulfhydryl-reducing reagent dithiothreitol (10 mM) antagonized the inhibitory action of Hg(2+). Inhibition of the volume-sensitive cation (30 microM Gd3+) and anion (1 mM 4,4'-diisothiocyanostilbene-2,2'-disulfonate) channels and Na+-K+ pump (10 microM ouabain) modified the size of osmotic swelling but had little effect on L(p). Although the observed L(p) is relatively small in magnitude, the low E(a) and the sulfhydryl reagent-induced modification of L(p) are characteristic of channel-mediated water transport. These data suggest that water flux across the sarcolemma of guinea-pig and rat heart cells occurs through parallel pathways, i.e., the majority passing through water channels and the remainder penetrating the lipid bilayers.

  14. Endotoxin pretreatment increases endogenous myocardial catalase activity and decreases ischemia-reperfusion injury of isolated rat hearts.

    PubMed Central

    Brown, J M; Grosso, M A; Terada, L S; Whitman, G J; Banerjee, A; White, C W; Harken, A H; Repine, J E

    1989-01-01

    Hearts isolated from rats pretreated 24 hr before with endotoxin had increased myocardial catalase activity, but the same superoxide dismutase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase activities, as hearts from untreated rats. Hearts isolated from rats pretreated with endotoxin 24 hr before also had increased myocardial function (decreased injury) after ischemia and reperfusion (Langendorff apparatus, 37 degrees C), as assessed by measurement of ventricular developed pressure, contractility (+dP/dt), and relaxation rate (-dP/dt), compared to control hearts. In contrast, hearts isolated from rats pretreated with endotoxin 1 hr before isolation or hearts perfused with endotoxin did not have increased catalase activity or decreased injury following ischemia and reperfusion. Aminotriazole pretreatment prevented increases in myocardial catalase activity and myocardial function after ischemia-reperfusion in hearts from endotoxin-pretreated rats. The results suggest that endotoxin pretreatment decreases cardiac ischemia-reperfusion injury and that increases in endogenous myocardial catalase activity contribute to protection. PMID:2648406

  15. Altered ventricular torsion and transmural patterns of myocyte relaxation precede heart failure in aging F344 rats.

    PubMed

    Campbell, Stuart G; Haynes, Premi; Kelsey Snapp, W; Nava, Kristofer E; Campbell, Kenneth S

    2013-09-01

    The purpose of this study was to identify and explain changes in ventricular and cellular function that contribute to aging-associated cardiovascular disease in aging F344 rats. Three groups of female F344 rats, aged 6, 18, and 22 mo, were studied. Echocardiographic measurements in isoflurane-anesthetized animals showed an increase in peak left ventricular torsion between the 6- and the 18-mo-old groups that was partially reversed in the 22-mo-old animals (P < 0.05). Epicardial, midmyocardial, and endocardial myocytes were subsequently isolated from the left ventricles of each group of rats. Unloaded sarcomere shortening and Ca(2+) transients were then measured in these cells (n = >75 cells for each of the nine age-region groups). The decay time of the Ca(2+) transient and the time required for 50% length relaxation both increased with age but not uniformly across the three regions (P < 0.02). Further analysis revealed a significant shift in the transmural distribution of these properties between 18 and 22 mo of age, with the largest changes occurring in epicardial myocytes. Computational modeling suggested that these changes were due in part to slower Ca(2+) dissociation from troponin in aging epicardial myocytes. Subsequent biochemical assays revealed a >50% reduction in troponin I phosphoprotein content in 22-mo-old epicardium relative to the other regions. These data suggest that between 18 and 22 mo of age (before the onset of heart failure), F344 rats display epicardial-specific myofilament-level modifications that 1) break from the progression observed between 6 and 18 mo and 2) coincide with aberrant patterns of cardiac torsion.

  16. Altered ventricular torsion and transmural patterns of myocyte relaxation precede heart failure in aging F344 rats

    PubMed Central

    Campbell, Stuart G.; Haynes, Premi; Kelsey Snapp, W.; Nava, Kristofer E.

    2013-01-01

    The purpose of this study was to identify and explain changes in ventricular and cellular function that contribute to aging-associated cardiovascular disease in aging F344 rats. Three groups of female F344 rats, aged 6, 18, and 22 mo, were studied. Echocardiographic measurements in isoflurane-anesthetized animals showed an increase in peak left ventricular torsion between the 6- and the 18-mo-old groups that was partially reversed in the 22-mo-old animals (P < 0.05). Epicardial, midmyocardial, and endocardial myocytes were subsequently isolated from the left ventricles of each group of rats. Unloaded sarcomere shortening and Ca2+ transients were then measured in these cells (n = >75 cells for each of the nine age-region groups). The decay time of the Ca2+ transient and the time required for 50% length relaxation both increased with age but not uniformly across the three regions (P < 0.02). Further analysis revealed a significant shift in the transmural distribution of these properties between 18 and 22 mo of age, with the largest changes occurring in epicardial myocytes. Computational modeling suggested that these changes were due in part to slower Ca2+ dissociation from troponin in aging epicardial myocytes. Subsequent biochemical assays revealed a >50% reduction in troponin I phosphoprotein content in 22-mo-old epicardium relative to the other regions. These data suggest that between 18 and 22 mo of age (before the onset of heart failure), F344 rats display epicardial-specific myofilament-level modifications that 1) break from the progression observed between 6 and 18 mo and 2) coincide with aberrant patterns of cardiac torsion. PMID:23792678

  17. Contribution of ventricular remodeling to pathogenesis of heart failure in rats.

    PubMed

    Brower, G L; Janicki, J S

    2001-02-01

    We previously reported an approximately 50% incidence of rats with symptoms of congestive heart failure (CHF) at 8 wk postinfrarenal aorto-caval fistula. However, it was not clear whether compensatory ventricular remodeling could continue beyond 8 wk or whether the remaining animals would have developed CHF or died. Therefore, the intent of this study was to complete the characterization of this model of sustained volume overload by determining the morbidity and mortality and the temporal response of left ventricular (LV) remodeling and function beyond 8 wk. The findings demonstrate an upper limit to LV hypertrophy and substantial increases in LV volume and compliance, matrix metalloproteinase activity, and collagen volume fraction associated with the development of CHF. There was an 80% incidence of morbidity and mortality following 21 wk of chronic volume overload. These findings indicate that the development of CHF is triggered by marked ventricular dilatation and increased compliance occurring once the myocardial hypertrophic response is exhausted.

  18. Swimming exercise training prior to acute myocardial infarction attenuates left ventricular remodeling and improves left ventricular function in rats.

    PubMed

    Dayan, Anat; Feinberg, Micha S; Holbova, Radka; Deshet, Naamit; Scheinowitz, Mickey

    2005-01-01

    The effect of exercise training prior to acute myocardial infarction (AMI) on left ventricular (LV) remodeling is poorly understood. This study investigated the protective effect of 3 weeks of swimming exercise training prior to AMI on cardiac morphology and function. Male Sprague-Dawley rats (n = 35) were randomly assigned to 3 groups: swimming training (n = 14, 90 min, 5 days/wk, 3 wk), sedentary (n =14), and controls (n = 7, no exercise, no MI). At the end of the training/sedentary period, rats were subjected to AMI (ExMI and SedMI) induced by surgical ligation of the left coronary artery. Thereafter, the rats remained sedentary for a 4-wk recovery period. Trans-thoracic echocardiography was performed in each group at the end of the exercise/sedentary period (pre-AMI), 24 hr after AMI, and following recovery (4 wk after AMI). No differences were observed in LV dimensions and function pre-AMI among the 3 groups; however, LV-end systolic diameter (LVESD) and LV-end systolic area (LVES-area) were significantly lower in the prior trained rats, 24 hr post-AMI with no additional change 4 wk post-AMI, during remodeling. Both LV-shortening fraction (SF%) and fractional area change (FAC%) were higher in the trained animals 4 wk post-AMI (39+/-12% vs 23+/-8%; p 0.002, and 48+/-14% vs. 38+/-9%; p 0.07, respectively). In conclusion, 3 wk of swimming exercise training prior to AMI significantly attenuated LV remodeling and improved LV function, despite no changes in LV dimensions or systolic function at the end of the exercise session. The data suggest that even a short-term training period is sufficient to induce cardiac protection.

  19. Structural characterization of rat ventricular tissue exposed to the smoke of two types of waterpipe

    PubMed Central

    Al-Awaida, Wajdy; Najjar, Hossam; Shraideh, Ziad

    2015-01-01

    Objective(s): this study focused on the effect of waterpipe smoke exposure toxicity on the structure of albino rat’s ventricular tissue and their recovery. Materials and Methods: Albino rats were divided into three groups: control, flavored, and unflavored. The control group was exposed to normal air while the flavored and unflavored groups were exposed to waterpipe smoke for a period of 90 days. Each group was followed by a period of 90 days of fresh air exposure. Following each period, the ventricular tissue was removed for biochemical and histopathological studies. Results: The ventricular tissues of waterpipe exposed rats showed some degree of separation between cardiac muscle fibers, infiltration of lymphocytes, and congestion of blood vessel. Also, thin cross sections of ventricular cells revealed pleomorphic mitochondria with partially disrupted cristae, partial disruption of the myofibrils, and deposited toxic materials. The unflavored waterpipe has more deleterious effects on heart ventricular tissues than the flavored one. Waterpipe smoke didn’t induce apoptosis in the ventricular tissue. We also found very high levels of plasma thiocyanate after exposure to smoke in the flavored and unflavored groups, while the control group showed no increase. After the recovery period, those tissues showed partial recovery. Conclusion: Waterpipe smoke induces structural changes in the heart ventricle tissues, causing a negative impact on the capacity of the cardiac muscle for pumping blood and may lead to heart attack due to accumulation of free radicals and tissue inflammation. Cessation of smoking is important in returning most of these changes to their normal structure. PMID:26730327

  20. Cardiotoxic effects of the Vipera ammodytes ammodytes venom fractions in the isolated perfused rat heart.

    PubMed

    Karabuva, Svjetlana; Brizić, Ivica; Latinović, Zorica; Leonardi, Adrijana; Križaj, Igor; Lukšić, Boris

    2016-10-01

    The nose-horned viper (Vipera ammodytes ammodytes) is the most venomous European snake. Its venom is known as haematotoxic, myotoxic and neurotoxic but it exerts also cardiotoxic effects. To further explore the cardiotoxicity of the venom we separated it into four fractions by gel filtration chromatography. Three fractions that contain polypeptides (A, B, and C) were tested for their effects on isolated rat heart. Heart rate (HR), incidence of arrhythmias (atrioventricular (AV) blocks, ventricular tachycardia, ventricular fibrillation, and asystolia), coronary flow (CF), systolic, developed and diastolic left ventricular pressure (LVP) were measured before, during, and after the application of venom fractions in three different concentrations. Fraction A, containing proteins of 60-100 kDa, displayed no effect on the rat heart. Fractions B and C disturbed heart functioning in similar way, but with different potency that was higher by the latter. This was manifested by significant decrease of HR and CF, the increase of diastolic, and the decrease of systolic and developed LVPs. All hearts treated with fraction C in the final CF concentrations 22.5 and 37.5 μg/mL suffered rapid and irreversible asystolia without AV blockade. They underwent also ventricular fibrillation and ventricular tachycardia. Fraction B affected hearts only at the highest dose inducing asystolia in all hearts, ventricular fibrillation in 80% and ventricular tachycardia in 70% of the hearts. Venom fraction C induced 71% of all recorded heart rhythm disturbances, significantly more than fraction B, which induced 29%. Most abundant proteins in fraction C were secreted phospholipases A2 among which the venom component acting on the heart is most probably to be looked for. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Chamber-specific effects of hypokalaemia on ventricular arrhythmogenicity in isolated, perfused guinea-pig heart.

    PubMed

    Osadchii, Oleg E; Bentzen, Bo Hjorth; Olesen, Soren Peter

    2009-04-01

    Diuretic-induced hypokalaemia has been shown to promote cardiac arrhythmias in hypertensive patients. The present study was designed to determine whether hypokalaemia increases arrhythmic susceptibility of the left ventricle (LV) or the right ventricle (RV), or both. Proarrhythmic effects of hypokalaemic perfusion (2.5 mm K(+) for 30 min) were assessed in isolated guinea-pig heart preparations using simultaneous recordings of volume-conducted electrocardiogram and monophasic action potentials from six ventricular epicardial sites. Effective refractory periods, ventricular fibrillation thresholds and inducibility of tachyarrhythmias by programmed electrical stimulation and tachypacing were determined at the LV and the RV epicardial stimulation sites. Hypokalaemia promoted spontaneous ventricular ectopic activity, an effect attributed to non-uniform prolongation of ventricular repolarization resulting in increased RV-to-LV transepicardial dispersion of refractoriness and action potential duration. Furthermore, hypokalaemic perfusion was associated with reduced ventricular fibrillation threshold and increased inducibility of tachyarrhythmias by programmed electrical stimulation and tachypacing as determined at the LV stimulation site. In contrast, the RV stimulation revealed no change in arrhythmic susceptibility of the RV chamber. Consistently, hypokalaemia reduced the LV effective refractory period but had no effect on the RV refractoriness. This change enabled generation of premature propagating responses by extrastimulus application at earlier time points during LV repolarization. Increased prematurity of extrastimulus-evoked propagating responses was associated with exaggerated local inhomogeneities in intraventricular conduction and action potential duration in hypokalaemic LV, thus creating a favourable stage for re-entrant tachyarrhythmias. Taken together, these findings suggest that proarrhythmic effects of hypokalaemia are mostly attributed to increased LV

  2. Assessment of left ventricular myocardial systolic acceleration in diabetic rats using velocity vector imaging.

    PubMed

    Zhang, Haibin; Wei, Zhangrui; Zhu, Xiaoxing; Li, Hongling; Yu, Ming; Duan, Yunyan; Zhu, Ting; Zhang, Jun; Zhou, Xiaodong; Zhu, Miaozhang

    2014-05-01

    The purpose of this study was to investigate how the myocardial acceleration during isovolumic contraction changed in rats with diabetic cardiomyopathy and a normal left ventricular ejection fraction (LVEF) by using velocity vector imaging. Velocity vector imaging was performed in 12 control rats and 15 rats with streptozotocin-induced diabetic cardiomyopathy 12 weeks after streptozotocin injection. The segmental radial displacement, velocity, acceleration, and percent wall thickening were measured at the mid-left ventricular (LV) level. Compared to control rats, rats with cardiomyopathy had a significant decrease in the peak radial acceleration during isovolumic contraction in most segments of the LV wall (including the anterior, anterolateral, inferolateral, and inferior segments; P < .05) but a similar LVEF, fractional shortening, and segmental displacement. Rats with cardiomyopathy also had a significant increase in LV end-diastolic and end-systolic diameters when corrected for body mass (P < .001; P = .003, respectively) and a significant decrease in the radial peak systolic velocities of the inferolateral and inferior wall segments (P < .05). In addition, rats with cardiomyopathy had a significant decrease in the peak radial diastolic acceleration in most segments of the LV wall (except for the anterolateral one; P< .05) but similar peak radial diastolic velocities in all LV wall segments compared to controls. Pathologic examination in rats with cardiomyopathy revealed ultrastructural impairment of the capillary and cardiocyte without any atherosclerotic lesion in the coronary artery compared to control rats. Myocardial acceleration during isovolumic contraction decreases in rats with diabetic cardiomyopathy and a preserved LVEF, suggesting the presence of regional LV systolic dysfunction.

  3. Resveratrol Treatment Reduces Cardiac Progenitor Cell Dysfunction and Prevents Morpho-Functional Ventricular Remodeling in Type-1 Diabetic Rats

    PubMed Central

    Delucchi, Francesca; Berni, Roberta; Frati, Caterina; Cavalli, Stefano; Graiani, Gallia; Sala, Roberto; Chaponnier, Christine; Gabbiani, Giulio; Calani, Luca; Rio, Daniele Del; Bocchi, Leonardo; Lagrasta, Costanza; Quaini, Federico; Stilli, Donatella

    2012-01-01

    Emerging evidence suggests that both adult cardiac cell and the cardiac stem/progenitor cell (CSPC) compartments are involved in the patho-physiology of diabetic cardiomyopathy (DCM). We evaluated whether early administration of Resveratrol, a natural antioxidant polyphenolic compound, in addition to improving cardiomyocyte function, exerts a protective role on (i) the progenitor cell pool, and (ii) the myocardial environment and its impact on CSPCs, positively interfering with the onset of DCM phenotype. Adult Wistar rats (n = 128) with streptozotocin-induced type-1 diabetes were either untreated (D group; n = 54) or subjected to administration of trans-Resveratrol (i.p. injection: 2.5 mg/Kg/day; DR group; n = 64). Twenty-five rats constituted the control group (C). After 1, 3 or 8 weeks of hyperglycemia, we evaluated cardiac hemodynamic performance, and cardiomyocyte contractile properties and intracellular calcium dynamics. Myocardial remodeling and tissue inflammation were also assessed by morphometry, immunohistochemistry and immunoblotting. Eventually, the impact of the diabetic “milieu” on CSPC turnover was analyzed in co-cultures of healthy CSPCs and cardiomyocytes isolated from D and DR diabetic hearts. In untreated animals, cardiac function was maintained during the first 3 weeks of hyperglycemia, although a definite ventricular remodeling was already present, mainly characterized by a marked loss of CSPCs and adult cardiac cells. Relevant signs of ventricular dysfunction appeared after 8 weeks of diabetes, and included: 1) a significant reduction in ±dP/dt in comparison with C group, 2) a prolongation of isovolumic contraction/relaxation times, 3) an impaired contraction of isolated cardiomyocytes associated with altered intracellular calcium dynamics. Resveratrol administration reduced atrial CSPC loss, succeeded in preserving the functional abilities of CSPCs and mature cardiac cells, improved cardiac environment by reducing

  4. Effects of Tribuli saponins on ventricular remodeling after myocardial infarction in hyperlipidemic rats.

    PubMed

    Guo, Yan; Shi, Da-Zhuo; Yin, Hui-Jun; Chen, Ke-Ji

    2007-01-01

    This experiment was designed to determine whether Tribuli saponins (TS) relieve left ventricular remodeling (VR) after myocardial infarction (MI) in a murine hyperlipemia (HL) model. MI and HL models were induced and high and low doses of TS and simvastatin were administrated to the rats. Four weeks later, echocardiographic observation was performed and the left and right ventricular weight index (LVWI, RVWI) was calculated. Echocardiographic results showed that both high dose of TS and simvastatin had a beneficial effect on increasing fractional shortening (FS) and ejection fraction (EF), reducing left ventricular end diastolic volume (LVEDV), systolic volume (LVESV), left ventricular dimension end diastole (LVDd) and systole (LVDs), and decreasing LVWI, as compared to those in the HL-MI model group (p < 0.05, 0.01). Both medicines had little impact on thickness of the anterior and posterior wall. No significant difference was observed between each treatment group (p > 0.05). In conclusion, TS not only lowered serum lipidemia, but also relieved left ventricular remodeling, and improved cardiac function in the early stage after MI.

  5. High rate of right ventricular infarction after ligation of mid left anterior descending artery in rats.

    PubMed

    Samsamshariat, Seyed Ahmad; Movahed, Mohammad-Reza

    2005-01-01

    The left anterior descending artery (LAD) supplies the left ventricle in humans. LAD ligation has been commonly used in rats to induce left ventricular (LV) infarction for research purposes. However, the myocardial supply territories of LAD are not well established in rats. We measured the infarction zone in rats after ligation of the mid-LAD. Twenty-four male Sprague-Dawley rats weighing 300-350 g were selected for LAD ligation for the induction of ischemic cardiomyopathy. The surgery was performed under full anesthesia. Left-sided thoracotomy was performed through cuts in the fifth and sixth ribs. Ligation of the LAD was performed 1 to 2 mm distal to a line between the left border of the pulmonary conus and the right border of the left atrial appendage. LAD was ligated after the first diagonal and septal branches. After 24 h, the hearts were removed and stained with Tetrazolium Tetrachloride (TTC) for the detection of infracted areas. Ligation of LAD induces 85% infarction of the right anterior free wall and anterior right ventricular septum and induces 100% infarction of the anterior free wall of the left ventricle and anterior septum. Infarction after LAD ligation extends all the way to the distal of the ligation site down to the apex of the heart. Mid-LAD ligation after the first septal and diagonal branches causes substantial right ventricular infarction in addition to LV infarct in rats. Therefore, the hemodynamic effect of right ventricle infarct should be considered in research involving LAD ligation in rats.

  6. Prenatal Isolated Ventricular Septal Defect May Not Be Associated with Trisomy 21.

    PubMed

    Shen, Ori; Lieberman, Sari; Farber, Benjamin; Terner, Daniel; Lahad, Amnon; Levy-Lahad, Ephrat

    2014-04-23

    The aim of this study was to examine if isolated fetal ventricular septal defect (VSD) is associated with trisomy 21. One hundred twenty six cases with prenatal VSD diagnosed by a pediatric cardiologist were reviewed. Cases with known risk factors for congenital heart disease, the presence of other major anomalies, soft signs for trisomy 21 or a positive screen test for trisomy 21 were excluded. Ninety two cases formed the study group. None of the cases in the study group had trisomy 21. The upper limit of prevalence for trisomy 21 in isolated VSD is 3%. When prenatal VSD is not associated with other major anomalies, soft markers for trisomy 21 or a positive nuchal translucency or biochemical screen, a decision whether to perform genetic amniocentesis should be individualized. The currently unknown association between isolated VSD and microdeletions and microduplications should be considered when discussing this option.

  7. Effects of an Isolated Complete Right Bundle Branch Block on Mechanical Ventricular Function.

    PubMed

    Zhang, Qin; Xue, Minghua; Li, Zhan; Wang, Haiyan; Zhu, Lei; Liu, Xinling; Meng, Haiyan; Hou, Yinglong

    2015-12-01

    The purpose of this study was to investigate the effects of an isolated complete right bundle branch block on mechanical ventricular function. Two groups of participants were enrolled in this study: a block group, consisting of 98 patients with isolated complete right bundle branch blocks without structural heart disease, and a control group, consisting of 92 healthy adults. The diameter, end-diastolic area, end-systolic area, and right ventricular (RV) fractional area change were obtained to evaluate morphologic and systolic function by 2-dimensional sonographic technology. Systolic and diastolic velocities and time interval parameters were measured to assess mechanical ventricular performance using pulsed wave tissue Doppler imaging. Although there was no significant difference in the RV fractional area change between the patients with blocks and controls, the diameter, end-diastolic area, and end-systolic area of the RV were significantly larger in the patients with blocks (P < .05). In the patients with blocks, the peak velocities during systole and early diastole and the ratio of the peak velocities during early and late diastole decreased. The block group had a prolonged pre-ejection period, electromechanical delay time, and isovolumic relaxation time, a decreased ejection time, and an increased pre-ejection period/ejection time ratio, and the myocardial performance index (Tei index) at the basal RV lateral wall was significantly increased. There were no significant differences in any echocardiographic parameters at different sites of the left ventricle. In patients with isolated complete right bundle branch blocks, systolic and diastolic functions are impaired in the RV, and follow-up is needed. © 2015 by the American Institute of Ultrasound in Medicine.

  8. Effect of Wenxin Granule on Ventricular Remodeling and Myocardial Apoptosis in Rats with Myocardial Infarction

    PubMed Central

    Wu, Aiming; Zhai, Jianying; Zhang, Dongmei; Lou, Lixia; Zhu, Haiyan; Gao, Yonghong; Chai, Limin; Xing, Yanwei; Lv, Xiying; Zhu, Lingqun; Zhao, Mingjing; Wang, Shuoren

    2013-01-01

    Aim. To determine the effect of a Chinese herbal compound named Wenxin Granule on ventricular remodeling and myocardial apoptosis in rats with myocardial infarction (MI). Methods. Male Sprague-Dawley (SD) rats were randomly divided into four groups: the control group, the model group, the metoprolol group, and the Wenxin Granule group (WXKL group) with sample size (n) of 7 rats in each group. An MI model was established in all rats by occlusion of the left anterior descending coronary artery (the control group was without occlusion). Wenxin Granule (1.35 g/kg/day), metoprolol (12 mg/kg/day), and distilled water (5 mL/kg/day for the control and model groups) were administered orally for 4 weeks. Ultrasonic echocardiography was used to examine cardiac structural and functional parameters. Myocardial histopathological changes were observed using haematoxylin and eosin (H&E) dyeing. Myocardial apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) staining. Serum angiotensin II (Ang II) concentration was measured using the enzyme-linked immunosorbent assay (ELISA). Results. It was found that Wenxin Granule could partially reverse ventricular remodeling, improve heart function, alleviate the histopathological damage, inhibit myocardial apoptosis, and reduce Ang II concentration in rats with MI. Conclusions. The results of the current study suggest that Wenxin Granule may be a potential alternative and complementary medicine for the treatment of MI. PMID:23997803

  9. Examination of isolated ventricular noncompaction (hypertrabeculation) as a distinct entity in adults.

    PubMed

    Roberts, William Clifford; Karia, Sumit Jagdish; Ko, Jong Mi; Grayburn, Paul Arthur; George, Betsy Ann; Hall, Shelley Anne; Kuiper, Johannes Jacob; Meyer, Dan Marshall

    2011-09-01

    Three patients (2 women) 36, 45, and 49 years of age underwent cardiac transplantation for what was diagnosed clinically as nonischemic dilated cardiomyopathy. Examination of the transthoracic echocardiogram and explanted heart in each disclosed marked hypertrabeculation involving the free wall of the very dilated left ventricle, a finding consistent with what has been termed "isolated ventricular noncompaction" (IVNC). Although these 3 cases anatomically fulfilled the echocardiographic definition of IVNC, review of previous publications containing gross photographs of the heart suggests that IVNC is overdiagnosed at least morphologically. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Xanthohumol Modulates Calcium Signaling in Rat Ventricular Myocytes: Possible Antiarrhythmic Properties.

    PubMed

    Arnaiz-Cot, Juan Jose; Cleemann, Lars; Morad, Martin

    2017-01-01

    Cardiac arrhythmia is a major cause of mortality in cardiovascular pathologies. A host of drugs targeted to sarcolemmal Na(+), Ca(2+), and K(+) channels has had limited success clinically. Recently, Ca(2+) signaling has been target of pharmacotherapy based on finding that leaky ryanodine receptors elevate local Ca(2+) concentrations causing membrane depolarizations that trigger arrhythmias. In this study, we report that xanthohumol, an antioxidant extracted from hops showing therapeutic effects in other pathologies, suppresses aberrant ryanodine receptor Ca(2+) release. The effects of xanthohumol (5-1000 nM) on Ca(2+) signaling pathways were probed in isolated rat ventricular myocytes incubated with Fluo-4 AM using the perforated patch-clamp technique. We found that 5-50 nM xanthohumol reduced the frequency of spontaneously occurring Ca(2+) sparks (>threefold) and Ca(2+) waves in control myocytes and in cells subjected to Ca(2+) overload caused by the following: 1) exposure to low K(+) solutions, 2) periods of high frequency electrical stimulation, 3) exposures to isoproterenol, or 4) caffeine. At room temperatures, 50-100 nM xanthohumol reduced the rate of relaxation of electrically- or caffeine-triggered Ca(2+)transients, without suppressing ICa, but this effect was small and reversed by isoproterenol at physiologic temperatures. Xanthohumol also suppressed the Ca(2+) content of the SR and its rate of recirculation. The stabilizing effects of xanthohumol on the frequency of spontaneously triggered Ca(2+) sparks and waves combined with its antioxidant properties, and lack of significant effects on Na(+) and Ca(2+) channels, may provide this compound with clinically desirable antiarrhythmic properties.

  11. Core isolation of critical arrhythmia elements for treatment of multiple scar-based ventricular tachycardias.

    PubMed

    Tzou, Wendy S; Frankel, David S; Hegeman, Timothy; Supple, Gregory E; Garcia, Fermin C; Santangeli, Pasquale; Katz, David F; Sauer, William H; Marchlinski, Francis E

    2015-04-01

    Radiofrequency ablation of multiple or unmappable ventricular tachycardias (VTs) remains a challenge with unclear end points. We present our experience with a new strategy isolating core elements of VT circuits. Patients with structural heart disease presenting for VT radiofrequency ablation at 2 centers were included. Strategy involved entrainment/activation mapping if VT was hemodynamically stable, and voltage mapping with electrogram analysis and pacemapping. Core isolation (CI) was performed incorporating putative isthmus and early exit site(s) based on standard criteria. If VT was noninducible, the dense scar (<0.5 mV) region was isolated. Successful CI was defined by exit block (20 mA at 2 ms) within the isolated region. VT inducibility was also assessed. Forty-four patients were included (mean age, 63; 95% male; 73% ischemic cardiomyopathy; mean left ventricular ejection fraction, 31%; 68% with multiple unstable VTs [mean, 3+2]). CI area was 11+12 versus 55+40 cm(2) total scar area. Additional substrate modification was performed in 27 (61%), and epicardial radiofrequency ablation was performed in 4 (9%) patients. CI was achieved in 37 (84%) and led to better VT-free survival (log rank P=0.013). CI is a novel strategy with a discrete and measurable end point beyond VT inducibility to treat patients with multiple or unmappable VTs. The CI region can be selected based on standard characterization of suspected VT isthmus surrogates thus limiting ablation target size. Exit block within the isolated area is achievable in most and may further improve long-term success. © 2015 American Heart Association, Inc.

  12. The Preventive Effects of Neural Stem Cells and Mesenchymal Stem Cells Intra-ventricular Injection on Brain Stroke in Rats.

    PubMed

    Hosseini, Seyed Mojtaba; Samimi, Nastaran; Farahmandnia, Mohammad; Shakibajahromi, Benafshe; Sarvestani, Fatemeh Sabet; Sani, Mahsa; Mohamadpour, Masoomeh

    2015-09-01

    Stroke is one of the most important causes of disability in developed countries and, unfortunately, there is no effective treatment for this major problem of central nervous system (CNS); cell therapy may be helpful to recover this disease. In some conditions such as cardiac surgeries and neurosurgeries, there are some possibilities of happening brain stroke. Inflammation of CNS plays an important role in stroke pathogenesis, in addition, apoptosis and neural death could be the other reasons of poor neurological out come after stroke. In this study, we examined the preventive effects of the neural stem cells (NSCs) and mesenchymal stem cells (MSCs) intra-ventricular injected on stroke in rats. The aim of this study was to investigate the preventive effects of neural and MSCs for stroke in rats. The MSCs were isolated by flashing the femurs and tibias of the male rats with appropriate media. The NSCs were isolated from rat embryo ganglion eminence and they cultured NSCs media till the neurospheres formed. Both NSCs and MSCs were labeled with PKH26-GL. One day before stroke, the cells were injected into lateral ventricle stereotactically. During following for 28 days, the neurological scores indicated that there are better recoveries in the groups received stem cells and they had less lesion volume in their brain measured by hematoxylin and eosin staining. Furthermore, the activities of caspase-3 were lower in the stem cell received groups than control group and the florescent microscopy images showed that the stem cells migrated to various zones of the brains. Both NSCs and MSCs are capable of protecting the CNS against ischemia and they may be good ways to prevent brain stroke consequences situations.

  13. Metabolites of MDMA induce oxidative stress and contractile dysfunction in adult rat left ventricular myocytes.

    PubMed

    Shenouda, Sylvia K; Varner, Kurt J; Carvalho, Felix; Lucchesi, Pamela A

    2009-03-01

    Repeated administration of 3,4-methylenedioxymethamphetamine (MDMA) (ecstasy) produces eccentric left ventricular (LV) dilation and diastolic dysfunction. While the mechanism(s) underlying this toxicity are unknown, oxidative stress plays an important role. MDMA is metabolized into redox cycling metabolites that produce superoxide. In this study, we demonstrated that metabolites of MDMA induce oxidative stress and contractile dysfunction in adult rat left ventricular myocytes. Metabolites of MDMA used in this study included alpha-methyl dopamine, N-methyl alpha-methyl dopamine and 2,5-bis(glutathion-S-yl)-alpha-MeDA. Dihydroethidium was used to detect drug-induced increases in reactive oxygen species (ROS) production in ventricular myocytes. Contractile function and changes in intracellular calcium transients were measured in paced (1 Hz), Fura-2 AM loaded, myocytes using the IonOptix system. Production of ROS in ventricular myocytes treated with MDMA was not different from control. In contrast, all three metabolites of MDMA exhibited time- and concentration-dependent increases in ROS that were prevented by N-acetyl-cysteine (NAC). The metabolites of MDMA, but not MDMA alone, significantly decreased contractility and impaired relaxation in myocytes stimulated at 1 Hz. These effects were prevented by NAC. Together, these data suggest that MDMA-induced oxidative stress in the left ventricle can be due, at least in part, to the metabolism of MDMA to redox active metabolites.

  14. Ventricular fibrillation-induced cardiac arrest in the rat as a model of global cerebral ischemia

    PubMed Central

    Dave, Kunjan R.; Della-Morte, David; Saul, Isabel; Prado, Ricardo; Perez-Pinzon, Miguel A.

    2013-01-01

    Cardiopulmonary arrest remains one of the leading causes of death and disability in Western countries. Although ventricular fibrillation (VF) models in rodents mimic the “square wave” type of insult (rapid loss of pulse and pressure) commonly observed in adult humans at the onset of cardiac arrest (CA), they are not popular because of the complicated animal procedure, poor animal survival and thermal injury. Here we present a modified, simple, reliable, ventricular fibrillation-induced rat model of CA that will be useful in studying mechanisms of CA-induced delayed neuronal death as well as the efficacy of neuroprotective drugs. CA was induced in male Sprague Dawley rats using a modified method of von Planta et al. In brief, VF was induced in anesthetized, paralyzed, mechanically ventilated rats by an alternating current delivered to the entrance of the superior vena cava into the heart. Resuscitation was initiated by administering a bolus injection of epinephrine and sodium bicarbonate followed by mechanical ventilation and manual chest compressions and countershock with a 10-J DC current. Neurologic deficit score was higher in the CA group compared to the sham group during early reperfusion periods, suggesting brain damage. Significant damage in CA1 hippocampus (21% normal neurons compared to control animals) was observed following histopathological assessment at seven days of reperfusion. We propose that this method of VF-induced CA in rat provides a tool to study the mechanism of CA-induced neuronal death without compromising heart functions. PMID:24187598

  15. The relationship between ventricular dilatation, neuropathological and neurobehavioural changes in hydrocephalic rats

    PubMed Central

    2012-01-01

    Background The motor and cognitive deficits observed in hydrocephalus are thought to be due to axonal damage within the periventricular white matter. This study was carried out to investigate the relationship between ventricular size, cellular changes in brain, and neurobehavioural deficits in rats with experimental hydrocephalus. Methods Hydrocephalus was induced in three-week old rats by intracisternal injection of kaolin. Behavioural and motor function were tested four weeks after hydrocephalus induction and correlated to ventricular enlargement which was classified into mild, moderate or severe. Gross brain morphology, routine histology and immunohistochemistry for oligodendrocytes (CNPase), microglia (Iba-1) and astrocytes (GFAP) were performed to assess the cellular changes. Results Decreases in open field activity and forelimb grip strength in hydrocephalus correlated with the degree of ventriculomegaly. Learning in Morris water maze was significantly impaired in hydrocephalic rats. Gradual stretching of the ependymal layer, thinning of the corpus callosum, extracellular oedema and reduced cortical thickness were observed as the degree of ventriculomegaly increased. A gradual loss of oligodendrocytes in the corpus callosum and cerebral cortex was most marked in the severely-hydrocephalic brains, whereas the widespread astrogliosis especially in the subependymal layer was most marked in the brains with mild hydrocephalus. Retraction of microglial processes and increase in Iba-1 immunoreactivity in the white matter was associated ventriculomegaly. Conclusions In hydrocephalic rats, oligodendrocyte loss, microglia activation, astrogliosis in cortical areas and thinning of the corpus callosum were associated with ventriculomegaly. The degree of ventriculomegaly correlated with motor and cognitive deficits. PMID:22938200

  16. Epicardial wavefronts arise from widely distributed transient sources during ventricular fibrillation in the isolated swine heart

    NASA Astrophysics Data System (ADS)

    Rogers, J. M.; Walcott, G. P.; Gladden, J. D.; Melnick, S. B.; Ideker, R. E.; Kay, M. W.

    2008-01-01

    It has been proposed that ventricular fibrillation (VF) waves emanate from stable localized sources, often called 'mother rotors'. However, evidence for the existence of these rotors is conflicting. Using a new panoramic optical mapping system that can image nearly the entire ventricular epicardium, we recently excluded epicardial mother rotors as the drivers of Wiggers' stage II VF in the isolated swine heart. Furthermore, we were unable to find evidence that VF requires sustained intramural sources. The present study was designed to test the following hypotheses: (i) VF is driven by a specific region, and (ii) rotors that are long-lived, though not necessarily permanent, are the primary generators of VF wavefronts. Using panoramic optical mapping, we mapped VF wavefronts from six isolated swine hearts. Wavefronts were tracked to characterize their activation pathways and to locate their originating sources. We found that the wavefronts that participate in epicardial re-entry were not confined to a compact region; rather they activated the entire epicardial surface. New wavefronts feeding into the epicardial activation pattern were generated over the majority of the epicardium and almost all of them were associated with rotors or repetitive breakthrough patterns that lasted for less than 2 s. These findings indicate that epicardial wavefronts in this model are generated by many transitory epicardial sources distributed over the entire surface of the heart.

  17. The herbal drug Catuama reverts and prevents ventricular fibrillation in the isolated rabbit heart.

    PubMed

    Pontieri, Vera; Neto, Augusto Scalabrini; de França Camargo, André Ferrari; Koike, Marcia Kiyomi; Velasco, Irineu Tadeu

    2007-01-01

    Catuama, an herbal drug very popular in Brazil, was tested on the reversion and prevention of ventricular fibrillation (VF) in the isolated rabbit heart. Catuama (a mixture of Trichilia catigua, Paullinia cupana, Ptychopetalum olacoides, and Zinziber officinalis) was perfused in the isolated perfused rabbit heart. Its effects on intraventricular conduction, heart rate, and monophasic action potential (MAP) duration were evaluated, and sustained VF was induced. The effects on reversion and reinduction of arrhythmia were observed, and new measures were taken in the hearts that reverted. Catuama and T catigua reverted VF in all hearts, prevented reinduction, and prolonged intraventricular conduction. Catuama prolonged MAP phase 2. On the other hand, P cupana reverted VF in 3 of 5 hearts, but depressed automatism, prolonged MAP phase 3, and did not prevent reinduction. Catuama reverted and prevented VF in this model. T catigua extract is probably the main agent responsible for the beneficial actions observed. Further studies are now in progress to clarify these actions.

  18. Ventricular-subcutaneous shunt for the treatment of experimental hydrocephalus in young rats: technical note.

    PubMed

    Santos, Marcelo Volpon; Garcia, Camila Araujo Bernardino; Jardini, Evelise Oliveira; Romeiro, Thais Helena; da Silva Lopes, Luiza; Machado, Hélio Rubens; de Oliveira, Ricardo Santos

    2016-08-01

    Hydrocephalus is a complex disease that affects cerebrospinal fluid (CSF) dynamics and is very common in children. To this date, CSF shunting is still the standard treatment for childhood hydrocephalus, but, nevertheless, the effects of such an operation on the developing brain are widely unknown. To help overcome this, experimental models of CSF shunts are surely very useful tools. The objective of this study was to describe a feasible and reliable technique of an adapted ventricular-subcutaneous shunt for the treatment of kaolin-induced hydrocephalus in young rats. We developed a ventricular-subcutaneous shunt (VSCS) technique which was used in 31 Wistar young rats with kaolin-induced hydrocephalus. Hydrocephalus was induced at 7 days of age, and shunt implantation was performed 7 days later. Our technique used a 0.7-mm gauge polypropylene catheter tunneled to a subcutaneous pocket created over the animal's back and inserted into the right lateral ventricle. All animals were sacrificed 14 days after shunt insertion. Twenty-four rats survived and remained well until the study was ended. No major complications were seen. Their weight gain went back to normal. They all underwent ambulatory behavioral testing prior and after VSCS, which showed improvement in their motor skills. We have also obtained magnetic resonance (MR) scans of 16 pups confirming reduction of ventricular size after shunting and indicating effective treatment. Histopathological analysis of brain samples before and after shunting showed reversion of ependymal and corpus callosum disruption, as well as fewer reactive astrocytes in shunted animals. An experimental CSF shunt technique was devised. Excessive CSF of hydrocephalic rats is diverted into the subcutaneous space where it can be resorbed. This technique has a low complication rate and is effective. It might be applied to various types of experimental studies involving induction and treatment of hydrocephalus.

  19. Estrogen fails to facilitate resuscitation from ventricular fibrillation in male rats

    PubMed Central

    Miao, Yang; Edelheit, Ari; Velmurugan, Sathya; Borovnik-Lesjak, Vesna; Radhakrishnan, Jeejabai; Gazmuri, Raúl J

    2015-01-01

    Administration of 17β-estradiol has been shown to exert myocardial protective effects in hemorrhagic shock. We hypothesized that similar protective effects could help improve resuscitation from cardiac arrest. Three series of 18, 40, and 12 rats each, underwent ventricular fibrillation for 8 minutes followed by 8 minutes of chest compression and delivery of electrical shocks. In series-1, rats were randomized 1:1 to receive a bolus dose of 17β-estradiol (1 mg/kg) or 0.9% NaCl before chest compression; in series-2, rats were randomized 1:1:1:1 to receive a continuous infusion of 0.9% NaCl or a 17β-estradiol solution designed to attain a plasma level of 100, 102, or 104 nM during chest compression; and in series-3, rats were randomized 1:1 to receive a continuous infusion of 17β-estradiol to attain a plasma level of 102 nM or 0.9% NaCl during chest compression, providing inotropic support during the post-resuscitation interval using dobutamine infusion. 17β-estradiol failed to facilitate resuscitation in each of the 3 series. In series-1 and series-2, resuscitability and short-term survival was reduced in 17β-estradiol groups attaining statistical significance in series-2 when the three 17β-estradiol groups were combined (p = 0.035). In series-3, all rats were resuscitated and survived for 180 minutes aided by dobutamine which partially reversed post-resuscitation myocardial dysfunction but without additional benefits on myocardial function in the 17β-estradiol group. The present study failed to support a beneficial effect of 17β-estradiol for resuscitation from cardiac arrest and raised the possibility of detrimental cardiac effects compromising initial resuscitability and subsequent survival in a male rat model of ventricular fibrillation and closed chest resuscitation. PMID:26045892

  20. Bi-ventricular finite element model of right ventricle overload in the healthy rat heart.

    PubMed

    Masithulela, Fulufhelo

    2016-11-25

    The recognition of RV overpressure is critical to human life, as this may signify morbidity and mortality. Right ventricle (RV) dysfunction is understood to have an impact on the performance of the left ventricle (LV), but the mechanisms remain poorly understood. It is understood that ventricular compliance has the ability to affect cardiac performance. In this study, a bi-ventricular model of the rat heart was used in preference to other, single-ventricle models. Finite element analysis (FEA) of the bi-ventricular model provides important information on the function of the healthy heart. The passive myocardium was modelled as a nearly incompressible, hyperelastic, transversely isotropic material using finite element (FE) methods. Bi-ventricular geometries of healthy rat hearts reconstructed from magnetic resonance images were imported in Abaqus©. In simulating the normal passive filling of the rat heart, pressures of 4.8 kPa and 0.0098 kPa were applied to the inner walls of the LV and RV respectively. In addition, to simulate the overpressure of the RV, pressures of 2.4 kPa and 4.8 kPa were applied to the endocardial walls of the LV and RV respectively. As boundary conditions, the circumferential and longitudinal displacements at the base were set to zero. The radial displacements at the base were left free. The results show that the average circumferential stress at the mid-wall in the overloaded model increased from 2.8 kPa to 18.2 kPa. The average longitudinal stress increased from 1.5 kPa to 9.7 kPa. Additionally, in the radial direction, the average stress increased from 0.1 kPa to 0.6 kPa in the mid-wall. The average circumferential strain was found to be 0.138 and 0.100 on the endocardium of the over pressured and healthy model respectively. The average circumferential stress at the epicardium, mid-wall and endocardium in the case of a normal heart is 10 times lower than in the overloaded heart model. The finite analysis method is able to provide

  1. Effects of tedisamil (KC-8857) on cardiac electrophysiology and ventricular fibrillation in the rabbit isolated heart.

    PubMed

    Chi, L; Park, J L; Friedrichs, G S; Banglawala, Y A; Perez, M A; Tanhehco, E J; Lucchesi, B R

    1996-03-01

    1. The direct cardiac electrophysiological and antifibrillatory actions of tedisamil (KC-8857) were studied in rabbit isolated hearts. 2. Tedisamil (1, 3, and 10 microM), prolonged the ventricular effective refractory period (VRP) from 120 +/- 18 ms (baseline) to 155 +/- 19, 171 +/- 20, and 205 +/- 14 ms, respectively. Three groups of isolated hearts (n = 6 each) were used to test the antifibrillatory action of tedisamil. Hearts were perfused with 1.25 microM pinacidil, a KATP channel activator. Hearts were subjected to hypoxia for 12 min followed by 40 min of reoxygenation. Ventricular fibrillation (VF) developed during hypoxia and reoxygenation in both the control and 1 microM tedisamil-treated groups (5/6 and 4/6, respectively). Tedisamil (3 microM) reduced the incidence of VF (0/6, P = 0.007 vs. control). 3. In a separate group of hearts, VF was initiated by electrical stimulation. The administration of 0.3 ml of 10 mM tedisamil, via the aortic cannula, terminated VF in all hearts, converting them to normal sinus rhythm. 4. Tedisamil (3 microM) reversed pinacidil-induced negative inotropic effects in rabbit isolated atrial muscle which were equilibrated under normoxia, as well as in atrial muscle subjected to hypoxia and reoxygenation. 5. The results demonstrate a direct antifibrillatory action of tedisamil in vitro. The mechanism responsible for the observed effects may involve modulation by tedisamil of the cardiac ATP-regulated potassium channel, in addition to its antagonism of IK and Ito.

  2. Effects of tedisamil (KC-8857) on cardiac electrophysiology and ventricular fibrillation in the rabbit isolated heart.

    PubMed Central

    Chi, L.; Park, J. L.; Friedrichs, G. S.; Banglawala, Y. A.; Perez, M. A.; Tanhehco, E. J.; Lucchesi, B. R.

    1996-01-01

    1. The direct cardiac electrophysiological and antifibrillatory actions of tedisamil (KC-8857) were studied in rabbit isolated hearts. 2. Tedisamil (1, 3, and 10 microM), prolonged the ventricular effective refractory period (VRP) from 120 +/- 18 ms (baseline) to 155 +/- 19, 171 +/- 20, and 205 +/- 14 ms, respectively. Three groups of isolated hearts (n = 6 each) were used to test the antifibrillatory action of tedisamil. Hearts were perfused with 1.25 microM pinacidil, a KATP channel activator. Hearts were subjected to hypoxia for 12 min followed by 40 min of reoxygenation. Ventricular fibrillation (VF) developed during hypoxia and reoxygenation in both the control and 1 microM tedisamil-treated groups (5/6 and 4/6, respectively). Tedisamil (3 microM) reduced the incidence of VF (0/6, P = 0.007 vs. control). 3. In a separate group of hearts, VF was initiated by electrical stimulation. The administration of 0.3 ml of 10 mM tedisamil, via the aortic cannula, terminated VF in all hearts, converting them to normal sinus rhythm. 4. Tedisamil (3 microM) reversed pinacidil-induced negative inotropic effects in rabbit isolated atrial muscle which were equilibrated under normoxia, as well as in atrial muscle subjected to hypoxia and reoxygenation. 5. The results demonstrate a direct antifibrillatory action of tedisamil in vitro. The mechanism responsible for the observed effects may involve modulation by tedisamil of the cardiac ATP-regulated potassium channel, in addition to its antagonism of IK and Ito. Images Figure 9 PMID:8882624

  3. A chloride current component induced by hypertrophy in rat ventricular myocytes.

    PubMed

    Bénitah, J P; Gómez, A M; Delgado, C; Lorente, P; Lederer, W J

    1997-05-01

    The effect of hypertrophy on membrane currents of rat left ventricular myocytes was studied with the whole cell voltage-clamp method. We found that the slope of the total time-independent current density-voltage relationship was increased in hypertrophied cells. No change in the zero-current potential was observed. Surprisingly, the dominant time-independent current, the inward rectifier K+ current (measured as the Ba(2+)-sensitive current density) was unchanged. We therefore investigated the identity of the outwardly rectifying Ba(2+)-resistant current seen in the hypertrophied rat ventricular myocytes but not present in control cells. We found that this current 1) was not carried by monovalent cations, 2) was partially blocked by anthracene-9-carboxylic acid (9-AC), and 3) was sensitive to variations in extracellular Cl concentration. These findings are consistent with the current being carried at least partially by Cl-. The presence of an additional Cl(-)-dependent component in hypertrophied cells is supported by the actions of 9-AC on the measured action potentials (APs). 9-AC had no effect on control cells APs but prolonged hypertrophied cell APs. We conclude that a Cl- current component develops in hypertrophied rat heart cells. This component appears to shorten the AP duration and might thus provide protection from cardiac arrhythmias.

  4. ET-receptor antagonism, myocardial gene expression, and ventricular remodeling during CHF in rats.

    PubMed

    Oie, E; Bjønerheim, R; Grogaard, H K; Kongshaug, H; Smiseth, O A; Attramadal, H

    1998-09-01

    Both myocardial and plasma endothelin-1 (ET-1) are elevated in congestive heart failure (CHF). However, the role played by endogenous ET-1 in the progression of CHF remains unknown. The aim of the present study was to investigate and correlate myocardial gene expression programs and left ventricular (LV) remodeling during chronic ET-receptor antagonism in CHF rats. After ligation of the left coronary artery, rats were randomized to oral treatment with a nonselective ET-receptor antagonist (bosentan, 100 mg . kg-1 . day-1, n = 11) or vehicle (saline, n = 13) for 15 days, starting 24 h after induction of myocardial infarction. Bosentan substantially attenuated LV dilatation during postinfarction failure as evaluated by echocardiography. Furthermore, bosentan decreased LV systolic and end-diastolic pressures and increased fractional shortening. Myocardial expression of preproET-1 mRNA and a fetal gene program characteristic of myocardial hypertrophy were increased in the CHF rats and were not affected by bosentan. Consistently, right ventricular-to-body weight ratios, diameters of cardiomyocytes, and echocardiographic analysis demonstrated a sustained hypertrophic response and a normalized relative wall thickness after intervention with bosentan. Thus the modest reduction of preload and afterload provided by bosentan substantially attenuates LV dilatation, causing improved pressure-volume relationships. However, the compensatory hypertrophic response was not altered by ET-receptor antagonism. Therefore, ET-1 does not appear to play a crucial role in the mechanisms of myocardial hypertrophy during the early phase of postinfarction failure.

  5. Systems approach to the study of stretch and arrhythmias in right ventricular failure induced in rats by monocrotaline

    PubMed Central

    Benoist, David; Stones, Rachel; Benson, Alan P.; Fowler, Ewan D.; Drinkhill, Mark J.; Hardy, Matthew E.L.; Saint, David A.; Cazorla, Olivier; Bernus, Olivier; White, Ed

    2014-01-01

    We demonstrate the synergistic benefits of using multiple technologies to investigate complex multi-scale biological responses. The combination of reductionist and integrative methodologies can reveal novel insights into mechanisms of action by tracking changes of in vivo phenomena to alterations in protein activity (or vice versa). We have applied this approach to electrical and mechanical remodelling in right ventricular failure caused by monocrotaline-induced pulmonary artery hypertension in rats. We show arrhythmogenic T-wave alternans in the ECG of conscious heart failure animals. Optical mapping of isolated hearts revealed discordant action potential duration (APD) alternans. Potential causes of the arrhythmic substrate; structural remodelling and/or steep APD restitution and dispersion were observed, with specific remodelling of the Right Ventricular Outflow Tract. At the myocyte level, [Ca2+]i transient alternans were observed together with decreased activity, gene and protein expression of the sarcoplasmic reticulum Ca2+-ATPase (SERCA). Computer simulations of the electrical and structural remodelling suggest both contribute to a less stable substrate. Echocardiography was used to estimate increased wall stress in failure, in vivo. Stretch of intact and skinned single myocytes revealed no effect on the Frank-Starling mechanism in failing myocytes. In isolated hearts acute stretch-induced arrhythmias occurred in all preparations. Significant shortening of the early APD was seen in control but not failing hearts. These observations may be linked to changes in the gene expression of candidate mechanosensitive ion channels (MSCs) TREK-1 and TRPC1/6. Computer simulations incorporating MSCs and changes in ion channels with failure, based on altered gene expression, largely reproduced experimental observations. PMID:25016242

  6. Comparison of sarcolemmal calcium channel current in rabbit and rat ventricular myocytes.

    PubMed Central

    Yuan, W; Ginsburg, K S; Bers, D M

    1996-01-01

    1. Fundamental properties of Ca2+ channel currents in rat and rabbit ventricular myocytes were measured using whole cell voltage clamp. 2. In rat, as compared with rabbit myocytes, Ca2+ channel current (ICa) was half-activated at about 10 mV more negative potential, decayed slower, was half-inactivated (in steady state) at about 5 mV more positive potential, and recovered faster from inactivation. 3. These features result in a larger steady-state window current in rat, and also suggest that under comparable voltage clamp conditions, including action potential (AP) clamp, more Ca2+ influx would be expected in rat myocytes. 4. Ca2+ channel current carried by Na+ and Cs+ in the absence of divalent ions (Ins) also activated at more negative potential and decayed more slowly in rat. 5. The reversal potential for Ins was 6 mV more positive in rabbit, consistent with a larger permeability ratio (PNa/PCs) in rabbit than in rat. ICa also reversed at slightly more positive potentials in rabbit (such that PCa/PCs might also be higher). 6. Ca2+ influx was calculated by integration of ICa evoked by voltage clamp pulses (either square pulses or pulses based on recorded rabbit or rat APs). For a given clamp waveform, the Ca2+ influx was up to 25% greater in rat, as predicted from the fundamental properties of ICa and Ins. 7. However, the longer duration of the AP in rabbit myocytes compensated for the difference in influx, such that the integrated Ca2+ influx via ICa in response to the species-appropriate waveform was about twice as large as that seen in rat. PMID:8799895

  7. Panoramic optical mapping reveals continuous epicardial reentry during ventricular fibrillation in the isolated swine heart.

    PubMed

    Rogers, Jack M; Walcott, Gregory P; Gladden, James D; Melnick, Sharon B; Kay, Matthew W

    2007-02-01

    During ventricular fibrillation (VF), activation waves are fragmented and the heart cannot contract synchronously. It has been proposed that VF waves emanate from stable sources ("mother rotors"). Previously, we used new optical mapping technology to image VF wavefronts from nearly the entire epicardial surface of six isolated swine hearts. We found that VF was not driven by epicardial rotors, but could not exclude the presence of stable rotors hidden within the ventricular walls. Here, we use graph theoretic analysis to show that, in all 17 VF episodes we analyzed, it was always possible to trace sequences of wavefronts through series of fragmentation and collision events from the beginning to the end of the episode. The set of wavefronts that were so related (the dominant component) consisted of 92%+/-1% of epicardial wavefronts. Because each such wavefront sequence constitutes a continuous activation front, this finding shows that complete reentrant pathways were always present on the epicardial surface and therefore, that wavefront infusion from nonepicardial sources was not strictly necessary for VF maintenance. These data suggest that VF in this model is not driven by localized sources; thus, new anti-VF treatments designed to target such sources may be less effective than global interventions.

  8. Dynamic sympathetic regulation of left ventricular contractility studied in the isolated canine heart.

    PubMed

    Miyano, H; Nakayama, Y; Shishido, T; Inagaki, M; Kawada, T; Sato, T; Miyashita, H; Sugimachi, M; Alexander, J; Sunagawa, K

    1998-08-01

    We investigated the dynamic sympathetic regulation of left ventricular end-systolic elastance (Ees) using an isolated canine ventricular preparation with functioning sympathetic nerves intact. We estimated the transfer function from both stellate ganglion stimulation to Ees and ganglion stimulation to heart rate (HR) for both left and right ganglia by means of the white noise approach and transformed those transfer functions into corresponding step responses. The HR response was much larger with right sympathetic stimulation than with left sympathetic stimulation (4.3 +/- 1.4 vs. 0.7 +/- 0.6 beats . min-1 . Hz-1, P < 0.01). In contrast, the Ees responses without pacing were not significantly different between left and right sympathetic stimulation (0.72 +/- 0.34 vs. 0.76 +/- 0. 42 mmHg . ml-1 . Hz-1). Fixed-rate pacing significantly decreased the Ees response to right sympathetic stimulation (0.53 +/- 0.43 mmHg . ml-1 . Hz-1, P < 0.01), but not to left sympathetic stimulation (0.67 +/- 0.32 mmHg . ml-1 . Hz-1, not significant). Although the mechanism by which the sympathetic nervous system regulates cardiac contractility is different depending on whether the left or right sympathetic nerves are activated, this difference does not affect the apparent response of Ees to dynamic sympathetic stimulation.

  9. Endothelin-1 and ET receptors impair left ventricular function by mediated coronary arteries dysfunction in chronic intermittent hypoxia rats.

    PubMed

    Wang, Jin-Wei; Li, Ai-Ying; Guo, Qiu-Hong; Guo, Ya-Jing; Weiss, James W; Ji, En-Sheng

    2017-01-01

    Obstructive sleep apnea (OSA) results in cardiac dysfunction and vascular endothelium injury. Chronic intermittent hypoxia (CIH), the main characteristic of OSAS, is considered to be mainly responsible for cardiovascular system impairment. This study is aimed to evaluate the role of endothelin-1(ET-1) system in coronary injury and cardiac dysfunction in CIH rats. In our study, Sprague-Dawley rats were exposed to CIH (FiO2 9% for 1.5 min, repeated every 3 min for 8 h/d, 7 days/week for 3 weeks). After 3 weeks, the left ventricular developed pressure (LVDP) and coronary resistance (CR) were measured with the langendorff mode in isolated hearts. Meanwhile, expressions of ET-1 and ET receptors were detected by immunohistochemical and western blot, histological changes were also observed to determine effects of CIH on coronary endothelial cells. Results suggested that decreased LVDP level combined with augmented coronary resistance was exist in CIH rats. CIH could induce endothelial injury and endothelium-dependent vasodilatation dysfunction in the coronary arteries. Furthermore, ET-1 and ETA receptor expressions in coronary vessels were increased after CIH exposure, whereas ETB receptors expression was decreased. Coronary contractile response to ET-1 in both normoxia and CIH rats was inhibited by ETA receptor antagonist BQ123. However, ETB receptor antagonist BQ788 enhanced ET-1-induced contractile in normoxia group, but had no significant effects on CIH group. These results indicate that CIH-induced cardiac dysfunction may be associated with coronary injury. ET-1 plays an important role in coronary pathogenesis of CIH through ETA receptor by mediating a potent vasoconstrictor response. Moreover, decreased ETB receptor expression that leads to endothelium-dependent vasodilatation decline, might be also participated in coronary and cardiac dysfunction.

  10. Paraplegia increased cardiac NGF content, sympathetic tonus, and the susceptibility to ischemia-induced ventricular tachycardia in conscious rats

    PubMed Central

    Lujan, Heidi L.; Chen, Ying; DiCarlo, Stephen E.

    2009-01-01

    Midthoracic spinal cord injury is associated with ventricular arrhythmias that are mediated, in part, by enhanced cardiac sympathetic activity. Furthermore, it is well known that sympathetic neurons have a lifelong requirement for nerve growth factor (NGF). NGF is a neurotrophin that supports the survival and differentiation of sympathetic neurons and enhances target innervation. Therefore, we tested the hypothesis that paraplegia is associated with an increased cardiac NGF content, sympathetic tonus, and susceptibility to ischemia-induced ventricular tachyarrhythmias. Intact and paraplegic (6–9 wk posttransection, T5 spinal cord transection) rats were instrumented with a radiotelemetry device for recording arterial pressure, temperature, and ECG, and a snare was placed around the left main coronary artery. Following recovery, the susceptibility to ventricular arrhythmias (coronary artery occlusion) was determined in intact and paraplegic rats. In additional groups of matched intact and paraplegic rats, cardiac nerve growth factor content (ELISA) and cardiac sympathetic tonus were determined. Paraplegia, compared with intact, increased cardiac nerve growth factor content (2,146 ± 286 vs. 180 ± 36 pg/ml, P < 0.05) and cardiac sympathetic tonus (154 ± 4 vs. 68 ± 4 beats/min, P < 0.05) and decreased the ventricular arrhythmia threshold (3.6 ± 0.2 vs. 4.9 ± 0.2 min, P < 0.05). Thus altered autonomic behavior increases the susceptibility to ventricular arrhythmias in paraplegic rats. PMID:19286942

  11. The Electrophysiological Effects of Qiliqiangxin on Cardiac Ventricular Myocytes of Rats

    PubMed Central

    Wei, Yidong; Liu, Xiaoyu; Wei, Haidong; Hou, Lei; Che, Wenliang; The, Erlinda; Li, Gang; Jhummon, Muktanand Vikash; Wei, Wanlin

    2013-01-01

    Qiliqiangxin, a Chinese herb, represents the affection in Ca channel function of cardiac myocytes. It is unknown whether Qiliqiangxin has an effect on Na current and K current because the pharmacological actions of this herb's compound are very complex. We investigated the rational usage of Qiliqiangxin on cardiac ventricular myocytes of rats. Ventricular myocytes were exposed acutely to 1, 10, and 50 mg/L Qiliqiangxin, and whole cell patch-clamp technique was used to study the acute effects of Qiliqiangxin on Sodium current (I Na), outward currents delayed rectifier outward K+ current (I K), slowly activating delayed rectifier outward K+ current (I Ks), transient outward K+ current (I to), and inward rectifier K+ current (I K1). Qiliqiangxin can decrease I Na by 28.53% ± 5.98%, and its IC50 was 9.2 mg/L. 10 and 50 mg/L Qiliqiangxin decreased by 37.2% ± 6.4% and 55.9% ± 5.5% summit current density of I to. 10 and 50 mg/L Qiliqiangxin decreased I Ks by 15.51% ± 4.03% and 21.6% ± 5.6%. Qiliqiangxin represented a multifaceted pharmacological profile. The effects of Qiliqiangxin on Na and K currents of ventricular myocytes were more profitable in antiarrhythmic therapy in the clinic. We concluded that the relative efficacy of Qiliqiangxin was another choice for the existing antiarrhythmic therapy. PMID:24250713

  12. Chronic nonocclusive coronary artery constriction in rats. Beta-adrenoceptor signal transduction and ventricular failure.

    PubMed Central

    Meggs, L G; Huang, H; Li, P; Capasso, J M; Anversa, P

    1991-01-01

    To determine the effects of chronic coronary artery constriction on the relationship between cardiac function and regulation of beta-adrenoceptor signal transduction, the left main coronary artery was narrowed in rats and the animals were killed 5 mo later. An average reduction in coronary luminal diameter of 44% was obtained and this change resulted in an increase in left ventricular end-diastolic pressure and a decrease in positive and negative dP/dt. Significant increases in left and right ventricular weights indicative of global cardiac hypertrophy were observed. Radioligand binding studies of beta-adrenoreceptors, agonist-stimulated adenylate cyclase activity, and ADP ribosylation of 45-kD substrate by cholera toxin were all depressed in the failing left ventricle. In contrast, in the hypertrophic non-failing right ventricle, beta-adrenoreceptor density was preserved and receptor antagonist affinity was increased. In spite of these findings at the receptor level, agonist stimulated cyclic AMP generation was reduced in the right ventricular myocardium. The quantity of the 45-kD substrate was also decreased. In conclusion, longterm nonocclusive coronary artery stenosis of moderate degree has profound detrimental effects on the contractile performance of the heart in association with marked attenuation of adrenergic support mechanisms. Images PMID:1661293

  13. Atelectasis causes vascular leak and lethal right ventricular failure in uninjured rat lungs.

    PubMed

    Duggan, Michelle; McCaul, Conán L; McNamara, Patrick J; Engelberts, Doreen; Ackerley, Cameron; Kavanagh, Brian P

    2003-06-15

    During mechanical ventilation, lung recruitment attenuates injury caused by high VT, improves oxygenation, and may optimize pulmonary vascular resistance (PVR). We hypothesized that ventilation without recruitment would induce injury in otherwise healthy lungs. Anesthetized rats were ventilated with conventional mechanical ventilation (VT 8 ml/kg; respiratory frequency 40 per minute) and 21% inspired oxygen, with or without a recruitment strategy consisting of recruitment maneuvers plus positive end-expiratory pressure, in the presence or absence of a laparotomy. Additional experiments examined the impact of atelectasis on right ventricular function using echocardiography, as well as functional residual capacity and PVR. Lack of recruitment resulted in reduced overall survival (59% nonrecruited vs. 100% recruited, p < 0.05), increased microvascular leak, greater impairment of oxygenation and lung compliance, increased PVR, and elevated plasma lactate. Echocardiography demonstrated that right ventricular dysfunction occurred in the absence of recruitment. Finally, samples from nonrecruited lungs demonstrated ultrastructural evidence of microvascular endothelial disruption. Although such effects clearly do not occur with comparable magnitude in the clinical context, the current data suggest novel mechanisms (microvascular leak, right ventricular dysfunction) whereby derecruitment may contribute to development of lung injury and adverse systemic outcome.

  14. A microcomputer system for haemodynamic measurements in isolated, working rat hearts.

    PubMed

    Snoeckx, L H; Schrijen, J J; van Bilsen, M; Lammers, W J; van der Nagel, T; van der Vusse, G J; Reneman, R S

    1986-01-01

    This study describes the application of an Apple IIe microcomputer in combination with a pre-processor in the on-line calculation of haemodynamic variables of the isolated working rat heart and of relative rapid changes in these variables, induced by variations in left atrial filling pressure (preload) and end-diastolic aortic pressure (afterload). Variables such as heart rate, systolic and diastolic left ventricular pressure, the maximal positive and negative first derivative of the left ventricular pressure, systolic and diastolic aortic pressure and aortic flow were continuously calculated and printed at minimal intervals of 6 s. A newly designed procedure to detect the activation of the electrogram, which was necessary to start the detection of a new cardiac cycle, is described.

  15. Calcium uptake by sarcoplasmic reticulum isolated from hearts of septic rats

    SciTech Connect

    McDonough, K.H.

    1988-08-01

    Myocardial sarcoplasmic reticulum (SR) plays a critical role in the regulation of the cytosolic calcium fluctuations that occur during the cardiac cycle. One function of the SR is to lower the calcium concentration so that myocardial relaxation and thus ventricular filling can occur. The aim of the present study was to determine if hyperdynamic sepsis induced a decrease in the capacity of SR to take up calcium. This defect would result in decreased ventricular filling and thus decreased cardiac output, as has previously been shown in isolated perfused working hearts removed from septic rats. Therefore, rats were anesthetized with ether, and sepsis was induced by the injection of an aliquot of a fecal homogenate into the peritoneal cavity. Control animals either underwent surgery and received an aliquot of sterilized fecal inoculum (sham) or were untreated (no surgery). On day 2 after surgery, animals were anesthetized with pentobarbital, and hearts were removed, weighted, and SR isolated. The rate of uptake of /sup 45/Ca/sup 2 +/ by SR from septic rats was not depressed compared to controls but in fact was elevated. Maximum /sup 45/Ca/sup 2 +/ accumulated by the SR and Ca/sup 2 +/-stimulated ATPase activity were similar in SR from control and septic hearts. These results suggest that the contractile dysfunction noted in the myocardium in early sepsis is probably not due to inadequate SR removal of Ca/sup 2 +/ during diastole.

  16. Lown-Ganong-Levine syndrome in a 3-month-old infant with isolated left ventricular noncompaction.

    PubMed

    Shabanian, Reza; Kiani, Abdolrazagh; Rad, Elaheh Malakan; Eslamiyeh, Hosein

    2010-02-01

    This report describes a 3-month-old boy with isolated left ventricular noncompaction admitted to a medical facility due to heart failure and dysrhythmia. His electrocardiogram showed a short PR interval and a normal QRS complex after abortion of supraventricular tachycardia in favor of Lown-Ganong-Levine syndrome or enhanced atrioventricular nodal conduction.

  17. Isolated right ventricular takotsubo cardiomyopathy: a case report and literature review.

    PubMed

    Elikowski, Waldemar; Małek-Elikowska, Małgorzata; Różańska, Paulina; Fertała, Natalia; Zawodna, Magdalena

    2016-12-22

    In about one quarter of patients with stress-induced takotsubo cardiomyopathy (TC) concomitant involvement of right ventricle (RV) can be observed. Opposite to this biventricular form of TC, isolated right ventricular takotsubo cardiomyopathy (RVTC) was described only in a few cases and so far has not been listed as a specific type of TC. The authors present a case of a 87-year-old demented female admitted with pneumonia in whom echocardiography revealed RV apical ballooning while the left ventricle function was quite normal. RV apical thrombus was also found. Initial ECG showed QR in V1, discrete ST elevation in V1-2 leads and low voltage of QRS complex in limb leads. There was only a slight increase in troponin I level but a marked BNP elevation. Despite treatment, the course of the disease ended in a fiasco. The authors compare the clinical picture of the patient presented with the data of the 6 remaining cases of isolated RVTC found in the literature. Routine echocardiographic evaluation of RV in different clinical situations which may trigger TC should show actual occurrence of isolated RVTC.

  18. Long-acting calcium channel antagonist pranidipine prevents ventricular remodeling after myocardial infarction in rats.

    PubMed

    Takeuchi, K; Omura, T; Yoshiyama, M; Yoshida, K; Otsuka, R; Shimada, Y; Ujino, K; Yoshikawa, J

    1999-01-01

    The purpose of this study was to examine the effects of the long-acting calcium channel antagonist pranidipine on ventricular remodeling, systolic and diastolic cardiac function, circulating humoral factors, and cardiac mRNA expression in myocardial infarcted rats. Myocardial infarction (MI) was produced by ligation of the coronary artery in Wistar rats. Three mg/kg per day of pranidipine was randomly administered to the infarcted rats. Hemodynamic measurements, Doppler echocardiographic examinations, analyses of the plasma levels of humoral factors, and myocardial mRNA expression were performed at 4 weeks after myocardial infarction. Left ventricular end-diastolic pressure (LVEDP) and central venous pressure (CVP) increased to 24.2 +/- 1.2mmHg and 5.4 +/- 0.6 mmHg. Pranidipine reduced LVEDP and CVP to 13.6 +/- 1.4mmHg (P < 0.01) and 2.5 +/- 0.4mmHg (P < 0.01). The weight of the left and right ventricles in MI was significantly higher than in the sham-operated rats (sham, 2.02 +/- 0.04 and 0.47 +/- 0.02g/kg; MI, 2.18 +/- 0.05 and 0.79 +/- 0.04g/ kg; P < 0.01). Left ventricular end-diastolic dimension (LVDd) in MI increased to 10.3 +/- 0.3mm (P < 0.01) (sham, 6.4 +/- 0.3mm). Pranidipine prevented an increase in the weight of the left and right ventricles (2.02 +/- 0.04 and 0.6 +/- 0.03g/kg, P < 0.01) and LVDd (7.9 +/-0.2mm, P < 0.01 to MI). Plasma renin activity (PRA), and plasma epinephrine, norepinephrine, and dopamine concentrations in MI were higher than those of the sham-operated rats. Pranidipine decreased the PRA and plasma cathecolamine levels of the myocardial infarcted rats to the level of the sham-operated rats. Moreover, the rats in MI showed systolic dysfunction, shown by decreased fractional shortening (sham, 31 +/- 2% vs MI, 15 +/- 1%; P < 0.01) and diastolic dysfunction shown by the E-wave deceleration rate (sham, 12.8 +/- 1.1 m/s2; MI, 32.6 +/- 2.1 m/s2; P < 0.01). Pranidipine significantly prevented systolic and diastolic dysfunction. The increases

  19. Effects of halothane, isoflurane and enflurane on isolated rat heart muscle.

    PubMed

    Miralles, F S; Carceles, M D; Laorden, M L; Hernandez, J

    1989-05-01

    Since the effects in the intact organism are complicated by central as well as peripheral effects, we compared the direct cardiac effects of three commonly used inhalational anaesthetics--halothane, isoflurane and enflurane--on isolated heart muscle. Concentration-response curves for inotropic, chronotropic and ventricular automaticity effects of halothane, isoflurane and enflurane (0.1-2% v/v) on electrically stimulated left atria, right atria and right ventricles of the rat were obtained. All three inhalational anaesthetics significantly decreased contractile force; the inhibitory concentration 50 (IC50) of enflurane was 0.55 +/- 0.06% v/v, significantly lower than halothane (0.96 +/- 0.08% v/v) and isoflurane (0.67 +/- 0.05% v/v). Similar results were obtained on atrial nomotopic rate. Halothane, isoflurane and enflurane produced negative chronotropic effects in this preparation. On the other hand, halothane and isoflurane significantly reduced the ventricular ectopic automaticity. However enflurane (0.3, 0.5, 1% v/v) increased ventricular rate. There were statistically significant differences between the IC50 values of atrial and ventricular rate for halothane and isoflurane. These results indicate: (a) direct negative inotropic and chronotropic effects for the three inhalational anaesthetics tested; (b) anti-dysrhythmic actions for halothane and isoflurane; and (c) dysrhythmogenic effects of enflurane.

  20. Salubrinal attenuates right ventricular hypertrophy and dysfunction in hypoxic pulmonary hypertension of rats.

    PubMed

    He, Yun-Yun; Liu, Chun-Lei; Li, Xin; Li, Rui-Jun; Wang, Li-Li; He, Kun-Lun

    2016-12-01

    The phosphorylation of eukaryotic translation initiation factor 2 alpha (p-eIF2α) is essential for cell survival during hypoxia. The aim of this study was to investigate whether salubrinal, an inhibitor of p-eIF2α dephosphorylation could attenuate pulmonary arterial hypertension (PAH) and right ventricular (RV) hypertrophy in rats exposed to hypobaric hypoxia. PAH of rats was induced by hypobaric hypoxia. Salubrinal supplemented was randomized in either a prevention or a reversal protocol. At the end of the follow-up point, we measured echocardiography, hemodynamics, hematoxylin-eosin and Masson's trichrome stainings. RNA-seq analysis is explored to identify changes in gene expression associated with hypobaric hypoxia with or without salubrinal. Compared with vehicle-treatment rats exposed to hypobaric hypoxia, salubrinal prevented and partly reversed the increase of the mean pulmonary artery pressure and RV hypertrophy. What's more, salubrinal reduced the percentage wall thickness (WT%) of pulmonary artery and RV collagen volume fraction (CVF) in both prevention and reversal protocols. We also found that salubrinal was capable of reducing endoplasmic reticulum stress and oxidative stress. The result of RNA-seq analysis revealed that chronic hypoxia stimulated the differential expression of a series of genes involved in cell cycle regulation and ventricular hypertrophy and so on. Some of these genes could be ameliorated by salubrinal. These results indicate that salubrinal could prevent and reverse well-established RV remodeling, and restore the genes and pathways altered in the right ventricles of rats exposed to hypobaric hypoxia. Copyright © 2016. Published by Elsevier Inc.

  1. Toluene and benzene inhalation influences on ventricular arrhythmias in the rat.

    PubMed

    Magos, G A; Lorenzana-Jiménez, M; Vidrio, H

    1990-01-01

    We have previously found that toluene did not share the capacity of benzene for increasing the arrhythmogenic action of epinephrine in the rat, but appeared to elicit the opposite effect. The present experiments were carried out to verify this observation in rats subjected to more severe ventricular arrhythmias. In animals previously inhaling either air, toluene or benzene and anesthetized with pentobarbital, arrhythmias were produced by coronary ligation or aconitine. In both models, toluene decreased and benzene increased the number of ectopic ventricular beats in the 30 min following induction of arrhythmia. Gas chromatographic measurement of toluene levels in the heart during and after inhalation revealed essentially constant concentrations at the time of arrhythmia evaluation, equivalent to approximately one-third the peak levels observed at the end of inhalation. Although the mechanism of the effect of toluene on arrhythmia could not be ascertained, nonspecific membrane stabilization or central serotonergic stimulation were considered as possible explanations. Since both mechanisms could be operant also in the case of benzene, the opposite effects of the solvents on arrhythmia could not be readily accounted for.

  2. Role of histamine H3 receptors during ischemia/reperfusion in isolated rat hearts.

    PubMed

    Yamamoto, Satoshi; Tamai, Isao; Takaoka, Masanori; Matsumura, Yasuo

    2004-03-01

    Histamine H3 receptors are involved in regulating the release of norepinephrine (NE), in both central and peripheral nervous systems. We investigated the effect of R-alpha-methylhistamine (R-HA), a selective H3 receptor agonist, and thioperamide (Thiop), a selective H3 receptor antagonist, on ischemia/reperfusion-induced changes in carrier-mediated NE release and cardiac function in isolated rat heart. Hearts were subjected to 40-minute ischemia followed by 30-minute reperfusion. Ischemia/reperfusion evoked massive NE release, which was markedly suppressed by the treatment with desipramine (DMI), a neuronal NE transporter blocker. Ischemia/reperfusion-induced cardiac dysfunction (decreases in left ventricular developed pressure, LVDP, and the first derivative of left ventricular pressure, dP/dt, and a rise in left ventricular end diastolic pressure, LVEDP) was also improved by the DMI treatment. The treatment with R-HA also significantly decreased the excessive NE release induced by the ischemia/reperfusion, improved the recovery of LVDP and dP/dt, and suppressed the rise in LVEDP. Thiop did not affect NE release and cardiac function after the reperfusion. When R-HA was administered concomitantly with Thiop, R-HA failed to attenuate ischemia/reperfusion-induced NE release and cardiac dysfunction. Thus, it seems likely that the ischemia/reperfusion-induced carrier-mediated NE release in rat hearts is negatively regulated by the activation of H3 receptors, probably located on cardiac noradrenergic nerve endings.

  3. Methanolic Extract of Ceplukan Leaf (Physalis minima L.) Attenuates Ventricular Fibrosis through Inhibition of TNF-α in Ovariectomized Rats.

    PubMed

    Lestari, Bayu; Permatasari, Nur; Rohman, Mohammad Saifur

    2016-01-01

    The increase of heart failure prevalence on menopausal women was correlated with the decrease of estrogen level. The aim of this study is to investigate the effects of ceplukan leaf (Physalis minima L.), which contains phytoestrogen physalin and withanolides, on ventricular TNF-α level and fibrosis in ovariectomized rats. Wistar rats were divided into six groups (control (-); OVX 5: 5-week ovariectomy (OVX); OVX 9: 9-week ovariectomy; treatments I, II, and III: 9-weeks OVX + 4-week ceplukan leaf's methanolic extract doses 500, 1500, and 2500 mg/kgBW, resp.). TNF-α levels were measured with ELISA. Fibrosis was counted as blue colored tissues percentage using Masson's Trichrome staining. This study showed that prolonged hypoestrogen increases ventricular fibrosis (p < 0.05). Ceplukan leaf treatment also resulted in a decrease of ventricular fibrosis and TNF-α level in dose dependent manner compared to without treatment group (p < 0.05). Furthermore, the TNF-α level was normalized in 2500 mg/kgBW Physalis minima L. (p < 0.05) treatment. The reduction of fibrosis positively correlated with TNF-α level (p < 0.05, r = 0.873). Methanolic extract of ceplukan leaf decreases ventricular fibrosis through the inhibition of ventricular TNF-α level in ovariectomized rats.

  4. Targeted ablation of cardiac sympathetic neurons reduces the susceptibility to ischemia-induced sustained ventricular tachycardia in conscious rats

    PubMed Central

    Lujan, Heidi L.; Palani, Gurunanthan; Zhang, Lijie

    2010-01-01

    The Cardiac Arrhythmia Suppression Trial demonstrated that antiarrhythmic drugs not only fail to prevent sudden cardiac death, but actually increase overall mortality. These findings have been confirmed in additional trials. The “proarrhythmic” effects of most currently available antiarrhythmic drugs makes it essential that we investigate novel strategies for the prevention of sudden cardiac death. Targeted ablation of cardiac sympathetic neurons may become a therapeutic option by reducing sympathetic activity. Thus cholera toxin B subunit (CTB) conjugated to saporin (a ribosomal inactivating protein that binds to and inactivates ribosomes; CTB-SAP) was injected into both stellate ganglia to test the hypothesis that targeted ablation of cardiac sympathetic neurons reduces the susceptibility to ischemia-induced, sustained ventricular tachycardia in conscious rats. Rats were randomly divided into three groups: 1) control (no injection); 2) bilateral stellate ganglia injection of CTB; and 3) bilateral stellate ganglia injection of CTB-SAP. CTB-SAP rats had a reduced susceptibility to ischemia-induced, sustained ventricular tachycardia. Associated with the reduced susceptibility to ventricular arrhythmias were a reduced number of stained neurons in the stellate ganglia and spinal cord (segments T1-T4), as well as a reduced left ventricular norepinephrine content and sympathetic innervation density. Thus CTB-SAP retrogradely transported from the stellate ganglia is effective at ablating cardiac sympathetic neurons and reducing the susceptibility to ventricular arrhythmias. PMID:20173045

  5. Methanolic Extract of Ceplukan Leaf (Physalis minima L.) Attenuates Ventricular Fibrosis through Inhibition of TNF-α in Ovariectomized Rats

    PubMed Central

    Lestari, Bayu; Permatasari, Nur; Rohman, Mohammad Saifur

    2016-01-01

    The increase of heart failure prevalence on menopausal women was correlated with the decrease of estrogen level. The aim of this study is to investigate the effects of ceplukan leaf (Physalis minima L.), which contains phytoestrogen physalin and withanolides, on ventricular TNF-α level and fibrosis in ovariectomized rats. Wistar rats were divided into six groups (control (—); OVX 5: 5-week ovariectomy (OVX); OVX 9: 9-week ovariectomy; treatments I, II, and III: 9-weeks OVX + 4-week ceplukan leaf's methanolic extract doses 500, 1500, and 2500 mg/kgBW, resp.). TNF-α levels were measured with ELISA. Fibrosis was counted as blue colored tissues percentage using Masson's Trichrome staining. This study showed that prolonged hypoestrogen increases ventricular fibrosis (p < 0.05). Ceplukan leaf treatment also resulted in a decrease of ventricular fibrosis and TNF-α level in dose dependent manner compared to without treatment group (p < 0.05). Furthermore, the TNF-α level was normalized in 2500 mg/kgBW Physalis minima L. (p < 0.05) treatment. The reduction of fibrosis positively correlated with TNF-α level (p < 0.05, r = 0.873). Methanolic extract of ceplukan leaf decreases ventricular fibrosis through the inhibition of ventricular TNF-α level in ovariectomized rats. PMID:26941790

  6. The role of catecholamines in the production of ischaemia-induced ventricular arrhythmias in the rat in vivo and in vitro.

    PubMed Central

    Daugherty, A.; Frayn, K. N.; Redfern, W. S.; Woodward, B.

    1986-01-01

    The role of catecholamines in the production of ischaemia-induced ventricular arrhythmias in vivo and in vitro was studied using coronary artery ligation in the rat. Increases in plasma catecholamine concentrations during coronary artery ligation in pentobarbitone-anaesthetized animals were prevented by either acute adrenalectomy or chronic adrenal demedullation, but these procedures did not protect against the occurrence of ventricular arrhythmias. Thus plasma catecholamines were not obligatory mediators of arrhythmogenesis. Three protocols were used in vitro to evaluate the possible influence of intramyocardial release of noradrenaline, produced by the local conditions of ischaemia, on the production of ventricular arrhythmias. During coronary artery ligation in isolated perfused hearts, no enhanced output of 3H could be detected from [3H]-noradrenaline loaded hearts, even in the presence of inhibitors of catecholamine uptake processes, although washout of lactate from ischaemic regions was readily demonstrable. Both optical isomers of propranolol were equally effective in reducing the incidence of arrhythmias, implying a non-specific effect, since the (+)-isomer possesses considerably less beta-adrenoceptor blocking activity. The equipotency of optical isomers of propranolol combined with a lack of effect of atenolol suggested that arrhythmia production was not a consequence of beta-adrenoceptor stimulation. The alpha-adrenoceptor blockers phentolamine and prazosin, both exerted antiarrhythmic actions of similar potency, but phenoxybenzamine and trimazosin had no significant effects. An evaluation of the pharmacological properties of the alpha-adrenoceptor blockers showed that those drugs which had demonstrable local anaesthetic properties also exerted significant antiarrhythmic effects. No relationship was found between potency of alpha-adrenoceptor blockade and antiarrhythmic efficacy. The overall conclusion from these multifaceted approaches was that

  7. Electromechanical and atrial and ventricular antiarrhythmic actions of CIJ-3-2F, a novel benzyl-furoquinoline vasodilator in rat heart

    PubMed Central

    Chang, Gwo-Jyh; Yeh, Yung-Hsin; Lin, Tsung-Pin; Chang, Chi-Jen; Chen, Wei-Jan

    2014-01-01

    BACKGROUND AND PURPOSE This study was designed to examine the antiarrhythmic efficacy and the underlying mechanisms of the benzyl-furoquinoline vasodilator, CIJ-3-2F, in rat cardiac preparations. EXPERIMENTAL APPROACH Conduction electrograms and left ventricular pressure were determined in Langendorff-perfused hearts. Action potentials were assessed with microelectrode techniques, calcium transients by fura-2 fluorescence and ionic currents by whole-cell patch-clamp techniques. KEY RESULTS In isolated hearts, CIJ-3-2F prolonged sinus cycle length, QT interval, Wenckebach cycle length, atrio-His bundle and His bundle-ventricular conduction intervals, refractory periods in atrium, AV node, His-Purkinje system and ventricle, and also increased left ventricular pressure. CIJ-3-2F reduced the incidences of both ischaemic and reperfusion-induced ventricular arrhythmias and prevented the induction of atrial tachyarrhythmias. In both atrial and papillary muscles, CIJ-3-2F decreased upstroke velocity and prolonged duration of the action potential. In ventricular myocytes, CIJ-3-2F moderately increased the amplitude of [Ca2+]i transients and cell shortening. CIJ-3-2F inhibited the transient outward K+ current (Ito) (IC50 = 4.4 μM) with accelerated inactivation, a slower rate of recovery from inactivation and use-dependency. CIJ-3-2F also suppressed the steady-state outward K+ current (Iss, IC50 = 3.6 μM, maximum inhibition = 65.7%) and both the inward Na+ current (INa, IC50 = 2.8 μM) and L-type Ca2+ current (ICa,L, IC50 = 4.9 μM, maximum inhibition = 69.4%). CONCLUSIONS AND IMPLICATIONS CIJ-3-2F blocked Na+ and Ito channels and, to some extent, also blocked Ca2+ and Iss channels, modifying cardiac electromechanical function. These effects are likely to underlie its antiarrhythmic properties. PMID:24820856

  8. Chronic exercise partially restores the transmural heterogeneity of action potential duration in left ventricular myocytes of spontaneous hypertensive rats.

    PubMed

    Roman-Campos, Danilo; Carneiro-Júnior, Miguel A; Prímola-Gomes, Thales N; Silva, Karina A; Quintão-Júnior, Judson F; Gondim, Antonio Ns; Duarte, Hugo L; Cruz, Jader S; Natali, Antonio J

    2012-02-01

    Hypertension leads to electrophysiological changes in the heart. Chronic exercise induced by a treadmill-running programme (TRP) is considered a potential non-pharmacological treatment for hypertension and may have implications in heart remodelling. However, it is not known whether the TRP is able to improve the electrophysiological properties of the heart in spontaneously hypertensive rats (SHR). In the present study, we investigated whether TRP affects the electrical properties of left ventricular (LV) myocytes isolated from different layers of the LV wall of SHR. Male SHR were divided into exercised (chronic treadmill running for 8 weeks; CEX-SHR) and sedentary (SED-SHR) groups. Age-matched normotensive Wistar male rats served as controls. Action potentials (AP) and transient outward potassium current (I(to) ) were recorded in subepicardial (EPI) and subendocardial (ENDO) LV myocytes. In normotensive controls, AP duration (APD) was longer in ENDO cells than in EPI cells. This sort of transmural heterogeneity in the LV was not observed in sedentary SHR and was partially restored in SHR subject to chronic exercise. This partial recovery was associated with an increase in I(to) density in EPI cells but not in ENDO cells. The electrophysiological changes observed in the CEX-SHR group were not accompanied by either amelioration of systolic blood pressure or a reduction in heart hypertrophy. These findings imply that a TRP is able to improve the electrophysiological parameters of isolated cardiac myocytes in SHR. This sort of adaptation contributes to the overall improvement of heart physiology in this model. © 2011 The Authors Clinical and Experimental Pharmacology and Physiology © 2011 Blackwell Publishing Asia Pty Ltd.

  9. Direct analysis of beta-adrenergic receptor subtypes on intact adult ventricular myocytes of the rat

    SciTech Connect

    Buxton, I.L.; Brunton, L.L.

    1985-01-01

    beta 1- and beta 2-Adrenergic receptors co-exist in the adult rat ventricle. Radioligand binding and cell purification techniques have been employed to determine the cellular origin of these receptors. The beta-adrenergic antagonist ligand (+/-)-(/sup 125/I) iodocyanopindolol binds to 2 X 10(5) receptors per purified adult rat cardiomyocyte, with a dissociation constant of 70 pM. The subtype-selective antagonists betaxolol (beta 1), practolol (beta 1), and zinterol (beta 2) compete for (/sup 125/I)iodocyanopindolol-binding sites on intact myocytes in monophasic manners with dissociation constants of 46, 845, and 923 nM, respectively. (/sup 125/I)iodocyanopindolol binding to membranes prepared from nonmyocyte elements of rat ventricle occurs with a dissociation constant of 43 pM and a capacity of 88 fmol/mg membrane protein. Computer analysis of competition of (/sup 125/I)iodocyanopindolol binding by betaxolol, practolol, and zinterol in nonmyocyte membranes demonstrates biphasic curves that comprise binding to both beta 1- and beta 2-receptors. These data demonstrate that purified adult ventricular myocytes possess only beta 1-receptors, and that the beta 2-receptors found in rat ventricle are located on nonmyocyte cell types.

  10. Food restriction induces in vivo ventricular dysfunction in spontaneously hypertensive rats without impairment of in vitro myocardial contractility.

    PubMed

    Okoshi, K; Fioretto, J R; Okoshi, M P; Cicogna, A C; Aragon, F F; Matsubara, L S; Matsubara, B B

    2004-04-01

    Cardiac structures, function, and myocardial contractility are affected by food restriction (FR). There are few experiments associating undernutrition with hypertension. The aim of the present study was to analyze the effects of FR on the cardiac response to hypertension in a genetic model of hypertension, the spontaneously hypertensive rat (SHR). Five-month-old SHR were fed a control or a calorie-restricted diet for 90 days. Global left ventricle (LV) systolic function was evaluated in vivo by transthoracic echocardiogram and myocardial contractility and diastolic function were assessed in vitro in an isovolumetrically beating isolated heart (Langendorff preparation). FR reduced LV systolic function (control (mean +/- SD): 58.9 +/- 8.2; FR: 50.8 +/- 4.8%, N = 14, P < 0.05). Myocardial contractility was preserved when assessed by the +dP/dt (control: 3493 +/- 379; FR: 3555 +/- 211 mmHg/s, P > 0.05), and developed pressure (in vitro) at diastolic pressure of zero (control: 152 +/- 16; FR: 149 +/- 15 mmHg, N = 9, P > 0.05) and 25 mmHg (control: 155 +/- 9; FR: 150 +/- 10 mmHg, N = 9, P > 0.05). FR also induced eccentric ventricular remodeling, and reduced myocardial elasticity (control: 10.9 +/- 1.6; FR: 9.2 +/- 0.9%, N = 9, P < 0.05) and LV compliance (control: 82.6 +/- 16.5; FR: 68.2 +/- 9.1%, N = 9, P < 0.05). We conclude that FR causes systolic ventricular dysfunction without in vitro change in myocardial contractility and diastolic dysfunction probably due to a reduction in myocardial elasticity.

  11. Perventricular device closure of isolated muscular ventricular septal defect in infants: A single centre experience☆

    PubMed Central

    Thakkar, Bhavesh; Patel, Nehal; Shah, Shaunak; Poptani, Vishal; Madan, Tarun; Shah, Chirag; Shukla, Anand; Prajapati, Vaishali

    2012-01-01

    Objectives To evaluate prospective single centre experience of mid-term safety and efficacy of perventricular device closure of isolated large muscular ventricular septal defect (mVSD) in high-risk infants. Background Surgical closures of large mVSD in infants represent a challenge with significant morbidity. Methods Between August 2008–2010, perventricular closure was attempted in 24 infants of 6.01 ± 2.37 months age and 4.27 ± 0.56 kg weight under TEE guidance. Results The device was successfully deployed in 21/24 infants. Size of mVSD was 8.42 ± 1.46 mm (6.1–12 mm). Mean procedure time was 28.8 ± 11.7 min. The closure rate was 84% immediately and 100% at 6 months. Four patients suffered major complications: 2-died, 1-esophageal perforation, 1-persistent CHB. At 26.23 ± 6.63 months follow-up two patients were symptomatic: 1-required device retrieval, 1-died of severe gastroenteritis. Conclusion Perventricular device closure of isolated mVSD appears feasible option at mid-term follow-up and may either substitute or complement the conventional surgical technique in selected cases depending on institutional paediatric cardiac surgery performance. PMID:23253407

  12. The Impact of Isolated Obesity on Right Ventricular Function in Young Adults

    PubMed Central

    Sokmen, Abdullah; Sokmen, Gulizar; Acar, Gurkan; Akcay, Ahmet; Koroglu, Sedat; Koleoglu, Murat; Yalcintas, Sila; Aydin, M. Naci

    2013-01-01

    Background Obesity is an independent risk factor for cardiovascular diseases. The effects of obesity on left ventricular structure and function have been reported, but relatively little is known regarding right ventricular (RV) function in obesity. Objective To evaluate subclinical RV alterations in obese, but otherwise healthy, young adults by conventional echocardiography and tissue Doppler imaging (TDI). Methods In this study, we included 35 normal weight healthy subjects with a body mass index (BMI) < 25 kg/m2 (group I), 27 subjects with a BMI of 30-34.99 kg/m2 (group II), and 42 subjects with a BMI ≥ 35 kg/m2 (group III). All subjects underwent transthoracic echocardiography. In addition to standard echocardiographic measurements, tricuspid annular peak systolic (Sm), peak early (Em), and late diastolic (Am) velocities, isovolumetric contraction (ICTm), relaxation (IRTm) time, and ejection time (ETm) were obtained by TDI, and RV myocardial performance index (MPIm) was calculated. Results In group II, RV Em/Am was significantly decreased and IRTm and MPIm were significantly increased compared to group I (p < 0.01). RV Sm, Em, and the Em/Am ratio were significantly lower and RV IRTm and MPIm were significantly higher in group III than in group II (p < 0.05 for RV Sm and IRTm and p < 0.01 for others). RV Am differed significantly between groups III and I (p < 0.05). BMI was significantly and negatively correlated with RV Sm, Em, and the Em/Am ratio, but positively correlated with RV MPI (p < 0.01). Conclusion Our study showed that isolated obesity in young normotensive adults was associated with subclinical abnormalities in RV structure and function. PMID:23842799

  13. Effects of phorbol ester on contraction, intracellular pH and intracellular Ca2+ in isolated mammalian ventricular myocytes.

    PubMed Central

    MacLeod, K T; Harding, S E

    1991-01-01

    1. We have investigated the actions of certain phorbol esters on the intracellular pH, intracellular Ca2+ and contractility of isolated rat and guinea-pig cardiac myocytes. Intracellular pH was measured using 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF) and intracellular Ca2+ was measured using Fura-2. 2. Application of the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (also called phorbol 12-myristate 13-acetate) (TPA) (which activates protein kinase C) to rat cardiac myocytes significantly increased cell shortening by 116 +/- 34% (n = 8) (p less than 0.02). The rate of change of cell length during contraction (i.e. +dL/dt) increased from 67.2 +/- 8.7 microns/s to 127.7 +/- 14.1 microns/s (n = 7). The rate of change of cell length during relaxation (-dL/dt) increased from 55.8 +/- 7.4 microns/s to 118.9 +/- 12.1 microns/s (n = 7). Time to peak shortening was unchanged. 3. Application of 4 alpha-phorbol 12,13-didecanoate, which does not activate protein kinase C, did not affect rat myocyte contractility. An insignificant decrease in contractility (by 7.5 +/- 7.5%) was observed (n = 5). The positive inotropic effect of TPA may therefore be evoked through an activation of protein kinase C. 4. In rat myocytes we have measured the changes of pHi and contractility (cell shortening) during an alkalosis and acidosis induced by exposure to and subsequent removal of NH4Cl both in the presence and absence of TPA. Recovery times from an acid load were significantly (p less than 0.05) enhanced by 15.1 +/- 6.9% (n = 13) in the presence of TPA. Recovery times of cell shortening were also more rapid (p less than 0.05) by an average of 59.1 +/- 10.6% (n = 5) in the presence of TPA. Recovery times were unchanged in the presence of 4-phorbol 12,13-didecanoate (which does not activate protein kinase C). 5. Since pHi recovery of an isolated myocyte from an acid load is partially inhibited by the presence of 1 mM-amiloride and inhibited by removing extracellular Na

  14. Simultaneous measurement of arterial and left ventricular pressure in conscious freely moving rats by telemetry.

    PubMed

    Segreti, Jason A; Polakowski, James S; Blomme, Eric A; King, Andrew J

    2016-01-01

    Comprehensive cardiovascular assessment in conscious rodents by utilizing telemetry has been limited by the restriction of current devices to one pressure channel. The purpose of this study was to test and validate a dual pressure transmitter that allows the simultaneous measurement of arterial pressure (AP) and left ventricular pressure (LVP) in conscious freely moving rats. Six rats were surgically implanted with dual pressure transmitters. Baseline hemodynamics and circadian rhythm were observed to return within 7days. AP, heart rate (HR), LVP and indices of left ventricular contractility were stable and demonstrated a prominent circadian rhythm over a two-week period of uninterrupted recordings. Administration of the vasodilator nifedipine produced the anticipated dose-dependent decrease in AP which was accompanied by a baroreflex mediated increase in HR and cardiac contractility. The negative inotrope verapamil produced the expected dose-dependent decreases in AP and cardiac contractility. Finally, a terminal validation of the dual pressure transmitter was performed under anesthesia by measuring AP and LVP simultaneously via telemetry and from a fluid filled arterial catheter and an intraventricular Millar catheter, respectively. A range of pressures and cardiac contractility were studied by administering sequential intravenous infusions of the positive inotrope dobutamine followed by verapamil. Linear regression analysis revealed a high level of agreement between pressures measured by the dual pressure transmitter and the exteriorized catheters. Histopathologic analysis of the heart revealed mild peri-catheter fibrosis. In conclusion, the simultaneous measurement of AP and LVP offers the potential for more detailed cardiovascular assessment in conscious rats. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Effects of anesthesia on echocardiographic assessment of left ventricular structure and function in rats.

    PubMed

    Stein, Adam B; Tiwari, Sumit; Thomas, Paul; Hunt, Greg; Levent, Cemil; Stoddard, Marcus F; Tang, Xian-Liang; Bolli, Roberto; Dawn, Buddhadeb

    2007-01-01

    Echocardiography is an essential diagnostic tool for accurate noninvasive assessment of cardiac structure and function in vivo. However, the use of anesthetic agents during echocardiographic studies is associated with alterations in cardiac anatomical and functional parameters. We sought to systematically compare the effects of three commonly used anesthetic agents on echocardiographic measurements of left ventricular (LV) systolic and diastolic function, LV dimensions, and LV mass in rats. Adult male Fischer 344 rats underwent echocardiographic studies under pentobarbital (PB, 25 mg/kg i.p.) (group I, n = 25), inhaled isoflurane (ISF, 1.5%) (group II, n = 25),or ketamine/xylazine (K/X, 37 mg/kg ketamine and 7 mg/kg xylazine i.p.) (group III, n = 25) anesthesia in a cross-over design. Echocardiography was also performed in an additional group of unanesthetized conscious rats (group IV, n = 5). Postmortem studies were performed to validate echocardiographic assessment of LV dimension and mass. Rats in group I exhibited significantly higher LV ejection fraction, fractional shortening, fractional area change, velocity of circumferential fiber shortening corrected for heart rate, and heart rate as compared with groups II and III. LV end-diastolic volume, end-diastolic diameter, and cross-sectional area in diastole were significantly smaller in group I compared with groups II and III. Cardiac output was significantly lower in group III compared with groups I and II. Postmortem LV mass measurements correlated well with echocardiographic estimation of LV mass for all anesthetic agents, and the correlation was best with PB anesthesia. Limited echocardiographic data obtained in conscious rats were similar to those obtained under PB anesthesia. We conclude that compared with ISF and K/X anesthesia, PB anesthesia at a lower dose yields echocardiographic LV structural and functional data similar to those obtained in conscious rats. In addition, PB anesthesia also facilitates

  16. Isolation of rat cardiac sarcoplasmic reticulum with improved Ca2+ uptake and ryanodine binding.

    PubMed

    Feher, J J; Davis, M D

    1991-03-01

    The instability of the oxalate-supported Ca2+ uptake activity of rat cardiac sarcoplasmic reticulum (CSR) in ventricular homogenates most likely accounts for the low specific activity of the rate of oxalate-supported Ca2+ uptake in previously reported fractions of isolated rat CSR. We have found that CSR vesicles with improved Ca2+ transport capabilities can be isolated if 1 M KCl is used to stabilize the CSR activity and to allow the extraction of the CSR from the cellular debris. The average rate of Ca2+ uptake by the isolated rat CSR in the presence of 10 mM oxalate at 37 degrees C was 0.45 mumols/min-mg in the absence of CSR Ca2+ channel blockers and 0.87 mumols/min-mg in the presence of 10 microM ruthenium red. The Ca(2+)-dependent ATPase activity under the conditions of oxlate-supported uptake was 1.25 mumols/min-mg and 0.84 mumols/min-mg in the absence and presence of 10 microM ruthenium red, respectively. The rat CSR vesicles bound 3H-ryanodine with a Kd of 1.45 nM and a Bmax of 3.7 pmol mg. The level of phosphorylated intermediate was 0.30 nmol/mg. The values Bmax, EP and Ca(2+)-ATPase activity are from one-third to one-half of those previously reported for isolated canine CSR vesicles. These results suggest that the isolated rat CSR may be quite similar to dog CSR.

  17. Improvement of left ventricular remodeling after myocardial infarction with eight weeks L-thyroxine treatment in rats

    PubMed Central

    2013-01-01

    Background Left ventricular (LV) remodeling following large transmural myocardial infarction (MI) remains a pivotal clinical issue despite the advance of medical treatment over the past few decades. Identification of new medications to improve the remodeling process and prevent progression to heart failure after MI is critical. Thyroid hormones (THs) have been shown to improve LV function and remodeling in animals post-MI and in the human setting. However, changes in underlying cellular remodeling resulting from TH treatment are not clear. Methods MI was produced in adult female Sprague–Dawley rats by ligation of the left descending coronary artery. L-thyroxine (T4) pellet (3.3 mg, 60 days sustained release) was used to treat MI rats for 8 weeks. Isolated myocyte shape, arterioles, and collagen deposition in the non-infarcted area were measured at terminal study. Results T4 treatment improved LV ±dp/dt, normalized TAU, and increased myocyte cross-sectional area without further increasing myocyte length in MI rats. T4 treatment increased the total LV tissue area by 34%, increased the non-infarcted tissue area by 41%, and increased the thickness of non-infarcted area by 36% in MI rats. However, myocyte volume accounted for only ~1/3 of the increase in myocyte mass in the non-infarct area, indicating the presence of more myocytes with treatment. T4 treatment tended to increase the total length of smaller arterioles (5 to 15 μm) proportional to LV weight increase and also decreased collagen deposition in the LV non-infarcted area. A tendency for increased metalloproteinase-2 (MMP-2) expression and tissue inhibitor of metalloproteinases (TIMPs) -1 to −4 expression was also observed in T4 treated MI rats. Conclusions These results suggest that long-term T4 treatment after MI has beneficial effects on myocyte, arteriolar, and collagen matrix remodeling in the non-infarcted area. Most importantly, results suggest improved survival of myocytes in the peri-infarct area

  18. Decreased transient outward K+ current in ventricular myocytes from acromegalic rats.

    PubMed

    Xu, X P; Best, P M

    1991-03-01

    Cardiac hypertrophy and heart failure are common to acromegalic patients who have abnormally high serum growth hormone (GH). While the function of cardiac muscle is clearly affected by chronically elevated GH, the electrical activity of myocytes from hearts with GH-dependent hypertrophy has not been studied. We used adult, female Wistar-Furth rats with induced GH-secreting tumors to study the effect of excessive GH on ion channels of cardiac myocytes. GH-secreting tumors were induced by subcutaneous inoculation of GH3 cells. Eight weeks after inoculation, the rats had doubled their body weight and heart size compared with age-matched controls. There were no differences in either action potential amplitude or resting potential of right ventricular myocytes from control and tumor-bearing rats. However, action potential duration increased significantly in tumor-bearing rats; the time to 50% repolarization was 23 +/- 14 ms (n = 10) compared with 6.6 +/- 1.5 ms (n = 14) in controls. The prolongation of the action potential was mainly due to a decrease in density of a transient outward current (It,o) carried by K+. The normalized conductance for It,o decreased from 0.53 +/- 0.10 nS/pF (n = 25) in controls to 0.33 +/- 0.09 nS/pF (n = 26) in tumor-bearing rats. The decrease in It,o) and increase in heart weight occurred with a similar time course. The increased action potential duration prolongs Ca2+ influx through L-type Ca2+ channels in the tumor-bearing animals; this may be important in cardiovascular adaptation.

  19. [Protective effect of total glycosides of Ranunculus japonicus on myocardial ischemic-reperfusion injury in isolated rat hearts].

    PubMed

    Gao, Xiao-Wei; Liu, Yuan; Yang, Zhi-Cheng; Tan, Yu-Zhi

    2014-08-01

    To study the protective effect of total glycosides of Ranunculus japonicus (TGRJ) on myocardial ischemic-reperfusion injury in isolated rat hearts. The SD rats were randomly divided into normal control group, ischemia-reperfusion group, and TGRJ in 0.05, 0.10 and 0.20 mg/mL groups. The ischemia-reperfusion injury model was built using Langendroff isolated rats hearts perfusion system. The indexes of heart function such as heart rate (HR), left ventricular systolic pressure (LVSP), left ventricular systolic pressure maximum rate of rise (+ dp/dt(max)), left ventricular diastolic pressure maximum rate of descent (-dp/dt(max)) and coronary flow (CF) before ischemia and later at 1, 5, 10, 20, 30 and 40 min after reperfusion were recorded. The activity of Lactate dehydrogenase (LDH) and creatine kinase (CK) at 20 and 40 min after reperfusion were determined. The myocardial tissues were stained with Triphenyltetrazolium chloride (TTC) and the percentage of myocardial infarction area was calculated. HR, LVDP, +dp/dt(max) and CF of the I/R group were significantly decreased after reperfusion, LDH and CK levels were increased and the area of myocardial infraction was 58.78%. TGRJ had improving effect on all above indexes. TGRJ has protective effet on the myo- cardial ischemic-reperfusion injury.

  20. Progressive development of pulmonary hypertension leading to right ventricular hypertrophy assessed by echocardiography in rats.

    PubMed

    Kato, Yosuke; Iwase, Mitsunori; Kanazawa, Hiroaki; Kawata, Natsuki; Yoshimori, Yukie; Hashimoto, Katsunori; Yokoi, Toyoharu; Noda, Akiko; Takagi, Kenzo; Koike, Yasuo; Nishizawa, Takao; Nishimura, Masahiko; Yokota, Mitsuhiro

    2003-07-01

    The present study aimed to evaluate the development of pulmonary hypertension by serial echocardiography, including measurements of pulmonary artery (PA) flow velocities, and correlate echocardiographic indices with pathological findings in rats administered monocrotaline (MCT). MCT (60 mg/kg body weight) or physiologic saline was administered to a total of 9 male Wistar rats at the age of 4 weeks (MCT group: n = 4, control group: n = 5, respectively). Echocardiography was performed serially until the age of 8 weeks. The ratio of right ventricular (RV) outflow tract dimensions to aortic dimensions increased progressively in the MCT group and became significantly greater than that of the control group after the age of 6 weeks. Peak PA velocity (Peak V) in the MCT group was significantly less than that of the control group at the ages of 7 and 8 weeks. The ratio of acceleration time to ejection time (AT/ET) in PA flow waveforms declined progressively and was significantly less than that of the control group after the age of 6 weeks. The ratio of RV weight to body weight (RVW/BW) in the MCT group was significantly greater than that of the control group. Both AT/ET ratio and Peak V were significantly inversely correlated with RVW/BW ratio. Furthermore, these echocardiographic findings were also significantly inversely correlated with the mean cross-sectional RV myocyte area. In conclusion, the progressive development of pulmonary hypertension leading to RV hypertrophy can be evaluated appropriately by echocardiography including PA flow Doppler indices in rats.

  1. Isolation of cardiac myocytes and fibroblasts from neonatal rat pups.

    PubMed

    Golden, Honey B; Gollapudi, Deepika; Gerilechaogetu, Fnu; Li, Jieli; Cristales, Ricardo J; Peng, Xu; Dostal, David E

    2012-01-01

    Neonatal rat ventricular myocytes (NRVM) and fibroblasts (FBs) serve as in vitro models for studying fundamental mechanisms underlying cardiac pathologies, as well as identifying potential therapeutic targets. Both cell types are relatively easy to culture as monolayers and can be manipulated using molecular and pharmacological tools. Because NRVM cease to proliferate after birth, and FBs undergo phenotypic changes and senescence after a few passages in tissue culture, primary cultures of both cell types are required for experiments. Below we describe methods that provide good cell yield and viability of primary cultures of NRVM and FBs from 0 to 3-day-old neonatal rat pups.

  2. Trypsin and alpha-chymotrypsin treatment abolishes glibenclamide sensitivity of KATP channels in rat ventricular myocytes.

    PubMed

    Nichols, C G; Lopatin, A N

    1993-03-01

    Cytoplasmic trypsin-treatment of voltage-sensitive potassium channels has been shown to cleave domains of the channel responsible for inactivation of the channel. Trypsin has also been reported to remove slow, irreversible inactivation, or run-down in ATP-sensitive potassium (KATP) channels. Cytoplasmic treatment of rat ventricular KATP channels with either crude, or pure trypsin (1-2 mg/ml) failed to prevent a slow run-down of channel activity. However, trypsin (porcine pancreatic type IX, or type II (Sigma Chem. Co.), or alpha-chymotrypsin (Sigma Chem. Co.) rapidly and irreversibly removed, or substantiallly decreased glibenclamide and tolbutamide-sensitivity of the channels without removing sensitivity to ATP. We conclude that glibenclamide must bind to either a separate protein, or to a separate domain on the channel in order to effect channel inhibition, and this domain is functionally disconnected from the channel by trypsin-, or alpha-chymotrypsin treatment.

  3. A Computational Model of Cytosolic and Mitochondrial [Ca2+] in Paced Rat Ventricular Myocytes

    PubMed Central

    Choi, Seong Woo; Jang, Chang Han; Kim, Hyoung Kyu; Leem, Chae Hun; Kim, Nari; Han, Jin

    2011-01-01

    We carried out a series of experiment demonstrating the role of mitochondria in the cytosolic and mitochondrial Ca2+ transients and compared the results with those from computer simulation. In rat ventricular myocytes, increasing the rate of stimulation (1~3 Hz) made both the diastolic and systolic [Ca2+] bigger in mitochondria as well as in cytosol. As L-type Ca2+ channel has key influence on the amplitude of Ca2+-induced Ca2+ release, the relation between stimulus frequency and the amplitude of Ca2+ transients was examined under the low density (1/10 of control) of L-type Ca2+ channel in model simulation, where the relation was reversed. In experiment, block of Ca2+ uniporter on mitochondrial inner membrane significantly reduced the amplitude of mitochondrial Ca2+ transients, while it failed to affect the cytosolic Ca2+ transients. In computer simulation, the amplitude of cytosolic Ca2+ transients was not affected by removal of Ca2+ uniporter. The application of carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone (FCCP) known as a protonophore on mitochondrial membrane to rat ventricular myocytes gradually increased the diastolic [Ca2+] in cytosol and eventually abolished the Ca2+ transients, which was similarly reproduced in computer simulation. The model study suggests that the relative contribution of L-type Ca2+ channel to total transsarcolemmal Ca2+ flux could determine whether the cytosolic Ca2+ transients become bigger or smaller with higher stimulus frequency. The present study also suggests that cytosolic Ca2+ affects mitochondrial Ca2+ in a beat-to-beat manner, however, removal of Ca2+ influx mechanism into mitochondria does not affect the amplitude of cytosolic Ca2+ transients. PMID:21994480

  4. SKF-96365 strongly inhibits voltage-gated sodium current in rat ventricular myocytes.

    PubMed

    Chen, Kui-Hao; Liu, Hui; Yang, Lei; Jin, Man-Wen; Li, Gui-Rong

    2015-06-01

    SKF-96365 (1-(beta-[3-(4-methoxy-phenyl) propoxy]-4-methoxyphenethyl)-1H-imidazole hydrochloride) is a general TRPC channel antagonist commonly used to characterize the potential functions of TRPC channels in cardiovascular system. Recent reports showed that SKF-96365 induced a reduction in cardiac conduction. The present study investigates whether the reduced cardiac conduction caused by SKF-96365 is related to the blockade of voltage-gated sodium current (I Na) in rat ventricular myocytes using the whole-cell patch voltage-clamp technique. It was found that SKF-96365 inhibited I Na in rat ventricular myocytes in a concentration-dependent manner. The compound (1 μM) negatively shifted the potential of I Na availability by 9.5 mV, increased the closed-state inactivation of I Na, and slowed the recovery of I Na from inactivation. The inhibition of cardiac I Na by SKF-96365 was use-dependent and frequency-dependent, and the IC₅₀ was decreased from 1.36 μM at 0.5 Hz to 1.03, 0.81, 0.61, 0.56 μM at 1, 2, 5, 10 Hz, respectively. However, the selective TRPC3 antagonist Pyr3 decreased cardiac I Na by 8.5% at 10 μM with a weak use and frequency dependence. These results demonstrate that the TRPC channel antagonist SKF-96365 strongly blocks cardiac I Na in use-dependent and frequency-dependent manners. Caution should be taken for interpreting the alteration of cardiac electrical activity when SKF-96365 is used in native cells as a TRPC antagonist.

  5. Dispersion-based reentry: mechanism of initiation of ventricular tachycardia in isolated rabbit hearts.

    PubMed

    Robert, E; Aya, A G; de la Coussaye, J E; Péray, P; Juan, J M; Brugada, J; Davy, J M; Eledjam, J J

    1999-02-01

    The aim of the study was to determine whether facilitation of reentry by potassium-channel openers is related to dispersion of refractoriness and/or modification of anisotropic properties of ventricular myocardium. The dispersion of ventricular effective refractory period (VERP), longitudinal and transverse ventricular conduction velocities (thetaL and thetaT, respectively), and wavelength [lambda = VERP x theta(L or T)] were studied in Langendorff-perfused left ventricular epicardium in 20 rabbits during infusion of incremental doses of levcromakalim or nicorandil. Dispersion of refractoriness was assessed using standard deviation of VERP mean (SD-VERP), dispersion index (DI; SD-VERP/mean VERP), and maximum dispersion (Dmax = VERPmax - VERPmin). Ventricular conduction velocities and anisotropic ratio were not modified, whatever the dose used. VERP and lambda were significantly shortened at high concentrations of levcromakalim and nicorandil. At these doses, SD-VERP, DI, and Dmax were increased significantly. Analysis of ventricular tachycardia induction, performed using a high-resolution ventricular mapping system, confirmed that heterogeneity and shortening of VERP were factors inducing functional conduction block. Our data suggest that, in rabbit left ventricular epicardium, functional conduction block facilitating the occurrence of reentry could be initiated by shortening and, especially, by dispersion of refractoriness during infusion of potassium-channel openers.

  6. Effect of paroxetine on left ventricular remodeling in an in vivo rat model of myocardial infarction.

    PubMed

    Lassen, Thomas Ravn; Nielsen, Jan Møller; Johnsen, Jacob; Ringgaard, Steffen; Bøtker, Hans Erik; Kristiansen, Steen Buus

    2017-05-01

    Left ventricular (LV) remodeling following a myocardial infarction (MI) involves formation of reactive oxygen species (ROS). Paroxetine, a selective serotonin reuptake inhibitor, has an antioxidant effect in the vascular wall. We investigated whether paroxetine reduces myocardial ROS formation and LV remodeling following a MI. In a total of 32 Wistar rats, MI was induced by a 30-min ligation of the left anterior descending artery followed by 7- or 28-day reperfusion. During the 28 days of reperfusion, LV remodeling was evaluated by magnetic resonance imaging (MRI) and echocardiography (n = 20). After 28 days of reperfusion, the susceptibility to ventricular tachycardia was evaluated prior to sacrifice and histological assessment of myocyte cross-sectional area, fibrosis, and presence of myofibroblasts. Myocardial ROS formation was measured with dihydroethidium after 7 days of reperfusion in separate groups (n = 12). Diastolic LV volume, evaluated by MRI (417 ± 60 vs. 511 ± 64 µL, p < 0.05), and echocardiography (515 ± 80 vs. 596 ± 83 µL, p < 0.05) as well as diastolic LV internal diameter evaluated with echocardiography (7.2 ± 0.6 vs. 8.1 ± 0.7 mm, p < 0.05) were lower in the paroxetine group than in controls. Furthermore, myocyte cross-sectional area was reduced in the paroxetine group compared with controls (277 ± 26 vs. 354 ± 23 mm(3), p < 0.05) and ROS formation was reduced in the remote myocardium (0.415 ± 0.19 normalized to controls, p < 0.05). However, no differences in the presence of fibrosis or myofibroblasts were observed. Finally, paroxetine reduced the susceptibility to ventricular tachycardia (induced in 2/11 vs. 6/8 rats, p < 0.05). Paroxetine treatment following MI decreases LV remodeling and susceptibility to arrhythmias, probably by reducing ROS formation.

  7. Effects of Sleep Deprivation on Action Potential and Transient Outward Potassium Current in Ventricular Myocytes in Rats

    PubMed Central

    Fang, Zhou; Ren, Yi-Peng; Lu, Cai-Yi; Li, Yang; Xu, Qiang; Peng, Li; Fan, Yong-Yan

    2015-01-01

    Background Sleep deprivation contributes to the development and recurrence of ventricular arrhythmias. However, the electrophysiological changes in ventricular myocytes in sleep deprivation are still unknown. Material/Methods Sleep deprivation was induced by modified multiple platform technique. Fifty rats were assigned to control and sleep deprivation 1, 3, 5, and 7 days groups, and single ventricular myocytes were enzymatically dissociated from rat hearts. Action potential duration (APD) and transient outward current (Ito) were recorded using whole-cell patch clamp technique. Results Compared with the control group, the phases of APD of ventricular myocytes in 3, 5, and 7 days groups were prolonged and APD at 20% and 50% level of repolarization (APD20 and APD50) was significantly elongated (The APD20 values of control, 1, 3, 5, and 7 days groups: 5.66±0.16 ms, 5.77±0.20 ms, 8.28±0.30 ms, 11.56±0.32 ms, 13.24±0.56 ms. The APD50 values: 50.66±2.16 ms, 52.77±3.20 ms, 65.28±5.30 ms, 83.56±7.32 ms, 89.24±5.56 ms. P<0.01, n=18). The current densities of Ito significantly decreased. The current density-voltage (I–V) curve of Ito was vitally suppressed downward. The steady-state inactivation curve and steady-state activation curve of Ito were shifted to left and right, respectively, in sleep deprivation rats. The inactivation recovery time of Ito was markedly retarded and the time of closed-state inactivation was markedly accelerated in 3, 5, and 7 days groups. Conclusions APD of ventricular myocytes in sleep deprivation rats was significantly prolonged, which could be attributed to decreased activation and accelerated inactivation of Ito. PMID:25694200

  8. Effects of sleep deprivation on action potential and transient outward potassium current in ventricular myocytes in rats.

    PubMed

    Fang, Zhou; Ren, Yi-Peng; Lu, Cai-Yi; Li, Yang; Xu, Qiang; Peng, Li; Fan, Yong-Yan

    2015-02-19

    Sleep deprivation contributes to the development and recurrence of ventricular arrhythmias. However, the electrophysiological changes in ventricular myocytes in sleep deprivation are still unknown. Sleep deprivation was induced by modified multiple platform technique. Fifty rats were assigned to control and sleep deprivation 1, 3, 5, and 7 days groups, and single ventricular myocytes were enzymatically dissociated from rat hearts. Action potential duration (APD) and transient outward current (Ito) were recorded using whole-cell patch clamp technique. Compared with the control group, the phases of APD of ventricular myocytes in 3, 5, and 7 days groups were prolonged and APD at 20% and 50% level of repolarization (APD20 and APD50) was significantly elongated (The APD20 values of control, 1, 3, 5, and 7 days groups: 5.66±0.16 ms, 5.77±0.20 ms, 8.28±0.30 ms, 11.56±0.32 ms, 13.24±0.56 ms. The APD50 values: 50.66±2.16 ms, 52.77±3.20 ms, 65.28±5.30 ms, 83.56±7.32 ms, 89.24±5.56 ms. P<0.01, n=18). The current densities of Ito significantly decreased. The current density-voltage (I-V) curve of Ito was vitally suppressed downward. The steady-state inactivation curve and steady-state activation curve of Ito were shifted to left and right, respectively, in sleep deprivation rats. The inactivation recovery time of Ito was markedly retarded and the time of closed-state inactivation was markedly accelerated in 3, 5, and 7 days groups. APD of ventricular myocytes in sleep deprivation rats was significantly prolonged, which could be attributed to decreased activation and accelerated inactivation of Ito.

  9. The calcium-frequency response in the rat ventricular myocyte: an experimental and modelling study.

    PubMed

    Gattoni, Sara; Røe, Åsmund Treu; Frisk, Michael; Louch, William E; Niederer, Steven A; Smith, Nicolas P

    2016-08-01

    In the majority of species, including humans, increased heart rate increases cardiac contractility. This change is known as the force-frequency response (FFR). The majority of mammals have a positive force-frequency relationship (FFR). In rat the FFR is controversial. We derive a species- and temperature-specific data-driven model of the rat ventricular myocyte. As a measure of the FFR, we test the effects of changes in frequency and extracellular calcium on the calcium-frequency response (CFR) in our model and three altered models. The results show a biphasic peak calcium-frequency response, due to biphasic behaviour of the ryanodine receptor and the combined effect of the rapid calmodulin buffer and the frequency-dependent increase in diastolic calcium. Alterations to the model reveal that inclusion of Ca(2+) /calmodulin-dependent protein kinase II (CAMKII)-mediated L-type channel and transient outward K(+) current activity enhances the positive magnitude calcium-frequency response, and the absence of CAMKII-mediated increase in activity of the sarco/endoplasmic reticulum Ca(2+) -ATPase induces a negative magnitude calcium-frequency response. An increase in heart rate affects the strength of cardiac contraction by altering the Ca(2+) transient as a response to physiological demands. This is described by the force-frequency response (FFR), a change in developed force with pacing frequency. The majority of mammals, including humans, have a positive FFR, and cardiac contraction strength increases with heart rate. However, the rat and mouse are exceptions, with the majority of studies reporting a negative FFR, while others report either a biphasic or a positive FFR. Understanding the differences in the FFR between humans and rats is fundamental to interpreting rat-based experimental findings in the context of human physiology. We have developed a novel model of rat ventricular electrophysiology and calcium dynamics, derived predominantly from experimental data

  10. Stabilization of mitochondrial membrane potential prevents doxorubicin-induced cardiotoxicity in isolated rat heart

    SciTech Connect

    Montaigne, David; Marechal, Xavier; Baccouch, Riadh; Modine, Thomas; Preau, Sebastien; Zannis, Konstantinos; Marchetti, Philippe; Lancel, Steve; Neviere, Remi

    2010-05-01

    The present study was undertaken to examine the effects of doxorubicin on left ventricular function and cellular energy state in intact isolated hearts, and, to test whether inhibition of mitochondrial membrane potential dissipation would prevent doxorubicin-induced mitochondrial and myocardial dysfunction. Myocardial contractile performance and mitochondrial respiration were evaluated by left ventricular tension and its first derivatives and cardiac fiber respirometry, respectively. NADH levels, mitochondrial membrane potential and glucose uptake were monitored non-invasively via epicardial imaging of the left ventricular wall of Langendorff-perfused rat hearts. Heart performance was reduced in a time-dependent manner in isolated rat hearts perfused with Krebs-Henseleit solution containing 1 muM doxorubicin. Compared with controls, doxorubicin induced acute myocardial dysfunction (dF/dt{sub max} of 105 +- 8 mN/s in control hearts vs. 49 +- 7 mN/s in doxorubicin-treated hearts; *p < 0.05). In cardiac fibers prepared from perfused hearts, doxorubicin induced depression of mitochondrial respiration (respiratory control ratio of 4.0 +- 0.2 in control hearts vs. 2.2 +- 0.2 in doxorubicin-treated hearts; *p < 0.05) and cytochrome c oxidase kinetic activity (24 +- 1 muM cytochrome c/min/mg in control hearts vs. 14 +- 3 muM cytochrome c/min/mg in doxorubicin-treated hearts; *p < 0.05). Acute cardiotoxicity induced by doxorubicin was accompanied by NADH redox state, mitochondrial membrane potential, and glucose uptake reduction. Inhibition of mitochondrial permeability transition pore opening by cyclosporine A largely prevented mitochondrial membrane potential dissipation, cardiac energy state and dysfunction. These results suggest that in intact hearts an impairment of mitochondrial metabolism is involved in the development of doxorubicin cardiotoxicity.

  11. Stabilization of mitochondrial membrane potential prevents doxorubicin-induced cardiotoxicity in isolated rat heart.

    PubMed

    Montaigne, David; Marechal, Xavier; Baccouch, Riadh; Modine, Thomas; Preau, Sebastien; Zannis, Konstantinos; Marchetti, Philippe; Lancel, Steve; Neviere, Remi

    2010-05-01

    The present study was undertaken to examine the effects of doxorubicin on left ventricular function and cellular energy state in intact isolated hearts, and, to test whether inhibition of mitochondrial membrane potential dissipation would prevent doxorubicin-induced mitochondrial and myocardial dysfunction. Myocardial contractile performance and mitochondrial respiration were evaluated by left ventricular tension and its first derivatives and cardiac fiber respirometry, respectively. NADH levels, mitochondrial membrane potential and glucose uptake were monitored non-invasively via epicardial imaging of the left ventricular wall of Langendorff-perfused rat hearts. Heart performance was reduced in a time-dependent manner in isolated rat hearts perfused with Krebs-Henseleit solution containing 1 microM doxorubicin. Compared with controls, doxorubicin induced acute myocardial dysfunction (dF/dt(max) of 105+/-8 mN/s in control hearts vs. 49+/-7 mN/s in doxorubicin-treated hearts; p<0.05). In cardiac fibers prepared from perfused hearts, doxorubicin induced depression of mitochondrial respiration (respiratory control ratio of 4.0+/-0.2 in control hearts vs. 2.2+/-0.2 in doxorubicin-treated hearts; p<0.05) and cytochrome c oxidase kinetic activity (24+/-1 microM cytochrome c/min/mg in control hearts vs. 14+/-3 microM cytochrome c/min/mg in doxorubicin-treated hearts; p<0.05). Acute cardiotoxicity induced by doxorubicin was accompanied by NADH redox state, mitochondrial membrane potential, and glucose uptake reduction. Inhibition of mitochondrial permeability transition pore opening by cyclosporine A largely prevented mitochondrial membrane potential dissipation, cardiac energy state and dysfunction. These results suggest that in intact hearts an impairment of mitochondrial metabolism is involved in the development of doxorubicin cardiotoxicity. Copyright 2010 Elsevier Inc. All rights reserved.

  12. [Intervention of systolic pressure and left ventricular hypertrophy in rats under cold stress].

    PubMed

    Sun, C F; Wang, S G; Peng, Y G; Shi, Y; Du, Y P; Shi, G X; Wen, T; Wang, Y K; Su, H

    2016-06-20

    To investigate the effects of different drugs on systolic blood pressure (SBP) and left ventricular hypertrophy (LVH) in spontaneously hypertensive rats under cold stress. A total of 40 male spontaneously hypertensive rats aged 10 weeks (160~200 g) were given adaptive feeding for 7 days at a temperature of 20±1°C and then randomly divided into control group, cold stress group, metoprolol group, amlodipine group, and benazepril group, with 8 rats in each group. SBP, body weight, and heart rate were measured once a week. After the rats were sacrificed by exsanguination, left ventricular weight (LVW) was measured, and left ventricular weight index (LVWI; mg/g) was calculated. Radioimmunoassay was used to measure the concentrations of endothelin-1 (ET-1) and angiotensin-II (Ang-II) in plasma and myocardium, and the chemical method was used to measure the concentrations of nitric oxide (NO) in plasma and myocardium. RT-PCR was used to measure the mRNA expression of endothelin-A receptor. Compared with the cold stress group, all medication groups showed significant reductions in SBP since week 5 (P<0.05). The cold stress group showed a significant increase in LVWI compared with the control group (3.38±0.27 mg/g vs 2.89±0.19 mg/g, P<0.05). The amlodipine group showed a significant reduction in LVWI compared with the cold stress group (2.98±0.28 mg/g vs 3.38±0.27 mg/g, P<0.05). The cold stress group showed a significant reduction in plasma NO concentration compared with the control group (104.9±19.5 μmol/L vs 129.3±17.8 μmol/L, P<0.05) ; compared with the cold stress group, all the medication groups showed significant increases in blood NO concentration (P<0.05). The cold stress group showed a significant increase in myocardial ET-1 concentration compared with the control group (6.3±1.5 pg/100 mg vs 4.5±1.9 pg/100 mg, P<0.05) ; compared with the cold stress group, the amlodipine group showed a significant reduction in myocardial ET-1 concentration (4.4±1.0 pg

  13. Krill oil attenuates left ventricular dilatation after myocardial infarction in rats

    PubMed Central

    2011-01-01

    Background In the western world, heart failure (HF) is one of the most important causes of cardiovascular mortality. Supplement with n-3 polyunsaturated fatty acids (PUFA) has been shown to improve cardiac function in HF and to decrease mortality after myocardial infarction (MI). The molecular structure and composition of n-3 PUFA varies between different marine sources and this may be of importance for their biological effects. Krill oil, unlike fish oil supplements, contains the major part of the n-3 PUFA in the form of phospholipids. This study investigated effects of krill oil on cardiac remodeling after experimental MI. Rats were randomised to pre-treatment with krill oil or control feed 14 days before induction of MI. Seven days post-MI, the rats were examined with echocardiography and rats in the control group were further randomised to continued control feed or krill oil feed for 7 weeks before re-examination with echocardiography and euthanization. Results The echocardiographic evaluation showed significant attenuation of LV dilatation in the group pretreated with krill oil compared to controls. Attenuated heart weight, lung weight, and levels of mRNA encoding classical markers of LV stress, matrix remodeling and inflammation reflected these findings. The total composition of fatty acids were examined in the left ventricular (LV) tissue and all rats treated with krill oil showed a significantly higher proportion of n-3 PUFA in the LV tissue, although no difference was seen between the two krill oil groups. Conclusions Supplement with krill oil leads to a proportional increase of n-3 PUFA in myocardial tissue and supplement given before induction of MI attenuates LV remodeling. PMID:22206454

  14. Intralipid prevents and rescues fatal pulmonary arterial hypertension and right ventricular failure in rats.

    PubMed

    Umar, Soban; Nadadur, Rangarajan D; Li, Jingyuan; Maltese, Federica; Partownavid, Parisa; van der Laarse, Arnoud; Eghbali, Mansoureh

    2011-09-01

    Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling leading to right ventricular (RV) hypertrophy and failure. Intralipid (ILP), a source of parenteral nutrition for patients, contains γ-linolenic acid and soy-derived phytoestrogens that are protective for lungs and heart. We, therefore, investigated the therapeutic potential of ILP in preventing and rescuing monocrotaline-induced PAH and RV dysfunction. PAH was induced in male rats with monocrotaline (60 mg/kg). Rats then received daily ILP (1 mL of 20% ILP per day IP) from day 1 to day 30 for prevention protocol or from day 21 to day 30 for rescue protocol. Other monocrotaline-injected rats were left untreated to develop severe PAH by day 21 or RV failure by approximately day 30. Saline or ILP-treated rats served as controls. Significant increase in RV pressure and decrease in RV ejection fraction in the RV failure group resulted in high mortality. Therapy with ILP resulted in 100% survival and prevented PAH-induced RV failure by preserving RV pressure and RV ejection fraction and preventing RV hypertrophy and lung remodeling. In preexisting severe PAH, ILP attenuated most lung and RV abnormalities. The beneficial effects of ILP in PAH seem to result from the interplay of various factors, among which preservation and/or stimulation of angiogenesis, suppression and/or reversal of inflammation, fibrosis and hypertrophy, in both lung and RV, appear to be major contributors. In conclusion, ILP not only prevents the development of PAH and RV failure but also rescues preexisting severe PAH.

  15. Evaluation of activity inotropic of a new steroid derivative using an isolated rat heart model

    PubMed Central

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Elodia, García-Cervera; Eduardo, Pool-Gómez; Maria, López-Ramos; Marcela, Rosas-Nexticapa; Lenin, Hau-Heredia; Bety, Sarabia-Alcocer; Landy, Campos-Ramos

    2014-01-01

    There are studies which indicate that some steroid derivatives have inotropic activity; nevertheless, the cellular site and mechanism of action at cardiovascular level is very confusing. In order, to clarify these phenomena in this study, a new estradiol derivative was synthesized with the objective of to evaluate its biological activity on left ventricular pressure and characterize their molecular mechanism. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in absence or presence of the estradiol derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by the OTBDS-estradiol-hexanoic acid derivative was evaluated by measuring left ventricular pressure in absence or presence of following compounds; tamoxifen, prazosin, metoprolol, indomethacin and nifedipine. The results showed that the OTBDS-estradiol-hexanoic acid derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions. Additionally, other data indicate that OTBDS-estradiol-hexanoic acid derivative increase left ventricular pressure in a dose-dependent manner (0.001 to 100 nM); nevertheless, this phenomenon was significantly inhibited only by nifedipine at a dose of 1 nM. These data suggest that positive inotropic activity induced by the OTBDS-estradiol-hexanoic acid derivative is via activation of L-type calcium channel. This phenomenon is a particularly interesting because the positive inotropic activity induced by this steroid derivative involves a molecular mechanism different in comparison with other positive inotropic drugs. PMID:24995077

  16. Evaluation of activity inotropic of a new steroid derivative using an isolated rat heart model.

    PubMed

    Lauro, Figueroa-Valverde; Francisco, Díaz-Cedillo; Elodia, García-Cervera; Eduardo, Pool-Gómez; Maria, López-Ramos; Marcela, Rosas-Nexticapa; Lenin, Hau-Heredia; Bety, Sarabia-Alcocer; Landy, Campos-Ramos

    2014-01-01

    There are studies which indicate that some steroid derivatives have inotropic activity; nevertheless, the cellular site and mechanism of action at cardiovascular level is very confusing. In order, to clarify these phenomena in this study, a new estradiol derivative was synthesized with the objective of to evaluate its biological activity on left ventricular pressure and characterize their molecular mechanism. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in absence or presence of the estradiol derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by the OTBDS-estradiol-hexanoic acid derivative was evaluated by measuring left ventricular pressure in absence or presence of following compounds; tamoxifen, prazosin, metoprolol, indomethacin and nifedipine. The results showed that the OTBDS-estradiol-hexanoic acid derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions. Additionally, other data indicate that OTBDS-estradiol-hexanoic acid derivative increase left ventricular pressure in a dose-dependent manner (0.001 to 100 nM); nevertheless, this phenomenon was significantly inhibited only by nifedipine at a dose of 1 nM. These data suggest that positive inotropic activity induced by the OTBDS-estradiol-hexanoic acid derivative is via activation of L-type calcium channel. This phenomenon is a particularly interesting because the positive inotropic activity induced by this steroid derivative involves a molecular mechanism different in comparison with other positive inotropic drugs.

  17. Pentraxin binding to isolated rat liver nuclei.

    PubMed Central

    Shephard, E G; Smith, P J; Coetzee, S; Strachan, A F; de Beer, F C

    1991-01-01

    The interaction of human C-reactive protein (CRP) and serum amyloid P-component (SAP) with isolated rat liver nuclei was studied to identify nuclear ligands for each pentraxin using the iodinatable heterobifunctional thiol-cleavable cross-linking reagent sulphosuccinimidyl-2-(p-azidosalicylamido)-1,3'-dithiopropio nate (SASD). Nuclei (100 micrograms of DNA) bound 21 pmol of 125I-labelled CRP Ca(2+)-dependently at saturation with half-saturation occurring at 200 pmol of 125I-CRP. By contrast, only 2.7 pmol of 125I-labelled SAP was bound at saturation, with half-saturation at 50 pmol. The binding of pentraxins to nuclei is, in addition to putative chromatin binding, due to nuclear-envelope binding, where 3.2 pmol 125I-labelled CRP binds Ca2+ dependently to nuclear envelopes (25 micrograms) at saturation, but only 0.62 pmol SAP is required to saturate. Specific photocross-linking of 125I-2-(p-azidosalicylamido)-1,3'-dithiopropionate (125I-ASD)-CRP and 125I-ASD-SAP to nuclei revealed transfer of 125I-photoreactive azides to nuclear-envelope proteins of 43, 46, 52 and 70 kDa. In addition, SAP binding to histones H2A, H2B, H3 and H4 was detected, whereas CRP bound only to H4. Neither pentraxin cross-linked to histone H1. Images Fig. 2. Fig. 3. Fig. 4. PMID:1930144

  18. Insulin internalization in isolated rat hepatocytes

    SciTech Connect

    Galan, J.; Trankina, M.; Noel, R.; Ward, W. )

    1990-02-26

    This project was designed to determine whether neomycin, an aminoglycoside antibiotic, has a significant effect upon the pathways of ligand endocytosis in isolated rat hepatocytes. The pathways studied include receptor-mediated endocytosis and fluid-phase endocytosis. Neomycin causes a dose-dependent acceleration of {sup 125}I-insulin internalization. Since fluid-phase endocytosis can also be a significant factor in {sup 125}I-insulin internalization, lucifer yellow (LY), a marker for fluid-phase endocytosis, was incorporated into an assay similar to the {sup 125}I-insulin internalization procedure. In the presence of 5 mM neomycin, a significant increase in LY uptake was evident at 0.2 and 0.4 mg/ml of LY. At 0.8 mg/ml, a decrease in LY uptake was observed. The increased rate of {sup 125}I-insulin internalization in the presence of neomycin was intriguing. Since one action of neomycin is to inhibit phosphoinositidase C, it suggests that the phosphotidylinositol cycle may be involved in ligand internalization by hepatocytes. At low insulin concentrations, receptor-mediated uptake predominates. Fluid-phase uptake can become an important uptake route as insulin concentrations are increased. Since neomycin stimulates fluid-phase endocytosis, it must also be taken into account when measuring ligand internalization.

  19. Intramyocardial sustained delivery of basic fibroblast growth factor improves angiogenesis and ventricular function in a rat infarct model.

    PubMed

    Iwakura, Atsushi; Fujita, Masatoshi; Kataoka, Kazuaki; Tambara, Keiichi; Sakakibara, Yutaka; Komeda, Masashi; Tabata, Yasuhiko

    2003-05-01

    Recently we have demonstrated that the release of basic fibroblast growth factor (bFGF) from a biodegradable gelatin hydrogel carrier depends on the degradation of hydrogel in vivo. The purpose of our study was to assess whether bFGF-incorporating gelatin hydrogels induce myocardial angiogenesis and improve left ventricular function in the infarcted myocardium of rats. Studies were conducted in 22 Lewis rats after a 4-week ligation of the proximal left anterior descending coronary artery. The rats were randomized into the following two groups: the control group (n = 11) had an intramyocardial injection of saline alone, and the FGF group (n = 11) had gelatin hydrogel microspheres containing 100 microg of bFGF injected into the border zone of the infarct area after the repeat left thoracotomy. For visualization of the regional myocardial blood flow in the rat heart, (201)Tl images were taken just before and 4 weeks after the treatment using a 4-head single photon emission computed tomography scanner with pinhole collimators. Left ventricular function was also assessed with echocardiography and a micromanometer-tipped catheter. Finally, the extent of myocardial angiogenesis was evaluated quantitatively in the postmortem analysis. The (201)Tl defect score in the control group remained unchanged before and after the treatment, whereas it decreased significantly in the FGF group. Both regional and global left ventricular function was significantly better in the FGF group compared with the control group. The vascular density in the border zone of the infarct in the FGF group was significantly higher than that in the control group. In conclusion, intramyocardial injection of bFGF-impregnated gelatin hydrogels induces functionally significant angiogenesis and improves left ventricular systolic and diastolic function in the infarcted myocardium of rats.

  20. Morphometry of right ventricular hypertrophy induced by myocardial infarction in the rat.

    PubMed Central

    Anversa, P.; Beghi, C.; McDonald, S. L.; Levicky, V.; Kikkawa, Y.; Olivetti, G.

    1984-01-01

    The growth response of the right ventricle was studied in rats following ligation of the left coronary artery, which produced infarcts comprising approximately 40% of the left ventricle. A month after surgery the weight of the right ventricle was increased 30%, and this hypertrophic change was characterized by a 17% wall thickening, consistent with the 13% greater diameter of myocytes. Myocardial hypertrophy was accompanied by an inadequate growth of the microvasculature that supports tissue oxygenation. This was seen by relative decreases in capillary luminal volume density (-27%) and capillary luminal surface density (-21%) and by an increase in the average maximum distance from the capillary wall to the mitochondria of myocytes (19%). In contrast, measurements of the mean myocyte volume per nucleus showed a proportional enlargement of these cells (32%), from 16,300 cu mu in control animals to 21,500 cu mu in experimental rats. Quantitative analysis of the right coronary artery revealed a 33% increase in its luminal area, commensurate with the magnitude of ventricular hypertrophy. PMID:6236695

  1. Long-term intake of sesamin improves left ventricular remodelling in spontaneously hypertensive rats.

    PubMed

    Li, Wen-xing; Kong, Xiang; Zhang, Jun-xiu; Yang, Jie-ren

    2013-02-26

    This study was designed to evaluate the in vivo cardioprotective effects of food-derived sesamin in spontaneously hypertensive rats (SHR). The study was performed with 17-week-old male normotensive Wistar-Kyoto rats (WKY) and SHR which are untreated or treated with orally administered sesamin for 16 weeks before they were sacrificed. Long-term treatment with sesamin obviously improved left ventricular (LV) hypertrophy and fibrosis in SHR, as indicated by the decrease of LV weight/body weight, myocardial cell size, cardiac fibrosis and collagen type I expression as well as the amelioration of the LV ultrastructure. These effects were associated with reduced systolic blood pressure, enhanced cardiac total antioxidant capability and decreased malondialdehyde content, nitrotyrosine level and transforming growth factor β1 (TGF-β1) expression. All these results suggest that chronic treatment with sesamin improves LV remodeling in SHR through alleviation of oxidative and nitrative stress, reduction of blood pressure and downregulation of TGF-β1 expression.

  2. Tyrosine kinase inhibitor BIBF1000 does not hamper right ventricular pressure adaptation in rats.

    PubMed

    de Raaf, Michiel Alexander; Herrmann, Franziska Elena; Schalij, Ingrid; de Man, Frances S; Vonk-Noordegraaf, Anton; Guignabert, Christophe; Wollin, Lutz; Bogaard, Harm Jan

    2016-09-01

    BIBF1000 is a small molecule tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), and platelet-derived growth factor receptor (PDGFR) and is a powerful inhibitor of fibrogenesis. BIBF1000 is very similar to BIBF1120 (nintedanib), a drug recently approved for the treatment of idiopathic pulmonary fibrosis (IPF). A safety concern pertaining to VEGFR, FGFR, and PDGFR inhibition is the possible interference with right ventricular (RV) responses to an increased afterload, which could adversely affect clinical outcome in patients with IPF who developed pulmonary hypertension. We tested the effect of BIBF1000 on the adaptation of the RV in rats subjected to mechanical pressure overload. BIBF1000 was administered for 35 days in pulmonary artery-banded (PAB) rats. RV adaptation was assessed by echocardiography, pressure volume loop analysis, histology, and determination of atrial natriuretic peptide (ANP) expression. BIBF1000 treatment resulted in growth attenuation but had no effects on RV function after PAB, given absence of changes in cardiac index, end-systolic elastance, connective tissue disposition, and capillary density. We conclude that, in this experimental model of increased afterload, combined VEGFR, FGFR, and PDGFR inhibition does not hamper RV adaptation to pressure overload. Copyright © 2016 the American Physiological Society.

  3. Both α1A- and α1B-adrenergic receptor subtypes couple to the transient outward current (ITo) in rat ventricular myocytes

    PubMed Central

    Homma, Nobuo; Hirasawa, Akira; Shibata, Katsushi; Hashimito, Keitaro; Tsujimoto, Gozoh

    2000-01-01

    Regulation of transient outward current (ITo) by α1-adrenergic (α1AR) plays a key role in cardiac repolarization. α1ARs comprise a heterogeneous family; two natively expressed subtypes (α1A and α1B) and three cloned subtypes (α1a, α1b and α1d) can be distinguished. We have examined the electrophysiological role of each α1AR subtype in regulating ITo in isolated rat ventricular myocytes. Reverse transcription-PCR study revealed the presence of three subtype mRNAs (α1a, α1b and α1d) in rat myocytes. Radioligand binding assay using [125I]-HEAT showed that the inhibition curves for α1AAR-selective antagonists (WB4101, 5-methylurapidil, (+)-niguldipine and KMD-3213) in rat ventricles best fit a two-site model, with 30% high and 70% low affinity binding sites. The high affinity sites were resistant to 100 μM chloroethylclonidine (CEC), while the low affinity sites were highly inactivated by CEC. Whole cell voltage clamp study revealed that methoxamine reduced a 4-aminopyridine(4-AP)-sensitive component of ITo in the isolated rat ventricle myocytes. Lower concentrations of KMD-3213 (1 nM) or 5-MU (10 nM) did not affect the methoxamine-induced reduction of ITo. On the other hand, CEC treatment (100 μM) of isolated myocytes reduced the methoxamine-induced reduction of ITo by 46%, and the remaining response was abolished by lower concentrations of KMD-3213 or 5-MU. The results indicate that rat ventricular myocytes express transcripts of the three α1AR subtypes (α1a, α1b and α1d); however, two pharmacologically distinct α1AR subtypes (α1A and α1B) are predominating in receptor populations, with approximately 30% α1AAR and 70% α1BAR. Although both α1A and α1BAR subtypes are coupled to the cardiac ITo, α1BARs predominantly mediate α1AR-induced effect. PMID:10725259

  4. Asiatic acid inhibits left ventricular remodeling and improves cardiac function in a rat model of myocardial infarction

    PubMed Central

    HUO, LIANYING; SHI, WENBING; CHONG, LING; WANG, JINLONG; ZHANG, KAI; LI, YUFENG

    2016-01-01

    Left ventricular remodeling results in cardiac dysfunction and accounts for the majority of the morbidity and mortality following myocardial infarction (MI). The aim of the present study was to investigate the effect of asiatic acid (AA) on cardiac function and left ventricular remodeling in a rat model of MI and explore the underlying mechanisms. Rats were subjected to coronary artery ligation to model MI and orally treated with AA. After 4 weeks, cardiac function was assessed by echocardiography. Cardiomyocyte cross-sectional area was recorded, and the expression levels of a number of inflammatory cytokines were detected using ELISA. The degree of interstitial fibrosis was determined by evaluating the mRNA expression levels of collagen II and III. Western blot analysis was performed to detect the expression levels of total and phosphorylated p38 MAPK and ERK1/2, to investigate whether they are involved in the mechanism underlying the effect of AA on the heart. Rats subjected to MI displayed significantly impaired cardiac function compared with those subjected to a sham procedure, while this change was reversed by treatment with AA. Furthermore, AA markedly inhibited cardiac hypertrophy, reduced the mRNA expression levels of inflammatory cytokines and decreased interstitial fibrosis in the infarct border zone of MI model rats compared with those in vehicle-treated MI model rats. Furthermore, the phosphorylation of p38 MAPK and ERK1/2 was blocked by AA in the MI rats but not in the sham rats. In summary, AA treatment preserved cardiac function and inhibited left ventricular remodeling, potentially by blocking the phosphorylation of p38 MAPK and ERK1/2 in the infarct border zone of the ischemic myocardium, indicating that AA may be a novel candidate for development as a therapy for MI. PMID:26889217

  5. Layer-specific strain analysis by speckle tracking echocardiography reveals differences in left ventricular function between rats and humans.

    PubMed

    Bachner-Hinenzon, Noa; Ertracht, Offir; Leitman, Marina; Vered, Zvi; Shimoni, Sara; Beeri, Ronen; Binah, Ofer; Adam, Dan

    2010-09-01

    The rat heart is commonly used as an experimental model of the human heart in both health and disease states, assuming that heart function of rats and humans is alike. When studying a rat model, echocardiography is usually performed on sedated rats, whereas standard echocardiography on adult humans does not require any sedation. Since echocardiography results of sedated rats are usually inferred to alert humans, in the present study, we tested the hypothesis that differences in left ventricular (LV) function may be present between rats sedated by a low dose of ketamine-xylazine and alert humans. Echocardiography was applied to 110 healthy sedated rats and 120 healthy alert humans. Strain parameters were calculated from the scans using a layer-specific speckle tracking echocardiography program. The results showed that layer longitudinal strain is equal in rats and humans, whereas segmental strain is heterogeneous (P < 0.05) in a different way in rats and humans (P < 0.05). Furthermore, layer circumferential strain is larger in humans (P < 0.001), and the segmental results showed different segmental heterogeneity in rats and humans (P < 0.05). Radial strain was found to be homogeneous at the apex and papillary muscle levels in humans and heterogeneous in rats (P < 0.001). Additionally, whereas LV twist was equal in rats and humans, in rats the rotation was larger at the apex (P < 0.01) and smaller at the base (P < 0.001). The torsion-to-shortening ratio parameter, which indicates the transmural distribution of contractile myofibers, was found to be equal in rats and humans. Thus, when evaluating LV function of sedated rats under ketamine-xylazine, it is recommended to measure the global longitudinal strain, LV twist, and torsion-to-shortening ratio, since no scaling is required when converting these parameters and inferring them to humans.

  6. Isolation of the Left Subclavian Artery with Right Aortic Arch in Association with Bilateral Ductus Arteriosus and Ventricular Septal Defect

    PubMed Central

    Lee, Ji Seong; Park, Ji Young; Ko, Seong Min; Seo, Dong-Man

    2015-01-01

    Right aortic arch with isolation of the left subclavian artery is a rare anomaly. The incidence of bilateral ductus arteriosus is sporadic, and a right aortic arch with isolation of the left subclavian artery in association with bilateral ductus arteriosus is therefore extremely rare. Since the symptoms and signs of isolation of the left subclavian artery can include the absence or underdevelopment of the left arm, subclavian steal syndrome, or pulmonary artery steal syndrome, the proper therapeutic approach is controversial. We report a case in which surgical reconstruction was used to treat isolation of the left subclavian artery with right aortic arch in association with bilateral ductus arteriosus and a ventricular septal defect. PMID:26665110

  7. Effects of the endogenous cannabinoid anandamide on voltage-dependent sodium and calcium channels in rat ventricular myocytes

    PubMed Central

    Al Kury, Lina T; Voitychuk, Oleg I; Yang, Keun-Hang Susan; Thayyullathil, Faisal T; Doroshenko, Petro; Ramez, Ali M; Shuba, Yaroslav M; Galadari, Sehamuddin; Howarth, Frank Christopher; Oz, Murat

    2014-01-01

    BACKGROUND AND PURPOSE The endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA) exerts negative inotropic and antiarrhythmic effects in ventricular myocytes. EXPERIMENTAL APPROACH Whole-cell patch-clamp technique and radioligand-binding methods were used to analyse the effects of anandamide in rat ventricular myocytes. KEY RESULTS In the presence of 1–10 μM AEA, suppression of both Na+ and L-type Ca2+ channels was observed. Inhibition of Na+ channels was voltage and Pertussis toxin (PTX) – independent. Radioligand-binding studies indicated that specific binding of [3H] batrachotoxin (BTX) to ventricular muscle membranes was also inhibited significantly by 10 μM metAEA, a non-metabolized AEA analogue, with a marked decrease in Bmax values but no change in Kd. Further studies on L-type Ca2+ channels indicated that AEA potently inhibited these channels (IC50 0.1 μM) in a voltage- and PTX-independent manner. AEA inhibited maximal amplitudes without affecting the kinetics of Ba2+ currents. MetAEA also inhibited Na+ and L-type Ca2+ currents. Radioligand studies indicated that specific binding of [3H]isradipine, was inhibited significantly by metAEA. (10 μM), changing Bmax but not Kd. CONCLUSION AND IMPLICATIONS Results indicate that AEA inhibited the function of voltage-dependent Na+ and L-type Ca2+ channels in rat ventricular myocytes, independent of CB1 and CB2 receptor activation. PMID:24758718

  8. Myocyte cellular hypertrophy and hyperplasia contribute to ventricular wall remodeling in anemia-induced cardiac hypertrophy in rats.

    PubMed Central

    Olivetti, G.; Quaini, F.; Lagrasta, C.; Ricci, R.; Tiberti, G.; Capasso, J. M.; Anversa, P.

    1992-01-01

    To determine the effects of chronic anemia on the functional and structural characteristics of the heart, 1-month-old male rats were fed a diet deficient in iron and copper, which led to a hemoglobin concentration of 4.63 g/dl, for 8 weeks. At sacrifice, under fentanyl citrate and droperidol anesthesia, systolic, diastolic, and mean arterial blood pressures were decreased, whereas differential pressure was increased. Left ventricular systolic pressure and the ventricular rate of pressure rise (mmHg/s) were reduced by 9% and 14%, respectively. Moreover, developed peak systolic ventricular pressure and maximal dP/dt diminished 14% and 12%. After perfusion fixation of the coronary vasculature and the myocardium, at a left ventricular intracavitary pressure equal to the in vivo measured end diastolic pressure, a 10% thickening of the left ventricular wall was measured in association with a 13% increase in the equatorial cavitary diameter and a 44% augmentation in ventricular mass. The 52% hypertrophy of the right ventricle was characterized by an 11% thicker wall and a 37% larger ventricular area. The 33% expansion in the aggregate myocyte volume of the left ventricle was found to be due to a 14% myocyte cellular hypertrophy and a 17% myocyte cellular hyperplasia. These cellular parameters were calculated from the estimation of the number of myocyte nuclei per unit volume of myocardium in situ and the evaluation of the distribution of nuclei per cell in enzymatically dissociated myocytes. Myocyte cellular hyperplasia provoked a 9% increase in the absolute number of cells across the left ventricular wall. In contrast, myocyte cellular hypertrophy (42%) was responsible for the increase in myocyte volume of the right ventricle. The proliferative response of left ventricular myocytes was not capable of restoring diastolic cell stress, which was enhanced by the changes in ventricular anatomy with anemia. In conclusion, chronic anemia induced an unbalanced load on the left

  9. 2.1 GHz electromagnetic field does not change contractility and intracellular Ca2+ transients but decreases β-adrenergic responsiveness through nitric oxide signaling in rat ventricular myocytes.

    PubMed

    Olgar, Yusuf; Hidisoglu, Enis; Celen, Murat Cenk; Yamasan, Bilge Eren; Yargicoglu, Piraye; Ozdemir, Semir

    2015-01-01

    Due to the increasing use of wireless technology in developing countries, particularly mobile phones, the influence of electromagnetic fields (EMF) on biologic systems has become the subject of an intense debate. Therefore, in this study we investigated the effect of 2.1 GHz EMF on contractility and beta-adrenergic (β-AR) responsiveness of ventricular myocytes. Rats were randomized to the following groups: Sham rats (SHAM) and rats exposed to 2.1 GHz EMF for 2 h/day for 10 weeks (EM-10). Sarcomere shortening and Ca(2+) transients were recorded in isolated myocytes loaded with Fura2-AM and electrically stimulated at 1 Hz, while L-type Ca(2+) currents (I(CaL)) were measured using whole-cell patch clamping at 36 ± 1°C. Cardiac nitric oxide (NO) levels were measured in tissue samples using a colorimetric assay kit. Fractional shortening and amplitude of the matched Ca(2+) transients were not changed in EM-10 rats. Although the isoproterenol-induced (10(-6) M) I(CaL) response was reduced in rats exposed to EMF, basal I(CaL) density in myocytes was similar between the two groups (p < 0.01). Moreover, EMF exposure led to a significant increase in nitric oxide levels in rat heart (p < 0.02). Long-term exposure to 2.1 GHz EMF decreases β-AR responsiveness of ventricular myocytes through NO signaling.

  10. Chronic exposure to zinc oxide nanoparticles increases ischemic-reperfusion injuries in isolated rat hearts

    NASA Astrophysics Data System (ADS)

    Milivojević, Tamara; Drobne, Damjana; Romih, Tea; Mali, Lilijana Bizjak; Marin, Irena; Lunder, Mojca; Drevenšek, Gorazd

    2016-10-01

    The use of zinc oxide nanoparticles (ZnO NPs) in numerous products is increasing, although possible negative implications of their long-term consumption are not known yet. Our aim was to evaluate the chronic, 6-week oral exposure to two different concentrations of ZnO NPs on isolated rat hearts exposed to ischemic-reperfusion injury and on small intestine morphology. Wistar rats of both sexes ( n = 18) were randomly divided into three groups: (1) 4 mg/kg ZnO NPs, (2) 40 mg/kg ZnO NPs, and (3) control. After 6 weeks of treatment, the hearts were isolated, the left ventricular pressure (LVP), the coronary flow (CF), the duration of arrhythmias and the lactate dehydrogenase release rate (LDH) were measured. A histological investigation of the small intestine was performed. Chronic exposure to ZnO NPs acted cardiotoxic dose-dependently. ZnO NPs in dosage 40 mg/kg maximally decreased LVP (3.3-fold) and CF (2.5-fold) and increased the duration of ventricular tachycardia (all P < 0.01) compared to control, whereas ZnO NPs in dosage 4 mg/kg acted less cardiotoxic. Goblet cells in the small intestine epithelium of rats, treated with 40 mg ZnO NPs/kg, were enlarged, swollen and numerous, the intestinal epithelium width was increased. Unexpectedly, ZnO NPs in both dosages significantly decreased LDH. A 6-week oral exposure to ZnO NPs dose-dependently increased heart injuries and caused irritation of the intestinal mucosa. A prolonged exposure to ZnO NPs might cause functional damage to the heart even with exposures to the recommended daily doses, which should be tested in future studies.

  11. Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart

    NASA Technical Reports Server (NTRS)

    Sung, Derrick; Mills, Robert W.; Schettler, Jan; Narayan, Sanjiv M.; Omens, Jeffrey H.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

    2003-01-01

    INTRODUCTION: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. METHODS AND RESULTS: Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P < 0.0001) and correspondingly decreased average apparent surface conduction velocity by 16%+/- 7% (P = 0.007). Ventricular loading did not significantly alter action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P < 0.0001). The dispersion of APD20 was decreased with loading from 19 +/- 2 msec to 13 +/- 2 msec (P = 0.024), whereas the dispersion of APD80 was not significantly changed. These electrophysiologic changes with ventricular loading were not affected by the nonspecific stretch-activated channel blocker streptomycin (200 microM) and were not attributable to changes in myocardial perfusion or the presence of an electromechanical decoupling agent (butanedione monoxime) during optical mapping. CONCLUSION: Acute loading of the left ventricle of the isolated rabbit heart decreased apparent epicardial conduction velocity and increased action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

  12. Ventricular filling slows epicardial conduction and increases action potential duration in an optical mapping study of the isolated rabbit heart

    NASA Technical Reports Server (NTRS)

    Sung, Derrick; Mills, Robert W.; Schettler, Jan; Narayan, Sanjiv M.; Omens, Jeffrey H.; McCulloch, Andrew D.; McCullough, A. D. (Principal Investigator)

    2003-01-01

    INTRODUCTION: Mechanical stimulation can induce electrophysiologic changes in cardiac myocytes, but how mechanoelectric feedback in the intact heart affects action potential propagation remains unclear. METHODS AND RESULTS: Changes in action potential propagation and repolarization with increased left ventricular end-diastolic pressure from 0 to 30 mmHg were investigated using optical mapping in isolated perfused rabbit hearts. With respect to 0 mmHg, epicardial strain at 30 mmHg in the anterior left ventricle averaged 0.040 +/- 0.004 in the muscle fiber direction and 0.032 +/- 0.006 in the cross-fiber direction. An increase in ventricular loading increased average epicardial activation time by 25%+/- 3% (P < 0.0001) and correspondingly decreased average apparent surface conduction velocity by 16%+/- 7% (P = 0.007). Ventricular loading did not significantly alter action potential duration at 20% repolarization (APD20) but did at 80% repolarization (APD80), from 179 +/- 7 msec to 207 +/- 5 msec (P < 0.0001). The dispersion of APD20 was decreased with loading from 19 +/- 2 msec to 13 +/- 2 msec (P = 0.024), whereas the dispersion of APD80 was not significantly changed. These electrophysiologic changes with ventricular loading were not affected by the nonspecific stretch-activated channel blocker streptomycin (200 microM) and were not attributable to changes in myocardial perfusion or the presence of an electromechanical decoupling agent (butanedione monoxime) during optical mapping. CONCLUSION: Acute loading of the left ventricle of the isolated rabbit heart decreased apparent epicardial conduction velocity and increased action potential duration by a load-dependent mechanism that may not involve stretch-activated channels.

  13. Influence of a change in stimulation rate on action potentials, currents and contractions in rat ventricular cells.

    PubMed

    Mitchell, M R; Powell, T; Terrar, D A; Twist, V W

    1985-07-01

    The effects of a change in stimulation rate on electrical activity and accompanying contraction were investigated in ventricular cells isolated from rat heart; the cells were stimulated to contract either by brief depolarization pulses which evoked action potentials, or, under voltage-clamp conditions, by step depolarizations. An increase in stimulation rate from 0.3 to 3 Hz resulted in a gradual reduction in the amplitude of contraction and attenuation of the late phase of the action potential. These changes were less marked at more depolarized potentials. The ventricular cells were voltage clamped at -40 mV and initially stimulated at 0.3 Hz by step depolarizations to 0 mV for 10 or 100 ms, which activated the second inward current (Isi) and an accompanying contraction. The amplitude and time course of contraction were similar with the two pulse durations. When the duration of the depolarization was 100 ms, an increase in stimulation rate to 3 Hz caused a gradual decline in the amplitude of Isi and of the evoked contraction; at the same time extra contractions and small, transient inward currents appeared in addition to the evoked contractions and Isis. There was a reduction in the early component of decay of Isi at 3 Hz. With a depolarizing pulse duration of 10 ms, an increase in stimulation rate to 3 or to 4.2 Hz did not change the amplitude of the evoked Isi or contraction and no extra contractions or currents appeared. Intracellular EGTA abolished all contractions in the cells and an increase in the rate of stimulation with 100 ms pulses did not then induce transient inward currents. There was some decrease in the Isi amplitude but this was not as marked as in the absence of EGTA and the time course of current decay was similar at the two rates. Ryanodine prevented the appearance of extra contractions and currents when the stimulation rate was increased to 3 Hz and, as in the presence of intracellular EGTA, there was a small decrease in Isi amplitude while

  14. Berberine attenuates adverse left ventricular remodeling and cardiac dysfunction after acute myocardial infarction in rats: role of autophagy.

    PubMed

    Zhang, Yao-Jun; Yang, Shao-Hua; Li, Ming-Hui; Iqbal, Javaid; Bourantas, Christos V; Mi, Qiong-Yu; Yu, Yi-Hui; Li, Jing-Jing; Zhao, Shu-Li; Tian, Nai-Liang; Chen, Shao-Liang

    2014-12-01

    The present study aimed to test the hypothesis that berberine, a plant-derived anti-oxidant, attenuates adverse left ventricular remodelling and improves cardiac function in a rat model of myocardial infarction (MI). Furthermore, the potential mechanisms that mediated the cardioprotective actions of berberine, in particular the effect on autophagy, were also investigated. Acute MI was induced by ligating the left anterior descending coronary artery of Sprague-Dawley rats. Cardiac function was assessed by transthoracic echocardiography. The protein activity/levels of autophagy related to signalling pathways (e.g. LC-3B, Beclin-1) were measured in myocardial tissue by immunohistochemical staining and western blot. Four weeks after MI, berberine significantly prevented cardiac dysfunction and adverse cardiac remodelling. MI rats treated with low dose berberine (10 mg/kg per day) showed higher left ventricular ejection fraction and fractional shortening than those treated with high-dose berberine (50 mg/kg per day). Both doses reduced interstitial fibrosis and post-MI adverse cardiac remodelling. The cardioprotective action of berberine was associated with increased LC-3B II and Beclin-1 expressions. Furthermore, cardioprotection with berberine was potentially related to p38 MAPK inhibition and phospho-Akt activation. The present in vivo study showed that berberine is effective in promoting autophagy, and subsequently attenuating left ventricular remodelling and cardiac dysfunction after MI. The potential underlying mechanism is augmentation of autophagy through inhibition of p38 MAPK and activation of phospho-Akt signalling pathways.

  15. Amyloid beta peptide 22-35 induces a negative inotropic effect on isolated rat hearts

    PubMed Central

    Yousefirad, Neda; Kaygısız, Ziya; Aydın, Yasemin

    2016-01-01

    Evidences indicate that deposition of amyloid beta peptides (Aβs) plays an important role in the pathogenesis of Alzheimer disease. Aβs may influence cardiovascular system and ileum contractions. But the effect of amyloid beta peptide 22-35 (Aβ22-35) on cardiovascular functions and contractions of ileum has not been studied. Therefore, the present study aimed to investigate the possible effects of this peptide on isolated rat heart and ileum smooth muscle. Langendorff-perfused rat heart preparations were established. The hearts were perfused under constant pressure (60 mmHg) with modified Krebs-Henseleit solution. Aβ22-35 at doses of 1, 10 and 100 nM significantly decreased left ventricular developed pressure (LVDP; an index of cardiac contractility) and maximal rate of pressure development of left ventricle (+dP/dtmax; another index of cardiac contractility). This peptide at doses studied had no significant effect on heart rate, coronary flow, monophasic action potential amplitude (MAPamp), MAP duration at 90% repolarization (MAP90) and ileum contractions. We suggest that Aβ22-35 exerts a negative inotropism on isolated rat hearts with unchanged heart rate, coronary flow, MAPamp, MAP90 and smooth muscle contractility of ileum. PMID:28078053

  16. Metformin attenuates ventricular hypertrophy by activating the AMP-activated protein kinase-endothelial nitric oxide synthase pathway in rats.

    PubMed

    Zhang, Cheng-Xi; Pan, Si-Nian; Meng, Rong-Sen; Peng, Chao-Quan; Xiong, Zhao-Jun; Chen, Bao-Lin; Chen, Guang-Qin; Yao, Feng-Juan; Chen, Yi-Li; Ma, Yue-Dong; Dong, Yu-Gang

    2011-01-01

    1. Metformin is an activator of AMP-activated protein kinase (AMPK). Recent studies suggest that pharmacological activation of AMPK inhibits cardiac hypertrophy. In the present study, we examined whether long-term treatment with metformin could attenuate ventricular hypertrophy in a rat model. The potential involvement of nitric oxide (NO) in the effects of metformin was also investigated. 2. Ventricular hypertrophy was established in rats by transaortic constriction (TAC). Starting 1 week after the TAC procedure, rats were treated with metformin (300 mg/kg per day, p.o.), N(G)-nitro-L-arginine methyl ester (L-NAME; 50 mg/kg per day, p.o.) or both for 8 weeks prior to the assessment of haemodynamic function and cardiac hypertrophy. 3. Cultured cardiomyocytes were used to examine the effects of metformin on the AMPK-endothelial NO synthase (eNOS) pathway. Cells were exposed to angiotensin (Ang) II (10⁻⁶ mol/L) for 24 h under serum-free conditions in the presence or absence of metformin (10⁻³ mol/L), compound C (10⁻⁶ mol/L), L-NAME (10⁻⁶ mol/L) or their combination. The rate of incorporation of [³H]-leucine was determined, western blotting analyses of AMPK-eNOS, neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) were undertaken and the concentration of NO in culture media was determined. 4. Transaortic constriction resulted in significant haemodynamic dysfunction and ventricular hypertrophy. Myocardial fibrosis was also evident. Treatment with metformin improved haemodynamic function and significantly attenuated ventricular hypertrophy. Most of the effects of metformin were abolished by concomitant L-NAME treatment. L-NAME on its own had no effect on haemodynamic function and ventricular hypertrophy in TAC rats. 5. In cardiomyocytes, metformin inhibited AngII-induced protein synthesis, an effect that was suppressed by the AMPK inhibitor compound C or the eNOS inhibitor L-NAME. The improvement in cardiac structure and

  17. Effects of Rosiglitazone with Insulin Combination Therapy on Oxidative Stress and Lipid Profile in Left Ventricular Muscles of Diabetic Rats

    PubMed Central

    Kavak, Servet; Ayaz, Lokman; Emre, Mustafa

    2012-01-01

    Purpose. In this study, we tested the hypothesis that rosiglitazone (RSG) with insulin is able to quench oxidative stress initiated by high glucose through prevention of NAD(P)H oxidase activation. Methods and Materials. Male albino Wistar rats were randomly divided into an untreated control group (C), a diabetic group (D) that was treated with a single intraperitoneal injection of streptozotocin (45 mgkg−1), and rosiglitazone group that was treated with RSG twice daily by gavage and insulin once daily by subcutaneous injection (group B). HbA1c and blood glucose levels in the circulation and malondialdehyde and 3-nitrotyrosine levels in left ventricular muscle were measured. Result. Treatment of D rats with group B resulted in a time-dependent decrease in blood glucose. We found that the lipid profile and HbA1c levels in group B reached the control group D rat values at the end of the treatment period. There was an increase in 3-nitrotyrosine levels in group D compared to group C. Malondialdehyde and 3-nitrotyrosine levels were found to be decreased in group B compared to group D (P < 0.05). Conclusion. Our data suggests that the treatment of diabetic rats with group B for 8 weeks may decrease the oxidative/nitrosative stress in left ventricular tissue of rats. Thus, in diabetes-related vascular diseases, group B treatment may be cardioprotective. PMID:22829806

  18. Effects of rosiglitazone with insulin combination therapy on oxidative stress and lipid profile in left ventricular muscles of diabetic rats.

    PubMed

    Kavak, Servet; Ayaz, Lokman; Emre, Mustafa

    2012-01-01

    In this study, we tested the hypothesis that rosiglitazone (RSG) with insulin is able to quench oxidative stress initiated by high glucose through prevention of NAD(P)H oxidase activation. Male albino Wistar rats were randomly divided into an untreated control group (C), a diabetic group (D) that was treated with a single intraperitoneal injection of streptozotocin (45 mg kg(-1)), and rosiglitazone group that was treated with RSG twice daily by gavage and insulin once daily by subcutaneous injection (group B). HbA1c and blood glucose levels in the circulation and malondialdehyde and 3-nitrotyrosine levels in left ventricular muscle were measured. Treatment of D rats with group B resulted in a time-dependent decrease in blood glucose. We found that the lipid profile and HbA1c levels in group B reached the control group D rat values at the end of the treatment period. There was an increase in 3-nitrotyrosine levels in group D compared to group C. Malondialdehyde and 3-nitrotyrosine levels were found to be decreased in group B compared to group D (P < 0.05). Our data suggests that the treatment of diabetic rats with group B for 8 weeks may decrease the oxidative/nitrosative stress in left ventricular tissue of rats. Thus, in diabetes-related vascular diseases, group B treatment may be cardioprotective.

  19. Age and hypertrophy alter the contribution of sarcoplasmic reticulum and Na+/Ca2+ exchange to Ca2+ removal in rat left ventricular myocytes.

    PubMed

    Fowler, Mark R; Naz, James R; Graham, Mark D; Orchard, Clive H; Harrison, Simon M

    2007-03-01

    Age and hypertension contribute significantly to cardiac morbidity and mortality, however the importance of each during the progression of hypertrophy is unclear. This investigation examined the effect of age and hypertension on Ca(2+) handling in rat ventricular myocytes by comparing a genetic model of hypertension and cardiac hypertrophy (spontaneously hypertensive rat, SHR) with its normotensive control (Wistar-Kyoto rat, WKY) at 5 and 8 months of age. Experiments were performed on single left ventricular myocytes isolated from SHR or WKY hearts. Intracellular Ca(2+) was measured optically using fura-2 or fluo-3. SHR myocytes had a significantly larger cell width and volume and a significantly decreased cell length/width ratio at 5 and 8 months compared to normotensive controls. Age had no effect on cell length, width, volume or the length/width ratio. Ca(2+) transient amplitude, sarcoplasmic reticulum (SR) Ca(2+) content and contraction amplitude were unaffected by age or hypertrophy. However at 8 months the contribution of the SR to Ca(2+) uptake during relaxation decreased, with a concomitant increase in the contribution of Na(+)/Ca(2+) exchanger (NCX) function to relaxation, in SHR and WKY myocytes. The incidence of non-synchronous SR Ca(2+) release decreased with age but not hypertrophy in SHR and WKY myocytes. These results show that the changes in Ca(2+) handling observed during progression of mild hypertrophy in SHR are the same as those that occur during ageing in normotensive control animals and can, therefore, be ascribed to maturation rather than hypertrophy.

  20. Case report. Isolated left ventricular myocardium non-compaction: MR imaging findings from three cases.

    PubMed

    Junqueira, F P; Fernandes, F D B; Coutinho, A C; De Pontes, P V; Domingues, R C

    2009-02-01

    The purpose of this study is to report three cases of left ventricular myocardium non-compaction (LVNC), with emphasis on the MRI findings. From May 2006 to February 2007, three patients -- 2 females (6 years and 42 years of age) and 1 male (18 years of age) -- presented to our radiology department, two of them with fatigue, shortness of breath and episodes of syncope and arrhythmia, for further investigation by cardiac MRI because an apparent asymmetrical pattern of hypertrophy of the left ventricular myocardium was suspected by transthoracic echocardiography. The 18-year-old patient was only experiencing arrhythmia, and arrhythmogenic right ventricular dysplasia was suspected. The images (produced by a 1.5T MRI system) were interpreted by two experienced radiologists and post-processed with Argus software (Siemens, Germany) for ejection fraction calculation. In all three patients, MRI aided in the correct identification of prominent ventricular myocardial trabeculations and deep intertrabecular recesses communicating with the ventricular cavity, as well as areas of hypokinesia with depressed systolic function, and showed the absence of myocardial delayed enhancement and other structural heart defects. In conclusion, cardiac MRI was useful for correctly identifying this rare congenital heart disorder and appears to increase diagnostic accuracy. Although considered a rare anomaly, radiologists should be capable of recognizing LVNC, as current non-invasive imaging methods have increased the frequency of this diagnosis and timely detection is vital in considering early-stage transplantation.

  1. Protein kinase A is activated by the n–3 polyunsaturated fatty acid eicosapentaenoic acid in rat ventricular muscle

    PubMed Central

    Szentandrássy, Norbert; Pérez-Bido, M R; Alonzo, E; Negretti, N; O'Neill, Stephen C

    2007-01-01

    During cardiac ischaemia antiarrhythmic n–3 polyunsaturated fatty acids (PUFAs) are released following activation of phospholipase A2, if they are in the diet prior to ischaemia. Here we show a positive lusitropic effect of one such PUFA, eicosapentaenoic acid (EPA) in the antiarrhythmic concentration range in Langendorff hearts and isolated rat ventricular myocytes due to activation of protein kinase A (PKA). Several different approaches indicated activation of PKA by EPA (5–10 μmol l−1): the time constant of decay of the systolic Ca2+ transient decreased to 65.3 ± 5.0% of control, Western blot analysis showed a fourfold increase in phospholamban phosphorylation, and PKA activity increased by 21.0 ± 7.3%. In addition myofilament Ca2+ sensitivity was reduced in EPA; this too may have resulted from PKA activation. We also found that EPA inhibited L-type Ca2+ current by 38.7 ± 3.9% but this increased to 63.3 ± 3.4% in 10 μmol l−1 H89 (to inhibit PKA), providing further evidence of activation of PKA by EPA. PKA inhibition also prevented the lusitropic effect of EPA on the systolic Ca2+ transient and contraction. Our measurements show, however, PKA activation in EPA cannot be explained by increased cAMP levels and alternative mechanisms for PKA activation are discussed. The combined lusitropic effect and inhibition of contraction by EPA may, respectively, combat diastolic dysfunction in ischaemic cardiac muscle and promote cell survival by preserving ATP. This is a further level of protection for the heart in addition to the well-documented antiarrhythmic qualities of these fatty acids. PMID:17510185

  2. Baroreflex failure increases the risk of pulmonary edema in conscious rats with normal left ventricular function.

    PubMed

    Sakamoto, Kazuo; Hosokawa, Kazuya; Saku, Keita; Sakamoto, Takafumi; Tobushi, Tomoyuki; Oga, Yasuhiro; Kishi, Takuya; Ide, Tomomi; Sunagawa, Kenji

    2016-01-15

    In heart failure with preserved ejection fraction (HFpEF), the complex pathogenesis hinders development of effective therapies. Since HFpEF and arteriosclerosis share common risk factors, it is conceivable that stiffened arterial wall in HFpEF impairs baroreflex function. Previous investigations have indicated that the baroreflex regulates intravascular stressed volume and arterial resistance in addition to cardiac contractility and heart rate. We hypothesized that baroreflex dysfunction impairs regulation of left atrial pressure (LAP) and increases the risk of pulmonary edema in freely moving rats. In 15-wk Sprague-Dawley male rats, we conducted sinoaortic denervation (SAD, n = 6) or sham surgery (Sham, n = 9), and telemetrically monitored ambulatory arterial pressure (AP) and LAP. We compared the mean and SD (lability) of AP and LAP between SAD and Sham under normal-salt diet (NS) or high-salt diet (HS). SAD did not increase mean AP but significantly increased AP lability under both NS (P = 0.001) and HS (P = 0.001). SAD did not change mean LAP but significantly increased LAP lability under both NS (SAD: 2.57 ± 0.43 vs. Sham: 1.73 ± 0.30 mmHg, P = 0.01) and HS (4.13 ± 1.18 vs. 2.45 ± 0.33 mmHg, P = 0.02). SAD markedly increased the frequency of high LAP, and SAD with HS prolonged the duration of LAP > 18 mmHg by nearly 20-fold compared with Sham (SAD + HS: 2,831 ± 2,366 vs. Sham + HS: 148 ± 248 s, P = 0.01). We conclude that baroreflex failure impairs volume tolerance and together with salt loading increases the risk of pulmonary edema even in the absence of left ventricular dysfunction. Baroreflex failure may contribute in part to the pathogenesis of HFpEF.

  3. An increased TREK-1-like potassium current in ventricular myocytes during rat cardiac hypertrophy.

    PubMed

    Wang, Weiping; Zhang, Man; Li, Pingping; Yuan, Hui; Feng, Nan; Peng, Ying; Wang, Ling; Wang, Xiaoliang

    2013-04-01

    To elucidate the expression and identify the functional changes of 2 pore domain potassium channel TREK-1 during cardiac hypertrophy in rats, left ventricular hypertrophy was induced by subcutaneous injection with isoproterenol. Western blot was used to detect the expression of TREK-1 channel protein, and inside-out and whole-cell recordings were used to record TREK-1 currents. The results showed that TREK-1 protein expression in endocardium was slightly higher than that in epicardium in control left ventricles. However, it was obviously upregulated by 89.8% during hypertrophy, 2.3-fold higher than in epicardium. Mechanical stretch, intracellular acidification, and arachidonic acid could activate a TREK-1-like current in cardiomyocytes. The slope conductances of cardiac TREK-1 and CHO/TREK-1 channels were 123 ± 7 and 113 ± 17 pS, respectively. The TREK-1 inhibitor L-3-n-butylphthalide (10 μM) reduced the currents in CHO/TREK-1 cells, normal cardiomyocytes, and hypertrophic cardiomyocytes by 48.5%, 54.3%, and 55.5%, respectively. The percentage of L-3-n-butylphthalide-inhibited outward whole-cell current in hypertrophic cardiomyocytes (23.7%) was larger than that in normal cardiomyocytes (14.2%). The percentage of chloroform-activated outward whole-cell current in hypertrophic cardiomyocytes (58.3%) was also larger than normal control (40.2%). Our results demonstrated that in hypertrophic rats, TREK-1 protein expression in endocardium was specifically increased and the ratio of TREK-1 channel current in cardiac outward currents was also enhanced. TREK-1 might balance potassium ion flow during hypertrophy and might be a potential drug target for heart protection.

  4. Posterior left atrial isolation for atrial fibrillation in left ventricular diastolic impairment is associated with better arrhythmia free survival.

    PubMed

    Nalliah, Chrishan; Lim, Toon Wei; Bhaskaran, Abhishek; Kizana, Eddy; Kovoor, Pramesh; Thomas, Liza; Ross, David L; Thomas, Stuart P

    2015-04-01

    Patients with left ventricular diastolic impairment (LVDI) have higher rates of arrhythmia recurrence following atrial fibrillation (AF) ablation. Past studies have implicated the posterior left atrium (LA) in atrial arrhythmia maintenance in conditions that cause LVDI. We prospectively compared posterior LA isolation (PLAI) with wide antral isolation (WAI) in patients with LVDI having AF ablation. We conducted a sub-study of a previously published large randomized control study that compared PLAI with WAI. Two hundred and twenty consecutive consenting patients referred for catheter ablation of AF (paroxysmal 135, persistent 48, long standing persistent 37) were recruited (female 43, mean age 59 ± 10 years). Transthoracic echocardiography identified 50 (23%) patients with LVDI and preserved left ventricular systolic function (ejection fraction ≥ 50%). Cox regression analysis was utilized to identify independent predictors of atrial arrhythmia after ablation. Patients were followed for median 4.6 (inter quartile range 4.0-5.5) years. Patients with LVDI having PLAI had better arrhythmia free survival than patients randomized to conventional ablation (Log rank P=0.028). The only independent predictor of recurrence utilizing Cox regression analysis was ablation strategy (2.3 [1.15-4.74], P=0.026). Posterior isolation of the LA results in superior atrial arrhythmia free survival in patients with LVDI. Further investigation is required to determine potential mechanisms. http://www.anzctr.org.au;ACTRN12606000467538. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

  5. Effects of cannabidiol on contractions and calcium signaling in rat ventricular myocytes.

    PubMed

    Ali, Ramez M; Al Kury, Lina T; Yang, Keun-Hang Susan; Qureshi, Anwar; Rajesh, Mohanraj; Galadari, Sehamuddin; Shuba, Yaroslav M; Howarth, Frank Christopher; Oz, Murat

    2015-04-01

    Cannabidiol (CBD), a major nonpsychotropic cannabinoid found in Cannabis plant, has been shown to influence cardiovascular functions under various physiological and pathological conditions. In the present study, the effects of CBD on contractility and electrophysiological properties of rat ventricular myocytes were investigated. Video edge detection was used to measure myocyte shortening. Intracellular Ca(2+) was measured in cells loaded with the Ca(2+) sensitive fluorescent indicator fura-2 AM. Whole-cell patch clamp was used to measure action potential and Ca(2+) currents. Radioligand binding was employed to study pharmacological characteristics of CBD binding. CBD (1μM) caused a significant decrease in the amplitudes of electrically evoked myocyte shortening and Ca(2+) transients. However, the amplitudes of caffeine-evoked Ca(2+) transients and the rate of recovery of electrically evoked Ca(2+) transients following caffeine application were not altered. CBD (1μM) significantly decreased the duration of APs. Further studies on L-type Ca(2+) channels indicated that CBD inhibits these channels with IC50 of 0.1μM in a voltage-independent manner. Radioligand studies indicated that the specific binding of [(3)H]Isradipine, was not altered significantly by CBD. The results suggest that CBD depresses myocyte contractility by suppressing L-type Ca(2+) channels at a site different than dihydropyridine binding site and inhibits excitation-contraction coupling in cardiomyocytes.

  6. Endogenous protein phosphatase 1 runs down gap junctional communication of rat ventricular myocytes.

    PubMed

    Duthe, F; Plaisance, I; Sarrouilhe, D; Hervé, J C

    2001-11-01

    Gap junctional channels are essential for normal cardiac impulse propagation. In ventricular myocytes of newborn rats, channel opening requires the presence of ATP to allow protein kinase activities; otherwise, channels are rapidly deactivated by the action of endogenous protein phosphatases (PPs). The lack of influence of Mg(2+) and of selective PP2B inhibition is not in favor of the involvements of Mg(2+)-dependent PP2C and PP2B, respectively, in the loss of channel activity. Okadaic acid (1 microM) and calyculin A (100 nM), both inhibitors of PP1 and PP2A activities, significantly retarded the loss of channel activity. However, a better preservation was obtained in the presence of selective PP1 inhibitors heparin (100 microg/ml) or protein phosphatase inhibitor 2 (I2; 100 nM). Conversely, the stimulation of endogenous PP1 activity by p-nitrophenyl phosphate, in the presence of ATP, led to a progressive fading of junctional currents unless I2 was simultaneously added. Together, these results suggest that a basal phosphorylation-dephosphorylation turnover regulates gap junctional communication which is rapidly deactivated by PP1 activity when the phosphorylation pathway is hindered.

  7. Modification of distinct ion channels differentially modulates Ca2+ dynamics in primary cultured rat ventricular cardiomyocytes

    PubMed Central

    Li, Xichun; Shen, Liping; Zhao, Fang; Zou, Xiaohan; He, Yuwei; Zhang, Fan; Zhang, Chunlei; Yu, Boyang; Cao, Zhengyu

    2017-01-01

    Primary cultured cardiomyocytes show spontaneous Ca2+ oscillations (SCOs) which not only govern contractile events, but undergo derangements that promote arrhythmogenesis through Ca2+ -dependent mechanism. We systematically examined influence on SCOs of an array of ion channel modifiers by recording intracellular Ca2+ dynamics in rat ventricular cardiomyocytes using Ca2+ specific fluorescence dye, Fluo-8/AM. Voltage-gated sodium channels (VGSCs) activation elongates SCO duration and reduces SCO frequency while inhibition of VGSCs decreases SCO frequency without affecting amplitude and duration. Inhibition of voltage-gated potassium channel increases SCO duration. Direct activation of L-type Ca2+ channels (LTCCs) induces SCO bursts while suppressing LTCCs decreases SCO amplitude and slightly increases SCO frequency. Activation of ryanodine receptors (RyRs) increases SCO duration and decreases both SCO amplitude and frequency while inhibiting RyRs decreases SCO frequency without affecting amplitude and duration. The potencies of these ion channel modifiers on SCO responses are generally consistent with their affinities in respective targets demonstrating that modification of distinct targets produces different SCO profiles. We further demonstrate that clinically-used drugs that produce Long-QT syndrome including cisapride, dofetilide, sotalol, and quinidine all induce SCO bursts while verapamil has no effect. Therefore, occurrence of SCO bursts may have a translational value to predict cardiotoxicants causing Long-QT syndrome. PMID:28102360

  8. Fourth ventricular administration of ghrelin induces relaxation of the proximal stomach in the rat.

    PubMed

    Kobashi, Motoi; Yanagihara, Mamoru; Fujita, Masako; Mitoh, Yoshihiro; Matsuo, Ryuji

    2009-02-01

    The effects of fourth ventricular administration of ghrelin on motility of the proximal stomach were examined in anesthetized rats. Intragastric pressure (IGP) was measured using a balloon situated in the proximal part of the stomach. Administration of ghrelin into the fourth ventricle induced relaxation of the proximal stomach in a dose-dependent manner. Significant reduction of IGP was observed at doses of 3, 10, or 30 pmol. The administration of ghrelin (10 or 30 pmol) with growth hormone secretagogue receptor (GHS-R) antagonist ([D-Lys3] GHRP-6; 1 nmol) into the fourth ventricle did not induce a significant change in IGP. The sole administration of [D-Lys3] GHRP-6 also did not induce a significant change in IGP. Bilateral sectioning of the vagi at the cervical level abolished the relaxation induced by the administration of ghrelin (10 or 30 pmol) into the fourth ventricle, suggesting that relaxation induced by ghrelin is mediated by vagal preganglionic neurons. Microinjections of ghrelin (200 fmol) into the caudal part of the dorsal vagal complex (DVC) induced obvious relaxation of the proximal stomach. Similar injections into the intermediate part of the DVC did not induce significant change. Dose-response analyses revealed that the microinjection of 2 fmol of ghrelin into the caudal DVC significantly reduced IGP. These results revealed that ghrelin induced relaxation in the proximal stomach via GHS-R situated in the caudal DVC.

  9. Biphasic effects of hyposmotic challenge on excitation-contraction coupling in rat ventricular myocytes.

    PubMed

    Brette, F; Calaghan, S C; Lappin, S; White, E; Colyer, J; Le Guennec, J Y

    2000-10-01

    The effects of short (1 min) and long (7-10 min) exposure to hyposmotic solution on excitation-contraction coupling in rat ventricular myocytes were studied. After short exposure, the action potential duration at 90% repolarization (APD(90)), the intracellular Ca(2+) concentration ([Ca(2+)](i)) transient amplitude, and contraction increased, whereas the L-type Ca(2+) current (I(Ca, L)) amplitude decreased. Fractional sarcoplasmic reticulum (SR) Ca(2+) release increased but SR Ca(2+) load did not. After a long exposure, I(Ca,L), APD(90), [Ca(2+)](i) transient amplitude, and contraction decreased. The abbreviation of APD(90) was partially reversed by 50 microM DIDS, which is consistent with the participation of Cl(-) current activated by swelling. After 10-min exposure to hyposmotic solution in cells labeled with di-8-aminonaphthylethenylpyridinium, t-tubule patterning remained intact, suggesting the loss of de-t-tubulation was not responsible for the fall in I(Ca,L). After long exposure, Ca(2+) load of the SR was not increased, and swelling had no effect on the site-specific phosphorylation of phospholamban, but fractional SR Ca(2+) release was depressed. The initial positive inotropic response to hyposmotic challenge may be accounted for by enhanced coupling between Ca(2+) entry and release. The negative inotropic effect of prolonged exposure can be accounted for by shortening of the action potential duration and a fall in the I(Ca,L) amplitude.

  10. Impaired cerebral mitochondrial oxidative phosphorylation function in a rat model of ventricular fibrillation and cardiopulmonary resuscitation.

    PubMed

    Jiang, Jun; Fang, Xiangshao; Fu, Yue; Xu, Wen; Jiang, Longyuan; Huang, Zitong

    2014-01-01

    Postcardiac arrest brain injury significantly contributes to mortality and morbidity in patients suffering from cardiac arrest (CA). Evidence that shows that mitochondrial dysfunction appears to be a key factor in tissue damage after ischemia/reperfusion is accumulating. However, limited data are available regarding the cerebral mitochondrial dysfunction during CA and cardiopulmonary resuscitation (CPR) and its relationship to the alterations of high-energy phosphate. Here, we sought to identify alterations of mitochondrial morphology and oxidative phosphorylation function as well as high-energy phosphates during CA and CPR in a rat model of ventricular fibrillation (VF). We found that impairment of mitochondrial respiration and partial depletion of adenosine triphosphate (ATP) and phosphocreatine (PCr) developed in the cerebral cortex and hippocampus following a prolonged cardiac arrest. Optimal CPR might ameliorate the deranged phosphorus metabolism and preserve mitochondrial function. No obvious ultrastructural abnormalities of mitochondria have been found during CA. We conclude that CA causes cerebral mitochondrial dysfunction along with decay of high-energy phosphates, which would be mitigated with CPR. This study may broaden our understanding of the pathogenic processes underlying global cerebral ischemic injury and provide a potential therapeutic strategy that aimed at preserving cerebral mitochondrial function during CA.

  11. A comparative assessment of fluo Ca2+ indicators in rat ventricular myocytes

    PubMed Central

    Hagen, Brian M.; Boyman, Liron; Kao, Joseph P.Y.; Lederer, W. Jonathan

    2012-01-01

    Summary The fluo family of indicators is frequently used in studying Ca2+ physiology; however, choosing which fluo indicator to use is not obvious. Indicator properties are typically determined in well-defined aqueous solutions. Inside cells, however, the properties can change markedly. We have characterized each of three fluo variants (fluo-2MA, fluo-3 and fluo-4) in two forms—the acetoxymethyl (AM) ester and the K+ salt. We loaded indicators into rat ventricular myocytes and used confocal microscopy to monitor depolarization-induced fluorescence changes and fractional shortening. Myocytes loaded with the indicator AM esters showed significantly different Ca2+ transients and fractional shortening kinetics. Loading the K+ salts via whole-cell patch-pipette eliminated differences between fluo-3 and fluo-4, but not fluo-2. Cells loaded with different indicator AM esters showed different staining patterns—suggesting differential loading into organelles. Ca2+ dissociation constants (Kd,Ca), measured in protein-rich buffers mimicking the cytosol were significantly higher than values determined in simple buffers. This increase in Kd,Ca (decrease in Ca2+ affinity) was greatest for fluo-3 and fluo-4, and least for fluo-2. We conclude that the structurally-similar fluo variants differ with respect to cellular loading, subcellular compartmentalization, and intracellular Ca2+ affinity. Therefore, judicious choice of fluo indicator and loading procedure is advisable when designing experiments. PMID:22721780

  12. A comparative assessment of fluo Ca2+ indicators in rat ventricular myocytes.

    PubMed

    Hagen, Brian M; Boyman, Liron; Kao, Joseph P Y; Lederer, W Jonathan

    2012-08-01

    The fluo family of indicators is frequently used in studying Ca(2+) physiology; however, choosing which fluo indicator to use is not obvious. Indicator properties are typically determined in well-defined aqueous solutions. Inside cells, however, the properties can change markedly. We have characterized each of three fluo variants (fluo-2MA, fluo-3 and fluo-4) in two forms-the acetoxymethyl (AM) ester and the K(+) salt. We loaded indicators into rat ventricular myocytes and used confocal microscopy to monitor depolarization-induced fluorescence changes and fractional shortening. Myocytes loaded with the indicator AM esters showed significantly different Ca(2+) transients and fractional shortening kinetics. Loading the K(+) salts via whole-cell patch-pipette eliminated differences between fluo-3 and fluo-4, but not fluo-2MA. Cells loaded with different indicator AM esters showed different staining patterns-suggesting differential loading into organelles. Ca(2+) dissociation constants (K(d,Ca)), measured in protein-rich buffers mimicking the cytosol were significantly higher than values determined in simple buffers. This increase in K(d,Ca) (decrease in Ca(2+) affinity) was greatest for fluo-3 and fluo-4, and least for fluo-2MA. We conclude that the structurally-similar fluo variants differ with respect to cellular loading, subcellular compartmentalization, and intracellular Ca(2+) affinity. Therefore, judicious choice of fluo indicator and loading procedure is advisable when designing experiments. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Ultrastructural localization of calsequestrin in adult rat atrial and ventricular muscle cells

    PubMed Central

    1985-01-01

    The distribution of calsequestrin in rat atrial and ventricular myocardial cells was determined by indirect immunocolloidal gold labeling of ultrathin frozen sections. The results presented show that calsequestrin is confined to the sarcoplasmic reticulum where it is localized in the lumen of the peripheral and the interior junctional sarcoplasmic reticulum as well as in the lumen of the corbular sarcoplasmic reticulum, but absent from the lumen of the network sarcoplasmic reticulum. Comparison of these results with our previous studies on the distribution of the Ca2+ + Mg2+-dependent ATPase of the cardiac sarcoplasmic reticulum show directly that the Ca2+ + Mg2+- dependent ATPase and calsequestrin are confined to distinct regions within the continuous sarcoplasmic reticulum membrane. Assuming that calsequestrin provides the major site of Ca2+ sequestration in the lumen of the sarcoplasmic reticulum, the results presented support the idea that both junctional (interior and peripheral) and specialized nonjunctional (corbular) regions of the sarcoplasmic reticulum are involved in Ca2+ storage and possibly release. Furthermore, the structural differences between the junctional and the corbular sarcoplasmic reticulum support the possibility that Ca2+ storage and/or release from the lumen of the junctional and the corbular sarcoplasmic reticulum are regulated by different physiological signals. PMID:4008530

  14. Barnidipine block of L-type Ca(2+) channel currents in rat ventricular cardiomyocytes.

    PubMed

    Wegener, J W; Meyrer, H; Rupp, J; Nawrath, H

    2000-08-01

    The effects of barnidipine and nifedipine on L-type Ca(2+) current (I(Ca(L))) were investigated in ventricular cardiomyocytes from rats. Both barnidipine and nifedipine reduced I(Ca(L)) in a concentration and voltage dependent manner; the EC(50) were 80 and 130 nM at a holding potential of -80 mV, respectively, and 18 and 6 nM at -40 mV, respectively. Both drugs induced a leftward shift of the steady-state inactivation curve of I(Ca(L)). Using a twin pulse protocol, the relationships between the amount of block of I(Ca(L)) by either drug, seen during the second pulse, and the length of the first pulse were described by monoexponential functions reflecting onset of block, dependent on drug concentration. The onset of block by barnidipine was three times faster than that by nifedipine. With both drugs, recovery of I(Ca(L)) was 50 times slower than under control conditions and described by monoexponential functions reflecting offset of block (independent of drug concentration). The offset of block with barnidipine was three times slower than that with nifedipine. The time constants of block and unblock of I(Ca(L)) by both drugs were used to calculate binding and unbinding and to predict their effects at two frequencies. It is suggested that barnidipine exhibits a higher affinity to the inactivated Ca(2+) channel state as compared to nifedipine.

  15. Barnidipine block of L-type Ca2+ channel currents in rat ventricular cardiomyocytes

    PubMed Central

    Wegener, Jörg W; Meyrer, Hans; Rupp, Johanna; Nawrath, Hermann

    2000-01-01

    The effects of barnidipine and nifedipine on L-type Ca2+ current (ICa(L)) were investigated in ventricular cardiomyocytes from rats.Both barnidipine and nifedipine reduced ICa(L) in a concentration and voltage dependent manner; the EC50 were 80 and 130 nM at a holding potential of −80 mV, respectively, and 18 and 6 nM at −40 mV, respectively.Both drugs induced a leftward shift of the steady-state inactivation curve of ICa(L).Using a twin pulse protocol, the relationships between the amount of block of ICa(L) by either drug, seen during the second pulse, and the length of the first pulse were described by monoexponential functions reflecting onset of block, dependent on drug concentration. The onset of block by barnidipine was three times faster than that by nifedipine.With both drugs, recovery of ICa(L) was 50 times slower than under control conditions and described by monoexponential functions reflecting offset of block (independent of drug concentration). The offset of block with barnidipine was three times slower than that with nifedipine.The time constants of block and unblock of ICa(L) by both drugs were used to calculate binding and unbinding and to predict their effects at two frequencies.It is suggested that barnidipine exhibits a higher affinity to the inactivated Ca2+ channel state as compared to nifedipine. PMID:10952695

  16. Comparative effects of clarithromycin on action potential and ionic currents from rabbit isolated atrial and ventricular myocytes.

    PubMed

    Gluais, Pascale; Bastide, Michìle; Caron, Jacques; Adamantidis, Monique

    2003-04-01

    Prolongation of QT interval by several antibacterial drugs is an unwanted side effect that may be associated with development of ventricular arrhythmias. The macrolide antibacterial agent clarithromycin has been shown to cause QT prolongation. To determine the electrophysiologic basis for this arrhythmogenic potential, we investigated clarithromycin effects on (i). action potentials recorded from rabbit Purkinje fibers and atrial and ventricular myocardium using conventional microelectrodes and (ii). potassium and calcium currents recorded from rabbit atrial and ventricular isolated myocytes using whole-cell patch clamp recordings. We found that (i). clarithromycin (3-100 microM) exerted concentration-dependent lengthening effects on action potential duration in all tissues, with higher efficacy and reverse frequency-dependence in Purkinje fibers. However, clarithromycin did not cause development of early afterdepolarizations, and the parameters other than action potential duration were almost unaffected; (ii). clarithromycin (10-100 microM) reduced the delayed rectifier current. Significant blockade (approximately 30%) was found at the concentration of 30 microM. At 100 microM, it decreased significantly the maximum peak of the calcium current amplitude but failed to alter the transient outward and inwardly rectifier currents. It was concluded that these effects might be an explanation for the QT prolongation observed in some patients treated with clarithromycin.

  17. Effects of injectable anesthetic combinations on left ventricular function and cardiac morphology in Sprague-Dawley rats.

    PubMed

    Sabatini, Carla F; O'Sullivan, M Lynne; Valcour, James E; Sears, William; Johnson, Ron J

    2013-01-01

    Novel anesthetic agents or combinations may provide superior general anesthesia for echocardiography in rodents with the potential for reduced adverse effects. This study sought to characterize the effects of 3 injectable anesthetics on left ventricular (LV) systolic function and cardiac morphology in healthy male and female rats. Rats underwent echocardiographic assessment after general anesthesia via pentobarbital or combinations of ketamine and medetomidine (KME) and ketamine and midazolam (KMI) according to a crossover Latin-square design. Blood samples for serum estradiol measurements were obtained from all females after echocardiography with each anesthetic. Rats given KMI showed superior LV systolic function with the highest values for fractional shortening (FS), ejection fraction (EF) and stroke volume, whereas heart rate was greatest with pentobarbital, followed by KMI and then KME. KME produced the greatest effects on cardiac morphology, most notably during systole, including reduced septal and posterior wall thickness and increased LV chamber dimensions and volumes. In addition, KME had the greatest cardiac-depressing effects on LV systolic function, including reduced FS, EF, and heart rate values. Compared with male rats, female rats had superior LV function with greater EF and FS values, whereas male rats showed higher heart rate. Significant negative correlations were noted between serum estradiol levels and FS and EF values in female rats receiving KME. We conclude that the combination of KMI may be a superior anesthetic for use in male and female rats undergoing echocardiography.

  18. Novel observations on the origin of ependymal cells in the ventricular zone of the rat spinal cord.

    PubMed

    Sevc, Juraj; Daxnerová, Zuzana; Haňová, Viera; Koval', Ján

    2011-02-01

    Despite extensive investigations of gliogenesis, the time of origin of ependymal cells in the spinal cord has not yet been fully elucidated. Using a single dose of 5-bromo-2-deoxyuridine combined with various survival times we monitored: mitotic activity (short survival time), the presence of newly formed cells in the ventricular zone (intermediate survival time) and the formation of ependymal cells (long survival time) during the late embryonic and early postnatal development in the ventricular zone of the spinal cord of rats. In the period of study it was found that the ependymal cells populated this region in two waves. Most of the ependymal cells originated around embryonic day 18 and then between postnatal days 8 and 15. In addition, it was observed that in the ventricular zone of the spinal cord, proliferation and production of ependymal cells continues at the slower rate at least until day 36 of postnatal development. Elucidation of the relationship between progenitors in the embryonic ventricular zone and the relative quiescent ependymal lining of the central canal in adulthood could be important in the search for the adult neural stem cell niche.

  19. Effects of horsefly (Tabanidae) salivary gland extracts on isolated perfused rat heart.

    PubMed

    Rajská, P; Knezl, V; Kazimírová, M; Takác, P; Roller, L; Vidlicka, L; Ciampor, F; Labuda, M; Weston-Davies, W; Nuttall, P A

    2007-12-01

    The speed with which horseflies (Diptera: Tabanidae) obtain a bloodmeal suggests they have potent vasodilators. We used isolated perfused rat heart to examine the vasoactivity of salivary gland extracts (SGEs) of three horsefly species, Hybomitra bimaculata Macquart, Tabanus bromius Linnaeus and Tabanus glaucopis Meigen. Administration of horsefly SGEs to the heart produced biphasic coronary responses: a decrease and subsequent increase in coronary flow (CF), characterized by initial vasoconstriction followed by prolonged vasodilation of coronary vessels. However, although SGEs of H. bimaculata induced a significant decrease in left ventricular pressure (LVP), the effect on changes in CF was not significant except at the highest dose tested. The ability to reduce LVP without significantly lowering CF, or affecting heart rate and rhythm, represents a unique set of properties that have considerable therapeutic potential if they can be reproduced by a single molecule.

  20. Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats

    PubMed Central

    Chen, Michael Yu-Chih

    2016-01-01

    In obstructive sleep apnea (OSA), recurrent obstruction of the upper airway leads to intermittent hypoxia (IH) during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON) or to a group receiving 10 weeks of exercise training (EXE). During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE), whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect. PMID:27977796

  1. Ethanol-Associated Cardiomyocyte Apoptosis and Left Ventricular Dilation Are Unrelated to Changes in Myocardial Telomere Length in Rats.

    PubMed

    Raymond, Andrew R; Becker, Jason; Woodiwiss, Angela J; Booysen, Hendrik L; Norton, Gavin R; Brooksbank, Richard L

    2016-04-01

    The aim of this work was to determine whether ethanol-associated myocardial apoptosis and cardiac dilation are related to myocardial telomere shortening in rats. Sprague-Dawley (SD) rats received either drinking water with (ethanol: n = 19) or without (control: n = 19) 5% (v/v) ethanol ad libitum, for 4 months. Left ventricular (LV) dimensions and function (echocardiography and isolated perfused heart preparations), cardiomyocyte apoptosis (terminal deoxynucleotide transferase-mediated dUTP nick-end labeling), and leukocyte and myocardial telomere length (real-time polymerase chain reaction) were determined at the end of the study. Ethanol administration resulted in a marked increase in cardiomyocyte apoptosis (ethanol 0.85 ± 0.13% vs control 0.36 ± 0.06%; P = .0021) and LV dilation (LV end-diastolic diameter: ethanol 8.20 ± 0.14 mm vs control 7.56 ± 0.11 mm [P = .0014]; volume intercept at 0 mm Hg (V0) of the LV end-diastolic pressure-volume relationship: ethanol 0.40 ± 0.03 mL vs control 0.31 ± 0.02 mL [P = .020]). However, there were no changes in systolic chamber function as indexed by LV endocardial fractional shortening or the slope of the LV systolic pressure-volume relationship (end systolic elastance). The percentage of myocardial apoptosis was correlated with the degree of LV dilation (% apoptosis vs LV EDD: r = 0.39; n = 38; P = .021; vs V0: r = 0.44; n = 19; P = .046). No differences in leukocyte or cardiac telomere length were noted between the ethanol and control groups. Furthermore, cardiac telomere length was not associated with indexes of LV dilation (LVEDD and V0) or cardiomyocyte apoptosis. Chronic ethanol-associated myocardial apoptosis and adverse remodeling occurs independently from changes in cardiac telomere length. Telomere shortening may not be a critical mechanism responsible for cardiomyocyte apoptosis and adverse cardiac remodeling. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Wenxin Keli attenuates ischemia-induced ventricular arrhythmias in rats: Involvement of L‑type calcium and transient outward potassium currents.

    PubMed

    Wang, Xi; Wang, Xin; Gu, Yongwei; Wang, Teng; Huang, Congxin

    2013-02-01

    Wenxin Keli is the first state‑sanctioned traditional Chinese medicine (TCM)-based antiarrhythmic drug. The present study aimed to examine whether long‑term treatment with Wenxin Keli reduces ischemia‑induced ventricular arrhythmias in rats in vivo, and if so, which mechanisms are involved. Male rats were treated with either saline (control group) or Wenxin Keli for 3 weeks and were subjected to myocardial ischemia for 30 min with assessment of the resulting ventricular arrhythmias. The L‑type calcium current (ICa,L) and transient outward potassium current (Ito) were measured by the patch clamp technique in normal rat cardiac ventricular myocytes. During the 30‑min ischemia, Wenxin Keli significantly reduced the incidence of ventricular fibrillation (VF) (P<0.05). The number of ventricular tachycardia (VT)+VF episodes and the severity of arrhythmias were significantly reduced by Wenxin Keli administration compared to the control group (P<0.05). In addition, Wenxin Keli inhibited ICa,L and Ito in a concentration‑dependent manner. These results suggest that long‑term treatment with Wenxin Keli may attenuate ischemia‑induced ventricular arrhythmias in rats and that ICa,L and Ito may be involved in this attenuation.

  3. Left ventricular mechanics in isolated mild mitral stenosis: a three dimensional speckle tracking study.

    PubMed

    Poyraz, Esra; Öz, Tuğba Kemaloğlu; Zeren, Gönül; Güvenç, Tolga Sinan; Dönmez, Cevdet; Can, Fatma; Güvenç, Rengin Çetin; Dayı, Şennur Ünal

    2017-03-11

    In a fraction of patients with mild mitral stenosis, left ventricular systolic function deteriorates despite the lack of hemodynamic load imposed by the dysfunctioning valve. Neither the predisposing factors nor the earlier changes in left ventricular contractility were understood adequately. In the present study we aimed to evaluate left ventricular mechanics using three-dimensional (3D) speckle tracking echocardiography. A total of 31 patients with mild rheumatic mitral stenosis and 27 healthy controls were enrolled to the study. All subjects included to the study underwent echocardiographic examination to collect data for two- and three-dimensional speckle-tracking based stain, twist angle and torsion measurements. Data was analyzed offline with a echocardiographic data analysis software. Patients with rheumatic mild MS had lower global longitudinal (p < 0.001) circumferential (p = 0.02) and radial (p < 0.01) strain compared to controls, despite ejection fraction was similar for both groups [(p = 0.45) for three dimensional and (p = 0.37) for two dimensional measurement]. While the twist angle was not significantly different between groups (p = 0.11), left ventricular torsion was significantly higher in mitral stenosis group (p = 0.03). All strain values had a weak but significant positive correlation with mitral valve area measured with planimetry. Subclinical left ventricular systolic dysfunction develops at an early stage in rheumatic mitral stenosis. Further work is needed to elucidate patients at risk for developing overt systolic dysfunction.

  4. Echocardiographic and pathoanatomical characteristics of isolated left ventricular non-compaction: a step towards classification as a distinct cardiomyopathy

    PubMed Central

    Jenni, R; Oechslin, E; Schneider, J; Jost, C; Kaufmann, P

    2001-01-01

    AIM—To determine clear cut echocardiographic criteria for isolated ventricular non-compaction (IVNC), a cardiomyopathy as yet "unclassified" by the World Health Organization. The disease is not widely known and its diagnosis mostly missed.
METHODS AND RESULTS—In seven out of a series of 34 patients with IVNC the in vivo echocardiographic characteristics were validated against the anatomical examination of the heart removed after death in four and due to heart transplantation in three patients. Four morphological criteria diagnostic for IVNC were found. (1) Coexisting cardiac abnormalities were absent (by definition). (2) A two layer structure was seen, with a compacted thin epicardial band and a much thicker non-compacted endocardial layer of trabecular meshwork with deep endomyocardial spaces. A maximal end systolic ratio of non-compacted to compacted layers of > 2 is diagnostic. (3) The predominant localisation of the pathology was to mid-lateral (seven of seven patients), apical (six), and mid-inferior (seven) areas. The pathological preparations confirmed the echocardiographic findings. Concomitant regional hypokinesia was not confined to the non-compacted segments. (4) There was colour Doppler evidence of deep perfused intertrabecular recesses.
CONCLUSIONS—Four clear cut echocardiographic diagnostic criteria were established. It is suggested that the WHO classification of cardiomyopathies be reconsidered to include IVNC as a distinct cardiomyopathy.


Keywords: isolated ventricular non-compaction; morphological criteria; cardiomyopathy; echocardiography; pathology PMID:11711464

  5. A high-resolution thermoelectric module-based calorimeter for measuring the energetics of isolated ventricular trabeculae at body temperature.

    PubMed

    Johnston, Callum M; Han, June-Chiew; Ruddy, Bryan P; Nielsen, Poul M F; Taberner, Andrew J

    2015-07-15

    Isolated ventricular trabeculae are the most common experimental preparations used in the study of cardiac energetics. However, the experiments have been conducted at subphysiological temperatures. We have overcome this limitation by designing and constructing a novel calorimeter with sufficiently high thermal resolution for simultaneously measuring the heat output and force production of isolated, contracting, ventricular trabeculae at body temperature. This development was largely motivated by the need to better understand cardiac energetics by performing such measurements at body temperature to relate tissue performance to whole heart behavior in vivo. Our approach uses solid-state thermoelectric modules, tailored for both temperature sensing and temperature control. The thermoelectric modules have high sensitivity and low noise, which, when coupled with a multilevel temperature control system, enable an exceptionally high temperature resolution with a noise-equivalent power an order of magnitude greater than those of other existing muscle calorimeters. Our system allows us to rapidly and easily change the experimental temperature without disturbing the state of the muscle. Our calorimeter is useful in many experiments that explore the energetics of normal physiology as well as pathophysiology of cardiac muscle. Copyright © 2015 the American Physiological Society.

  6. [Electrophysiological characteristics of the isolated muscle spindle in rats].

    PubMed

    Zhao, Xue-Hong; Fan, Xiao-Li; Song, Xin-Ai; Shi, Lei

    2011-06-25

    The aim of this study was to observe the electrophysiological characteristics of the isolated rat muscle spindle. The muscle spindle was isolated from rat soleus and the afferent discharge of the isolated muscle spindle was recorded by air-gap technique. In the basic physiological salt solution, the spontaneous impulses of muscle spindle were at a lower level with irregular intervals. The mean frequency of afferents was (51.78 ± 25.63) impulses/1 000 s (n = 13). The muscle spindle afferents were significantly increased and maintained over time by the addition of certain amino acids during the observation. The number of the action potential recorded per 1 000 s was 200-1 000 [mean: (687.62 ± 312.56) impulses/1 000 s, n = 17]. In addition to the typical propagated action potential, a large number of abortive spikes were observed. The results indicate that the activities of isolated muscle spindles in rats can be well maintained by the addition of certain amino acids. The results initially establish and provide the possibility for further research conducted in isolated rat muscle spindles.

  7. A Na+-activated K+ current (IK,Na) is present in guinea-pig but not rat ventricular myocytes.

    PubMed

    Lawrence, C; Rodrigo, G C

    1999-05-01

    The effects of removing extracellular Ca2+ and Mg2+ on the membrane potential, membrane current and intracellular Na+ activity (aiNa) were investigated in guinea-pig and rat ventricular myocytes. Membrane potential was recorded with a patch pipette and whole-cell membrane currents using a single-electrode voltage clamp. Both guinea-pig and rat cells depolarize when the bathing Ca2+ and Mg2+ are removed and the steady-state aiNa increases rapidly from a resting value of 6.4+/- 0.6 mM to 33+/-3.8 mM in guinea-pig (n=9) and from 8.9+/-0.8 mM to 29.3+/-3.0 mM (n=5) in rat ventricular myocytes. Guinea-pig myocytes partially repolarized when, in addition to removal of the bathing Ca2+ and Mg2+, K+ was also removed, however rat cells remained depolarized. A large diltiazem-sensitive inward current was recorded in guinea-pig and rat myocytes, voltage-clamped at -20 mV, when the bathing divalent cations were removed. When the bathing K+ was removed after Ca2+ and Mg2+ depletion, a large outward K+ current developed in guinea-pig, but not in rat myocytes. This current had a reversal potential of -80+/-0.7 mV and was not inhibited by high Mg2+ or glybenclamide indicating that it is not due to activation of non-selective cation or adenosine triphosphate (ATP)-sensitive K channels. The current was not activated when Li+ replaced the bathing Na+ and was blocked by R-56865, suggesting that it was due to the activation of KNa channels.

  8. Decorin and colchicine as potential treatments for post-haemorrhagic ventricular dilatation in a neonatal rat model.

    PubMed

    Hoque, Nicholas; Thoresen, Marianne; Aquilina, Kristian; Hogan, Sarah; Whitelaw, Andrew

    2011-01-01

    Post-haemorrhagic ventricular dilatation (PHVD) after intraventricular haemorrhage (IVH) remains a significant problem in preterm infants. Due to serious disadvantages of ventriculoperitoneal shunt dependence, there is an urgent need for non-surgical interventions. Considerable experimental and clinical evidence implicates transforming growth factor β (TGFβ) in the pathogenesis of PHVD. Colchicine and decorin are both compounds with anti-TGFβ properties. The former downregulates TGFβ production and is in clinical use for another fibrotic disease, and the latter inactivates TGFβ. We hypothesized that administration of decorin or colchicine, which both have anti-TGFβ properties, would reduce ventricular dilatation in a model of PHVD. 142 rat pups underwent intraventricular blood injection on postnatal days (PN) 7 and 8. Sixty-nine pups were randomized to colchicine 20 and 50 μg/kg/day or water by gavage for 13 days. Seventy were randomized to decorin 4 mg/kg or saline by intraventricular injection on PN8 and PN13. At PN21, the ventricular area was measured on coronal brain sections. Negative geotaxis was tested at PN14 in controls and in the decorin study group. Ventricular size was not different between animals receiving either drug or water/saline. Intraventricular blood impaired neuromotor performance, but decorin had no effect. Two drugs that block TGFβ by different mechanisms do not reduce ventricular dilatation in this model. Together with our previous work on losartan and pirfenidone, we conclude that blocking TGFβ alone does not prevent the development of PHVD. Copyright © 2011 S. Karger AG, Basel.

  9. Hemodynamic instability after pulmonary veins isolation in a patient with dual chamber pacemaker: The phantom injury of the ventricular lead.

    PubMed

    Kiuchi, Márcio Galindo; Lobato, Guilherme Miglioli; Chen, Shaojie

    2017-06-01

    The standard treatment of sinus node dysfunction (SND) is the pacemaker implantation, and the ideal methodology for the management of atrial fibrillation (AF) is rhythm control, but this is sometimes very hard to accomplish. For such actions, complete isolation of all pulmonary veins (PVI) is currently widely accepted as the best endpoint. In this case, we report a female patient, 81 years old, with controlled hypertension, without coronary artery disease, bearer of bilateral knee replacement, and dual chamber pacemaker implanted 1.5 years ago owing to sinus node disease, presenting the following symptoms: presyncope episodes associated with sustained irregular palpitation tachycardia. The evaluation of the pacemaker-recorded episodes of atrial fibrillation, the echocardiogram-presented normal systolic function and measurements, as well as the resting myocardial scintigraphy and with drug use did not demonstrate ischemia and/or fibrosis. The patient was in use of valsartan 320 mg daily, amlodipine 10 mg daily, sotalol hydrochloride 120 mg 2 times daily, and dabigatran 110 mg 2 times daily. At the end of the PVI, the patient presented hemodynamic instability, with a decrease in heart rate to 30 bpm and invasive arterial blood pressure to 60/30 mmHg. The pericardial puncture was quickly carried out with the possibility of cardiac tamponade as the first hypothesis, but no pericardial effusion was found. Next, we detected acute capture loss from the ventricular pacemaker lead, unvarying with high voltage and pulse width, even with stable impedance, sense and keeping the same position visualized by fluoroscopy. And there was soon afterwards induction of sustained ventricular tachycardia degenerating to spontaneous ventricular fibrillation. Electrical cardioversion-defibrillation was performed with 200J, and the sinus rhythm was reestablished, but there was a dead short, and the pacemaker generator was burned and disabled. So, we can speculate that

  10. Developmental analysis reveals mismatches in the expression of K+ channel alpha subunits and voltage-gated K+ channel currents in rat ventricular myocytes

    PubMed Central

    1996-01-01

    In the experiments here, the developmental expression of the functional Ca(2+)-independent, depolarization-activated K+ channel currents, Ito and IK, and of the voltage-gated K+ channel (Kv) alpha subunits, Kv1.2, Kv1.4, Kv1.5, Kv2.1, and Kv4.2 in rat ventricular myocytes were examined quantitatively. Using the whole-cell patch clamp recording method, the properties and the densities of Ito and IK in ventricular myocytes isolated from postnatal day 5 (P5), 10 (P10), 15 (P15), 20 (P20), 25 (P25), 30 (P30), and adult (8-12 wk) rats were characterized and compared. These experiments revealed that mean Ito densities increase fourfold between birth and P30, whereas IK densities vary only slightly. Neither the time- nor the voltage-dependent properties of the currents vary measurably, suggesting that the subunits underlying functional Ito and IK channels are the same throughout postnatal development. In parallel experiments, the developmental expression of each of the voltage-gated K+ channel alpha subunits, Kv1.2, Kv1.4, Kv1.5, Kv2.1, and Kv4.2, was examined quantitatively at the mRNA and protein levels using subunit-specific probes. RNase protection assays revealed that Kv1.4 message levels are high at birth, increase between P0 and P10, and subsequently decrease to very low levels in adult rat ventricles. The decrease in message is accompanied by a marked reduction in Kv1.4 protein, consistent with our previous suggestion that Kv1.4 does not contribute to the formation of functional K+ channels in adult rat ventricular myocytes. In contrast to Kv1.4, the mRNA levels of Kv1.2, Kv1.5, Kv2.1, and Kv4.2 increase (three- to five- fold) between birth and adult. Western analyses, however, revealed that the expression patterns of these subunits proteins vary in distinct ways: Kv1.2 and Kv4.2, for example, increase between P5 and adult, whereas Kv1.5 remains constant and Kv2.1 decreases. Throughout development, therefore, there is a mismatch between the numbers of Kv alpha

  11. Cardiac mast cell stabilization and cardioprotective effect of ischemic preconditioning in isolated rat heart.

    PubMed

    Parikh, V; Singh, M

    1998-05-01

    This study was designed to investigate the effect of disodium cromoglycate (DSCG), a mast cell stabilizer, on cardioprotective effect of ischemic preconditioning. Isolated rat heart was subjected to 30 min of global ischemia followed by 30 min of reperfusion. Ischemic preconditioning was provided by four episodes of 5-min global ischemia followed by 5 min of reperfusion before sustained ischemia. Ischemic preconditioning and DSCG (10 and 100 microM) treatment markedly decreased the release of lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary effluent and percentage incidence of ventricular premature beats (VPBs) and ventricular tachycardia/fibrillation (VT/VF) during reperfusion. Ischemic preconditioning and DSCG treatment also significantly reduced ischemia/reperfusion-induced mast cell peroxidase (MPO) release, a marker of mast cell degranulation. A significant increase in MPO release was observed immediately after ischemic preconditioning, and the release was found to be inhibited in hearts perfused with DSCG (10 and 100 microM) during ischemic preconditioning. DSCG administered during ischemic preconditioning (DSCG in ischemic preconditioning) attenuated the cardioprotective and antiarrhythmic effects of ischemic preconditioning. DSCG in ischemic preconditioning produced no marked effect on ischemia/reperfusion-induced MPO release. These findings tentatively suggest that DSCG administration during ischemic preconditioning abolishes its cardioprotective effect, perhaps by stabilizing resident cardiac mast cells.

  12. Positive inotropic activity induced by a dehydroisoandrosterone derivative in isolated rat heart model.

    PubMed

    Figueroa-Valverde, L; Díaz-Cedillo, F; García-Cervera, E; Pool Gómez, E; López-Ramos, M; Rosas-Nexticapa, M; Martinez-Camacho, R

    2013-10-01

    Experimental studies indicate that some steroid derivatives have inotropic activity; nevertheless, there is scarce information about the effects of the dehydroisoandrosterone and its derivatives at cardiovascular level. In addition, to date the cellular site and mechanism of action of dehydroisoandrosterone at cardiovascular level is very confusing. In order, to clarify those phenomena in this study, a dehydroisoandrosterone derivative was synthesized with the objective of to evaluate its activity on perfusion pressure and coronary resistance and compare this phenomenon with the effect exerted by dehydroisoandrosterone. The Langendorff technique was used to measure changes on perfusion pressure and coronary resistance in an isolated rat heart model in absence or presence of dehydroisoandrosterone and its derivative. Additionally, to characterize the molecular mechanism involved in the inotropic activity induced by dehydroisoandrosterone derivative was evaluated by measuring left ventricular pressure in absence or presence of following compounds; flutamide, prazosin, metoprolol and nifedipine. The results showed that dehydroisoandrosterone derivative significantly increased the perfusion pressure and coronary resistance in comparison with the control conditions and dehydroisoandrosterone. Additionally, other data indicate that dehydroisoandrosterone derivative increase left ventricular pressure in a dose-dependent manner [1 × 10(-9)-1 × 10(-4) mmol]; nevertheless, this phenomenon was significantly inhibited by nifedipine at a dose of 1 × 10(-6) mmol. In conclusion, these data suggest that dehydroisoandrosterone derivative induces positive inotropic activity through of activation the L-type calcium channel.

  13. ATP counteracts the rundown of gap junctional channels of rat ventricular myocytes by promoting protein phosphorylation.

    PubMed

    Verrecchia, F; Duthe, F; Duval, S; Duchatelle, I; Sarrouilhe, D; Herve, J C

    1999-04-15

    1. The degree of cell-to-cell coupling between ventricular myocytes of neonatal rats appeared well preserved when studied in the perforated version of the patch clamp technique or, in double whole-cell conditions, when ATP was present in the patch pipette solution. In contrast, when ATP was omitted, the amplitude of junctional current rapidly declined (rundown). 2. To examine the mechanism(s) of ATP action, an 'internal perfusion technique' was adapted to dual patch clamp conditions, and reintroduction of ATP partially reversed the rundown of junctional channels. 3. Cell-to-cell communication was not preserved by a non-hydrolysable ATP analogue (5'-adenylimidodiphosphate, AMP-PNP), indicating that the effect most probably did not involve direct interaction of ATP with the channel-forming proteins. 4. An ATP analogue supporting protein phosphorylation but not active transport processes (adenosine 5'-O-(3-thiotriphosphate), ATPgammaS) maintained normal intercellular communication, suggesting that the effect was due to kinase activity rather than to altered intracellular Ca2+. 5. A broad spectrum inhibitor of endogenous serine/threonine protein kinases (H7) reversibly reduced the intercellular coupling. A non-specific exogenous protein phosphatase (alkaline phosphatase) mimicked the effects of ATP deprivation. The non-specific inhibition of endogenous protein phosphatases resulted in the preservation of substantial cell-to-cell communication in ATP-free conditions. 6. The activity of gap junctional channels appears to require both the presence of ATP and protein kinase activity to counteract the tonic activity of endogenous phosphatase(s).

  14. Anisotropic conduction block and reentry in neonatal rat ventricular myocyte monolayers

    PubMed Central

    de Diego, Carlos; Chen, Fuhua; Xie, Yuanfang; Pai, Rakesh K.; Slavin, Leonid; Parker, John; Lamp, Scott T.; Qu, Zhilin; Valderrábano, Miguel

    2011-01-01

    Anisotropy can lead to unidirectional conduction block that initiates reentry. We analyzed the mechanisms in patterned anisotropic neonatal rat ventricular myocyte monolayers. Voltage and intracellular Ca (Cai) were optically mapped under the following conditions: extrastimulus (S1S2) testing and/or tetrodotoxin (TTX) to suppress Na current availability; heptanol to reduce gap junction conductance; and incremental rapid pacing. In anisotropic monolayers paced at 2 Hz, conduction velocity (CV) was faster longitudinally than transversely, with an anisotropy ratio [AR = CVL/CVT, where CVL and CVT are CV in the longitudinal and transverse directions, respectively], averaging 2.1 ± 0.8. Interventions decreasing Na current availability, such as S1S2 pacing and TTX, slowed CVL and CVT proportionately, without changing the AR. Conduction block preferentially occurred longitudinal to fiber direction, commonly initiating reentry. Interventions that decreased gap junction conductance, such as heptanol, decreased CVT more than CVL, increasing the AR and causing preferential transverse conduction block and reentry. Rapid pacing resembled the latter, increasing the AR and promoting transverse conduction block and reentry, which was prevented by the Cai chelator 1,2-bis oaminophenoxy ethane-N,N,N′,N′-tetraacetic acid (BAPTA). In contrast to isotropic and uniformly anisotropic monolayers, in which reentrant rotors drifted and self-terminated, bidirectional anisotropy (i.e., an abrupt change in fiber direction exceeding 45°) caused reentry to anchor near the zone of fiber direction change in 77% of monolayers. In anisotropic monolayers, unidirectional conduction block initiating reentry can occur longitudinal or transverse to fiber direction, depending on whether the experimental intervention reduces Na current availability or decreases gap junction conductance, agreeing with theoretical predictions. PMID:21037233

  15. CyPA-CD147-ERK1/2-cyclin D2 signaling pathway is upregulated during rat left ventricular hypertrophy.

    PubMed

    Tang, Fu-Cai; Wang, Hong-Yan; Ma, Ming-Ming; Guan, Tian-Wang; Pan, Long; Yao, Dun-Chen; Chen, Ya-Lan; Chen, Wei-Bei; Tu, Yong-Sheng; Fu, Xiao-Dong

    2015-08-25

    The changes of serum cyclophilin A (CyPA), its receptor CD147 and the downstream signaling pathway during the process of cardiac hypertrophy remain unknown. The present study aims to investigate the relationships between CyPA-CD147-ERK1/2-cyclin D2 signaling pathway and the development of cardiac hypertrophy. Left ventricular hypertrophy was prepared by 2-kidney, 2-clip in Sprague-Dawley rats and observed for 1 week, 4 and 8 weeks. Left ventricular hypertrophy was evaluated by ratio of left ventricular heart weight to body weight (LVW/BW) and cardiomyocyte cross sectional area (CSA). CyPA levels in serum were determined with a rat CyPA ELISA kit. Expressions of CyPA, CD147, phospho-ERK1/2 and cyclin D2 in left ventricular myocytes were determined by Western blot and immunostaining. Compared with sham groups, systolic blood pressure reached hypertensive levels at 4 weeks in 2K2C groups. LVW/BW and CSA in 2K2C groups were significantly increased at 4 and 8 weeks after clipping. ELISA results indicated a prominent increase in serum CyPA level associated with the degree of left ventricular hypertrophy. Western blot revealed that the expressions of CyPA, CD147, phospho-ERK1/2 and cyclin D2 in left ventricular tissues were also remarkably increased as the cardiac hypertrophy developed. The results of the present study demonstrates that serum CyPA and CyPA-CD147-ERK1/2-cyclin D2 signaling pathway in ventricular tissues are time-dependently upregulated and activated with the process of left ventricular hypertrophy. These data suggest that CyPA-CD147 signaling cascade might play a role in the pathogenesis of left ventricular hypertrophy, and CyPA might be a prognosticator of the degree of left ventricular hypertrophy.

  16. Drug-induced changes in action potential duration are proportional to action potential duration in rat ventricular myocardium.

    PubMed

    Bárándi, László; Harmati, Gábor; Horváth, Balázs; Szentandrássy, Norbert; Magyar, János; Varró, András; Nánási, Péter P; Bányász, Tamás

    2010-09-01

    Several cardioactive agents exhibit direct or reverse rate-dependent effects on action potential duration (APD) depending on the experimental conditions. Recently, a new theory has been proposed, suggesting that the reverse rate-dependent mode of drug-action may be a common property of canine, rabbit, guinea pig and human cardiac tissues, and this phenomenon is based on the dependence of drug-action on baseline APD. The aim of the present work was to examine the limitations of this hypothesis by studying the APD lengthening effect of K(+) channel blockers and the APD shortening effect of Ca(2+) channel blockers during the electrical restitution process of rat ventricular action potentials. Rat ventricular muscle was chosen because it has a set of ion currents markedly different from those of other species, its APD is shorter by one order of magnitude than that of the "plateau-forming" larger mammals, and most importantly, its APD increases at higher heart rates - opposite to many other species. The restitution of APD was studied as a function of the diastolic interval, a parameter indicating the proximity of action potentials. It was found that drug-induced APD changes in rat myocardium are proportional with the pre-drug value of APD but not with the diastolic interval, indicating that not the proximity of consecutive action potentials, but the baseline APD itself may determine the magnitude of drug-induced APD changes.

  17. Traditional Chinese medicine suppresses left ventricular hypertrophy by targeting extracellular signal-regulated kinases signaling pathway in spontaneously hypertensive rats.

    PubMed

    Xiong, Xingjiang; Yang, Xiaochen; Duan, Lian; Liu, Wei; Zhang, Yun; Liu, Yongmei; Wang, Pengqian; Li, Shengjie; Li, Xiaoke

    2017-02-22

    Chinese herbal medicine Bu-Shen-Jiang-Ya decoction (BSJYD) is reported to be beneficial for hypertension. Over expression of extracellular signal regulated kinases (ERK) pathway plays an important role in left ventricular hypertrophy (LVH). This study aimed to observe effects of BSJYD on LVH in spontaneously hypertensive rats (SHRs) and explore its possible mechanism on regulation of ERK pathway. Sixty 12-week-old SHRs were randomly allocated into 5 groups: BSJYD high dose group, middle dose group, low dose group, captopril group, and control group. Besides, a control group of Wistar-Kyoto rats was established. All rats were treated for 8 weeks. Systolic blood pressure (SBP), heart rate (HR), pathology, and left ventricular mass index (LVMI) were measured. Western blotting and Real-time PCR were used to assess the expressions of BDNF, Ras, ERK1/2, and c-fox levels. SBP and HR were significantly decreased compared with the control group and LVMI was markedly improved by BSJYD treatment in a dose-dependent manner. BSJYD inhibited the expression of BDNF, Ras, ERK1/2, and c-fox mRNA in LVH. In conclusion, BSJYD suppressed hypertension-induced cardiac hypertrophy by inhibiting the expression of ERK pathway. These changes in gene expression may be a possible mechanism by which BSJYD provides myocardial protection from hypertension.

  18. Length-tension relationships of sub-epicardial and sub-endocardial single ventricular myocytes from rat and ferret hearts.

    PubMed

    Cazorla, O; Le Guennec, J Y; White, E

    2000-05-01

    In vivo the sub-epicardial myocardium (EPI) and sub-endocardial myocardium (ENDO) operate over different ranges of sarcomere length (SL). However, it has not been previously shown whether EPI and ENDO work upon different ranges of the same or differing length-tension curves. We have compared the SL-tension relationship of intact, single ventricular EPI and ENDO myocytes from rat and ferret hearts. Cells were attached to carbon fibres of known compliance in order to stretch them and to record force at rest (passive tension) and during contractions (active tension). In both species, ENDO cells were significantly stiffer (i.e. had steeper SL-passive tension relationships) than EPI cells. Ferret ENDO cells had significantly steeper SL-active tension relationships than EPI cells; rat cells tended to behave similarly but no significant regional differences in active properties were observed. There were no inter-species differences in the active and passive properties of EPI cells, but ferret ENDO cells displayed significantly steeper passive and active SL-tension relationships than rat ENDO. We conclude that in vivo, ferret EPI and ENDO myocytes will function over different ranges of different SL-tension curves. There is a close relationship between SL and active tension (the Frank-Starling law of the heart), and our observations suggest that regional differences in the response to ventricular dilation will depend on both the change in SL and differing regional slopes of the SL-active tension curves.

  19. Cardiac magnetic resonance, transthoracic and transoesophageal echocardiography: a comparison of in vivo assessment of ventricular function in rats.

    PubMed

    Richardson, J D; Bertaso, A G; Frost, L; Psaltis, P J; Carbone, A; Koschade, B; Wong, D T; Nelson, A J; Paton, S; Williams, K; Azarisman, S; Worthley, M I; Teo, K S; Gronthos, S; Zannettino, A C W; Worthley, S G

    2013-10-01

    In vivo assessment of ventricular function in rodents has largely been restricted to transthoracic echocardiography (TTE). However 1.5 T cardiac magnetic resonance (CMR) and transoesophageal echocardiography (TOE) have emerged as possible alternatives. Yet, to date, no study has systematically assessed these three imaging modalities in determining ejection fraction (EF) in rats. Twenty rats underwent imaging four weeks after surgically-induced myocardial infarction. CMR was performed on a 1.5 T scanner, TTE was conducted using a 9.2 MHz transducer and TOE was performed with a 10 MHz intracardiac echo catheter. Correlation between the three techniques for EF determination and analysis reproducibility was assessed. Moderate-strong correlation was observed between the three modalities; the greatest between CMR and TOE (intraclass correlation coefficient (ICC) = 0.89), followed by TOE and TTE (ICC = 0.70) and CMR and TTE (ICC = 0.63). Intra- and inter-observer variations were excellent with CMR (ICC = 0.99 and 0.98 respectively), very good with TTE (0.90 and 0.89) and TOE (0.87 and 0.84). Each modality is a viable option for evaluating ventricular function in rats, however the high image quality and excellent reproducibility of CMR offers distinct advantages even at 1.5 T with conventional coils and software.

  20. Traditional Chinese medicine suppresses left ventricular hypertrophy by targeting extracellular signal-regulated kinases signaling pathway in spontaneously hypertensive rats

    PubMed Central

    Xiong, Xingjiang; Yang, Xiaochen; Duan, Lian; Liu, Wei; Zhang, Yun; Liu, Yongmei; Wang, Pengqian; Li, Shengjie; Li, Xiaoke

    2017-01-01

    Chinese herbal medicine Bu-Shen-Jiang-Ya decoction (BSJYD) is reported to be beneficial for hypertension. Over expression of extracellular signal regulated kinases (ERK) pathway plays an important role in left ventricular hypertrophy (LVH). This study aimed to observe effects of BSJYD on LVH in spontaneously hypertensive rats (SHRs) and explore its possible mechanism on regulation of ERK pathway. Sixty 12-week-old SHRs were randomly allocated into 5 groups: BSJYD high dose group, middle dose group, low dose group, captopril group, and control group. Besides, a control group of Wistar-Kyoto rats was established. All rats were treated for 8 weeks. Systolic blood pressure (SBP), heart rate (HR), pathology, and left ventricular mass index (LVMI) were measured. Western blotting and Real-time PCR were used to assess the expressions of BDNF, Ras, ERK1/2, and c-fox levels. SBP and HR were significantly decreased compared with the control group and LVMI was markedly improved by BSJYD treatment in a dose-dependent manner. BSJYD inhibited the expression of BDNF, Ras, ERK1/2, and c-fox mRNA in LVH. In conclusion, BSJYD suppressed hypertension-induced cardiac hypertrophy by inhibiting the expression of ERK pathway. These changes in gene expression may be a possible mechanism by which BSJYD provides myocardial protection from hypertension. PMID:28225023

  1. The inflammatory state provokes sexual dimorphism in left ventricular and electrocardiographic effects of chronic cyclosporine in rats

    PubMed Central

    El-Bassossy, Hany M.; Banjar, Zainy M.; El-Mas, Mahmoud M.

    2017-01-01

    Although cardiotoxicity has been recognized as an adverse effect of cyclosporine A (CSA), no information exists regarding sex specificity of CSA cardiotoxicity. We tested the hypothesis that left ventricular (LV) and electrocardiographic (ECG) effects of CSA and related inflammatory/histopathological derangements are sex related. CSA reduced the LV slope of end-systolic pressure volume relationship and increased isovolumic relaxation constant. These effects were more pronounced in male compared to female rats, suggesting LV systolic and diastolic dysfunction. ECG recordings showed elevated ST segments and increased QTc and T peak trend intervals in CSA-treated male rats, markers of LV ischemia and arrhythmogenesis. In female rats, CSA delayed AV conduction, as reflected by prolonged PR interval. Other sex-related effects for CSA included (i) increased blood cholesterol, and reduced rates of rise and fall in LV pressure and nuclear factor kappa B and angiotensin receptors type 1 expressions in male rats, and (ii) increased LV adiponectin in females. Histopatholgically, CSA caused vascular congestion, blood extravasation, and pyknotic or even absent nuclei in both sexes. In conclusion, rats exhibit sex-independent susceptibility to negative LV and histopathological influences of CSA. These effects become more intensified in male rats, perhaps on account of aggravated ischemic and inflammatory milieus. PMID:28211883

  2. Pentaerythritol Tetranitrate Targeting Myocardial Reactive Oxygen Species Production Improves Left Ventricular Remodeling and Function in Rats With Ischemic Heart Failure.

    PubMed

    Fraccarollo, Daniela; Galuppo, Paolo; Neuser, Jonas; Bauersachs, Johann; Widder, Julian D

    2015-11-01

    Reduced nitric oxide bioavailability contributes to progression of cardiac dysfunction and remodeling in ischemic heart failure. Clinical use of organic nitrates as nitric oxide donors is limited by development of nitrate tolerance and reactive oxygen species formation. We investigated the effects of long-term therapy with pentaerythritol tetranitrate (PETN), an organic nitrate devoid of tolerance, in rats with congestive heart failure after extensive myocardial infarction. Seven days after coronary artery ligation, rats were randomly allocated to treatment with PETN (80 mg/kg BID) or placebo for 9 weeks. Long-term PETN therapy prevented the progressive left ventricular dilatation and improved left ventricular contractile function and relaxation in rats with congestive heart failure. Mitochondrial superoxide anion production was markedly increased in the failing left ventricular myocardium and nearly normalized by PETN treatment. Gene set enrichment analysis revealed that PETN beneficially modulated the dysregulation of mitochondrial genes involved in energy metabolism, paralleled by prevention of uncoupling protein-3, thioredoxin-2, and superoxide dismutase-2 downregulation. Moreover, PETN provided a remarkable protective effect against reactive fibrosis in chronically failing hearts. Mechanistically, induction of heme oxygenase-1 by PETN prevented mitochondrial superoxide generation, NOX4 upregulation, and ensuing formation of extracellular matrix proteins in fibroblasts from failing hearts. In summary, PETN targeting reactive oxygen species generation prevented the changes of mitochondrial antioxidant enzymes and progressive fibrotic remodeling, leading to amelioration of cardiac functional performance. Therefore, PETN might be a promising therapeutic option in the treatment of ischemic heart diseases involving oxidative stress and impairment in nitric oxide bioactivity. © 2015 American Heart Association, Inc.

  3. Ethyl acetate fraction of Allium hirtifolium improves functional parameters of isolated hearts of diabetic rats

    PubMed Central

    Khaleghi, Sara; Hesari, Mahvash; Godini, Aliashraf; Shackebaei, Dareuosh; Mostafaie, Ali

    2017-01-01

    Objective: Allium hirtifolium (Persian shallot) has a hypoglycemic effect on diabetic animals. The aim of this study was to assess the effect of the ethyl acetate fraction of Allium hirtifolium on the function of isolated hearts of diabetic rats. Methods: The control and diabetic animals were randomly divided into four groups: saline- or extract-treated controls (n=10 and n=6, respectively) and saline- or extract-treated diabetic rats (n=8 and n=9, respectively), which received normal saline or extract for four weeks by daily gavage. The hearts were perfused according to the Langendorff method. Cardiac function parameters, including left ventricular developed pressure (LVDP), heart rate (HR), rate pressure product (RPP; LVDP´HR), and dp/dt were measured. Results The findings of this study showed that in the extract-treated diabetic rats, LVDP (94.5±9.1 mm Hg, mean±SEM), HR (249±15 beats/min), RPP (22732±1246) and +dp/dt (2598±230) at the baseline were significantly higher than those in the saline-treated diabetic animals, (71.5±4.0), (189±6), (13923±984), and (1701±124), respectively. Furthermore, RPP and HR were also significantly higher than the corresponding values obtained in the saline-treated diabetic rats after ischemia. Conclusion Besides blood glucose lowering action, oral administration of the ethyl acetate fraction of Allium hirtifolium significantly improved the baseline and post-ischemic cardiac function parameters in streptozotocin-induced diabetic rats. PMID:28344215

  4. Arterial-ventricular and interventricular interaction in isolated post-capillary and combined pulmonary hypertension in severe mitral stenosis.

    PubMed

    Venkateshvaran, Ashwin; Sola, Srikanth; Govind, Satish Chandra; Dash, Pravat Kumar; Vyavahare, Sagar; Lund, Lars H; la Merkely, Bé; Nagy, Anikó Ilona; Manouras, Aristomenis

    2016-08-01

    Isolated post-capillary pulmonary hypertension (Ipc-PH) is characterized by elevated left atrial pressures that are passively transmitted upstream, whereas combined pre- and post-capillary PH (Cpc-PH) demonstrates additional reactive changes in pulmonary vasculature. The increased load imposed on the right ventricle (RV) influences left ventricular (LV) mechanics by means of interventricular interaction. However, there is lack of evidence to substantiate the effect of possible additional alterations in the arterio-ventricular (AV) coupling and their effect on LV function. Considering the discrepant RV load in Cpc-PH and Ipc-PH, we sought to investigate whether these two conditions are also characterized by differential alterations in AV coupling. Invasive hemodynamic and echocardiographic data of 120 patients with PH due to severe rheumatic mitral stenosis before and immediately after percutaneous valvulotomy, along with 40 age-matched healthy controls, were analyzed. Effective arterial (E a) and ventricular elastance (E es) were measured. PH patients demonstrated elevated LV afterload (E a) along with AV uncoupling, and these derangements were more evident in the Cpc-PH group [E a: 3.3 (2.3-5.4) vs 2.6 (2.1-3.5) mmHg/mL, E a/E es: 0.73 (0.6-0.9) vs 0.88 (0.7-1.2), p < 0.05]. In addition, PH was associated with reduced LV deformation, which was mainly determined by elevated E a, while the effect of interventricular interaction was limited to the septal wall. Our results suggest that in addition to the interventricular interaction, an abnormal AV coupling contributes to the altered LV mechanics that has been associated with adverse prognosis in Cpc-PH.

  5. Exercise capacity and ventricular function in patients treated for isolated pulmonary valve stenosis or tetralogy of Fallot.

    PubMed

    Luijnenburg, Saskia E; de Koning, Wilfred B; Romeih, Soha; van den Berg, Jochem; Vliegen, Hubert W; Mulder, Barbara J M; Helbing, Willem A

    2012-07-26

    We hypothesized 1) that long-term ventricular outcome and exercise capacity would be better in patients with isolated pulmonary valve stenosis (PS) treated with balloon pulmonary valvuloplasty (BPV) than in patients operated for tetralogy of Fallot (TOF), and 2) that ventricular outcome and exercise capacity would not be different in PS patients and healthy controls. We included 21 PS patients after BPV (16.2 ± 5.2 years) and 21 patients operated for TOF (16.6 ± 5.6 years), matching them for gender, age at treatment, and age at study. Patients underwent cardiovascular magnetic resonance (CMR) imaging, exercise testing, 12-lead ECG and 24-hour Holter monitoring for assessment of right ventricular (RV) size and function, pulmonary regurgitation (PR), exercise capacity and electrocardiographic status. Healthy controls for CMR imaging and exercise testing were matched for gender and age at study. RV volumes and PR percentage were significantly larger in TOF patients than in PS patients; biventricular ejection fraction (EF) was not different. PR was mild in most PS patients. RV end-systolic volume was significantly larger in PS patients than in healthy controls; RVEF was significantly lower. Both patient groups had similar exercise test results. Peak workload and VO(2) max. were significantly lower in PS patients than in healthy controls. Longstanding mild PR in PS patients can lead to an enlarged RV, reduced RV function and reduced exercise capacity. Despite more PR and larger RV volumes in TOF patients, exercise capacity and biventricular function are similar in both patient groups. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  6. Lateral evaginations from the third ventricle into the rat mediobasal hypothalamus: an amplification of the ventricular route.

    PubMed

    Amat, P; Pastor, F E; Blazquez, J L; Pelaez, B; Sanchez, A; Alvarez-Morujo, A J; Toranzo, D; Amat-Peral, G

    1999-01-01

    In this work we report the existence of several evaginations extending out of the third ventricle within the mediobasal hypothalamus of the rat. In coronal sections, these evaginations appear as very narrow canaliculi integrating a canalicular system, which increases the contact surface between the ventricular lining and the nervous tissue. Consequently these evaginations enlarge the ventricular route for the transport of active principles present in the cerebrospinal fluid, such as (neuro)hormones and neurotransmitters. The mediobasal hypothalamus includes the arcuate nucleus and the median eminence (both involved in neuroendocrine mechanisms and in the regulation of pituitary function). A possible implication of our finding is that the neuroactive substance-containing ventricular cerebrospinal fluid may reach the intercellular spaces of the surrounding neuropil of the arcuate nucleus. According to literature these substances cross the ependyma of the lateral wall of the infundibular recess of the third ventricle. We suggest that such substances might also pass through the ependymal lining of the canalicular system, which displays the same ultrastructural characteristics as the rest of the ependyma of the lateral wall of the third ventricle. Therefore, the arcuate neurons may be influenced not only by synaptic inputs (afferent fibers) but also by non-synaptic diffusion neurotransmission (by means of neuroactive substances present in the cerebrospinal fluid).

  7. Evaluation of remodeling in left and right ventricular myocytes from heterozygous (mRen2)27 transgenic rats.

    PubMed

    Chouabe, Christophe; Ricci, Estelle; Kurdi, Mazen; Legrand, Claude; Bricca, Giampiero; Bonvallet, Robert

    2009-03-01

    Cardiac remodeling was assessed both in the pressure-overloaded left ventricle and in the normotensive right ventricle of hypertensive transgenic rats (mRen2)27 (TGR27). The present study combined histology, electrophysiology, molecular biology and biochemistry techniques. A significant increase in action potential (AP) duration was recorded both in right and left ventricular myocytes wheareas only in the latter ones were hypertrophic. The increase in AP duration is mainly supported by the reduction of the transient outward K current (I(to)) density since no significant modification was observed for the L-type calcium current (I(Ca,L)), the sodium-calcium exchange current (I(NCX)), the delayed rectifier current (I(K)) and the inward rectifier current (I(K1)). The lower amplitude of I(to) current was associated with a lower Kv4.3 protein expression both in right and left ventricles while Kv4.3 mRNA levels was decreased only in left ventricle. Thus, a differential ventricular remodeling takes place in the TGR27 model. The possible cause of electrical remodeling in right ventricular myocytes of TGR27 is discussed.

  8. Effects of L-propionylcarnitine on electrical and mechanical alterations induced by amphiphilic lipids in isolated guinea pig ventricular muscle.

    PubMed

    Aomine, M; Arita, M; Shimada, T

    1988-01-01

    We examined the effects of L-propionylcarnitine (Prop. C), a short-chain acylcarnitine, on amphiphile (L-lysophosphatidylcholine or L-palmitoylcarnitine)-induced electrophysiological and ultrastructural changes in isolated guinea pig ventricular papillary muscles, under acidic conditions (pH 6.9). Conventional microelectrode, tension-recording, and electron microscope techniques were used. Both amphiphiles, at a concentration of 10(-4) M, significantly decreased the resting membrane potential, action potential amplitude, and action potential duration, but increased the developed and resting tension. Such amphiphile-induced electrical changes were not observed in muscles pretreated with the beta-blocker, atenolol, although the mechanical changes remained unaffected. The application of Prop. C (10(-2) M), in the continued presence of the amphiphiles caused a return of the action potential duration and the developed tension to the control level. However, the resting potential and action potential amplitude remained unaffected; in fact, the maximum upstroke velocity (Vmax) of the action potential tended to decrease further. Pretreatment with Prop. C prevented all the amphiphile-induced electrophysiological and mechanical changes, except for Vmax. Electron microscopic studies revealed that amphiphile-induced ultrastructural changes were prevented, at least in part, in the presence of Prop. C. Thus, Prop. C antagonizes some of deleterious effects of amphiphiles, such as lysophosphatidylcholine and palmitoylcarnitine, upon the electrical and mechanical activities of the ventricular muscle, under acidic conditions.

  9. Evaluation of right ventricle by speckle tracking and conventional echocardiography in rats with right ventricular heart failure.

    PubMed

    Kimura, Koichi; Daimon, Masao; Morita, Hiroyuki; Kawata, Takayuki; Nakao, Tomoko; Okano, Tomoko; Lee, Seitetsu L; Takenaka, Katsu; Nagai, Ryozo; Yatomi, Yutaka; Komuro, Issei

    2015-05-13

    Speckle tracking echocardiography (STE) has been reported to be a promising technique for evaluating right ventricular (RV) function in the clinical setting. On the other hand, the usefulness of STE for RV evaluation in small animal models has not been clarified, although the rat model is among the most commonly used animal models to develop novel effective treatments against pulmonary hypertension and RV heart failure (HF).We validated the use of STE and conventional echocardiographic variables for evaluating RV functions in a rat model by comparing the echocardiographic values of RVHF rats (n = 12) induced by monocrotaline injection with those of control rats (n = 12).Most conventional echocardiographic variables demonstrated that RVHF rats have significant RV dysfunction. The area under the curve (AUC) values to distinguish RV dysfunction in RVHF rats from normal RV function in control rats using fractional area change (FAC), tricuspid annular plane systolic excursion (TAPSE), RV myocardial performance index (MPI), peak tissue Doppler tricuspid annular velocities at systole (Sa), and at early diastole (Ea) were 0.71, 0.98, 0.79, 0.92, and 0.91, respectively. However, using STE analysis for RV evaluation, limited reproducibility was observed (variability 19-37 %, ICC 0.74-0.88) and the only circumferential strain showed significantly lower absolute values (P = 0.039, AUC = 0.76).To evaluate RV function in rat models, circumferential strain may be useful, however, the reproducibility and diagnostic utility were limited. Conventional echocardiographic variables such as TAPSE, tissue Doppler Sa, and Ea have superior diagnostic utility.

  10. Isolation and characterization of hepatic mast cells from cholestatic rats

    PubMed Central

    Hargrove, Laura; Graf-Eaton, Allyson; Kennedy, Lindsey; Demieville, Jennifer; Owens, Jennifer; Hodges, Kyle; Ladd, Brittany; Francis, Heather

    2016-01-01

    Mast cells (MCs) are immune cells that release histamine and other mediators. MC number increases after bile duct ligation (BDL) and blocking mast cell-derived histamine decrease biliary proliferation. We aimed to isolate and characterize MCs from cholestatic livers. Rats were subjected to BDL starting at 6 hrs and up to 14 days. MC infiltration was evaluated by toluidine blue. BDL rats were perfused using standard collagenase perfusion. Following enzymatic digestion, tissue was passed through a fine gauge needle. Suspensions were incubated with MAb AA4, washed and incubated with goat anti-mouse coated Dynal® beads. MCs were stained with toluidine blue, and in isolated MCs, the expression of FCεRI and MC proteases was measured. The expression of histidine decarboxylase, histamine receptors, VEGF-receptors and TIE 1 and 2 was evaluated by qPCR. Histamine and VEGF-A secretion was measured in MC supernatants. MC purity was evaluated by CK-19, CK-8, albumin, VAP-1 and α-SMA expression. In vitro, cholangiocytes and HSCs were treated with isolated MC supernatants from BDL rats treated with either NaCl or cromolyn sodium (to block MC histamine release) and biliary proliferation and hepatic fibrosis were measured. MCs infiltrate the liver and surround bile ducts starting at day 2. We isolated a virtually pure preparation of mature, functional MCs. TEM images reveal distinct secretory granules and isolated MCs secrete histamine. MCs express FCεRI, chymase, tryptase, RMCPI and RMCPII, but were virtually void of other cell markers. Biliary proliferation and fibrosis increased following treatment with MC supernatants from BDL rats + NaCl and these parameters decreased in cells treated with MC supernatants from BDL + cromolyn sodium. In conclusion, we have isolated and characterized MCs from cholestatic livers. MCs regulate cholestatic liver injury and hepatic fibrosis. This tool provides a better understanding of the paracrine influence of mast cells on biliary

  11. Sitagliptin decreases ventricular arrhythmias by attenuated glucose-dependent insulinotropic polypeptide (GIP)-dependent resistin signalling in infarcted rats

    PubMed Central

    Lee, Tsung-Ming; Chen, Wei-Ting; Chang, Nen-Chung

    2016-01-01

    Myocardial infarction (MI) was associated with insulin resistance, in which resistin acts as a critical mediator. We aimed to determine whether sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, can attenuate arrhythmias by regulating resistin-dependent nerve growth factor (NGF) expression in postinfarcted rats. Normoglycaemic male Wistar rats after ligating coronary artery were randomized to either vehicle or sitagliptin for 4 weeks starting 24 h after operation. Post-infarction was associated with increased myocardial noradrenaline [norepinephrine (NE)] levels and sympathetic hyperinnervation. Compared with vehicle, sympathetic innervation was blunted after administering sitagliptin, as assessed by immunofluorescent analysis of tyrosine hydroxylase, growth-associated factor 43 and neurofilament and western blotting and real-time quantitative RT-PCR of NGF. Arrhythmic scores in the sitagliptin-treated infarcted rats were significantly lower than those in vehicle. Furthermore, sitagliptin was associated with reduced resistin expression and increased Akt activity. Ex vivo studies showed that glucose-dependent insulinotropic polypeptide (GIP) infusion, but not glucagon-like peptide-1 (GLP-1), produced similar reduction in resistin levels to sitagliptin in postinfarcted rats. Furthermore, the attenuated effects of sitagliptin on NGF levels can be reversed by wortmannin (a phosphatidylinositol 3-kinase antagonist) and exogenous resistin infusion. Sitagliptin protects ventricular arrhythmias by attenuating sympathetic innervation in the non-diabetic infarcted rats. Sitagliptin attenuated resistin expression via the GIP-dependent pathway, which inhibited sympathetic innervation through a signalling pathway involving phosphatidylinositol 3-kinase (PI3K) and Akt protein. PMID:26811539

  12. Sitagliptin decreases ventricular arrhythmias by attenuated glucose-dependent insulinotropic polypeptide (GIP)-dependent resistin signalling in infarcted rats.

    PubMed

    Lee, Tsung-Ming; Chen, Wei-Ting; Chang, Nen-Chung

    2016-01-25

    Myocardial infarction (MI) was associated with insulin resistance, in which resistin acts as a critical mediator. We aimed to determine whether sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, can attenuate arrhythmias by regulating resistin-dependent nerve growth factor (NGF) expression in postinfarcted rats. Normoglycaemic male Wistar rats after ligating coronary artery were randomized to either vehicle or sitagliptin for 4 weeks starting 24 h after operation. Post-infarction was associated with increased myocardial noradrenaline [norepinephrine (NE)] levels and sympathetic hyperinnervation. Compared with vehicle, sympathetic innervation was blunted after administering sitagliptin, as assessed by immunofluorescent analysis of tyrosine hydroxylase, growth-associated factor 43 and neurofilament and western blotting and real-time quantitative RT-PCR of NGF. Arrhythmic scores in the sitagliptin-treated infarcted rats were significantly lower than those in vehicle. Furthermore, sitagliptin was associated with reduced resistin expression and increased Akt activity. Ex vivo studies showed that glucose-dependent insulinotropic polypeptide (GIP) infusion, but not glucagon-like peptide-1 (GLP-1), produced similar reduction in resistin levels to sitagliptin in postinfarcted rats. Furthermore, the attenuated effects of sitagliptin on NGF levels can be reversed by wortmannin (a phosphatidylinositol 3-kinase antagonist) and exogenous resistin infusion. Sitagliptin protects ventricular arrhythmias by attenuating sympathetic innervation in the non-diabetic infarcted rats. Sitagliptin attenuated resistin expression via the GIP-dependent pathway, which inhibited sympathetic innervation through a signalling pathway involving phosphatidylinositol 3-kinase (PI3K) and Akt protein. © 2016 Authors.

  13. Glycolytic inhibition: effects on diastolic relaxation and intracellular calcium handling in hypertrophied rat ventricular myocytes.

    PubMed Central

    Kagaya, Y; Weinberg, E O; Ito, N; Mochizuki, T; Barry, W H; Lorell, B H

    1995-01-01

    We tested the hypothesis that glycolytic inhibition by 2-deoxyglucose causes greater impairment of diastolic relaxation and intracellular calcium handling in well-oxygenated hypertrophied adult rat myocytes compared with control myocytes. We simultaneously measured cell motion and intracellular free calcium concentration ([Ca2+]i) with indo-1 in isolated paced myocytes from aortic-banded rats and sham-operated rats. There was no difference in either the end-diastolic or peak-systolic [Ca2+]i between control and hypertrophied myocytes (97 +/- 18 vs. 105 +/- 15 nM, 467 +/- 92 vs. 556 +/- 67 nM, respectively). Myocytes were first superfused with oxygenated Hepes-buffered solution containing 1.2 mM CaCl2, 5.6 mM glucose, and 5 mM acetate, and paced at 3 Hz at 36 degrees C. Exposure to 20 mM 2-deoxyglucose as substitution of glucose for 15 min caused an upward shift of end-diastolic cell position in both control (n = 5) and hypertrophied myocytes (n = 10) (P < 0.001 vs. baseline), indicating an impaired extent of relaxation. Hypertrophied myocytes, however, showed a greater upward shift in end-diastolic cell position and slowing of relaxation compared with control myocytes (delta 144 +/- 28 vs. 55 +/- 15% of baseline diastolic position, P < 0.02). Exposure to 2-deoxyglucose increased end-diastolic [Ca2+]i in both groups (P < 0.001 vs. baseline), but there was no difference between hypertrophied and control myocytes (218 +/- 38 vs. 183 +/- 29 nM, respectively). The effects of 2-deoxyglucose were corroborated in isolated oxygenated perfused hearts in which glycolytic inhibition which caused severe elevation of isovolumic diastolic pressure and prolongation of relaxation in the hypertrophied hearts compared with controls. In summary, the inhibition of the glycolytic pathway impairs diastolic relaxation to a greater extent in hypertrophied myocytes than in control myocytes even in well-oxygenated conditions. The severe impairment of diastolic relaxation induced by 2

  14. Peroxidation of docosahexaenoic acid is responsible for its effects on ITO and ISS in rat ventricular myocytes

    PubMed Central

    Judé, S; Bedut, S; Roger, S; Pinault, M; Champeroux, P; White, E; Le Guennec, J-Y

    2003-01-01

    Exposure to docosahexaenoïc acid (DHA), a long-chain polyunsaturated fatty acid, is known to block several ionic currents such as the transient outward current ITO. It has also been reported to activate certain potassium channels. It has been suggested that these effects, observed in single-cell experiments, participate in the antiarrhythmic properties of these compounds in vivo. DHA is highly prone to peroxidation. To investigate the influence peroxidation may have on the effects of DHA on ion channels, we studied ITO and the steady-state outward current ISS in isolated rat ventricular myocytes under ruptured whole-cell patch-clamp conditions. A measure of 10 μM DHA alone reduced ITO, evoked by a pulse to +70 mV, by 74.8±10.8% (n=7) and activated a delayed outward current with kinetic properties different from ISS. When an antioxidant, alpha-tocopherol (1 μM), was added together with DHA, the blockade of ITO was reduced to 38.5±7.7% (n=8) and the delayed outward current was not activated. α-Tocopherol alone had no effect on these currents. When an oxidant, hydrogen peroxide (1 μM), was applied together with DHA, the blockade of ITO was almost complete (98.4±1.0%, n=7) and a large delayed outward current was activated. A measure of 1 μM hydrogen peroxide alone had no effect on these currents. Measurements of nonperoxidized DHA in experimental solutions confirmed the negative relation between DHA concentration and the effects on the currents. We conclude that rather than DHA itself, it is the peroxidation products of DHA that block ITO and activate a delayed outward current in in vitro single-cell experiments. These findings have important implications for the extrapolation of in vitro experimental findings to the antiarrhythmic effects of DHA in vivo because, in vivo, peroxidation of DHA is unlikely to occur. PMID:12813005

  15. Reduced contraction strength with increased intracellular [Ca2+] in left ventricular trabeculae from failing rat hearts

    PubMed Central

    Ward, Marie-Louise; Pope, Adèle J; Loiselle, Denis S; Cannell, Mark B

    2003-01-01

    Intracellular calcium ([Ca2+]i) and isometric force were measured in left ventricular (LV) trabeculae from spontaneously hypertensive rats (SHR) with failing hearts and normotensive Wistar-Kyoto (WKY) controls. At a physiological stimulation frequency (5 Hz), and at 37 °C, the peak stress of SHR trabeculae was significantly (P ≤; 0.05) reduced compared to WKY (8 ± 1 mN mm−2(n = 8)vs. 21 ± 5 mN mm−2(n = 8), respectively). No differences between strains in either the time-to-peak stress, or the time from peak to 50 % relaxation were detected. Measurements using fura-2 showed that in the SHR both the peak of the Ca2+ transient and the resting [Ca2+]i were increased compared to WKY (peak: 0.69 ± 0.08 vs. 0.51 ± 0.08 μm (P ≤ 0.1) and resting: 0.19 ± 0.02 vs. 0.09 ± 0.02 μm (P ≤ 0.05), SHR vs. WKY, respectively). The decay of the Ca2+ transient was prolonged in SHR, with time constants of: 0.063 ± 0.002 vs. 0.052 ± 0.003 s (SHR vs. WKY, respectively). Similar results were obtained at 1 Hz stimulation, and for[Ca2+]o between 0.5 and 5 mm. The decay of the caffeine-evoked Ca2+ transient was slower in SHR (9.8 ± 0.7 s (n = 8)vs. 7.7 ± 0.2 s (n = 8) in WKY), but this difference was removed by use of the SL Ca2+-ATPase inhibitor carboxyeosin. Histological examination of transverse sections showed that the fractional content of perimysial collagen was increased in SHR compared to WKY (18.0 ± 4.6 % (n = 10)vs. 2.9 ± 0.9 % (n = 11) SHR vs. WKY, respectively). Our results show that differences in the amplitude and the time course of the Ca2+ transient between SHR and WKY do not explain the reduced contractile performance of SHR myocardium per se. Rather, we suggest that, in this animal model of heart failure, contractile function is compromised by increased collagen, and its three-dimensional organisation, and not by reduced availability of intracellular Ca2+. PMID:12527740

  16. Ca exchange under non-perfusion-limited conditions in rat ventricular cells: Identification of subcellular compartments

    SciTech Connect

    Langer, G.A.; Rich, T.L.; Orner, F.B. )

    1990-08-01

    Freshly prepared ventricular myocytes from rat hearts, aliquots of which were tested for sarcolemmal integrity by La exposure, were labeled at high 45Ca specific activity. Isotope was subsequently washed out at a perfusion rate of 2.8 ml/s with washout solution sampled each 1 s. No initial unrecorded period of washout was imposed. Four compartments were distinguishable: (1) a rapid compartment (RC) containing 2.6 mmol Ca/kg dry wt of La-displaceable Ca, half time (t1/2) less than 1 s; (2) an intermediate compartment(s) (IC) containing 2.1 mmol, t1/2 = 3 and 19 s; (3) a slow compartment (SC) containing 1.6 mmol, t1/2 = 3.6 min; (4) an inexchangeable compartment that demonstrated no 45Ca uptake after 60-min labeling containing 1.2 mmol. Introduction of 10 mM caffeine as a probe for sarcoplasmic reticulum (SR) content at various times during the washouts caused an increased release of 45Ca. The net increased 45Ca release plotted as a function of time at which caffeine was introduced produced a biexponential curve with t1/2s of 2 and 22 s, very similar to the t1/2s of the IC. Ryanodine (1 microM) significantly reduced the caffeine-induced 45Ca release, confirming the SR locus of the IC. Cells were perfused with 10 mM NaH2PO4 to specifically increase mitochondrial 45Ca labeling. Subsequent removal of PO4 at various times during washouts produced large increases in effluent 45Ca. A plot of the net peak release of 45Ca vs. time of PO4 removal was monoexponential with t1/2 = 3.3 min, very similar to the SC t1/2. The large La-accessible RC remains unlocalized, but the rapidity of its exchange places it in the sarcolemma and/or at sites in rapid equilibrium with the sarcolemma.

  17. The effects of caffeine on tension development and intracellular calcium transients in rat ventricular muscle.

    PubMed Central

    Konishi, M; Kurihara, S; Sakai, T

    1984-01-01

    The effects of caffeine on tension and intracellular [Ca2+] were investigated in rat ventricular muscle using the Ca2+-sensitive photoprotein, aequorin. Contracture was induced by rapid application of 0.5-10 mM-caffeine solution at 20 degrees C. In normal Tyrode solution at 8 degrees C, or in Na+-deficient solution in which Na+ was isotonically replaced by sucrose, peak tension of caffeine contracture was potentiated and relaxation was prolonged. Caffeine contracture could not be induced immediately after a prior contracture. Repriming time was 10 min in Tyrode solution, and was much shorter in Na+-deficient solution or in high-K+ solution containing 105.9 mM-K+. Caffeine prolonged the plateau of action potential dose dependently. At low temperature, prolongation of the plateau phase by caffeine was more marked. Twitch tension showed a triphasic change after application of caffeine; peak tension transiently increased in a potentiating phase (P phase), and then decreased below control level in an inhibitory phase (I phase) followed by gradual recovery in a recovery phase (R phase). The effects of caffeine on the Ca2+ transients during a twitch were also complex, depending on time after application and dose of caffeine. In low caffeine concentration (below 0.5 mM) the peak of the Ca2+ transient was potentiated in the I phase, although the peak tension was suppressed. At high concentration (above 3 mM) the peaks of both the Ca2+ transient and twitch tension were suppressed. In every concentration of caffeine tested (0.1-5 mM), time to the Ca2+ transient and twitch tension peaks was prolonged, and the falling phases of both were delayed. Caffeine might release Ca2+ from intracellular store(s) and enhance the slow inward current. The Ca2+ transient obtained in this study clearly indicate that the prolonged time to peak tension in the presence of caffeine is due to the slow rise of intracellular [Ca2+] and prolonged time to peak of the Ca2+ transient. It is also quite

  18. Protein kinase C-alpha-induced hypertrophy of neonatal rat ventricular myocytes.

    PubMed

    Vijayan, Kalpana; Szotek, Erika L; Martin, Jody L; Samarel, Allen M

    2004-12-01

    Protein kinase C (PKC) isoenzymes play a critical role in cardiomyocyte hypertrophy. At least three different phorbol ester-sensitive PKC isoenzymes are expressed in neonatal rat ventricular myocytes (NRVMs): PKC-alpha, -delta, and -epsilon. Using replication-defective adenoviruses (AdVs) that express wild-type (WT) and dominant-negative (DN) PKC-alpha together with phorbol myristate acetate (PMA), which is a hypertrophic agonist and activator of all three PKC isoenzymes, we studied the role of PKC-alpha in signaling-specific aspects of the hypertrophic phenotype. PMA induced nuclear translocation of endogenous and AdV-WT PKC-alpha in NRVMs. WT PKC-alpha overexpression increased protein synthesis and the protein-to-DNA (P/D) ratio but did not affect cell surface area (CSA) or cell shape compared with uninfected or control AdV beta-galactosidase (AdV betagal)-infected cells. PMA-treated uninfected cells displayed increased protein synthesis, P/D ratio, and CSA and elongated morphology. PMA did not further enhance protein synthesis or P/D ratio in AdV-WT PKC-alpha-infected cells. To assess the requirement of PKC-alpha for these PMA-induced changes, AdV-DN PKC-alpha or AdV betagal-infected NRVMs were stimulated with PMA. Without PMA, AdV-DN PKC-alpha had no effects on protein synthesis, P/D ratio, CSA, or shape vs. AdV betagal-infected NRVMs. PMA increased protein synthesis, P/D ratio, and CSA in AdV betagal-infected cells, but these parameters were significantly reduced in PMA-stimulated AdV-DN PKC-alpha-infected NRVMs. Overexpression of DN PKC-alpha enhanced PMA-induced cell elongation. Neither WT PKC-alpha nor DN PKC-alpha affected atrial natriuretic factor gene expression. Insulin-like growth factor-1 also induced nuclear translocation of endogenous PKC-alpha. PMA but not WT PKC-alpha overexpression induced ERK1/2 activation. However, AdV-DN PKC-alpha partially blocked PMA-induced ERK activation. Thus PKC-alpha is necessary for certain aspects of PMA-induced NRVM

  19. Early social isolation augments alcohol consumption in rats.

    PubMed

    Lesscher, Heidi M B; Spoelder, Marcia; Rotte, Marthe D; Janssen, Martijn J; Hesseling, Peter; Lozeman-van't Klooster, José G; Baars, Annemarie M; Vanderschuren, Louk J M J

    2015-10-01

    There is a considerable degree of individual vulnerability for alcohol use disorder (AUD) as only a subpopulation of individuals who regularly consume alcohol develop AUD. It is therefore very important to understand the factors and mechanisms that contribute towards the individual risk for AUD. In this respect, social influences, in particular during development, may be relevant for AUD as disruptions in early social experiences are associated with an increased risk for AUD. Social play, the most prominent form of social behaviour shown by young mammals, is rewarding and considered to be important for social, emotional and cognitive development. Recent studies suggest that early social isolation, effectively depriving animals from social play, increases the risk for addictive behaviour. The aim of this study was therefore to explore the long-term consequences of early social isolation on alcohol consumption and motivation for alcohol. To this end, rats were socially isolated from postnatal days 21-42, followed by 4 weeks of social housing, and voluntary alcohol consumption and operant responding for alcohol were determined in adulthood. We observed enhanced levels of alcohol consumption in adulthood in previously isolated rats, whereas operant responding for alcohol was not altered. The impact of early social isolation was independent of the individual variation in alcohol consumption. These data indicate that social isolation, during a developmental period when social play is highly abundant, enhances the propensity to consume alcohol in adulthood. This implies that early social experience may be a protective factor against excessive alcohol use.

  20. An injectable capillary-like microstructured alginate hydrogel improves left ventricular function after myocardial infarction in rats.

    PubMed

    Rocca, Domenico G Della; Willenberg, Bradley J; Qi, Yanfei; Simmons, Chelsey S; Rubiano, Andres; Ferreira, Leonardo F; Huo, Tianyao; Petersen, John W; Ruchaya, Prashant J; Wate, Prateek S; Wise, Elizabeth A; Handberg, Eileen M; Cogle, Christopher R; Batich, Christopher D; Byrne, Barry J; Pepine, Carl J

    2016-10-01

    A new post-myocardial infarction (MI) therapy is injection of high-water-content polymeric biomaterial gels (hydrogels) into damaged myocardium to modulate cardiac negative remodeling and preserve heart function. We investigated the therapeutic potential of a novel gelatinized alginate hydrogel with a unique microstructure of uniform capillary-like channels (termed Capgel). Shortly (48h) after induced anterior MI, Sprague Dawley rats received intramyocardial injection of Capgel directly into the antero-septal wall at the infarct border zone (n=12) or no injection (n=10, controls). Echocardiograms were performed at 48h (week 0) and 4weeks (week 4) to evaluate left ventricular function. Echocardiograms showed 27% improvement of left ventricular systolic function over time with gel injection: fractional shortening increased from 26±3% at week 0 to 33±2% at week 4 (p=0.001). Capgel was present at the injection site after 4weeks, but was minimal at 8weeks. The remaining gel was heavily populated by CD68(+) macrophages with CD206(+) clusters and blood vessels. An in vitro experiment was performed to assess Angiotensin-(1-7) released from Capgel. Angiotensin-(1-7) was released from the Capgel in a sustained manner for 90days. Use of Capgel, a degradable, bioactive hydrogel composed of gelatinized capillary-alginate gel, appears safe for intramyocardial injection, is associated with improved left ventricular function after MI in rats, and may provide a long-term supply of Angiotensin-(1-7). Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Measurement of left ventricular hemodynamic parameters in closed-chest rats under control and various pathophysiologic conditions.

    PubMed

    Zimmer, H G

    1983-01-01

    A prototype of a recently developed mikro-tip pressure transducer catheter (3 French) was inserted into the left ventricle of closed-chest rats via the right carotid artery. In thiobutabarbital-sodium anesthesia, heart rate (409 +/- 7 beats/min), left ventricular systolic pressure (LVSP: 142 +/- 4 mm Hg) and the maximal rate of rise of left ventricular pressure (LV dP/dtmax: 6073 +/- 187 mm Hg/sec, mean values +/- SEM, n = 19) were measured. The baroreceptor reflex was intact under these experimental conditions. In closed-chest guinea pigs, all functional parameters determined were lower (heart rate: 271 +/- 11 beats/min; LVSP: 94 +/- 6 mm Hg; LV dP/dtmax: 3248 +/- 295 mm Hg/sec, mean values +/- SEM, n = 9). To test the applicability of the new catheter tip manometer, cardiac hemodynamic parameters were determined in rats under various pathophysiologic conditions: Several periods of asphyxia were followed by progressive depressions in heart rate, LVSP and LV dP/dtmax, and acute as well as chronic stimulation with catecholamines (noradrenaline and isoproterenol) and with triiodothyronine was characterized by a pronounced positive inotropic and chronotropic effect. The technique described has many potential applications in cardiovascular studies on intact small laboratory animals.

  2. ISOLATION OF RAT LIVER PLASMA MEMBRANES

    PubMed Central

    Touster, Oscar; Aronson, N. N.; Dulaney, John T.; Hendrickson, Herman

    1970-01-01

    Nucleotide pyrophosphatase and phosphodiesterase I of rat liver have been found to be localized primarily in cell particulates highly enriched with respect to the most commonly accepted plasma membrane marker, 5'-nucleotidase, and therefore should themselves be assigned a plasma membrane localization. The observation that plasma membranes sediment in isotonic sucrose with both nuclear and microsomal fractions was exploited to obtain plasma membrane preparations from each fraction. Both preparations are similar in chemical and enzymic composition. Moreover, the preparative method developed in this study appears to give the best combination of yield, purity, and reproducibility available. The question of the possible identity of nucleotide pyrophosphatase and phosphodiesterase I is considered, and evidence is presented suggesting that these activities may be manifestations of the same enzyme. PMID:5497542

  3. The ethanolic extract of Kaempferia parviflora reduces ischaemic injury in rat isolated hearts.

    PubMed

    Malakul, Wachirawadee; Ingkaninan, Kornkanok; Sawasdee, Pattara; Woodman, Owen L

    2011-09-01

    The ethanolic extract of Kaempferia parviflora (KPE) has been reported to contain a range of flavonoids and to enhance endothelial synthesis of NO. We investigated the vascular relaxant, antioxidant and cardioprotective activities of KPE. Vascular function was assessed in rat aortic rings and superoxide generation determined using lucigenin enhanced chemiluminescence. Ischaemia and reperfusion were induced in rat isolated, perfused hearts. KPE caused vasorelaxation (R(max) 102 ± 2%), which was partly inhibited by removal of the endothelium (R(max) 91 ± 1%) or by N(G)-nitro-l-arginine (L-NNA, R(max) 83 ± 3%) or 1H-[1,2,4] oxadiazolo[4,3-a]quinoxaline-1-one (ODQ, R(max) 80 ± 2%). In addition KPE caused concentration-dependent inhibition of the contractile response to exogenous Ca(2+). KPE (10(-3)M) also significantly inhibited superoxide radical generation induced by of xanthine/xanthine oxidase (2.3 ± 0.4% of control) to a similar extent to the xanthine oxidase inhibitor allopurinol (10(-4)M, 1.6 ± 0.5%) or by rat isolated aorta in the presence of NADPH (30.0 ± 6.3% of control) similarly to the NADPH oxidase inhibitor diphenyliodonium (5 × 10(-6)M, 23.1 ± 5.6%). In the presence of oxidant stress generated by pyrogallol endothelium-dependent relaxation of rat aortic rings was impaired (ACh R(max) control 99 ± 1%; pyrogallol 44 ± 5%), an effect that was significantly reduced by KPE (10(-4)M, ACh R(max) 82 ± 4%). In addition, KPE was found to attenuate the ventricular dysfunction caused by 20 min global ischaemia and 30 min reperfusion (I/R) in rat isolated hearts (dP/dt IR 1016 ± 242, IR+KPE 2238±233 mm Hg/s). KPE is an effective vasodilator and antioxidant that is able to prevent myocardial ischaemia-reperfusion injury. We suggest that KPE may be useful as an adjunct to thrombolytic therapy in the management of reperfusion injury. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  4. Isolated perfused liver model: the rat and guinea pig compared.

    PubMed

    Chaïb, Samira; Charrueau, Christine; Neveux, Nathalie; Coudray-Lucas, Colette; Cynober, Luc; De Bandt, Jean-Pascal

    2004-05-01

    Although the rat is the most commonly used species for the study of hepatic metabolism, the physiology of the guinea pig is closer to human physiology. We compared the model of isolated perfused guinea pig liver with the classic model of isolated perfused rat liver, especially with respect to amino acid metabolism. After validation of an anesthetic mixture of ketamine, diazepam, and xylazine for the guinea pig, isolated perfused livers were harvested for both species. Three groups of animals were compared for the study of liver metabolic fluxes: 6-wk-old male Sprague-Dawley rats (R; 230 +/- 10 g, n = 5), young male Hartley guinea pigs (YG; 223 +/- 8 g, n = 6) matched to rats by liver weight, and adult male Hartley guinea pigs (AG; 389 +/- 5 g, n = 6) matched to rats by age. Results (mean +/- standard error of the mean) were compared by analysis of variance and Newman-Keuls tests. Both models displayed a satisfactory hepatic viability, but differences were noted, with higher portal flows (R: 3.1 +/- 0.3 versus YG: 4.5 +/- 0.3 and AG: 4.2 +/- 0.3 mL. min(-1). g(-1); P < 0.05, YG and AG versus R) and bile flows (R: 0.34 +/- 0.01 versus YG: 2.38 +/- 0.22 versus AG: 3.17 +/- 0.28 microL. min(-1). g(-1); P < 0.05, YG and AG versus R, and YG versus AG) and higher amino acid fluxes (P < 0.05) leading to greater nitrogen uptake (P < 0.05) in guinea pigs. We performed a second set of experiments to evaluate the influence of anesthesia and portal flow on this last parameter. In these experiments, rats were anesthetized with ketamine, diazepam, and xylazine and guinea pig livers were perfused at rat blood flow. Apart from a 50% anesthesia-related mortality for rats, bile flow and metabolic parameters were only slightly modified. However, some amino acid fluxes were statistically different (aspartate, serine, and histidine; P < 0.05), as confirmed by a higher transfer constant. Our results indicate that the isolated perfused guinea pig liver is a suitable model for the study of

  5. Depressive behavior induced by social isolation of predisposed female rats.

    PubMed

    Zanier-Gomes, Patrícia Helena; de Abreu Silva, Tomaz Eugênio; Zanetti, Guilherme Cia; Benati, Évelyn Raquel; Pinheiro, Nanci Mendes; Murta, Beatriz Martins Tavares; Crema, Virgínia Oliveira

    2015-11-01

    Depression is a mood disorder that is more prevalent in women and has been closely associated with chronic stress. Many models of depression have been suggested that consider different forms of stress. In fact, stress is present in the life of every human being, but only a few develop depression. Accordingly, it seems wrong to consider all stressed animals to be depressed, emphasizing the importance of predisposition for this mood disorder. Based on this finding, we evaluated a predisposition to depressive behavior of female rats on the forced swim test (FST), and the more immobile the animal was during the FST, the more predisposed to depression it was considered to be. Then, animals were subjected to the stress of social isolation for 21 days and were re-evaluated by the FST. The Predisposed/Isolated rats presented higher immobility times. Once all the rats had prior experience in the FST, we calculated an Index of Increase by Isolation, confirming the previous results. Based on this result, we considered the Predisposed/Isolated group as presenting depressive behavior ('Depressed') and the Nonpredisposed/Nonisolated group as the control group ('Nondepressed'). The animals were distributed into 4 new groups: Nondepressed/Vehicle, Nondepressed/Amitriptyline, Depressed/Vehicle, Depressed/Amitriptyline. After 21 days of treatment, only the Depressed/Vehicle group differed from the other 3 groups, demonstrating the efficacy of amitriptyline in treating the depressive behavior of the Depressed animals, validating the model. This study shows that conducting an FST prior to any manipulation can predict predisposition to depressive behavior in female rats and that the social isolation of predisposed animals for 21 days is effective in inducing depressive behavior. This behavior can be considered real depressive behavior because it takes into account predisposition, chronic mild stress, and the prevalent gender.

  6. Low vagally-mediated heart rate variability and increased susceptibility to ventricular arrhythmias in rats bred for high anxiety.

    PubMed

    Carnevali, Luca; Trombini, Mimosa; Graiani, Gallia; Madeddu, Denise; Quaini, Federico; Landgraf, Rainer; Neumann, Inga D; Nalivaiko, Eugene; Sgoifo, Andrea

    2014-04-10

    In humans, there is a documented association between anxiety disorders and cardiovascular disease. Putative underlying mechanisms may include an impairment of the autonomic nervous system control of cardiac function. The primary objective of the present study was to characterize cardiac autonomic modulation and susceptibility to arrhythmias in genetic lines of rats that differ largely in their anxiety level. To reach this goal, electrocardiographic recordings were performed in high-anxiety behavior (HAB, n=10) and low-anxiety behavior (LAB, n=10) rats at rest, during stressful stimuli and under autonomic pharmacological manipulations, and analyzed by means of time- and frequency-domain indexes of heart rate variability. During resting conditions, HAB rats displayed a reduced heart rate variability, mostly in terms of lower parasympathetic (vagal) modulation compared to LAB rats. In HAB rats, this relatively low cardiac vagal control was associated with smaller heart rate responsiveness to acute stressors compared to LAB counterparts. In addition, beta-adrenergic pharmacological stimulation induced a larger incidence of ventricular tachyarrhythmias in HABs compared to LABs. At sacrifice, a moderate increase in heart-body weight ratio was observed in HAB rats. We conclude that high levels of anxiety-related behavior in rats are associated with signs of i) impaired autonomic modulation of heart rate (low vagally-mediated heart rate variability), ii) poor adaptive heart rate responsiveness to stressful stimuli, iii) increased arrhythmia susceptibility, and iv) cardiac hypertrophy. These results highlight the utility of the HAB/LAB model for investigating the mechanistic basis of the comorbidity between anxiety disorders and cardiovascular disease. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Spatiotemporal complexity of ventricular fibrillation revealed by tissue mass reduction in isolated swine right ventricle. Further evidence for the quasiperiodic route to chaos hypothesis.

    PubMed Central

    Kim, Y H; Garfinkel, A; Ikeda, T; Wu, T J; Athill, C A; Weiss, J N; Karagueuzian, H S; Chen, P S

    1997-01-01

    We have presented evidence that ventricular fibrillation is deterministic chaos arising from quasiperiodicity. The purpose of this study was to determine whether the transition from chaos (ventricular fibrillation, VF) to periodicity (ventricular tachycardia) through quasiperiodicity could be produced by the progressive reduction of tissue mass. In isolated and perfused swine right ventricular free wall, recording of single cell transmembrane potentials and simultaneous mapping (477 bipolar electrodes, 1.6 mm resolution) were performed. The tissue mass was then progressively reduced by sequential cutting. All isolated tissues fibrillated spontaneously. The critical mass to sustain VF was 19.9 +/- 4.2 g. As tissue mass was decreased, the number of wave fronts decreased, the life-span of reentrant wave fronts increased, and the cycle length, the diastolic interval, and the duration of action potential lengthened. There was a parallel decrease in the dynamical complexity of VF as measured by Kolmogorov entropy and Poincaré plots. A period of quasiperiodicity became more evident before the conversion from VF (chaos) to a more regular arrhythmia (periodicity). In conclusion, a decrease in the number of wave fronts in ventricular fibrillation by tissue mass reduction causes a transition from chaotic to periodic dynamics via the quasiperiodic route. PMID:9366563

  8. Left ventricular aneurysm and prognosis in patients with first acute transmural anterior myocardial infarction and isolated left anterior descending artery disease.

    PubMed

    Shen, W F; Tribouilloy, C; Mirode, A; Dufossé, H; Lesbre, J P

    1992-01-01

    To determine the clinical and angiographic factors responsible for left ventricular aneurysm formation and the prognosis of patients with aneurysm, 79 patients with a first acute transmural anterior myocardial infarction and angiographically documented isolated left anterior descending artery disease were retrospectively evaluated. Presence of large infarct size and left ventricular volumes, reduced left ventricular function, and evidence of clinical functional impairment were more common in patients with aneurysm (n = 31) than in those without (n = 48). Patients with aneurysm often had total occlusion of the proximal left anterior descending artery without collateral vessels on angiography. During a mean follow-up of 53 months, 10 patients with and three without aneurysm died (P less than 0.01). Compared to survivors with or without aneurysm, the nonsurvivors were older, had significantly larger infarct size and left ventricular volumes and poor systolic function. The incidence of total occlusion of the left anterior descending artery without collaterals was higher in nonsurvivors. In patients with aneurysm, stepwise multivariate analysis revealed that left ventricular ejection fraction and the status of left anterior descending artery obstruction and collaterals were independent predictors of mortality. The study indicates that in patients with a first acute transmural anterior myocardial infarction and isolated anterior descending artery disease, left ventricular aneurysm often results from a large infarct caused by total occlusion of the proximal left anterior descending artery without collateral supply to the infarct region. The reduced survival rate for patients with aneurysm is primarily related to severe global left ventricular dysfunction which may be determined by assessing the residual flow to the infarct region.

  9. Pioglitazone Attenuates Acute Cocaine Toxicity in Rat Isolated Heart: Potential Protection by Metabolic Modulation

    PubMed Central

    Weinberg, Guy L.; Ripper, Richard; Bern, Sarah; Lin, Bocheng; Edelman, Lucas; DiGregorio, Guido; Piano, Mariann; Feinstein, Douglas L.

    2013-01-01

    Background The authors test whether cocaine depresses mitochondrial acylcarnitine exchange and if a drug that enhances glucose metabolism could protect against cocaine-induced cardiac dysfunction. Methods Oxygen consumption with and without cocaine was compared in rat cardiac mitochondria using either octanoylcarnitine (lipid) or pyruvate (non-lipid) substrates. Isolated hearts from rats with or without pioglitazone-supplemented diet were exposed to cocaine. Results Cocaine 0.5mM inhibited respiration supported by octanoylcarnitine (82 +/− 10.4 and 45.7 +/− 4.24 ngatomO min −1 mg −1 protein +/− SEM, for control and cocaine treatment, respectively; p < 0.02) but not pyruvate-supported respiration (281 +/− 12.5 and 267 +/− 12.7 ngatomO min −1 mg −1 protein +/− SEM; p = 0.45). Cocaine altered contractility, lusitropy, coronary resistance and lactate production in isolated heart. These effects were each blunted in pioglitazone-treated hearts. Pioglitazone diet attenuated the drop in rate-pressure product (p = 0.002), cocaine-induced diastolic dysfunction (p = 0.04) and myocardial vascular resistance (p = 0.05) compared to controls. Lactate production was higher in pretreated hearts (p = 0.008) and in ventricular myocytes cultured with pioglitazone (p = 0.0001). Conclusions Cocaine inhibited octanoylcarnitine-supported mitochondrial respiration. Pioglitazone diet significantly attenuated the effects of cocaine on isolated heart. The authors postulate that inhibition of acylcarnitine exchange could contribute to cocaine-induced cardiac dysfunction and that metabolic modulation warrants further study a potential treatment for such toxicity. PMID:21487283

  10. Mechanisms of action of diltiazem in isolated human atrial and ventricular myocardium.

    PubMed

    Sutton, M S; Morad, M

    1987-05-01

    A comparative study of human atrial fibers (HAF), human ventricular fibers (HVF), frog ventricle, and frog skeletal muscle demonstrated marked differences in tension development in the presence of diltiazem. There was no significant difference between the tension developed by HAF and by HVF over a range of diltiazem concentrations when the differences in resting membrane potential were corrected by increasing external K+ concentration. In human myocardium, diltiazem resulted in both a voltage and use-dependent blockade of the calcium channel. Comparison of the tension-dose response curves in human myocardium, frog ventricle and skeletal muscle showed that diltiazem was most effective at decreasing tension in frog heart, and least effective in skeletal muscle with human myocardium being intermediate. In skeletal muscle, neither tension development nor the birefringence signal related to the Ca2+ release from the sarcoplasmic reticulum was significantly altered by Diltiazem in concentrations less than 10(-6) M, but in concentrations greater than 10(-5) M both were suppressed. Diltiazem suppressed tension in human myocardium over the range of membrane potentials associated with Ca2+ channel activity, while at more positive potentials, diltiazem appeared to have little effect on the tension-voltage relations. Diltiazem had no effect upon tension development induced by acetyl strophanthidin in human myocardium or upon the Ca2+ sensitivity of chemically skinned atrial or ventricular fibers. Thus the tension-suppressant effect of diltiazem in human myocardium appears to be mediated by a combination of voltage-dependent block of the Ca2+ channel and inhibition of Ca2+ release from internal stores, and not from alterations in either Na+-Ca2+ coupled transport or Ca2+ sensitivity of the myofilaments.

  11. Cardiac actions of phencyclidine in isolated guinea pig and rat heart: possible involvement of slow channels

    SciTech Connect

    Temma, K.; Akera, T.; Ng, Y.C.

    1985-03-01

    The mechanisms responsible for the positive inotropic effect of phencyclidine were studied in isolated preparations of guinea pig and rat heart. In electrically paced left atrial muscle preparations, phencyclidine increased the force of contraction; rat heart muscle preparations were more sensitive than guinea pig heart muscle preparations. The positive inotropic effect of phencyclidine was not significantly reduced by a combination of phentolamine and nadolol; however, the effect was competitively blocked by verapamil in the presence of phentolamine and nadolol. Inhibition of the outward K+ current by tetraethylammonium chloride also produced a positive inotropic effect; however, the effect of tetraethylammonium was reduced by phentolamine and nadolol, and was almost insensitive to verapamil. The inotropic effect of phencyclidine was associated with a marked prolongation of the action potential duration and a decrease in maximal upstroke velocity of the action potential, with no change in the resting membrane potential. The specific (/sup 3/H)phencyclidine binding observed with membrane preparations from guinea pig ventricular muscle was saturable with a single class of high-affinity binding site. This binding was inhibited by verapamil, diltiazem, or nitrendipine, but not by ryanodine or tetrodotoxin. These results suggest that the positive inotropic effect of phencyclidine results from enhanced Ca/sup 2 +/ influx via slow channels, either by stimulation of the channels or secondary to inhibition of outward K/sup +/ currents.

  12. Isolated permanent right ventricular assist device implantation with the HeartWare continuous-flow ventricular assist device: first results from the European Registry for Patients with Mechanical Circulatory Support.

    PubMed

    Bernhardt, Alexander M; De By, Theo M M H; Reichenspurner, Hermann; Deuse, Tobias

    2015-07-01

    Isolated right ventricular (RV) dysfunction with preserved left ventricular function is difficult to treat and associated with high mortality. Temporary devices for right ventricular support [right ventricular assist device (RVAD)] are available and have been used for short-term right heart assistance. In some patients, RV function does not recover and long-term devices are needed. Recently, isolated RVAD implantation with a permanent HeartWare HeartWare ventricular assist device (HVAD) device has been reported in patients with acute RV infarction and chronic graft failure. However, isolated implantation on the right side remains rare and is still an off-label use for this pump. To gather European data, we queried the European Registry for Patients with Mechanical Circulatory Support (EUROMACS) database, in which procedures and outcome data for patients receiving mechanical circulatory support are registered. Until May 2014, data of 8 patients (mean age 55.0 ± 17.3 years, 100% males) with an isolated HVAD for RV support were submitted to the EUROMACS registry. All patients were in INTERMACS classes 1-3. Device strategy was rescue therapy in 6 patients (75.0%) and destination therapy in 2 patients (25.0%). Indications for RVAD placement were acute myocardial infarction in 4 (50.0%), failure to wean from cardiopulmonary bypass in 2 (25.0%) and post-cardiotomy RV failure in another 2 patients (25.0%). Intra- and postoperative results of the EUROMACS registry were analysed. Inflow cannulas were implanted into the right atrium (RA) in 6 patients (75.0%) and into the RV in 2 patients (25.0%). CPB was used in 6 patients (75.0%). Four patients (50.0%) survived the first 30 days. During follow-up, 1 patient died after 44 days due to multiorgan failure. In the surviving three patients, 2 patients were transplanted after 29 and 419 days, respectively, and, in 1 patient, the device was explanted for pump thrombosis and recovered RV function. In this very specific and sick

  13. Intrauterine endotoxin-induced impairs pulmonary vascular function and right ventricular performance in infant rats and improvement with early vitamin D therapy.

    PubMed

    Mandell, Erica; Powers, Kyle N; Harral, Julie W; Seedorf, Gregory J; Hunter, Kendall S; Abman, Steven H; Dodson, R Blair

    2015-12-15

    High pulmonary vascular resistance (PVR), proximal pulmonary artery (PA) impedance, and right ventricular (RV) afterload due to remodeling contribute to the pathogenesis and severity of pulmonary hypertension (PH). Intra-amniotic exposure to endotoxin (ETX) causes sustained PH and high mortality in rat pups at birth, which are associated with impaired vascular growth and RV hypertrophy in survivors. Treatment of ETX-exposed pups with antenatal vitamin D (vit D) improves survival and lung growth, but the effects of ETX exposure on RV-PA coupling in the neonatal lung are unknown. We hypothesized that intrauterine ETX impairs RV-PA coupling through sustained abnormalities of PA stiffening and RV performance that are attenuated with vit D therapy. Fetal rats were exposed to intra-amniotic injections of ETX, ETX+vit D, or saline at 20 days gestation (term = 22 days). At postnatal day 14, pups had pressure-volume measurements of the RV and isolated proximal PA, respectively. Lung homogenates were assayed for extracellular matrix (ECM) composition by Western blot. We found that ETX lungs contain decreased α-elastin, lysyl oxidase, collagen I, and collagen III proteins (P < 0.05) compared control and ETX+vit D lungs. ETX-exposed animals have increased RV mechanical stroke work (P < 0.05 vs. control and ETX+vit D) and elastic potential energy (P < 0.05 vs. control and ETX+vit D). Mechanical stiffness and ECM remodeling are increased in the PA (P < 0.05 vs. control and ETX+vit D). We conclude that intrauterine exposure of fetal rats to ETX during late gestation causes persistent impairment of RV-PA coupling throughout infancy that can be prevented with early vit D treatment.

  14. Gap junction modifier rotigaptide decreases the susceptibility to ventricular arrhythmia by enhancing conduction velocity and suppressing discordant alternans during therapeutic hypothermia in isolated rabbit hearts.

    PubMed

    Hsieh, Yu-Cheng; Lin, Jiunn-Cherng; Hung, Chen-Ying; Li, Cheng-Hung; Lin, Shien-Fong; Yeh, Hung-I; Huang, Jin-Long; Lo, Chu-Pin; Haugan, Ketil; Larsen, Bjarne D; Wu, Tsu-Juey

    2016-01-01

    Therapeutic hypothermia (TH) may increase the susceptibility to ventricular arrhythmias by decreasing ventricular conduction velocity (CV) and facilitating arrhythmogenic spatially discordant alternans (SDA). The purpose of this study was to test the hypothesis that rotigaptide, a gap junction enhancer, can increase ventricular CV, delay the onset of SDA, and decrease the susceptibility to pacing-induced ventricular fibrillation (PIVF) during TH. Langendorff-perfused isolated rabbit hearts were subjected to 30-minute moderate hypothermia (33°C) followed by 20-minute treatment with rotigaptide (300 nM, n = 8) or vehicle (n = 5). The same protocol was also performed at severe hypothermia (30°C; n = 8 for rotigaptide, n = 5 for vehicle). Using an optical mapping system, epicardial CV and SDA threshold were evaluated by S1 pacing. Ventricular fibrillation inducibility was evaluated by burst pacing for 30 seconds at the shortest pacing cycle length (PCL) that achieved 1:1 ventricular capture. Rotigaptide increased ventricular CV during 33°C (PCL 300 ms, from 76 ± 6 cm/s to 84 ± 7 cm/s, P = .039) and 30°C (PCL 300 ms, from 62 ± 6 cm/s to 68 ± 4 cm/s, P = .008). Rotigaptide decreased action potential duration dispersion at 33°C (P = .01) and 30°C (P = .035). During 30°C, SDA thresholds (P = .042) and incidence of premature ventricular complexes (P = .025) were decreased by rotigaptide. PIVF inducibility was decreased by rotigaptide at 33°C (P = .039) and 30°C (P = .042). Rotigaptide did not change connexin43 expressions and distributions during hypothermia. Rotigaptide protects the hearts against ventricular arrhythmias by increasing ventricular CV, delaying the onset of SDA, and reducing repolarization heterogeneity during TH. Enhancing cell-to-cell coupling by rotigaptide might be a novel approach to prevent ventricular arrhythmias during TH. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

  15. Metformin HCl has curative effect on rebuilding of ventricular diastolic functions in high-fat-diet fed rats.

    PubMed

    Topal, Askin Ender; Kelle, Ilker; Akkoc, Hasan; Yilmaz, Sedat; Yilmaz, Sedat; Akkus, Murat

    2017-05-01

    Myocardial lipid accumulation due to diabetes and/or obesity plays a role in the progression of left ventricular diastolic dysfunction. Our aims were to exhibit the correlation between histopathologic stage of the liver and cardiac functions, and to evaluate the effects of metformin HCl and rosiglitazone on myocardial functions. Thirty-two male Sprague-Dawley rats were divided into four groups to exhibit the correlation between histopathologic stage of the liver and cardiac functions and to determine whether metformin HCl and rosiglitazone have effects on cardiac functions. For 20 weeks, one group was fed standard rat basic diet, whereas the other groups were on high-fat-diet. During the last 4 weeks, metformin HCl was given to the third group, rosiglitazone to the fourth group. Histological evaluation of rat livers yielded significantly higher steatosis grade in high-fat-diet group and different fibrosis stages among groups. Also, there was significant correlation between diastolic functions and steatosis grade/fibrosis stage of rat liver. Electrophysiological study of hearts via Langendorff technique showed better coronary perfusion pressures and diastolic functions in standard-diet and metformin HCl groups compared to other groups. Metformin HCl improves LV diastolic dysfunction and coronary perfusion pressures.

  16. Speckle-tracking echocardiography correctly identifies segmental left ventricular dysfunction induced by scarring in a rat model of myocardial infarction.

    PubMed

    Popović, Zoran B; Benejam, Carlos; Bian, Jing; Mal, Niladri; Drinko, Jeannie; Lee, Kwangdeok; Forudi, Farhad; Reeg, Rachel; Greenberg, Neil L; Thomas, James D; Penn, Marc S

    2007-06-01

    Speckle-tracking echocardiography (STE) uses a two-dimensional echocardiographic image to estimate two orthogonal strain components. The aim of this study was to assess sensitivity of circumferential (S(circ)) and radial (S(rad)) strains to infarct-induced left ventricular (LV) remodeling and scarring of the LV in a rat. To assess the relationship among S(circ), S(rad), and scar size, two-dimensional echocardiographic LV short-axis images (12 MHz transducer, Vivid 7 echo machine) were collected in 34 Lewis rats 4 to 10 wk after ligation of the left anterior descending artery. Percent segmental fibrosis was assessed from histological LV cross sections stained by Masson trichrome. Ten normal rats served as echocardiographic controls. S(circ) and S(rad) were assessed by STE. Histological data showed consistent scarring of anterior and lateral segments with variable extension to posterior and inferior segments. Both S(circ) and S(rad) significantly decreased after myocardial infarction (P<0.0001 for both). As anticipated, S(circ) and S(rad) were lowest in the infarcted segments. Multiple linear regression showed that segmental S(circ) were similarly dependent on segmental fibrosis and end-systolic diameter (P<0.0001 for both), whereas segmental S(rad) measurements were more dependent on end-systolic diameter (P<0.0001) than on percent fibrosis (P<0.002). STE correctly identifies segmental LV dysfunction induced by scarring that follows myocardial infarction in rats.

  17. Comparison of Macitentan and Bosentan on Right Ventricular Remodeling in a Rat Model of Non-vasoreactive Pulmonary Hypertension

    PubMed Central

    Landskroner, Kyle; Bauer, Yasmina; Vercauteren, Magali; Rey, Markus; Renault, Berengère; Studer, Rolf; Vezzali, Enrico; Freti, Diego; Hadana, Hakim; Schläpfer, Manuela; Cattaneo, Christophe; Bortolamiol, Céline; Weber, Edgar; Whitby, Brian R.; Delahaye, Stéphane; Wanner, Daniel; Steiner, Pauline; Nayler, Oliver; Hess, Patrick; Clozel, Martine

    2015-01-01

    Aims: We compared the efficacy of macitentan, a novel dual endothelin A/endothelin B receptor antagonist, with that of another dual endothelin receptor antagonist, bosentan, in a rat model of non-vasoreactive pulmonary hypertension (PH) with particular emphasis on right ventricular (RV) remodeling. Methods and Results: Unlike monocrotaline or hypoxic/sugen rats, bleomycin-treated rats presented a non-vasoreactive PH characterized by the absence of pulmonary dilatation to adenosine. We therefore chose the bleomycin rat model to compare the effects of the maximally effective doses of macitentan and bosentan on pulmonary vascular and RV remodeling. Macitentan (100 mg·kg−1·d−1), but not bosentan (300 mg·kg−1·d−1), significantly prevented pulmonary vascular remodeling, RV hypertrophy, and cardiomyocyte diameter increase. Cardiac protection by macitentan was associated with a significant attenuation of genes related to cell hypertrophy and extracellular matrix remodeling. Microautoradiography and high performance liquid chromatography analysis showed greater distribution of macitentan than bosentan in the RV and pulmonary tissue. Conclusions: Macitentan was more efficacious than bosentan in preventing the development of pulmonary and RV hypertrophies in a model of non-vasoreactive PH. Greater ability to distribute into the tissue could contribute to the greater structural improvement by macitentan compared with bosentan. PMID:26230396

  18. Toxicity of ethacrynic acid in isolated rat hepatocytes.

    PubMed

    Yamamoto, K; Masubuchi, Y; Narimatsu, S; Kobayashi, S; Horie, T

    2002-04-01

    Ethacrynic acid, a loop diuretic drug, caused lipid peroxidation in isolated rat hepatocytes. The thiobarbituric acid reactive substances (TBARS) formation showed a good correlation with the leakage of glutamic-oxaloacetic acid transaminase (GOT) from the hepatocytes. The addition of antioxidants such as N, N'-diphenyl-p-phenylenediamine (DPPD) and promethazine to the isolated rat hepatocyte suspension containing ethacrynic acid prevented the lipid peroxidation and decreased the GOT leakage to some extent. SKF-525A inhibited the oxidative metabolism of ethacrynic acid and decreased the TBARS formation, suggesting that the lipid peroxidation was caused by the oxidative metabolism. The intracellular reduced glutathione markedly decreased in the hepatocyte suspension containing ethacrynic acid and the hepatocellular protein sulfhydryls were decreased, which was negatively correlated with the GOT leakage. Thus the ethacrynic acid-induced hepatotoxicity was found to be related to the lipid peroxidation and the decrease of cellular protein sulfhydryls.

  19. Isolation rearing induced fear-like behavior without affecting learning abilities of Wistar rats.

    PubMed

    Molina-Hernandez, M; Tellez-Alcantara, P; Perez-Garcia, J

    2001-07-01

    1. Isolation-reared rats display fear-like behavior and depressive-like behavior in several behavioral tasks, suggesting that isolation rearing may model certain aspects of human psychopathologies. 2. After weaning (20 days old), male and female Wistar rats were isolation-reared during 20, 50 or 70 days. After that, they were tested in the elevated plus maze test, and in the open field test. Another group of isolation-reared rats (70 days of isolation) were tested in an auto-shaping task. 3. Isolation-reared rats displayed high levels of fear-like behavior in the elevated plus-maze test, and hyperlocomotion in the open field test. But, isolation-reared rats learned an auto-shaping task. 4. In conclusion, isolation rearing induced fear-like behavior, without affect learning abilities of rats.

  20. [Effects of Chinese herbal medicines Shengmai injection and Xuesaitong injection on ventricular fibrillation threshold and connexin 43 expression in rats with myocardial infarction].

    PubMed

    Wu, Ai-Ming; Zhang, Dong-Mei; Lou, Li-Xia; Zhai, Jian-Ying; Lü, Xi-Ying; Chai, Li-Min; Wang, Shuo-Ren

    2011-07-01

    To explore the effects of Shengmai injection and Xuesaitong injection, compound Chinese herbal medicines for replenishing qi and activating blood, on ventricular fibrillation threshold, heart structure and connexin 43 (Cx43) expression in rats with myocardial infarction (MI). One hundred male SD rats were randomly divided into sham operation group, model group, Yiqi Huoxue (YQHX) group (Shengmai injection plus Xuesaitong injection) and captopril group. MI model of rats was established by ligating left anterior descending coronary artery, and rats in sham operation group were prepared in the same way except for the ligation of coronary artery. Rats were treated with corresponding drugs for 1 month from next day after modeling. After treatment ventricular fibrillation threshold was detected, and heart weight index, left ventricular internal diameter and percentage of myocardial infarction were measured. Expression of Cx43 mRNA in myocardium was detected by real-time fluorescent quantitative polymerase chain reaction, and expression of Cx43 protein was observed by immunohistochemical method. Compared with the sham operation group, ventricular fibrillation threshold decreased significantly, heart weight index and left ventricular internal diameter increased, while expressions of Cx43 mRNA and protein decreased remarkably in the model group (P<0.01). Compared with the model group, ventricular fibrillation threshold was increased significantly, heart weight index, left ventricular internal diameter and percentage of myocardial infarction were decreased significantly in the YQHX group and captopril group (P<0.05 or P<0.01). When it comes to expression of Cx43, both Cx43 mRNA and protein expressions were increased remarkably in the YQHX group compared with the model group (P<0.05 or P<0.01), while only density mean and integral optical density of Cx43 protein expression were increased significantly in the captopril group (P<0.05). The enhancements on Cx43 mRNA and positive

  1. A rare case of isolated left ventricular non-compaction. Importance of image technology and disease awareness for a correct diagnosis.

    PubMed

    Mariotti, Egidio; Pierantozzi, Attilio; Bocconcelli, Paolo

    2006-07-01

    In 1999 a 50-year-old man with sustained monomorphic ventricular tachycardia came to our institution for investigation using fundamental echocardiographic imaging. A diagnosis of hypertrophic cardiomyopathy with dilatation and apical thrombus was made. In 2003, a new echocardiographic machine equipped with second harmonic imaging modality became available and after a second investigation the diagnosis was changed to isolated left ventricular non-compaction. The echocardiogram showed hypertrabeculations involving not only the mid-septum but also the basal septum (anterior and posterior) and a thin epicardial layer without the thickened endocardial component.

  2. Effect of exercise training on Ca²⁺ release units of left ventricular myocytes of spontaneously hypertensive rats.

    PubMed

    Carneiro-Júnior, M A; Quintão-Júnior, J F; Drummond, L R; Lavorato, V N; Drummond, F R; Amadeu, M A; Oliveira, E M; Felix, L B; Cruz, J S; Mill, J G; Natali, A J; Prímola-Gomes, T N

    2014-11-01

    In cardiomyocytes, calcium (Ca²⁺) release units comprise clusters of intracellular Ca²⁺ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca²⁺ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca²⁺ sparks (HC=7.61 ± 0.26 vs NC=4.79 ± 0.19 per 100 µm/s) and decreased its amplitude (HC=0.260 ± 0.08 vs NC=0.324 ± 0.10 ΔF/F0), full width at half-maximum amplitude (HC=1.05 ± 0.08 vs NC=1.26 ± 0.01 µm), total duration (HC=11.51 ± 0.12 vs NC=14.97 ± 0.24 ms), time to peak (HC=4.84 ± 0.06 vs NC=6.31 ± 0.14 ms), and time constant of decay (HC=8.68 ± 0.12 vs NC=10.21 ± 0.22 ms). These changes were partially reversed in HT rats (frequency of Ca²⁺ sparks=6.26 ± 0.19 µm/s, amplitude=0.282 ± 0.10 ΔF/F0, full width at half-maximum amplitude=1.14 ± 0.01 µm, total duration=13.34 ± 0.17 ms, time to peak=5.43 ± 0.08 ms, and time constant of decay=9.43 ± 0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release

  3. Effect of exercise training on Ca2+ release units of left ventricular myocytes of spontaneously hypertensive rats

    PubMed Central

    Carneiro-Júnior, M.A.; Quintão-Júnior, J.F.; Drummond, L.R.; Lavorato, V.N.; Drummond, F.R.; Amadeu, M.A.; Oliveira, E.M.; Felix, L.B.; Cruz, J.S.; Mill, J.G.; Natali, A.J.; Prímola-Gomes, T.N.

    2014-01-01

    In cardiomyocytes, calcium (Ca2+) release units comprise clusters of intracellular Ca2+ release channels located on the sarcoplasmic reticulum, and hypertension is well established as a cause of defects in calcium release unit function. Our objective was to determine whether endurance exercise training could attenuate the deleterious effects of hypertension on calcium release unit components and Ca2+ sparks in left ventricular myocytes of spontaneously hypertensive rats. Male Wistar and spontaneously hypertensive rats (4 months of age) were divided into 4 groups: normotensive (NC) and hypertensive control (HC), and normotensive (NT) and hypertensive trained (HT) animals (7 rats per group). NC and HC rats were submitted to a low-intensity treadmill running protocol (5 days/week, 1 h/day, 0% grade, and 50-60% of maximal running speed) for 8 weeks. Gene expression of the ryanodine receptor type 2 (RyR2) and FK506 binding protein (FKBP12.6) increased (270%) and decreased (88%), respectively, in HC compared to NC rats. Endurance exercise training reversed these changes by reducing RyR2 (230%) and normalizing FKBP12.6 gene expression (112%). Hypertension also increased the frequency of Ca2+ sparks (HC=7.61±0.26 vs NC=4.79±0.19 per 100 µm/s) and decreased its amplitude (HC=0.260±0.08 vs NC=0.324±0.10 ΔF/F0), full width at half-maximum amplitude (HC=1.05±0.08 vs NC=1.26±0.01 µm), total duration (HC=11.51±0.12 vs NC=14.97±0.24 ms), time to peak (HC=4.84±0.06 vs NC=6.31±0.14 ms), and time constant of decay (HC=8.68±0.12 vs NC=10.21±0.22 ms). These changes were partially reversed in HT rats (frequency of Ca2+ sparks=6.26±0.19 µm/s, amplitude=0.282±0.10 ΔF/F0, full width at half-maximum amplitude=1.14±0.01 µm, total duration=13.34±0.17 ms, time to peak=5.43±0.08 ms, and time constant of decay=9.43±0.15 ms). Endurance exercise training attenuated the deleterious effects of hypertension on calcium release units of left ventricular myocytes. PMID:25296357

  4. Performance of two-dimensional Doppler echocardiography for the assessment of infarct size and left ventricular function in rats.

    PubMed

    Nozawa, E; Kanashiro, R M; Murad, N; Carvalho, A C C; Cravo, S L D; Campos, O; Tucci, P J F; Moises, V A

    2006-05-01

    Although echocardiography has been used in rats, few studies have determined its efficacy for estimating myocardial infarct size. Our objective was to estimate the myocardial infarct size, and to evaluate anatomic and functional variables of the left ventricle. Myocardial infarction was produced in 43 female Wistar rats by ligature of the left coronary artery. Echocardiography was performed 5 weeks later to measure left ventricular diameter and transverse area (mean of 3 transverse planes), infarct size (percentage of the arc with infarct on 3 transverse planes), systolic function by the change in fractional area, and diastolic function by mitral inflow parameters. The histologic measurement of myocardial infarction size was similar to the echocardiographic method. Myocardial infarct size ranged from 4.8 to 66.6% when determined by histology and from 5 to 69.8% when determined by echocardiography, with good correlation (r = 0.88; P < 0.05; Pearson correlation coefficient). Left ventricular diameter and mean diastolic transverse area correlated with myocardial infarct size by histology (r = 0.57 and r = 0.78; P < 0.0005). The fractional area change ranged from 28.5 +/- 5.6 (large-size myocardial infarction) to 53.1 +/- 1.5% (control) and correlated with myocardial infarct size by echocardiography (r = -0.87; P < 0.00001) and histology (r = -0.78; P < 00001). The E/A wave ratio of mitral inflow velocity for animals with large-size myocardial infarction (5.6 +/- 2.7) was significantly higher than for all others (control: 1.9 +/- 0.1; small-size myocardial infarction: 1.9 +/- 0.4; moderate-size myocardial infarction: 2.8 +/- 2.3). There was good agreement between echocardiographic and histologic estimates of myocardial infarct size in rats.

  5. Repeated sauna therapy attenuates ventricular remodeling after myocardial infarction in rats by increasing coronary vascularity of noninfarcted myocardium.

    PubMed

    Sobajima, Mitsuo; Nozawa, Takashi; Shida, Takuya; Ohori, Takashi; Suzuki, Takayuki; Matsuki, Akira; Inoue, Hiroshi

    2011-08-01

    Repeated sauna therapy (ST) increases endothelial nitric oxide synthase (eNOS) activity and improves cardiac function in heart failure as well as peripheral blood flow in ischemic limbs. The present study investigates whether ST can increase coronary vascularity and thus attenuate cardiac remodeling after myocardial infarction (MI). We induced MI by ligating the left coronary artery of Wistar rats. The rats were placed in a far-infrared dry sauna at 41°C for 15 min and then at 34°C for 20 min once daily for 4 wk. Cardiac hemodynamic, histopathological, and gene analyses were performed. Despite the similar sizes of MI between the ST and non-ST groups (51.4 ± 0.3 vs. 51.1 ± 0.2%), ST reduced left ventricular (LV) end-diastolic (9.7 ± 0.4 vs. 10.7 ± 0.5 mm, P < 0.01) and end-systolic (8.6 ± 0.5 vs. 9.6 ± 0.6 mm, P < 0.01) dimensions and attenuated MI-induced increases in LV end-diastolic pressure. Cross-sectional areas of cardiomyocytes were smaller in ST rats and associated with a significant reduction in myocardial atrial natriuretic peptide mRNA levels. Vascular density was reduced in the noninfarcted myocardium of non-ST rats, and the density of cells positive for CD31 and for α-smooth muscle actin was decreased. These decreases were attenuated in ST rats compared with non-ST rats and associated with increases in myocardial eNOS and vascular endothelial growth factor mRNA levels. In conclusion, ST attenuates cardiac remodeling after MI, at least in part, through improving coronary vascularity in the noninfarcted myocardium. Repeated ST might serve as a novel noninvasive therapy for patients with MI.

  6. Left ventricular pressure-volume measurements and myocardial gene expression profile in type 2 diabetic Goto-Kakizaki rats.

    PubMed

    Korkmaz-Icöz, Sevil; Lehner, Alice; Li, Shiliang; Vater, Adrian; Radovits, Tamás; Brune, Maik; Ruppert, Mihály; Sun, Xiaoxin; Brlecic, Paige; Zorn, Markus; Karck, Matthias; Szabó, Gábor

    2016-10-01

    The Goto-Kakizaki (GK) rat, a non-obese model of type 2 diabetes mellitus (T2DM), was generated by the selective inbreeding of glucose-intolerant Wistar rats. This is a convenient model for studying diabetes-induced cardiomyopathy independently from the effects of the metabolic syndrome. We investigated the myocardial functional and structural changes and underlying molecular pathomechanisms of short-term and mild T2DM. The presence of DM was confirmed by an impaired oral glucose tolerance in the GK rats compared with the age-matched nondiabetic Wistar rats. Data from cardiac catheterization showed that in GK rats, although the systolic indexes were not altered, the diastolic stiffness was increased compared with nondiabetics (end-diastolic-pressure-volume-relationship: 0.12 ± 0.04 vs. 0.05 ± 0.01 mmHg/μl, P < 0.05). Additionally, DM was associated with left-ventricular hypertrophy and histological evidence of increased myocardial fibrosis. The plasma pro-B-type natriuretic peptide, the cardiac troponin-T, glucose, and the urinary glucose concentrations were significantly higher in GK rats. Among the 125 genes surveyed using PCR arrays, DM significantly altered the expression of five genes [upregulation of natriuretic peptide precursor-A and connective tissue growth factor, downregulation of c-reactive protein, interleukin-1β, and tumor necrosis factor (TNF)-α mRNA-level]. Of the altered genes, which were evaluated by Western blot, only TNF-α protein expression was significantly decreased. The ECG recordings revealed no significant differences. In conclusion, while systolic dysfunction, myocardial inflammation, and abnormal electrical conduction remain absent, short-term and mild T2DM induce the alteration of cardiac TNF-α at both the mRNA and protein levels. Further assessments are required to reveal if TNF-α plays a role in the early stage of diabetic cardiomyopathy development. Copyright © 2016 the American Physiological Society.

  7. Pentitols and insulin release by isolated rat islets of Langerhans

    PubMed Central

    Montague, W.; Taylor, K. W.

    1968-01-01

    1. Insulin secretion was studied in isolated islets of Langerhans obtained by collagenase digestion of rat pancreas. In addition to responding to glucose and mannose as do whole pancreas and pancreas slices in vitro, isolated rat islets also secrete insulin in response to xylitol, ribitol and ribose, but not to sorbitol, mannitol, arabitol, xylose or arabinose. 2. Xylitol and ribitol readily reduce NAD+ when added to a preparation of ultrasonically treated islets. 3. Adrenaline (1μm) inhibits the effects of glucose and xylitol on insulin release. Mannoheptulose and 2-deoxy-glucose, however, inhibit the response to glucose but not that to xylitol. 4. The intracellular concentration of glucose 6-phosphate is increased when islets are incubated with glucose but not with xylitol, suggesting that xylitol does not promote insulin release by conversion into glucose 6-phosphate. 5. Theophylline (5mm) potentiates the effect of 20mm-glucose on insulin release from isolated rat islets of Langerhans, but has no effect on xylitol-mediated release. These results indicate that xylitol does not stimulate insulin release by alterations in the intracellular concentrations of cyclic AMP. 6. A possible role for the metabolism of hexoses via the pentose phosphate pathway in the stimulation of insulin release is discussed. PMID:4879533

  8. Isolation and characterization of endosomes from rat liver

    SciTech Connect

    Kennedy, G.C.

    1987-01-01

    Three fractions of rat liver endosomes, called 50 Kg Light, 50 Kg Heavy, and 150 Kg have been isolated on 16% Percoll gradients. The 50 Kg Heavy fraction accumulates ligand as a function of time after injection, using either /sup 125/I-asialoorosomucoid (/sup 125/I-ASOR) or /sup 125/I-immunoglobulin A (/sup 125/I-IgA) as ligands. A pulse-chase protocol was also used to study the kinetics of ligand entry into the endosomal compartments. A double-label, 3,3'-diaminobenzidine (DAB)-induced density shift protocol was used to study the internalization of two ligands with different destinations in the hepatocyte. Rats were injected intraportally with /sup 125/I-ASOR-HRP and /sup 131/I-IgA and the liver was fractionated at various times post-injection. The three ligand-containing endosomal fractions were isolated and each subjected to the DAB shift procedure. This treatment causes organelles containing /sup 125/I-ASOR-HRP and another ligand occupying the same compartment to shift to a higher density. Thus, information on whether the /sup 131/I-IgA is colocalized or segregated from the /sup 125/I-ASOR-HRP can be obtained. The authors have used an instantaneous pulse, temperature shift protocol to study the heterogeneity of these three endosomal fractions isolated from rat liver.

  9. Isolated pulmonary regurgitation causes decreased right ventricular longitudinal function and compensatory increased septal pumping in a porcine model.

    PubMed

    Kopic, S; Stephensen, S S; Heiberg, E; Arheden, H; Bonhoeffer, P; Ersbøll, M; Vejlstrup, N; Søndergaard, L; Carlsson, M

    2017-06-05

    Longitudinal ventricular contraction is a parameter of cardiac performance with predictive power. Right ventricular (RV) longitudinal function is impaired in patients with free pulmonary regurgitation (PR) following corrective surgery for Tetralogy of Fallot (TOF). It remains unclear whether this is a consequence of the surgical repair, or whether it is inherent to PR. The aim of this study was to assess the relationship between longitudinal, lateral and septal pumping in a porcine model of isolated PR. Piglets were divided into a control (n = 8) group and a treatment (n = 12) group, which received a stent in the pulmonary valve orifice, inducing PR. After 2-3 months, animals were subjected to cardiac magnetic resonance imaging. A subset of animals (n = 6) then underwent percutaneous pulmonary valve replacement (PPVR) with follow-up 1 month later. Longitudinal, lateral and septal contributions to stroke volume (SV) were quantified by measuring volumetric displacements from end-diastole to end-systole in the cardiac short axis and long axis. PR resulted in a lower longitudinal contribution to RV stroke volume, compared to controls (60.0 ± 2.6% vs. 73.6 ± 3.8%; P = 0.012). Furthermore, a compensatory increase in septal contribution to RVSV was observed (11.0 ± 1.6% vs. -3.1 ± 1.5%; P < 0.0001). The left ventricle (LV) showed counter-regulation with an increased longitudinal LVSV. Changes in RV longitudinal function were reversed by PPVR. These findings suggest that PR contributes to decreased RV longitudinal function in the absence of scarring from cardiac surgery. Measurement of longitudinal RVSV may aid risk stratification and timing for interventional correction of PR in TOF patients. © 2017 The Authors. Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.

  10. Isolation and characterization of intact mitochondria from neonatal rat brain.

    PubMed

    Rajapakse, N; Shimizu, K; Payne, M; Busija, D

    2001-12-01

    Poor outcome after neonatal brain injury may be associated with alterations in mitochondrial function. Thus, isolated mitochondria have been a useful tool in understanding the underlying mechanisms of mitochondrial dysfunction. However, isolation and characterization of mitochondria from neonatal rat brain are not fully described. Thus, the aim of this study was to develop a rapid method for the isolation and characterization of functional mitochondria from neonatal rat brain. Mitochondria were isolated from 7-day-old rat brain weighing approximately 500 mg using a discontinuous Percoll density gradient. Brains were homogenized in 12% Percoll/sucrose buffer and layered onto a 26% Percoll/40% Percoll gradient followed by centrifugation. Four methods were used for assessing mitochondrial integrity and function: (1) electron microscopy to assess the morphology of the mitochondria and to determine the relative purity of the preparation; (2) fluorescence of chloromethyl-X-rosamine (Mito Tracker Red) in mitochondria as an indicator of mitochondrial membrane potential (Delta psi(m)); (3) state 3 and 4 respiration; and (4) protein import into mitochondria using an in vitro-synthesized mitochondrial malate dehydrogenase (mMDH). These studies demonstrated that the morphology of mitochondria is maintained with intact outer membranes and well-developed cristae, and Delta psi(m) is preserved. Respiration measurements revealed tightly coupled mitochondria with a respiration control ratio (RCR) of 4.1+/-0.18 (n=6). Import of precursor mMDH into mitochondria increased in a time-dependent manner maximizing at 15 min. The results indicate that neonatal brain mitochondria isolated using this method are well coupled, morphologically intact and are capable of protein import across the outer and inner mitochondrial membranes.

  11. Left ventricular pressure-volume relationships during normal growth and development in the adult rat--studies in 8- and 50-week-old male Wistar rats.

    PubMed

    Bal, M P; de Vries, W B; van der Leij, F R; van Oosterhout, M F M; Baan, J; van der Wall, E E; van Bel, F; Steendijk, P

    2005-11-01

    Left ventricular (LV) pressure-volume relations provide relatively load-independent indexes of systolic and diastolic LV function, but few data are available on pressure-volume relations during growth and development in the normal adult heart. Furthermore, to quantify intrinsic ventricular function the indexes should be normalized for heart weight. However, in many studies the indexes are reported in absolute terms, or body weight-correction is used as a surrogate for heart weight-correction. We determined pressure-volume relations in young (8-week-old, n = 13) and middle-aged (50-week-old, n = 19) male Wistar rats in relation to their heart and body weights. The animals were anaesthetized and a 2F pressure-conductance catheter was introduced into the LV to measure pressure-volume relations. Heart and body weights were significantly higher in the 50-week-old rats, whereas the heart-to-body weight ratio was significantly lower (2.74 +/- 0.32 vs. 4.41 +/- 0.37 mg g(-1), P < 0.001). Intrinsic systolic function, quantified by the slopes of the end-systolic pressure-volume relation (E(ES)), the dP/dt(MAX) vs. end-diastolic volume relation (S-dP), and the preload recruitable stroke work relation (PRSW), normalized for heart weight, was slightly decreased in the 50-week-old rats (S-dP: -6%, P < 0.004; PRSW: -3%, P < 0.06). Heart weight-corrected diastolic indexes were not significant different. The absolute indexes qualitatively showed the same results, but body-weight corrected pressure-volume indexes showed improved systolic function and significantly depressed diastolic function. Intrinsic systolic function slightly decreases from the juvenile to the middle-aged period in normal male Wistar rats. Furthermore, correction of pressure-volume indexes for body weight is not an adequate surrogate for heart weight-correction in these animals.

  12. [Heart transplantation for the treatment of isolated left ventricular myocardial noncompaction. First case in Mexico].

    PubMed

    Zetina-Tun, Hugo Jesús; Careaga-Reyna, Guillermo; Galván-Díaz, José; Sánchez-Uribe, Magdalena

    2016-10-20

    Myocardial noncompaction of the left ventricle is a congenital cardiomyopathy characterised by left ventricular hypertrabeculation and prominent intertrabecular recesses. The incidence ranges from 0.15% to 2.2%. Clinical manifestations include heart failure, arrhythmias, and stroke. Prognosis is fatal in most cases. Heart transplantation is a therapeutic option for this cardiomyopathy, and few had been made worldwide. The case is presented of a 20 year-old male with noncompacted myocardium of the left ventricle, who had clinical signs of heart failure. His functional class was IV on the New York Heart Association scale. He was successfully transplanted. Its survival to 15 months is optimal in class I New York Heart Association, and endomyocardial biopsies have been reported without evidence of acute rejection. It is concluded that heart transplantation modified the natural history and improved survival in patients with this congenital heart disease. Copyright © 2016 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

  13. Endogenous triacylglycerol utilization by the isolated rat atria.

    PubMed

    Varela, A; Savino, E A

    1988-03-01

    The isolated atria from 24 h fasted rats, either in the presence of glucose or in a substrate-free medium containing 2-deoxyglucose, mobilized the endogenous triacylglycerol (TG) to a greater extent than those from fed rats. The TG of the fasted atria had almost disappeared at the end of the 90 min incubation in the substrate-free plus 2-deoxyglucose medium, whereas in those from fed rats a mobilization-resistant portion of about 40% of the TG pool remained. This finding coincided with a lower decay of the contractile and pacemaker activities in the atria from fasted rats. Insulin abolished the TG mobilization in the atria from fed rats in the presence of glucose, but it was ineffective in the fasted atria. These data suggest that the endogenous-TG and glucose share in supporting the atrial functions, that insulin is involved in the control of TG consumption only in the fed state and that the greater TG mobilization in the fasted atria, at least partly, meets the energy requirements of the tissue.

  14. Persistence of neoangiogenesis and cardiomyocyte divisions in right ventricular myocardium of rats born and raised in hypoxic conditions.

    PubMed

    Moravec, Mireille; Turek, Zdenek; Moravec, Josef

    2002-03-01

    Effects of chronic hypoxia on capillary and myocyte growth were examined in rats born and raised in a low pressure chamber (equivalent of 3500 m a.s.l.). The animals were sacrificed at the age of 3 months and their hearts were used to study right ventricular growth and vascularization. The results of our cytological and morphometric analysis suggest the persistence of capillary neogenesis in this particular model of cardiac hypertrophy. Under the optical microscope, we observed significant changes in capillary spatial patterns such as the presence of sinusoids and irregular capillary sprouts. This resulted in a significant shortening of the effective diffusion distance and in a slight decrease in the calculated diameter of the Krogh cylinder. Concomitant to the remodeling of the terminal capillary network, the right ventricular myocardium of hypoxic rats exhibited peculiar changes in myocyte cytology. The principal alteration consisted in the ectopic subsarcolemmal location of some of muscle cell nuclei which appeared enlarged and rounded, sometimes irregularly folded. At the E. M. level, they presented chromatine condensation, nucleolemmal folding and, occasionally, nuclear splitting. Irregular chromatin densifications at the equatorial position were also encountered but we never observed nucleolemmal dissolution or typical metaphase plaques which excludes the presence of mitotic division. Some of the marginalized nuclei were progressively excluded from original binucleate cells into small cytoplasmic processes that invaded the adjacent neo-formed pericapillar spaces and gave rise to small well-organized cardiomyocytes. This apparent fragmentation of cardiomyocytes may evoke the description of the apoptotic process which is believed to be stimulated in hypoxic tissues. However, we could not confirm that myocyte fragmentation that we describe is followed by shrinkage necrosis or by any mobilization of adjacent resident cells. Nuclear exclusions into pericapillary

  15. Metabolic Inhibition Strongly Inhibits Na+-Dependent Mg2+ Efflux in Rat Ventricular Myocytes

    PubMed Central

    Tashiro, Michiko; Inoue, Hana; Konishi, Masato

    2009-01-01

    Abstract We measured intracellular Mg2+ concentration ([Mg2+]i) in rat ventricular myocytes using the fluorescent indicator furaptra (25°C). In normally energized cells loaded with Mg2+, the introduction of extracellular Na+ induced a rapid decrease in [Mg2+]i: the initial rate of decrease in [Mg2+]i (initial Δ[Mg2+]i/Δt) is thought to represent the rate of Na+-dependent Mg2+ efflux (putative Na+/Mg2+ exchange). To determine whether Mg2+ efflux depends directly on energy derived from cellular metabolism, in addition to the transmembrane Na+ gradient, we estimated the initial Δ[Mg2+]i/Δt after metabolic inhibition. In the absence of extracellular Na+ and Ca2+, treatment of the cells with 1 μM carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone, an uncoupler of mitochondria, caused a large increase in [Mg2+]i from ∼0.9 mM to ∼2.5 mM in a period of 5–8 min (probably because of breakdown of MgATP and release of Mg2+) and cell shortening to ∼50% of the initial length (probably because of formation of rigor cross-bridges). Similar increases in [Mg2+]i and cell shortening were observed after application of 5 mM potassium cyanide (KCN) (an inhibitor of respiration) for ≥90 min. The initial Δ[Mg2+]i/Δt was diminished, on average, by 90% in carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone-treated cells and 92% in KCN-treated cells. When the cells were treated with 5 mM KCN for shorter times (59–85 min), a significant decrease in the initial Δ[Mg2+]i/Δt (on average by 59%) was observed with only a slight shortening of the cell length. Intracellular Na+ concentration ([Na+]i) estimated with a Na+ indicator sodium-binding benzofuran isophthalate was, on average, 5.0–10.5 mM during the time required for the initial Δ[Mg2+]i/Δt measurements, which is well below the [Na+]i level for half inhibition of the Mg2+ efflux (∼40 mM). Normalization of intracellular pH using 10 μM nigericin, a H+ ionophore, did not reverse the inhibition of the Mg2+ efflux

  16. Metabolic inhibition strongly inhibits Na+-dependent Mg2+ efflux in rat ventricular myocytes.

    PubMed

    Tashiro, Michiko; Inoue, Hana; Konishi, Masato

    2009-06-17

    We measured intracellular Mg2+ concentration ([Mg2+]i) in rat ventricular myocytes using the fluorescent indicator furaptra (25 degrees C). In normally energized cells loaded with Mg2+, the introduction of extracellular Na+ induced a rapid decrease in [Mg2+]i: the initial rate of decrease in [Mg2+]i (initial Delta[Mg2+]i/Deltat) is thought to represent the rate of Na+-dependent Mg2+ efflux (putative Na+/Mg2+ exchange). To determine whether Mg2+ efflux depends directly on energy derived from cellular metabolism, in addition to the transmembrane Na+ gradient, we estimated the initial Delta[Mg2+]i/Deltat after metabolic inhibition. In the absence of extracellular Na+ and Ca2+, treatment of the cells with 1 microM carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone, an uncoupler of mitochondria, caused a large increase in [Mg2+]i from approximately 0.9 mM to approximately 2.5 mM in a period of 5-8 min (probably because of breakdown of MgATP and release of Mg2+) and cell shortening to approximately 50% of the initial length (probably because of formation of rigor cross-bridges). Similar increases in [Mg2+]i and cell shortening were observed after application of 5 mM potassium cyanide (KCN) (an inhibitor of respiration) for > or = 90 min. The initial Delta[Mg2+]i/Deltat was diminished, on average, by 90% in carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone-treated cells and 92% in KCN-treated cells. When the cells were treated with 5 mM KCN for shorter times (59-85 min), a significant decrease in the initial Delta[Mg2+]i/Deltat (on average by 59%) was observed with only a slight shortening of the cell length. Intracellular Na+ concentration ([Na+]i) estimated with a Na+ indicator sodium-binding benzofuran isophthalate was, on average, 5.0-10.5 mM during the time required for the initial Delta[Mg2+]i/Deltat measurements, which is well below the [Na+]i level for half inhibition of the Mg2+ efflux (approximately 40 mM). Normalization of intracellular pH using 10 micro

  17. Tickling during adolescence alters fear-related and cognitive behaviors in rats after prolonged isolation.

    PubMed

    Hori, Miyo; Yamada, Kazuo; Ohnishi, Junji; Sakamoto, Shigeko; Furuie, Hiroki; Murakami, Kazuo; Ichitani, Yukio

    2014-05-28

    Social interactions during adolescence are important especially for neuronal development and behavior. We recently showed that positive emotions induced by repeated tickling could modulate fear-related behaviors and sympatho-adrenal stress responses. In the present study, we examined whether tickling during early to late adolescence stage could reverse stress vulnerability induced by socially isolated rearing. Ninety-five male Fischer rats were reared under different conditions from postnatal day (PND) 21 to 53: group-housed (three rats/cage), isolated-nontickled (one rat/cage) and isolated-tickled (received tickling stimulation for 5min a day). Auditory fear conditioning was then performed on the rats at PND 54. Isolated-tickled rats exhibited significantly lower freezing compared with group-housed rats in the first retention test performed 48h after conditioning and compared with isolated-nontickled rats in the second retention test performed 96h after conditioning. Moreover, group-housed and isolated-tickled rats tended to show a significant decrease in freezing responses in the second retention test; however, isolated-nontickled rats did not. In the Morris water maze task that was trained in adulthood (PND 88), but not in adolescence (PND 56), isolated-nontickled rats showed slower decrease of escape latency compared to group-housed rats; however, tickling treatment significantly improved this deficit. These results suggest that tickling stimulation can alleviate the detrimental effects of isolated rearing during adolescence on fear responses and spatial learning. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Cardioprotective effect of aqueous extract of Chichorium intybus on ischemia-reperfusion injury in isolated rat heart.

    PubMed

    Sadeghi, Najmeh; Dianat, Mahin; Badavi, Mohammad; Malekzadeh, Ahad

    2015-01-01

    Several studies have shown that Chichorium intybus (C. intybus) which possesses flavonoid compounds has an effective role in treatment of cardiovascular diseases. Contractile dysfunction mostly occurs after acute myocardial infarction, cardiac bypass surgery, heart transplantation and coronary angioplasty. The aim of the present study was to investigate the effect of aqueous extract of C. intybus on ischemia- reperfusion injury in isolated rat heart. The animals were divided into four groups (Sham, Control, 1 mg/ml and 3 mg/ml of extract) of 8 rats. The aorta was cannulated, and then the heart was mounted on a Langendorff apparatus. Next, a balloon was inserted into the left ventricle (LV) and peak positive value of time derivate of LV pressure (+dp/dt), coronary flow (CF), and left ventricular systolic pressure (LVSP) in pre-ischemia and reperfusion period were calculated by a Power Lab system. All groups underwent a 30-minute global ischemia followed by a 60-minute reperfusion. The results showed that heart rate (HR), coronary flow, and left ventricular developed pressure (LVDP) and rate of pressure product (RPP) significantly decreased in the control group during reperfusion, while these values in the groups receiving the extract (3mg/ml) improved significantly during reperfusion (p<0.001). It seems that flavonoid compounds of aqueous extract of C. intybus reduce ischemia - reperfusion injuries, suggesting its protective effect on heart function after ischemia.

  19. Cardioprotective effect of aqueous extract of Chichorium intybus on ischemia-reperfusion injury in isolated rat heart

    PubMed Central

    Sadeghi, Najmeh; Dianat, Mahin; Badavi, Mohammad; Malekzadeh, Ahad

    2015-01-01

    Objective: Several studies have shown that Chichorium intybus (C. intybus) which possesses flavonoid compounds has an effective role in treatment of cardiovascular diseases. Contractile dysfunction mostly occurs after acute myocardial infarction, cardiac bypass surgery, heart transplantation and coronary angioplasty. The aim of the present study was to investigate the effect of aqueous extract of C. intybus on ischemia- reperfusion injury in isolated rat heart. Materials and Methods: The animals were divided into four groups (Sham, Control, 1 mg/ml and 3 mg/ml of extract) of 8 rats. The aorta was cannulated, and then the heart was mounted on a Langendorff apparatus. Next, a balloon was inserted into the left ventricle (LV) and peak positive value of time derivate of LV pressure (+dp/dt), coronary flow (CF), and left ventricular systolic pressure (LVSP) in pre-ischemia and reperfusion period were calculated by a Power Lab system. All groups underwent a 30-minute global ischemia followed by a 60-minute reperfusion. Results: The results showed that heart rate (HR), coronary flow, and left ventricular developed pressure (LVDP) and rate of pressure product (RPP) significantly decreased in the control group during reperfusion, while these values in the groups receiving the extract (3mg/ml) improved significantly during reperfusion (p<0.001). Conclusion: It seems that flavonoid compounds of aqueous extract of C. intybus reduce ischemia - reperfusion injuries, suggesting its protective effect on heart function after ischemia. PMID:26693414

  20. Alterations in the force-frequency relationship by tert-butylbenzohydroquinone, a putative SR Ca2+ pump inhibitor, in rabbit and rat ventricular muscle.

    PubMed Central

    Baudet, S.; Do, E.; Noireaud, J.; Le Marec, H.

    1996-01-01

    1. The effects of 2,5 di-(tert-butyl)-1,4-benzohydroquinone (TBQ), a putative inhibitor of the sarcoplasmic reticulum (SR) Ca2+ pump, on twitch tension, time course and SR Ca2+ content have been studied at different stimulation frequencies (0.5-3 Hz) in isolated preparations from the rabbit and rat right ventricle, at 37 degrees C. 2. At 0.5Hz, 30 microM TBQ induced a marked negative inotropic effect in both species (-57% in the rabbit and -68% in the rat) and decreased the rate of rise and fall of twitch tension. In parallel, SR Ca2+ content (assessed by rapid cooling contractures) was depressed in the rabbit by 42%. The force-frequency relationship (positive for the rabbit and negative for the rat) was significantly attenuated. In the rabbit, this alteration was shown to rely on insufficient SR Ca2+ reloading with increasing frequencies. 3. Exposure of TBQ-treated preparations to 8 mM extracellular Ca2+ or 5 microM isoprenaline were effective in reloading the SR with Ca2+ whereas 20 mM caffeine emptied this compartment. 4. In the rabbit ventricle, increase in stimulation frequency shortened control twitch time course by decreasing both the time to peak tension (TTP) and the time to half relaxation (t1/2). TBQ did not differentially affect the pattern for t1/2 but significantly attenuated the frequency-induced decrease of TTP. 5. In rabbit ventricular muscle, the action potential duration increased between 0.5 and 3 Hz whether or not TBQ was present. However, TBQ induced a small but significant additional action potential shortening. 6. TBQ decreased twitch tension in the rat ventricle between 0.5 and 3 Hz but the negative staircase was not differentially affected by the SR Ca2+ pump inhibitor. In control conditions and in the presence of 30 microM TBQ, t1/2 was frequency-independent but TBQ consistently increased this parameter (by approximately 29%). 7. These data argue in favour of a specific and partial inhibition of the SR Ca2+ pump by 30 microM TBQ in the

  1. Acipimox stimulates leptin production from isolated rat adipocytes.

    PubMed

    Wang-Fisher, Y-L; Han, J; Guo, W

    2002-08-01

    Acipimox is a nicotinic acid-derived antilipolytic drug devoid of major side effects, and has been used in a number of human trials. This work reports the effects of Acipimox on leptin production from isolated rat adipocytes, in comparison with nicotinic acid and insulin. For cells isolated from normal animals, all these three reagents stimulated leptin release to a similar extent. Acipimox and nicotinic acid were more potent than insulin in stimulating leptin release from cells isolated from diabetic animals, probably because of impaired insulin sensitivity in cells from these diseased animals. Co-incubation of Acipimox with norepinephrine or dibutyryl cAMP diminished its stimulatory effects on leptin release, in parallel with increased lipolysis, suggesting that intracellular free fatty acids play an important role in mediating leptin production in adipocytes.

  2. Enzymatic antioxidant defense in isolated rat hepatocytes exposed to cadmium.

    PubMed

    Skrzycki, M; Czeczot, H; Majewska, M; Podsiad, M; Karlik, W; Grono, D; Wiechetek, M

    2010-01-01

    The aim of the study was the evaluation of cadmium effects on the activity of antioxidant enzymes in rat hepatocytes. The studies were conducted with isolated rat hepatocytes incubated for 1 or 2 hours in a modified (deprived of carbonates with phosphates) Williams' E medium (MWE) in the presence of cadmium chloride (25, 50 and 200 microM). Hepatocytes incubated in the MWE medium without cadmium chloride were used as a control. The application of the modified Williams' E medium allowed for the appearance of cadmium compounds in a soluble form that is indispensable for suitable estimation of its toxic action. There were evaluated markers of the oxidative stress such as: concentration of thiobarbiturate reactive substances (TBARS)--proportional to the level of lipid peroxidation, concentration of reduced glutathione (GSH), and the activity of antioxidant enzymes, including superoxide dismutase (SOD1 and SOD2), catalase (CAT), total glutathione peroxidase (GSHPx), selenium--dependent glutathione peroxidase (SeGSHPx), glutathione transferase (GST) and glutathione reductase (GSHR). Alterations of antioxidant enzymes activity, the level of TBARS and GSH in isolated rat hepatocytes caused by cadmium in vitro, were shown to depend on the concentration and time of exposure of cells to this metal. The increased level of TBARS and GSH was observed as well as changes in the activity of antioxidant enzymes. The activity of SOD isoenzymes and CAT was increased, whereas GSHPx and GST were decreased. These results indicate that cadmium induces oxidative stress followed by alterations in the cellular antioxidant enzyme system in isolated rat hepatocytes.

  3. Non-targeted metabolomics identified a common metabolic signature of lethal ventricular tachyarrhythmia (LVTA) in two rat models.

    PubMed

    Wang, Xingxing; Wang, Dian; Yu, Xiaojun; Zhang, Guohong; Wu, Jiayan; Zhu, Guanghui; Su, Ruibing; Lv, Junyao

    2016-06-21

    Lethal ventricular tachyarrhythmia (LVTA) is the predominant underlying mechanism of sudden cardiac death (SCD). The aim of this study is to characterize the metabolic features of myocardia following LVTA, and identify potential biomarkers to diagnose LVTA. We developed two LVTA rat models induced by aconitine injection or coronary artery ligation, which represent cardiac ion channel disease-related and cardiac ischemia-related SCD, respectively. The myocardial metabolic profile was investigated by gas chromatography-mass spectrometry and proton nuclear magnetic resonance-based metabolomics. Twenty-three aconitine-injected and 14 coronary artery ligation-treated rats developed LVTA SCD. A total of 38 differential metabolites of myocardia were identified in aconitine-induced LVTA rats, of which 31 metabolites showed a similar change in coronary artery ligation-related LVTA rats. Fatty acids (stearic, palmitic, linoleic, elaidic, and myristic) and branched-chain amino acids (valine, leucine, and isoleucine) were the most down-regulated metabolites. Furthermore, elevated ADP, phosphate, lactate, glutamate, aspartate, threonine, choline and arginine were also observed. Major pathways regarding these dysregulated metabolites post LVTA are energy excessive consumption and deficit, ionic imbalance, oxidative stress, cardiac cytotoxicity and membrane injury. Valine, stearic acid and leucine collectively enable a precision of 92.9% to distinguish LVTA from its control, and are correlated with several arrhythmia indices. Our results uncovered a common metabolic feature of LVTA in myocardia in two rat models, which represent cardiac ion channel disease and cardiac ischemia, respectively. l-Valine, l-leucine and stearic acid jointly confer good potential for distinguishing LVTA, which might be potential biomarkers of LVTA-related SCD.

  4. Rats with high left ventricular end-diastolic pressure can be identified by Doppler echocardiography one week after myocardial infarction.

    PubMed

    Saraiva, R M; Kanashiro-Takeuchi, R M; Antonio, E L; Campos, O; P J F, Tucci; Moisés, V A

    2007-11-01

    The severity of left ventricular (LV) dysfunction in rats with myocardial infarction (MI) varies widely. Because homogeneity in baseline parameters is essential for experimental investigations, a study was conducted to establish whether Doppler echocardiography (DE) could accurately identify animals with high LV end-diastolic pressure as a marker of LV dysfunction soon after MI. Direct measurements of LV end-diastolic pressure were made and DE was performed simultaneously 1 week after surgically induced MI (N = 16) or sham-operation (N = 17) in female Wistar rats (200 to 250 g). The ratio of peak early (E) to late (A) diastolic LV filling velocities and the ratio of E velocity to peak early (Em) diastolic myocardial velocity were the best predictors of high LV end-diastolic pressure (>12 mmHg) soon after MI. Cut-off values of 1.77 for the E/A ratio (P = 0.001) identified rats with elevated LV end-diastolic pressure with 90% sensitivity and 80% specificity. Cut-off values of 20.4 for the E/Em ratio (P = 0.0001) identified rats with elevated LV end-diastolic pressure with 81.8% sensitivity and 80% specificity. Moreover, E/A and E/Em ratios were the only echocardiographic parameters independently associated with LV end-diastolic pressure in multiple linear regression analysis. Therefore, DE identifies rats with high LV end-diastolic pressure soon after MI. These findings have implications for using serial DE in animal selection and in the assessment of their response to experimental therapies.

  5. Remote ischemic preconditioning impairs ventricular function and increases infarct size after prolonged ischemia in the isolated neonatal rabbit heart.

    PubMed

    Schmidt, Michael R; Støttrup, Nicolaj B; Michelsen, Marie M; Contractor, Hussain; Sørensen, Keld E; Kharbanda, Rajesh K; Redington, Andrew N; Bøtker, Hans E

    2014-03-01

    Remote ischemic preconditioning (rIPC) reduces myocardial injury in adults and children undergoing cardiac surgery. We compared the effect of rIPC in adult and neonatal rabbits to investigate whether protection against ischemia-reperfusion injury can be achieved in the newborn heart by (1) in vivo rIPC and (2) dialysate from adult rabbits undergoing rIPC. Isolated hearts from newborn and adult rabbits were randomized into 3 subgroups (control, in vivo rIPC, and dialysate obtained from adult, remotely preconditioned rabbits). Remote preconditioning was induced by four 5-minute cycles of lower limb ischemia. Left ventricular (LV) function was assessed using a balloon-tipped catheter, glycolytic flux by tracer kinetics, and infarct size by tetrazolium staining. Isolated hearts underwent stabilization while perfused with standard Krebs-Henseleit buffer (control and in vivo rIPC) or Krebs-Henseleit buffer with added dialysate, followed by global no-flow ischemia and reperfusion. Within the age groups, the baseline LV function was similar in all subgroups. In the adult rabbit hearts, rIPC and rIPC dialysate attenuated glycolytic flux and protected against ischemia-reperfusion injury, with better-preserved LV function compared with that of the controls. In contrast, in the neonatal hearts, the glycolytic flux was lower and LV function was better preserved in the controls than in the rIPC and dialysate groups. In the adult hearts, the infarct size was reduced in the rIPC and dialysate groups compared with that in the controls. In the neonatal hearts, the infarct size was smaller in the controls than in the rIPC and dialysate groups. Remote ischemic preconditioning does not protect against ischemia-reperfusion injury in isolated newborn rabbit hearts and might even cause deleterious effects. Similar adverse effects were induced by dialysate from remotely preconditioned adult rabbits. Copyright © 2014 The American Association for Thoracic Surgery. All rights reserved.

  6. High-frequency periodic sources underlie ventricular fibrillation in the isolated rabbit heart.

    PubMed

    Chen, J; Mandapati, R; Berenfeld, O; Skanes, A C; Jalife, J

    The mechanism(s) underlying ventricular fibrillation (VF) remain unclear. We hypothesized that at least some forms of VF are not random and that high-frequency periodic sources of activity manifest themselves as spatiotemporal periodicities, which drive VF. Twenty-four VF episodes from 8 Langendorff-perfused rabbit hearts were studied using high-resolution video imaging in conjunction with ECG recordings and spectral analysis. Sequential wavefronts that activated the ventricles in a spatially and temporally periodic fashion were identified. In addition, we analyzed the lifespan and dynamics of wavelets in VF, using a new method of phase mapping that enables identification of phase singularity points (PSs), which flank individual wavelets. Spatiotemporal periodicity was found in 21 of 24 episodes. Complete reentry on the epicardial surface was observed in 3 of 24 episodes. The cycle length of discrete regions of spatiotemporal periodicity correlated highly with the dominant frequency of the optical pseudo-ECG (R(2)=0.75) and with the global bipolar electrogram (R(2)=0.79). The lifespan of PSs was short (14.7+/-14.4 ms); 98% of PSs existed for <1 rotation. The mean number of waves entering (6.50+/-0.69) exceeded the mean number of waves that exited our mapping field (4.25+/-0.56; P<0.05). These results strongly suggest that ongoing stable sources are responsible for the majority of the frequency content of VF and therefore play a role in its maintenance. In this model, multiple wavelets resulting from wavebreaks do not appear to be responsible for the sustenance of this arrhythmia, but are rather the consequence of breakup of high-frequency activation from a dominant reentrant source.

  7. Metabolic stress in isolated mouse ventricular myocytes leads to remodeling of t tubules.

    PubMed

    Cheng, Lu-Feng; Wang, Fuzhen; Lopatin, Anatoli N

    2011-11-01

    Cardiac ventricular myocytes possess an extensive t-tubular system that facilitates the propagation of membrane potential across the cell body. It is well established that ionic currents at the restricted t-tubular space may lead to significant changes in ion concentrations, which, in turn, may affect t-tubular membrane potential. In this study, we used the whole cell patch-clamp technique to study accumulation and depletion of t-tubular potassium by measuring inward rectifier potassium tail currents (I(K1,tail)), and inward rectifier potassium current (I(K1)) "inactivation". At room temperatures and in the absence of Mg(2+) ions in pipette solution, the amplitude of I(K1,tail) measured ~10 min after the establishment of whole cell configuration was reduced by ~18%, but declined nearly twofold in the presence of 1 mM cyanide. At ~35°C I(K1,tail) was essentially preserved in intact cells, but its amplitude declined by ~85% within 5 min of cell dialysis, even in the absence of cyanide. Intracellular Mg(2+) ions played protective role at all temperatures. Decline of I(K1,tail) was accompanied by characteristic changes in its kinetics, as well as by changes in the kinetics of I(K1) inactivation, a marker of depletion of t-tubular K(+). The data point to remodeling of t tubules as the primary reason for the observed effects. Consistent with this, detubulation of myocytes using formamide-induced osmotic stress significantly reduced I(K1,tail), as well as the inactivation of inward I(K1). Overall, the data provide strong evidence that changes in t tubule volume/structure may occur on a short time scale in response to various types of stress.

  8. Islands of spatially discordant APD alternans underlie arrhythmogenesis by promoting electrotonic dyssynchrony in models of fibrotic rat ventricular myocardium

    PubMed Central

    Majumder, Rupamanjari; Engels, Marc C.; de Vries, Antoine A. F.; Panfilov, Alexander V.; Pijnappels, Daniël A.

    2016-01-01

    Fibrosis and altered gap junctional coupling are key features of ventricular remodelling and are associated with abnormal electrical impulse generation and propagation. Such abnormalities predispose to reentrant electrical activity in the heart. In the absence of tissue heterogeneity, high-frequency impulse generation can also induce dynamic electrical instabilities leading to reentrant arrhythmias. However, because of the complexity and stochastic nature of such arrhythmias, the combined effects of tissue heterogeneity and dynamical instabilities in these arrhythmias have not been explored in detail. Here, arrhythmogenesis was studied using in vitro and in silico monolayer models of neonatal rat ventricular tissue with 30% randomly distributed cardiac myofibroblasts and systematically lowered intercellular coupling achieved in vitro through graded knockdown of connexin43 expression. Arrhythmia incidence and complexity increased with decreasing intercellular coupling efficiency. This coincided with the onset of a specialized type of spatially discordant action potential duration alternans characterized by island-like areas of opposite alternans phase, which positively correlated with the degree of connexinx43 knockdown and arrhythmia complexity. At higher myofibroblast densities, more of these islands were formed and reentrant arrhythmias were more easily induced. This is the first study exploring the combinatorial effects of myocardial fibrosis and dynamic electrical instabilities on reentrant arrhythmia initiation and complexity. PMID:27072041

  9. Effect of lithium on ventricular remodelling in infarcted rats via the Akt/mTOR signalling pathways.

    PubMed

    Lee, Tsung-Ming; Lin, Shinn-Zong; Chang, Nen-Chung

    2017-04-28

    Activation of phosphoinositide 3-kinase (PI3K)/Akt signalling is the molecular pathway driving physiological hypertrophy. As lithium, a PI3K agonist, is highly toxic at regular doses, we assessed the effect of lithium at a lower dose on ventricular hypertrophy after myocardial infarction (MI). Male Wistar rats after induction of MI were randomized to either vehicle or lithium (1 mmol/kg per day) for 4 weeks. The dose of lithium led to a mean serum level of 0.39 mM, substantially lower than the therapeutic concentrations (0.8-1.2 mM). Infarction in the vehicle was characterized by pathological hypertrophy in the remote zone; histologically, by increased cardiomyocyte sizes, interstitial fibrosis and left ventricular dilatation; functionally, by impaired cardiac contractility; and molecularly, by an increase of p-extracellular-signal-regulated kinase (ERK) levels, nuclear factor of activated T cells (NFAT) activity, GATA4 expression and foetal gene expressions. Lithium administration mitigated pathological remodelling. Furthermore, lithium caused increased phosphorylation of eukaryotic initiation factor 4E binding protein 1 (p-4E-BP1), the downstream target of mammalian target of rapamycin (mTOR). Blockade of the Akt and mTOR signalling pathway with deguelin and rapamycin resulted in markedly diminished levels of p-4E-BP1, but not ERK. The present study demonstrated that chronic lithium treatment at low doses mitigates pathological hypertrophy through an Akt/mTOR dependent pathway.

  10. Islands of spatially discordant APD alternans underlie arrhythmogenesis by promoting electrotonic dyssynchrony in models of fibrotic rat ventricular myocardium

    NASA Astrophysics Data System (ADS)

    Majumder, Rupamanjari; Engels, Marc C.; de Vries, Antoine A. F.; Panfilov, Alexander V.; Pijnappels, Daniël A.

    2016-04-01

    Fibrosis and altered gap junctional coupling are key features of ventricular remodelling and are associated with abnormal electrical impulse generation and propagation. Such abnormalities predispose to reentrant electrical activity in the heart. In the absence of tissue heterogeneity, high-frequency impulse generation can also induce dynamic electrical instabilities leading to reentrant arrhythmias. However, because of the complexity and stochastic nature of such arrhythmias, the combined effects of tissue heterogeneity and dynamical instabilities in these arrhythmias have not been explored in detail. Here, arrhythmogenesis was studied using in vitro and in silico monolayer models of neonatal rat ventricular tissue with 30% randomly distributed cardiac myofibroblasts and systematically lowered intercellular coupling achieved in vitro through graded knockdown of connexin43 expression. Arrhythmia incidence and complexity increased with decreasing intercellular coupling efficiency. This coincided with the onset of a specialized type of spatially discordant action potential duration alternans characterized by island-like areas of opposite alternans phase, which positively correlated with the degree of connexinx43 knockdown and arrhythmia complexity. At higher myofibroblast densities, more of these islands were formed and reentrant arrhythmias were more easily induced. This is the first study exploring the combinatorial effects of myocardial fibrosis and dynamic electrical instabilities on reentrant arrhythmia initiation and complexity.

  11. Effects of Buyang Huanwu Decoction on Ventricular Remodeling and Differential Protein Profile in a Rat Model of Myocardial Infarction

    PubMed Central

    Zhou, Ying Chun; Liu, Bin; Li, Ying Jia; Jing, Lin Lin; Wen, Ge; Tang, Jing; Xu, Xin; Lv, Zhi Ping; Sun, Xue Gang

    2012-01-01

    Buyang Huanwu decoction (BYHWD) is a well-known and canonical Chinese medicine formula from “Correction on Errors in Medical Classics” in Qing dynasty. Here, we show that BYHWD could alleviate the ventricular remodeling induced by left anterior descending (LAD) artery ligation in rats. BYHWD treatment (18 g/kg/day) decreased heart weight/body weight (HW/BW), left ventricle (LV) dimension at end diastole (LVDd) and increased LV ejection fraction (LVEF) and LV fractional shortening (LVFS) significantly compared to model group at the end of 12 weeks. The collagen volume of BYHWD group was more significantly decreased than that of model group. Proteomic analysis showed that atrial natriuretic factor (ANF) was downregulated; heat shock protein beta-6 (HSPB6) and peroxiredoxin-6 (PRDX6) were upregulated in BYHWD-treated group among successfully identified proteins. The apoptotic index (AI) was reduced by BYHWD accompanied by decreased expression of Bax and caspase 3 activity, increased Bcl-2/Bax ratio, and phosphorylation of HSPB6 compared to that of model group. Taken together, these results suggest that BYHWD can alleviate ventricular remodeling induced by LAD artery ligation. The antiremodeling effects of BYHWD are conferred by decreasing AI through affecting multiple targets including increased Bcl-2/Bax ratio and decreased caspase 3 activity that might be via upregulated PRDX6, phosphorylation of HSPB6 and subsequently reduction of ANF. PMID:23049607

  12. Effects of buyang huanwu decoction on ventricular remodeling and differential protein profile in a rat model of myocardial infarction.

    PubMed

    Zhou, Ying Chun; Liu, Bin; Li, Ying Jia; Jing, Lin Lin; Wen, Ge; Tang, Jing; Xu, Xin; Lv, Zhi Ping; Sun, Xue Gang

    2012-01-01

    Buyang Huanwu decoction (BYHWD) is a well-known and canonical Chinese medicine formula from "Correction on Errors in Medical Classics" in Qing dynasty. Here, we show that BYHWD could alleviate the ventricular remodeling induced by left anterior descending (LAD) artery ligation in rats. BYHWD treatment (18 g/kg/day) decreased heart weight/body weight (HW/BW), left ventricle (LV) dimension at end diastole (LVDd) and increased LV ejection fraction (LVEF) and LV fractional shortening (LVFS) significantly compared to model group at the end of 12 weeks. The collagen volume of BYHWD group was more significantly decreased than that of model group. Proteomic analysis showed that atrial natriuretic factor (ANF) was downregulated; heat shock protein beta-6 (HSPB6) and peroxiredoxin-6 (PRDX6) were upregulated in BYHWD-treated group among successfully identified proteins. The apoptotic index (AI) was reduced by BYHWD accompanied by decreased expression of Bax and caspase 3 activity, increased Bcl-2/Bax ratio, and phosphorylation of HSPB6 compared to that of model group. Taken together, these results suggest that BYHWD can alleviate ventricular remodeling induced by LAD artery ligation. The antiremodeling effects of BYHWD are conferred by decreasing AI through affecting multiple targets including increased Bcl-2/Bax ratio and decreased caspase 3 activity that might be via upregulated PRDX6, phosphorylation of HSPB6 and subsequently reduction of ANF.

  13. Differential Effects of Prevention and Reversal Treatment with Lisinopril on Left Ventricular Remodelling in a Rat Model of Heart Failure

    PubMed Central

    Brower, Gregory L.; Levick, Scott P.; Janicki, Joseph S.

    2015-01-01

    Background Angiotensin converting enzyme (ACE) inhibitors such as lisinopril, represent the front line pharmacological treatment for heart failure, which is characterised by marked left ventricular (LV) dilatation and hypertrophy. This study sought to determine whether initiating treatment with ACE inhibitors at different stages in the remodelling process would alter the efficacy of treatment. Methods To this end, LV size and function were determined in the aortocaval (AV) fistula model of volume overload-induced heart failure. Sprague-Dawley rats were assigned to sham, untreated AV fistula (21 weeks), AV fistula treated with lisinopril (21 weeks), or AV fistula treated with lisinopril from six to 21 weeks post-fistula groups. Results Administration of lisinopril for the entire 21-week period prevented LV dilatation, attenuated myocardial hypertrophy and prevented changes in myocardial compliance and contractility, whereas delaying initiation of treatment until six weeks post-fistula attenuated LV dilatation and hypertrophy, however, the delayed onset of treatment had no beneficial effect on ventricular compliance or systolic function. Conclusions The results demonstrate differential effects that can occur with ACE inhibitors depending on the stage during the remodelling process at which treatment is administered. PMID:25837018

  14. Differential Effects of Prevention and Reversal Treatment with Lisinopril on Left Ventricular Remodelling in a Rat Model of Heart Failure.

    PubMed

    Brower, Gregory L; Levick, Scott P; Janicki, Joseph S

    2015-09-01

    Angiotensin converting enzyme (ACE) inhibitors such as lisinopril, represent the front line pharmacological treatment for heart failure, which is characterised by marked left ventricular (LV) dilatation and hypertrophy. This study sought to determine whether initiating treatment with ACE inhibitors at different stages in the remodelling process would alter the efficacy of treatment. To this end, LV size and function were determined in the aortocaval (AV) fistula model of volume overload-induced heart failure. Sprague-Dawley rats were assigned to sham, untreated AV fistula (21 weeks), AV fistula treated with lisinopril (21 weeks), or AV fistula treated with lisinopril from six to 21 weeks post-fistula groups. Administration of lisinopril for the entire 21-week period prevented LV dilatation, attenuated myocardial hypertrophy and prevented changes in myocardial compliance and contractility, whereas delaying initiation of treatment until six weeks post-fistula attenuated LV dilatation and hypertrophy, however, the delayed onset of treatment had no beneficial effect on ventricular compliance or systolic function. The results demonstrate differential effects that can occur with ACE inhibitors depending on the stage during the remodelling process at which treatment is administered. Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.

  15. Effect of oligomer procyanidins on reperfusion arrhythmias and lactate dehydrogenase release in the isolated rat heart.

    PubMed

    Al-Makdessi, Samar; Sweidan, Hicham; Jacob, Ruthard

    2006-01-01

    The antiarrhythmic effect of an oral 3-week-pretreatment with oligomer procyanidins derived from Vitis vinifera was investigated on the isolated perfused heart after global no-flow ischemia (procyanidin-treated group: n = 9, control group: n = 13). Hearts were perfused with a modified Krebs-Henseleit solution in which the K+ content was reduced to 3.0 mmol/l in order to lower the fibrillation threshold. Monophasic action potentials in addition to ECG were recorded. The durations of ischemia and reperfusion were 20 and 30 min, respectively. Arrhythmias including ventricular fibrillation (VF), ventricular tachycardia (VT), flutter (Fl) and bradycardia were evaluated. During the reperfusion, irreversible VF occurred in most of control hearts. The incidence of VF (percentage of the hearts in which VF occurred) was lowered by oligomer procyanidins from 84.6 to 55.6 %, and the duration of the episodes of VF (expressed as percentage relative to the total duration) was significantly shortened from 76.1 +/- 27.9 % to 36.6 +/- 40.6 % (p = 0.036). Simultaneously, the percentage of duration of normal sinus rhythm (NSR) increased from 19.5 +/- 30.3 % to 46.2 +/- 35.9 % (n.s.). VF occuring in the procyanidin-treated hearts could be reversed in two hearts within few minutes to a stage of "reversible arrhythmias" consisting of short episodes (1 to 60 s) of either Fl or VT or bradycardia or NSR alternating with each other. LDH (lactate dehydrogenase) release in the first drops appearing from the reperfused heart was significantly reduced in the procyanidin-treated rats (66.7 +/- 36.2 mU/min, n = 8) in comparison to controls (159.7 +/- 79.0 mU/min, n = 10; p = 0.010). These results demonstrate an antiarrhythmic and cytoprotective effect of oral pretreatment with oligomer procyanidins under the given experimental conditions.

  16. Acetaldehyde at clinically relevant concentrations inhibits inward rectifier potassium current I(K1) in rat ventricular myocytes.

    PubMed

    Bébarová, M; Matejovič, P; Šimurdová, M; Šimurda, J

    2015-01-01

    Considering the effects of alcohol on cardiac electrical behavior as well as the important role of the inward rectifier potassium current I(K1) in arrhythmogenesis, this study was aimed at the effect of acetaldehyde, the primary metabolite of ethanol, on I(K1) in rat ventricular myocytes. Acetaldehyde induced a reversible inhibition of I(K1) with IC(50) = 53.7+/-7.7 microM at -110 mV; a significant inhibition was documented even at clinically-relevant concentrations (at 3 microM by 13.1+/-3.0 %). The inhibition was voltage-independent at physiological voltages above -90 mV. The I(K1) changes under acetaldehyde may contribute to alcohol-induced alterations of cardiac electrophysiology, especially in individuals with a genetic defect of aldehyde dehydrogenase where the acetaldehyde level may be elevated.

  17. Alterations in echocardiographic left ventricular function after percutaneous coronary stenting in diabetic patients with isolated severe proximal left anterior descending artery stenosis.

    PubMed

    Nabati, Maryam; Taghavi, Morteza; Saffar, Naser; Yazdani, Jamshid; Bagheri, Babak

    There are conflicting theories regarding the use of percutaneous coronary intervention (PCI) of isolated severe proximal left anterior descending (LAD) artery stenosis in place of left internal mammary artery grafting in diabetic patients. The aim of this study was to investigate the effect of PCI on left ventricular function and determine difference between diabetics and non-diabetics. A prospective study was conducted on 50 patients with isolated severe proximal LAD stenosis: 23 diabetic and 27 non-diabetic patients. Successful PCI with everolimus-eluting stents was performed for all of the patients. These patients underwent transthoracic echocardiography within 24h before and 1 month after PCI, and alterations in the left ventricular parameters were compared between the two groups. There was a significant 12% increment in the mitral annular peak systolic velocity (s') (p=0.02), 21% decrement in the trans mitral early filling deceleration time (DT) (p<0.001), 10% decrement in the systolic left ventricular internal dimension (LVIDs) (p=0.002), significant increment in the left ventricular ejection fraction (LVEF) (p=0.004), and significant decrement in the left atrial diameter (p=0.006) in the diabetic patients after performing PCI. Conversely, the non-diabetic patients showed a statistically significant 14% increase in the DT, 6.3% decrease in the s' velocity, 8% increase in the LVIDs, significant increment in the left atrial diameter and no change in LVEF after PCI. Our study demonstrated that everolimus-eluting stents favorably improved the markers of left ventricular systolic and diastolic function in diabetic patients with isolated severe proximal LAD stenosis compared with those of non-diabetic patients with the same condition. Copyright © 2016. Published by Elsevier B.V.

  18. Characterization of the cyclic nucleotide phosphodiesterase subtypes involved in the regulation of the L-type Ca2+ current in rat ventricular myocytes

    PubMed Central

    Verde, Ignacio; Vandecasteele, Grégoire; Lezoualc'h, Frank; Fischmeister, Rodolphe

    1999-01-01

    The effects of several phosphodiesterase (PDE) inhibitors on the L-type Ca current (ICa) and intracellular cyclic AMP concentration ([cAMP]i) were examined in isolated rat ventricular myocytes. The presence of mRNA transcripts encoding for the different cardiac PDE subtypes was confirmed by RT–PCR.IBMX (100 μM), a broad-spectrum PDE inhibitor, increased basal ICa by 120% and [cAMP]i by 70%, similarly to a saturating concentration of the β-adrenoceptor agonist isoprenaline (1 μM). However, MIMX (1 μM), a PDE1 inhibitor, EHNA (10 μM), a PDE2 inhibitor, cilostamide (0.1 μM), a PDE3 inhibitor, or Ro 20-1724 (0.1 μM), a PDE4 inhibitor, had no effect on basal ICa and little stimulatory effects on [cAMP]i (20–30%).Each selective PDE inhibitor was then tested in the presence of another inhibitor to examine whether a concomitant inhibition of two PDE subtypes had any effect on ICa or [cAMP]i. While all combinations tested significantly increased [cAMP]i (40–50%), only cilostamide (0.1 μM)+Ro20-1724 (0.1 μM) produced a significant stimulation of ICa (50%). Addition of EHNA (10 μM) to this mix increased ICa to 110% and [cAMP]i to 70% above basal, i.e. to similar levels as obtained with IBMX (100 μM) or isoprenaline (1 μM).When tested on top of a sub-maximal concentration of isoprenaline (1 nM), which increased ICa by (≈40% and had negligible effect on [cAMP]i, each selective PDE inhibitor induced a clear stimulation of [cAMP]i and an additional increase in ICa. Maximal effects on ICa were ≈8% for MIMX (3 μM), ≈20% for EHNA (1–3 μM), ≈30% for cilostamide (0.3–1 μM) and ≈50% for Ro20-1724 (0.1 μM).Our results demonstrate that PDE1-4 subtypes regulate ICa in rat ventricular myocytes. While PDE3 and PDE4 are the dominant PDE subtypes involved in the regulation of basal ICa, all four PDE subtypes determine the response of ICa to a stimulus activating cyclic AMP production, with the rank order of potency PDE4>PDE3

  19. Chronic Hypobaric Hypoxia Induces Right Ventricular Hypertrophy and Apoptosis in Rats: Therapeutic Potential of Nanocurcumin in Improving Adaptation.

    PubMed

    Nehra, Sarita; Bhardwaj, Varun; Kar, Santosh; Saraswat, Deepika

    2016-12-01

    Nehra, Sarita, Varun Bhardwaj, Santosh Kar, and Deepika Saraswat. Chronic hypobaric hypoxia induces right ventricular hypertrophy and apoptosis in rats: therapeutic potential of nanocurcumin in improving adaptation. High Alt Med Biol. 17:342-352, 2016.-a sustained work load on the right heart on ascent to high altitudes promotes right ventricular hypertrophy (RVH), which eventually undergoes decompensation and promotes pathological damage. However, the exact set of events leading to damage remains unidentified. Curcumin is a natural antioxidant and antihypertrophic agent, but it has poor biostability. Nanotized curcumin (nanocurcumin) has emerged as a promising agent with improved biostability while retaining the therapeutic properties of curcumin. The present study aimed at analyzing the therapeutic properties of nanocurcumin in ameliorating cardiac damage due to chronic hypobaric hypoxia (HH)-induced RVH in comparison to curcumin. Sprague-Dawley rats exposed to HH (25,000 feet, effective oxygen fraction in air [FIO2] ∼0.08, temperature 28°C ± 1°C, relative humidity 55% ± 2% for 3, 7, 14, and 21 days) developed RVH with increased interstitial collagen content, Fulton's index, and cardiomyocyte cross-sectional area while upregulating atrial natriuretic peptide. Tissue damage due to apoptotic cell death was evident by cytochrome-c/caspase-3 activation and TUNEL assay. Concomitant modulation of cyclic guanosine monophosphate (cGMP)/cGK-1, calmodulin-dependent protein kinase II (CaMkinase II), and intracellular calcium levels with increased free radical-induced damage and lipid peroxidation further contributed to the right heart pathology. Nanocurcumin supplementation decreased HH-induced RVH and apoptosis while modulating cardiac cGMP/cGK-1 signaling, and maintaining CaMkinase II, intracellular calcium levels and redox status better than curcumin. Nanocurcumin-mediated antiapoptotic effects might have benefited residents and sojourners at high altitude in

  20. Comparison between Radionuclide Ventriculography and Echocardiography for Quantification of Left Ventricular Systolic Function in Rats Exposed to Doxorubicin

    PubMed Central

    de Oliveira, Luciano Fonseca Lemos; O'Connell, João Lucas; de Carvalho, Eduardo Elias Vieira; Pulici, Érica Carolina Campos; Romano, Minna Moreira Dias; Maciel, Benedito Carlos; Simões, Marcus Vinicius

    2017-01-01

    Background Radionuclide ventriculography (RV) is a validated method to evaluate the left ventricular systolic function (LVSF) in small rodents. However, no prior study has compared the results of RV with those obtained by other imaging methods in this context. Objectives To compare the results of LVSF obtained by RV and echocardiography (ECHO) in an experimental model of cardiotoxicity due to doxorubicin (DXR) in rats. Methods Adult male Wistar rats serving as controls (n = 7) or receiving DXR (n = 22) in accumulated doses of 8, 12, and 16 mg/kg were evaluated with ECHO performed with a Sonos 5500 Philips equipment (12-MHz transducer) and RV obtained with an Orbiter-Siemens gamma camera using a pinhole collimator with a 4-mm aperture. Histopathological quantification of myocardial fibrosis was performed after euthanasia. Results The control animals showed comparable results in the LVSF analysis obtained with ECHO and RV (83.5 ± 5% and 82.8 ± 2.8%, respectively, p > 0.05). The animals that received DXR presented lower LVSF values when compared with controls (p < 0.05); however, the LVSF values obtained by RV (60.6 ± 12.5%) were lower than those obtained by ECHO (71.8 ± 10.1%, p = 0.0004) in this group. An analysis of the correlation between the LVSF and myocardial fibrosis showed a moderate correlation when the LVSF was assessed by ECHO (r = -0.69, p = 0.0002) and a stronger correlation when it was assessed by RV (r = -0.79, p < 0.0001). On multiple regression analysis, only RV correlated independently with myocardial fibrosis. Conclusion RV is an alternative method to assess the left ventricular function in small rodents in vivo. When compared with ECHO, RV showed a better correlation with the degree of myocardial injury in a model of DXR-induced cardiotoxicity. PMID:28146205

  1. Direct cardiac toxicity of the tentacle-only extract from the jellyfish Cyanea capillata demonstrated in isolated rat heart.

    PubMed

    Beilei, Wang; Lin, Zhang; Qian, He; Qianqian, Wang; Tao, Wang; Jia, Lu; Xiaojuan, Wen; Xuting, Ye; Liang, Xiao; Liming, Zhang

    2012-04-01

    Previous studies in our laboratory have shown that the cardiotoxicity is the main reason for rat death caused by tentacle-only extract from jellyfish Cyanea capillata. However, the direct cardiotoxicity in vitro and its mechanisms of toxic action remain unclear. The current studies were performed by using the Langendorff-perfused isolated heart model, which showed a dose-dependent hemodynamic and electrocardiogram changes. Heart injury-related enzymes increased. Histopathological analysis showed early ischemic damage in the myocardium. The Ca channel blockers nifedipine and verapamil led to a marked improvement in recovery of cardiac function, including heart rate, left ventricular developed pressure, positive and negative first derivatives of intraventricular pressure, coronary flow, left ventricular end-diastolic pressure, and electrocardiogram changes. Tentacle-only extract-induced cardiac dysfunction could be partly improved by the pretreatments of both propranolol and phentolamine, but not by either atropine or neostigmine at all. In conclusion, we have verified the direct cardiotoxicity of tentacle-only extract from jellyfish C. capillata by the Langendorff isolated heart model, which consisted of 3 separate parts: sinoatrial node malfunction, cardiomyocyte injury, and coronary spasm. The potential mechanism might be attributed to the overactivation of L-type Ca channel, β- and α-adrenergic receptors, but not cholinergic receptors.

  2. Gene delivery to postnatal rat brain by non-ventricular plasmid injection and electroporation.

    PubMed

    Molotkov, Dmitry A; Yukin, Alexey Y; Afzalov, Ramil A; Khiroug, Leonard S

    2010-09-17

    Creation of transgenic animals is a standard approach in studying functions of a gene of interest in vivo. However, many knockout or transgenic animals are not viable in those cases where the modified gene is expressed or deleted in the whole organism. Moreover, a variety of compensatory mechanisms often make it difficult to interpret the results. The compensatory effects can be alleviated by either timing the gene expression or limiting the amount of transfected cells. The method of postnatal non-ventricular microinjection and in vivo electroporation allows targeted delivery of genes, siRNA or dye molecules directly to a small region of interest in the newborn rodent brain. In contrast to conventional ventricular injection technique, this method allows transfection of non-migratory cell types. Animals transfected by means of the method described here can be used, for example, for two-photon in vivo imaging or in electrophysiological experiments on acute brain slices.

  3. Chronic enalapril treatment increases transient outward potassium current in cardiomyocytes isolated from right ventricle of spontaneously hypertensive rats.

    PubMed

    Rodrigues Junior, Luiz Fernando; de Azevedo Carvalho, Ana Carolina; Pimentel, Enildo Broetto; Mill, José Geraldo; Nascimento, José Hamilton Matheus

    2017-03-01

    It has been well established that chronic pressure overload resulting from hypertension leads to ventricular hypertrophy and electrophysiological remodeling. The transient outward potassium current (I to) reduction described in hypertensive animals delays ventricular repolarization, leading to complex ventricular arrhythmias and sudden death. Antihypertensive drugs, as angiotensin-converting enzyme inhibitors (ACEi), can restore I to and reduce the incidence of arrhythmic events. The purpose of this study was to evaluate the differential effects of long-term treatment with ACEi or direct-acting smooth muscle relaxant on the I to of left and right ventricle myocytes of spontaneously hypertensive rats (SHR). Animals were divided into four groups: normotensive Wistar-Kyoto rats (WKY), hypertensive (SHR), SHR treated for 6 weeks with enalapril 10 mg/kg/day (SHRE), or hydralazine 20 mg/kg/day (SHRH). Systolic blood pressure (SBP) and hypertrophy index (heart weight/body weight (HW/BW)) were determined at the end of treatment period. Cell membrane capacitance (C m) and I to were assessed in cardiomyocytes isolated from left and right ventricles. The SHR exhibited significantly increased SBP and HW/BW when compared to the WKY. The treated groups, SHRE and SHRH, restored normal SBP but not HW/BW. The SHR group exhibited a diminished I to in the left but not the right ventricle. Both the treated groups restored I to in the left ventricle. However, in the right ventricle, only enalapril treatment modified I to. The SHRE group exhibited a significant increase in I to compared to all the other groups. These findings suggest that enalapril may increase I to by a pressure overload independent mechanism.

  4. Continuous administration of insulin-like growth factor-I and basic fibroblast growth factor does not affect left ventricular geometry after acute myocardial infarction in rats.

    PubMed

    Scheinowitz, M; Abramov, D; Kotlyar, A; Savion, N; Eldar, M

    1998-02-28

    We examined the long-term effect of exogenous administration of bFGF and IGF-I on myocardial geometry in 72 Sprague-Dawley male rats subjected to AMI. A preloaded miniature osmotic pump subsequently implanted in the peritoneum for continuous infusion (1 week) of IGF-I, bFGF, IGF-I+bFGF or rat albumin. Six weeks following AMI the rats were killed and cross-section slices were analyzed for left ventricular geometry. No differences were observed between IGF-I-treated, bFGF-treated, IGF-I+bFGF-treated and control groups in all parameters of the left ventricle.

  5. Hormonal modulation of benzodiazepines' actions on rat isolated uterus.

    PubMed

    Yiu, M K; Kwan, Y W; Ngan, M P

    1996-04-29

    Effects of various benzodiazepines were investigated in ovariectomized rat isolated uterus which had been chronically pre-treated with different female sex hormones: oestrogen, progesterone and oestrogen + progesterone. Uteri obtained from all groups developed a spontaneous, rhythmic activity. The spontaneous activity observed in control uterus was either inhibited in a concentration-dependent manner by diazepam, 4'-chlorodiazepam, clonazepam or 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxam ide (PK 11195), or was abolished in [Ca2+]o-free solution. Diazepam, 4'-chlorodiazepam, clonazepam and PK 11195 all caused a concentration-dependent relaxation of the [K+]o-pre-contracted uterus with the relative order of potency: PK 11195 > 4'-chlorodiazepam > diazepam > clonazepam. Administration of [Ca2+]o (1 microM to 10 mM) caused a concentration-dependent contraction of uterus, bathed in [Ca2+]o-free physiological salt solution obtained from different pre-treatment groups. Incubation with different concentrations (microM) of diazepam, 4'-chlorodiazepam, clonazepam and PK 11195 caused a decrease in response to [Ca2+]o-induced contraction in all groups of rat uteri. These results indicate that micromolar benzodiazepine binding sites exist in rat uterus. Diazepam, 4'-chlorodiazepam, clonazepam and PK 11195 caused relaxation of pre-contracted rat uterus and this effect may involve the inhibition of influx of [Ca2+]o and the relaxing effects of different benzodiazepines observed in this study can be modulated by pre-treatment with different female hormones.

  6. Mechanisms of the statins cytotoxicity in freshly isolated rat hepatocytes.

    PubMed

    Abdoli, Narges; Heidari, Reza; Azarmi, Yadollah; Eghbal, Mohammad Ali

    2013-06-01

    Statins are potent drugs, used as lipid-lowering agents in cardiovascular diseases. Hepatotoxicity is one of the serious adverse effects of statins, and the exact mechanism of hepatotoxicity is not yet clear. In this study, the cytotoxic effects of the most commonly used statins, that is, atorvastatin, lovastatin, and simvastatin toward isolated rat hepatocytes, were evaluated. Markers, such as cell death, reactive oxygen species (ROS) formation, lipid peroxidation, mitochondrial membrane potential, and the amount of reduced and oxidized glutathione in the statin-treated hepatocytes, were investigated. It was found that the statins caused cytotoxicity toward rat hepatocytes dose dependently. An elevation in ROS formation, accompanied by a significant amount of lipid peroxidation and mitochondrial depolarization, was observed. Cellular glutathione reservoirs were decreased, and a significant amount of oxidized glutathione was formed. This study suggests that the adverse effect of statins toward hepatocytes is mediated through oxidative stress and the hepatocytes mitochondria play an important role in the statin-induced toxicity.

  7. Complete inhibition of creatine kinase in isolated perfused rat hearts

    SciTech Connect

    Fossel, E.T.; Hoefeler, H.

    1987-01-01

    Transient exposure of an isolated isovolumic perfused rat heart to low concentrations (0.5 mM) of perfusate-born iodoacetamide resulted in complete inhibition of creatine kinase and partial inhibition of glyceraldehyde-3-phosphate dehydrogenase in the heart. At low levels of developed pressure, hearts maintained mechanical function, ATP, and creatine phosphate levels at control values. However, iodoacetamide-inhibited hearts were unable to maintain control values of end diastolic pressure or peak systolic pressure as work load increased. Global ischemia resulted in loss of all ATP without loss of creatine phosphate, indicating lack of active creatine kinase. These results indicate that isovolumic perfused rat hearts are able to maintain normal function and normal levels of high-energy phosphates without active creatine kinase at low levels of developed pressure. /sup 31/P-NMR of the heart was carried out.

  8. Structural and functional effects of social isolation on the hippocampus of rats with traumatic brain injury.

    PubMed

    Khodaie, Babak; Lotfinia, Ahmad Ali; Ahmadi, Milad; Lotfinia, Mahmoud; Jafarian, Maryam; Karimzadeh, Fariba; Coulon, Philippe; Gorji, Ali

    2015-02-01

    Social isolation has significant long-term psychological and physiological consequences. Both social isolation and traumatic brain injury (TBI) alter normal brain function and structure. However, the influence of social isolation on recovery from TBI is unclear. This study aims to evaluate if social isolation exacerbates the anatomical and functional deficits after TBI in young rats. Juvenile male rats were divided into four groups; sham operated control with social contacts, sham control with social isolation, TBI with social contacts, and TBI with social isolation. During four weeks after brain injury in juvenile rats, we evaluated the animal behaviors by T-maze and open-field tests, recorded brain activity with electrocorticograms and assessed structural changes by histological procedures in the hippocampal dentate gyrus, CA1, and CA3 areas. Our findings revealed significant memory impairments and hyperactivity conditions in rats with TBI and social isolation compared to the other groups. Histological assessments showed an increase of the mean number of dark neurons, apoptotic cells, and caspase-3 positive cells in all tested areas of the hippocampus in TBI rats with and without social isolation compared to sham rats. Furthermore, social isolation significantly increased the number of dark cells, apoptotic neurons, and caspase-3 positive cells in the hippocampal CA3 region in rats with TBI. This study indicates the harmful effect of social isolation on anatomical and functional deficits induced by TBI in juvenile rats. Prevention of social isolation may improve the outcome of TBI.

  9. Effects of propafenone on electrical and mechanical activities of single ventricular myocytes isolated from guinea-pig hearts.

    PubMed Central

    Honjo, H.; Watanabe, T.; Kamiya, K.; Kodama, I.; Toyama, J.

    1989-01-01

    1. The effects of propafenone on the transmembrane action potential and sarcomere shortening during twitch contraction were investigated in single ventricular myocytes isolated from guinea-pig hearts. 2. Propafenone at low concentrations (3-5 x 10(-7) M) slightly lengthened action potential duration (APD), but shortened it at higher concentrations. The shortening of APD was accompanied by an attenuation of sarcomere shortening during twitch contraction. 3. Propafenone (greater than 10(-6) M) caused a concentration-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential. In the presence of propafenone (3 x 10(-6) M), trains of stimuli led to an exponential decline in Vmax. A time constant for the recovery of Vmax from the use-dependent block was 4.8 s. 4. In myocytes treated with propafenone (3 x 10(-6) M), the Vmax of test action potentials preceded by the conditioning clamp pulses to 0 mV was progressively decreased by increasing the duration of single clamp pulse or by increasing the number of multiple brief clamp pulses. 5. These findings suggest that propafenone has use-dependent inhibitory action on the sodium channel by binding to the channel during both activated and inactivated states, and that the unbinding rate is comparable to that of Class-I antiarrhythmic drugs with intermediate kinetics. Propafenone may also have an inhibitory action on calcium and potassium channels. PMID:2758239

  10. A modified rat model of isolated bilateral pulmonary contusion

    PubMed Central

    WANG, SHAOHUA; RUAN, ZHENG; ZHANG, JIE; ZHENG, JIN

    2012-01-01

    The aim of the present study was to create a feasible specific rat model of isolated bilateral pulmonary contusion (PC) and to evaluate the relationship between severity of hypoxemia and quantity of contusion lesions. Anesthetized rats were placed in a prone position. Injury energy ranging from 2.1 to 3.0 J was produced by a falling weight passed through a specially designed arched shield to the bilateral chest wall of rats. After injury (4 h), the contusion volume was measured using computer-generated three-dimensional reconstruction from a chest computed tomographic scan and expressed as a percentage of total lung volume. Arterial partial pressure of oxygen (PaO2) in blood gas analysis and contusion volume percentage were used to assess the severity of contusion. Heart and lung biopsy was used to confirm the diagnosis and rule out the existence of myocardial contusion. There were 3 cases of death and 1 case of death in the 3.0 J and the 2.4 J group, respectively. PaO2 in the 2.7 J group was significantly lower than that in the lower energy groups (P<0.001). The percentage of pulmonary contusion in the 2.7 J group was significantly higher compared to that of the lower energy groups (P<0.001). PaO2 was negatively correlated with contusion percentage (R2=0.76). Hemorrhage, edema and neutrophil infiltration were determined by lung biopsy. No evidence of myocardial contusion was documented in multiple heart biopsies. The method illustrated in this research effectively duplicates isolated bilateral pulmonary contusion in rats, the severity of which is highly correlated with the contusion size. Thus, 2.7 J can be regarded as the maximal energy for sublethal injury. PMID:23181112

  11. ARISTOLOCHIC ACID I METABOLISM IN THE ISOLATED PERFUSED RAT KIDNEY

    PubMed Central

    Priestap, Horacio A.; Torres, M. Cecilia; Rieger, Robert A.; Dickman, Kathleen G.; Freshwater, Tomoko; Taft, David R.; Barbieri, Manuel A.; Iden, Charles R.

    2012-01-01

    Aristolochic acids are natural nitro-compounds found globally in the plant genus Aristolochia that have been implicated in the severe illness in humans termed aristolochic acid nephropathy (AAN). Aristolochic acids undergo nitroreduction, among other metabolic reactions, and active intermediates arise that are carcinogenic. Previous experiments with rats showed that aristolochic acid I (AA-I), after oral administration or injection, is subjected to detoxication reactions to give aristolochic acid Ia, aristolactam Ia, aristolactam I and their glucuronide and sulfate conjugates that can be found in urine and faeces. Results obtained with whole rats do not clearly define the role of liver and kidney in such metabolic transformation. In this study, in order to determine the specific role of the kidney on the renal disposition of AA-I and to study the biotransformations suffered by AA-I in this organ, isolated kidneys of rats were perfused with AA-I. AA-I and metabolite concentrations were determined in perfusates and urines using HPLC procedures. The isolated perfused rat kidney model showed that AA-I distributes rapidly and extensively in kidney tissues by uptake from the peritubular capillaries and the tubules. It was also established that the kidney is able to metabolize AA-I into aristolochic acid Ia, aristolochic acid Ia O-sulfate, aristolactam Ia, aristolactam I and aristolactam Ia O-glucuronide. Rapid demethylation and sulfation of AA-I in the kidney generate aristolochic acid Ia and its sulfate conjugate that are voided to the urine. Reduction reactions to give the aristolactam metabolites occur to a slower rate. Renal clearances showed that filtered AA-I is reabsorbed at the tubules whereas the metabolites are secreted. The unconjugated metabolites produced in the renal tissues are transported to both urine and perfusate whereas the conjugated metabolites are almost exclusively secreted to the urine. PMID:22118289

  12. Resveratrol attenuates left ventricular remodeling in old rats with COPD induced by cigarette smoke exposure and LPS instillation.

    PubMed

    Hu, Yi Xin; Cui, Hua; Fan, Li; Pan, Xiu Jie; Wu, Ji Hua; Shi, Suo Zhu; Cui, Shao Yuan; Wei, Zhi Min; Liu, Lin

    2013-12-01

    The objective of this study was to investigate left cardiac damage and the cardioprotective effects of resveratrol in old rats with COPD. Rats 22 months old were divided into three groups: control (CTL), smoking and lipopolysaccharides (SM/LPS), and SM/LPS plus resveratrol (SM/LPS-Res). Cardiac function, pathology, oxidative stress, and apoptosis index were measured. Expression of myocardial SIRT1 was studied by real-time quantitative polymerase chain reaction (PCR) and Western blot detection. The heart weight-body weight ratio (LVW/BW) increased in the SM/LPS group compared with the CTL group. Both the LVW/BW and the area of fibrosis in the SM/LPS-Res group decreased compared with those in the SM/LPS group. 8-OHdG expression increased in cardiac tissue of rats in the SM/LPS group, which could be inhibited by resveratrol. Resveratrol significantly increased the activity of superoxide dismutase (SOD) and reduced the cardiac malonyldialdehyde (MDA) level in the SM/LPS-Res group. There was a significant decrease in the extent of cardiomyocyte apoptosis in the SM/LPS-Res group compared with the SM/LPS group. SIRT1 mRNA increased in the SM/LPS-Res group compared with the SM/LPS group. In conclusion, resveratrol attenuated cardiac oxidative damage and left ventricular remodeling and enhanced the decreased expression of SIRT1 in hearts of old rats with emphysema and thus might be a therapeutic modality for cardiac injury complicated in chronic obstructive pulmonary disease (COPD).

  13. Reduced subcommissural organ glycoprotein immunoreactivity precedes aqueduct closure and ventricular dilatation in H-Tx rat hydrocephalus.

    PubMed

    Somera, K C; Jones, H C

    2004-03-01

    The H-Tx rat has fetal-onset hydrocephalus associated with closure of the cerebral aqueduct and a reduction in the secretory cells of the subcommissural organ (SCO), a circumventricular organ situated in the dorsal wall of the cerebral aqueduct. The objective of this study was to determine the role of the SCO in hydrocephalus pathogenesis. Serial brain sections through aqueduct regions containing the SCO from H-Tx rats, together with non-hydrocephalic Fischer F344 rats, were studied at E16, before hydrocephalus onset, at E17, the beginning of onset, and at P0 when the hydrocephalus was overt. Tissues were immunostained by AFRU, an antibody against the SCO glycoprotein, and for the intermediate filament nestin. The area of SCO cells with AFRU immunostaining and the severity of lateral ventricle dilatation were quantified by image analysis. At E16 all fetuses had distinct SCO ependymal cells, open aqueducts and normal lateral ventricles. The H-Tx fetuses fell into two groups with large areas and small areas of AFRU immunoreactivity, all with a full complement of SCO cells. By E17, fetuses with small areas of immunoreactivity had reduced numbers of tall SCO secretory cells, and most had aqueducts closed posteriorly and dilated ventricles. Three additional fetuses with small areas of immunoreactivity had narrow but patent aqueducts and normal ventricles, and another had an open aqueduct and dilated ventricles. At P0, pups previously identified as hydrocephalic had small areas of AFRU immunoreactivity, an aqueduct that was closed anteriorly but open posteriorly, ventricular dilatation, and an absence of SCO secretory cells. The aqueduct even when closed was lined by typical ependymal cells throughout. Decreased nestin immunostaining accompanied the SCO changes. It is concluded that reduced SCO glycoprotein immunoreactivity precedes both aqueduct closure and expansion of the lateral ventricles in the H-Tx rat.

  14. Effects of Aged Garlic Extract on Left Ventricular Diastolic Function and Fibrosis in a Rat Hypertension Model

    PubMed Central

    Hara, Yuki; Noda, Akiko; Miyata, Seiko; Minoshima, Makoto; Sugiura, Mari; Kojima, Jun; Otake, Masafumi; Furukawa, Mayuko; Cheng, Xian Wu; Nagata, Kohzo; Murohara, Toyoaki

    2013-01-01

    Daily consumption of garlic is known to lower the risk of hypertension and ischemic heart disease. In this study, we examined whether aged garlic extract (AGE) prevents hypertension and the progression of compensated left ventricular (LV) hypertrophy in Dahl salt-sensitive (DS) rats. DS rats were randomly divided into three groups: those fed an 8% NaCl diet until 18 weeks of age (8% NaCl group), those additionally treated with AGE (8% NaCl + AGE group), and control rats maintained on a diet containing 0.3% NaCl until 18 weeks of age (0.3% NaCl group). AGE was administered orally by gastric gavage once a day until 18 weeks of age. LV mass was significantly higher in the 8% NaCl + AGE group than in the 0.3% NaCl group at 18 weeks of age, but significantly lower in the 8% NaCl + AGE group than in the 8% NaCl group. No significant differences were observed in systolic blood pressure (SBP) between the 8% NaCl and 8% NaCl + AGE groups at 12 and 18 weeks of age. LV end-diastolic pressure and pressure half-time at 12 and 18 weeks of age were significantly lower in the 8% NaCl + AGE group compared with the 8% NaCl group. AGE significantly reduced LV interstitial fibrosis at 12 and 18 weeks of age. Chronic AGE intake attenuated LV diastolic dysfunction and fibrosis without significantly decreasing SBP in hypertensive DS rats. PMID:24172194

  15. Uptake of free choline by isolated perfused rat liver.

    PubMed Central

    Zeisel, S H; Story, D L; Wurtman, R J; Brunengraber, H

    1980-01-01

    The uptake of free choline by isolated perfused rat liver was characterized. A saturable uptake mechanism [Ka = 0.17 +/- 0.07 mM (SD); Vmax = 0.84 +/- 0.16 mumol/min X g dry weight] and a nonsaturable mechanism (through which uptake is proportional to choline concentration in the perfusate) were identified. Most of the choline transported into hepatocytes was converted to betaine, phosphorylcholine, or lecithin. Free choline also accumulated within the intracellular space, suggesting that choline oxidase activity does not always limit choline's uptake by the liver. PMID:6933493

  16. Uptake of Free Choline by Isolated Perfused Rat Liver

    NASA Astrophysics Data System (ADS)

    Zeisel, Steven H.; Story, David L.; Wurtman, Richard J.; Brunengraber, Henri

    1980-08-01

    The uptake of free choline by isolated perfused rat liver was characterized. A saturable uptake mechanism [Ka=0.17± 0.07 mM (SD); Vmax=0.84± 0.16\\ μ mol/min × g dry weight] and a nonsaturable mechanism (through which uptake is proportional to choline concentration in the perfusate) were identified. Most of the choline transported into hepatocytes was converted to betaine, phosphorylcholine, or lecithin. Free choline also accumulated within the intracellular space, suggesting that choline oxidase activity does not always limit choline's uptake by the liver.

  17. The arrhythmogenic transient inward current iTI and related contraction in isolated guinea-pig ventricular myocytes.

    PubMed Central

    Fedida, D; Noble, D; Rankin, A C; Spindler, A J

    1987-01-01

    1. The arrhythmogenic transient inward current, iTI, and contractions were recorded in isolated guinea-pig ventricular myocytes, after exposure to strophanthidin or low external K+ (0.5 mM), using a single-microelectrode voltage-clamp technique and an optical measure of contraction. 2. The inward current, iTI, and after-contraction occurred on repolarization after a depolarizing pre-pulse. Longer pre-pulses to more positive potentials increased the size and reduced the latency of iTI. Oscillatory currents and contractions also occurred during pulses to positive potentials. 3. The voltage dependence of iTI was studied by repolarizing to different potentials after a constant depolarizing pulse. Inward currents preceded after-contractions at all potentials. The iTI was maximal at about -50 mV, diminishing in magnitude at more negative and positive potentials. It remained inward at potentials up to +47 mV. The contraction exhibited a similar voltage dependence. The current-voltage relation varied in the same cell with longer exposure to glycosides. Thus, the voltage dependence of iTI reflected not only that of an underlying ionic mechanism but also the effects of potential on intracellular Ca2+ oscillations which trigger iTI. 4. Uniformity of internal Ca2+ transients was achieved by clamping to different potentials at the peak of an inward current. The iTI remained inward at positive potentials. An inward tail current, seen on repolarizing during iTI at the end of a depolarizing pre-pulse, progressively increased at negative potentials. This voltage dependence may be close to that of the Ca2+-activated inward current responsible for iTI. 5. Replacement of Na+ by Li+ initially increased the magnitude of iTI, but further exposure abolished the inward current, while the after-contractions continued to increase. The potential dependence of iTI was not affected by exposure to zero Na+. Replacement of Ca2+ by Sr2+ also abolished iTI and the after-contraction, but the main

  18. Altered Left Ventricular Ion Channel Transcriptome in a High-Fat-Fed Rat Model of Obesity: Insight into Obesity-Induced Arrhythmogenesis.

    PubMed

    Ashrafi, Reza; Yon, Marianne; Pickavance, Lucy; Yanni Gerges, Joseph; Davis, Gershan; Wilding, John; Jian, Kun; Zhang, Henggui; Hart, George; Boyett, Mark

    2016-01-01

    Introduction. Obesity is increasingly common and is associated with an increased prevalence of cardiac arrhythmias. The aim of this study was to see whether in obesity there is proarrhythmic gene expression of ventricular ion channels and related molecules. Methods and Results. Rats were fed on a high-fat diet and compared to control rats on a normal diet (n = 8). After 8 weeks, rats on the high-fat diet showed significantly greater weight gain and higher adiposity. Left ventricle samples were removed at 8 weeks and mRNA expression of ion channels and other molecules was measured using qPCR. Obese rats had significant upregulation of Cav1.2, HCN4, Kir2.1, RYR2, NCX1, SERCA2a, and RYR2 mRNA and downregulation of ERG mRNA. In the case of HCN4, it was confirmed that there was a significant increase in protein expression. The potential effects of the mRNA changes on the ventricular action potential and intracellular Ca(2+) transient were predicted using computer modelling. Modelling predicted prolongation of the ventricular action potential and an increase in the intracellular Ca(2+) transient, both of which would be expected to be arrhythmogenic. Conclusion. High-fat diet causing obesity results in arrhythmogenic cardiac gene expression of ion channels and related molecules.

  19. Antioxidant effects of hydrogen sulfide on left ventricular remodeling in smoking rats are mediated via PI3K/Akt-dependent activation of Nrf2.

    PubMed

    Zhou, Xiang; Zhao, Liangping; Mao, Jinning; Huang, Jian; Chen, Jianchang

    2015-03-01

    There is growing evidence that oxidative stress plays critical roles in the pathogenesis of cardiac remodeling. In the present study, we established a rat model of passive smoking and investigated the antioxidant effects of hydrogen sulfide (H2S) on smoking-induced left ventricular remodeling. Cardiac structure and function were evaluated using 2-dimensional echocardiography. Myocardial fibrosis was detected by Masson's trichrome staining and immunohistochemistry. Oxidative stress was assessed by measuring malondialdehyde levels, superoxide dismutase and glutathione peroxidase activities, and reactive oxygen species generation in the myocardium. Neonatal rat cardiomyocytes transfected with specific siRNA and exposed to cigarette smoke condensate and H2S donor sodium hydrosulfide were used to confirm the involvement of Nrf2 and PI3K/Akt signaling in the antioxidant effects of H2S. Our results indicated that H2S could protect against left ventricular remodeling in smoking rats via attenuation of oxidative stress. Moreover, H2S was also found to increase the phosphorylation of Akt and GSK3β and decrease the nuclear expression of Fyn, which consequently leads to nuclear translocation of Nrf2 and elevated expression of HO-1 and NQO1. In conclusion, H2S may exert antioxidant effects on left ventricular remodeling in smoking rats via PI3K/Akt-dependent activation of Nrf2 signaling.

  20. Altered Left Ventricular Ion Channel Transcriptome in a High-Fat-Fed Rat Model of Obesity: Insight into Obesity-Induced Arrhythmogenesis

    PubMed Central

    Yon, Marianne; Pickavance, Lucy; Yanni Gerges, Joseph; Davis, Gershan; Wilding, John; Jian, Kun; Hart, George; Boyett, Mark

    2016-01-01

    Introduction. Obesity is increasingly common and is associated with an increased prevalence of cardiac arrhythmias. The aim of this study was to see whether in obesity there is proarrhythmic gene expression of ventricular ion channels and related molecules. Methods and Results. Rats were fed on a high-fat diet and compared to control rats on a normal diet (n = 8). After 8 weeks, rats on the high-fat diet showed significantly greater weight gain and higher adiposity. Left ventricle samples were removed at 8 weeks and mRNA expression of ion channels and other molecules was measured using qPCR. Obese rats had significant upregulation of Cav1.2, HCN4, Kir2.1, RYR2, NCX1, SERCA2a, and RYR2 mRNA and downregulation of ERG mRNA. In the case of HCN4, it was confirmed that there was a significant increase in protein expression. The potential effects of the mRNA changes on the ventricular action potential and intracellular Ca2+ transient were predicted using computer modelling. Modelling predicted prolongation of the ventricular action potential and an increase in the intracellular Ca2+ transient, both of which would be expected to be arrhythmogenic. Conclusion. High-fat diet causing obesity results in arrhythmogenic cardiac gene expression of ion channels and related molecules. PMID:27747100

  1. Activation of ATP-sensitive K+ channels by epoxyeicosatrienoic acids in rat cardiac ventricular myocytes

    PubMed Central

    Lu, Tong; Hoshi, Toshinori; Weintraub, Neal L; Spector, Arthur A; Lee, Hon-Chi

    2001-01-01

    We examined the effects of epoxyeicosatrienoic acids (EETs), which are cytochrome P450 metabolites of arachidonic acid (AA), on the activities of the ATP-sensitive K+ (KATP) channels of rat cardiac myocytes, using the inside-out patch-clamp technique. In the presence of 100 μm cytoplasmic ATP, the KATP channel open probability (Po) was increased by 240 ± 60% with 0.1 μm 11,12-EET and by 400 ± 54% with 5 μm 11,12-EET (n = 5 –10, P < 0.05 vs. control), whereas neither 5 μm AA nor 5 μm 11,12-dihydroxyeicosatrienoic acid (DHET), which is the epoxide hydrolysis product of 11,12-EET, had any effect on Po. The half-maximal activating concentration (EC50) was 18.9 ± 2.6 nm for 11,12-EET (n = 5) and 19.1 ± 4.8 nm for 8,9-EET (n = 5), P = n.s. vs. 11,12-EET). Furthermore, 11,12-EET failed to alter the inhibition of KATP channels by glyburide. Application of 11,12-EET markedly decreased the channel sensitivity to cytoplasmic ATP. The half-maximal inhibitory concentration of ATP (IC50) was increased from 21.2 ± 2.0 μm at baseline to 240 ± 60 μm with 0.1 μm 11,12-EET (n = 5, P < 0.05 vs. control) and to 780 ± 30 μm with 5 μm 11,12-EET (n = 11, P < 0.05vs. control). Increasing the ATP concentration increased the number of kinetically distinguishable closed states, promoting prolonged closure durations. 11,12-EET antagonized the effects of ATP on the kinetics of the KATP channels in a dose and voltage-dependent manner. 11,12-EET (1 μm) reduced the apparent association rate constant of ATP to the channel by 135-fold. Application of 5 μm 11,12-EET resulted in hyperpolarization of the resting membrane potential in isolated cardiac myocytes, which could be blocked by glyburide. These results suggest that EETs are potent activators of the cardiac KATP channels, modulating channel behaviour by reducing the channel sensitivity to ATP. Thus, EETs could be important endogenous regulators of cardiac electrical excitability. PMID:11744757

  2. Computational analysis of the regulation of Ca2+ dynamics in rat ventricular myocytes

    NASA Astrophysics Data System (ADS)

    Bugenhagen, Scott M.; Beard, Daniel A.

    2015-10-01

    Force-frequency relationships of isolated cardiac myocytes show complex behaviors that are thought to be specific to both the species and the conditions associated with the experimental preparation. Ca2+ signaling plays an important role in shaping the force-frequency relationship, and understanding the properties of the force-frequency relationship in vivo requires an understanding of Ca2+ dynamics under physiologically relevant conditions. Ca2+ signaling is itself a complicated process that is best understood on a quantitative level via biophysically based computational simulation. Although a large number of models are available in the literature, the models are often a conglomeration of components parameterized to data of incompatible species and/or experimental conditions. In addition, few models account for modulation of Ca2+ dynamics via β-adrenergic and calmodulin-dependent protein kinase II (CaMKII) signaling pathways even though they are hypothesized to play an important regulatory role in vivo. Both protein-kinase-A and CaMKII are known to phosphorylate a variety of targets known to be involved in Ca2+ signaling, but the effects of these pathways on the frequency- and inotrope-dependence of Ca2+ dynamics are not currently well understood. In order to better understand Ca2+ dynamics under physiological conditions relevant to rat, a previous computational model is adapted and re-parameterized to a self-consistent dataset obtained under physiological temperature and pacing frequency and updated to include β-adrenergic and CaMKII regulatory pathways. The necessity of specific effector mechanisms of these pathways in capturing inotrope- and frequency-dependence of the data is tested by attempting to fit the data while including and/or excluding those effector components. We find that: (1) β-adrenergic-mediated phosphorylation of the L-type calcium channel (LCC) (and not of phospholamban (PLB)) is sufficient to explain the inotrope-dependence; and (2) that

  3. Mapping and confirmation of a major left ventricular mass QTL on rat chromosome 1 by contrasting SHRSP and F344 rats.

    PubMed

    Grabowski, Katja; Koplin, Gerold; Aliu, Bujar; Schulte, Leonard; Schulz, Angela; Kreutz, Reinhold

    2013-09-16

    An abnormal increase in left ventricular (LV) mass, i.e., LV hypertrophy (LVH), represents an important target organ damage in arterial hypertension and has been associated with poor clinical outcome. Genetic factors are contributing to variation in LV mass in addition to blood pressure and other factors such as dietary salt intake. We set out to map quantitative trait loci (QTL) for LV mass by comparing the spontaneously hypertensive stroke-prone (SHRSP) rat with LVH and normotensive Fischer rats (F344) with contrasting low LV mass. To this end we performed a genome-wide QTL mapping analysis in 232 F2 animals derived from SHRSP and F344 exposed to high-salt (4% in chow) intake for 8 wk. We mapped one major QTL for LV mass on rat chromosome 1 (RNO1) that demonstrated strong linkage (peak logarithm of odds score 8.4) to relative LV weight (RLVW) and accounted for ∼19% of the variance of this phenotype in F2 rats. We therefore generated a consomic SHRSP-1(F344) strain in which RNO1 from F344 was introgressed into the SHRSP background. Consomic and SHRSP animals showed similar blood pressures during conventional intra-arterial measurements, while RLVW was already significantly lower (-17.7%, P<0.05) in SHRSP-1(F344) in response to a normal-salt diet; a similar significant reduction of LV mass was also observed in consomic rats after high-salt intake (P<0.05 vs. SHRSP). Thus, a major QTL on RNO1 was confirmed with significant impact on LV mass in the hypertensive background of SHRSP.

  4. Isolation of high density lipoproteins from rat intestinal epithelial cells.

    PubMed Central

    Magun, A M; Brasitus, T A; Glickman, R M

    1985-01-01

    Previous studies have defined forms of high density lipoproteins (HDL) in rat mesenteric lymph, suggesting that they have a secretory origin. This study describes the isolation and characterization of intestinal intracellular HDL. Two preparations were made as follows: (a) Rat enterocytes were isolated and a Golgi organelle fraction was prepared. (b) Cell homogenates were subjected to nitrogen cavitation and a cytoplasmic fraction was prepared. Lipoproteins were isolated from both preparations by sequential ultracentrifugation. When the HDL fraction (1.07-1.21 g/ml) was subjected to isopyknic density gradient ultracentrifugation, a peak of apoproteins A-I and B (apoA-I and apoB, respectively) was found at a density of 1.11-1.14 g/ml. Electron microscopy of the fraction showed spherical particles ranging in size from 6 to 13 nm. Immunoelectrophoresis revealed a precipitin arc in the alpha region against apoA-I which extended into the pre-beta region where a precipitin arc against apoB was also seen. ApoB antisera depleted the pre-beta particles whereas the alpha migrating particles remained. Lipid analysis of the whole HDL fraction revealed phospholipid, cholesteryl ester, and triglyceride as the major lipids. [3H]leucine was then administered into the duodenum and a radiolabeled intracellular HDL fraction was isolated. The newly synthesized apoproteins of the HDL fraction, as determined by gel electrophoresis, were apoB, apoA-I, and apolipoprotein A-IV (ApoA-IV). Immunoprecipitation of the apoB particles revealed apoA-I and apoA-IV in the supernatant. These data demonstrate that there are at least two intracellular intestinal forms of HDL particles, one of which contains apoB. The other particle contains apoA-I and apoA-IV, has alpha mobility, is spherical, and resembles a particle found in the lymph. Images PMID:3965504

  5. Exogenous reactive oxygen species deplete the isolated rat heart of antioxidants.

    PubMed

    Vaage, J; Antonelli, M; Bufi, M; Irtun, O; DeBlasi, R A; Corbucci, G G; Gasparetto, A; Semb, A G

    1997-01-01

    The effects of reactive oxygen species (ROS) on myocardial antioxidants and on the activity of oxidative mitochondrial enzymes were investigated in the following groups of isolated, perfused rat hearts. I: After stabilization the hearts freeze clamped in liquid nitrogen (n = 7). II: Hearts frozen after stabilization and perfusion for 10 min with xanthine oxidase (XO) (25 U/l) and hypoxanthine (HX) (1 mM) as a ROS-producing system (n = 7). III: Like group II, but recovered for 30 min after perfusion with XO + HX (n = 9). IV: The hearts were perfused and freeze-clamped as in group III, but without XO + HX (n = 7). XO + HX reduced left ventricular developed pressure and coronary flow to approximately 50% of the baseline value. Myocardial content of hydrogen peroxide (H2O2) and malondialdehyde (MDA) increased at the end of XO + HX perfusion, indicating that generation of ROS and lipid peroxidation occurred. Levels of H2O2 and MDA normalized during recovery. Superoxide dismutase, reduced glutathione and alpha-tocopherol were all reduced after ROS-induced injury. ROS did not significantly influence the tissue content of coenzyme Q10 (neither total, oxidized, nor reduced), cytochrome c oxidase, and succinate cytochrome c reductase. The present findings indicate that the reduced contractile function was not correlated to reduced activity of the mitochondrial electron transport chain. ROS depleted the myocardium of antioxidants, leaving the heart more sensitive to the action of oxidative injury.

  6. Rat brain docosahexaenoic acid metabolism is not altered by a 6 day intracerebral ventricular infusion of bacterial lipopolysaccharide

    PubMed Central

    Rosenberger, Thad A.; Villacreses, Nelly E.; Weis, Margaret T.; Rapoport, Stanley I.

    2010-01-01

    In a rat model of neuroinflammation, produced by a 6-day intracerebral ventricular infusion of bacterial lipopolysaccharide (LPS), we reported that the brain concentrations of non-esterified brain arachidonic acid (AA, 20:4 n-6) and its eicosanoid products PGE2 and PGD2 were increased, as were AA turnover rates in certain brain phospholipids and the activity of AA-selective cytosolic phospholipase A2 (cPLA2). The activity of Ca2+-independent iPLA2, which is thought to be selective for the release of docosahexaenoic acid (DHA, 22:6 n-3) from membrane phospholipid, was unchanged. In the present study, we measured parameters of brain DHA metabolism in comparable artificial cerebrospinal fluid (control) and LPS-infused rats. In contrast to the reported changes in markers of AA metabolism, the brain non-esterified DHA concentration and DHA turnover rates in individual phospholipids were not significantly altered by LPS infusion. The formation rates of AA-CoA and DHA-CoA in a microsomal brain fraction were also unaltered by the LPS infusion. These observations indicate that LPS-treatment upregulates markers of brain AA but not DHA metabolism. All of which are consistent with other evidence that suggest different sets of enzymes regulate AA and DHA recycling within brain phospholipids and that only selective increases in brain AA metabolism occur following a 6 day LPS infusion. PMID:20026368

  7. Gamma-linolenic acid provides additional protection against ventricular fibrillation in aged rats fed linoleic acid rich diets.

    PubMed

    Charnock, J S

    2000-02-01

    Ligation of the coronary artery in rats produces severe ventricular fibrillation (VF) and malignant cardiac arrhythmia. Mortality increases with the age of the animal. Diets rich in saturated fatty acids (SF) but low in linoleic acid (LA) increase, but diets high in LA and low in SF decrease the severity of VF and mortality in older animals. The effects of an LA enriched diet can be blocked by inhibition of cyclooxygenase suggesting that conversion of LA to eicosanoids is central to the development of VF. Conversion of LA to gamma-linolenic acid (GLA) via delta-6 desaturase is the first step in the process. The activity of delta-6 desaturase declines with age. Thus inclusion of GLA in the diet of older animals may provide an additional benefit over LA alone. Dietary supplements of evening primrose oil (EPO) to one year old rats reduced ischaemic VF more than a supplement of sunflower seed oil (SSO) without GLA. Substitution of borage oil (more GLA than EPO but less LA than either EPO or SSO) was without additional benefit.

  8. Comparison of Quantitative Characteristics of Early Post-resuscitation EEG Between Asphyxial and Ventricular Fibrillation Cardiac Arrest in Rats.

    PubMed

    Chen, Bihua; Chen, Gang; Dai, Chenxi; Wang, Pei; Zhang, Lei; Huang, Yuanyuan; Li, Yongqin

    2017-05-08

    Quantitative electroencephalogram (EEG) analysis has shown promising results in studying brain injury and functional recovery after cardiac arrest (CA). However, whether the quantitative characteristics of EEG, as potential indicators of neurological prognosis, are influenced by CA causes is unknown. The purpose of this study was designed to compare the quantitative characteristics of early post-resuscitation EEG between asphyxial CA (ACA) and ventricular fibrillation CA (VFCA) in rats. Thirty-two Sprague-Dawley rats of both sexes were randomized into either ACA or VFCA group. Cardiopulmonary resuscitation was initiated after 5-min untreated CA. Characteristics of early post-resuscitation EEG were compared, and the relationships between quantitative EEG features and neurological outcomes were investigated. Compared with VFCA, serum level of S100B, neurological deficit score and brain histopathologic damage score were dramatically higher in the ACA group. Quantitative measures of EEG, including onset time of EEG burst, time to normal trace, burst suppression ratio, and information quantity, were significantly lower for CA caused by asphyxia and correlated with the 96-h neurological outcome and survival. Characteristics of earlier post-resuscitation EEG differed between cardiac and respiratory causes. Quantitative measures of EEG not only predicted neurological outcome and survival, but also have the potential to stratify CA with different causes.

  9. Protein kinase C isozyme expression in right ventricular hypertrophy induced by pulmonary hypertension in chronically hypoxic rats.

    PubMed

    Zeng, Chao; Liang, Bin; Jiang, Rui; Shi, Yiwei; Du, Yongcheng

    2017-10-01

    In chronic hypoxia, pulmonary hypertension (PH) induces right ventricular hypertrophy (RVH). Evidence indicates that protein kinase C (PKC) serves a crucial role in hypoxia‑induced RVH. The present study investigated PKC isoform-specific expression and its involvement in RVH. Rats were exposed to normobaric hypoxia for a number of days to induce PH. PKC isoform‑specific membrane translocation and protein expression in the myocardium were evaluated by western blotting and immunostaining. A total of six isoforms of conventional PKC (cPKC; α, βI and βII) and of novel PKC (nPKC; δ, ε and η), were detected in the rat myocardium. Hypoxic exposure (1‑21 days) induced PH with RVH and vascular remodeling. nPKCδ membrane translocation at 3‑7 days and cPKCβI expression at 1‑21 days in the RV following hypoxic exposure were significantly decreased as compared with the normoxia control group. Membrane translocation of cPKCβII at 14‑21 days and of nPKCη at 7‑21 days in the left ventricle following hypoxic exposure was significantly increased when compared with the control. The results of the present study suggested that the alterations in membrane translocation, and nPKCδ and cPKCβI expression, are associated with RVH following PH, and the upregulation of cPKCβII membrane translocation is involved in left‑sided heart failure.

  10. (/sup 3/H)-8-cyclopentyl-1,3-dipropylxanthine binding to A1 adenosine receptors of intact rat ventricular myocytes

    SciTech Connect

    Martens, D.; Lohse, M.J.; Schwabe, U.

    1988-09-01

    The purpose of the present study was the identification of A1 adenosine receptors in intact rat ventricular myocytes, which are thought to mediate the negative inotropic effects of adenosine. The adenosine receptor antagonist (/sup 3/H)-8-cyclopentyl-1,3-dipropylxanthine was used as radioligand. Binding of the radioligand to intact myocytes was rapid, reversible, and saturable with a binding capacity of 40,000 binding sites per cell. The dissociation constant of the radioligand was 0.48 nM. The adenosine receptor antagonists 8-cyclopentyl-1,3-dipropylxanthine, xanthine amine congener, and theophylline were competitive inhibitors with affinities in agreement with results obtained for A1 receptors in other tissues. Competition experiments using the adenosine receptor agonists R-N(6)-phenylisopropyladenosine, 5'-N-ethylcarboxamidoadenosine, and S-N(6)-phenylisopropyladenosine gave monophasic displacement curves with Ki values of 50 nM, 440 nM, and 4,300 nM, which agreed well with the GTP-inducible low affinity state in cardiac membranes. The low affinity for agonists was not due to agonist-induced desensitization, and correlated well with the corresponding IC50 values for the inhibition of cyclic AMP accumulation by isoprenaline. It is suggested that only a low affinity state of A1 receptors can be detected in intact rat myocytes due to the presence of high concentrations of guanine nucleotides in intact cells.

  11. Echo planar imaging of isolated perfused rat hearts at 4.7 T: a comparison of Langendorff and working heart preparations.

    PubMed

    Blackband, S J; Chatham, J C; O'Dell, W; Day, S

    1990-08-01

    The implementation of echo planar imaging at 4.7 T is demonstrated using a homebuilt gradient and radiofrequency assembly. The application of such a technique to the study of the isolated perfused rat heart is demonstrated. Langendorff and working heart perfusion preparations are compared and changes in the left ventricular volume shown are to be much larger in the working heart preparation. Such a methodology is expected to provide a useful model for the study of cardiac function and dynamics in the normal and diseased states under controlled perfusion conditions.

  12. Novel approaches to determine contractile function of the isolated adult zebrafish ventricular cardiac myocyte

    PubMed Central

    Dvornikov, Alexey V; Dewan, Sukriti; Alekhina, Olga V; Pickett, F Bryan; de Tombe, Pieter P

    2014-01-01

    The zebrafish (Danio rerio) has been used extensively in cardiovascular biology, but mainly in the study of heart development. The relative ease of its genetic manipulation may indicate the suitability of this species as a cost-effective model system for the study of cardiac contractile biology. However, whether the zebrafish heart is an appropriate model system for investigations pertaining to mammalian cardiac contractile structure–function relationships remains to be resolved. Myocytes were isolated from adult zebrafish hearts by enzymatic digestion, attached to carbon rods, and twitch force and intracellular Ca2+ were measured. We observed the modulation of twitch force, but not of intracellular Ca2+, by both extracellular [Ca2+] and sarcomere length. In permeabilized cells/myofibrils, we found robust myofilament length-dependent activation. Moreover, modulation of myofilament activation–relaxation and force redevelopment kinetics by varied Ca2+ activation levels resembled that found previously in mammalian myofilaments. We conclude that the zebrafish is a valid model system for the study of cardiac contractile structure–function relationships. PMID:24591576

  13. Intraventricular migration of an isolated fourth ventricular cysticercus following cerebrospinal fluid shunting

    PubMed Central

    Khalid, Saifullah; Obaid, Amber; Sharma, Raman M.; Mahmood, Asad; Narayanasamy, Sabarish

    2016-01-01

    Background: Isolated intraventricular neurocysticercosis (NCC) is less frequently seen and can be missed on plain magnetic resonance imaging (MRI). Three-dimensional constructive interference in steady state (CISS) sequence is an extremely helpful sequence in identifying the lesion but is rarely used routinely. Case Description: Here, we report a case of young male adult who presented with diminution of vision and headache. MRI of the brain revealed hydrocephalus, and on using CISS sequence only, the lesion could be identified in the fourth ventricle. He was treated with medical management, and ventriculoperitoneal shunting of cerebrospinal fluid was done to relieve the hydrocephalus. It resulted in immediate relief with aggravation of headache few days later. Repeat MRI revealed intraventricular migration into the left foramen of monro leading to left lateral ventricle dilatation necessitating endoscopic removal of the lesion. Conclusion: CISS sequence is definitely the sequence of choice in identifying intraventricular NCC. Ventriculoperitoneal shunting can result in the intraventricular migration of the cyst due to sudden decompression necessitating repeat surgery. Endoscopic removal of NCC has a high success rate with limited complications. PMID:28031989

  14. Toxicity of valproic acid in isolated rat liver mitochondria.

    PubMed

    Jafarian, Iman; Eskandari, Mohammad Reza; Mashayekhi, Vida; Ahadpour, Morteza; Hosseini, Mir-Jamal

    2013-10-01

    Valproic acid (VPA), an anticonvulsant and mood-stabilizing drug, is widely used for the treatment of different types of seizures and myoclonic epilepsy. Several mechanisms have been suggested for VPA hepatotoxicity, and most of them are associated with oxidative stress. It seems that oxidative stress by VPA treatment has been associated with mitochondrial dysfunction. Therefore, this study investigated the mitochondrial toxicity mechanisms of VPA on freshly isolated rat mitochondria for better understanding pathogenesis of VPA in mitochondrial toxicity. Rat liver mitochondria were obtained by differential ultracentrifugation and were then incubated with different concentrations of VPA (25-200 µM). Our results showed that VPA could induce oxidative stress via rising in mitochondrial reactive oxygen species formation, lipid peroxidation, mitochondrial membrane potential collapse, mitochondrial swelling and finally release of cytochrome c. These effects were well inhibited by pretreatment of isolated mitochondria with cyclosporin A and butylated hydroxytoluene. Based on these results, it is clear that VPA exerts mitochondrial toxicity by impairing mitochondrial functions leading to oxidative stress and cytochrome c expulsion, which start cell death signaling.

  15. Experimental studies on islets isolation, purification and function in rats.

    PubMed

    Pang, Xinlu; Xue, Wujun; Feng, Xinshun; Tian, Xiaohui; Teng, Yan; Ding, Xiaoming; Pan, Xiaoming; Guo, Qi; He, Xiaoli

    2015-01-01

    To develop a simple and effective method of islet isolation and purification in rats. Collagenase P was injected into pancreatic duct followed by incubation in water bath to digest the pancreas and isolate islet, then discontinuous gravity gradient purification was used to purify the islet. The purified islets were identified by dithizone staining. The viability of islets was assessed by fluorescence staining of acridine orange (AO) and propidium iodide (PI). The function of purified islets was determined by glucose-stimulated insulin release test and transplantation of rat with streptozocin-induced diabetes. 738±193 islets were recovered after purification. The average purity was 77±13%, the viability of islets was more than 95%. When inspected by glucose stimulation, the secreted insulin concentration was 24.31±5.47 mIU/L when stimulated by low concentration glucose and 37.62±4.29 mIU/L by high concentration glucose. There was significant difference between the two phases (P<0.05). The blood sugar concentration recovered to normal level after two days in the animals with islet transplantation. In conclusion, islets can be procured with good function and shape by using the method of injecting collagenase into pancreatic duct followed by incubation in water bath and purification using discontinuous gravity gradient.

  16. Experimental studies on islets isolation, purification and function in rats

    PubMed Central

    Pang, Xinlu; Xue, Wujun; Feng, Xinshun; Tian, Xiaohui; Teng, Yan; Ding, Xiaoming; Pan, Xiaoming; Guo, Qi; He, Xiaoli

    2015-01-01

    To develop a simple and effective method of islet isolation and purification in rats. Collagenase P was injected into pancreatic duct followed by incubation in water bath to digest the pancreas and isolate islet, then discontinuous gravity gradient purification was used to purify the islet. The purified islets were identified by dithizone staining. The viability of islets was assessed by fluorescence staining of acridine orange (AO) and propidium iodide (PI). The function of purified islets was determined by glucose-stimulated insulin release test and transplantation of rat with streptozocin-induced diabetes. 738±193 islets were recovered after purification. The average purity was 77±13%, the viability of islets was more than 95%. When inspected by glucose stimulation, the secreted insulin concentration was 24.31±5.47 mIU/L when stimulated by low concentration glucose and 37.62±4.29 mIU/L by high concentration glucose. There was significant difference between the two phases (P<0.05). The blood sugar concentration recovered to normal level after two days in the animals with islet transplantation. In conclusion, islets can be procured with good function and shape by using the method of injecting collagenase into pancreatic duct followed by incubation in water bath and purification using discontinuous gravity gradient. PMID:26885021

  17. The effect of cinnamon extract on isolated rat uterine strips.

    PubMed

    Alotaibi, Mohammed

    2016-03-01

    Cinnamon is a spice used by some populations as a traditional remedy to control blood pressure and thus hypertension. Cinnamon extract decreases contractility in some smooth muscles, but its effect on uterine smooth muscle is unknown. The aim of this study was to determine the physiological and pharmacological effects of cinnamon extract (CE) on the contractions of isolated rat uterine strips and to investigate its possible mechanism of action. Isolated longitudinal uterine strips were dissected from non-pregnant rats, mounted vertically in an organ bath chamber, and exposed to different concentrations of CE (10-20mg/mL). The effect of CE was investigated in the presence of each of the following solutions: 60mM KCl, 5nM oxytocin, and 1μM Bay K8644. CE significantly decreased the force of uterine contraction in a concentration-dependent manner and significantly attenuated the uterine contractions elicited by KCl and oxytocin. In addition, CE significantly decreased the contractile force elicited when L-type Ca(2+) channels were activated by Bay K8644. CE's major mechanism may be inhibition of L-type Ca(2+) channels, which limits calcium influx. These data demonstrate that CE can be a potent tocolytic that can decrease uterine activity regardless of how the force was produced, even when the uterus was stimulated by agonists. As a result, cinnamon may be used to alleviate menstrual pain associated with dysmenorrhoea or prevent unwanted uterine activity in early pregnancy.

  18. Isolation and purification of rat liver morphine UDP-glucuronosyltransferase

    SciTech Connect

    Puig, J.F.; Tephly, T.R.

    1986-03-05

    The enhancement of rat liver microsomal morphine (M) and 4-hydroxybiphenyl (4-HBP) UDP-glucuronyltransferase (UDPGT) activities by phenobarbital treatment has been proposed to represent increased activity of a single enzyme form, GT-2. They have separated M and 4-HBP UDPGT activities from Emulgen 911-solubilized microsomes obtained from livers of phenobarbital-treated Wistar rats. A sensitive assay procedure was developed to quantify M-UDPGT and 4-HBP-UDPGT activities using /sup 14/C-UDP-glucuronic acid (UDPGA) and reversed phase C-18 minicolumns whereby the radioactive glucuronides were differentially eluted from labeled UDPGA. Trisacryl DEAE, and chromatofocusing procedures were employed to separate M-UDPGT and 4-HBP-UDPGT in the presence of exogenous phosphatidylcholine (PC). The PC is necessary to stabilize UDPGT activities. M-UDPGT was isolated to apparent homogeneity and displayed a monomeric molecular weight of 56,000 daltons on SDS-PAGE. It reacted with M but not with 4-HBP, bilirubin, p-nitrophenol, testosterone, androsterone, estrone, 4-aminobiphenyl or ..cap alpha..-naphthylamine. 4-HBP-UDPGT did not react with M. Therefore, M and 4-HBP glucuronidations are catalyzed by separate enzymes in rat liver microsomes.

  19. The impact of social isolation on immunological parameters in rats.

    PubMed

    Krügel, Ute; Fischer, Johannes; Bauer, Katrin; Sack, Ulrich; Himmerich, Hubertus

    2014-03-01

    In various toxicological studies, single housing of rodents is preferred to standardize for regulatory purposes. However, housing conditions can have severe, often underestimated, impact on results in toxicological examinations. As different husbandry conditions have been shown to impose stress, we investigated their influence on plasma cytokines. Adult male Wistar rats were assigned to one group housed in cages of four and another housed singly for 28 days. Eight animals per group were tested in the forced swim test (FST) for symptoms of "behavioral despair," and in another eight animals per group, plasma concentrations of the stress hormone ACTH, of the pro-inflammatory cytokines TNF-α, IFN-γ, IL-2 and IL-22, and of the anti-inflammatory cytokines IL-4 and IL-10 were analyzed. Group-housed animals had significantly lower body weight than individually housed animals. The FST revealed symptoms of "behavioral despair" of individually housed rats accompanied by higher levels of ACTH and TNF-α but also of IL-4 and IL-10. No significant differences between housing conditions were found for IFN-γ, IL-2 and IL-22. Social isolation by husbandry conditions, apart from any other manipulation, alters the behavioral and immunological status of rats and must be considered when immunological effects are examined in various experimental protocols.

  20. Cyanide-induced injury to the isolated perfused rat liver.

    PubMed

    Younes, M; Strubelt, O

    1988-11-01

    In order to study the events that follow cyanide-induced inhibition of oxidative metabolism and produce cellular injury, isolated, haemoglobin-free perfused rat livers from fasted rats were exposed to KCN (100 mg/l). KCN reduced the oxygen consumption of the livers by about 80%. Hepatotoxicity was evident by a marked release of enzymes (LDH, SDH) and of glutathione (mainly GSSG) into the perfusate, by a depletion of hepatic glutathione and by an accumulation of calcium in the liver. Cyanide-induced hepatotoxicity could be prevented completely by feeding the rats before preparing the liver as well as by addition of fructose to the perfusate of fasted livers. Both treatments resulted in an increased energy supply from anaerobic glycolysis as evidenced by a large release of lactate + pyruvate into the perfusate. The toxic actions of cyanide were markedly attenuated by deferrioxamine as well as by allopurinol. These antitoxic actions occurred without changes in anaerobic glycolysis. Omission of calcium from the perfusate, however, did not influence cyanide toxicity. Thus, energy supply from anaerobic glycolysis seems to be sufficient for the basic functions of the liver to occur, when oxidative metabolism is inhibited by cyanide. The effects of deferrioxamine and allopurinol indicate the involvement of radical intermediates and/or Fe2+ in cyanide-induced cellular toxicity. An influx of calcium from the extracellular to the intracellular space is not involved in cyanide-induced hepatocellular injury.

  1. Isolation and characterization of the rat tryptophan oxygenase gene.

    PubMed Central

    Schmid, W; Scherer, G; Danesch, U; Zentgraf, H; Matthias, P; Strange, C M; Röwekamp, W; Schütz, G

    1982-01-01

    Tryptophan oxygenase (TO, EC 1.13.1.12) from rat liver is subject to glucocorticoid and developmental control. To study the mechanism of regulation, TO mRNA sequences and the chromosomal TO gene were cloned. From a cDNA library prepared from rat liver poly(A)+ RNA enriched for TO mRNA, a recombinant plasmid containing TO cDNA sequences was identified by translation of hybrid-selected RNA and immunoprecipitation with antibodies directed against TO. This cDNA clone hybridizes to a mRNA 2000 bases long that is inducible by dexamethasone. With this clone as probe we isolated from a bacteriophage lambda rat DNA library genomic clones which together span a region of 32 kilobase pairs (kb). Heteroduplex analysis revealed that the gene extends over 19 kb and is interrupted by at least 11 introns. To characterize the presumptive control region the DNA sequence around the 5' end of the TO gene was determined. S1 nuclease protection experiments revealed two separate start sites for TO mRNA transcription within this region. Images Fig. 1. Fig. 2. Fig. 4. Fig. 6. Fig. 7. PMID:6327261

  2. Chronic hypoxia decreases arterial and venous compliance in isolated perfused rat lungs: an effect that is reversed by exogenous l-arginine

    PubMed Central

    Jin, Yi; Chen, Bernadette; Calvert, Thomas J.; Chicoine, Louis G.; Liu, Yusen

    2013-01-01

    Chronic hypoxia (CH)-induced pulmonary hypertension is characterized by vasoconstriction and vascular remodeling, leading to right ventricular dysfunction. Given the role of arterial compliance (Ca) in right ventricular work, a decrease in Ca would add to right ventricular work. Nitric oxide (NO) is a potent vasodilator made by NO synthases from l-arginine (l-Arg). However, little is known of the effect of l-Arg on vascular compliance (Cv) in the lung. We hypothesized that exposure to CH would decrease Ca and that this effect would be reversed by exogenous l-Arg. Sprague-Dawley rats were exposed to either normoxia or CH for 14 days; the lungs were then isolated and perfused. Vascular occlusions were performed and modeled using a three-compliance, two-resistor model. Pressure-flow curves were generated, and a distensible vessel model was used to estimate distensibility and a vascular resistance parameter (R0). Hypoxia resulted in the expected increase in arterial resistance (Ra) as well as a decrease in both Ca and Cv. l-Arg had little effect on Ra, Ca, or Cv in isolated lungs from normoxic animals. l-Arg decreased Ra in lungs from CH rats and redistributed compliance to approximately that found in normoxic lungs. CH increased R0, and l-Arg reversed this increase in R0. l-Arg increased exhaled NO, and inhibition of l-Arg uptake attenuated the l-Arg-induced increase in exhaled NO. These data demonstrate that the CH-induced decrease in Ca was reversed by l-Arg, suggesting that l-Arg may improve CH-induced right ventricular dysfunction. PMID:23103497

  3. Coronary vasodilator effects of endogenous cannabinoids in vasopressin-preconstricted unpaced rat isolated hearts.

    PubMed

    Wagner, Jens A; Abesser, Marco; Karcher, Jan; Laser, Martin; Kunos, George

    2005-09-01

    The mechanisms by which cannabinoids alter coronary vascular tone and cardiac performance are controversial. We investigated the effects of various cannabinoids in spontaneously beating Langendorff-perfused rat hearts. Bolus injections of anandamide (0.1-1 micromol) caused no change in coronary flow (CF) or left ventricular systolic pressure (LVSP). In hearts preperfused with vasopressin to induce vasoconstrictor tone, anandamide or the selective CB1 receptor agonist ACEA (1-100 nmol) dose-dependently increased CF by up to 267% and LVSP by 20 mm Hg. The metabolically stable endocannabinoid derivatives, R-methanandamide and noladin ether, displayed similar effects. In contrast, Delta-THC (10-100 nmol), the major psychoactive ingredient of cannabis, strongly decreased CF and LVSP. The CB2 receptor agonist JWH-133 (10-100 nmol) elicited vasodilator and positive inotropic effects only at higher doses. The CB1 antagonists SR141716A and AM-251 as well as the potassium channel inhibitors tetraethylammonium and iberiotoxin blocked the anandamide-induced increases in CF and LVSP, whereas the CB2 antagonist SR144528 and the putative "CB3 antagonist" O-1918 did not have an inhibitory effect. Immunohistochemistry revealed the presence of cardiac CB1 but no CB2 receptors. Anandamide and 2-arachidonoylglycerol were detected in heart tissue. However, combined application of fatty acid amidohydrolase inhibitors and the transport inhibitor AM-404 to augment tissue levels of endocannabinoids was without effect on CF or LVSP. We conclude that in the rat isolated heart with reestablished vasoconstrictor tone, cannabinoids including anandamide elicit coronary vasodilation and a secondary increase in contractility via CB1 receptors and potassium channels.

  4. Physiologic significance of the phosphorylation potential in isolated perfused rat hearts (/sup 31/P NMR)

    SciTech Connect

    Watters, T.; Wikman-Coffelt, J.; Wu, S.; Wendland, M.; James, T.; Sievers, R.; Botvinick, E.; Parmley, W.

    1986-03-05

    The authors assessed the metabolic and mechanical effects of changes in coronary perfusion pressure (CPP) and afterload (A) in isolated working apex-ejecting rat hearts perfused with Krebs-Henseleit solution containing an excess of O/sub 2/ and substrate. Log(phosphorylation potential) or log (ATP)/(ADP)x (Pi), designated (L), and log (PCR)/(Pi), designated (L*), were calculated from HPLC measurements after rapid freeze-clamping. Increasing CPP from 80-140 cm H/sub 2/O caused an increase in coronary flow(flow), developed pressure(DevP), O/sub 2/ consumption (VO/sub 2/), L, L*, and CO. L and L* were directly related to VO/sub 2/ and CO. Increasing A from 80-140 cm H/sub 2/O caused an increase in DevP and VO/sub 2/, but a decrease in L, L*, and CO. L and L* were inversely linearly related to VO/sub 2/ but were directly linearly related to CO. In both experiments, L and L* are directly related to CO, suggesting that determination of L* (which can be done with /sup 31/P NMR spectroscopy) may be a useful non-invasive method for determining cardiac pump function curves. L and L* may be related to the Frank-Starling mechanism. In a separate experiment using /sup 31/P NMR spectroscopy of isovolumic (left ventricular balloon) perfused rat hearts, increasing CPP caused a direct linear increase in flow, DevP, and L*, confirming the L* results reported above with CPP experiments using the rapid freeze-clamp technique.

  5. Physiologic significance of the phosphorylation potential in isolated perfused rat hearts (31-P NMR)

    SciTech Connect

    Watters, T.; Wikman-Coffelt, J.; Wu, S.; Wendland, M.; James, T.; Sievers, R.; Botvinick, E.; Parmley, W.

    1986-03-05

    The authors assessed the metabolic and mechanical effects of changes in coronary perfusion pressure (CPP) and afterload (A) in isolated working apex-ejecting rat hearts perfused with Krebs-Henseleit solution containing an excess of O/sub 2/ and substrate. Log (phosphorylation potential) or log (ATP)/(ADP)x (Pi), designated (L), and log (PCR)/(Pi), designated (L*), were calculated from HPLC measurements after rapid freeze-clamping. Increasing CPP from 80-140 cm H/sub 2/O caused an increase in coronary flow (flow), developed pressure (DevP), O/sub 2/ consumption (VO/sub 2/), L, L*, and CO. L and L* were directly related to VO/sub 2/ and CO. Increasing A from 80-140 cm H/sub 2/O caused an increase in DevP and VO/sub 2/, but a decrease in L, L*, and CO. L and L* were inversely linearly related to VO/sub 2/ but were directly linearly related to CO. In both experiments, L and L* are directly related to CO, suggesting that determination of L* (which can be done with 31-P NMR spectroscopy) may be a useful non-invasive method for determining cardiac pump function curves. L and L* may be related to the Frank-Starling mechanism. In a separate experiment using 31-P NMR spectroscopy of isovolumic (left ventricular balloon) perfused rat hearts, increasing CPP caused a direct linear increase in flow, DevP, and L*, confirming the L* results reported above with CPP experiments using the rapid freeze-clamp technique.

  6. A self-calibrating telemetry system for measurement of ventricular pressure-volume relations in conscious, freely moving rats.

    PubMed

    Uemura, Kazunori; Kawada, Toru; Sugimachi, Masaru; Zheng, Can; Kashihara, Koji; Sato, Takayuki; Sunagawa, Kenji

    2004-12-01

    Using Bluetooth wireless technology, we developed an implantable telemetry system for measurement of the left ventricular pressure-volume relation in conscious, freely moving rats. The telemetry system consisted of a pressure-conductance catheter (1.8-Fr) connected to a small (14-g) fully implantable signal transmitter. To make the system fully telemetric, calibrations such as blood resistivity and parallel conductance were also conducted telemetrically. To estimate blood resistivity, we used four electrodes arranged 0.2 mm apart on the pressure-conductance catheter. To estimate parallel conductance, we used a dual-frequency method. We examined the accuracy of calibrations, stroke volume (SV) measurements, and the reproducibility of the telemetry. The blood resistivity estimated telemetrically agreed with that measured using an ex vivo cuvette method (y=1.09x - 11.9, r2= 0.88, n=10). Parallel conductance estimated by the dual-frequency (2 and 20 kHz) method correlated well with that measured by a conventional saline injection method (y=1.59x - 1.77, r2= 0.87, n=13). The telemetric SV closely correlated with the flowmetric SV during inferior vena cava occlusions (y=0.96x + 7.5, r2=0.96, n=4). In six conscious rats, differences between the repeated telemetries on different days (3 days apart on average) were reasonably small: 13% for end-diastolic volume, 20% for end-systolic volume, 28% for end-diastolic pressure, and 6% for end-systolic pressure. We conclude that the developed telemetry system enables us to estimate the pressure-volume relation with reasonable accuracy and reproducibility in conscious, untethered rats.

  7. Assessment of regional left ventricular myocardial function in rats after acute occlusion of left anterior descending artery by two-dimensional speckle tracking imaging.

    PubMed

    Fu, Qian; Xie, Mingxing; Wang, Jing; Wang, Xinfang; Lv, Qing; Lu, Xiaofang; Fang, Lingyun; Chang, Long

    2009-12-01

    This study evaluated the change in regional left ventricular myocardial function in rats following acute occlusion of the left anterior descending coronary artery (LAD) by using two-dimensional speckle tracking imaging (2D-STI). Sixty Wistar rats were randomly divided into two groups, a myocardial infarction (MI) group, in which 50 rats were subjected to LAD occlusion for 30-45 min, and a sham-operated (SHAM) group that contained 10 rats serving as control. Echocardiography was performed at baseline and 1, 4 and 8 week(s) after the operation. High frequency two-dimensional images of left ventricular short axis at papillary muscle level were recorded. Peak systolic radial strain (PRS) and circumferential strain (PCS) were measured in the mid-ventricle in short-axis view by using EchoPAC workstation. Left ventricular internal diameter at diastole (LVIDd) and systole (LVIDs), fractional shortening (FS), ejection fraction (EF) and left ventricular mass (LVM) were measured by anatomical M-model echocardiography. Infarct size was measured using triphenyl tetrazolium chloride (TTC) staining 1 week and 8 weeks after the operation. Fibrosis of left ventricular myocardium was displayed using Van Gieson staining 1 week after the infarction. In terms of the TTC staining results, the left ventricle fell into three categories: infarcted, peri-infarcted and remote myocardial regions. Compared with those at baseline and in the SHAM group, (1) PRS and PCS in the infarcted, peri-infarcted and remote myocardial regions were significantly decreased in the MI group within 1 week after the operation (P<0.05) and the low levels lasted 8 weeks; (2) Compared with those at baseline, LVIDd, LVIDs, FS, EF and LVM in the MI group showed no significant difference 1 week after the operation (P>0.05). However, LVIDd, LVIDs and LVM were increased significantly 4 and 8 weeks after the operation (P<0.05), and FS and EF were decreased substantially (P<0.05). Van Gieson staining showed that fibrosis

  8. Isolation and Molecular Identification of Bartonellae from Wild Rats (Rattus Species) in Malaysia

    PubMed Central

    Tay, Sun Tee; Mokhtar, Aida Syafinaz; Zain, Siti Nursheena Mohd; Low, Kiat Cheong

    2014-01-01

    This study describes our investigation on the prevalence and molecular identification of bartonellae from Rattus diardii and R. norvegicus in the urban areas of Malaysia. Of 95 rats investigated, Bartonella tribocorum, B. rattimassiliensis, B. coopersplainsensis, B. elizabethae, and B. queenslandensis were isolated from kidney and spleen homogenates of four rats. Bartonellae DNA was amplified from the rat organ tissues by using primers specific for the bartonellae RNA polymerase beta subunit (rpoB) gene in nine other rats. Sequence analysis of the rpoB gene fragments shows the identification of B. queenslandensis in five rats, B. elizabethae in three rats, and B. tribocorum in one rat. Combining the results of isolation and molecular detection of bartonellae, we found that the prevalence of Bartonella infection in the Rattus spp. investigated in this study was 13.7%. Implementation of effective rat control program in the urban areas is necessary to prevent the spillover of bartonellosis from rats to humans. PMID:24732465

  9. Water and nonelectrolyte permeability of isolated rat hepatocytes

    SciTech Connect

    Alpini, G.; Garrick, R.A.; Jones, M.J.; Nunes, R.; Tavoloni, N.

    1986-12-01

    We have measured the diffusive permeability coefficients of isolated rat hepatocytes to /sup 3/H/sub 2/O, (/sup 14/C)urea, (/sup 14/C)erythritol, (/sup 14/C)mannitol, (/sup 3/H)sucrose, and (/sup 3/H)inulin, employing a technique previously developed for erythrocytes (Redwood et al., J. Gen. Physiol 64:706-729, 1974). Diffusion coefficients for the tracer molecules were measured in packed hepatocytes, supernatant fluid, and intracellular medium (lysed hepatocytes) and were calculated assuming one-dimensional semi-infinite diffusion through a homogeneous medium. By applying the series-parallel pathway model, the following permeability coefficients (10(-5) cm/sec) for the hepatocyte plasma membrane were obtained. /sup 3/H/sub 2/O, 98.6 +/- 18.4; (/sup 14/C)urea, 18.2 +/- 5.3; (/sup 14/C)erythritol, 4.8 +/- 1.6; (/sup 14/C)mannitol, 3.1 +/- 1.4; (/sup 3/H)sucrose, 0; (/sup 3/H)inulin, 0. These results indicate that isolated rat hepatocytes are highly permeable to water and polar nonelectrolytes, when compared with other transporting epithelia. This relatively high cellular permeability is consistent with a model in which nonelectrolyte permeation is via an aqueous pathway of equivalent pore diameter of 8-12 A. The finding that (/sup 14/C)erythritol and (/sup 14/C)mannitol cross the hepatocyte plasma membrane indicates that these molecules enter the bile canaliculus through the transcellular route. Conversely, the failure of (/sup 3/H)sucrose and (/sup 3/H)inulin to permeate the hepatocyte in the isolated condition supports the concept that biliary entry of these large carbohydrates, at least that fraction which cannot be accounted for by a vesicular mechanism, must occur via the transjunctional shunt pathway.

  10. Effect of Late Gadolinium Enhancement on the Recovery of Left Ventricular Systolic Function After Pulmonary Vein Isolation.

    PubMed

    Addison, Daniel; Farhad, Hoshang; Shah, Ravi V; Mayrhofer, Thomas; Abbasi, Siddique A; John, Roy M; Michaud, Gregory F; Jerosch-Herold, Michael; Hoffmann, Udo; Stevenson, William G; Kwong, Raymond Y; Neilan, Tomas G

    2016-09-26

    The factors that predict recovery of left ventricular (LV) systolic dysfunction among patients with atrial fibrillation (AF) are not completely understood. Late gadolinium enhancement (LGE) of the LV has been reported among patients with AF, and we aimed to test whether the presence LGE was associated with subsequent recovery of LV systolic function among patients with AF and LV dysfunction. From a registry of 720 consecutive patients undergoing a cardiac magnetic resonance study prior to pulmonary vein isolation (PVI), patients with LV systolic dysfunction (ejection fraction [EF] <50%) were identified. The primary outcome was recovery of LVEF defined as an EF >50%; a secondary outcome was a combined outcome of subsequent heart failure (HF), admission, and death. Of 720 patients, 172 (24%) had an LVEF of <50% prior to PVI. The mean LVEF pre-PVI was 41±6% (median 43%, range 20% to 49%). Forty-three patients (25%) had LGE (25 [58%] ischemic), and the extent of LGE was 7.5±4% (2% to 19%). During follow-up (mean 42 months), 91 patients (53%) had recovery of LVEF, 68 (40%) had early recurrence of AF, 65 (38%) had late AF, 18 (5%) were admitted for HF, and 23 died (13%). Factors associated with nonrecovery of LVEF were older age, history of myocardial infarction, early AF recurrence, late AF recurrence, and LGE. In a multivariable model, the presence of LGE and any recurrence of AF had the strongest association with persistence of LV dysfunction. Additionally, all patients without recurrence of AF and LGE had normalization of LVEF, and recovery of LVEF was associated with reduced HF admissions and death. In patients with AF and LV dysfunction undergoing PVI, the absence of LGE and AF recurrence are predictors of LVEF recovery and LVEF recovery in AF with associated reduction in subsequent death and heart failure. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  11. Acute Reversal of Phospholamban Inhibition Facilitates the Rhythmic Whole-cell Propagating Calcium Waves in Isolated Ventricular Myocytes

    PubMed Central

    Chan, Yi-Hsin; Tsai, Wei-Chung; Song, Zhen; Ko, Christopher Y.; Qu, Zhilin; Weiss, James N.; Lin, Shien-Fong; Chen, Peng-Sheng; Jones, Larry R.; Chen, Zhenhui

    2015-01-01

    Phospholamban (PLB) inhibits the activity of cardiac sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a). Phosphorylation of PLB during sympathetic activation reverses SERCA2a inhibition, increasing SR Ca2+ uptake. However, sympathetic activation also modulates multiple other intracellular targets in ventricular myocytes (VMs), making it impossible to determine the specific effects of reversal of PLB inhibition on the spontaneous SR Ca2+ release. Therefore, it remains unclear how PLB regulates rhythmic activity in VMs. Here we used the Fab fragment of 2D12, a monoclonal anti-PLB antibody, to test how acute reversal of PLB inhibition affects the spontaneous SR Ca2+ release in normal VMs. Ca2+ sparks and spontaneous Ca2+ waves (SCWs) were recorded in the line-scan mode of confocal microscopy using the Ca2+ fluorescent dye Fluo-4 in isolated permeabilized mouse VMs. Fab, which reverses PLB inhibition, significantly increased the frequency, amplitude, and spatial/temporal spread of Ca2+ sparks in VMs exposed to 50 nM free [Ca2+]. At physiological diastolic free [Ca2+] (100–200 nM), Fab facilitated the formation of whole-cell propagating SCWs. At higher free [Ca2+], Fab increased the frequency and velocity, but decreased the decay time of the SCWs. cAMP had little additional effect on the frequency or morphology of Ca2+ sparks or SCWs after Fab addition. These findings were complemented by computer simulations. In conclusion, acute reversal of PLB inhibition alone significantly increased the spontaneous SR Ca2+ release, leading to the facilitation and organization of whole-cell propagating SCWs in normal VMs. PLB thus plays a key role in subcellular Ca2+ dynamics and rhythmic activity of VMs. PMID:25596331

  12. Treatment with a copper-selective chelator causes substantive improvement in cardiac function of diabetic rats with left-ventricular impairment

    PubMed Central

    2013-01-01

    Background Defective copper regulation is implicated as a causative mechanism of organ damage in diabetes. Treatment with trientine, a divalent-copper-selective chelator, improves arterial and renal structure/function in diabetes, wherein it also ameliorates left-ventricular (LV) hypertrophy. However, direct in vivo evidence that trientine can improve cardiac function in heart failure has hitherto been lacking. Methods To determine whether trientine treatment could improve in vivo outcome, we measured cardiac function in groups of trientine-treated diabetic (TETA-DIA), non-drug-treated diabetic (DIA) and sham-treated control (SHAM) rats, by using in vivo high-field cardiac magnetic-resonance imaging (cMRI) and an ex vivo isolated-perfused working heart method. Forty age-matched animals underwent a cMRI scan after which 12 were randomized to the SHAM group and 28 underwent streptozotocin-injection; of these, 25 developed stable diabetes, and 12 were then randomized to receive no treatment for 16 weeks (DIA) and the other 13 to undergo 8-weeks’ untreated diabetes followed by 8-weeks’ drug treatment (TETA-DIA). Animals were studied again by cMRI at 8 and 16 weeks following disease induction, and finally by measurement of ex vivo cardiac function. Results After eight weeks diabetes, rats (DIA/TETA-DIA) had developed significant impairment of LV function, as judged by impairment of ejection fraction (LVEF), cardiac output (CO), and LV mass (LVM)/body-mass (all P < 0.001), as well as other functional indexes. LVEF, CO (both P < 0.001) and the other indexes deteriorated further at 16 weeks in DIA, whereas trientine (TETA-DIA) improved cardiac function by elevating LVEF and CO (both P < 0.001), and also partially reversed the increase in LVM/body-mass (P < 0.05). In ex vivo hearts from DIA, the CO response to increasing preload pressure was deficient compared with SHAM (P < 0.001) whereas the preload-CO relationship was significantly improved in

  13. Treatment with a copper-selective chelator causes substantive improvement in cardiac function of diabetic rats with left-ventricular impairment.

    PubMed

    Lu, Jun; Pontré, Beau; Pickup, Stephen; Choong, Soon Y; Li, Mingming; Xu, Hong; Gamble, Gregory D; Phillips, Anthony R J; Cowan, Brett R; Young, Alistair A; Cooper, Garth J S

    2013-01-31

    Defective copper regulation is implicated as a causative mechanism of organ damage in diabetes. Treatment with trientine, a divalent-copper-selective chelator, improves arterial and renal structure/function in diabetes, wherein it also ameliorates left-ventricular (LV) hypertrophy. However, direct in vivo evidence that trientine can improve cardiac function in heart failure has hitherto been lacking. To determine whether trientine treatment could improve in vivo outcome, we measured cardiac function in groups of trientine-treated diabetic (TETA-DIA), non-drug-treated diabetic (DIA) and sham-treated control (SHAM) rats, by using in vivo high-field cardiac magnetic-resonance imaging (cMRI) and an ex vivo isolated-perfused working heart method. Forty age-matched animals underwent a cMRI scan after which 12 were randomized to the SHAM group and 28 underwent streptozotocin-injection; of these, 25 developed stable diabetes, and 12 were then randomized to receive no treatment for 16 weeks (DIA) and the other 13 to undergo 8-weeks' untreated diabetes followed by 8-weeks' drug treatment (TETA-DIA). Animals were studied again by cMRI at 8 and 16 weeks following disease induction, and finally by measurement of ex vivo cardiac function. After eight weeks diabetes, rats (DIA/TETA-DIA) had developed significant impairment of LV function, as judged by impairment of ejection fraction (LVEF), cardiac output (CO), and LV mass (LVM)/body-mass (all P < 0.001), as well as other functional indexes. LVEF, CO (both P < 0.001) and the other indexes deteriorated further at 16 weeks in DIA, whereas trientine (TETA-DIA) improved cardiac function by elevating LVEF and CO (both P < 0.001), and also partially reversed the increase in LVM/body-mass (P < 0.05). In ex vivo hearts from DIA, the CO response to increasing preload pressure was deficient compared with SHAM (P < 0.001) whereas the preload-CO relationship was significantly improved in TETA-DIA animals (P < 0

  14. [Effects of Fluoxetine on Nogo Expression and Collagen Production with Decrease of Pulmonary Artery Pressure in Rats with Right Ventricular Failure.

    PubMed

    Ran, Xun; Zhao, Jian-Xun; Nie, Hu; Chen, Yu-Cheng

    2016-11-01

    To investigate the effect of fluoxetine on neurite growth inhibitor (Nogo) expession and collagen production of cardiac tissue in rats with right heart failure and pulmonary hypertension. Thirty one male SD rats were randomly divided into the treatment group,right heart failure group and normal control group.The rats in the treatment group and right heart failure group received intrapertioneal injection of monocrotaline (MCT,60 mg/kg) to induce pulmonary hypertension and right heart failure.After 21 days,the rats in treatment group were given fluoxetine of 10 mg/(kg×d) by gavage per day for 21 days,the rats in the other two groups were given saline.HE staining was used to observe the pulmonary artery and right ventricular myocardial tissue in rats.The collagen formation in right ventricular myocardium was observed by Masson staining.The expressions of Nogo-A, Nogo-B,type1collagen and type 3 collagen mRNA in myocardium were measured by real-time fluorescence quantitative PCR,while the semi quantitative measurement of Nogo protein level was detected by Western blot. After the intervention of fluoxetine,pulmonary artery stenosis was significantly reduced,myocardial tissue lesion decreased,collagen synthesis decreased in right ventricular myocardium.RT-PCR showed that mRNA of Nogo-A decreased,and mRNA of Nogo-B increased (P<0.05).Western blot showed that the expression of Nogo-A protein decreased,while Nogo-B1 protein expression increased (P<0.05),Nogo-B2 expression was not significantly changed (P>0.05). Nogo may affect the collagen synthesis in right heart failure,and partly involved in myocardial fibrosis.

  15. Myocardial reverse remodeling after pressure unloading is associated with maintained cardiac mechanoenergetics in a rat model of left ventricular hypertrophy.

    PubMed

    Ruppert, Mihály; Korkmaz-Icöz, Sevil; Li, Shiliang; Németh, Balázs Tamás; Hegedűs, Péter; Brlecic, Paige; Mátyás, Csaba; Zorn, Markus; Merkely, Béla; Karck, Matthias; Radovits, Tamás; Szabó, Gábor

    2016-09-01

    Pressure unloading represents the only effective therapy in increased afterload-induced left ventricular hypertrophy (LVH) as it leads to myocardial reverse remodeling (reduction of increased left ventricular mass, attenuated myocardial fibrosis) and preserved cardiac function. However, the effect of myocardial reverse remodeling on cardiac mechanoenergetics has not been elucidated. Therefore, we aimed to provide a detailed hemodynamic characterization in a rat model of LVH undergoing pressure unloading. Pressure overload was induced in Sprague-Dawley rats by abdominal aortic banding for 6 (AB 6th wk) or 12 wk (AB 12th wk). Sham-operated animals served as controls. Aortic debanding procedure was performed after the 6th experimental week (debanded 12th wk) to investigate the regression of LVH. Pressure unloading resulted in significant reduction of LVH (heart weight-to-tibial length ratio: 0.38 ± 0.01 vs. 0.58 ± 0.02 g/mm, cardiomyocyte diameter: 18.3 ± 0.1 vs. 24.1 ± 0.8 μm debanded 12th wk vs. AB 12th wk, P < 0.05), attenuated the extracellular matrix remodeling (Masson's score: 1.37 ± 0.13 vs. 1.73 ± 0.10, debanded 12th wk vs. AB 12th wk, P < 0.05), provided protection against the diastolic dysfunction, and reversed the maladaptive contractility augmentation (slope of end-systolic pressure-volume relationship: 1.39 ± 0.24 vs. 2.04 ± 0.09 mmHg/μl, P < 0.05 debanded 12th wk vs. AB 6th wk, P < 0.05). In addition, myocardial reverse remodeling was also associated with preserved ventriculoarterial coupling and increased mechanical efficiency (50.6 ± 2.8 vs. 38.9 ± 2.5%, debanded 12th wk vs. AB 12th wk, P < 0.05), indicating a complete functional and mechanoenergetic recovery. According to our best knowledge, this is the first study demonstrating that the regression of LVH is accompanied by maintained cardiac mechanoenergetics. Copyright © 2016 the American Physiological Society.

  16. [Effects of different Chinese medicine therapeutic methods on the ventricular remodeling and the heart function in chronic heart failure rats of Shen-yang deficiency syndrome].

    PubMed

    Wang, Jing; Wu, Shi-Da; Chen, Shou-Chun

    2012-09-01

    To observe the effects of warming yang method, nourishing yin method, activating blood method, and the combined treatment method on the ventricular remodeling (VR) and the heart function of heart failure (HF) rats of Shen-yang deficiency syndrome (SYDS). The Sprague-Dawley (SD) HF rat model of SYDS was established by continuously intravenous dripping adriamycin after economizing bilateral thyroid tissues. Rats were then randomly divided into the model group (administered with normal saline at the daily dose of 6 mL/kg by gastrogavage), the warming yang group (administered with Wenyang Jianxinling Extractum at the daily dose of 6 mL/kg by gastrogavage), the activating blood group (administered with Ligusticum Wallichii and Salvia Miltiorrhiza Extractum at the daily dose of 6 mL/kg by gastrogavage), the nourishing yin group (administered with Radix Ophiopogonis and Rhizoma Anemarrhenae Extractum at the daily dose of 6 mL/kg by gastrogavage), and the combined treatment group (administered with Yin-Yang Supplementing Extractum at the daily dose of 6 mL/kg by gastrogavage), 10 in each group. Another 10 SD rats were taken as the normal control group. They ate food and drank water freely. All rats were intervened for four successive weeks. The left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), maximal rate of left ventricular pressure of development ( +dp/dtmax), and maximal rate of left ventricular pressure of decline (-dp/dtmax) were observed. The systolic blood pressure (SBP) and the diastolic blood pressure (DBP) were determined. The mean arterial pressure (MAP) was calculated. The heart rate (HR) was recorded. Then all rats were killed and their hearts were taken out to weigh the heart mass (HM), the left ventricular mass (LVM), the right ventricular mass (RVM). The heart mass index (HMI) and the left ventricular mass index (LVMI) were calculated. The mRNA expression of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor

  17. Unique preferential conduction within the isolated septal substrate in a patient with ventricular tachycardia complicated with non-ischemic dilated cardiomyopathy.

    PubMed

    Watanabe, Masaya; Yokoshiki, Hisashi; Mitsuyama, Hirofumi; Mizukami, Kazuya; Tsutsui, Hiroyuki

    2013-01-01

    We describe the case of a 67-year-old woman with non-ischemic dilated cardiomyopathy who underwent successful radiofrequency catheter ablation for ventricular tachycardia (VT) originated from the isolated ventricular septal substrate. Pacemapping exhibited either left, identical to clinical VT, or right bundle branch block like wide QRS morphology. Time interval from the stimulus to QRS onset (St-QRS) was prolonged at the center of the substrate, while St-QRS at the border was shortened. Difference in the morphology of pacemapping was dependent on whether or not the pacing stimulus could propagate directly into the right ventricle due to the possible intramural conduction disturbance. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Contractility of Right Ventricular Myocardium in Male and Female Rats during Physiological and Pathological Hypertrophy.

    PubMed

    Protsenko, Yu L; Balakin, A A; Kuznetsov, D A; Kursanov, A G; Lisin, R V; Mukhlynina, E A; Lookin, O N

    2017-01-01

    Sex differences in the morphogenesis and adaptation of the mechanisms controlling myocardium contractility during physiological and pathological hypertrophy of the right ventricle were demonstrated in mature rats. The study revealed sex-dependent effects of physiological and pathological cardiac hypertrophy on the coefficient of variation of the cardiomyocyte diameter, length-dependent control of the contractile force, and the maximum velocity of isotonic shortening.

  19. beta-Adrenergic modulation of the inwardly rectifying potassium channel in isolated human ventricular myocytes. Alteration in channel response to beta-adrenergic stimulation in failing human hearts.

    PubMed Central

    Koumi, S; Backer, C L; Arentzen, C E; Sato, R

    1995-01-01

    The beta-adrenergic modulation of the inwardly-rectifying K+ channel (IK1) was examined in isolated human ventricular myocytes using patch-clamp techniques. Isoproterenol (ISO) reversibly depolarized the resting membrane potential and prolonged the action potential duration. Under the whole-cell C1- -free condition, ISO applied via the bath solution reversibly inhibited macroscopic IdK1. The reversal potential of the ISO-sensitive current was shifted by approximately 60 mV per 10-fold change in the external K+ concentration and was sensitive to Ba2+. The ISO-induced inhibition of IK1 was mimicked by forskolin and dibutyrl cAMP, and was prevented by including a cAMP-dependent protein kinase (PKA) inhibitor (PKI) in the pipette solution. In single-channel recordings from cell-attached patches, bath applied ISO could suppress IK1 channels by decreasing open state probability. Bath application of the purified catalytic sub-unit of PKA to inside-out patches also inhibited IK1 and the inhibition could be antagonized by alkaline phosphatase. When beta-adrenergic modulation of IK1 was compared between ventricular myocytes isolated from the failing and the nonfailing heart, channel response to ISO and PKA was significantly reduced in myocytes from the failing heart. Although ISO inhibited IK1 in a concentration-dependent fashion in both groups, a half-maximal concentration was greater in failing (0.12 microM) than in nonfailing hearts (0.023 microM). These results suggest that IK1 in human ventricular myocytes can be inhibited by a PKA-mediated phosphorylation and the modulation is significantly reduced in ventricular myocytes from the failing heart compared to the nonfailing heart. Images PMID:8675658

  20. Isolation and Molecular Characterization of Leptospira interrogans and Leptospira borgpetersenii Isolates from the Urban Rat Populations of Kuala Lumpur, Malaysia

    PubMed Central

    Benacer, Douadi; Zain, Siti Nursheena Mohd; Amran, Fairuz; Galloway, Renee L.; Thong, Kwai Lin

    2013-01-01

    Rats are considered the principal maintenance hosts of Leptospira. The objectives of this study were isolation and identification of Leptospira serovars circulating among urban rat populations in Kuala Lumpur. Three hundred urban rats (73% Rattus rattus and 27% R. norvegicus) from three different sites were trapped. Twenty cultures were positive for Leptospira using dark-field microscopy. R. rattus was the dominant carrier (70%). Polymerase chain reaction (PCR) confirmed that all isolates were pathogenic Leptospira species. Two Leptospira serogroups, Javanica and Bataviae, were identified using microscopic agglutination test (MAT). Pulsed-field gel electrophoresis (PFGE) identified two serovars in the urban rat populations: L. borgpetersenii serovar Javanica (85%) and L. interrogans serovar Bataviae (15%). We conclude that these two serovars are the major serovars circulating among the urban rat populations in Kuala Lumpur. Despite the low infection rate reported, the high pathogenicity of these serovars raises concern of public health risks caused by rodent transmission of leptospirosis. PMID:23358635

  1. A novel hydrodynamic approach of drag-reducing polymers to improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats

    PubMed Central

    Zhang, Xinlu; Wang, Xu; Hu, Feng; Zhou, Boda; Chen, Hai-Bin; Zha, Daogang; Liu, Yili; Guo, Yansong; Zheng, Lemin; Xiu, Jiancheng

    2016-01-01

    Drag-reducing polymers (DRPs), when added in minute concentrations, have been shown to decrease peripheral vascular resistance. In this study, the effect of DRPs on the hypertension-induced left ventricular hypertrophy and aortic remodeling was evaluated in spontaneously hypertensive rats (SHR). Male SHR and age-matched Wistar rats were divided into four groups and received intravenous injection of normal saline (NS) or DRPs. Body weight (BW), heart rate (HR) and systolic blood pressure (SBP) were measured. Echocardiography was used to evaluate the changes in left ventricle (LV) function and global wall motion. The LV and aorta were stained by hematoxylin and eosin. Cell size of cardiomyocytes and aortic medial thickness were evaluated for each section. The expression of endothelin-1 (ET-1) of LV and aorta was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. There was no significant difference in the increase of SBP among SHR + NS, SHR + 10DRP and SHR + 20DRP groups. SHR + NS group had markedly smaller left ventricular end-systolic diameter and left ventricular end-diastolic diameter but bigger anterior and posterior systolic wall thicknesses, while there was no significant difference in fractional shortening and ejection fraction. The cross-sectional areas (CSAs) of cardiomyocytes and the medial thickness of the aorta in SHR + 10 (ppm) DRP and SHR + 20 (ppm) DRP groups were significantly reduced compared with SHR + NS group. The expression of ET-1 in SHR + 10DRP and SHR + 20DRP groups was significantly attenuated. These results suggest that chronic treatment with DRPs can protect against left ventricular hypertrophy and aortic remodeling. DRPs may offer a new approach to the treatment of left ventricular hypertrophy and aortic remodeling caused by hypertension. PMID:28008249

  2. A novel hydrodynamic approach of drag-reducing polymers to improve left ventricular hypertrophy and aortic remodeling in spontaneously hypertensive rats.

    PubMed

    Zhang, Xinlu; Wang, Xu; Hu, Feng; Zhou, Boda; Chen, Hai-Bin; Zha, Daogang; Liu, Yili; Guo, Yansong; Zheng, Lemin; Xiu, Jiancheng

    Drag-reducing polymers (DRPs), when added in minute concentrations, have been shown to decrease peripheral vascular resistance. In this study, the effect of DRPs on the hypertension-induced left ventricular hypertrophy and aortic remodeling was evaluated in spontaneously hypertensive rats (SHR). Male SHR and age-matched Wistar rats were divided into four groups and received intravenous injection of normal saline (NS) or DRPs. Body weight (BW), heart rate (HR) and systolic blood pressure (SBP) were measured. Echocardiography was used to evaluate the changes in left ventricle (LV) function and global wall motion. The LV and aorta were stained by hematoxylin and eosin. Cell size of cardiomyocytes and aortic medial thickness were evaluated for each section. The expression of endothelin-1 (ET-1) of LV and aorta was examined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry. There was no significant difference in the increase of SBP among SHR + NS, SHR + 10DRP and SHR + 20DRP groups. SHR + NS group had markedly smaller left ventricular end-systolic diameter and left ventricular end-diastolic diameter but bigger anterior and posterior systolic wall thicknesses, while there was no significant difference in fractional shortening and ejection fraction. The cross-sectional areas (CSAs) of cardiomyocytes and the medial thickness of the aorta in SHR + 10 (ppm) DRP and SHR + 20 (ppm) DRP groups were significantly reduced compared with SHR + NS group. The expression of ET-1 in SHR + 10DRP and SHR + 20DRP groups was significantly attenuated. These results suggest that chronic treatment with DRPs can protect against left ventricular hypertrophy and aortic remodeling. DRPs may offer a new approach to the treatment of left ventricular hypertrophy and aortic remodeling caused by hypertension.

  3. Calcium-activated non-selective cation channel in ventricular cells isolated from adult guinea-pig hearts.

    PubMed Central

    Ehara, T; Noma, A; Ono, K

    1988-01-01

    1. A class of Ca2+-activated non-selective cation channel was identified in ventricular cells, which were dissociated from adult guinea-pig hearts using collagenase. 2. Under cell-attached conditions the patch electrode filled with a Na+-rich solution recorded no obvious single-channel current at the resting membrane potential. Subsequent superfusion of the ventricular cell with a Na+-free Tyrode solution induced an inward-going single-channel current as well as contracture of the cell. Kinetics of this channel were not affected by varying the membrane potential. 3. Single-channel currents showing a conductance similar to those observed in the cell-attached patches were recorded in isolated inside-out membrane patches when the inner side of the membrane was exposed to a free Ca2+ concentration ([Ca2+]i) higher than 0.3 microM. The slope conductance of the channel was 14.8 +/- 2.9 pS (mean +/- S.D., n = 17) at 20-25 degrees C. 4. The reversal potential examined in the inside-out patch was about 0 mV irrespective of the Na+-rich, K+-rich, Li+-rich or Cs+-rich solutions on either side of the membrane, thereby indicating that the channel was almost equally permeable to these cations. 5. The open probability of the channel was increased by raising [Ca2+]i with the maximum value of 0.93 +/- 0.17 (n = 4) at about 10 microM [Ca2+]i. The dose-response relation was fitted to the saturation kinetics with a Hill coefficient of 3.0 and a half-maximum concentration of 1.2 microM [Ca2+]i. 6. The gating kinetics were complex; both the open and closed time histograms showed at least two exponential components with time constants of 3.8 +/- 1.3 ms and 140 +/- 110 ms for open time and 1.8 +/- 1.1 ms and 14.9 +/- 5.3 ms for closed time (n = 4) at 10 microM [Ca2+]i. Reduction of [Ca2+]i resulted in both a decrease of the time constant of the slow component in the open time histogram and an increase of the two time constants of the closed time histogram. 7. Contribution of the channel

  4. Proteomic analysis of lamellar bodies isolated from rat lungs

    PubMed Central

    Wang, Pengcheng; Chintagari, Narendranath Reddy; Narayanaperumal, Jeyaparthasarathy; Ayalew, Sahlu; Hartson, Steven; Liu, Lin

    2008-01-01

    Background Lamellar bodies are lysosome-related secretory granules and store lung surfactant in alveolar type II cells. To better understand the mechanisms of surfactant secretion, we carried out proteomic analyses of lamellar bodies isolated from rat lungs. Results With peptide mass fingerprinting by Matrix Assisted Laser Desorption/Ionization – Time of Flight mass spectrometry, 44 proteins were identified with high confidence. These proteins fell into diverse functional categories: surfactant-related, membrane trafficking, calcium binding, signal transduction, cell structure, ion channels, protein processing and miscellaneous. Selected proteins were verified by Western blot and immunohistochemistry. Conclusion This proteomic profiling of lamellar bodies provides a basis for further investigations of functional roles of the identified proteins in lamellar body biogenesis and surfactant secretion. PMID:18577212

  5. Inhibition of phosphatidylethanolamine synthesis by glucagon in isolated rat hepatocytes.

    PubMed Central

    Tijburg, L B; Houweling, M; Geelen, M J; Van Golde, L M

    1989-01-01

    Exposure of isolated rat hepatocytes to glucagon or chlorophenylthio cyclic AMP led to an inhibition of the incorporation of [1,2-14C]ethanolamine into phosphatidylethanolamine. Pulse-chase experiments and measurement of the activities of the enzymes involved in the CDP-ethanolamine pathway provided evidence that the inhibitory effect of glucagon on the synthesis de novo of phosphatidylethanolamine was not caused by a diminished conversion of ethanolamine phosphate into CDP-ethanolamine. The observations suggested that the glucagon-induced inhibition of the biosynthesis of phosphatidylethanolamine is probably due to a decreased supply of diacylglycerols, resulting in a decreased formation of phosphatidylethanolamine from CDP-ethanolamine and diacylglycerols. PMID:2539092

  6. Isolation of plasma membrane-associated membranes from rat liver.

    PubMed

    Suski, Jan M; Lebiedzinska, Magdalena; Wojtala, Aleksandra; Duszynski, Jerzy; Giorgi, Carlotta; Pinton, Paolo; Wieckowski, Mariusz R

    2014-02-01

    Dynamic interplay between intracellular organelles requires a particular functional apposition of membrane structures. The organelles involved come into close contact, but do not fuse, thereby giving rise to notable microdomains; these microdomains allow rapid communication between the organelles. Plasma membrane-associated membranes (PAMs), which are microdomains of the plasma membrane (PM) interacting with the endoplasmic reticulum (ER) and mitochondria, are dynamic structures that mediate transport of proteins, lipids, ions and metabolites. These structures have gained much interest lately owing to their roles in many crucial cellular processes. Here we provide an optimized protocol for the isolation of PAM, PM and ER fractions from rat liver that is based on a series of differential centrifugations, followed by the fractionation of crude PM on a discontinuous sucrose gradient. The procedure requires ∼8-10 h, and it can be easily modified and adapted to other tissues and cell types.

  7. Real-time measurement of the length of a single sarcomere in rat ventricular myocytes: a novel analysis with quantum dots.

    PubMed

    Serizawa, Takahiro; Terui, Takako; Kagemoto, Tatsuya; Mizuno, Akari; Shimozawa, Togo; Kobirumaki, Fuyu; Ishiwata, Shin'ichi; Kurihara, Satoshi; Fukuda, Norio

    2011-11-01

    As the dynamic properties of cardiac sarcomeres are markedly changed in response to a length change of even ∼0.1 μm, it is imperative to quantitatively measure sarcomere length (SL). Here we show a novel system using quantum dots (QDs) that enables a real-time measurement of the length of a single sarcomere in cardiomyocytes. First, QDs were conjugated with anti-α-actinin antibody and applied to the sarcomeric Z disks in isolated skinned cardiomyocytes of the rat. At partial activation, spontaneous sarcomeric oscillations (SPOC) occurred, and QDs provided a quantitative measurement of the length of a single sarcomere over the broad range (i.e., from ∼1.7 to ∼2.3 μm). It was found that the SPOC amplitude was inversely related to SL, but the period showed no correlation with SL. We then treated intact cardiomyocytes with the mixture of the antibody-QDs and FuGENE HD, and visualized the movement of the Z lines/T tubules. At a low frequency of 1 Hz, the cycle of the motion of a single sarcomere consisted of fast shortening followed by slow relengthening. However, an increase in stimulation frequency to 3-5 Hz caused a phase shift of shortening and relengthening due to acceleration of relengthening, and the waveform became similar to that observed during SPOC. Finally, the anti-α-actinin antibody-QDs were transfected from the surface of the beating heart in vivo. The striated patterns with ∼1.96-μm intervals were observed after perfusion under fluorescence microscopy, and an electron microscopic observation confirmed the presence of QDs in and around the T tubules and Z disks, but primarily in the T tubules, within the first layer of cardiomyocytes of the left ventricular wall. Therefore, QDs are a useful tool to quantitatively analyze the movement of single sarcomeres in cardiomyocytes, under various experimental settings.

  8. The Effects of Swiprosin-1 on the Formation of Pseudopodia-Like Structures and β-Adrenoceptor Coupling in Cultured Adult Rat Ventricular Cardiomyocytes

    PubMed Central

    Nippert, Franziska; Schreckenberg, Rolf; Hess, Antonia; Weber, Martin; Schlüter, Klaus-Dieter

    2016-01-01

    Background Recent findings suggest that adult terminally differentiated cardiomyocytes adapt to stress by cellular de- and redifferentiation. In the present study we tested the hypothesis that swiprosin-1 is a key player in this process. Furthermore, the relationship between swiprosin-1 and β-adrenoceptor coupling was analyzed. Methods In order to study the function of swiprosin-1 in adult rat ventricular cardiomyocytes (ARVC) they were isolated and cultured in a medium containing 20% fetal calf serum (FCS). Changes in cell morphology of ARVC during cultivation were quantified by light and confocal laser scan microscopy. Small interfering RNA (siRNA) was used to reduce the expression of swiprosin-1. The impact of calcium on swiprosin-1 dependent processes was investigated with Bapta-AM. Immunoblot techniques and qRT-PCR were performed to measure mRNA and protein expression. Results In culture, ARVC first lost their contractile elements, which was followed by a formation of pseudopodia-like structures (spreading). Swiprosin-1 was detected in ARVC at all time points. However, swiprosin-1 expression was increased when ARVC started to spread. Reduction of swiprosin-1 expression with siRNA delayed ARVC spreading. Similarly, Bapta-AM attenuated swiprosin-1 expression and spreading of ARVC. Furthermore, swiprosin-1 expression correlated with the expression of G protein-coupled receptor kinase 2 (GRK2). Moreover, silencing of swiprosin-1 was associated with a down regulation of GRK2 and caused a sensitization of β-adrenergic receptors. Conclusion Swiprosin-1 is required for ARVC to adapt to culture conditions. Additionally, it seems to be involved in the desensitization of β-adrenergic receptors. Assuming that ARVC adapt to cardiac stress in a similar way, swiprosin-1 may play a key role in cardiac remodeling. PMID:27992454

  9. Effects of ethanol on antioxidant capacity in isolated rat hepatocytes

    PubMed Central

    Yang, Sien-Sing; Huang, Chi-Chang; Chen, Jiun-Rong; Chiu, Che-Lin; Shieh, Ming-Jer; Lin, Su-Jiun; Yang, Suh-Ching

    2005-01-01

    AIM: To investigate dose-response and time-course of the effects of ethanol on the cell viability and antioxidant capacity in isolated rat hepatocytes. METHODS: Hepatocytes were isolated from male adult Wistar rats and seeded into 100-mm dishes. Hepatocytes were treated with ethanol at concentrations between 0 (C), 10 (E10), 50 (E50), and 100 (E100) mmol/L (dose response) for 12, 24, and 36 h (time course). Then, lactate dehydrogenase (LDH) leakage, malondialdehyde (MDA) concentration, glutathione (GSH) level, and activities of glutathione peroxidase (GPX), glutathione reductase (GRD), superoxide dismutase (SOD), and catalase (CAT) were measured. RESULTS: Our data revealed that LDH leakage was significantly increased by about 30% in group E100 over those in groups C and E10 at 24 and 36 h, The MDA concentration in groups C, E10 and E50 were significantly lower than that in group E100 at 36 h. Furthermore, the concentration of MDA in group E100 at 36 h was significantly higher by 4.5- and 1.7-fold, respectively, than that at 12 and 24 h. On the other hand, the GSH level in group E100 at 24 and 36 h was significantly decreased, by 32% and 28%, respectively, compared to that at 12 h. The activities of GRD and CAT in group E100 at 36 h were significantly less than those in groups C and E10. However, The GPX and SOD activities showed no significant change in each group. CONCLUSION: These results suggest that long-time incubation with higher concentration of ethanol (100 mmol/L) decreased the cell viability by means of reducing GRD and CAT activities and increasing lipid peroxidation. PMID:16437627

  10. Social isolation prevents exercise-induced proliferation of hippocampal progenitor cells in female rats.

    PubMed

    Leasure, J Leigh; Decker, Linda

    2009-10-01

    Social isolation negatively affects the behavior and health of laboratory rats. Recently, it has been found that social isolation retards exercise-induced neurogenesis in the hippocampal dentate gyrus (DG) of male rats (Stranahan et al. (2006) Nat Neurosci 9:526-533). Since male and female rats react differently to housing changes and exercise opportunities, we investigated whether social isolation would also suppress the exercise-dependent increase in proliferation of dentate gyrus progenitor cells in females. Accordingly, female rats were housed either alone (isolated) or in groups (social) with (exercise) or without (sedentary) the opportunity to run in an exercise wheel. Proliferating progenitor cells were labeled with bromodeoxyuridine (BrdU). As expected, exercise increased the number of BrdU+ cells in socially housed animals. However, isolation prevented this running-induced increase. Our results expand upon previous findings by showing that the female brain is also susceptible to the suppressive effect of social isolation on exercise-induced neurogenesis.

  11. IMPACT OF ISOPRENALINE AND CAFFEINE ON DEVELOPMENT OF LEFT VENTRICULAR HYPERTROPHY AND RENAL HEMODYNAMIC IN WISTAR KYOTO RATS.

    PubMed

    Ahmad, Ashfaq; Sattar, Munavvar Z A; Rathore, Hassaan A; Khan, Safia Akhtar; Lazhari, Mohammed A; Hashmi, Fayaz; Abdullah, Nor A; Johns, Edward J

    2015-01-01

    Left ventricular hypertrophy (LVH) is a compensatory mechanism in response to an increased work load on the heart. This study investigated the impact of chronic isoprenaline and caffeine (I/C model) administration on cardiac geometry, systemic hemodynamic and physiological data in rats as LVH develops. LVH was induced by administering isoprenaline (5 mg/kg s.c. every 72 h) and caffeine (62 mg/L) in drinking water for 14 days to Wistar Kyoto (WKY) rats. Mean arterial pressure (MAP), systolic blood pressure (SBP), heart weight, LV weight, LV chamber diameter and thickness of myocardium were observed as LVH indicators. MAP was significantly higher (142 ± 13 vs. 119 ± 2 mmHg, respectively) while heart rate (HR) in LVH was lower (314 ± 9 vs. 264 ± 18 BPM) compared to control WKY. Heart weight, LV weight and kidney weight were 31%, 38% and 7%, respectively, greater in the LVH group as compared to the control WKY (all p < 0.05).The myocardium thickness was 101% greater while LV chamber diameter was 44% smaller in the LVH group as compared to the control WKY (p < 0.05). The superoxide dismutase (SOD), glutathione reductase (GSH) and total antioxidant capacity (T-AOC) levels were significantly reduced while malonodialdehyde (MDA) level increased in LVH as compared to control WKY (all p < 0.05). In conclusion, isoprenaline and caffeine (I/C) induces LVH and cardiac hypertrophy with increases in blood pressure, fluid excretion and reduced renal hemodynamics. Prooxidant mechanism of the body and arterial stiffness are dominant in this disease model. This model of LVH is easily generated and associated with low mortality.

  12. Sodium alterations in isolated rat heart during cardioplegic arrest

    SciTech Connect

    Schepkin, V.D.; Choy, I.O.; Budinger, T.F.

    1996-12-01

    Triple-quantum-filtered (TQF) Na nuclear magnetic resonance (NMR) without chemical shift reagent is used to investigate Na derangement in isolated crystalloid perfused rat hearts during St. Thomas cardioplegic (CP) arrest. The extracellular Na contribution to the NMR TQF signal of a rat heart is found to be 73 {+-} 5%, as determined by wash-out experiments at different moments of ischemia and reperfusion. With the use of this contribution factor, the estimated intracellular Na ([Na{sup +}]{sub i}) TQF signal is 222 {+-} 13% of preischemic level after 40 min of CP arrest and 30 min of reperfusion, and the heart rate pressure product recovery is 71 {+-} 8%. These parameters are significantly better than for stop-flow ischemia: 340 {+-} 20% and 6 {+-} 3%, respectively. At 37{degrees}C, the initial delay of 15 min in [Na{sup +}]{sub i} growth occurs during CP arrest along with reduced growth later ({approximately}4.0%/min) in comparison with stop-flow ischemia ({approximately}6.7%/min). The hypothermia (21{degrees}C, 40 min) for the stop-flow ischemia and CP dramatically decreases the [Na{sup +}]{sub i} gain with the highest heart recovery for CP ({approximately}100%). These studies confirm the enhanced sensitivity of TQF NMR to [Na{sup +}]{sub i} and demonstrate the potential of NMR without chemical shift reagent to monitor [Na{sup +}]{sub i} derangements. 48 refs., 7 figs., 1 tab.

  13. Antiarrhythmic effect of L-propionylcarnitine in isolated cardiac preparations.

    PubMed

    Carbonin, P U; Ramacci, M T; Pahor, M; Di Gennaro, M; Gambassi, G; Lo Giudice, P; Sgadari, A; Pacifici, L

    1991-06-01

    The effects of L-propionylcarnitine on reperfusion-induced ventricular arrhythmias were studied in isolated hearts from spontaneously hypertensive rats. During reperfusion, 60% (n = 15) of the hearts from control spontaneously hypertensive rats hearts developed irreversible ventricular fibrillation. In contrast, irreversible ventricular fibrillation did not occur in hearts from normotensive Wistar Kyoto rats (n = 11, p less than 0.01). In a second group of spontaneously hypertensive rats, the addition of 10(-6) M L-propionylcarnitine to the medium during ischemia and reperfusion reduced the incidence of irreversible ventricular fibrillation to 14% (n = 14, p less than 0.05 versus control spontaneously hypertensive rats, NS versus Wistar Kyoto rats). Concentrations of L-propionylcarnitine from 10(-6) to 10(-2) M were tested on isolated guinea pig papillary muscles using microelectrodes. Resting potential, action potential amplitude, action potential duration and active tension were not modified by L-propionylcarnitine; and 10(-3) M L-propionylcarnitine did not influence the oscillatory afterpotentials induced by digitalis. We conclude that reperfusion ventricular arrhythmias are more severe in spontaneously hypertensive rats than in Wistar Kyoto rats and that the antiarrhythmic effect of L-propionylcarnitine in spontaneously hypertensive rats is mediated by myocardial protection from damage induced by reperfusion.

  14. H2 and H3 relaxin inhibit high glucose-induced apoptosis in neonatal rat ventricular myocytes.

    PubMed

    Zhang, Xiaohui; Ma, Xiao; Zhao, Meng; Zhang, Bo; Chi, Jinyu; Liu, Wenxiu; Chen, Wenjia; Fu, Yu; Liu, Yue; Yin, Xinhua

    2015-01-01

    High concentrations of glucose induce cardiomyocyte apoptosis, and contribute to diabetic cardiomyopathy. Relaxin-2 and relaxin-3 are two members of the relaxin peptide family that are cardioprotective. However, it remains unknown whether relaxin-2 or relaxin-3 can regulate apoptosis in high glucose treated-neonatal rat ventricular myocytes (NRVMs). In cultured NRVMs, 33 mmol/l high glucose (HG) increased apoptosis in a time-dependent manner. HG-increased the protein expression of cleaved caspase-8 and -9, two initiators of the extrinsic and intrinsic pathways of apoptosis, Caspase-3 was attenuated by human recombinant relaxin-2 (H2 relaxin) or relaxin-3 (H3 relaxin), indicating that H2 and H3 relaxin inhibited HG-induced apoptosis. Furthermore, endoplasmic reticulum stress (ERS) markers CHOP and caspase-12 were markedly increased in HG-treated NRVMs, leading to apoptosis; this effect was also effectively attenuated by H2 relaxin or H3 relaxin. Treatment of NRVMs with HG reduced autophagy which cannot be adjusted by H2 relaxin or H3 relaxin. In conclusion, HG-induced apoptosis in NRVMs was mediated, in part, by the activation of the extrinsic and intrinsic pathways of apoptosis and ERS, all inhibited by H2 relaxin or H3 relaxin.

  15. ISOLATION AND STRUCTURAL STUDIES ON SYNAPTIC COMPLEXES FROM RAT BRAIN

    PubMed Central

    Cotman, Carl W.; Taylor, Dwan

    1972-01-01

    A fraction enriched in synaptic complexes has been isolated from rat brain. The major structural elements of synaptic complexes after isolation are a sector of pre- and postsynaptic plasma membranes joined together by a synaptic cleft and a postsynaptic density (PSD) located on the inner surface of the postsynaptic membrane. On its outer surface, the postsynaptic membrane has a series of projections which extend about halfway into the cleft and which occur along the entire length of the PSD. Proteolytic enzymes at high concentrations remove the PSD and open the synaptic cleft; at low concentrations the PSD is selectively destroyed. By contrast, the structural integrity of the PSD is resistant to treatment with NaCl, EGTA, and low concentrations of urea. Pre- and postsynaptic membranes also remain joined by the synaptic cleft after NaCl, EGTA, or mild urea treatment. High concentrations of urea cause the partial dissociation of the PSD. We conclude that polypeptides are probably one of the major components of the PSD and that the structural integrity of the PSD depends on polypeptides because disruption of the covalent or hydrophobic bonding of these polypeptides leads to a progressive loss of PSD structure. PMID:4656707

  16. Glucocorticoid control of steroidogenesis in isolated rat adrenocortical cells.

    PubMed

    Carsia, R V; Malamed, S

    1983-08-17

    The role of end-product glucocorticoids in the regulation of corticosteroidogenesis in isolated adrenocortical cells was investigated. Trypsin-isolated cells from male rat adrenal glands were incubated with or without corticotropin (ACTH) and with or without corticosterone. Endogenous corticosterone production was determined by radioimmunoassay at the end of incubation. Cessation of ACTH-induced corticosterone production was apparent after 2-4 h of incubation. The suppression occurred later with lower cell concentrations. Corticosterone production was partially restored after washing the suppressed cells. Supernatant fluid from suppressed cell suspensions also suppressed steroidogenesis of a fresh population of cells. However, the suppressing property of the supernatant fluid was abolished after the removal of corticosterone by charcoal-dextran treatment, suggesting that corticosterone or other steroids caused the suppression. Exogenous corticosterone induced suppression over a wide range of ACTH concentrations, but did not change the half-maximal steroidogenic concentration of ACTH, indicating that the suppression does not change the sensitivity of the cells to ACTH. Suppression occurred within 30-60 min after corticosterone had been added to the incubation medium either at the start of incubation or while steroidogenesis was in progress. Suppression varied directly with the concentration of exogenous corticosterone. These data indicate that glucocorticoids can directly and acutely suppress corticosteroidogenesis and thus control adrenocortical function in concert with other regulators such as ACTH and Ca2+.

  17. Cytotoxicity of ortho-phenylphenol in isolated rat hepatocytes.

    PubMed

    Nakagawa, Y; Moldéus, P; Moore, G A

    1992-01-22

    The effects of ortho-phenylphenol (OPP) and its metabolites, phenyl-hydroquinol (PHQ) and phenyl-benzoquinone (PBQ), on isolated rat hepatocytes were investigated. Addition of OPP (0.5-1.0 mM) to cells caused a dose-dependent cell death accompanied by the depletion of intracellular levels of ATP, glutathione (GSH) and protein thiols. GSH loss correlated with the formation of oxidized GSH. In addition, PHQ and especially PBQ (both at 0.5 mM) resulted in acute cell death with rapid depletion of ATP, GSH and protein thiols, and further low doses of PBQ (10-50 microM) elicited serious impairment of mitochondrial functions related to oxidative phosphorylation and Ca fluxes in isolated liver mitochondria. These results indicate that mitochondria are a target for these compounds and that OPP is itself toxic to hepatocytes even when metabolism is inhibited. The loss of cellular GSH and protein thiols accompanied by the impairment of mitochondrial function may be the main mechanisms of cytotoxicity induced by OPP and its metabolites.

  18. 'Cross talk' between opioid peptide and adrenergic receptor signaling in isolated rat heart.

    PubMed

    Pepe, S; Xiao, R P; Hohl, C; Altschuld, R; Lakatta, E G

    1997-04-15

    Cardiac myocyte sarcolemma contains both catecholamine and opioid peptide receptors (OPRs). Opioid peptides are coreleased with catecholamines from nerve terminals in the heart. We investigated whether OPR stimulation influences the effects of beta-adrenergic receptor (beta-AR) stimulation in the isolated, isovolumic rat heart and whether the mechanism of such an interaction involves both beta-AR subtypes or an alteration in beta-AR-mediated increase in cAMP. Norepinephrine (NE, 10(-7) mol/L) increased peak left ventricular systolic pressure (LVSP) and cAMP more than twofold compared with controls. The delta-OPR agonist leucine-enkephalin (LE, 10(-8) mol/L) markedly inhibited the beta1-AR-induced positive inotropic effect and increase in cAMP but alone had no effect on basal LVSP or basal cAMP levels. The OPR antagonist naloxone 10(-8) mol/L added to LE+NE perfusate reversed the LE-induced decrease in cAMP and LVSP even though naloxone alone had no effect on LVSP and cAMP levels. LE could not counteract the twofold increase in LVSP produced by the nondegradable cAMP analog CPT-cAMP 2.3x10(-5) mol/L or a high concentration of forskolin (10(-7) mol/L) but did reverse the 173+/-11.8% and 135+/-13.6% increases in LVSP stimulated by 10(-8) and 0.5x10(-8) mol/L forskolin, respectively. LE inhibited cAMP production at all concentrations of forskolin (10(-7), 10(-8), and 0.5x10(-8) mol/L). Pertussis toxin (PTX) pretreatment abolished LE effects on beta1-AR stimulation. Zinterol 10(-5) and 10(-6) mol/L, a specific beta2-AR agonist that elicits a cAMP-independent inotropic effect in rat heart, caused 225+/-14% and 182+/-5% increases in LVSP that could not be reversed by addition of LE. Potent, inhibitory "cross talk" between delta-OPR and beta1-AR signaling pathways occurs via a PTX-sensitive G(i/o) protein involved in adenylyl cyclase inhibition in rat heart.

  19. Effects of Aronia melanocarpa Fruit Juice on Isolated Rat Hepatocytes

    PubMed Central

    Kondeva-Burdina, Magdalena; Valcheva-Kuzmanova, Stefka; Markova, Tsvetelina; Mitcheva, Mitka; Belcheva, Anna

    2015-01-01

    Background: Aronia melanocarpa (Michx.) Elliot fruits are very rich in polyphenols – procyanidins, flavonoids, and phenolic acids. Objective: On rat hepatocytes, isolated by two-stepped collagenase perfusion, we investigated the effect of A. melanocarpa fruit juice (AMFJ) in two models of liver toxicity caused by (i) metabolic bioactivation of carbon tetrachloride (CCl4), and (ii) tert-butyl hydroperoxide (t-BuOOH)-induced oxidative stress. Materials and Methods: Isolated rat hepatocytes are a suitable model for hepatotoxicity studies. We determined the main parameters of the functional and metabolic status of rat hepatocytes: Cell viability (measured by trypan blue exclusion) and the levels of lactate dehydrogenase (LDH), reduced glutathione (GSH), and malondialdehyde (MDA). These parameters were used to investigate the protective effects of AMFJ in the two toxicity models. The effects of AMFJ were compared with those of silymarin. The cells were treated either with AMFJ or silymarin at increasing concentrations of 5 μg/ml, 10 μg/ml, 30 μg/ml, 50 μg/ml, and 100 μg/ml which were used for measuring of IC50. Results: In both toxicity models – CCl4 and t-BuOOH, AMFJ showed statistically significant cytoprotective and antioxidant activities. AMFJ prevented the loss of cell viability and GSH depletion, decreased LDH leakage and MDA production. The effects of AMFJ at the concentrations of 5, 10, 30, and 50 μg/ml were similar to those of the same concentrations of silymarin, while the effect of the highest AMFJ concentration of 100 μg/ml was higher than that of the same silymarin concentration. The effects were concentration-dependent and more prominent in the t-BuOOH model, compared to those in the CCl4 model. Conclusion: The cytoprotective and antioxidant effects of AMFJ established in this study might be due to its polyphenolic ingredients, which could influence the cytochrome P450-mediated metabolism of the experimental hepatotoxic substances (CCl4 and t

  20. Oral pretreatment with a green tea polyphenol for cardioprotection against ischemia-reperfusion injury in an isolated rat heart model.

    PubMed

    Yanagi, Shigeki; Matsumura, Kazuaki; Marui, Akira; Morishima, Manabu; Hyon, Suong-Hyu; Ikeda, Tadashi; Sakata, Ryuzo

    2011-02-01

    Ischemia-reperfusion injury is among the most serious problems in cardiac surgery. Epigallocatechin-3-gallate, a major polyphenolic component of green tea, is thought to be cardioprotective through its antioxidant activities. We investigated cardioprotective effects of oral epigallocatechin-3-gallate pretreatment against ischemia-reperfusion injury in isolated rat hearts and considered possible underlying mechanisms. Rats were given epigallocatechin-3-gallate solution orally at 0.1, 1, or 10 mmol/L (n=12 per group) for 2 weeks; controls (n=12) received tap water alone for 2 weeks. Subsequently, Langendorff-perfused hearts were subjected to global ischemia for 30 minutes, followed by 60 minutes of reperfusion. Recoveries at 60 minutes after reperfusion of left ventricular developed pressure and maximum positive and minimum negative first derivatives of left ventricular pressure were significantly higher in 1-mmol/L group than in 0.1-mmol/L (P<.0001), 10-mmol/L (P<.05), and control (P<.0001) groups. Oxidative stress after reperfusion, as reflected by 8-hydroxy-2'-deoxyguanosine index, was lower in 1-mmol/L group than in control (P<.01) and 0.1-mmol/L (P<.05) groups. Western blot analysis after reperfusion showed p38 activation and active caspase-3 expression to be lower in 1-mmol/L group than in control group (P<.05). Oral pretreatment with epigallocatechin-3-gallate preserved cardiac function after ischemia-reperfusion, an effect that may involve its antioxidative, antiapoptotic properties, although a high dose did not lead to dramatic improvement in cardiac function. Oral epigallocatechin-3-gallate pretreatment may be a novel and simple cardioprotective method for preventing perioperative cardiac dysfunction in cardiac surgery. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  1. Heterogeneity of Kv2.1 mRNA expression and delayed rectifier current in single isolated myocytes from rat left ventricle.

    PubMed

    Schultz, J H; Volk, T; Ehmke, H

    2001-03-16

    Expression of the voltage-gated K(+) channel Kv2.1, a possible molecular correlate for the cardiac delayed rectifier current (I(K)), has recently been shown to vary between individual ventricular myocytes. The functional consequences of this cell-to-cell heterogeneity in Kv2.1 expression are not known. Using multiplex single-cell reverse transcriptase-polymerase chain reaction (RT-PCR), we detected Kv2.1 mRNA in 47% of isolated midmyocardial myocytes from the rat left ventricular free wall that were positive for alpha-myosin heavy chain mRNA (n=74). Whole-cell patch-clamp recordings demonstrated marked differences in the magnitude of I(K) (200 to 1450 pA at V(Pip)=40 mV) between individual myocytes of the same origin. Furthermore, the tetraethylammonium (TEA)-sensitive outward current (I(TEA)), known to be partly encoded by Kv2.1 in mice, revealed a wide range of current magnitudes between single cells (150 to 1130 pA at V(Pip)=40 mV). Combined patch-clamp recordings and multiplex single-cell RT-PCR analysis of the same myocytes, however, showed no differences in I(K) or I(TEA) magnitude or inactivation kinetics between myocytes expressing Kv2.1 mRNA and those that did not express Kv2.1 mRNA. In contrast, in all midmyocardial myocytes expressing the transient outward potassium current (I(to1)), Kv4 mRNA, which has been shown to underlie I(to1), was detected (n=10). These results indicate that I(K) heterogeneity among individual left ventricular myocytes cannot be explained by the distribution pattern of Kv2.1 mRNA. Other mechanisms besides Kv2.1 mRNA expression appear to determine magnitude and kinetics of I(K) in rat ventricular myocytes.

  2. Ramipril attenuates left ventricular remodeling by regulating the expression of activin A-follistatin in a rat model of heart failure

    PubMed Central

    Wei, Qun; Liu, Haiyan; Liu, Miao; Yang, Chunyan; Yang, Jie; Liu, Zhonghui; Yang, Ping

    2016-01-01

    Prior studies have shown that overexpression of ACT A can lead to ventricular remodeling in rat models of heart failure. Furthermore, recently work studying demonstrated that stimulation of activin An expression in rat aortic smooth muscle (RASM) cells by angiotensin II (Ang II). Ramipril is a recently developed angiotensin converting enzyme (ACE) inhibitor. To investigate the effects of Ramipril on expression of ACT A-FS, we established the rat model of heart failure after myocardial infarction (MI), and divided into either a sham operation (SO), MI, or MI-Ramipril group. We found that Ramipril significantly attenuates collagen-I and III deposition (col-I and III). Notably, we determined that expression of ACT A and II activin receptor (ActRII) were significantly down-regulated in the non-infarcted area of the left ventricle in the Ramipril group, whereas the mRNA and protein levels of FS were markedly up-regulated. Our data suggested that Ramipril benefited left ventricular remodeling by reducing fibrosis and collagen accumulation in the left ventricle of rats after myocardial infarction. This observation was also associated with down-regulation of ACT A expression. This study elucidated a new protective mechanism of Ramipril and suggests a novel strategy for treatment of post-infarct remodeling and subsequent heart failure. PMID:27642098

  3. Enduring and sex-specific effects of adolescent social isolation in rats on adult stress reactivity.

    PubMed

    Weintraub, Ari; Singaravelu, Janani; Bhatnagar, Seema

    2010-07-09

    In adolescence, gender differences in rates of affective disorders emerge. For both adolescent boys and girls, peer relationships are the primary source of life stressors though adolescent girls are more sensitive to such stressors. Social stressors are also powerful stressors for non-human social species like rodents. In a rat model, we examined how social isolation during adolescence impacts stress reactivity and specific neural substrates in adult male and female rats. Rats were isolated during adolescence by single housing from day 30 to 50 of age and control rats were group housed. On day 50, isolated rats and control rats were re-housed in same-treatment same-sex groups. Adult female rats isolated as adolescents exhibited increased adrenal responses to acute and to repeated stress and exhibited increased hypothalamic vasopressin mRNA and BDNF mRNA in the CA3 hippocampal subfield. In contrast, adult male rats isolated as adolescents exhibited a lower corticosterone response to acute stress, exhibited a reduced state of anxiety as assessed in the elevated plus maze and reduced Orexin mRNA compared to adult males group-housed as adolescents. These data point to a markedly different impact of isolation experienced in adolescence on endocrine and behavioral endpoints in males compared to females and identify specific neural substrates that may mediate the long-lasting effects of stress in adolescence.

  4. Left ventricular regional variations in myosin isoform shift in Dahl salt-sensitive hypertensive rats.

    PubMed

    Sakurai, Shigeki; Ashida, Terunao; Ieki, Keiko; Takahashi, Naoyuki; Fujii, Jun

    2003-03-01

    To evaluate the effects of chronic pressure overload on different parts of the left ventricle (LV), we examined a myosin isoform shift from V1 to V3 as a biochemical marker of LV hypertrophy in Dahl salt-sensitive (DS) rats. Six-week-old DS rats were fed an 8% (high salt, HS; n = 24) or a 0.3% (low salt, LS; n = 12) NaCl diet. After 2 or 4 weeks, the hearts were dissected and the LVs were separated into four parts (the base and mid-portion of the interventricular septum (IVS), and the base and mid-portion of the LV free wall) for isomyosin analysis. The myosin isoform shift was analyzed by pyrophosphate gel electrophoresis. Both blood pressure and LV/body weight ratio were clearly increased in the HS group. The myosin isoform shift from V1 to V3, which was measured as a decrease in the percentage of V1 isomyosin, was demonstrated only in the base of LV, with significant predominance in the IVS at 2 weeks and in all four parts at 4 weeks in the HS group. In the LS group, a myosin isoform shift was demonstrated only in the basal portion of the LV at 4 weeks. We concluded that, in rats with salt-induced hypertension, the myosin isoform shift from V1 to V3 starts at the base of the LV, and particularly at the base of the IVS, and then spreads across the entire LV. These results suggest that pressure overload from hypertension may be strongest at the base of the IVS, and that LV hypertrophy may originate at the IVS base.

  5. Long-term cardiovascular effects of neonatal dexamethasone treatment: hemodynamic follow-up by left ventricular pressure-volume loops in rats.

    PubMed

    Bal, Miriam P; de Vries, Willem B; van Oosterhout, Matthijs F M; Baan, Jan; van der Wall, Ernst E; van Bel, Frank; Steendijk, Paul

    2008-02-01

    Dexamethasone is clinically applied in preterm infants to treat or prevent chronic lung disease. However, concern has emerged about adverse side effects. The cardiovascular short-term side effects of neonatal dexamethasone treatment are well documented, but long-term consequences are unknown. Previous studies showed suppressed mitosis during dexamethasone treatment, leading to reduced ventricular weight, depressed systolic function, and compensatory dilatation in prepubertal rats. In addition, recent data indicated a reduced life expectancy. Therefore, we investigated the long-term effects of neonatal dexamethasone treatment on cardiovascular function. Neonatal rats were treated with dexamethasone or received saline. Cardiac function was determined in 8-, 50-, and 80-wk-old animals, representing young adult, middle-aged, and elderly stages. A pressure-conductance catheter was introduced into the left ventricle to measure pressure-volume loops. Subsequently, the hearts were collected for histological examination. Our results showed reduced ventricular and body weights in dexamethasone-treated rats at 8 and 80 wk, but not at 50 wk. Cardiac output and diastolic function were unchanged, but systolic function was depressed at 50 and 80 wk, evidenced by reduced ejection fractions and rightward shifts of the end-systolic pressure-volume relationships. We concluded that previously demonstrated early adverse effects of neonatal dexamethasone treatment are transient but that reduced ventricular weight and systolic dysfunction become manifest again in elderly rats. Presumably, cellular hypertrophy initially compensates for the dexamethasone treatment-induced lower number of cardiomyocytes, but this mechanism falls short at a later stage, leading to systolic dysfunction. If applicable to humans, cardiac screening of a relatively large patient group to enable secondary prevention may be indicated.

  6. Cinaciguat prevents the development of pathologic hypertrophy in a rat model of left ventricular pressure overload.

    PubMed

    Németh, Balázs Tamás; Mátyás, Csaba; Oláh, Attila; Lux, Árpád; Hidi, László; Ruppert, Mihály; Kellermayer, Dalma; Kökény, Gábor; Szabó, Gábor; Merkely, Béla; Radovits, Tamás

    2016-11-17

    Pathologic myocardial hypertrophy develops when the heart is chronically pressure-overloaded. Elevated intracellular cGMP-levels have been reported to prevent the development of pathologic myocardial hypertrophy, therefore we investigated the effects of chronic activation of the cGMP producing enzyme, soluble guanylate cyclase by Cinaciguat in a rat model of pressure overload-induced cardiac hypertrophy. Abdominal aortic banding (AAB) was used to evoke pressure overload-induced cardiac hypertrophy in male Wistar rats. Sham operated animals served as controls. Experimental and control groups were treated with 10 mg/kg/day Cinaciguat (Cin) or placebo (Co) p.o. for six weeks, respectively. Pathologic myocardial hypertrophy was present in the AABCo group following 6 weeks of pressure overload of the heart, evidenced by increased relative heart weight, average cardiomyocyte diameter, collagen content and apoptosis. Cinaciguat did not significantly alter blood pressure, but effectively attenuated all features of pathologic myocardial hypertrophy, and normalized functional changes, such as the increase in contractility following AAB. Our results demonstrate that chronic enhancement of cGMP signalling by pharmacological activation of sGC might be a novel therapeutic approach in the prevention of pathologic myocardial hypertrophy.

  7. Cinaciguat prevents the development of pathologic hypertrophy in a rat model of left ventricular pressure overload

    PubMed Central

    Németh, Balázs Tamás; Mátyás, Csaba; Oláh, Attila; Lux, Árpád; Hidi, László; Ruppert, Mihály; Kellermayer, Dalma; Kökény, Gábor; Szabó, Gábor; Merkely, Béla; Radovits, Tamás

    2016-01-01

    Pathologic myocardial hypertrophy develops when the heart is chronically pressure-overloaded. Elevated intracellular cGMP-levels have been reported to prevent the development of pathologic myocardial hypertrophy, therefore we investigated the effects of chronic activation of the cGMP producing enzyme, soluble guanylate cyclase by Cinaciguat in a rat model of pressure overload-induced cardiac hypertrophy. Abdominal aortic banding (AAB) was used to evoke pressure overload-induced cardiac hypertrophy in male Wistar rats. Sham operated animals served as controls. Experimental and control groups were treated with 10 mg/kg/day Cinaciguat (Cin) or placebo (Co) p.o. for six weeks, respectively. Pathologic myocardial hypertrophy was present in the AABCo group following 6 weeks of pressure overload of the heart, evidenced by increased relative heart weight, average cardiomyocyte diameter, collagen content and apoptosis. Cinaciguat did not significantly alter blood pressure, but effectively attenuated all features of pathologic myocardial hypertrophy, and normalized functional changes, such as the increase in contractility following AAB. Our results demonstrate that chronic enhancement of cGMP signalling by pharmacological activation of sGC might be a novel therapeutic approach in the prevention of pathologic myocardial hypertrophy. PMID:27853261

  8. The H{sub 1}–H{sub 2} domain of the α{sub 1} isoform of Na{sup +}–K{sup +}–ATPase is involved in ouabain toxicity in rat ventricular myocytes

    SciTech Connect

    Xiong, Chen; Li, Jun-xia; Guo, Hui-cai; Zhang, Li-nan; Guo, Wei; Meng, Jing; Wang, Yong-li

    2012-07-01

    The composition of different isoforms of Na{sup +}-K{sup +}-ATPase (NKA, Na/K pump) in ventricular myocytes is an important factor in determining the therapeutic effect and toxicity of cardiac glycosides (CGs) on heart failure. The mechanism whereby CGs cause these effects is still not completely clear. In the present study, we prepared two site-specific antibodies (SSA78 and WJS) against the H{sub 1}–H{sub 2} domain of α{sub 1} and α{sub 2} isoforms of NKA in rat heart, respectively, and compared their influences on the effect of ouabain (OUA) in isolated rat ventricular myocytes. SSA78 or WJS, which can specifically bind with the α{sub 1} or α{sub 2} isoform, were assessed with enzyme linked immunosorbent assay (ELISA), Western blot and immunofluorescent staining methods. Preincubation of myocytes with SSA78 inhibited low OUA affinity pump current but not high OUA affinity pump current, reduced the rise in cytosolic calcium concentration ([Ca{sup 2+}]{sub i}), attenuated mitochondrial Ca{sup 2+} overload, restored mitochondrial membrane potential reduction, and delayed the decrease of the myocardial contractile force as well as the occurrence of arrhythmic contraction induced by high concentrations (1 mM) but not low concentrations (1 μM) of OUA. Similarly, preincubation of myocytes with WJS inhibited high OUA affinity pump current, reduced the increase of [Ca{sup 2+}]{sub i} and the contractility induced by 1 μM but not that induced by 1 mM OUA. These results indicate that the H{sub 1}–H{sub 2} domain of the NKA α{sub 1} isoform mediates OUA-induced cardiac toxicity in rat ventricular myocytes, and inhibitors for this binding site may be used as an adjunct to CGs treatment for cardiovascular disease. -- Highlights: ► We prepared two antibodies against the H{sub 1}-H{sub 2} domain of α{sub 1} and α{sub 2} isoforms of NKA. ► The H{sub 1}-H{sub 2} domain of the NKA α{sub 1} isoform mediates OUA-induced cardiac toxicity. ► The H{sub 1}-H{sub 2

  9. An investigation on cardioprotective potential of Marrubium vulgare aqueous fraction against ischemia-reperfusion injury in isolated rat heart.

    PubMed

    Garjani, Alireza; Tila, Dena; Hamedeyazdan, Sanaz; Vaez, Haleh; Rameshrad, Maryam; Pashaii, Mahdiyeh; Fathiazad, Fatemeh

    2017-02-15

    The aim of this study was to evaluate the cardioprotective effects of aqueous fraction of M. vulgare hydroalcoholic extract on cardiac parameters in ischemic-reperfused isolated rat hearts. The aerial parts of the plant were extracted with methanol 70% by maceration. The water-soluble portion of the total hydroalcoholic extract was prepared with liquid-liquid extraction (LLE). Afterwards, the antioxidant activity, total phenolic and flavonoids content of the aqueous fraction were determined. In order to evaluate the effects of the aqueous fraction on cardiac parameters and I/R injury, the Langendroff method was used on Male Wistar rats. Harvested hearts were cannulated immediately to the langendroff apparatus and subjected into 30 min regional ischemia and 2 hrs reperfusion, either by a modified Krebs-Henseleit Buffer Solution (KHBS) or enriched KHBS with plant extract (10, 20, 40 µg/mL). The aqueous fraction was found to be a scavenger of DPPH radical with RC50 value of 47µg/mL. The total phenolic and flavonoids content of the fraction was 6.05g gallic acid equivalent and 36.13mg quercetin equivalent per 100g of dry plant material. In addition, 40 µg/mL of M. vulgare aqueous fraction significantly decreased infarct size in comparison to control group. All doses considerably reduced the total ventricular ectopic beats (VEBs) during 30 min of ischemia. The extract at dose of 40 µg/mL noticeably decreased the arrhythmias during the first 30 min of reperfusion. The results of the study indicated aqueous fraction of M. vulgare possesses a protective effect against I/R injuries in isolated rat hearts.

  10. Morphine treatment during juvenile isolation increases social activity and opioid peptides release in the adult rat.

    PubMed

    Van den Berg, C L; Kitchen, I; Gerrits, M A; Spruijt, B M; Van Ree, J M

    1999-05-29

    The consequences of juvenile isolation and morphine treatment on general activity, social activity and endogenous opioid release during a social interaction test were investigated in the adult rat. Rats were either isolated or socially housed during weeks 4 and 5 of age and treated daily during this isolation period subcutaneously with either saline or morphine. Directly after a social interaction test at 10 weeks of age, rats were injected with [3H]-diprenorphine and subsequently prepared for in vivo autoradiography. The autoradiographic technique was used to visualise neuroanatomical changes in opioid receptor occupancy, probably reflecting changes in opioid peptide release, as a result of social activity. Juvenile isolation increased general activity during the social interaction test, an effect which was accompanied by a reduction of opioid receptor occupancy in many brain areas, suggesting an increased opioid peptide release as a consequence of socially-induced general activity. Morphine treatment in isolated rats caused an increase in adult social activity and enhanced opioid peptide release in some cortical regions and the ventral tegmental area as compared to saline treated rats. Both social activity and opioid receptor occupancy were unaffected by morphine treatment in non-isolated rats. The present study underscores the role of opioid systems in adult social behaviors as a consequence of juvenile isolation. The results suggest a relationship between social activity and opioid peptide release during social contact. Increased social activity seems to be accompanied by elevated opioid peptide release in distinct brain areas after morphine treatment during juvenile isolation.

  11. Calcium-linked adjustment of myocardial metabolism to changing mechanical demands in the isolated rat heart.

    PubMed

    Rubányi, G; Kovách, A G

    1980-01-01

    Isolated rat hearts perfused by the modified Langendorff technique were used to study the effects of changes in perfusate calcium concentration (Cap2+) on left ventricular mechanical performance, O2-consumption, NADH-fluorescence and lactate release in the presence of glucose or pyruvate as the sole exogenous substrate. Stepwise elevation of Ca2+ from 0.31 to 7.8 mM resulted in a continuous increase of contractile activity and O2-consumption independent of the substrate present. Redox changes similar to State 3 to 4 transition (NAD+ reduction) were observed when mechanical activity was reduced by perfusing the hearts with 0.65 or 0.31 mM Cap2+, which was also substrate independent. At high Cap2+ (2.6--7.8 mM) increase of contractile activity and O2-consumption was accompanied by Cap2+ dependent NAD+ reduction in the presence of glucose. Inhibition of glycolisis by pyruvate reversed the direction of NADH response (NADH oxidation following Cap2+ elevation). Myocardial lactate relealse was increased by elevation of Cap2+ from 1.3 to 5.2 mM in the presence of glucose, but this effect was significantly inhibited in the pyruvate perfused hearts. It is concluded that NADH signal originates from both the cytosolic and mitochondrial NADH compartment. The direction of NAD+/NADH redox state changes following Cap2+ elevation is grately influenced by the substrate preferentially consumed by the heart. The data suggest that calcium increases the availability of reducing equivalents to the respiratory chain thereby ensuring adequate supply of ATP when myocardial mechanical demands are changing.

  12. Beneficial effects of quinidine on post-ischemic contractile failure of isolated rat hearts.

    PubMed

    Liu, J X; Tanonaka, K; Sanbe, A; Yamamoto, K; Takeo, S

    1993-10-01

    The present study was undertaken to determine whether quinidine may improve ischemia/reperfusion-induced functional and metabolic injury of isolated rat hearts. Thirty-five-min ischemia and the subsequent 60-min reperfusion resulted in no post-ischemic force generation, an increase in left ventricular end-diastolic pressure (about 1500%) and a sustained rise in perfusion pressure (136 +/- 15% of initial). This was associated with an increase in the release of creatine kinase and ATP metabolites from the reperfused heart, a decrease in tissue high-energy phosphates, changes in tissue sodium, calcium, potassium and magnesium contents, and a reduction in the triphenyltetrazolium chloride (TTC)-stained area, an indicator of infarction. Hearts were treated with 3-100 microM quinidine 3 min before ischemia. Quinidine at concentrations of 10 microM or greater resulted in post-ischemic contractile recovery in a concentration-dependent manner (61 +/- 8 to 95 +/- 8% of initial). Ischemia/reperfusion-induced metabolic and histologic alterations were also suppressed by treatment with quinidine in a concentration-dependent manner. The results suggest that quinidine has a cardioprotective effect in ischemic/reperfused hearts. Because transmembrane fluxes of ions, substrates, and enzymes were suppressed by treatment with quinidine, protection of cardiac cell membrane function and/or integrity against ischemia/reperfusion-induced ionic imbalance, presumably sodium imbalance, across the sarcolemma is a possible mechanism by which quinidine may act. Slightly higher levels of ATP were detected in the treated hearts at 10 and 15 min, but not at 35 min of ischemia. Such preservation of high-energy phosphates might also be beneficial for protecting myocardial cells against ischemic damage.

  13. Interplay Between Cytosolic Free Zn(2+) and Mitochondrion Morphological Changes in Rat Ventricular Cardiomyocytes.

    PubMed

    Billur, Deniz; Tuncay, Erkan; Okatan, Esma Nur; Olgar, Yusuf; Durak, Aysegul Toy; Degirmenci, Sinan; Can, Belgin; Turan, Belma

    2016-11-01

    The Zn(2+) in cardiomyocytes is buffered by structures near T-tubulus and/or sarcoplasmic/endoplasmic reticulum (S(E)R) while playing roles as either an antioxidant or a toxic agent, depending on the concentration. Therefore, we aimed first to examine a direct effect of ZnPO4 (extracellular exposure) or Zn(2+) pyrithione (ZnPT) (intracellular exposure) application on the structure of the mitochondrion in ventricular cardiomyocytes by using histological investigations. The light microscopy data demonstrated that Zn(2+) exposure induced marked increases on cellular surface area, an indication of hypertrophy, in a concentration-dependent manner. Furthermore, a whole-cell patch-clamp measurement of cell capacitance also supported the hypertrophy in the cells. We observed marked increases in mitochondrial matrix/cristae area and matrix volume together with increased lysosome numbers in ZnPO4- or ZnPT-incubated cells by using transmission electron microscopy, again in a concentration-dependent manner. Furthermore, we observed notable clustering and vacuolated mitochondrion, markedly disrupted and damaged myofibrils, and electron-dense small granules in Zn(2+)-exposed cells together with some implications of fission-fusion defects in the mitochondria. Moreover, we observed marked depolarization in mitochondrial membrane potential during 1-μM ZnPT minute applications by using confocal microscopy. We also showed that 1-μM ZnPT incubation induced significant increases in the phosphorylation levels of GSK3β (Ser21 and Ser9), Akt (Ser473), and NFκB (Ser276 and Thr254) together with increased expression levels in ER stress proteins such as GRP78 and calregulin. Furthermore, a new key player at ER-mitochondria sites, promyelocytic leukemia protein (PML) level, was markedly increased in ZnPT-incubated cells. As a summary, our present data suggest that increased cytosolic free Zn(2+) can induce marked alterations in mitochondrion morphology as well as depolarization in

  14. Cobra venom cardiotoxin induces perturbations of cytosolic calcium homeostasis and hypercontracture in adult rat ventricular myocytes.

    PubMed

    Wang, H X; Lau, S Y; Huang, S J; Kwan, C Y; Wong, T M

    1997-10-01

    The effects of Cobra venom cardiotoxin (CTX) on the cellular morphology, twitch amplitude and intracellular calcium ([Ca2+]i) of the ventricular myocytes were studied. [Ca2+]i and twitch amplitude were determined with a fluorometric ratio method using Fura-2/AM and Calcium Green-1 as calcium indicators, and a videomicroscopic technique, respectively. Addition of 0.001-1 microM CTX led to a time-dependent loss of rod shaped cells, beginning at 1 min, and remaining stable by 20 min. CTX 1 microM initially caused a transient augmentation in amplitude of the electrically induced-[Ca2+]i transient and twitch amplitude in the single cardiac myocyte. This was followed by a prolongation in duration of [Ca2+]i. Eventually, cells became inexcitable and abruptly underwent contracture, and [Ca2+]i remained elevated. In the absence of electrical stimulation, 1 microM CTX induced a Ca2+ spike followed by a sustained elevation of [Ca2+]i, an effect different from that of 40 mm KCl or 10 mm caffeine, which caused a transient elevation in [Ca2+]i. Digital imaging microscopy of Calcium Green-1 fluorescence revealed that the increase in [Ca2+]i was accompanied by changes in cell shape without leakage of fluorescence dye in the early stage after administration of the toxin. In the absence of [Ca2+]o, the initial [Ca2+]i spike was reduced, but the second phase of elevation of [Ca2+]i still occurred. In addition, experiments using Mn2+ quench technique suggested that Ca2+-influx was induced by CTX, and that both ryanodine and thapsigargin, known to deplete Ca2+ from its intracellular pool, abolished the second phase of the elevation of [Ca2+]i. The effects of cardiotoxin were abolished by 10 mM Ni2+ and 10 mM -Ca2+-o, but not by 5 microM verapamil. In conclusion, the observations indicate that CTX causes an initial increase followed by a second sustained elevation in [Ca2+]i, which is accompanied by changes in cell shape-from rod to round-and hypercontracture. The initial [Ca2+]i spikes

  15. Bioactivation of fluorotelomer alcohols in isolated rat hepatocytes.

    PubMed

    Martin, Jonathan W; Chan, Katie; Mabury, Scott A; O'Brien, Peter J

    2009-02-12

    Fluorotelomer alcohols (FTOHs; C(x)F(2x+1)C(2)H(4)OH) are intermediates in the production of specialty surfactants and stain-repellent polymers. The magnitude and pathways of human exposure to FTOHs are not understood, but FTOHs are present in ambient air and house dust, and FTOH-derivatives are used in food-contact applications. Previously, electrophilic FTOH biotransformation products were detected in rat hepatocytes, and liver lesions were found in FTOH exposed rodents. To begin elucidating the mechanism(s) of action, freshly isolated rat hepatocytes were incubated with FTOHs, or FTOH biotransformation products, and toxicity was followed in the presence or absence of carbonyl scavengers and metabolic enzyme modulators. The LC(50) depended on perfluorinated chain length, with the shortest (4:2 FTOH; x=4) and longest (8:2 FTOH; x=8) FTOHs tested being more toxic than the medium chain length FTOH (6:2 FTOH; x=6); a structure-toxicity relationship that is consistent with that for 2-alkenals. For hepatocytes treated with 8:2 FTOH, cytotoxicity corresponded to depletion of glutathione (GSH), increased protein carbonylation, and lipid peroxidation. Aminobenzotriazole, a P450 inhibitor, diminished cytotoxicity for all FTOHs tested, and decreased protein carbonylation and lipid peroxidation for 8:2 FTOH, indicating that a biotransformation product was responsible for FTOH cytotoxicity. Preincubation of hepatocytes with hydralazine or aminoguanidine decreased the cytotoxicity of 8:2 FTOH, suggesting that reactive aldehyde intermediates contributed to the cytotoxicity. A GSH-reactive alpha/beta-unsaturated acid metabolite was also more toxic than the corresponding FTOH, and may have contributed to the observed effects. Overall, these results suggested that FTOH toxicity was related to electrophilic aldehydes or acids through GSH depletion and protein carbonylation. Further research into the nature of protein modification is warranted for these current-use fluorochemicals.

  16. Influence of decompression sickness on vasocontraction of isolated rat vessels.

    PubMe