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Sample records for rat heart comparison

  1. Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo

    SciTech Connect

    Herrmann, Julia E.; Heale, Jason; Bieraugel, Mike; Ramos, Meg; Fisher, Robyn L.; Vickers, Alison E.M.

    2014-01-15

    Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100 μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24 h. In this in vivo rat study (0.5 mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48 h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70 kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices. - Highlights: • Human response to isoproterenol induced cardiac injury evaluated in heart slices. • Isoproterenol altered apoptosis, energy, inflammation and remodeling pathways. • Human model verified by comparison to rat heart slices and rat heart in vivo. • Human and rat respond to isoproterenol

  2. Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo.

    PubMed

    Herrmann, Julia E; Heale, Jason; Bieraugel, Mike; Ramos, Meg; Fisher, Robyn L; Vickers, Alison E M

    2014-01-15

    Human response to isoproterenol induced cardiac injury was evaluated by gene and protein pathway changes in human heart slices, and compared to rat heart slices and rat heart in vivo. Isoproterenol (10 and 100μM) altered human and rat heart slice markers of oxidative stress (ATP and GSH) at 24h. In this in vivo rat study (0.5mg/kg), serum troponin concentrations increased with lesion severity, minimal to mild necrosis at 24 and 48h. In the rat and the human heart, isoproterenol altered pathways for apoptosis/necrosis, stress/energy, inflammation, and remodeling/fibrosis. The rat and human heart slices were in an apoptotic phase, while the in vivo rat heart exhibited necrosis histologically and further progression of tissue remodeling. In human heart slices genes for several heat shock 70kD members were altered, indicative of stress to mitigate apoptosis. The stress response included alterations in energy utilization, fatty acid processing, and the up-regulation of inducible nitric oxide synthase, a marker of increased oxidative stress in both species. Inflammation markers linked with remodeling included IL-1α, Il-1β, IL-6 and TNFα in both species. Tissue remodeling changes in both species included increases in the TIMP proteins, inhibitors of matrix degradation, the gene/protein of IL-4 linked with cardiac fibrosis, and the gene Ccl7 a chemokine that induces collagen synthesis, and Reg3b a growth factor for cardiac repair. This study demonstrates that the initial human heart slice response to isoproterenol cardiac injury results in apoptosis, stress/energy status, inflammation and tissue remodeling at concentrations similar to that in rat heart slices.

  3. Natriuretic Peptides as Cardiovascular Safety Biomarkers in Rats: Comparison With Blood Pressure, Heart Rate, and Heart Weight.

    PubMed

    Engle, Steven K; Watson, David E

    2016-02-01

    Cardiovascular (CV) toxicity is an important cause of failure during drug development. Blood-based biomarkers can be used to detect CV toxicity during preclinical development and prioritize compounds at lower risk of causing such toxicities. Evidence of myocardial degeneration can be detected by measuring concentrations of biomarkers such as cardiac troponin I and creatine kinase in blood; however, detection of functional changes in the CV system, such as blood pressure, generally requires studies in animals with surgically implanted pressure transducers. This is a significant limitation because sustained changes in blood pressure are often accompanied by changes in heart rate and together can lead to cardiac hypertrophy and myocardial degeneration in animals, and major adverse cardiovascular events (MACE) in humans. Increased concentrations of NPs in blood correlate with higher risk of cardiac mortality, all-cause mortality, and MACE in humans. Their utility as biomarkers of CV function and toxicity in rodents was investigated by exploring the relationships between plasma concentrations of NTproANP and NTproBNP, blood pressure, heart rate, and heart weight in Sprague Dawley rats administered compounds that caused hypotension or hypertension, including nifedipine, fluprostenol, minoxidil, L-NAME, L-thyroxine, or sunitinib for 1-2 weeks. Changes in NTproANP and/or NTproBNP concentrations were inversely correlated with changes in blood pressure. NTproANP and NTproBNP concentrations were inconsistently correlated with relative heart weights. In addition, increased heart rate was associated with increased heart weights. These studies support the use of natriuretic peptides and heart rate to detect changes in blood pressure and cardiac hypertrophy in short-duration rat studies.

  4. Comparison of carbon dioxide and argon euthanasia: effects on behavior, heart rate, and respiratory lesions in rats.

    PubMed

    Burkholder, Tanya H; Niel, Lee; Weed, James L; Brinster, Lauren R; Bacher, John D; Foltz, Charmaine J

    2010-07-01

    In this study we compared rat (n = 16) responses to euthanasia with either gradual-fill CO(2) or rapid induction argon gas by evaluating the animals' heart rate via radiotelemetry, behavior, and vocalizations. We also evaluated the histologic effects of the gases. Rats were placed in an open test chamber 24 h before the start of the experiment. During baseline tests, rats were exposed to oxygen to evaluate the effects of the noise and movement of gas entering the chamber; 1 wk later, rats were euthanized by gas displacement with either 10%/min CO(2) or 50%/min argon gas. Rats tended to have higher heart rats and were more active during the baseline test, but these parameters were normal before the euthanasia experiment, suggesting that the rats had acclimated to the equipment. Heart rate, behavior, and ultrasonic vocalizations were recorded for 2 min after gas introduction in both groups. All rats appeared conscious throughout the test interval. The heart rates of rats exposed to argon did not change, whereas those of rats exposed to CO(2) declined significantly. Unlike those exposed to CO(2), rats euthanized with argon gas gasped and demonstrated seizure-like activity. There were no differences in the pulmonary lesions resulting from death by either gas. Our results suggest that argon as a sole euthanasia agent is aversive to rats. CO(2) using a 10%/min displacement may be less aversive than more rapid displacements. Future research investigating methods of euthanasia should allow sufficient time for the rats to acclimate to the test apparatus.

  5. Comparison of slow inactivation in human heart and rat skeletal muscle Na+ channel chimaeras

    PubMed Central

    O'Reilly, John P; Wang, Sho-Ya; Kallen, Roland G; Wang, Ging Kuo

    1999-01-01

    Voltage-gated Na+ channels undergo two types of inactivation in response to depolarization. One type, fast inactivation, occurs with a time scale of milliseconds. The other, slow inactivation, occurs over seconds to minutes. In addition, these two processes appear to be distinct at the molecular level. However, the molecular mechanism of Na+ channel slow inactivation is unknown. We used patch clamp techniques to study slow inactivation, activation and fast inactivation in α-subunit cDNA clones for wild-type human heart Na+ channels (hH1) and rat skeletal muscle Na+ channels (μ1) transiently expressed in human embryonic kidney (HEK) cells. Our experiments showed that the Na+ channel slow inactivation phenotype (development, steady state and recovery) differed dramatically between hH1 and μ1. Slow inactivation in μ1 had a faster onset, a steeper voltage dependence, and was more complete compared with hH1. In addition, recovery from slow inactivation was much slower for μ1 than for hH1. Activation and fast inactivation kinetics were also different in hH1 and μ1. In hH1, fast inactivation was slower and V½ values of activation and steady-state fast inactivation (h∞) were more negative than in μ1. To better understand the molecular basis of Na+ channel slow inactivation, Na+ channel chimaeras were constructed with domains from hH1 and μ1. The slow inactivation phenotype in the chimaeras (domains denoted by subscripts) μ1(1)hH1(2,3,4), μ1(1,2)hH1(3,4) and μ1(1,2,3)hH1(4) was intermediate compared with that of wild-type. However, the chimaera μ1(1)hH1(2,3,4) was more like wild-type hH1, while the chimaeras μ1(1,2)hH1(3,4) and μ1(1,2,3)hH1(4) were more similar to wild-type μ1. In the chimaeras, activation resembled that of μ1, fast inactivation resembled that of hH1, and steady-state fast inactivation fell between that of hH1 and μ1. The data demonstrate that all four domains can modulate the Na+ channel slow inactivation phenotype. However, domains D1

  6. Orally supplemented catechin increases heme amounts and catalase activities in rat heart blood mitochondria: a comparison between middle-aged and young rats.

    PubMed

    Cueno, Marni E; Tamura, Muneaki; Imai, Kenichi; Ochiai, Kuniyasu

    2013-11-01

    Orally-administered catechin has long been known to have several beneficial effects on the mammalian host, however, the effects of orally supplemented catechin on the host through gingival tissues have not yet been established. Here, we elucidated the effects of orally supplemented catechin in the rat heart blood mitochondria. We used middle-aged (40 week-old) and young (4 week-old) rats throughout the study. We indirectly verified blood serum catechin levels by measuring O-methyl catechin derivatives using HPLC. Interestingly, we observed higher blood serum O-methyl levels in middle-aged rats as compared to young rats. Subsequently, we isolated blood mitochondria, verified its purity, and measured heme, hydrogen peroxide, and catalase (CAT) levels. We found that catechin induces an increase in blood mitochondrial heme amounts and is associated with an increase in blood mitochondrial CAT activity which is surprisingly higher in middle-aged rats as compared to young rats. This would imply that orally supplemented catechin induces heme increase that preferentially favours CAT activity and is more beneficial to the middle-aged rats.

  7. Comparison of arrhythmogenicity and proinflammatory activity induced by intramyocardial or epicardial myoblast sheet delivery in a rat model of ischemic heart failure.

    PubMed

    Pätilä, Tommi; Miyagawa, Shigeru; Imanishi, Yukiko; Fukushima, Satsuki; Siltanen, Antti; Mervaala, Eero; Kankuri, Esko; Harjula, Ari; Sawa, Yoshiki

    2015-01-01

    Although cell therapy of the failing heart by intramyocardial injections of myoblasts to results in regenerative benefit, it has also been associated with undesired and prospectively fatal arrhythmias. We hypothesized that intramyocardial injections of myoblasts could enhance inflammatory reactivity and facilitate electrical cardiac abnormalities that can be reduced by epicardial myoblast sheet delivery. In a rat model of ischemic heart failure, myoblast therapy either by intramyocardial injections or epicardial cell sheets was given 2 weeks after occlusion of the coronary artery. Ventricular premature contractions (VPCs) were assessed, using an implanted three-lead electrocardiograph at 1, 7, and 14 days after therapy, and 16-point epicardial electropotential mapping (EEPM) was used to evaluate ventricular arrhythmogenicity under isoproterenol stress. Cardiac functioning was assessed by echocardiography. Both transplantation groups showed therapeutic benefit over sham therapy. However, VPCs were more frequent in the Injection group on day 1 and day 14 after therapy than in animals receiving epicardial or sham therapy (p < 0.05 and p < 0.01, respectively). EEPM under isoproterenol stress showed macroreentry at the infarct border area, leading to ventricular tachycardias in the Injection group, but not in the myoblast sheet- or sham-treated groups (p = 0.045). Both transplantation types modified the myocardial cytokine expression profile. In animals receiving epicardial myoblast therapy, selective reductions in the expressions of interferon gamma, interleukin (IL)-1β and IL12 were observed, accompanied by reduced infiltration of inflammatory CD11b- and CD68-positive leukocytes, compared with animals receiving myoblasts as intramyocardial injections. Intramyocardial myoblast delivery was associated with enhanced inflammatory and immunomodulatory reactivity and increased frequency of VPCs. In comparison to intramyocardial injection, the epicardial route may serve as

  8. Utility of a Novel Biofeedback Device for Within-Breath Modulation of Heart Rate in Rats: A Quantitative Comparison of Vagus Nerve vs. Right Atrial Pacing

    PubMed Central

    O'Callaghan, Erin L.; Chauhan, Ashok S.; Zhao, Le; Lataro, Renata M.; Salgado, Helio C.; Nogaret, Alain; Paton, Julian F. R.

    2016-01-01

    In an emerging bioelectronics era, there is a clinical need for physiological devices incorporating biofeedback that permits natural and demand-dependent control in real time. Here, we describe a novel device termed a central pattern generator (CPG) that uses cutting edge analog circuitry producing temporally controlled, electrical stimulus outputs based on the real time integration of physiological feedback. Motivated by the fact that respiratory sinus arrhythmia (RSA), which is the cyclical changes in heart rate every breath, is an essential component of heart rate variability (HRV) (an indicator of cardiac health), we have explored the versatility and efficiency of the CPG for producing respiratory modulation of heart rate in anesthetized, spontaneously breathing rats. Diaphragmatic electromyographic activity was used as the input to the device and its output connected to either the right cervical vagus nerve or the right atrium for pacing heart rate. We found that the CPG could induce respiratory related heart rate modulation that closely mimicked RSA. Whether connected to the vagus nerve or right atrium, the versatility of the device was demonstrated by permitting: (i) heart rate modulation in any phase of the respiratory cycle, (ii) control of the magnitude of heart rate modulation, and (iii) instant adaptation to changes in respiratory frequency. Vagal nerve pacing was only possible following transection of the nerve limiting its effective use chronically. Pacing via the right atrium permitted better flexibility and control of heart rate above its intrinsic level. This investigation now lays the foundation for future studies using this biofeedback technology permitting closer analysis of both the function and dysfunction of RSA. PMID:26869940

  9. Radiation-induced heart disease in rats

    SciTech Connect

    Lauk, S.; Kiszel, Z.; Buschmann, J.; Trott, K.R.

    1985-04-01

    After local irradiation of the rat heart with X ray doses of over 10 Gy (single dose), animals developed symptoms of radiation-induced heart disease, which at higher doses would lead to fatal cardiac failure. The LD 50 at 1 year was between 15 Gy and 20 Gy. The pericardium and epicardium responded to irradiation with exudative pericarditis after 4 months. Focal myocardial damage was secondary to progressive capillary damage.

  10. Transthoracic echocardiography in rats. Evalution of commonly used indices of left ventricular dimensions, contractile performance, and hypertrophy in a genetic model of hypertrophic heart failure (SHHF-Mcc-facp-Rats) in comparison with Wistar rats during aging.

    PubMed

    Reffelmann, Thorsten; Kloner, Robert A

    2003-09-01

    Two-weekly echocardiographic examinations were conducted in nine SHHF-Mc-fa(cp) rats in comparison with eight age-matched Wistar rats. In the SHHF-rats, characterized by progressive LV-dilation and decreasing contractile function between 77-87 weeks of age, left ventricular (LV) hypertrophy was most sensitively demonstrated by increased LV-mass-index (p < 0.001). LV-areas and area-ejection fraction (EF) (2D-images) discriminated more sensitively in the early stages than M-mode-derived diameters and fractional shortening (FS); midwall shortening was the most sensitive parameter of reduced systolic function. Post-mortem measurements showed an excellent correlation with calculated LV-mass (r = 0.91). Post-mortem LV-volumes correlated significantly with diastolic LV-diameters, LV-areas, and calculated LV-volumes (r = 0.56-0.59). Mean within-subject standard deviations in controls were 0.5-0.6 mm (LV-diameters), 3.1-4.6 mm(2) (LV-areas), approximately 10% of the mean for FS, area-EF and midwall shortening, and approximately 20% for wall thickness and LV-mass. The data might be used to choose the most sensitive parameters, and to estimate sample size for echocardiographic investigations in rats.

  11. Skeletal muscle electrical stimulation improves baroreflex sensitivity and heart rate variability in heart failure rats.

    PubMed

    Lazzarotto Rucatti, Ananda; Jaenisch, Rodrigo Boemo; Rossato, Douglas Dalcin; Bonetto, Jéssica Hellen Poletto; Ferreira, Janaína; Xavier, Leder Leal; Sonza, Anelise; Dal Lago, Pedro

    2015-12-01

    The goal of the current study was to evaluate the effects of electrical stimulation (ES) on the arterial baroreflex sensitivity (BRS) and cardiovascular autonomic control in rats with chronic heart failure (CHF). Male Wistar rats were designated to one of four groups: placebo sham (P-Sham, n=9), ES sham (ES-Sham, n=9), placebo CHF (P-CHF, n=9) or ES CHF (ES-CHF, n=9). The ES was adjusted at a low frequency (30 Hz), duration of 250 μs, with hold and rest time of 8s (4 weeks, 30 min/day, 5 times/week). It was applied on the gastrocnemius muscle with intensity to produce a visible muscle contraction. The rats assigned to the placebo groups performed the same procedures with the equipment turned off. The two-way ANOVA and the post hoc Student-Newman-Keuls tests (P<0.05) were used to data comparison. The BRS was higher in ES-Sham group compared to the P-Sham group and the ES-CHF group compared to the P-CHF group. ES was able to decrease heart rate sympatho-vagal modulation and peripheral sympathetic modulation in ES-CHF compared to P-CHF group. Interestingly, heart rate sympatho-vagal modulation was similar between ES-CHF and P-Sham groups. Thus, ES enhances heart rate parasympathetic modulation on heart failure (ES-CHF) compared to placebo (P-CHF), with consequent decrease of sympatho-vagal balance in the ES-CHF group compared to the P-CHF. The results show that a 4 week ES protocol in CHF rats enhances arterial BRS and cardiovascular autonomic control.

  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. A two-dimensional electrophoresis database of rat heart proteins.

    PubMed

    Li, X P; Pleissner, K P; Scheler, C; Regitz-Zagrosek, V; Salnikow, J; Jungblut, P R

    1999-01-01

    More than 3000 myocardial protein species of Wistar Kyoto rat, an important animal model, were separated by high-resolution two-dimensional gel electrophoresis (2-DE) and characterized in terms of isoelectric point (pI) and molecular mass (Mr). Currently, the 2-DE database contains 64 identified proteins; forty-three were identified by peptide mass fingerprinting (PMF) using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), nine by exclusive comparison with other 2-DE heart protein databases, and in only 12 cases of 60 attempts N-terminal sequencing was successful. We used the Make2ddb software package downloaded from the ExPASy server for the construction of a rat myocardial 2-DE database. The Make2ddb package simplifies the creation of a new 2-DE database if the Melanie II software and a Sun workstation under Solaris are available. Our 2-DE database of rat heart proteins can be accessed at URL http://gelmatching.inf.fu-berlin.de/pleiss/2d.

  14. Prevention of anemia alleviates heart hypertrophy in copper deficient rats

    SciTech Connect

    Lure, M.D.; Fields, M.; Lewis, C.G. Univ. of Maryland, College Park Georgetown Univ., Washington, DC )

    1991-03-11

    The present investigation was designed to examine the role of anemia in the cardiomegaly and myocardial pathology of copper deficiency. Weanling rats were fed a copper deficient diet containing either starch (ST) or fructose (FRU) for five weeks. Six rats consuming the FRU diet were intraperitoneally injected once a week with 1.0 ml/100g bw of packed red blood cells (RBC) obtained from copper deficient rats fed ST. FRU rats injected with RBC did not develop anemia. Additionally, none of the injected rats exhibited heart hypertrophy or gross pathology and all survived. In contrast, non-injected FRU rats were anemic, exhibited severe signs of copper deficiency which include heart hypertrophy with gross pathology, and 44% died. Maintaining the hematocrit with RBC injections resulted in normal heart histology and prevented the mortality associated with the fructose x copper interaction. The finding suggest that the anemia associated with copper deficiency contributes to heart pathology.

  15. Comparison of aconitine-modified human heart (hH1) and rat skeletal (μ1) muscle Na+ channels: an important role for external Na+ ions

    PubMed Central

    Wright, Sterling N

    2002-01-01

    Neurotoxins such as aconitine (AC) bind to receptor site 2 on voltage-gated sodium channels and modify channel kinetics. Although AC modification typically induces hyperpolarizing shifts in sodium channel activation, the effects on channel inactivation seem to vary depending on the tissue origin of the channel. In the present study, the α subunits of human heart (hH1) and rat skeletal muscle (μ1) sodium channels were transiently expressed in human embryonic kidney (HEK293t) cells. Whole-cell currents were examined before and after AC modification of the channels to determine whether the toxin had isoform-specific effects on channel kinetics. The magnitudes of the hyperpolarizing shifts in steady-state current activation and inactivation were similar for AC-modified hH1 and μ1 channels, and AC modification did not alter the voltage dependence of macroscopic current decay of either channel subtype. There were two notable differences between hH1 and μ1 channels after AC modification. First, the steady-state availability of AC-modified μ1 channels decreased by 5–10 % after very negative conditioning pulses. Second, AC-modified μ1 channels inactivated completely at all voltages, whereas AC-modified hH1 channels exhibited sustained inward currents at voltages near the threshold of current activation. Interestingly, AC-modified hH1 channels inactivated completely if the external solution did not contain sodium ions. The data demonstrate that AC modification affects the activation of hH1 and μ1 channels similarly but affects inactivation of the two channels distinctly. The results also imply that the reduced inactivation of AC-modified hH1 channels at least partially depends on the presence of extracellular sodium. PMID:11826163

  16. Altered carnitine transport in pressure-overload hypertrophied rat hearts

    SciTech Connect

    O'Rourke, B.; Foster, K.; Reibel, D.K.

    1986-03-01

    The authors have previously observed reduced carnitine levels in hypertrophied hearts of rats subjected to aortic constriction. In an attempt to determine the mechanism for reduced myocardial carnitine content, carnitine transport was examined in isolated perfused hearts. Hearts were excised from sham-operated and aortic-constricted rats 3 weeks following surgery and perfused at 60 mm Hg aortic pressure with buffer containing various concentrations of L-/sup 14/C-carnitine. Carnitine uptake by control and hypertrophied hearts was linear throughout 30 minutes of perfusion with 40 ..mu..M carnitine. Total carnitine uptake was significantly reduced by 25% in hypertrophied hearts at each time point examined. The reduction in uptake by hypertrophied hearts was also evident when hearts were perfused with 100 or 200 ..mu..M carnitine. When 0.05 mM mersalyl acid was included in the buffer to inhibit the carrier-mediated component of transport, no difference in carnitine uptake was observed indicating that the transport of carnitine by diffusion was unaltered in the hypertrophied myocardium. Carrier-mediated carnitine uptake (total uptake - uptake by diffusion) was significantly reduced by approximately 40% in hypertrophied hearts at all concentrations examined. Thus, the reduction in carnitine content in the pressure-overload hypertrophied rat heart appears to be due to a reduction in carrier-mediated carnitine uptake by the heart.

  17. 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.

  18. Mechanisms for altered carnitine content in hypertrophied rat hearts

    SciTech Connect

    Reibel, D.K.; O'Rourke, B.; Foster, K.A.

    1987-03-01

    Carnitine levels are reduced in hypertrophied hearts of rats subjected to aortic constriction (banding) and evaluated in hypertrophied hearts of spontaneously hypertensive rats (SHR). In an attempt to determine the mechanisms for these alterations, L-(/sup 14/C)carnitine transport was examined in isolated perfused hearts. Total carnitine uptake was significantly reduced by approx.20% in hypertrophied hearts of banded rats at all perfusate carnitine concentrations employed. The reduction in total uptake was due to a 40% reduction in carrier-mediated carnitine uptake with no difference in uptake by diffusion. In contrast, carnitine uptake was not altered in isolated hypertrophied hearts of SHR. However, serum carnitine levels were elevated in SHR, which could result in increased myocardial carnitine uptake in vivo. The data suggest that altered carnitine content in hypertrophied hearts of aortic-banded rats is due to an alteration in the carrier-mediated carnitine transport system in the myocardium. However, altered carnitine content in hypertrophied hearts of SHR is not due to a change in the carnitine transport system per se but may rather be due to a change in serum carnitine levels.

  19. Calcium transport mechanisms in muskrat and rat hearts.

    PubMed

    McKean, T A

    2001-11-01

    Mammalian hearts experience calcium overload during extreme and prolonged hypoxia and the calcium overload may lead to enzyme activation and cell death. Several calcium transport systems were examined in muskrat hearts and compared to those found in rat hearts to determine if there is a species difference that might be related to the muskrats' superior ability to survive hypoxia. Radiolabeled nitredendipine binding was determined in rat and muskrat hearts to estimate the density of voltage gated calcium channels in surface membranes. There were no species differences. Calcium release channel density in the sarcoplasmic reticulum was estimated by the determination of radiolabeled ryanodine binding in muskrat and rat heart SR membranes. No differences were revealed between species. The SR uptake of calcium was measured in SR membranes from the hearts of the two species. No differences were found in the B(max) values, however, the muskrat SR membranes did have a slightly lower K(m) value. There were large species differences in Na(+)/Ca(2+) exchange in SL membranes with the muskrat heart having approximately 3.5 times the transport capacity of rat SL membranes. During hypoxic conditions in which there is extensive ATP depletion leading to [Na(+)](i) accumulation and discharge of cellular membrane potential, the Na(+)/Ca(2+) exchanger may operate in the reverse mode and import calcium into the cell and accelerate hypoxic damage. Prior to reaching this state a robust Na(+)/Ca(2+) exchange would facilitate the maintenance of normal diastolic calcium levels and calcium cycling. Muskrats hearts are hypoxia tolerant by virtue of their ability to reduce metabolic demand and generate ATP anaerobically thus, maintaining a favorable ATP balance. Therefore, the relative overexpression of Na(+)/Ca(2+) exchangers in muskrat hearts may be beneficial in the preservation of contractile function and calcium homeostasis in this freshwater diving mammal.

  20. The changes of vaccinia related kinase 1 in grafted heart after rat heart transplantation

    PubMed Central

    Qian, Shiguo; Yang, Xuechao; Wu, Kunpeng; Lv, Qiangsheng; Zhang, Yuanyuan; Dai, Jiahong; Chen, Cheng

    2014-01-01

    Objective To assess the expression and significance of vaccinia-related kinase 1 (VRK1) after rat heart transplantation. Materials and methods Lewis and Wistar rats weighing 250 to 300 g were used as donors and recipients. Allografts were from Wistar transplanted into Lewis, and isografts were transplanted from Lewis into Lewis. Grafts were harvested at 1, 3, 5, and 7 days after transplantation. We performed Western Blot of heart tissues after cardiac transplantation. To analyze VRK1 express between the isografts and allografts for immunohistochemical staining. At 5th day after heart transplantation use related cytokines VRK1 for immunohistochemical. We used double immunofluorescent staining on transverse cryosections of graft tissues by co-labeling with different markers, including those for VRK1, activate caspase-3, α-actinin, VCAM-1, CD4. Results Compared with rare expression in syngeneic Lewis rat hearts, VRK1 protein level in allogeneic hearts were detected at various survival times after heterotopic heart transplantation, which observably expressed on day 5 postoperative. In addition, we examined the expression of activate caspase-3 in allogeneic hearts, which has a similar expression with VRK1. Immunohistochemical and immunofluorescent method displayed that VRK1 was widely expressed in cytoplasm of cardiac tissue and activate caspase-3 was also expressed in cardiomyocytes. However, the VRK1 wasn’t express in inflammation. Conclusions The VRK1 expression has increased after heart transplantation in allograft and isograft, and VRK1 may play a significant role in myocardial apoptosis after heterotopic heart transplantation in rats. PMID:25589968

  1. Norepinephrine turnover in heart of the copper deficient rat

    SciTech Connect

    Seidel, K.E.; Failla, M.L.; Rosebrough, R. )

    1989-02-01

    Weaned male SD rats were fed a modified AIN-76A diet containing 62% sucrose and either 7 ppm (+Cu) or 0.5 ppm (-Cu) copper for 5 weeks. Dietary copper deprivation resulted in lower concentrations of copper in liver and serum and enlarged hearts. Tissue levels of norepinephrine (NE) and dopamine (DPA) were quantified by HPLC using electrochemical detection. Cardiac concentration of NE and DPA and 26% lower and 63% higher, respectively, in -Cu rats than in +Cu controls. Altered cardiac levels of NE and DPA in -Cu rats were also evident after overnight fasting, a stress that depresses SNS activity. NE turnover was investigated after inhibition of tyrosine hydroxylase by injection of {alpha}-methyl-p-tyrosine methyl ester (250 mg/kg). The fractional rate of NE turnover in the heart was 4.6%/hour for rats fed -Cu and +Cu diets. Calculated NE turnover was greater in heart of +Cu rats than -Cu rats (26 vs. 19 ng/g/hr). NE and DPA concentration in brain, pancreas, and spleen were not affected by dietary copper. These data suggest that synthesis of NE in cardiac nerve endings of the weaned rats sensitive to dietary copper deficiency.

  2. Physiologic consequences of local heart irradiation in rats

    SciTech Connect

    Geist, B.J.; Lauk, S.; Bornhausen, M.; Trott, K.R. )

    1990-05-01

    Noninvasive methods have been used to study the long-term cardiovascular and pulmonary functional changes at rest and after exercise in adult rats following local heart irradiation with single x-ray doses of 15, 17.5 or 20 Gy, and in non-irradiated control animals. Rats that had undergone a chronic exercise program were compared with untrained cohorts. The earliest dysfunction detected was an increased respiratory rate (f) at 10 weeks after irradiation in the highest dose group. In contrast, both telemetric heart-rate (HR) and rhythm and indirect systolic blood pressure measurements performed at rest only revealed changes starting at 43 weeks after irradiation with 20 Gy, up to which point the rats showed no clinical signs of heart failure. However, the number of minutes required for the recovery of the HR to pre-exercise levels following the implementation of a standardized exercise challenge was elevated in untrained rats compared with their trained cohorts at 18 weeks after irradiation with 20 Gy. Increases in recovery times were required in the two lowest dose groups, starting at 26 weeks after irradiation. It was concluded that the reserve capacity of the cardiopulmonary system masks functional decrements at rest for many months following local heart irradiation, necessitating the use of techniques which reveal reductions in reserve capacities. Further, the influence of local irradiation to the heart and lungs deserves closer scrutiny due to mutual interactions.

  3. Dynamics of the formation of rhythmic activity of the heart in fetuses and newborn rats.

    PubMed

    Timopheeva, O P; Vdovichenko, N D; Kuznetsov, S V

    2012-02-01

    The development of heart activity and its relationship with respiratory and motor activities were studied in rat fetuses with preserved placental circulation on gestation days 15-20 (E15-20) and in newborn rats (P0). During the studied period, the heart rate in fetuses increased from 175.93±6.10 bpm (E15) to 271.82±5.93 bpm (E20). After birth, the heart rate decreased to 220.94±8.73 bpm. Heart rate variability in the decasecond and near-minute ranges was detected. At E16 stage it is presented by slow regular oscillations lasting for 20-35 sec with an amplitude of 10-45 msec. Comparison of functional activities of the cardiac and somatic motor systems showed that at E16, fluctuations in heart rate are independent of the bouts of motor excitation. During growing, the degree of synchronization of heart rate variability with physical activity increased. E17-18 stage is characterized by short-term episodes of heart rate deceleration associated with motor activity; their duration and amplitude did not depend much on the force of movement. At E19-20, decelerations typical of early gestation terms were replaced by acceleration-type reactions typical for mature organism, which is related to maturation of coordination function of the nervous system. In the heart rhythm, respiratory arrhythmia appears during episodes of rhythmic breathing. Newborn rats demonstrated acceleration episodes; their parameters depend on the force of motor bouts; respiratory arrhythmia was not observed.

  4. Mesenchymal Stem Cells Improve Heart Rate Variability and Baroreflex Sensitivity in Rats with Chronic Heart Failure

    PubMed Central

    de Morais, Sharon Del Bem Velloso; da Silva, Luiz Eduardo Virgilio; Lataro, Renata Maria; Silva, Carlos Alberto Aguiar; de Oliveira, Luciano Fonseca Lemos; de Carvalho, Eduardo Elias Vieira; Simões, Marcus Vinicius; da Silva Meirelles, Lindolfo; Fazan, Rubens

    2015-01-01

    Heart failure induced by myocardial infarct (MI) attenuates the heart rate variability (HRV) and baroreflex sensitivity, which are important risk factors for life-threatening cardiovascular events. Therapies with mesenchymal stem cells (MSCs) have shown promising results after MI. However, the effects of MSCs on hemodynamic (heart rate and arterial pressure) variability and baroreflex sensitivity in chronic heart failure (CHF) following MI have not been evaluated thus far. Male Wistar rats received MSCs or saline solution intravenously 1 week after ligation of the left coronary artery. Control (noninfarcted) rats were also evaluated. MI size was assessed using single-photon emission computed tomography (SPECT). The left ventricular ejection fraction (LVEF) was evaluated using radionuclide ventriculography. Four weeks after MSC injection, the animals were anesthetized and instrumented for chronic ECG recording and catheters were implanted in the femoral artery to record arterial pressure. Arterial pressure and HRVs were determined in time and frequency domain (spectral analysis) while HRV was also examined using nonlinear methods: DFA (detrended fluctuation analysis) and sample entropy. The initial MI size was the same among all infarcted rats but was reduced by MSCs. CHF rats exhibited increased myocardial interstitial collagen and sample entropy combined with the attenuation of the following cardiocirculatory parameters: DFA indices, LVEF, baroreflex sensitivity, and HRV. Nevertheless, MSCs hampered all these alterations, except the LVEF reduction. Therefore, 4 weeks after MSC therapy was applied to CHF rats, MI size and myocardial interstitial fibrosis decreased, while baroreflex sensitivity and HRV improved. PMID:26059001

  5. Fatty acid utilization in pressure-overload hypertrophied rat hearts

    SciTech Connect

    Reibel, D.K.; O'Rourke, B.

    1986-03-05

    The authors have previously shown that the levels of total tissue coenzyme A and carnitine are reduced in hypertrophied hearts of rats subjected to aortic constriction. It was therefore of interest to determine if these changes were associated with alterations in fatty acid oxidation by the hypertrophied myocardium. Hearts were excised from sham-operated and aortic-constricted rats and perfused at 10 cm H/sub 2/O left atrial filling pressure with a ventricular afterload of 80 cm of H/sub 2/O with buffer containing 1.2 mM /sup 14/C-linoleate. Heart rate and peak systolic pressure were not different in control and hypertrophied hearts. /sup 14/CO/sub 2/ production was linear in both groups of hearts between 10 and 30 minutes of perfusion. The rate of fatty acid oxidation determined by /sup 14/CO/sub 2/ production during this time was 0.728 +/- 0.06 ..mu..moles/min/g dry in control hearts and 0.710 +/- 0.02 ..mu..moles/min/g dry in hypertrophied hearts. Comparable rates of fatty acid oxidation were associated with comparable rates of O/sub 2/ consumption in the two groups of hearts (39.06 +/- 3.50 and 36.78 +/- 2.39 ..mu..moles/g dry/min for control and hypertrophied hearts, respectively). The data indicate that the ability of the hypertrophied heart to oxidize fatty acids under these perfusion conditions is not impaired in spite of significant reductions in tissue levels of coenzyme A and carnitine.

  6. 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

  7. Pycnogenol® and its fractions influence the function of isolated heart in rats with experimental diabetes mellitus.

    PubMed

    Kralova, Eva; Jankyova, Stanislava; Mucaji, Pavel; Gresakova, Eva; Stankovicova, Tatiana

    2015-02-01

    The aim of this study was to test the effect of Pycnogenol(®) (PYC) mixture and its three fractions (buthanolic, water, ethyl acetate) on heart function in rats with experimental diabetes mellitus (DM) and compare their effects to the diabetic group. Their antioxidant activity "in vitro" was also determined. DM rats (streptozotocin over 3 consecutive days at a dose of 25 mg/kg of body weight) had increased systolic blood pressure, thicker left ventriculi wall (LV) and weaker myocardial contraction, prolonged QT interval in comparison to controls rats. In comparison to the diabetic group, PYC (20 mg/kg b.w./day) suppressed the influence of DM on the LV, improved contraction, increased coronary flow and displayed negative effect on electrical activity of hearts. The most effective of PYC's fractions was the water fraction. It improved biometric parameters and hemodynamic function of the DM hearts, enhanced shortening the QT interval, reduced the amount of dysrhythmias of the DM hearts and had the strongest antioxidant activity. In conclusion, DM damaged isolated rat heart function. Only the water fraction improved the function of the diabetic heart. The different results of three fractions and PYC on myocardial function may be caused by a various lipo- and hydro-philic action of the PYC components.

  8. Carvedilol protected diabetic rat hearts via reducing oxidative stress

    PubMed Central

    Huang, He; Shan, Jiang; Pan, Xiao-hong; Wang, Hui-ping; Qian, Ling-bo

    2006-01-01

    Oxidative stress plays a dominant role in the pathogenesis of diabetes mellitus. Bcl-2 gene has close connection with antioxidant stress destruction in many diseases including diabetes. Carvedilol, an adrenoceptor blocker, also has antioxidant properties. To study the effect of carvedilol on the antioxidant status in diabetic hearts, we investigated carvedilol-administrated healthy and streptozotocin-induced diabetic rats. After small and large dosage carvedilol-administered for 5 weeks, hemodynamic parameters, the levels of malondialdehyde, activities of antioxidant enzymes and expression of Bcl-2 mRNA in the cardiac tissues were measured. The diabetic rats not only had cardiac disfunction, weaker activities of antioxidant enzymes, but also showed lower expression of Bcl-2. Carvedilol treatment increased activities of antioxidant enzymes and expression of Bcl-2 in healthy rats as well as diabetic rats. These results indicated that carvedilol partly improves cardiac function via its antioxidant properties in diabetic rats. PMID:16909474

  9. Arrhythmogenic effect of androgens on the rat heart.

    PubMed

    Argenziano, Mariana; Tiscornia, Gisela; Moretta, Rosalia; Casal, Leonardo; Potilinski, Constanza; Amorena, Carlos; Gras, Eduardo Garcia

    2017-01-01

    In most species androgens shorten the cardiac action potential and reduce the risk of afterdepolarizations. Despite the central role of the rat model in physiological studies, the effects of androgens on the rat heart are still inconclusive. We therefore performed electrophysiological studies on the perfused rat right ventricular free wall. We found a correlation between androgenic activity and a propensity to generate ventricular ectopic action potentials. We also found that the testosterone treatment increased action potential duration at 90 % of repolarization (APD90), while androgenic inhibition increased the time to peak and decreased APD90. We observed that the voltage-gated potassium channel Kv4.3 and the bi-directional membrane ion transporter NCX in the rat myocardium were regulated by androgenic hormones. One possible explanation for these findings is that due to the expression of specific ion channels in the rat myocardium, the action potential response to its hormonal background is different from those described in other experimental models. Our results indicate that androgenic control of NCX expression plays a key role in determining arrhythmogenicity in the rat heart.

  10. Melatonin protects against ischemic heart failure in rats.

    PubMed

    Şehirli, Ahmet Özer; Koyun, Derya; Tetik, Şermin; Özsavcı, Derya; Yiğiner, Ömer; Çetinel, Şule; Tok, Olgu Enis; Kaya, Zehra; Akkiprik, Mustafa; Kılıç, Ertugrul; Şener, Göksel

    2013-09-01

    Ischemic injury, which occurs as a result of sympathetic hyperactivity, plays an important role in heart failure. Melatonin is thought to have antiatherogenic, antioxidant, and vasodilatory effects. In this study, we investigated whether melatonin protects against ischemic heart failure (HF). In Wistar albino rats, HF was induced by left anterior descending (LAD) coronary artery ligation and rats were treated with either vehicle or melatonin (10 mg/kg) for 4 weeks. At the end of this period, echocardiographic measurements were recorded and the rats were decapitated to obtain plasma and cardiac tissue samples. Lactate dehydrogenase, creatine kinase, aspartate aminotransferase, alanine aminotransferase, and lysosomal enzymes (β-D-glucuronidase, β-galactosidase, β-D-N-acetyl-glucosaminidase, acid phosphatase, and cathepsin-D) were studied in plasma samples, while malondialdehyde and glutathione levels and Na+, K+-ATPase, caspase-3 and myeloperoxidase activities were determined in the cardiac samples. Sarco/endoplasmic reticulum calcium ATPase (SERCA) and caveolin-3 levels in cardiac tissues were evaluated using Western blot analyses. Furthermore, caveolin-3 levels were also determined by histological analyses. In the vehicle-treated HF group, cardiotoxicity resulted in decreased cardiac Na+, K+-ATPase and SERCA activities, GSH contents and caveolin-3 levels, while plasma LDH, CK, and lysosomal enzyme activities and cardiac MDA and Myeloperoxidase (MPO) activities were found to be increased. On the other hand, melatonin treatment reversed all the functional and biochemical changes. The present results demonstrate that Mel ameliorates ischemic heart failure in rats. These observations highlight that melatonin is a promising supplement for improving defense mechanisms in the heart against oxidative stress caused by heart failure.

  11. Mitochondrial and Metabolic Gene Expression in the Aged Rat Heart

    PubMed Central

    Barton, Gregory P.; Sepe, Joseph J.; McKiernan, Susan H.; Aiken, Judd M.; Diffee, Gary M.

    2016-01-01

    Aging is associated with a decline in cardiac function. Exercise intervention has been suggested as a way to improve this decrement. Age-related decline in cardiac function is associated with decreases in fatty acid oxidation, mitochondrial function, and AMP-activated protein kinase (AMPK) activity. The molecular mechanisms involved with age-related changes in mitochondrial function and substrate metabolism are poorly understood. We determined gene expression differences in hearts of Young (6 mo), Old (33 mo), and old exercise trained (Old + EXE) (34 mo) FBN rats, using Qiagen PCR arrays for Glucose, Fatty acid, and Mitochondrial metabolism. Old rats demonstrated decreased (p < 0.05) expression for key genes in fatty acid oxidation, mitochondrial function, and AMPK signaling. There were no differences in the expression of genes involved in glucose metabolism with age. These gene expression changes occurred prior to altered protein translation as we found no differences in the protein content of peroxisome proliferator activated receptor gamma, coactivators 1 alpha (PGC-1α), peroxisome proliferator activated receptor alpha (PPARα), and AMPKα2 between young and old hearts. Four months of exercise training did not attenuate the decline in the gene expression in aged hearts. Despite this lack of change in gene expression, exercise-trained rats demonstrated increased exercise capacity compared to their sedentary counterparts. Taken together, our results show that differential expression of genes associated with fatty acid metabolism, AMPK signaling and mitochondrial function decrease in the aging heart which may play a role in age-related declines in fatty acid oxidation, AMPK activity, and mitochondrial function in the heart. PMID:27601998

  12. Development of neuropeptide Y-mediated heart innervation in rats.

    PubMed

    Masliukov, Petr M; Moiseev, Konstantin; Emanuilov, Andrey I; Anikina, Tatyana A; Zverev, Alexey A; Nozdrachev, Alexandr D

    2016-02-01

    Neuropeptide Y (NPY) plays a trophic role in the nervous and vascular systems and in cardiac hypertrophy. However, there is no report concerning the expression of NPY and its receptors in the heart during postnatal development. In the current study, immunohistochemistry and Western blot analysis was used to label NPY, and Y1R, Y2R, and Y5R receptors in the heart tissue and intramural cardiac ganglia from rats of different ages (newborn, 10 days old, 20 days old, 30 days old, 60 days old, 1 year old, and 2 years old).The obtained data suggest age-dependent changes of NPY-mediated heart innervation. The density of NPY-immunoreactive (IR) fibers was the least in newborn animals and increased in the first 20 days of life. In the atria of newborn and 10-day-old rats, NPY-IR fibers were more abundant compared with the ventricles. The vast majority of NPY-IR fibers also contained tyrosine hydroxylase, a key enzyme in catecholamine synthesis.The expression of Y1R increased between 10 and 20 days of life. Faint Y2R immunoreactivity was observed in the atria and ventricles of 20-day-old and older rats. In contrast, the highest level of the expression of Y5R was found in newborn pups comparing with more adult rats. All intramural ganglionic neurons were also Y1R-IR and Y5R-IR and Y2R-negative in all studied animals.Thus, the increasing of density of NPY-containing nerve fibers accompanies changes in relation of different subtypes of NPY receptors in the heart during development.

  13. Oxidative Damage in the Aging Heart: an Experimental Rat Model

    PubMed Central

    Marques, Gustavo Lenci; Neto, Francisco Filipak; Ribeiro, Ciro Alberto de Oliveira; Liebel, Samuel; de Fraga, Rogério; Bueno, Ronaldo da Rocha Loures

    2015-01-01

    Introduction: Several theories have been proposed to explain the cause of ‘aging’; however, the factors that affect this complex process are still poorly understood. Of these theories, the accumulation of oxidative damage over time is among the most accepted. Particularly, the heart is one of the most affected organs by oxidative stress. The current study, therefore, aimed to investigate oxidative stress markers in myocardial tissue of rats at different ages. Methods: Seventy-two rats were distributed into 6 groups of 12 animals each and maintained for 3, 6, 9, 12, 18 and 24 months. After euthanasia, the heart was removed and the levels of non-protein thiols, lipid peroxidation, and protein carbonylation, as well as superoxide dismutase and catalase activities were determined. Results: Superoxide dismutase, catalase activity and lipid peroxidation were reduced in the older groups of animals, when compared with the younger group. However, protein carbonylation showed an increase in the 12-month group followed by a decrease in the older groups. In addition, the levels of non-protein thiols were increased in the 12-month group and not detected in the older groups. Conclusion: Our data showed that oxidative stress is not associated with aging in the heart. However, an increase in non-protein thiols may be an important factor that compensates for the decrease of superoxide dismutase and catalase activity in the oldest rats, to maintain appropriate antioxidant defenses against oxidative insults. PMID:27006709

  14. The NO stimulator, Catestatin, improves the Frank-Starling response in normotensive and hypertensive rat hearts.

    PubMed

    Angelone, T; Quintieri, A M; Pasqua, T; Filice, E; Cantafio, P; Scavello, F; Rocca, C; Mahata, S K; Gattuso, A; Cerra, M C

    2015-08-01

    The myocardial response to mechanical stretch (Frank-Starling law) is an important physiological cardiac determinant. Modulated by many endogenous substances, it is impaired in the presence of cardiovascular pathologies and during senescence. Catestatin (CST:hCgA352-372), a 21-amino-acid derivate of Chromogranin A (CgA), displays hypotensive/vasodilatory properties and counteracts excessive systemic and/or intra-cardiac excitatory stimuli (e.g., catecholamines and endothelin-1). CST, produced also by the myocardium, affects the heart by modulating inotropy, lusitropy and the coronary tone through a Nitric Oxide (NO)-dependent mechanism. This study evaluated the putative influence elicited by CST on the Frank-Starling response of normotensive Wistar-Kyoto (WKY) and hypertensive (SHR) hearts by using isolated and Langendorff perfused cardiac preparations. Functional changes were evaluated on aged (18-month-old) WKY rats and SHR which mimic human chronic heart failure (HF). Comparison to WKY rats, SHR showed a reduced Frank-Starling response. In both rat strains, CST administration improved myocardial mechanical response to increased end-diastolic pressures. This effect was mediated by EE/IP3K/NOS/NO/cGMP/PKG, as revealed by specific inhibitors. CST-dependent positive Frank-Starling response is paralleled by an increment in protein S-Nitrosylation. Our data suggested CST as a NO-dependent physiological modulator of the stretch-induced intrinsic regulation of the heart. This may be of particular importance in the aged hypertrophic heart, whose function is impaired because of a reduced systolic performance accompanied by delayed relaxation and increased diastolic stiffness.

  15. 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

  16. Autoradiographic characterization of beta-adrenoceptors in rat heart valve leaflets

    SciTech Connect

    Pinto, J.E.; Nazarali, A.J.; Torda, T.; Saavedra, J.M.

    1989-03-01

    beta-Adrenoceptors were localized and characterized in valve leaflets of the rat heart. Sixteen micrometer-thick tissue sections containing the mitral and aortic valves were incubated with (-)3-(/sup 125/I)iodocyanopindolol followed by autoradiography with computerized microdensitometry and comparison with /sup 125/I-labeled standards. beta-Adrenoceptors were present in all the valves studied. The selective beta 1-adrenoceptor antagonist CGP 20712 A (100 nM) displaced not more than 20% of the total binding sites, suggesting that most of the beta-adrenoceptors in the valve leaflets are of the beta 2-subtype. Forskolin-binding sites were detected in the mitral valve leaflet by incubation of adjacent tissue sections with (12-/sup 3/H)forskolin. Our results indicate that catecholamines could regulate the function of the heart valves through stimulation of beta 2-adrenoceptors.

  17. Heart Alterations after Domoic Acid Administration in Rats

    PubMed Central

    Vieira, Andres C.; Cifuentes, José Manuel; Bermúdez, Roberto; Ferreiro, Sara F.; Castro, Albina Román; Botana, Luis M.

    2016-01-01

    Domoic acid (DA) is one of the best known marine toxins, causative of important neurotoxic alterations. DA effects are documented both in wildlife and experimental assays, showing that this toxin causes severe injuries principally in the hippocampal area. In the present study we have addressed the long-term toxicological effects (30 days) of DA intraperitoneal administration in rats. Different histological techniques were employed in order to study DA toxicity in heart, an organ which has not been thoroughly studied after DA intoxication to date. The presence of DA was detected by immunohistochemical assays, and cellular alterations were observed both by optical and transmission electron microscopy. Although histological staining methods did not provide any observable tissue damage, transmission electron microscopy showed several injuries: a moderate lysis of myofibrils and loss of mitochondrial conformation. This is the first time the association between heart damage and the presence of the toxin has been observed. PMID:26978401

  18. Effect of suprachiasmatic lesions on diurnal heart rate rhythm in the rat

    NASA Technical Reports Server (NTRS)

    Saleh, M. A.; Winget, C. M.

    1977-01-01

    Heart rate and locomotor activity of rats kept under 12L/12D illumination regimen were recorded every six minutes for ten days using implantable radio transmitters. Some of the rats then received bilateral RF lesions into the suprachiasmatic nucleus (SCN). Control sham operations were performed on the rest of the animals. After recovery from surgery, recording of heart rate and locomotor activity was continued for ten days. SCN-lesioned rats showed no significant diurnal fluctuation in heart rate, while normal and sham-operated rats showed the normal diurnal rhythm in that function. The arrhythmic diurnal heart-rate pattern of SCN rats appeared to be correlated with their sporadic activity pattern. The integrity of the suprachiasmatic nucleus is therefore necessary for the generation and/or expression of diurnal rhythmicity in heart rate in the rat.

  19. 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.

  20. Endothelin-1 contributes to the Frank-Starling response in hypertrophic rat hearts.

    PubMed

    Piuhola, Jarkko; Szokodi, István; Kinnunen, Pietari; Ilves, Mika; deChâtel, Rudolf; Vuolteenaho, Olli; Ruskoaho, Heikki

    2003-01-01

    Endothelin-1 is involved in mechanical load-induced cardiac growth processes; it also has effects on contractility. The interaction of endothelin-1 and the Frank-Starling response is unknown. The present study aimed to characterize the role of endothelin-1 in the regulation of the Frank-Starling response, one of the major mechanisms regulating cardiac contractile force, in both normal and hypertrophied hearts. Nontransgenic rat hearts and hypertrophic hearts of hypertensive double transgenic rats harboring human angiotensinogen and renin genes were studied in a Langendorff isolated heart setup with a liquid-filled balloon inside the left ventricle used to measure contractile parameters. The rats were studied at compensated phase, before showing any signs of heart failure. Compensated hypertrophy in double transgenic rat hearts resulted in improved contractility at a given level of preload when compared with nontransgenic rat hearts. Hearts of both rat lines showed preserved Frank-Starling responses, that is, increased contractile function in response to increased end-diastolic pressure. The mixed endothelin A/B receptor antagonist bosentan attenuated the Frank-Starling response by 53% (P<0.01) in the double transgenic hearts but not in nontransgenic hearts. The diastolic parameters remained unaffected. The left ventricles of the double transgenic rat hearts showed an 82% higher level of endothelin type A receptor mRNA and a 25% higher level of immunoreactive endothelin-1 compared with nontransgenic rat hearts. The type 1 angiotensin II receptor antagonist CV-11974 had no significant effect on contractile function in response to load in either strain. These results show that endogenous endothelin-1 contributes to the Frank-Starling response in hypertrophied rat hearts by affecting systolic performance.

  1. [Comparison of the mean-term physiological effects of cis or trans docosenoic acids in the rat. I. Digestibility of fatty acids. Effects on growth, organ weights and heart histology].

    PubMed

    Astorg, P O; Levillain, R

    1979-01-01

    The mean-term physiological effects of brassidic acid (n-9, trans docosenoic acid) and of erucic acid (n-9, cis docosenoic acid) have been compared to those of their C 18 homologues, elaidic and oleic acid, in a 2(3) factorial experiment; the 3 tested factors are: 1) the chain length of the dietary monoenes (C 22:1 vs. C 18:1), 2) the geometrical configuration of their double bond (trans vs. cis) and 3) the dietary level of linoleic acid (30% vs. 1,7% of dietary fatty acids). Wistar weanling rats have been fed for 16 weeks semi-synthetic diets containing 15% of lipids by weight, in which the fatty acids under study (brassidic, erucic elaidic) ranged to 40%. Although caution has been taken to optimize the digestibility of brassidic acid (interesterification of the lipid mixture, reduced level of calcium in the diet, addition of monoglycerides), it remains lower that of erucic acid. However, because of different levels of food consumption, the absorbed amounts of the two isomers are about the same. With a high dietary supply of linoleic acid, the dietary monoenes (C 22:1 or C 18:1), cis or trans) do not induce great changes in the weight gain of the rats, when adjusted to food consumption; linoleic acid subdeficiency lowers this adjusted weight gain, except when the diet contains oleic acid as the only monoene. These effects do not parallel those observed on the absolute growth of the rats. The trans monoenes, and to a lesser extent, erucic acid, induce an increase of liver weight (adjusted to body weight). The light microscopic histological study of the heart does not reveal any difference between the brassidic acid fed-rats and those fed the C 18:1 monoenes (elaidic, oleic). In contrast, erucic acid induces definite lesions of the myocardium. The dietary level of linoleic acid has little influence on the incidence and the severity of the lesions. The effects of these dietary fatty acids on the lipid contents and fatty acid compositions of different organs will be

  2. Effects of gender on heart injury after intracerebral hemorrhage in rats.

    PubMed

    Ye, Zi; Xie, Qing; Xi, Guohua; Keep, Richard F; Hua, Ya

    2011-01-01

    Intracerebral hemorrhage (ICH)-induced brain injury is less in female than in male rats, and estrogen can reduce such injury in males. Myocardial injury occurs after ischemic and hemorrhagic stroke, and the current study investigated the effects of gender on heart injury after ICH in rats. In the first part of the study, male and female rats had an intracerebral injection of 100 μL autologous blood, and sham-operated rats had a needle insertion. In the second part of the study, male rats were treated with 17β-estrodiol or vehicle 2 h after ICH. All rats were then killed after 3 days and heart samples collected for histology and Western blot analysis. ICH caused heart injury, including petechial hemorrhage in male and female rats. To quantify heart stress following ICH, heat shock proteins (HSP) 32 and 27 were measured by Western blot analysis. We found that heart HSP-32 levels were higher in female compared to male rats after ICH (p<0.01), but there was no effect of gender in sham-operated rats (p>0.05), nor were there gender differences in myocardial HSP27 levels. Treatment with 17β-estrodiol increased HSP-32 levels in male ICH rats (p<0.05). In conclusion, an ICH results in heart injury by an unknown mechanism. Gender and estrogen affect the heart response to ICH.

  3. The Influence of a High Salt Diet on a Rat Model of Isoproterenol-Induced Heart Failure

    EPA Science Inventory

    Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4 weeks) isoproterenol (ISO) infusion exacerbated cardiomyopathy in Spontaneously Hypertensive Heart Failure (SHHF) rats. Others have shown...

  4. A RAT MODEL OF HEART FAILURE INDUCED BY ISOPROTERENOL AND A HIGH SALT DIET

    EPA Science Inventory

    Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4wk) isoproterenol (ISO) infusion in Spontaneously Hypertensive Heart Failure (SHHF) rats caused cardiac injury with minimal hypertrophy. O...

  5. Successful transplantation of rat hearts subjected to extended cold preservation with a novel preservation solution.

    PubMed

    Wakayama, Kenji; Fukai, Moto; Yamashita, Kenichiro; Kimura, Taichi; Hirokata, Gentaro; Shibasaki, Susumu; Fukumori, Daisuke; Haga, Sanae; Sugawara, Mitsuru; Suzuki, Tomomi; Taniguchi, Masahiko; Shimamura, Tsuyoshi; Furukawa, Hiroyuki; Ozaki, Michitaka; Kamiyama, Toshiya; Todo, Satoru

    2012-06-01

    Since prolonged cold preservation of the heart deteriorates the outcome of heart transplantation, a more protective preservation solution is required. We therefore developed a new solution, named Dsol, and examined whether Dsol, in comparison to UW, could better inhibit myocardial injury resulting from prolonged cold preservation. Syngeneic heterotopic heart transplantation in Lewis rats was performed after cold preservation with UW or Dsol for 24 or 36 h. In addition to graft survival, myocardial injury, ATP content, and Ca(2+) -dependent proteases activity were assessed in the 24-h preservation group. The cytosolic Ca(2+) concentration of H9c2 cardiomyocytes after 24-h cold preservation was assessed. Dsol significantly improved 7-day graft survival after 36-h preservation. After 24-h preservation, Dsol was associated with significantly faster recovery of ATP content and less activation of calpain and caspase-3 after reperfusion. Dsol diminished graft injury significantly, as revealed by the lower levels of infarction, apoptosis, serum LDH and AST release, and graft fibrosis at 7-day. Dsol significantly inhibited Ca(2+) overload during cold preservation. Dsol inhibited myocardial injury and improved graft survival by suppressing Ca(2+) overload during the preservation and the activation of Ca(2+) -dependent proteases. Dsol is therefore considered a better alternative to UW to ameliorate the outcome of heart transplantation.

  6. Mitochondrial respiration in hearts of copper-deficient rats

    SciTech Connect

    Bode, A.M.; Saari, J.T. USDA/ARS, Grand Forks, ND )

    1991-03-11

    Morphological observations indicate that dietary copper deficiency causes structural damage of cardiac mitochondria. The purpose of this study was to determine whether mitochondrial function is impaired as well. Male, weanling Sprague-Dawley rats were fed diets deficient or sufficient in copper for 4 wks. Copper deficiency was verified by measurement of plasma (ND (CuD) vs 0.46 {plus minus} 0.15 {mu}g/ml (CuS)) and kidney copper. Mitochondria were isolated and P/O ratio, state 3 and state 4 respiration rate and acceptor control index (ACI) were determined using succinate or pyruvate/malate as substrate. Determinations were made polarographically at 30C in a reaction medium consisting of 0.25 M sucrose, 0.1 mM EDTA, 200 mM MgCl and 200 mM sodium phosphate buffer. State 3 respiration rate in mitochondria from CuD hearts was 30% lower than in CuS mitochondria when succinate was used as substrate and 28% lower when pyruvate/malate was used. Copper deficiency reduced state 4 respiration rate by 31% when succinate was used and 16% when pyruvate/malate was used. P/O ratio and ACI were not significantly affected by copper deficiency. The observed decreases in respiration rates are consistent with decreased cytochrome c oxidase activity shown by others to occur in mitochondria isolated from hearts of copper-deficient rats.

  7. The efficiency coefficient of the rat heart and muscular system after physical training and hypokinesia

    NASA Technical Reports Server (NTRS)

    Alyukhin, Y. S.; Davydov, A. F.

    1982-01-01

    The efficiency of an isolated heart did not change after prolonged physical training of rats for an extreme load. The increase in oxygen consumption by the entire organism in 'uphill' running as compared to the resting level in the trained rats was 14% lower than in the control animals. Prolonged hypokinesia of the rats did not elicit a change in the efficiency of the isolated heart.

  8. Changes in ECG and enzyme activity in rat heart after myocardial infarction: effect of TPP and MnCl2.

    PubMed

    Tylicki, A; Czerniecki, J; Godlewska, A; Kieliszek, M; Zebrowski, T; Bielawski, T; Wojcik, B

    2008-06-01

    Heart infarction is one of the main causes of death in the human population. Assurance of a sufficient level of bioenergetic processes is very important for the heart after infarction. Mn2+ as well as thiamine pyrophosphate (TPP) are positive effectors of the pyruvate dehydrogenase complex (PDH) and the 2-oxoglutarate dehydrogenase complex (OGDH), both of which play a very important role in the Krebs cycle. Thus, we have established the effect of MnCl2 (10mg/kg) and TPP (20mg/kg)--4 injections every 12 h--on the activity of PDH, OGDH, lactate dehydrogenase (LDH) and malate dehydrogenase (MDH). Additionally, we perform an analysis of ECG to affirm the changes in the heart electrophysiology of healthy rats after MnCl2 and TPP treatment. We then analyzed changes in the activity of these enzymes after experimental myocardial infarction in rats. We observed a decrease of OGDH and MDH activity in rat hearts after infarction in comparison with sham-operated rats. Treatment of healthy rats with MnCl2 caused an increase of OGDH activity. Moreover both MnCl2 and TPP caused an increase of PDH activity and a decrease of MDH activity (TPP revealed a stronger effect). We found no changes in LDH activity. Electrocardiography data showed a slight shortening of the QT interval and an enhanced heartbeat rate after treatment with MnCl2. TPP caused only elongation of the QT interval. In conclusion, application of MnCl2 enhanced the activity of some very important enzymes in the respiration process (PDH and OGDH). This effect, connected with enhanced heartbeat and a slightly shortened ventricle relaxation, may have potential application during the key period of convalescence following heart infarction.

  9. Beneficial effect of prolonged heme oxygenase 1 activation in a rat model of chronic heart failure

    PubMed Central

    Collino, Massimo; Pini, Alessandro; Mugelli, Niccolò; Mastroianni, Rosanna; Bani, Daniele; Fantozzi, Roberto; Papucci, Laura; Fazi, Marilena; Masini, Emanuela

    2013-01-01

    SUMMARY We and others have previously demonstrated that heme oxygenase 1 (HO-1) induction by acute hemin administration exerts cardioprotective effects. Here, we developed a rat model of heart failure to investigate whether a long-term induction of HO-1 by chronic hemin administration exerted protective effects. Sprague Dawley rats that underwent permanent ligation of the left coronary artery were closely monitored for survival rate analysis and sacrificed on day 28 post-operation. Administration of hemin (4 mg/kg body weight) every other day for 4 weeks induced a massive increase in HO-1 expression and activity, as shown by the increased levels of the two main metabolic products of heme degradation, bilirubin and carbon monoxide (CO). These effects were associated with significant improvement in survival and reduced the extension of myocardial damage. The ischemic hearts of the hemin-treated animals displayed reduced oxidative stress and apoptosis in comparison with the non-treated rats, as shown by the decreased levels of lipid peroxidation, free-radical-induced DNA damage, caspase-3 activity and Bax expression. Besides, chronic HO-1 activation suppressed the elevated levels of myeloperoxidase (MPO) activity, interleukin 1β (IL-1β) production and tumor necrosis factor-α (TNFα) production that were evoked by the ischemic injury, and increased the plasma level of the anti-inflammatory cytokine IL-10. Interestingly, HO-1 inhibitor zinc protoporphyrin IX (ZnPP-IX; 1 mg/kg) lowered bilirubin and CO concentrations to control values, thus abolishing all the cardioprotective effects of hemin. In conclusion, the results demonstrate that chronic HO-1 activation by prolonged administration of hemin improves survival and exerts protective effects in a rat model of myocardial ischemia by exerting a potent antioxidant activity and disrupting multiple levels of the apoptotic and inflammatory cascade. PMID:23592614

  10. Calcium Activation Profile In Electrically Stimulated Intact Rat Heart Cells

    NASA Astrophysics Data System (ADS)

    Geerts, Hugo; Nuydens, Rony; Ver Donck, Luc; Nuyens, Roger; De Brabander, Marc; Borgers, Marcel

    1988-06-01

    Recent advances in fluorescent probe technology and image processing equipment have made available the measurement of calcium in living systems on a real-time basis. We present the use of the calcium indicator Fura-2 in intact normally stimulated rat heart cells for the spatial and dynamic measurement of the calcium excitation profile. After electric stimulation (1 Hz), the activation proceeds from the center of the myocyte toward the periphery. Within two frame times (80 ms), the whole cell is activated. The activation is slightly faster in the center of the cell than in the periphery. The mean recovery time is 200-400 ms. There is no difference along the cell's long axis. The effect of a beta-agonist and of a calcium antagonist is described.

  11. Comparison of the Physiology of the Spaceflight and Hindlimb Suspended Rat

    NASA Technical Reports Server (NTRS)

    Grindeland, R. E.; Booth, F. W.

    1994-01-01

    The suspended rat has been used extensively as a simulation of the spaceflight animal. In suspension, hindlimbs are unloaded from the acceleration of gravity, much as they are in spaceflight. Comparisons of data from spaceflight (microgravity) and suspended (1G) rats have suggested that suspension my be an appropriate model, but no direct comparisons had been made between the spaceflight and suspended rat. Cosmos 2044 afforded the first opportunity to directly compare the effects of hindlimb suspension (HS) and spaceflight (SF) on a broad range of physiological and histological parameters. This paper reports on the comparison of skelton, skeletal muscle, heart, neural, pulmonary, kidney, liver, intestine, blood plasma, immune function, red blood cells, and endocrine and reproductive functions and systems.

  12. Zinc antagonizes homocysteine-induced fetal heart defects in rats.

    PubMed

    He, Xiaoyu; Hong, Xinru; Zeng, Fang; Kang, Fenhong; Li, Li; Sun, Qinghua

    2009-09-01

    It has been suggested that zinc may have a protective role against heart defects during fetal development. We investigated the effects of zinc on the development of fetal cardiac malformations induced by homocysteine. Pregnant Sprague-Dawley rats were randomized into one of five groups: control (C), homocysteine (H), homocysteine + zinc (Z), homocysteine + folic acid (F), or homocysteine + zinc + folic acid (ZF) (each n = 8). Homocysteine (8 nmol/day) was administered intraperitoneally in the H, Z, F, and ZF groups on gestation days (GD) 8, 9, and 10. Zinc (30 mg/kg day), folic acid (30 mg/kg day), or both (30 mg/kg day each) were administered intragastrically daily in the Z, F, and ZF groups, respectively, throughout the pregnancy. In each group, two fetuses were removed on GD 13, 15, 17, and 19 and examined for cardiac malformations; maternal copper/zinc-containing-superoxide dismutase (Cu/Zn-SOD) activity and metallothionein type I (MT-1) mRNA expression were measured simultaneously. The prevalence of cardiac malformations was significantly higher in group H than in group C, and significantly lower in group Z than in group H at the studied time points. Cu/Zn-SOD activity and MT-1 mRNA levels were significantly lower in group H than in group C, and significantly higher in group Z than in group H. Our data suggest that zinc antagonizes homocysteine-induced teratogenic effects on the fetal heart, possibly via the inhibition of excessive peroxidation.

  13. 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.

  14. Effects of thyroid state on respiration of perfused rat and guinea pig hearts

    SciTech Connect

    Read, L.C.; Wallace, P.G.; Berry, M.N. )

    1987-09-01

    The effects of thyroid state on the respiration of the isolated heart were investigated using retrograde perfused rat and guinea pig hearts. In both species, hypothyroidism caused a marked depression in circulating thyroid hormone concentrations and in the respiration of the isolated, retrograde perfused heart. Hypothyroidism was caused by injecting animals with Na{sup 131}I. The effects on myocardial respiration could be attributed to changes in the contraction frequency and in the oxygen consumption per beat, with little contribution from basal respiration. Treatment of animals with thyroxine elevated plasma thyroid hormones to a similar extent in rats and guinea pigs. In the latter, thyroxine treatment was associated with substantial increases in the contraction frequency and the oxygen consumption per beat of the isolated heart. In contrast, only small changes were apparent in the retrograde perfused rat heart, observations that were confirmed in rat hearts perfused at near physiological work loads. It was concluded that rat hearts isolated from normal animals function at near maximal thyroid state, in contrast to the guinea pig heart, which requires higher circulating concentrations of thyroid hormones to attain maximal responses.

  15. Symbolic dynamics for arrhythmia identification from heart variability of rats with cardiac failures

    NASA Astrophysics Data System (ADS)

    Letellier, C.; Roulin, E.; Loriot, S.; Morin, J.-P.; Dionnet, F.

    2004-12-01

    Heart rate variability of rats is investigated using concepts from the nonlinear dynamical system theory. Among the important techniques offered, symbolic dynamics is very appealing by its power to investigate patterns which can be repeated in a time series. The present analysis was performed in six control rats and six chronic cardiac insufficient rats (myocardial infarction due to left descendent coronary artery ligation). Rats are left in clean atmosphere or exposed to atmosphere containing diluted engine emission pollutants. The evolution of the heart rate variability is then investigated with a three element symbolic dynamics which allows to distinguish extrasystoles from tachycardia or bradycardia using the symbol sequences.

  16. [Protective effect of peptide semax the rat heart in acute myocardial infarction].

    PubMed

    Golubeva, A V; Gavrilova, S A; Lipina, T V; Shornikova, M V; Postnikov, A B; Andreeva, L A; Chentsov, Iu S; Koshelev, V B

    2006-06-01

    Semax, a member of ACTH-derived peptides family, has been employed in the treatment of acute ischemic stroke in patients. It decreased neurological deficit and reduced NO hyperproduction in the rat brain, caused by acute cerebral hypoperfusion. We suggested that semax is also able to protect rat heart from ischemic damage in acute myocardial infaction (AMI). AMI was induced by left coronary artery occlusion, myocardial ischemic area averaged 30 % of left ventricle. In 2 hours after coronary occlusion, the AMI group developed 11 % reduced mean arterial blood pressure and 48 % increased diastolic blood pressure in left ventricle in comparison with sham-operated control group. However, infusion of either dobutamine, which directly stimulates myocardial contractility, or sodium nitroprusside and phenylephrine, that change vascular resistance and thus cardiac afterload, did not reveal distinctions in hemodynamic parameters between groups. These data indicate absense or only moderate cardiac dysfunction in rats with AMI and are consistent wih morphometrical and histochemical studies that did not detect any necrotic or apoptotic (TUNEL-test) changes in left ventricular cardiomyocytes in spite of development of distinct ischemic disturbances of mitochondria and nuclear in about 50 % of cardiomyocytes in 2 hours after AMI. Semax (150 microg/kg), given i. p. 15 min and 2 hours after coronary occlusion, caused no effect on cardiac function, but completely prevented ischemia-induced ultrastructural changes of cardiomyocytes. This protective effect was accompanied by the ability of peptide to blunt the increase in plasma concentrations of nitrates, observed in AMI group.

  17. Effects of increased heart work on glycolysis and adenine nucleotides in the perfused heart of normal and diabetic rats

    PubMed Central

    Opie, L. H.; Mansford, K. R. L.; Owen, Patricia

    1971-01-01

    1. In the isolated perfused rat heart, the contractile activity and the oxygen uptake were varied by altering the aortic perfusion pressure, or by the atrial perfusion technique (`working heart'). 2. The maximum increase in the contractile activity brought about an eightfold increase in the oxygen uptake. The rate of glycolytic flux rose, while tissue contents of hexose monophosphates, citrate, ATP and creatine phosphate decreased, and contents of ADP and AMP rose. 3. The changes in tissue contents of adenine nucleotides during increased heart work were time-dependent. The ATP content fell temporarily (30s and 2min) after the start of left-atrial perfusion; at 5 and 10min values were normal; and at 30 and 60min values were decreased. ADP and AMP values were increased in the first 15min, but were at control values 30 or 60min after the onset of increased heart work. 4. During increased heart work changes in the tissue contents of adenine nucleotide and of citrate appeared to play a role in altered regulation of glycolysis at the level of phosphofructokinase activity. 5. In recirculation experiments increased heart work for 30min was associated with increased entry of [14C]glucose (11.1mm) and glycogen into glycolysis and a comparable increase in formation of products of glycolysis (lactate, pyruvate and 14CO2). There was no major accumulation of intermediates. Glycogen was not a major fuel for respiration. 6. Increased glycolytic flux in Langendorff perfused and working hearts was obtained by the addition of insulin to the perfusion medium. The concomitant increases in the tissue values of hexose phosphates and of citrate contrasted with the decreased values of hexose monophosphates and of citrate during increased glycolytic flux obtained by increased heart work. 7. Decreased glycolytic flux in Langendorff perfused hearts was obtained by using acute alloxan-diabetic and chronic streptozotocin-diabetic rats; in the latter condition there were decreased tissue

  18. Behavioral and Biological Effects of Housing Conditions and Stress in Male Rats - Relevance to Heart Disease

    DTIC Science & Technology

    2006-08-01

    investigators have defined adolescence in the rat as 21-42 days old and up to day 55 for male rats (Spear & Brake , 1983; Ojeda & Urbanski, 1994; Faraday...based on Elliott et al. (2003) as recommended by R. Virmani (1999). Calipers (10mm) were used to measure the length of each heart form base to apex...experiment. First, the heart measures included in the experiment were simple and were made with 10 mm calipers . Electronic digital calipers would

  19. Digitoxin improves cardiovascular autonomic control in rats with heart failure.

    PubMed

    Fardin, Núbia Mantovan; Antonio, Ednei Luiz; Montemor, Jairo Augusto Silva; da Veiga, Glaucia Luciano; Tucci, Paulo José Ferreira; Campos, Ruy R

    2016-06-01

    The effects of chronic treatment with digitoxin on arterial baroreceptor sensitivity for heart rate (HR) and renal sympathetic nerve activity (rSNA) control, cardiopulmonary reflex, and autonomic HR control in an animal model of heart failure (HF) were evaluated. Wistar rats were treated with digitoxin, which was administered in their daily feed (1 mg/kg per day) for 60 days. The following 3 experimental groups were evaluated: sham, HF, and HF treated with digitoxin (HF + DIG). We observed an increase in rSNA in the HF group (190 ± 29 pps, n = 5) compared with the sham group (98 ± 14 pps, n = 5). Digitoxin treatment prevented an increase in rSNA (98 ± 14 pps, n = 7). Therefore, arterial baroreceptor sensitivity was decreased in the HF group (-1.24 ± 0.07 bpm/mm Hg, n = 8) compared with the sham group (-2.27 ± 0.23 bpm/mm Hg, n = 6). Digitoxin did not alter arterial baroreceptor sensitivity in the HF + DIG group. Finally, the HF group showed an increased low frequency band (LFb: 23 ± 5 ms(2), n = 8) and a decreased high frequency band (HFb: 77 ± 5 ms(2), n = 8) compared with the sham group (LFb: 14 ± 3 ms(2); HFb: 86 ± 3 ms(2), n = 9); the HF+DIG group exhibited normalized parameters (LFb: 15 ± 3 ms(2); HFb: 85 ± 3 ms(2), n = 9). In conclusion, the benefits of decreasing rSNA are not directly related to improvements in peripheral cardiovascular reflexes; such occurrences are due in part to changes in the central nuclei of the brain responsible for autonomic cardiovascular control.

  20. [Complex study of the rat heart at isoproterenol damage].

    PubMed

    Kapel'ko, V I; Lakomkin, V L; Lukoshkova, E V; Gramovich, V V; Vyborov, O N; Abramov, V S; Undrovinas, N A; Ermishkin, V V; Lakomkin, S V; Veselova, S P; Zhdanov, V S; Shirinskiĭ, V P

    2014-01-01

    Introduction of isoproterenol (an agonist of beta-adrenoreceptors) to rats is one of the widespread experimental models of cardiac failure. It is caused by damage of cardiomyocytes with the subsequent development of substitutive fibrosis. The purpose of the given work was the complex characteristic of cardiac function by means of invasive and noninvasive (echocardiography and impedansometry) methods of research. Isoproterenol was injected twice with a daily interval in dozes 85, 120, 150 or 180 mg/kg. Echocardiographic study of the heart in 2 weeks revealed obvious attributes of cardiac failure (left ventricular dilatation, lowered ejection fraction) in the groups which have received high cumulative dozes of isoproterenol (300-360 mg/kg). The catheterization of the left ventricle in these groups has shown raised enddiastolic pressure, decreased maximal rate of pressure development and fall, and also lowered indices of myocardial contractility and relaxability. In the groups which have received smaller isoproterenol dozes, apparent decrease in relaxability parameters (constants of isovolumic and auxovolumic relaxation) has been revealed at only slightly changed parameters of contractility. A strong correlation between echocardiographic and invasive parameters of myocardial contractility has been found. The phase analysis of the cardiac cycle has shown a lengthening of isometric phases of contraction and relaxation, as well as duration of ejection due to shortening duration of filling of both ventricles. Cardiomyocytes isolated from hearts with obvious cardiac failure responded to electrostimulation by arrhythmic contractions and also by much slowed and incomplete removal of free Ca++ from the myoplasm. Results allow to conclude that relatively smaller extent of myocardial damage is accompanied by decreased relaxability at slightly changed contractility, while at greater degree of damage both processes fail, but delay of relaxation still prevails.

  1. Engineered heart tissue graft derived from somatic cell nuclear transferred embryonic stem cells improve myocardial performance in infarcted rat heart.

    PubMed

    Lü, Shuanghong; Li, Ying; Gao, Shaorong; Liu, Sheng; Wang, Haibin; He, Wenjun; Zhou, Jin; Liu, Zhiqiang; Zhang, Ye; Lin, Qiuxia; Duan, Cumi; Yang, Xiangzhong Jerry; Wang, Changyong

    2010-12-01

    The concept of regenerating diseased myocardium by implanting engineered heart tissue (EHT) is intriguing. Yet it was limited by immune rejection and difficulties to be generated at a size with contractile properties. Somatic cell nuclear transfer is proposed as a practical strategy for generating autologous histocompatible stem (nuclear transferred embryonic stem [NT-ES]) cells to treat diseases. Nevertheless, it is controversial as NT-ES cells may pose risks in their therapeutic application. EHT from NT-ES cell-derived cardiomyocytes was generated through a series of improved techniques in a self-made mould to keep the EHTs from contraction and provide static stretch simultaneously. After 7 days of static and mechanical stretching, respectively, the EHTs were implanted to the infarcted rat heart. Four weeks after transplantation, the suitability of EHT in heart muscle repair after myocardial infarction was evaluated by histological examination, echocardiography and multielectrode array measurement. The results showed that large (thickness/diameter, 2-4 mm/10 mm) spontaneously contracting EHTs was generated successfully. The EHTs, which were derived from NT-ES cells, inte grated and electrically coupled to host myocardium and exerted beneficial effects on the left ventricular function of infarcted rat heart. No teratoma formation was observed in the rat heart implanted with EHTs for 4 weeks. NT-ES cells can be used as a source of seeding cells for cardiac tissue engineering. Large contractile EHT grafts can be constructed in vitro with the ability to survive after implantation and improve myocardial performance of infarcted rat hearts.

  2. Whole-body heat shock protects the ischemic rat heart by stimulating mitochondria respiration.

    PubMed

    Broderick, Tom L

    2006-01-01

    Whole-body heat shock (HS) leads to an enhancement of postischemic mechanical function and an improvement in glucose use by the rat heart. Here, we examine the effect of HS on isolated mitochondrial metabolism during reperfusion in the working rat heart. Rats were anesthetized, and their body temperature was raised to 41-42 degrees C for 15 min. Control rats were treated the same way but were not exposed to hyperthermia. Twenty-four hours after HS or sham treatment, rats were reanesthetized and the hearts were removed for perfusion with Krebs-Henseleit buffer, containing 11 mmol glucose/L and 1.2 mmol palmitate/L prebound to 3% albumin. Hearts were subjected to 25 min of global ischemia followed by 30 min of reperfusion. At the end of reperfusion, heart mitochondria were isolated using differential centrifugation and respiration measured in the presence of pyruvate, glutamate, or palmitoylcarnitine. Hearts subjected to HS showed an enhanced recovery of function, expressed as aortic flow, during the reperfusion period, compared with sham hearts. This improved functional status was associated with a significant increase in state 3 respiration in the presence of pyruvate, glutamate, or palmitoylcarnitine. These results show that HS offers protection against ischemic damage, and that a possible mechanism might be the enhanced myocardial metabolism of fuels.

  3. The effect of prefixation on the quality of vascular corrosion casts of rat heart.

    PubMed

    Reddy, P A; Douglas, J E; Schulte, M; Hossler, F E

    1995-01-01

    To help define the optimal conditions for the preparation of vascular corrosion casts of rat heart, we examined the effect of prefixation with aldehyde fixatives on the perfusion rates of rat heart and on the quality of vascular casts. For these studies, beating hearts were removed from rats, cannulated via the aortic stump, arrested with KCl, perfused retrograde with buffered saline or fixative, and infused with resin to prepare corrosion casts. Fixatives used were 2.5% glutaraldehyde or 2% paraformaldehyde, and the casting resin consisted of a Mercox-methylmethacrylate mixture (4:1). All perfusion pressures were monitored at 80 to 100 mm Hg using a mercury manometer. The perfusion rate of control hearts was 13 to 14 mL/min. Prefixation with glutaraldehyde and paraformaldehyde reduced perfusion to 8.5 and 8.1 mL/min, respectively. Cast quality was observed grossly and with the scanning electron microscope. Control hearts yielded high quality, complete casts with 2570 capillaries/mm(2+). Casts from prefixed hearts exhibited areas of incomplete vessel filling and resisted complete tissue maceration, leaving tissue remnants adhering to the vessel replicas. Casts from glutaraldehyde-fixed hearts were of very poor quality. Our results indicate that prefixation is an unnecessary step in the preparation of vascular casts of rat heart and is inconsistent with cast quality.

  4. Impaired alpha1-adrenergic responses in aged rat hearts.

    PubMed

    Montagne, Olivier; Le Corvoisier, Philippe; Guenoun, Thierry; Laplace, Monique; Crozatier, Bertrand

    2005-06-01

    To determine age-related changes in the cardiac effect of alpha1-adrenergic stimulation, both cardiomyocyte Ca2+-transient and cardiac protein kinase C (PKC) activity were measured in 3-month- (3MO) and 24-month- (24MO) old Wistar rats. Ca2+ transients obtained under 1 Hz pacing by microfluorimetry of cardiomyocyte loaded with indo-1 (405/480 nm fluorescence ratio) were compared in control conditions (Kreb's solution alone) and after alpha1-adrenergic stimulation (phenylephrine or cirazoline, an alpha1-specific agonist). PKC activity and PKC translocation index (particulate/total activity) were also assayed before and after alpha1-adrenergic stimulation. In 3MO, cirazoline induced a significant increase in Ca2+ transient for a 10(-9) M concentration which returned to control values for larger concentrations. In contrast, in 24MO, we observed a constant negative effect of cirazoline on the Ca2+ transient with a significant decrease at 10(-6) M compared with both baseline and Kreb's solution. Preliminary experiments showed that, in a dose-response curve to phenylephrine, the response of Ca2+ transient was maximal at 10(-7) M. This concentration induced a significant increase in Ca2+ transient in 3MO and a significant decrease in 24MO. The same concentration was chosen to perform PKC activity measurements under alpha1-adrenergic stimulation. In the basal state, PKC particulate activity was higher in 24MO than that in 3MO but was not different in cytosolic fractions; so that the translocation index was higher in 24MO (P < 0.01). After phenylephrine, a translocation of PKC toward the particulate fraction was observed in 3MO but not in 24MO. In conclusion, cardiac alpha1-adrenoceptor response was found to be impaired in aged hearts. The negative effect of alpha1-adrenergic stimulation on Ca2+ transient in cardiomyocytes obtained from old rats can be related to an absence of alpha1-adrenergic-induced PKC translocation.

  5. Inhibition of Cyclooxygenase-2 Reduces Hypothalamic Excitation in Rats with Adriamycin-Induced Heart Failure

    PubMed Central

    Liu, Wei; Zang, Wei-Jin; Bao, Cui-Yu; Qin, Da-Nian

    2012-01-01

    Background The paraventricular nucleus (PVN) of the hypothalamus plays an important role in the progression of heart failure (HF). We investigated whether cyclooxygenase-2 (COX-2) inhibition in the PVN attenuates the activities of sympathetic nervous system (SNS) and renin-angiotensin system (RAS) in rats with adriamycin-induced heart failure. Methodology/Principal Finding Heart failure was induced by intraperitoneal injection of adriamycin over a period of 2 weeks (cumulative dose of 15 mg/kg). On day 19, rats received intragastric administration daily with either COX-2 inhibitor celecoxib (CLB) or normal saline. Treatment with CLB reduced mortality and attenuated both myocardial atrophy and pulmonary congestion in HF rats. Compared with the HF rats, ventricle to body weight (VW/BW) and lung to body weight (LW/BW) ratios, heart rate (HR), left ventricular end-diastolic pressure (LVEDP), left ventricular peak systolic pressure (LVPSP) and maximum rate of change in left ventricular pressure (LV±dp/dtmax) were improved in HF+CLB rats. Angiotensin II (ANG II), norepinephrine (NE), COX-2 and glutamate (Glu) in the PVN were increased in HF rats. HF rats had higher levels of ANG II and NE in plasma, higher level of ANG II in myocardium, and lower levels of ANP in plasma and myocardium. Treatment with CLB attenuated these HF-induced changes. HF rats had more COX-2-positive neurons and more corticotropin releasing hormone (CRH) positive neurons in the PVN than did control rats. Treatment with CLB decreased COX-2-positive neurons and CRH positive neurons in the PVN of HF rats. Conclusions These results suggest that PVN COX-2 may be an intermediary step for PVN neuronal activation and excitatory neurotransmitter release, which further contributes to sympathoexcitation and RAS activation in adriamycin-induced heart failure. Treatment with COX-2 inhibitor attenuates sympathoexcitation and RAS activation in adriamycin-induced heart failure. PMID:23152801

  6. Schisandrin B-induced glutathione antioxidant response and cardioprotection are mediated by reactive oxidant species production in rat hearts.

    PubMed

    Chen, Na; Ko, Ming

    2010-01-01

    To investigate the involvement of reactive oxidant species (ROS), presumably arising from cytochrome P-450 (CYP)-catalyzed metabolism of schisandrin B (Sch B), in triggering glutathione antioxidant response, Sch B induced reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent and CYP-catalyzed reaction and associated ROS production were examined in rat heart microsomes. Sch B analogs were also studied for comparison. Using rat heart microsomes as a source of CYP, Sch B and schisandrin C (Sch C), but not schisandrin A and dimethyl diphenyl bicarboxylate (an intermediate compound derived from the synthesis of Sch C), were found to serve as co-substrate for the CYP-catalyzed NADPH oxidation reaction, with concomitant production of ROS. The stimulation of CYP-catalyzed NADPH oxidation reaction and/or ROS production by Sch B or Sch C correlated with the increase in mitochondrial reduced glutathione level and protection against ischemia/reperfusion (I/R) injury in rat hearts. The involvement of ROS in Sch B-induced cardioprotection was further confirmed by the suppressive effect produced by N-acetylcysteine or alpha-tocopherol pretreatment. Taken together, these results suggest that Sch B-induced glutathione antioxidant response and cardioprotection may be mediated by ROS arising from CYP-catalyzed reaction.

  7. Influence of microwaves on the beating rate of isolated rat hearts

    SciTech Connect

    Yee, K.C.; Chou, C.K.; Guy, A.W.

    1988-01-01

    Previous reports have shown that microwave exposure can decrease the beating rate of isolated rat hearts. These experiments were conducted at room temperature and with the hearts exposed to air. We observed arrhythmia frequently at room temperature, and the variation of heart beat was so large that it makes the results difficult to reproduce. Therefore, we employed a double-circulating system to provide perfusion through the coronary artery and around the outside of the heart to maintain the rat hearts at 37.7 degrees C. No arrhythmias were observed in our experiments, and the hearts were beating for at least 1 h. The effects of 16-Hz modulated 2,450-MHz pulsed microwaves (10 microseconds, 100 pps) on the beating rate of 50 isolated rat hearts were studied. Results showed no statistically significant changes of heart rate in exposed groups at SARs of 2 and 10 W/kg compared with the control group. The effect seen at 200 W/kg was shown to be similar to that resulting from heating the heart.

  8. The in vivo effect of different bedding materials on the antioxidant levels of rat heart, lung and liver tissue.

    PubMed

    Potgieter, F J; Wilke, P I; van Jaarsveld, H; Alberts, D W

    1996-03-01

    Several experimental effects due to wood-derived bedding have been reported. Female Sprague Dawley rats were kept on pine shavings, eucalyptus pulp, vermiculite and in wire-bottomed cages without bedding for 14 days whereafter normal values for the antioxidants ascorbic acid and reduced glutathione (G-SH) in rat heart lung and liver tissue were determined and compared. Statistically significant differences were observed for lung G-SH between pine shavings and eucalyptus pulp (p < 0.0183), and heart G-SH between vermiculite and eucalyptus pulp (p < 0.0948). The highest levels of liver G-SH were obtained using pine shavings compared to vermiculite (p < 0.0001), eucalyptus pulp (p < 0.0002) and wire floor (p < 0.0001). Statistically significant differences in ascorbic acid concentrations could only be described between the wire-bottomed cages and eucalyptus pulp (p < 0.0333) for lung tissue and between pine shavings and eucalyptus pulp for liver tissue (p < 0.042). Although no statistically significant differences were observed in heart ascorbic acid levels between the different bedding applications, the concentration obtained using vermiculite was approximately 50% higher than that observed with the other materials. Pine shavings, eucalyptus pulp and wire floors demonstrated virtually the same heart tissue ascorbic acid levels. It was thus demonstrated that bedding material can alter the tissue antioxidant concentration of laboratory animals, limiting the comparison of this type of result between institutions to those using identical environmental conditions.

  9. Activity of cholinesterases of blood and heart in rats of different sex and age during muscular loads and hypokinesia

    NASA Technical Reports Server (NTRS)

    Rozanova, V. D.; Antonova, G. A.

    1979-01-01

    The activity of acetylcholinesterase (Ache) and butyrilcholinesterase (Bche) in the blood and the heart of 3 and 13 month old control male rats is considerably lower than in female rats. In 25 month old rats, no sex differences in the Ache and Bche were revealed in the heart. In 3 and 13 month old male and female rats, under conditions of muscular exercises, the Ache and Bche activity is lower, and in hypokinetic male rats -- higher than that in respective control animals. In all the rats, irrespective of sex, age, and motor conditions, Ache and Bche activity tended to decrease from the sinoatrial node to the heart apex.

  10. Myocardial kinetics of carbon-11-epinephrine in the isolated working rat heart

    SciTech Connect

    Nguyen, N.T.B.; DeGrado, T.R.; Chakraborty, P.

    1997-05-01

    The kinetics of EPI were studied in the isolated rat heart model to evaluate {sup 11}C-epinephrine (EPI) as a radiotracer for the assessment of sympathetic neuronal function in the heart. Isolated rat hearts were perfused in a working mode. Carbon-11-EPI was added to the perfusate during wash-in period of 20 min, followed by a washout period of 40 min. Radioactivity in the heart was externally monitored and time-activity curves were recorded as a function of time. Effluent samples were collected throughout each study to determine the fraction of {sup 11}C radioactivity as intact tracer. Time-activity curves of control hearts showed that {sup 11}C-EPI is taken up and retained by the myocardium. Desipramine inhibition (DMI) of uptake-1 resulted in a significant decrease in myocardial uptake and retention of {sup 11}C-EPI by 91% compared to controls. Addition of DMI to the perfusion medium during washout did not affect kinetics of {sup 11}C-EPI compared to control hearts. Reserpine pretreated rat hearts also showed significant decrease in tracer retention of 95% compared to controls. The metabolic data showed that, in control conditions, about 61% of {sup 11}C-EPI taken up by the rat heart is rapidly metabolized and released. Carbon-11-EPI traces sympathetic nerve terminals in the isolated rat heart. Uptake blockade by DMI and reserpine suggest that uptake and storage of {sup 11}C-EPI appear to be similar to that of norepinephrine. However, the prominent metabolic pathway warrants further consideration. These results suggest that {sup 11}C-EPI may be a suitable radiolabeled tracer for the evaluation of sympathetic vesicular function of the heart by PET. 23 refs., 3 figs., 3 tabs.

  11. Chronic administration of an endothelin-A receptor antagonist improves exercise capacity in rats with myocardial infarction-induced congestive heart failure.

    PubMed

    Miyauchi, Takashi; Fujimori, Akira; Maeda, Seiji; Iemitsu, Motoyuki; Sakai, Satoshi; Shikama, Hisataka; Tanabe, Takumi; Matsuda, Mitsuo; Goto, Katsutoshi; Yamaguchi, Iwao

    2004-11-01

    The effects of long-term administration of YM598, a selective endothelin-A antagonist, on improving the exercise tolerance of chronic heart failure model rats were examined using a treadmill exercise loading test. Rats were acclimatized to the treadmill apparatus and the coronary artery was ligated to prepare a myocardial infarction-induced congestive heart failure (CHF) model. Starting 10 days postoperatively, when the acute phase of infarction was over, YM598 was administered orally once daily for approximately 25 weeks at a dose of 1 mg/kg. At weeks 20 and 24 the treadmill test was performed. YM598 prolonged running time, which had been shortened as a result of heart failure. The weights, relative to the body weight, of the left and right ventricles and lungs of surviving rats with CHF were significantly greater than those of sham-operated rats, suggesting hypertrophy of the ventricles and congestion of the lungs. Administration of YM598 markedly reduced ventricular hypertrophy and pulmonary congestion. Examination of cardiac function revealed that, in surviving CHF rats, the peak positive first derivative of left ventricular pressure was significantly lower, and left ventricular end-diastolic pressure, right ventricular systolic pressure and central venous pressure were significantly higher in comparison to sham-operated rats. These data demonstrate that, in rats with CHF, the contractile and diastolic capacity of the left ventricle decreased and pulmonary hypertension and systemic congestion occurred. Long-term administration of YM598 improved left ventricular function of CHF rats to the level of sham-operated rats, and reduced the workload placed on the right side of the heart. Histological examination revealed that long-term treatment with YM598 prevented fibrosis of the surviving left ventricular myocardium. In conclusion, long-term administration of YM598 to rats with CHF improved exercise tolerance and inhibited remodeling of cardiac muscles, leading to

  12. Perinatal hypothyroidism modulates antioxidant defence status in the developing rat liver and heart.

    PubMed

    Zhang, Hongmei; Dong, Yan; Su, Qing

    2017-02-01

    In the present study, we investigated oxidative stress parameters and antioxidant defence status in perinatal hypothyroid rat liver and heart. We found that the proteincarbonyl content did not differ significantly between the three groups both in the pup liver and in the heart. The OH˙ level was significantly decreased in the hypothyroid heart but not in the liver compared with controls. A slight but not significant decrease in SOD activity was observed in both perinatal hypothyroid liver and heart. A significantly increased activity of CAT was observed in the liver but not in the heart of hypothyroid pups. The GPx activity was considerably increased compared with controls in the perinatal hypothyroid heart and was unaltered in the liver of hypothyroid pups. We also found that vitamin E levels in the liver decreased significantly in hypothyroidism and were unaltered in the heart of perinatal hypothyroid rats. The GSH content was elevated significantly in both hypothyroid liver and heart. The total antioxidant capacity was higher in the liver of the hypothyroid group but not in the hypothyroid heart. Thyroxine replacement could not repair the above changes to normal. In conclusion, perinatal hypothyroidism modulates the oxidative stress status of the perinatal liver and heart.

  13. Prolongation of rat heart allografts by donor-specific blood transfusion treated with ultraviolet irradiation

    SciTech Connect

    Oluwole, S.F.; Iga, C.; Lau, H.; Hardy, M.A.

    1985-07-01

    The effect of donor-specific blood transfusion was compared to that of UVB-irradiated donor-specific blood transfusion on heart allograft survival in inbred rats with major histocompatibility differences. In one series ACI rats received heterotopic heart grafts from Lewis rats and 1 mL transfusion of donor-type blood at 1, 2, and 3 weeks prior to the transplantation. Fifty percent of the grafts were permanently accepted (survival greater than 200 days). Following UVB-irradiated donor-specific blood transfusion, 55% of the grafts survived indefinitely. In a mixed lymphocyte reaction ACI lymphocytes are weak responders to Lewis lymphocytes. In another series, Lewis rats received ACI hearts. Donor-specific transfusions at 1, 2, and 3 weeks prior to transplantation did not significantly alter the survival of heart allografts. Lewis lymphocytes react strongly to ACI stimulator cells in a mixed lymphocyte reaction. However, when the donor blood was UVB-irradiated prior to transfusion, the ACI allograft survival was significantly prolonged in this ACI-to-Lewis strain combination. When Lewis rats received W/F hearts following either donor-specific or UVB-irradiated donor-specific transfusions, the hearts' survival was similarly and significantly prolonged, but did not become permanent. Mixed lymphocyte reaction reveals that the stimulation index of Lewis lymphocytes against W/F lymphocytes is greater than that of ACI versus Lewis, but is less than that between Lewis responder cells against ACI stimulators.

  14. Alterations in Glutathione Redox Metabolism, Oxidative Stress, and Mitochondrial Function in the Left Ventricle of Elderly Zucker Diabetic Fatty Rat Heart

    PubMed Central

    Raza, Haider; John, Annie; Howarth, Frank C.

    2012-01-01

    The Zucker diabetic fatty (ZDF) rat is a genetic model in which the homozygous (FA/FA) male animals develop obesity and type 2 diabetes. Morbidity and mortality from cardiovascular complications, due to increased oxidative stress and inflammatory signals, are the hallmarks of type 2 diabetes. The precise molecular mechanism of contractile dysfunction and disease progression remains to be clarified. Therefore, we have investigated molecular and metabolic targets in male ZDF (30–34 weeks old) rat heart compared to age matched Zucker lean (ZL) controls. Hyperglycemia was confirmed by a 4-fold elevation in non-fasting blood glucose (478.43 ± 29.22 mg/dL in ZDF vs. 108.22 ± 2.52 mg/dL in ZL rats). An increase in reactive oxygen species production, lipid peroxidation and oxidative protein carbonylation was observed in ZDF rats. A significant increase in CYP4502E1 activity accompanied by increased protein expression was also observed in diabetic rat heart. Increased expression of other oxidative stress marker proteins, HO-1 and iNOS was also observed. GSH concentration and activities of GSH-dependent enzymes, glutathione S-transferase and GSH reductase, were, however, significantly increased in ZDF heart tissue suggesting a compensatory defense mechanism. The activities of mitochondrial respiratory enzymes, Complex I and Complex IV were significantly reduced in the heart ventricle of ZDF rats in comparison to ZL rats. Western blot analysis has also suggested a decreased expression of IκB-α and phosphorylated-JNK in diabetic heart tissue. Our results have suggested that mitochondrial dysfunction and increased oxidative stress in ZDF rats might be associated, at least in part, with altered NF-κB/JNK dependent redox cell signaling. These results might have implications in the elucidation of the mechanism of disease progression and designing strategies for diabetes prevention. PMID:23203193

  15. Early life permethrin insecticide treatment leads to heart damage in adult rats.

    PubMed

    Vadhana, M S Dhivya; Carloni, Manuel; Nasuti, Cinzia; Fedeli, Donatella; Gabbianelli, Rosita

    2011-09-01

    Early life environmental exposure to xenobiotics could represent a critical period for the onset of permanent alterations in the structure and function of different organs. Cardiovascular diseases can be related to various factors including environmental toxicants. The aim of the present study was to evaluate the effect of early life permethrin treatment (1/50 LD(50), from 6th to 21st day of life) on heart of adult rats. Increased DNA damage, decreased heart cell membrane fluidity, increased cholesterol content, protein and lipid oxidation were measured in heart cells from adult rats treated with permethrin during the neonatal period with respect to control rats. Moreover, the same group showed higher levels of cholesterol, IL-1β, IL-2, IFN-γ, rat-Rantes and IL-10 cytokines and decreased albumin content in plasma. Lower cholesterol levels and perturbation in the phospholipid lateral diffusion together with decreased GSH levels and increased GPx activity were measured in heart mitochondria of the treated group. Our findings support the evidence that the neonatal period has a critical role in the development of heart disease in adulthood. We hypothesize that the alterations observed in adult rats could depend on epigenetic changes that occurred during this period which influence gene expression throughout the rat's life, leading to alterations of certain parameters related to cardiac function.

  16. Effect of ethanol of heart rate and blood pressure in nonstressed and stressed rats

    SciTech Connect

    Sparrow, M.G.; Roggendorf, H.; Vogel, W.H.

    1987-06-29

    The effect of ethanol on the cardiovascular system (ECG, heart rate, blood pressure) was studied in anesthetized, nonstressed or stressed rats. In anesthetized rats, ethanol showed no effect on heart rate or ECG. In nonstressed rats, ethanol sedated the animals but increased heart rate significantly. This ethanol induced tachycardia seemed the result of a direct stimulation of the sympathetic nerves to the heart. Blood pressure was not significantly affected by ethanol in these nonstressed rats. In stressed rats, marked behavioral excitation and significant increases in heart rate and blood pressure were noted. Ethanol pretreatment calmed the animals considerably during restraint. Ethanol did reduce slightly the stress-induced tachycardia but markedly reduced or antagonized stress-induced blood pressure increases. No major changes in the ECG were noted during these studies with the exception of a few individual animals which showed pathologic ECG responses to ethanol. These data show that ethanol affects cardiovascular functions differently in anesthetized, non stressed or stressed rats, and that ethanol can significantly reduce or antagonize stress-induced behavioral excitation, tachycardia and hypertension. 32 references, 4 tables.

  17. Static magnetic field influence on rat brain function detected by heart rate monitoring.

    PubMed

    Veliks, Viktors; Ceihnere, Edīte; Svikis, Igors; Aivars, Juris

    2004-04-01

    The aim of the present study was to identify the effects of a static magnetic field (SMF) on rat brain structures that control autonomic functions, specifically heart rate and heart rhythmicity. The experiments were carried out on 44 male Wistar rats under ketamine-xylazine anesthesia. SMF was induced using samarium-cobalt fused magnets (20 x 20 x 10 mm in size) placed bitemporally. Magnetic induction intensity was 100 mT on the surface of the head. Duration of magnetic field application was 15 min. An electrocardiogram was recorded from limb lead II, and both heart rate (average duration of cardiac cycles) and heart rhythmicity were analyzed before and after SMF application. SMF evoked changes in both heart rate and rhythm in 80% of the animals; the predominant effects were bradycardia and disappearance of respiratory sinus arrhythmia. However, the effectiveness of SMF in large measure depends on both functional peculiarities and functional activities of brain autonomic centers.

  18. Long-term physiological T3 supplementation in hypertensive heart disease in rats.

    PubMed

    Weltman, Nathan Y; Pol, Christine J; Zhang, Youhua; Wang, Yibo; Koder, Adrienne; Raza, Sarah; Zucchi, Riccardo; Saba, Alessandro; Colligiani, Daria; Gerdes, A Martin

    2015-09-15

    Animal studies suggest that hypertension leads to cardiac tissue hypothyroidism, a condition that can by itself lead to heart failure. We have previously shown that short-term thyroid hormone treatment in Spontaneously Hypertensive Heart Failure (SHHF) rats near heart failure is beneficial. This study tested the hypothesis that therapeutic, long-term T3 treatment in SHHF rats can prevent or attenuate cardiac dysfunction. Female SHHF rats were treated orally with a physiological T3 dose (0.04 μg/ml) from 12 to 24 mo of age. Age-matched female SHHF and Wistar-Kyoto rats served as hypertensive and normotensive controls, respectively. SHHF rats had reduced serum free thyroid hormone levels and cardiac tissue T3 levels, LV dysfunction, and elevated LV collagen content compared with normotensive controls. Restoration of serum and cardiac tissue thyroid hormone levels in T3-treated rats was associated with no change in heart rate, but strong trends for improvement in LV systolic function and collagen levels. For instance, end-systolic diameter, fractional shortening, systolic wall stress, and LV collagen levels were no longer significantly different from controls. In conclusion, longstanding hypertension in rats led to chronic low serum and cardiac tissue thyroid hormone levels. Long-term treatment with low-dose T3 was safe. While cardiac dysfunction could not be completely prevented in the absence of antihypertensive treatment, T3 may offer additional benefits as an adjunct therapy with possible improvement in diastolic function.

  19. Bone Marrow Mesenchymal Stem Cell Transplantation Retards the Natural Senescence of Rat Hearts

    PubMed Central

    Zhang, Mingyu; Liu, Di; Li, Shuang; Chang, Lingling; Zhang, Yu; Liu, Ruixue; Sun, Fei; Duan, Wenqi; Du, Weijie; Wu, Yanping; Zhao, Tianyang; Xu, Chaoqian

    2015-01-01

    Bone marrow mesenchymal stem cells (BMSCs) have been shown to offer a wide variety of cellular functions including the protective effects on damaged hearts. Here we investigated the antiaging properties of BMSCs and the underlying mechanism in a cellular model of cardiomyocyte senescence and a rat model of aging hearts. Neonatal rat ventricular cells (NRVCs) and BMSCs were cocultured in the same dish with a semipermeable membrane to separate the two populations. Monocultured NRVCs displayed the senescence-associated phenotypes, characterized by an increase in the number of β-galactosidase-positive cells and decreases in the degradation and disappearance of cellular organelles in a time-dependent manner. The levels of reactive oxygen species and malondialdehyde were elevated, whereas the activities of antioxidant enzymes superoxide dismutase and glutathione peroxidase were decreased, along with upregulation of p53, p21Cip1/Waf1, and p16INK4a in the aging cardiomyocytes. These deleterious alterations were abrogated in aging NRVCs cocultured with BMSCs. Qualitatively, the same senescent phenotypes were consistently observed in aging rat hearts. Notably, BMSC transplantation significantly prevented these detrimental alterations and improved the impaired cardiac function in the aging rats. In summary, BMSCs possess strong antisenescence action on the aging NRVCs and hearts and can improve cardiac function after transplantation in aging rats. The present study, therefore, provides an alternative approach for the treatment of heart failure in the elderly population. PMID:25855590

  20. Comparative analysis of the gap junction protein from rat heart and liver: is there a tissue specificity of gap junctions?

    PubMed

    Gros, D B; Nicholson, B J; Revel, J P

    1983-12-01

    Gap junctions have been isolated from both rat heart and liver, tissues where junctions are typical in appearance and physiology. The purity of the fractions obtained was monitored by electron microscopy (thin-sectioning and negative staining) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The myocardial gap junctions are comprised of a single polypeptide of Mr 28,000, apparently derived from a protein of Mr 30,000. Hepatic gap junctions are also comprised of a single native protein of Mr 28,000 as previously reported. Exhaustive trypsin digestion of the isolated junctions cleaves both of these proteins similarly, while leaving their characteristic junctional lattice structures intact. However, comparison of heart and liver junctional proteins by two-dimensional peptide mapping of tryptic and alpha-chymotryptic fragments, followed by high pressure liquid chromatography, reveals no homology between these proteins.

  1. 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

  2. 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.

  3. Brain and heart sodium channel subtype mRNA expression in rat cerebral cortex.

    PubMed Central

    Yarowsky, P J; Krueger, B K; Olson, C E; Clevinger, E C; Koos, R D

    1991-01-01

    The expression of mRNAs coding for the alpha subunit of rat brain and rat heart sodium channels has been studied in adult and neonatal rat cerebral cortex using the reverse transcription-polymerase chain reaction (RT-PCR). Rat brain sodium channel subtype I, II, IIA, and III sequences were simultaneously amplified in the same PCR using a single oligonucleotide primer pair matched to all four subtype sequences. Identification of each subtype-specific product was inferred from the appearance of unique fragments when the product was digested with specific restriction enzymes. By using this RT-PCR method, products arising from mRNAs for all four brain sodium channel subtypes were identified in RNA extracted from adult rat cerebral cortex. The predominant component was type IIA with lesser levels of types I, II, and III. In contrast, the type II and IIA sequences were the predominant RT-PCR products in neonatal rat cortex, with slightly lower levels of type III and undetectable levels of type I. Thus, from neonate to adult, type II mRNA levels decrease relative to type IIA levels. Using a similar approach, we detected mRNA coding for the rat heart sodium channel in neonatal and adult rat cerebral cortex and in adult rat heart. These results reveal that mRNAs coding for the heart sodium channel and all four previously sequenced rat brain sodium channel subtypes are expressed in cerebral cortex and that type II and IIA channels may be differentially regulated during development. Images PMID:1658783

  4. PPAR ligands improve impaired metabolic pathways in fetal hearts of diabetic rats.

    PubMed

    Kurtz, Melisa; Capobianco, Evangelina; Martinez, Nora; Roberti, Sabrina Lorena; Arany, Edith; Jawerbaum, Alicia

    2014-10-01

    In maternal diabetes, the fetal heart can be structurally and functionally affected. Maternal diets enriched in certain unsaturated fatty acids can activate the nuclear receptors peroxisome proliferator-activated receptors (PPARs) and regulate metabolic and anti-inflammatory pathways during development. Our aim was to investigate whether PPARα expression, lipid metabolism, lipoperoxidation, and nitric oxide (NO) production are altered in the fetal hearts of diabetic rats, and to analyze the putative effects of in vivo PPAR activation on these parameters. We found decreased PPARα expression in the hearts of male but not female fetuses of diabetic rats when compared with controls. Fetal treatments with the PPARα ligand leukotriene B4 upregulated the expression of PPARα and target genes involved in fatty acid oxidation in the fetal hearts. Increased concentrations of triglycerides, cholesterol, and phospholipids were found in the hearts of fetuses of diabetic rats. Maternal treatments with diets supplemented with 6% olive oil or 6% safflower oil, enriched in unsaturated fatty acids that can activate PPARs, led to few changes in lipid concentrations, but up-regulated PPARα expression in fetal hearts. NO production, which was increased in the hearts of male and female fetuses in the diabetic group, and lipoperoxidation, which was increased in the hearts of male fetuses in the diabetic group, was reduced by the maternal treatments supplemented with safflower oil. In conclusion, impaired PPARα expression, altered lipid metabolism, and increased oxidative and nitridergic pathways were evidenced in hearts of fetuses of diabetic rats and were regulated in a gender-dependent manner by treatments enriched with PPAR ligands.

  5. 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.

  6. The effect of endotoxin on heart rate dynamics in diabetic rats.

    PubMed

    Meamar, Morvarid; Dehpour, Tara; Mazloom, Roham; Sharifi, Fatemeh; Raoufy, Mohammad R; Dehpour, Ahmad R; Mani, Ali R

    2015-05-01

    The effect of endotoxin on heart rate variability (HRV) was assessed in diabetic and controls rats using a telemetric system. Endotoxin induced a reduction in sample entropy of cardiac rhythm in control animals. However, this effect was significantly blunted in streptozotocin-induced diabetic rats. Since uncoupling of cardiac pacemaker from cholinergic control is linked to reduced HRV in endotoxemia, chronotropic responsiveness to cholinergic stimulation was assessed in isolated atria. Endotoxemia was associated with impaired responsiveness to carbacholine in control rats. However, endotoxemia did not impair cholinergic responsiveness in diabetic atria. These findings corroborates with development of endotoxin tolerance in diabetic rats.

  7. Improved preservation of the rat heart with celsior solution supplemented with cariporide plus glyceryl trinitrate.

    PubMed

    Gao, Ling; Hicks, Mark; MacDonald, Peter S

    2005-08-01

    Our aim was to investigate whether the addition of glyceryl trinitrate (GTN), a source of nitric oxide, and/or cariporide, a Na/H exchange inhibitor, to a commercial preservation solution (Celsior) improved and extended cardiac preservation. After baseline indices of cardiac function (aortic flow, coronary flow, heart rate, cardiac output) were measured in an isolated working rat heart model, hearts were arrested and stored at 2-3 degrees C for 6 or 10 h in Celsior solution alone, Celsior supplemented with either 0.1 mg/mL GTN or 10 microM cariporide or both. After storage, functional measurements were repeated and recovery of each parameter was expressed as a percentage of its pre-storage baseline. After 6 h storage, recovery of cardiac function was significantly better in hearts stored in GTN- or cariporide-supplemented Celsior solution compared with Celsior solution alone. The beneficial effect of GTN was significantly abrogated in hearts perfused with glibenclamide prior to storage. Significant recovery of cardiac function after 10 h storage was only observed in hearts stored in Celsior solution supplemented with both GTN and cariporide. Combined supplementation with GTN and cariporide extends the safe period of storage of the rat heart and may be a useful approach to enhancing preservation of the donor heart.

  8. Amygdala central nucleus lesions attenuate acoustic startle stimulus-evoked heart rate changes in rats.

    PubMed

    Young, B J; Leaton, R N

    1996-04-01

    Amygdala central nucleus (CNA) lesions were used to test the hypothesis that stimulus-evoked heart rate changes can reflect the development of fear during acoustic startle testing. A 120-dB white noise startle stimulus produced freezing as well as phasic heart rate accelerations and decelerations, and an abrupt decrease in tonic heart rate, in sham-operated rats. These responses were all significantly reduced in CNA-lesioned rats. In contrast, an 87-dB stimulus elicited only significant phasic decelerations that were similarly attenuated by the CNA lesions. In a follow-up experiment, the CNA lesions also attenuated phasic cardiac decelerations evoked by a conditioned stimulus-like, 85-dB pure tone. The results support the contention (B. J. Young & R.N. Leaton, 1994) that heart rate changes can reflect fear conditioned during acoustic startle testing and, in addition, suggest that the amygdala mediates responses to nonsignal acoustic stimuli.

  9. Heart failure alters matrix metalloproteinase gene expression and activity in rat skeletal muscle.

    PubMed

    Carvalho, Robson Francisco; Dariolli, Rafael; Justulin Junior, Luis Antonio; Sugizaki, Mário Mateus; Politi Okoshi, Marina; Cicogna, Antonio Carlos; Felisbino, Sérgio Luis; Dal Pai-Silva, Maeli

    2006-12-01

    Heart failure is associated with a skeletal muscle myopathy with cellular and extracellular alterations. The hypothesis of this investigation is that extracellular changes may be associated with enhanced mRNA expression and activity of matrix metalloproteinases (MMP). We examined MMP mRNA expression and MMP activity in Soleus (SOL), extensor digitorum longus (EDL), and diaphragm (DIA) muscles of young Wistar rat with monocrotaline-induced heart failure. Rats injected with saline served as age-matched controls. MMP2 and MMP9 mRNA contents were determined by RT-PCR and MMP activity by electrophoresis in gelatin-containing polyacrylamide gels in the presence of SDS under non-reducing conditions. Heart failure increased MMP9 mRNA expression and activity in SOL, EDL and DIA and MMP2 mRNA expression in DIA. These results suggest that MMP changes may contribute to the skeletal muscle myopathy during heart failure.

  10. Treatment with alpha-melanocyte stimulating hormone preserves calcium regulatory proteins in rat heart allografts.

    PubMed

    Colombo, Gualtiero; Sordi, Andrea; Lonati, Caterina; Carlin, Andrea; Turcatti, Flavia; Leonardi, Patrizia; Gatti, Stefano; Catania, Anna

    2008-08-01

    Prevention of graft dysfunction is a major objective in transplantation medicine. Previous research on experimental heart transplantation indicated that treatment with the immunomodulatory peptide alpha-melanocyte stimulating hormone (alpha-MSH) improves histopathology, prolongs allograft survival, and reduces expression of the main tissue injury mediators. Because calcium-handling is critical in heart graft function, we determined the effects of transplantation injury and influences of alpha-MSH treatment on representative calcium regulatory proteins in rat heart allografts. Hearts from Brown Norway rats were transplanted heterotopically into MHC incompatible Lewis rats. Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), protein kinase C epsilon (PKC epsilon), sarcoplasmic/endoplasmic reticulum calcium-ATPase 2 (SERCA2a), arrestin-beta1 (Arrb1), cholinergic receptor M2 (Chrm2), and inositol 1,4,5-triphosphate receptor 1 (InsP(3)R1) were examined in: (1) non-transplanted donor hearts; (2) allografts from saline-treated rats; and (3) allografts from rats treated with the synthetic alpha-MSH analog Nle4-DPhe7-alpha-MSH (NDP-alpha-MSH) (100 microg i.p. every 12h). Transplantation injury was associated with severe reduction in calcium regulatory protein transcription and expression level. NDP-alpha-MSH administration partly reversed inhibition of protein transcription and almost completely prevented protein loss. Finally, because certain effects of cyclic 3'-5'-adenosine monophosphate (cAMP) signaling on calcium handling in cardiac myocytes depend on activation of exchange protein directly activated by cAMP 1 (Epac1), we determined Epac1 mRNA and protein expression in heart allografts. Transplantation injury markedly reduced Epac1. NDP-alpha-MSH treatment significantly preserved both Epac1 protein and mRNA in the allografts. Administration of alpha-MSH or related melanocortins could reduce transplantation-induced dysfunction through protection of heart calcium

  11. Tissue distribution comparison between healthy and fatty liver rats after oral administration of hawthorn leaf extract.

    PubMed

    Yin, Jingjing; Qu, Jianguo; Zhang, Wenjie; Lu, Dongrui; Gao, Yucong; Ying, Xixiang; Kang, Tingguo

    2014-05-01

    Hawthorn leaves, a well-known traditional Chinese medicine, have been widely used for treating cardiovascular and fatty liver diseases. The present study aimed to investigate the therapeutic basis treating fatty liver disease by comparing the tissue distribution of six compounds of hawthorn leaf extract (HLE) in fatty liver rats and healthy rats after oral administration at first day, half month and one month, separately. Therefore, a sensitive and specific HPLC method with internal standard was developed and validated to determine chlorogenic acid, vitexin-4''-O-glucoside, vitexin-2''-O-rhamnoside, vitexin, rutin and hyperoside in the tissues including heart, liver, spleen, kidney, stomach and intestine. The results indicated that the six compounds in HLE presented some bioactivity in treating rat fatty liver as the concentrations of the six compounds varied significantly in inter- and intragroup comparisons (healthy and/or fatty liver group).

  12. Sexual dimorphism in the expression of mitochondria-related genes in rat heart at different ages.

    PubMed

    Vijay, Vikrant; Han, Tao; Moland, Carrie L; Kwekel, Joshua C; Fuscoe, James C; Desai, Varsha G

    2015-01-01

    Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Moreover, sex and age are considered major risk factors in the development of CVDs. Mitochondria are vital for normal cardiac function, and regulation of mitochondrial structure and function may impact susceptibility to CVD. To identify potential role of mitochondria in sex-related differences in susceptibility to CVD, we analyzed the basal expression levels of mitochondria-related genes in the hearts of male and female rats. Whole genome expression profiling was performed in the hearts of young (8-week), adult (21-week), and old (78-week) male and female Fischer 344 rats and the expression of 670 unique genes related to various mitochondrial functions was analyzed. A significant (p<0.05) sexual dimorphism in expression levels of 46, 114, and 41 genes was observed in young, adult and old rats, respectively. Gene Ontology analysis revealed the influence of sex on various biological pathways related to cardiac energy metabolism at different ages. The expression of genes involved in fatty acid metabolism was significantly different between the sexes in young and adult rat hearts. Adult male rats also showed higher expression of genes associated with the pyruvate dehydrogenase complex compared to females. In young and adult hearts, sexual dimorphism was not noted in genes encoding oxidative phosphorylation. In old rats, however, a majority of genes involved in oxidative phosphorylation had higher expression in females compared to males. Such basal differences between the sexes in cardiac expression of genes associated with energy metabolism may indicate a likely involvement of mitochondria in susceptibility to CVDs. In addition, female rats showed lower expression levels of apoptotic genes in hearts compared to males at all ages, which may have implications for better preservation of cardiac mass in females than in males.

  13. Sexual Dimorphism in the Expression of Mitochondria-Related Genes in Rat Heart at Different Ages

    PubMed Central

    Vijay, Vikrant; Han, Tao; Moland, Carrie L.; Kwekel, Joshua C.; Fuscoe, James C.; Desai, Varsha G.

    2015-01-01

    Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Moreover, sex and age are considered major risk factors in the development of CVDs. Mitochondria are vital for normal cardiac function, and regulation of mitochondrial structure and function may impact susceptibility to CVD. To identify potential role of mitochondria in sex-related differences in susceptibility to CVD, we analyzed the basal expression levels of mitochondria-related genes in the hearts of male and female rats. Whole genome expression profiling was performed in the hearts of young (8-week), adult (21-week), and old (78-week) male and female Fischer 344 rats and the expression of 670 unique genes related to various mitochondrial functions was analyzed. A significant (p<0.05) sexual dimorphism in expression levels of 46, 114, and 41 genes was observed in young, adult and old rats, respectively. Gene Ontology analysis revealed the influence of sex on various biological pathways related to cardiac energy metabolism at different ages. The expression of genes involved in fatty acid metabolism was significantly different between the sexes in young and adult rat hearts. Adult male rats also showed higher expression of genes associated with the pyruvate dehydrogenase complex compared to females. In young and adult hearts, sexual dimorphism was not noted in genes encoding oxidative phosphorylation. In old rats, however, a majority of genes involved in oxidative phosphorylation had higher expression in females compared to males. Such basal differences between the sexes in cardiac expression of genes associated with energy metabolism may indicate a likely involvement of mitochondria in susceptibility to CVDs. In addition, female rats showed lower expression levels of apoptotic genes in hearts compared to males at all ages, which may have implications for better preservation of cardiac mass in females than in males. PMID:25615628

  14. Behavior of silica particles introduced into an isolated rat heart as potential drug carriers.

    PubMed

    Borak, B; Arkowski, J; Skrzypiec, M; Ziółkowski, P; Krajewska, B; Wawrzyńska, M; Grotthus, B; Gliniak, H; Szelag, A; Mazurek, W; Biały, D; Maruszewski, K

    2007-12-01

    Silica powders consisting of small spherical particles (50-200 nm) have been obtained by the sol-gel method. A suspension of such particles in the Krebs-Hanseleit solution has been introduced into the coronary circulation of a beating perfused rat heart. The influence of the suspension on the heart muscle and the coronary vessels in the rat body has been histopathologically examined. The particles have not left the lumen of the vessels and have not caused any side effects. These observations suggest the possibility of using such silica particles as a carrier for selected drugs.

  15. The Anabolic Androgenic Steroid Nandrolone Decanoate Disrupts Redox Homeostasis in Liver, Heart and Kidney of Male Wistar Rats

    PubMed Central

    Frankenfeld, Stephan P.; Oliveira, Leonardo P.; Ortenzi, Victor H.; Rego-Monteiro, Igor CC.; Chaves, Elen A.; Ferreira, Andrea C.; Leitão, Alvaro C.; Carvalho, Denise P.; Fortunato, Rodrigo S.

    2014-01-01

    The abuse of anabolic androgenic steroids (AAS) may cause side effects in several tissues. Oxidative stress is linked to the pathophysiology of most of these alterations, being involved in fibrosis, cellular proliferation, tumorigenesis, amongst others. Thus, the aim of this study was to determine the impact of supraphysiological doses of nandrolone decanoate (DECA) on the redox balance of liver, heart and kidney. Wistar male rats were treated with intramuscular injections of vehicle or DECA (1 mg.100 g−1 body weight) once a week for 8 weeks. The activity and mRNA levels of NADPH Oxidase (NOX), and the activity of catalase, glutathione peroxidase (GPx) and total superoxide dismutase (SOD), as well as the reduced thiol and carbonyl residue proteins, were measured in liver, heart and kidney. DECA treatment increased NOX activity in heart and liver, but NOX2 mRNA levels were only increased in heart. Liver catalase and SOD activities were decreased in the DECA-treated group, but only catalase activity was decreased in the kidney. No differences were detected in GPx activity. Thiol residues were decreased in the liver and kidney of treated animals in comparison to the control group, while carbonyl residues were increased in the kidney after the treatment. Taken together, our results show that chronically administered DECA is able to disrupt the cellular redox balance, leading to an oxidative stress state. PMID:25225984

  16. The anabolic androgenic steroid nandrolone decanoate disrupts redox homeostasis in liver, heart and kidney of male Wistar rats.

    PubMed

    Frankenfeld, Stephan P; Oliveira, Leonardo P; Ortenzi, Victor H; Rego-Monteiro, Igor C C; Chaves, Elen A; Ferreira, Andrea C; Leitão, Alvaro C; Carvalho, Denise P; Fortunato, Rodrigo S

    2014-01-01

    The abuse of anabolic androgenic steroids (AAS) may cause side effects in several tissues. Oxidative stress is linked to the pathophysiology of most of these alterations, being involved in fibrosis, cellular proliferation, tumorigenesis, amongst others. Thus, the aim of this study was to determine the impact of supraphysiological doses of nandrolone decanoate (DECA) on the redox balance of liver, heart and kidney. Wistar male rats were treated with intramuscular injections of vehicle or DECA (1 mg.100 g(-1) body weight) once a week for 8 weeks. The activity and mRNA levels of NADPH Oxidase (NOX), and the activity of catalase, glutathione peroxidase (GPx) and total superoxide dismutase (SOD), as well as the reduced thiol and carbonyl residue proteins, were measured in liver, heart and kidney. DECA treatment increased NOX activity in heart and liver, but NOX2 mRNA levels were only increased in heart. Liver catalase and SOD activities were decreased in the DECA-treated group, but only catalase activity was decreased in the kidney. No differences were detected in GPx activity. Thiol residues were decreased in the liver and kidney of treated animals in comparison to the control group, while carbonyl residues were increased in the kidney after the treatment. Taken together, our results show that chronically administered DECA is able to disrupt the cellular redox balance, leading to an oxidative stress state.

  17. Impairment of energy metabolism in intact residual myocardium of rat hearts with chronic myocardial infarction.

    PubMed Central

    Neubauer, S; Horn, M; Naumann, A; Tian, R; Hu, K; Laser, M; Friedrich, J; Gaudron, P; Schnackerz, K; Ingwall, J S

    1995-01-01

    The purpose of this study was to test the hypothesis that energy metabolism is impaired in residual intact myocardium of chronically infarcted rat heart, contributing to contractile dysfunction. Myocardial infarction (MI) was induced in rats by coronary artery ligation. Hearts were isolated 8 wk later and buffer-perfused isovolumically. MI hearts showed reduced left ventricular developed pressure, but oxygen consumption was unchanged. High-energy phosphate contents were measured chemically and by 31P-NMR spectroscopy. In residual intact left ventricular tissue, ATP was unchanged after MI, while creatine phosphate was reduced by 31%. Total creatine kinase (CK) activity was reduced by 17%, the fetal CK isoenzymes BB and MB increased, while the "adult" mitochondrial CK isoenzyme activity decreased by 44%. Total creatine content decreased by 35%. Phosphoryl exchange between ATP and creatine phosphate, measured by 31P-NMR magnetization transfer, fell by 50% in MI hearts. Thus, energy reserve is substantially impaired in residual intact myocardium of chronically infarcted rats. Because phosphoryl exchange was still five times higher than ATP synthesis rates calculated from oxygen consumption, phosphoryl transfer via CK may not limit baseline contractile performance 2 mo after MI. In contrast, when MI hearts were subjected to acute stress (hypoxia), mechanical recovery during reoxygenation was impaired, suggesting that reduced energy reserve contributes to increased susceptibility of MI hearts to acute metabolic stress. PMID:7883957

  18. 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

  19. Hydrogen-containing saline attenuates doxorubicin-induced heart failure in rats.

    PubMed

    Wu, Shujing; Zhu, Liqun; Yang, Jing; Fan, Zhixin; Dong, Yanli; Luan, Rui; Cai, Jingjing; Fu, Lu

    2014-08-01

    Interactions between doxorubicin (DOX) and iron generate reactive oxygen species and contribute to DOX-induced heart failure. Hydrogen, as a selective antioxidant, is a promising potential therapeutic option for the treatment of a variety of diseases. Therefore, we investigated the preventive effects of hydrogen treatment on DOX-induced heart failure in rats. We found that cardiac function was significantly improved and that the plasma levels of oxidative-stress markers and myocardial autophagic activity were decreased in animals treated with hydrogen-containing saline. Therefore, we conclude that hydrogen-containing saline may have beneficial effects for doxorubicin-induced heart failure.

  20. Metabolic adaptations of skeletal muscle to voluntary wheel running exercise in hypertensive heart failure rats.

    PubMed

    Schultz, R L; Kullman, E L; Waters, R P; Huang, H; Kirwan, J P; Gerdes, A M; Swallow, J G

    2013-01-01

    The Spontaneously Hypertensive Heart Failure (SHHF) rat mimics the human progression of hypertension from hypertrophy to heart failure. However, it is unknown whether SHHF animals can exercise at sufficient levels to observe beneficial biochemical adaptations in skeletal muscle. Thirty-seven female SHHF and Wistar-Furth (WF) rats were randomized to sedentary (SHHFsed and WFsed) and exercise groups (SHHFex and WFex). The exercise groups had access to running wheels from 6-22 months of age. Hindlimb muscles were obtained for metabolic measures that included mitochondrial enzyme function and expression, and glycogen utilization. The SHHFex rats ran a greater distance and duration as compared to the WFex rats (P<0.05), but the WFex rats ran at a faster speed (P<0.05). Skeletal muscle citrate synthase and beta-hydroxyacyl-CoA dehydrogenase enzyme activity was not altered in the SHHFex group, but was increased (P<0.05) in the WFex animals. Citrate synthase protein and gene expression were unchanged in SHHFex animals, but were increased in WFex rats (P<0.05). In the WFex animals muscle glycogen was significantly depleted after exercise (P<0.05), but not in the SHHFex group. We conclude that despite robust amounts of aerobic activity, voluntary wheel running exercise was not sufficiently intense to improve the oxidative capacity of skeletal muscle in adult SHHF animals, indicating an inability to compensate for declining heart function by improving peripheral oxidative adaptations in the skeletal muscle.

  1. Electroacupuncture improves cardiac function and remodeling by inhibition of sympathoexcitation in chronic heart failure rats.

    PubMed

    Ma, Luyao; Cui, Baiping; Shao, Yongfeng; Ni, Buqing; Zhang, Weiran; Luo, Yonggang; Zhang, Shijiang

    2014-05-15

    Chronic heart failure (CHF) is responsible for significant morbidity and mortality worldwide, mainly as a result of neurohumoral activation. Acupuncture has been used to treat a wide range of diseases and conditions. In this study, we investigated the effects of electroacupuncture (EA) on the sympathetic nerve activity, heart function, and remodeling in CHF rats after ligation of the left anterior descending coronary artery. CHF rats were randomly selected to EA and control groups for acute and chronic experiments. In the acute experiment, both the renal sympathetic nerve activity and cardiac sympathetic afferent reflex elicited by epicardial application of capsaicin were recorded. In the chronic experiment, we performed EA for 30 min once a day for 1 wk to test the long-term EA effects on heart function, remodeling, as well as infarct size in CHF rats. The results show EA significantly decreased the renal sympathetic nerve activity effectively, inhibited cardiac sympathetic afferent reflex, and lowered the blood pressure of CHF rats. Treating CHF rats with EA for 1 wk dramatically increased left ventricular ejection fraction and left ventricular fraction shortening, reversed the enlargement of left ventricular end-systolic dimension and left ventricular end-diastolic dimension, and shrunk the infarct size. In this experiment, we demonstrated EA attenuates sympathetic overactivity. Additionally, long-term EA improves cardiac function and remodeling and reduces infarct size in CHF rats. EA is a novel and potentially useful therapy for treating CHF.

  2. [Effect of the sharply strengthened motor activity on heart pumping ability of rats and mechanisms of its regulation].

    PubMed

    Nikitin, A S; Abzalov, R A; Abzalov, N I; Vafina, E Z

    2013-08-01

    The indicators of heart pumping ability of rats at a muscular loading of the maximum power and also in the conditions of transition from sharply strengthened motor activity regime on a strengthened motor activity regime at adrenergic influence stimulation and blockade were investigated. At rats of 100-daily age at the strengthened motor activity heart rate is less, and blood stroke volume is more, than in the rats, subject to muscular loading of the maximum power. The adrenergic influence on the heart's pumping ability of sharply strengthened motor activity rats is much more, than of unlimited motor activity rats. At the α1-adrenoreceptors blockade at 100-daily rats the decreasing in intensity of muscular loading causes increased in adrenergic influence on heart pumping ability.

  3. Chemical sympathectomy restores baroreceptor-heart rate reflex and heart rate variability in rats with chronic nitric oxide deficiency.

    PubMed

    Chaswal, M; Das, S; Prasad, J; Katyal, A; Fahim, M

    2015-01-01

    Nitric oxide (NO) plays a crucial role not only in regulation of blood pressure but also in maintenance of cardiac autonomic tone and its deficiency induced hypertension is accompanied by cardiac autonomic dysfunction. However, underlying mechanisms are not clearly defined. We hypothesized that sympathetic activation mediates hemodynamic and cardiac autonomic changes consequent to deficient NO synthesis. We used chemical sympathectomy by 6-hydroxydopamine to examine the influence of sympathetic innervation on baroreflex sensitivity (BRS) and heart rate variability (HRV) of chronic N(G)-nitro-L-arginine methyl ester (L-NAME) treated adult Wistar rats. BRS was determined from heart rate responses to changes in systolic arterial pressure achieved by intravenous administration of phenylephrine and sodium nitroprusside. Time and frequency domain measures of HRV were calculated from 5-min electrocardiogram recordings. Chronic L-NAME administration (50 mg/kg per day for 7 days orally through gavage) in control rats produced significant elevation of blood pressure, tachycardia, attenuation of BRS for bradycardia and tachycardia reflex and fall in time as well as frequency domain parameters of HRV. Sympathectomy completely abolished the pressor as well as tachycardic effect of chronic L-NAME. In addition, BRS and HRV improved after removal of sympathetic influence in chronic L-NAME treated rats. These results support the concept that an exaggerated sympathetic activity is the principal mechanism of chronic L-NAME hypertension and associated autonomic dysfunction.

  4. Improvement of Heart Failure by Human Amniotic Mesenchymal Stromal Cell Transplantation in Rats

    PubMed Central

    Razavi Tousi, Seyed Mohammad Taghi; Faghihi, Mahdieh; Nobakht, Maliheh; Molazem, Mohammad; Kalantari, Elham; Darbandi Azar, Amir; Aboutaleb, Nahid

    2016-01-01

    Background: Recently, stem cells have been considered for the treatment of heart diseases, but no marked improvement has been recorded. This is the first study to examine the functional and histological effects of the transplantation of human amniotic mesenchymal stromal cells (hAMSCs) in rats with heart failure (HF). Methods: This study was conducted in the years 2014 and 2015. 35 male Wistar rats were randomly assigned into 5 equal experimental groups (7 rats each) as 1- Control 2- Heart Failure (HF) 3- Sham 4- Culture media 5- Stem Cell Transplantation (SCT). Heart failure was induced using 170 mg/kg/d of isoproterenol subcutaneously injection in 4 consecutive days. The failure confirmed by the rat cardiac echocardiography on day 28. In SCT group, 3×106 cells in 150 µl of culture media were transplanted to the myocardium. At the end, echocardiographic and hemodynamic parameters together with histological evaluation were done. Results: Echocardiography results showed that cardiac ejection fraction in HF group increased from 58/73 ± 9% to 81/25 ± 6/05% in SCT group (p value < 0.001). Fraction shortening in HF group was increased from 27/53 ± 8/58% into 45/55 ± 6/91% in SCT group (p value < 0.001). Furthermore, hAMSCs therapy significantly improved mean diastolic blood pressure, mean arterial pressure, left ventricular systolic pressure, rate pressure product, and left ventricular end-diastolic pressure compared to those in the HF group, with the values reaching the normal levels in the control group. A marked reduction in fibrosis tissue was also found in the SCT group (p value < 0.001) compared with the animals in the HF group. Conclusion: The transplantation of hAMSCs in rats with heart failure not only decreased the level of fibrosis but also conferred significant improvement in heart performance in terms of echocardiographic and hemodynamic parameters. PMID:27956912

  5. Effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart.

    PubMed

    Kansal, Sunil Kumar; Jyoti, Uma; Sharma, Samridhi; Kaura, Arun; Deshmukh, Rahul; Goyal, Sandeep

    2015-06-01

    Hyperlipidemia is regarded as independent risk factor in the development of ischemic heart disease, and it can increase the myocardial susceptibility to ischemia-/reperfusion (I/R)-induced injury. Hyperlipidemia attenuates the cardioprotective response of ischemic preconditioning (IPC). The present study investigated the effect of zinc supplements in the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat hearts. Hyperlipidemia was induced in rat by feeding high-fat diet (HFD) for 6 weeks then the serum lipid profile was observed. In experiment, the isolated Langendorff rat heart preparation was subjected to 4 cycles of ischemic preconditioning (IPC), then 30 min of ischemia followed by 120 min of reperfusion. Myocardial infarct size was elaborated morphologically by triphenyltetrazolium chloride (TTC) staining and biochemically by lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) release from coronary effluent and left ventricular collagen content. However, the effect of zinc supplement, i.e., zinc pyrithione (10 μM) perfused during reperfusion for 120 min, significantly abrogated the attenuated cardioprotective effect of ischemic preconditioning in hyperlipidemic rat heart whereas administration of chelator of this zinc ionophore, i.e., N,N,N',N'-tetrakis(2-pyridylmethyl)ethylene diamine (TPEN; 10 μM), perfused during reperfusion 2 min before the perfusion of zinc pyrithione abrogated the cardioprotective effect of zinc supplement during experiment in hyperlipidemic rat heart. Thus, the administration of zinc supplements limits the infarct size, LDH, and CK-MB and enhanced the collagen level which suggests that the attenuated cardioprotective effect of IPC in hyperlipidemic rat is due to zinc loss during reperfusion caused by ischemia/reperfusion.

  6. 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.

  7. 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.

  8. Characterization of spinal afferent neurons projecting to different chambers of the rat heart.

    PubMed

    Guić, Maja Marinović; Kosta, Vana; Aljinović, Jure; Sapunar, Damir; Grković, Ivica

    2010-01-29

    The pattern of distribution of spinal afferent neurons (among dorsal root ganglia-DRGs) that project to anatomically and functionally different chambers of the rat heart, as well as their morphological and neurochemical characteristics were investigated. Retrograde tracing using a patch loaded with Fast blue (FB) was applied to all four chambers of the rat heart and labeled cardiac spinal afferents were characterized by using three neurochemical markers. The majority of cardiac projecting neurons were found from T1 to T4 DRGs, whereas the peak was at T2 DRG. There was no difference in the total number of FB-labeled neurons located in ipsilateral and contralateral DRGs regardless of the chambers marked with the patch. However, significantly more FB-labeled neurons projected to the ventricles compared to the atria (859 vs. 715). The proportion of isolectin B(4) binding in FB-labeled neurons was equal among all neurons projecting to different heart chambers (2.4%). Neurofilament 200 positivity was found in greater proportions in DRG neurons projecting to the left side of the heart, whereas calretinin-immunoreactivity was mostly represented in neurons projecting to the left atrium. Spinal afferent neurons projecting to different chambers of the rat heart exhibit a variety of neurochemical phenotypes depending on binding capacity for isolectin B(4) and immunoreactivity for neurofilament 200 and calretinin, and thus represent important baseline data for future studies.

  9. Nicotine-induced perturbations on heart rate, body temperature and locomotor activity daily rhythms in rats.

    PubMed

    Pelissier, A L; Gantenbein, M; Bruguerolle, B

    1998-08-01

    The aim of this study was to evaluate the influence of nicotine on the daily rhythms of heart rate, body temperature and locomotor activity in unrestrained rats by use of implanted radiotelemetry transmitters. The study was divided into three seven-day periods: a control period, a treatment period and a recovery period. The control period was used for baseline measurement of heart rate, body temperature and locomotor activity. During the treatment period three rats received nicotine (1 mg kg(-1), s.c.) at 0900 h. Three rats received saline under the same experimental conditions. Heart rate, body temperature and locomotor activity were continuously monitored and plotted every 10 min. During the three periods a power spectrum analysis was used to determine the dominant period of rhythmicity. If daily rhythms of heart rate, body temperature and locomotor activity were detected, the characteristics of these rhythms, i.e. the mesors, amplitudes and acrophases, were determined by cosinor analysis, expressed as means +/- s.e.m. and compared by analysis of variance. Nicotine did not suppress daily rhythmicity but induced decreases of amplitudes and phase-advances of acrophases for heart rate, body temperature and locomotor activity. These perturbations might result from the effects of nicotine on the suprachiasmatic nucleus, the hypothalamic clock that co-ordinates biological rhythms.

  10. Evidence for the Primo Vascular System above the Epicardia of Rat Hearts

    PubMed Central

    Lee, Ho-Sung; Lee, Jeong Yim; Kang, Dae-In; Kim, Se Hoon; Lee, Inhyung; Park, Sang Hyun; Yoon, Seung Zhoo; Ryu, Yeon Hee; Lee, Byung-Cheon

    2013-01-01

    We for the first time reported evidence for the existence of a novel network, a PVS, abovethe epicardium of the rat heart. (1) We were consecutively able to visualize the PVs and the PNs above the epicardial spaces of five rats' hearts by using Cr-Hx spraying or injection. (2) Hematoxylin and eosin (H&E) and toluidine blue staining of the PVs and the PNs showed that they consisted of a basophilic matrix; specifically the PNs contained several mast cells, some of which were degranulating into pericardial space. Also, 4′, 6-diamidino-2 phenylindole (DAPI) images of the PVs and the PNs showed that they contained various kinds of cells. (3) Transmission electron microscopic (TEM) longitudinal image of the PVs showed that the sinuses contained many granules with high-electron-density cores in parallel with putative endothelial cells. (4) TEM images of the PNs demonstrated that they consisted of lumen-containing cells surrounded by fibers and that they had mast cells that were degranulating toward the epicardium of the rat heart. The above data suggest that mast-cells-containing novel network exists above the epicardium of the rat heart. PMID:24023576

  11. Evidence for the Primo Vascular System above the Epicardia of Rat Hearts.

    PubMed

    Lee, Ho-Sung; Lee, Jeong Yim; Kang, Dae-In; Kim, Se Hoon; Lee, Inhyung; Park, Sang Hyun; Yoon, Seung Zhoo; Ryu, Yeon Hee; Lee, Byung-Cheon

    2013-01-01

    We for the first time reported evidence for the existence of a novel network, a PVS, abovethe epicardium of the rat heart. (1) We were consecutively able to visualize the PVs and the PNs above the epicardial spaces of five rats' hearts by using Cr-Hx spraying or injection. (2) Hematoxylin and eosin (H&E) and toluidine blue staining of the PVs and the PNs showed that they consisted of a basophilic matrix; specifically the PNs contained several mast cells, some of which were degranulating into pericardial space. Also, 4', 6-diamidino-2 phenylindole (DAPI) images of the PVs and the PNs showed that they contained various kinds of cells. (3) Transmission electron microscopic (TEM) longitudinal image of the PVs showed that the sinuses contained many granules with high-electron-density cores in parallel with putative endothelial cells. (4) TEM images of the PNs demonstrated that they consisted of lumen-containing cells surrounded by fibers and that they had mast cells that were degranulating toward the epicardium of the rat heart. The above data suggest that mast-cells-containing novel network exists above the epicardium of the rat heart.

  12. Dexamethasone Treatment of Newborn Rats Decreases Cardiomyocyte Endowment in the Developing Heart through Epigenetic Modifications.

    PubMed

    Gay, Maresha S; Li, Yong; Xiong, Fuxia; Lin, Thant; Zhang, Lubo

    2015-01-01

    The potential adverse effect of synthetic glucocorticoid, dexamethasone therapy on the developing heart remains unknown. The present study investigated the effects of dexamethasone on cardiomyocyte proliferation and binucleation in the developing heart of newborn rats and evaluated DNA methylation as a potential mechanism. Dexamethasone was administered intraperitoneally in a three day tapered dose on postnatal day 1 (P1), 2 and 3 to rat pups in the absence or presence of a glucocorticoid receptor antagonist Ru486, given 30 minutes prior to dexamethasone. Cardiomyocytes from P4, P7 or P14 animals were analyzed for proliferation, binucleation and cell number. Dexamethasone treatment significantly increased the percentage of binucleated cardiomyocytes in the hearts of P4 pups, decreased myocyte proliferation in P4 and P7 pups, reduced cardiomyocyte number and increased the heart to body weight ratio in P14 pups. Ru486 abrogated the effects of dexamethasone. In addition, 5-aza-2'-deoxycytidine (5-AZA) blocked the effects of dexamethasone on binucleation in P4 animals and proliferation at P7, leading to recovered cardiomyocyte number in P14 hearts. 5-AZA alone promoted cardiomyocyte proliferation at P7 and resulted in a higher number of cardiomyocytes in P14 hearts. Dexamethasone significantly decreased cyclin D2, but not p27 expression in P4 hearts. 5-AZA inhibited global DNA methylation and blocked dexamethasone-mediated down-regulation of cyclin D2 in the heart of P4 pups. The findings suggest that dexamethasone acting on glucocorticoid receptors inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via increased DNA methylation in a gene specific manner.

  13. Long-term effects of type 2 diabetes mellitus on heart rhythm in the Goto-Kakizaki rat.

    PubMed

    Howarth, Frank C; Jacobson, Michael; Shafiullah, Mohamed; Adeghate, Ernest

    2008-03-01

    In vivo biotelemetry studies have demonstrated a variety of heart rhythm disturbances in type 1 diabetes mellitus. In the streptozotocin (STZ)-induced diabetic rat, these disturbances have included reductions in heart rate (HR) and heart rate variability (HRV) and an electrocardiogram that displays prolonged QRS duration and Q-T interval. The aim of this study was to investigate the chronic effects of type 2 diabetes mellitus on heart rhythm in the Goto-Kakizaki (GK) rat. Transmitter devices were surgically implanted in the peritoneal cavity of young male GK and age-matched Wistar control rats. Electrodes from the transmitter were arranged in Einthoven bipolar lead II configuration. Electrocardiogram, physical activity and body temperature data were recorded in rats from age 2 to 15 months. Data were acquired for 2 weeks each month. Non-fasting blood glucose, glucose tolerance and body weight were measured periodically. In GK rats, growth rate and maximal attained body weight were significantly reduced and non-fasting blood glucose was progressively increased compared with age-matched Wistar control animals. Heart rate was significantly lower in GK compared with control rats at 2, 7 and 15 months of age. At 2 months of age, HR was 316 +/- 6 beats min(-1) in GK rats compared with 370 +/- 7 beats min(-1) in Wistar control animals. There was a progressive age-dependent decline in HRV in Wistar control rats; however, HRV in GK rats did not alter significantly with age. Heart rate variability was significantly reduced in GK compared with Wistar control rats at 2 and 7 months. At 2 months of age, HRV was 28 +/- 2 beats min(-1) in GK rats compared with 38 +/- 3 beats min(-1) in Wistar control rats. Reduced HR in GK rats may be an inherited characteristic. The absence of age-dependent reductions in HRV in GK rats may be a consequence of an underlying impairment of autonomic control which manifests at early age.

  14. Prenatal exposure to PFOS caused mitochondia-mediated apoptosis in heart of weaned rat.

    PubMed

    Zeng, Huai-Cai; He, Qing-Zhi; Li, Yuan-Yuan; Wu, Cheng-Qiu; Wu, Yi-Mou; Xu, Shun-Qing

    2015-09-01

    Perfluorooctanyl sulfonate (PFOS), a cardiac toxicity compound, has been widely detected in the environment and in organisms. However, the toxic mechanism is not clear. Our previous study indicated that prenatal PFOS exposure led to swollen mitochondrial with vacuolar structure and loss of cristae in offsping's heart. The purpose of this study was to investigate the effect of PFOS on the apoptosis in developing heart and mitochondria-mediated apoptosis pathway. Pregnant Sprague-Dawley (SD) rats were exposed to PFOS at doses of 0.1, 0.6, and 2.0 mg/kg-d and 0.05% Tween 80 as control by gavage from gestation day 2 (GD 2) to GD 21. Apoptosis, as well as expression of apoptosis related genes associated with mitochondrial-mediated apoptosis pathway, including p53, bcl-2, bax, cytochrome c, caspase-9, and caspase-3 were analyzed in heart tissues from weaned (postnatal day 21, PND 21) offspring. The results showed that prenatal PFOS exposure resulted in apoptosis in the offspring's heart. The mRNA and protein expression levels of p53, bax, cytochrome c, caspase-9, and caspase-3 in the offspring's heart were enhanced in various PFOS-treated groups, meanwhile, the bcl-2 expression levels were decreased. Our results indicated that prenatal PFOS exposure induced the apoptosis of weaned offspring rat heart tissue via mitochondria-mediated apoptotic pathway.

  15. Gene Expression in Rat Hearts Following Oral Administration of a Single Hepatotoxic Dose of Acetaminophen

    PubMed Central

    Kil, Hong Ryang; Park, Kwangsik; Noh, Chung Il

    2012-01-01

    Purpose Toxicity caused by acetaminophen and its toxic mechanisms in the liver have been widely studied, including effects involving metabolism and oxidative stress. However, its adverse effects on heart have not been sufficiently investigated. This study evaluated the cardiac influence and molecular events occurring within the myocardium in rats treated with a dose of acetaminophen large enough to induce conventional liver damage. Materials and Methods Male rats were orally administered a single dose of acetaminophen at 1,000 mg/kg-body weight, and subsequently examined for conventional toxicological parameters and for gene expression alterations to both the heart and liver 24 hours after administration. Results Following treatment, serum biochemical parameters including aspartate aminotransferase and alanine aminotransferase were elevated. Histopathological alterations of necrosis were observed in the liver, but not in the heart. However, alterations in gene expression were observed in both the liver and heart 24 hours after dosing. Transcriptional profiling revealed that acetaminophen changed the expression of genes implicated in oxidative stress, inflammatory processes, and apoptosis in the heart as well as in the liver. The numbers of up-regulated and down-regulated genes in the heart were 271 and 81, respectively, based on a two-fold criterion. Conclusion The induced expression of genes implicated in oxidative stress and inflammatory processes in the myocardium reflects molecular levels of injury caused by acetaminophen (APAP), which could not be identified by conventional histopathology. PMID:22187249

  16. Polyol pathway and modulation of ischemia-reperfusion injury in Type 2 diabetic BBZ rat hearts

    PubMed Central

    Li, Qing; Hwang, Yuying C; Ananthakrishnan, Radha; Oates, Peter J; Guberski, Dennis; Ramasamy, Ravichandran

    2008-01-01

    We investigated the role of polyol pathway enzymes aldose reductase (AR) and sorbitol dehydrogenase (SDH) in mediating injury due to ischemia-reperfusion (IR) in Type 2 diabetic BBZ rat hearts. Specifically, we investigated, (a) changes in glucose flux via cardiac AR and SDH as a function of diabetes duration, (b) ischemic injury and function after IR, (c) the effect of inhibition of AR or SDH on ischemic injury and function. Hearts isolated from BBZ rats, after 12 weeks or 48 weeks diabetes duration, and their non-diabetic littermates, were subjected to IR protocol. Myocardial function, substrate flux via AR and SDH, and tissue lactate:pyruvate (L/P) ratio (a measure of cytosolic NADH/NAD+), and lactate dehydrogenase (LDH) release (a marker of IR injury) were measured. Zopolrestat, and CP-470,711 were used to inhibit AR and SDH, respectively. Myocardial sorbitol and fructose content, and associated changes in L/P ratios were significantly higher in BBZ rats compared to non-diabetics, and increased with disease duration. Induction of IR resulted in increased ischemic injury, reduced ATP levels, increases in L/P ratio, and poor cardiac function in BBZ rat hearts, while inhibition of AR or SDH attenuated these changes and protected hearts from IR injury. These data indicate that AR and SDH are key modulators of myocardial IR injury in BBZ rat hearts and that inhibition of polyol pathway could in principle be used as a therapeutic adjunct for protection of ischemic myocardium in Type 2 diabetic patients. PMID:18957123

  17. Platelet deposition in rat heart allografts and the effect of a thromboxane receptor antagonist

    SciTech Connect

    Foegh, M.L.; Khirabadi, B.S.; Ramwell, P.W.

    1986-07-01

    The effect of a thromboxane antagonist, L640,035 on platelet deposition in heart allografts was studied. Twenty Lewis rats received heterotopic allografts from Lewis x Brown-Norway F1 hybrid. All recipients received azathioprine (5 mg/kg/day). The rats were divided into three groups. Groups II and III were also treated daily with either the vehicle for L640,035 or L640,035 respectively. Syngeneic indium-111-labeled platelet deposition was determined in the allograft and the native heart at 6, 9, and 13 days after transplantation; group III was studied on the sixth and ninth day only. A rapidly increasing platelet deposition was seen in allografts from rats given azathioprine; whereas the thromboxane antagonist prevented the increase in platelet deposition on the ninth day.

  18. Arachidonic acid incorporation and turnover is decreased in sympathetically denervated rat heart.

    PubMed

    Patrick, Casey B; McHowat, Jane; Rosenberger, Thad A; Rapoport, Stanley I; Murphy, Eric J

    2005-06-01

    Heart sympathetic denervation can accompany Parkinson's disease, but the effect of this denervation on cardiac lipid-mediated signaling is unknown. To address this issue, rats were sympathetically denervated with 6-hydroxydopamine (6-OHDA, 50 mg/kg ip) and infused with 170 muCi/kg of either [1-(14)C]palmitic acid ([1-(14)C]16:0) or [1-(14)C]arachidonic acid ([1-(14)C]20:4 n-6), and kinetic parameters were assessed using a steady-state radiotracer model. Heart norepinephrine and epinephrine levels were decreased 82 and 85%, respectively, in denervated rats, and this correlated with a 34% reduction in weight gain in treated rats. Fatty acid tracer uptake was not significantly different between groups for either tracer, although the dilution coefficient lambda was increased in [1-(14)C]20:4 n-6-infused rats, which indicates that less 20:4 n-6 was recycled in denervated rats. In [1-(14)C]16:0-infused rats, incorporation rate and turnover values of 16:0 in stable lipid compartments were unchanged, which is indicative of preservation of beta-oxidation. In [1-(14)C]20:4 n-6-infused rats, there were dramatic reductions in incorporation rate (60-84%) and turnover value (56-85%) in denervated rats that were dependent upon the lipid compartment. In addition, phospholipase A(2) activity was reduced 40% in treated rats, which is consistent with the reduction observed in 20:4 n-6 turnover. These results demonstrate marked reductions in 20:4 n-6 incorporation rate and turnover in sympathetic denervated rats and thereby suggest an effect on lipid-mediated signal transduction mediated by a reduction in phospholipase A(2) activity.

  19. Heart rate reactivity in HAD and LAD rats during Pavlovian fear conditioning.

    PubMed

    Rorick, Linda M; Finn, Peter R; Steinmetz, Joseph E

    2004-01-01

    Recently, we reported that High-Alcohol-Drinking (HAD) rats exhibited selective deficits in active avoidance learning under alcohol-naive conditions, and that administration of moderate doses of alcohol (0.5 and 1.0 g/kg) facilitated learning in these rats (Blankenship et al., 2000; Rorick et al., 2003b). We hypothesized that the deficits resulted from excessive fear in the aversive learning context and that the anxiolytic properties of alcohol may have contributed to the improved learning that was observed after alcohol administration. This hypothesis was supported by a recent study in which prolonged freezing in HAD rats was seen after a classical fear conditioning procedure (Rorick et al., 2003a). To provide additional evidence that HAD rats indeed exhibit behaviors consistent with the expression of increased fear in aversive learning contexts, we employed a Pavlovian fear conditioning task to measure heart rate in HAD and Low-Alcohol-Drinking (LAD) rats. In this study, HAD (HAD-1 and HAD-2) and LAD (LAD-1 and LAD-2) rats were assigned to one of three pre-exposure conditions: Context Only, Context/Tone, or Sequential (Context Only followed by Context/Tone) Pre-Exposure. Following pre-exposure, fear conditioning acquisition and extinction procedures were identical for all groups. Results indicated that although no baseline differences were observed between HAD and LAD rats, HAD rats receiving Context-Only pre-exposure exhibited excessive heart rate reactivity to the tone conditional stimulus during fear conditioning acquisition, compared to LAD rats receiving the same pre-exposure conditions. These findings support the hypothesis that HAD rats exhibit behaviors consistent with increased fear in aversive learning contexts, as measured by autonomic conditioning.

  20. Is rate–pressure product of any use in the isolated rat heart? Assessing cardiac ‘effort’ and oxygen consumption in the Langendorff‐perfused heart

    PubMed Central

    Aksentijević, Dunja; Lewis, Hannah R.

    2016-01-01

    New Findings What is the central question of this study? Rate–pressure product (RPP) is commonly used as an index of cardiac ‘effort’. In canine and human hearts (which have a positive force–frequency relationship), RPP is linearly correlated with oxygen consumption and has therefore been widely adopted as a species‐independent index of cardiac work. However, given that isolated rodent hearts demonstrate a negative force–frequency relationship, its use in this model requires validation. What is the main finding and its importance? Despite its widespread use, RPP is not correlated with oxygen consumption (or cardiac ‘effort’) in the Langendorff‐perfused isolated rat heart. This lack of correlation was also evident when perfusions included a range of metabolic substrates, insulin or β‐adrenoceptor stimulation. Langendorff perfusion of hearts isolated from rats and mice has been used extensively for physiological, pharmacological and biochemical studies. The ability to phenotype these hearts reliably is, therefore, essential. One of the commonly used indices of function is rate–pressure product (RPP); a rather ill‐defined index of ‘work’ or, more correctly, ‘effort’. Rate–pressure product, as originally described in dog or human hearts, was shown to be correlated with myocardial oxygen consumption (MV˙O2). Despite its widespread use, the application of this index to rat or mouse hearts (which, unlike the dog or human, have a negative force–frequency relationship) has not been characterized. The aim of this study was to examine the relationship between RPP and MV˙O2 in Langendorff‐perfused rat hearts. Paced hearts (300–750 beats min−1) were perfused either with Krebs–Henseleit (KH) buffer (11 mm glucose) or with buffer supplemented with metabolic substrates and insulin. The arteriovenous oxygen consumption (MV˙O2) was recorded. Metabolic status was assessed using 31P magnetic resonance spectroscopy and lactate efflux

  1. Lysophosphatidic Acid Pretreatment Attenuates Myocardial Ischemia/Reperfusion Injury in the Immature Hearts of Rats

    PubMed Central

    Chen, Haibo; Liu, Si; Liu, Xuewen; Yang, Jinjing; Wang, Fang; Cong, Xiangfeng; Chen, Xi

    2017-01-01

    The cardioprotection of the immature heart during cardiac surgery remains controversial due to the differences between the adult heart and the newborn heart. Lysophosphatidic acid (LPA) is a small bioactive molecule with diverse functions including cell proliferation and survival via its receptor: LPA1–LPA6. We previously reported that the expressions of LPA1 and LPA3 in rat hearts were much higher in immature hearts and then declined rapidly with age. In this study, we aimed to investigate whether LPA signaling plays a potential protective role in immature hearts which had experienced ischemia/reperfusion (I/R) injury. The results showed that in Langendorff-perfused immature rat hearts (2 weeks), compared to I/R group, LPA pretreatment significantly enhanced the cardiac function, attenuated myocardial infarct size and CK-MB release, decreased myocardial apoptosis and increased the expression of pro-survival signaling molecules. All these effects could be abolished by Ki16425, an antagonist to LPA1 and LPA3. Similarly, LPA pretreatment protected H9C2 from hypoxia-reoxygenation (H/R) induced apoptosis and necrosis in vitro. The mechanisms underlying the anti-apoptosis effects were related to activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinas B (AKT) signaling pathways as well as phosphorylation of the downstream effector of AKT, glycogen synthase kinase 3 beta (GSK3β), through LPA1 and/or LPA3. What's more, we found that LPA preconditioning increased glucose uptake of H9C2 subjected to H/R by the activation of AMP-Activated Protein Kinase (AMPK) but not the translocation of GLUT4. In conclusion, our study indicates that LPA is a potent survival factor for immature hearts against I/R injuries and has the potential therapeutic function as a cardioplegia additive for infantile cardiac surgery. PMID:28377726

  2. Severe Calorie Restriction Reduces Cardiometabolic Risk Factors and Protects Rat Hearts from Ischemia/Reperfusion Injury

    PubMed Central

    Melo, Dirceu S.; Costa-Pereira, Liliane V.; Santos, Carina S.; Mendes, Bruno F.; Costa, Karine B.; Santos, Cynthia Fernandes F.; Rocha-Vieira, Etel; Magalhães, Flávio C.; Esteves, Elizabethe A.; Ferreira, Anderson J.; Guatimosim, Sílvia; Dias-Peixoto, Marco F.

    2016-01-01

    Background and Aims: Recent studies have proposed that if a severe caloric restriction (SCR) is initiated at the earliest period of postnatal life, it can lead to beneficial cardiac adaptations later on. We investigated the effects of SCR in Wistar rats from birth to adult age on risk factors for cardiac diseases (CD), as well as cardiac function, redox status, and HSP72 content in response to ischemia/reperfusion (I/R) injury. Methods and Results: From birth to the age of 3 months, CR50 rats were fed 50% of the food that the ad libitum group (AL) was fed. Food intake was assessed daily and body weight were assessed weekly. In the last week of the SCR protocol, systolic blood pressure and heart rate were measured and the double product index was calculated. Also, oral glucose and intraperitoneal insulin tolerance tests were performed. Thereafter, rats were decapitated, visceral fat was weighed, and blood and hearts were harvested for biochemical, functional, tissue redox status, and western blot analyzes. Compared to AL, CR50 rats had reduced the main risk factors for CD. Moreover, the FR50 rats showed increased cardiac function both at baseline conditions (45% > AL rats) and during the post-ischemic period (60% > AL rats) which may be explained by a decreased cardiac oxidative stress and increased HSP72 content. Conclusion: SCR from birth to adult age reduced risk factors for CD, increased basal cardiac function and protected hearts from the I/R, possibly by a mechanism involving ROS. PMID:27092082

  3. In vitro influence of ascorbate on lipid peroxidation in rat testis and heart microsomes.

    PubMed

    Melin, A M; Peuchant, E; Perromat, A; Clerc, M

    1997-04-01

    Lipid peroxidation (LPO) in rat testis and heart microsomes was compared using the ADP/Fe2+ as initiator with and without ascorbate at different concentrations. The extent of LPO was estimated by the levels of TBARS and PUFA. Without ascorbate, LPO was higher in heart than in testis despite elevated levels of catalase in heart. With increased ascorbate concentrations, a biphasic effect of LPO was observed. For a concentration < or = 0.2 mM, ascorbate acted as pro-oxidant and increased TBARS correlated with decreased PUFA were observed both in testis and heart. Above 0.2 mM, ascorbate acts as antioxidant but differences in the rate of LPO were observed. In heart decreased TBARS correlated with increased PUFA whereas in testis TBARS only decreased, PUFA were not significantly modified. These results suggest different mechanisms in LPO initiation in the two organs. Increasing concentrations of H2O2 produced directly elevated TBARS levels in testis while a lag phase was observed in heart before the increase, suggesting that H2O2 was the essential ROS produced by ascorbate-ADP/Fe2+. The effects of scavengers such as catalase and ethanol showed an inhibitory effect on TBARS production only in testis, suggesting the role of H2O2/OH. as an initiator of LPO. In heart, catalase produced a slight increase in TBARS levels whereas no modification was observed with ethanol, suggesting a possible direct activation by ADP/Fe2+ through a metal-oxo intermediate.

  4. Hydrogen sulfide post-conditioning preserves interfibrillar mitochondria of rat heart during ischemia reperfusion injury.

    PubMed

    Banu, Shakila A; Ravindran, Sriram; Kurian, Gino A

    2016-07-01

    Cardiac mitochondrial dysfunction is considered to be the main manifestation in the pathology of ischemia reperfusion injury, and by restoring its functional activity, hydrogen sulfide (H2S), a novel endogenous gaseotransmitter renders cardioprotection. Given that interfibrillar (IFM) and subsarcolemmal (SSM) mitochondria are the two main types in the heart, the present study investigates the specific H2S-mediated action on IFM and SSM during ischemic reperfusion in the Langendorff rat heart model. Rats were randomly divided into five groups, namely normal, ischemic control, reperfusion control (I/R), ischemic post-conditioning (POC), and H2S post-conditioning (POC_H2S). In reperfusion control, cardiac contractility decreased, and lactate dehydrogenase, creatine kinase, and infracted size increased compared to both normal and ischemic group. In hearts post-conditioned with H2S and the classical method improved cardiac mechanical function and decreased cardiac markers in the perfusate and infarct size significantly. Both POC and POC_H2S exerts its cardioprotective effect of preserving the IFM, as evident by significant improvement in electron transport chain enzyme activities and mitochondrial respiration. The in vitro action of H2S on IFM and SSM from normal and I/R rat heart supports H2S and mediates cardioprotection via IFM preservation. Our study indicates that IFM play an important role in POC_H2S mediated cardioprotection from reperfusion injury.

  5. Cardioprotective properties of citicoline against hyperthyroidism-induced reperfusion damage in rat hearts.

    PubMed

    Hernández-Esquivel, Luz; Pavón, Natalia; Buelna-Chontal, Mabel; González-Pacheco, Héctor; Belmont, Javier; Chávez, Edmundo

    2015-06-01

    Hyperthyroidism represents an increased risk factor for cardiovascular morbidity, especially when the heart is subjected to an ischemia/reperfusion process. The aim of this study was to explore the possible protective effect of the nucleotide citicoline on the susceptibility of hyperthyroid rat hearts to undergo reperfusion-induced damage, which is associated with mitochondrial dysfunction. Hence, we analyzed the protective effect of citicoline on the electrical behavior and on the mitochondrial function in rat hearts. Hyperthyroidism was established after a daily i.p. injection of triiodothyronine (at 2 mg/kg of body weight) during 5 days. Thereafter, citicoline was administered i.p. (at 125 mg/kg of body weight) for 5 days. In hyperthyroid rat hearts, citicoline protected against reperfusion-induced ventricular arrhythmias. Moreover, citicoline maintained the accumulation of mitochondrial Ca(2+), allowing mitochondria to reach a high transmembrane electric gradient that protected against the release of cytochrome c. It also preserved the activity of the enzyme aconitase that inhibited the release of cytokines. The protection also included the inhibition of oxidative stress-induced mDNA disruption. We conclude that citicoline protects against the reperfusion damage that is found in the hyperthyroid myocardium. This effect might be due to its inhibitory action on the permeability transition in mitochondria.

  6. Patterns of heart rate responses to hydralazine in normotensive and hypertensive rats.

    PubMed

    Vidrio, H

    1996-01-01

    Hydralazine (H) induces hypotension accompanied by cardiac stimulation due to activation of the arterial baroreflex. Both clinical and experimental observations suggest, however, that in certain conditions H hypotension can be accompanied by unchanged or even depressed cardiac performance. The present study determined whether varying patterns of heart rate responses could be detected in large populations of conscious normotensive (n = 61) and renal hypertensive (n = 59) rats receiving a single dose of H. These patterns were compared with those of normotensive pentobarbital-anesthetized rats (n = 43). In the three groups, hypotension was accompanied by either tachycardia, unchanged heart rate or bradycardia. Tachycardia was found in 52% of normotensive conscious rats, in 51% of hypertensives and in only 14% of anesthetized animals. Heart rate did not change in 26, 35 and 23%, while bradycardia was detected in 22, 14 and 63%, respectively. These results were explained by postulating the initiation by H of two reflexes with opposite effects on heart rate: the arterial baroreflex producing tachycardia and a cardiac mechanoreceptor reflex producing bradycardia. These reactions would compete with each other, with results depending on their relative sensitivity in a given animal.

  7. Biochemical and pharmacological characterization of nuclear urotensin-II binding sites in rat heart

    PubMed Central

    Doan, ND; Nguyen, TTM; Létourneau, M; Turcotte, K; Fournier, A; Chatenet, D

    2012-01-01

    BACKGROUND AND PURPOSE During the past decade, a few GPCRs have been characterized at the nuclear membrane where they exert complementary physiological functions. In this study, we investigated (1) the presence of a functional urotensin-II (U-II) receptor (UT) in rat heart nuclear extracts and (2) the propensity of U-II and U-II-related peptide (URP) to cross the plasma membrane in a receptor-independent manner. EXPERIMENTAL APPROACH Biochemical and pharmacological methods including competitive binding assays, photoaffinity labelling, immunoblotting as well as de novo RNA synthesis were used to characterize the presence of functional UT receptors in rat heart nuclei. In addition, confocal microscopy and flow cytometry analysis were used to investigate the cellular uptake of fluorescent U-II and URP derivatives. KEY RESULTS The presence of specific U-II binding sites was demonstrated in rat heart nuclear extracts. Moreover, such subcellular localization was also observed in monkey heart extracts. In vitro transcription initiation assays on rat, freshly isolated, heart nuclei suggested that nuclear UT receptors are functional, and that U-II, but not URP, participates in nuclear UT-associated gene expression. Surprisingly, hU-II and URP efficiently crossed the plasma membrane in a receptor-independent mechanism involving endocytosis through caveolin-coated pits; this uptake of hU-II, but not that of URP, was dependent on extracellular pH. CONCLUSION Our results suggest that (1) U-II and URP can differentially modulate nuclear UT functions such as gene expression, and (2) both ligands can reach the internal cellular space through a receptor-independent mechanism. PMID:22044114

  8. Insulin resistance improves metabolic and contractile efficiency in stressed rat heart.

    PubMed

    Harmancey, Romain; Lam, Truong N; Lubrano, Genna M; Guthrie, Patrick H; Vela, Deborah; Taegtmeyer, Heinrich

    2012-08-01

    Insulin resistance is a prominent feature in heart failure, while hyperglycemia impairs cardiac contraction. We propose that decreased insulin-mediated glucose uptake by the heart preserves cardiac function in response to metabolic and hemodynamic stress. To test this hypothesis, we fed rats a high-sucrose diet (HSD). Energy substrate metabolism and cardiac work were determined ex vivo in a sequential protocol simulating metabolic and hemodynamic stress. Compared to chow-fed, control rats, HSD impaired myocardial insulin responsiveness and induced profound metabolic changes in the heart, characterized by reduced rates of glucose uptake (7.91 ± 0.30 vs. 10.73 ± 0.67 μmol/min/g dry weight; P<0.001) but increased rates of glucose oxidation (2.38 ± 0.17 vs. 1.50 ± 0.15 μmol/min/g dry weight; P<0.001) and oleate oxidation (2.29 ± 0.11 vs. 1.96 ± 0.12 μmol/min/g dry weight; P<0.05). Tight coupling of glucose uptake and oxidation and improved cardiac efficiency were associated with a reduction in glucose 6-phosphate and oleoyl-CoA levels, as well as a reduction in the content of uncoupling protein 3. Our results suggest that insulin resistance lessens fuel toxicity in the stressed heart. This calls for a new exploration of the mechanisms regulating substrate uptake and oxidation in the insulin-resistant heart.

  9. Enhanced phosphodiesteratic breakdown and turnover of phosphoinositides during reperfusion of ischemic rat heart.

    PubMed

    Otani, H; Prasad, M R; Engelman, R M; Otani, H; Cordis, G A; Das, D K

    1988-11-01

    In this study, we examined phosphoinositide metabolism during ischemia and reperfusion using an isolated and perfused rat heart. When myocardial phosphoinositides were prelabeled with [3H]inositol, reperfusion after 30 minutes of normothermic global ischemia resulted in significant accumulations of radiolabeled inositol phosphate, inositol bisphosphate, and inositol trisphosphate. Isotopic incorporation of [3H]inositol into phosphatidylinositol, phosphatidylinositol-4-phosphate, and phosphatidylinositol-4,5-bisphosphate was increased significantly in the heart reperfused with [3H]inositol after 30 minutes of ischemia compared with that perfused with [3H]inositol after 30 minutes of nonischemic perfusion. However, isotopic incorporation of [3H]glycerol into diacylglycerol, phosphatidic acid, and all of the three phosphoinositides was diminished in the reperfused hearts. Reperfusion of the ischemic heart prelabeled with [14C]arachidonic acid resulted in significant increases in [14C]diacylglycerol and [14C]phosphatidic acid. The enhanced accumulations of [3H]inositol phosphates during reperfusion were not affected by treatment with prazosin plus atropine or indomethacin, but were inhibited by hypoxic reperfusion, reperfusion with Ca2+-free buffer, or by mepacrine. These results suggest that myocardial reperfusion stimulates phosphodiesteratic breakdown and turnover of phosphoinositides, and increased Ca2+ influx caused by reperfusion may be involved in the mechanism of stimulation of phosphatidylinositol-specific phospholipase C activity in the rat heart.

  10. Effects of dietary magnesium on sodium-potassium pump action in the heart of rats

    SciTech Connect

    Fischer, P.W.; Giroux, A.

    1987-12-01

    Sprague-Dawley rats were fed a basal AIN-76 diet containing 80, 200, 350, 500 or 650 mg of magnesium per kilogram of diet for 6 wk. Ventricular slices, as well as microsomal fractions, were prepared from the hearts and were used to determine sodium-potassium pump activity. Sodium-potassium pump activity was assessed in the microsomal membranes by determining the ouabain-inhibitable Na+, K+-ATPase activity and (/sup 3/H)ouabain binding, and in the ventricular slices, by determining ouabain-sensitive /sup 86/Rb uptake under K+-free conditions. The ATPase activity increased with increasing dietary magnesium, so that in the hearts of those animals that were fed 500 and 650 mg of magnesium/kg diet, it was significantly greater than the activity in the hearts of the animals fed 80 and 200 mg/kg diet. Similarly, /sup 86/Rb uptake by heart slices from rats fed 500 and 650 mg of magnesium/kg diet was significantly greater than the uptake by heart slices from animals fed 80 and 200 mg/kg diet. (/sup 3/H)Ouabain binding did not change with increasing dietary magnesium. Thus, magnesium deficiency appears to have no effect on the number of sodium-potassium pump sites, but does decrease the activity of the pump. It is suggested that this leads to an increase in intracellular Na+, resulting in a change in the membrane potential, and may contribute to the arrhythmias associated with magnesium deficiency.

  11. Studies on Pentoxifylline and Tocopherol Combination for Radiation-Induced Heart Disease in Rats

    SciTech Connect

    Liu Hui; Xiong Mai; Xia Yunfei; Cui Nianji; Lu Rubiao; Deng Ling; Lin Yuehao; Rong Tiehua

    2009-04-01

    Purpose: To investigate whether the application of pentoxifylline (PTX) and tocopherol l (Vit. E) could modify the development of radiation-induced heart disease and downregulate the expression of transforming growth factor (TGF)-{beta}1mRNA in rats. Methods and Materials: A total of 120 Sprague-Dawley rats were separated into four groups: control group, irradiated group, experimental group 1, and experiment group 2. Supplementation was started 3 days before irradiation; in experimental group 1, injection of PTX (15 mg/kg/d) and Vit. E (5.5 mg/kg/d) continued till the 12th week postirradiation, whereas in experimental group 2 it was continued until the 24th week postirradiation. All rats were administrated a single dose of 20 Gy irradiation to the heart except the control group. Histopathologic evaluation was performed at various time points (Days 1, 2, 4, 8, and 12 and 24th week) up to 24 weeks after irradiation. Changes of levels of TGF-{beta}1 mRNA expression were also investigated at the same time points using competitive polymerase chain reaction. Results: Compared with the irradiated group, levels of TGF-{beta}1 mRNA of the rat hearts were relatively low in the two experimental groups on the 12th week postirradiation. In experimental group 1, there was a rebound expression of TGF-{beta}1 mRNA on the 24th week postirradiation, whereas that of the experimental group 2 remained low (p < 0.05). The proportions of collagen fibers of the two experimental groups were lower than that of irradiated group (p < 0.05). A rebound could be observed in the experimental group 1. Conclusion: PTX and Vit. E downregulated the expression of TGF-{beta}1 mRNA. The irradiated rat hearts showed a marked pathologic response to the drugs. The withdrawal of drugs in the 12th week postirradiation could cause rebound effects of the development of fibrosis.

  12. The effects of increased heart work on the tricarboxylate cycle and its interactions with glycolysis in the perfused rat heart

    PubMed Central

    Neely, J. R.; Denton, R. M.; England, P. J.; Randle, P. J.

    1972-01-01

    1. The work of the perfused rat heart was acutely increased by raising the aortic pressure in the Langendorff preparation from 50 to 120mmHg; within 1 min in perfusions with media containing glucose or glucose+acetate, rates of oxygen consumption and tricarboxylate-cycle turnover increased 2.5-fold, glycolysis rate doubled and oxidation of triglyceride fatty acid was strikingly enhanced. 2. Increased cardiac work had no significant effects on the heart concentrations of creatine phosphate, ATP, ADP or 5′-AMP. The only significant changes in tricarboxylate-cycle intermediates were a decrease in malate in perfusions with glucose and decreases in acetyl-CoA and citrate and an increase in aspartate in perfusions with glucose+acetate. 3. Measurements of intracellular concentrations of hexose phosphates, glucose and glycogen indicated that work accelerated glycolysis by activation of phosphofructokinase and subsequently hexokinase; the activation could not be accounted for by changes in the known effectors of phosphofructokinase. 4. Acetate at either perfusion pressure increased heart concentrations of acetyl-CoA, citrate, glutamate and malate and decreased that of aspartate; acetate increased tricarboxylate-cycle turnover by 50–60% and inhibited glycolysis and pyruvate oxidation. 5. In view of the markedly different effects of acetate and of cardiac work on the concentrations of cycle intermediates the changes that accompany acetate utilization may be specifically concerned with the regulatory functions of the cycle in control of glycolysis and pyruvate oxidation and not with the associated increase in cycle turnover. It is suggested that the concentrations of key metabolites controlling the rate of cycle turnover may fluctuate with each heart beat and that this may explain why no significant changes (for example, in adenine nucleotide concentrations) have been detected with increased work in the present study. PMID:5085551

  13. Effect of age and methacholine on the rate and coronary flow of isolated hearts of diabetic rats.

    PubMed

    Li, X S; Tanz, R D; Chang, K S

    1989-08-01

    1. Isolated hearts perfused by the method of Langendorff from 6, 12 and 24 week streptozotocin (STZ) diabetic rats displayed a significant bradycardia following 60 min equilibration. The rate of hearts from 12-week diabetic rats (164 +/- 17) displayed the greatest bradycardia compared to age-matched controls (268 +/- 15; P less than 0.001), and diabetics treated with insulin (232 +/- 17; P less than 0.01), but by 52 weeks the heart rate of the 3 groups was similar. With advancing age the effect of STZ diabetes on the rate of rat isolated perfused hearts remained unchanged but the rate of the control and diabetic + insulin groups declined. 2. Hearts from 6-52 week STZ-treated rats were found to be more sensitive to the negative chronotropic effect of methacholine, the greatest difference occurring in hearts from the 12 week animals. Atropine (10(-7) M) did not affect the resting heart rate of age-matched controls or diabetics but blocked methacholine (2.6 x 10(-6) M)-induced bradycardia in both, suggesting that the site of action of diabetic bradycardia is not the muscarinic receptors. 3. At the end of equilibration there was a significant decrease in coronary flow in hearts from 12 week diabetic animals. In spontaneously beating diabetic rat hearts administration of methacholine (2.6 x 10(-6) M) produced a significantly greater decrease in coronary flow in the 12, 24 and 52 week diabetic hearts. When electrically paced (5 Hz) however, there was no difference in response to methacholine between the three groups except at 52 weeks between the age-matched control and diabetic groups. This suggests that the more pronounced reduction induced by methacholine on the coronary flow of diabetic hearts is secondary to its negative chronotropic effect. 4. In general, hearts from diabetic animals treated with insulin respond similarly to their agematched controls in the presence and absence of methacholine.

  14. Toxic effect of the glycoalkaloids solanine and tomatine on cultured neonatal rat heart cells.

    PubMed

    Bergers, W W; Alink, G M

    1980-06-01

    The toxic effects of the glycoalkaloids, alpha-solanine and tomatine, were studied in beating heart cell cultures from 1--2-day-old rats. After addition of alpha-solanine (80 microgram/ml) and tomatine (40 microgram/ml) to the culture medium, the cells ceased beating within a few minutes. At a concentration of 40 microgram/ml alpha-solanine and 20 microgram/ml tomatine, both compounds caused a pronounced increase of the contraction frequency, lasting for at least 2h. K-strophantin, a reference heart glycoside, caused arrhythmic beating at 20 microgram/ml and complete cessation of contractions at 160 microgram/ml.

  15. Relationship between fibronectin expression during gastrulation and heart formation in the rat embryo.

    PubMed

    Suzuki, H R; Solursh, M; Baldwin, H S

    1995-11-01

    By utilizing myosin immunostaining, we were able to identify early rat myocardium as a thin epithelial sheet and realized that its cohesive movement toward the midline leads to the straight heart tube formation. Localization study of fibronectin mRNA and protein was, therefore, carried out to investigate its tissue origin and possible roles in facilitating mesoderm migration and heart formation. Fibronectin mRNAs were first detected throughout the mesoderm during the early primitive streak stage, suggesting that the mesoderm is the source of fibronectin. By pre-head fold (pre-somite) and head fold (early somite) stages, the mesoderm became largely down-regulated for fibronectin mRNAs, while it was also at these stages when myosin-positive myocardium formed itself into the epithelium and was subsequently folding toward the midline. Thus, there appears to be little fibronectin synthesis during and directly relevant to early heart tube formation. Later, during the early straight heart tube stage (5 somite and older), endocardium became highly positive for fibronectin mRNAs, suggesting that the endocardium is the major source of fibronectin for the cardiac jelly. Based on the results, we present a map for the early mammalian heart in which the heart is a single crescentic band lying in front of the prechordal plate. We also suggest a process for heart tube formation based on the cohesive movement of the myocardial epithelium. During heart tube formation, fibronectin protein had been deposited previously by the mesoderm and was found uniformly in the ECM and not newly produced by any adjacent tissue. The data contradict the endodermal guidance of heart migration by fibronectin gradient and suggest, instead, a permissive role for the fibronectin substrate.

  16. Overtraining does not induce oxidative stress and inflammation in blood and heart of rats.

    PubMed

    Stanojevic, D; Jakovljevic, V; Barudzic, N; Zivkovic, V; Srejovic, I; Parezanovic Ilic, K; Cubrilo, D; Ahmetovic, Z; Peric, D; Rosic, M; Radovanovic, D; Djordjevic, D

    2016-01-01

    The aim of our research was to evaluate the changes in levels of cytokines and redox state parameters in blood and isolated heart of rats subjected to different swimming protocols. Rats were divided into 3 groups: 1) controls, 2) moderately trained rats that during all 12 weeks swam 1 h/day, 5 days/week, and 3) overtrained rats that in 10(th) week swam twice, 11(th) week 3 times, and in 12(th) week 4 times a day for 1 h. After sacrificing, blood from jugular vein was collected, and the heart excised and perfused on a Langendorff apparatus. Samples of the coronary effluent were collected during coronary autoregulation. Levels of superoxide anion radical (O(2)(-)), hydrogen peroxide (H(2)O(2)), nitric oxide (NO) and thiobarbituric acid reactive substances (TBARS) were measured in plasma and coronary effluent, while reduced glutathione (GSH), activities of superoxide dismutase (SOD) and catalase (CAT) were measured in erythrocytes. Venous blood was also used for interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) determination. Moderate training protocol induced the decrease of TBARS in plasma, while both training protocols induced the decrease of O(2)(-) and H(2)O(2) in coronary effluent. There was no significant difference in levels of cytokines between groups. The results of study add evidence about beneficial effects of moderate-intensity training on blood and cardiac redox state of rats, and furthermore, shows that exercising frequently, if the intensity stays within moderate range, may not have detrimental effects.

  17. Functional evaluation of rat hearts transplanted after preservation in a high-pressure gaseous mixture of carbon monoxide and oxygen

    PubMed Central

    Hatayama, Naoyuki; Inubushi, Masayuki; Naito, Munekazu; Hirai, Shuichi; Jin, Yong-Nan; Tsuji, Atsushi B.; Seki, Kunihiro; Itoh, Masahiro; Saga, Tsuneo; Li, Xiao-Kang

    2016-01-01

    We recently succeeded in resuscitating an extracted rat heart following 24–48 hours of preservation in a high-pressure gaseous mixture of carbon monoxide (CO) and oxygen (O2). This study aimed to examine the function of rat hearts transplanted after being preserved in the high-pressure CO and O2 gas mixture. The hearts of donor rats were preserved in a chamber filled with CO and O2 under high pressure for 24 h (CO24h) or 48 h at 4 °C. For the positive control (PC) group, hearts immediately extracted from donor rats were used for transplantation. The preserved hearts were transplanted into recipient rats by heterotopic cervical heart transplantation. CO toxicity does not affect the grafts or the recipients. Light microscopy and [18F]-fluorodeoxyglucose positron emission tomography revealed that there were no significant differences in the size of the myocardial infarction or apoptosis of myocardial cells in post-transplant hearts between the PC and CO24h groups. Furthermore, at 100 days after the transplantation, the heart rate, weight and histological staining of the post-transplanted hearts did not differ significantly between the PC and CO24h groups. These results indicate that the function of rat hearts is well preserved after 24 hours of high-pressure preservation in a CO and O2 gas mixture. Therefore, high-pressure preservation in a gas mixture can be a useful method for organ preservation. PMID:27562456

  18. Acute Effects of Vagotomy on Baroreflex Equilibrium Diagram in Rats with Chronic Heart Failure

    PubMed Central

    Kawada, Toru; Li, Meihua; Zheng, Can; Sugimachi, Masaru

    2016-01-01

    The arterial baroreflex system can be divided into the neural arc, from pressure input to efferent sympathetic nerve activity (SNA), and the peripheral arc, from SNA to arterial pressure (AP). Plotting the neural and peripheral arcs on a pressure–SNA plane yields a baroreflex equilibrium diagram. We examined the effects of vagotomy on the open-loop static characteristics of the carotid sinus baroreflex in normal control rats (NC, n = 10) and rats with heart failure after myocardial infarction (MI, n = 10). In the NC group, vagotomy shifted the neural arc toward higher SNA and decreased the slope of the peripheral arc. Consequently, the operating-point SNA increased without a significant change in the operating-point AP on the baroreflex equilibrium diagram. These vagotomy-induced effects were not observed in the MI group, suggesting a loss of vagal modulation of the carotid sinus baroreflex function in heart failure. PMID:27594790

  19. 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

  20. 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)

  1. X-ray intravital microscopy for functional imaging in rat hearts using synchrotron radiation coronary microangiography

    SciTech Connect

    Umetani, K.; Fukushima, K.

    2013-03-15

    An X-ray intravital microscopy technique was developed to enable in vivo visualization of the coronary, cerebral, and pulmonary arteries in rats without exposure of organs and with spatial resolution in the micrometer range and temporal resolution in the millisecond range. We have refined the system continually in terms of the spatial resolution and exposure time. X-rays transmitted through an object are detected by an X-ray direct-conversion type detector, which incorporates an X-ray SATICON pickup tube. The spatial resolution has been improved to 6 {mu}m, yielding sharp images of small arteries. The exposure time has been shortened to around 2 ms using a new rotating-disk X-ray shutter, enabling imaging of beating rat hearts. Quantitative evaluations of the X-ray intravital microscopy technique were extracted from measurements of the smallest-detectable vessel size and detection of the vessel function. The smallest-diameter vessel viewed for measurements is determined primarily by the concentration of iodinated contrast material. The iodine concentration depends on the injection technique. We used ex vivo rat hearts under Langendorff perfusion for accurate evaluation. After the contrast agent is injected into the origin of the aorta in an isolated perfused rat heart, the contrast agent is delivered directly into the coronary arteries with minimum dilution. The vascular internal diameter response of coronary arterial circulation is analyzed to evaluate the vessel function. Small blood vessels of more than about 50 {mu}m diameters were visualized clearly at heart rates of around 300 beats/min. Vasodilation compared to the control was observed quantitatively using drug manipulation. Furthermore, the apparent increase in the number of small vessels with diameters of less than about 50 {mu}m was observed after the vasoactive agents increased the diameters of invisible small blood vessels to visible sizes. This technique is expected to offer the potential for direct

  2. X-ray intravital microscopy for functional imaging in rat hearts using synchrotron radiation coronary microangiography

    NASA Astrophysics Data System (ADS)

    Umetani, K.; Fukushima, K.

    2013-03-01

    An X-ray intravital microscopy technique was developed to enable in vivo visualization of the coronary, cerebral, and pulmonary arteries in rats without exposure of organs and with spatial resolution in the micrometer range and temporal resolution in the millisecond range. We have refined the system continually in terms of the spatial resolution and exposure time. X-rays transmitted through an object are detected by an X-ray direct-conversion type detector, which incorporates an X-ray SATICON pickup tube. The spatial resolution has been improved to 6 μm, yielding sharp images of small arteries. The exposure time has been shortened to around 2 ms using a new rotating-disk X-ray shutter, enabling imaging of beating rat hearts. Quantitative evaluations of the X-ray intravital microscopy technique were extracted from measurements of the smallest-detectable vessel size and detection of the vessel function. The smallest-diameter vessel viewed for measurements is determined primarily by the concentration of iodinated contrast material. The iodine concentration depends on the injection technique. We used ex vivo rat hearts under Langendorff perfusion for accurate evaluation. After the contrast agent is injected into the origin of the aorta in an isolated perfused rat heart, the contrast agent is delivered directly into the coronary arteries with minimum dilution. The vascular internal diameter response of coronary arterial circulation is analyzed to evaluate the vessel function. Small blood vessels of more than about 50 μm diameters were visualized clearly at heart rates of around 300 beats/min. Vasodilation compared to the control was observed quantitatively using drug manipulation. Furthermore, the apparent increase in the number of small vessels with diameters of less than about 50 μm was observed after the vasoactive agents increased the diameters of invisible small blood vessels to visible sizes. This technique is expected to offer the potential for direct

  3. X-ray intravital microscopy for functional imaging in rat hearts using synchrotron radiation coronary microangiography.

    PubMed

    Umetani, K; Fukushima, K

    2013-03-01

    An X-ray intravital microscopy technique was developed to enable in vivo visualization of the coronary, cerebral, and pulmonary arteries in rats without exposure of organs and with spatial resolution in the micrometer range and temporal resolution in the millisecond range. We have refined the system continually in terms of the spatial resolution and exposure time. X-rays transmitted through an object are detected by an X-ray direct-conversion type detector, which incorporates an X-ray SATICON pickup tube. The spatial resolution has been improved to 6 μm, yielding sharp images of small arteries. The exposure time has been shortened to around 2 ms using a new rotating-disk X-ray shutter, enabling imaging of beating rat hearts. Quantitative evaluations of the X-ray intravital microscopy technique were extracted from measurements of the smallest-detectable vessel size and detection of the vessel function. The smallest-diameter vessel viewed for measurements is determined primarily by the concentration of iodinated contrast material. The iodine concentration depends on the injection technique. We used ex vivo rat hearts under Langendorff perfusion for accurate evaluation. After the contrast agent is injected into the origin of the aorta in an isolated perfused rat heart, the contrast agent is delivered directly into the coronary arteries with minimum dilution. The vascular internal diameter response of coronary arterial circulation is analyzed to evaluate the vessel function. Small blood vessels of more than about 50 μm diameters were visualized clearly at heart rates of around 300 beats/min. Vasodilation compared to the control was observed quantitatively using drug manipulation. Furthermore, the apparent increase in the number of small vessels with diameters of less than about 50 μm was observed after the vasoactive agents increased the diameters of invisible small blood vessels to visible sizes. This technique is expected to offer the potential for direct

  4. Exposure of rats to ozone: evidence of damage to heart and brain

    SciTech Connect

    Rahman, I.; Massaro, G.D.; Massaro, D. )

    1992-01-01

    Ozone is a strong oxidizing agent, and in many locations it is a major atmospheric pollutant. It is phytotoxic and an important cause of lung dysfunction in humans. Recently, a significant association has been established between total atmospheric oxidants, of which ozone is one, and daily cardiovascular mortality rates. In this article, we show that exposure of rats to ozone for 5 days, in a concentration found in major urban centers, results in an increased concentration of thiobarbituric acid-reactive material (an indicator of lipid peroxidation) in heart and brain tissue as well as elevated activity of catalase and glutathione peroxidase (enzymic scavengers of peroxides) in these tissues. We examined the heart anatomically and found evidence of extracellular and intracellular edema. These findings indicate that the heart and brain are damaged by a concentration of ozone present in major urban centers; they may have important implications for chronic illness and degenerative processes in humans.

  5. [Pharmacologic effects of mansonine on arrhythmias induced in isolated rat heart].

    PubMed

    Ehile, E E; Mensah-Nyagan, A; Guédé, G F; Aka, K J

    1991-01-01

    The effect of 3 x 10(-13) M Mansonine (MSN) was observed on arrythmias induced on isolated rat heart, perfused with either hypopotassic solution, atropine solution, or MacEwen physiological saline at 18 degrees C. Generally the reversal of induced arrythmias was complete with the hypopotassic solution, and partial with the MacEwen solution at 18 degrees C. On the other hand, when atropine and MSN were combined, their effects induced heart arrest, probably due to an intracellular calcium accumulation. In this case, the heart recovery occurred by preventing the calcium influx, either through EDTA chelation, or blockade of calcium channels. It was concluded that MSN probably acts like most cardiac glycosides, by blocking the Na(+)-K+ ATPase. This may activate a calcium influx, which causes the subsequent positive inotropic effect, as well as a negative chronotropic effect due to an increase of the membrane activation set point.

  6. Pharmacology of Casimiroa edulis; Part I. Blood pressure and heart rate effects in the anesthetized rat.

    PubMed

    Magos, G A; Vidrio, H

    1991-02-01

    The effect of an alcoholic extract of seeds of Casimiroa edulis on blood pressure and heart rate was determined in rats anesthetized with pentobarbital and compared with that of histamine. The extract induced hypotension, accompanied at high doses by tachycardia. Hypotension after histamine was more transient and was not accompanied by changes in heart rate. Experiments with a variety of autonomic antagonists revealed that extract-induced hypotension was not mediated by histamine H2, muscarinic, or beta-adrenergic receptors, but involved an H1 mechanism. After H1 blockade, the depressor response was reversed to a pressor effect, mediated by alpha-adrenoceptor stimulation. The increase in heart rate was due in part to H1 and in part to beta-adrenergic receptor activation. It was suggested that imidazole derivatives could be responsible for the depressor effect observed. The pressor response could be caused by these or other components of the extract.

  7. Estrogen attenuates chronic volume overload induced structural and functional remodeling in male rat hearts.

    PubMed

    Gardner, Jason D; Murray, David B; Voloshenyuk, Tetyana G; Brower, Gregory L; Bradley, Jessica M; Janicki, Joseph S

    2010-02-01

    We have previously reported gender differences in ventricular remodeling and development of heart failure using the aortocaval fistula model of chronic volume overload in rats. In contrast to males, female rats exhibited no adverse ventricular remodeling and less mortality in response to volume overload. This gender-specific cardioprotection was lost following ovariectomy and was partially restored using estrogen replacement. However, it is not known if estrogen treatment would be as effective in males. The purpose of this study was to evaluate the structural and functional effects of estrogen in male rats subjected to chronic volume overload. Four groups of male rats were studied at 3 days and 8 wk postsurgery as follows: fistula and sham-operated controls, with and without estrogen treatment. Biochemical and histological studies were performed at 3 days postsurgery, with chronic structural and functional effects studied at 8 wk. Measurement of systolic and diastolic pressure-volume relationships was obtained using a blood-perfused isolated heart preparation. Both fistula groups developed significant ventricular hypertrophy after 8 wk of volume overload. Untreated rats with fistula exhibited extensive ventricular dilatation, which was coupled with a loss of systolic function. Estrogen attenuated left ventricular dilatation and maintained function in treated rats. Estrogen treatment was also associated with a reduction in oxidative stress and circulating endothelin-1 levels, as well as prevention of matrix metalloproteinase-2 and -9 activation and breakdown of ventricular collagen in the early stage of remodeling. These data demonstrate that estrogen attenuates ventricular remodeling and disease progression in male rats subjected to chronic volume overload.

  8. Donor pretreatment with carbon monoxide prevents ischemia/reperfusion injury following heart transplantation in rats

    PubMed Central

    Fujisaki, Noritomo; Kohama, Keisuke; Nishimura, Takeshi; Yamashita, Hayato; Ishikawa, Michiko; Kanematsu, Akihiro; Yamada, Taihei; Lee, Sungsoo; Yumoto, Tetsuya; Tsukahara, Kohei; Kotani, Joji; Nakao, Atsunori

    2016-01-01

    Because inhaled carbon monoxide (CO) provides potent anti-inflammatory and antioxidant effects against ischemia reperfusion injury, we hypothesized that treatment of organ donors with inhaled CO would decrease graft injury after heart transplantation. Hearts were heterotopically transplanted into syngeneic Lewis rats after 8 hours of cold preservation in University of Wisconsin solution. Donor rats were exposed to CO at a concentration of 250 parts per million for 24 hours via a gas-exposure chamber. Severity of myocardial injury was determined by total serum creatine phosphokinase and troponin I levels at three hours after reperfusion. In addition, Affymetrix gene array analysis of mRNA transcripts was performed on the heart graft tissue prior to implantation. Recipients of grafts from CO-exposed donors had lower levels of serum troponin I and creatine phosphokinase; less upregulation of mRNA for interleukin-6, intercellular adhesion molecule-1, and tumor necrosis factor-α; and fewer infiltrating cells. Although donor pretreatment with CO altered the expression of 49 genes expressly represented on the array, we could not obtain meaningful data to explain the mechanisms by which CO potentiated the protective effects. Pretreatment with CO gas before organ procurement effectively protected cardiac grafts from ischemia reperfusion-induced injury in a rat heterotopic cardiac transplant model. A clinical report review indicated that CO-poisoned organ donors may be comparable to non-poisoned donors. PMID:27867479

  9. Protective role of grape seed proanthocyanidin antioxidant properties on heart of streptozotocin-induced diabetic rats

    PubMed Central

    Mansouri, Esrafil; Khorsandi, Layasadat; Abdollahzade Fard, Amin

    2015-01-01

    Grape seed proanthocyanidin (GSP) bears a very powerful antioxidant effects. Studies demonstrated that proanthocyanidins protect against free radicals mediated cardiovascular and renal disorders. The present study was designed to assess the effect of GSP on the heart of diabetic rats. Forty rats were divided into four groups of 10 animals each: Group I: control, Group II: control group were given GSP, Group III: diabetic group, Group IV: diabetic group treated with GSP. Diabetes was induced by a single dose of streptozotocin, and then GSP (200 mg kg-1 body weight) was administrated for four weeks. Blood glucose, glycosylated hemoglobin (HbA1c) and also the levels of lipid peroxidation and antioxidant enzymes were examined in the heart tissues of all groups. Oral administration of GSP to diabetic rats significantly reduced (p < 0.05) heart weight, blood glucose, HbA1c and lipid peroxidation level, but increased (p < 0.05) body weight and activities antioxidant enzymes when compared to diabetic group. The results indicated that GSP could be useful for prevention or early treatment of cardiac disorder caused by diabetes. PMID:26261706

  10. Oxidative Stress in the Heart of Rats Infected with Trypanosoma evansi

    PubMed Central

    Baldissera, Matheus D.; Souza, Carine de F.; Bertoncheli, Cláudia M.; da Silveira, Karine L.; Grando, Thirssa H.; Porto, Bianca C. Z.; Leal, Daniela B. R.; Silva, Aleksandro S. Da; Mendes, Ricardo E.; Stefani, Lenita M.; Monteiro, Silvia G.

    2016-01-01

    This study was conducted to investigate the occurrence of oxidative stress in the heart tissue of rats infected with Trypanosoma evansi. Rats were divided into 2 groups (A and B) with 12 animals each, and further subdivided into 4 subgroups (A1 and A2, 6 animals/each; and B1 and B2, 6 animals/each). Animals in the groups B1 and B2 were subcutaneously inoculated with T. evansi. Thiobarbituric acid reactive substances (TBARS), superoxide dismutase activity (SOD), glutathione S-transferase activity (GST), reduced glutathione activity (GSH), and non-protein thiols (NPSH) in the heart tissue were evaluated. At day 5 and 15 post-infection (PI), an increase in the TBARS levels and a decrease in the SOD activity (P<0.05) were observed. GSH and GST activities were decreased in infected animals at day 15 PI (P<0.05). Considering the proper functioning of the heart, it is possible that the changes in the activity of these enzymes involved in the oxidative stress may be related, at least in part, in the pathophysiology of rats infected with T. evansi. PMID:27417077

  11. Protective role of grape seed proanthocyanidin antioxidant properties on heart of streptozotocin-induced diabetic rats.

    PubMed

    Mansouri, Esrafil; Khorsandi, Layasadat; Abdollahzade Fard, Amin

    2015-01-01

    Grape seed proanthocyanidin (GSP) bears a very powerful antioxidant effects. Studies demonstrated that proanthocyanidins protect against free radicals mediated cardiovascular and renal disorders. The present study was designed to assess the effect of GSP on the heart of diabetic rats. Forty rats were divided into four groups of 10 animals each: Group I: control, Group II: control group were given GSP, Group III: diabetic group, Group IV: diabetic group treated with GSP. Diabetes was induced by a single dose of streptozotocin, and then GSP (200 mg kg(-1) body weight) was administrated for four weeks. Blood glucose, glycosylated hemoglobin (HbA1c) and also the levels of lipid peroxidation and antioxidant enzymes were examined in the heart tissues of all groups. Oral administration of GSP to diabetic rats significantly reduced (p < 0.05) heart weight, blood glucose, HbA1c and lipid peroxidation level, but increased (p < 0.05) body weight and activities antioxidant enzymes when compared to diabetic group. The results indicated that GSP could be useful for prevention or early treatment of cardiac disorder caused by diabetes.

  12. Decreased adrenoceptor stimulation in heart failure rats reduces NGF expression by cardiac parasympathetic neurons.

    PubMed

    Hasan, Wohaib; Smith, Peter G

    2014-04-01

    Postganglionic cardiac parasympathetic and sympathetic nerves are physically proximate in atrial cardiac tissue allowing reciprocal inhibition of neurotransmitter release, depending on demands from central cardiovascular centers or reflex pathways. Parasympathetic cardiac ganglion (CG) neurons synthesize and release the sympathetic neurotrophin nerve growth factor (NGF), which may serve to maintain these close connections. In this study we investigated whether NGF synthesis by CG neurons is altered in heart failure, and whether norepinephrine from sympathetic neurons promotes NGF synthesis. NGF and proNGF immunoreactivity in CG neurons in heart failure rats following chronic coronary artery ligation was investigated. NGF immunoreactivity was decreased significantly in heart failure rats compared to sham-operated animals, whereas proNGF expression was unchanged. Changes in neurochemistry of CG neurons included attenuated expression of the cholinergic marker vesicular acetylcholine transporter, and increased expression of the neuropeptide vasoactive intestinal polypeptide. To further investigate norepinephrine's role in promoting NGF synthesis, we cultured CG neurons treated with adrenergic receptor (AR) agonists. An 82% increase in NGF mRNA levels was detected after 1h of isoproterenol (β-AR agonist) treatment, which increased an additional 22% at 24h. Antagonist treatment blocked isoproterenol-induced increases in NGF transcripts. In contrast, the α-AR agonist phenylephrine did not alter NGF mRNA expression. These results are consistent with β-AR mediated maintenance of NGF synthesis in CG neurons. In heart failure, a decrease in NGF synthesis by CG neurons may potentially contribute to reduced connections with adjacent sympathetic nerves.

  13. The Role of α7 Nicotinic Acetylcholine Receptor in Modulation of Heart Rate Dynamics in Endotoxemic Rats

    PubMed Central

    Mazloom, Roham; Eftekhari, Golnar; Rahimi, Maryam; Khori, Vahid; Hajizadeh, Sohrab; Dehpour, Ahmad R.; Mani, Ali R.

    2013-01-01

    Previous reports have indicated that artificial stimulation of the vagus nerve reduces systemic inflammation in experimental models of sepsis. This phenomenon is a part of a broader cholinergic anti-inflammatory pathway which activates the vagus nerve to modulate inflammation through activation of alpha7 nicotinic acetylcholine receptors (α7nACHR). Heart rate variability represents the complex interplay between autonomic nervous system and cardiac pacemaker cells. Reduced heart rate variability and increased cardiac cycle regularity is a hallmark of clinical conditions that are associated with systemic inflammation (e.g. endotoxemia and sepsis). The present study was aimed to assess the role of α7nACHR in modulation of heart rate dynamics during systemic inflammation. Systemic inflammation was induced by injection of endotoxin (lipopolysaccharide) in rats. Electrocardiogram and body temperature were recorded in conscious animals using a telemetric system. Linear and non-linear indices of heart rate variability (e.g. sample entropy and fractal-like temporal structure) were assessed. RT-PCR and immunohistochemistry studies showed that α7nACHR is expressed in rat atrium and is mainly localized at the endothelial layer. Systemic administration of an α7nACHR antagonist (methyllycaconitine) did not show a significant effect on body temperature or heart rate dynamics in naïve rats. However, α7nACHR blockade could further reduce heart rate variability and elicit a febrile response in endotoxemic rats. Pre-treatment of endotoxemic animals with an α7nACHR agonist (PHA-543613) was unable to modulate heart rate dynamics in endotoxemic rats but could prevent the effect of endotoxin on body temperature within 24 h experiment. Neither methyllycaconitine nor PHA-543613 could affect cardiac beating variability of isolated perfused hearts taken from control or endotoxemic rats. Based on our observations we suggest a tonic role for nicotinic acetylcholine receptors in

  14. The effects of prenatal exposure to a 900-MHz electromagnetic field on the 21-day-old male rat heart.

    PubMed

    Türedi, Sibel; Hancı, Hatice; Topal, Zehra; Ünal, Deniz; Mercantepe, Tolga; Bozkurt, İlyas; Kaya, Haydar; Odacı, Ersan

    2015-01-01

    The growing spread of mobile phone use is raising concerns about the effect on human health of the electromagnetic field (EMF) these devices emit. The purpose of this study was to investigate the effects on rat pup heart tissue of prenatal exposure to a 900 megahertz (MHz) EMF. For this purpose, pregnant rats were divided into experimental and control groups. Experimental group rats were exposed to a 900 MHz EMF (1 h/d) on days 13-21 of pregnancy. Measurements were performed with rats inside the exposure box in order to determine the distribution of EMF intensity. Our measurements showed that pregnant experimental group rats were exposed to a mean electrical field intensity of 13.77 V/m inside the box (0.50 W/m(2)). This study continued with male rat pups obtained from both groups. Pups were sacrificed on postnatal day 21, and the heart tissues were extracted. Malondialdehyde, superoxide dismutase and catalase values were significantly higher in the experimental group rats, while glutathione values were lower. Light microscopy revealed irregularities in heart muscle fibers and apoptotic changes in the experimental group. Electron microscopy revealed crista loss and swelling in the mitochondria, degeneration in myofibrils and structural impairments in Z bands. Our study results suggest that exposure to EMF in the prenatal period causes oxidative stress and histopathological changes in male rat pup heart tissue.

  15. Effect of Angiotensin(1-7) on Heart Function in an Experimental Rat Model of Obesity

    PubMed Central

    Blanke, Katja; Schlegel, Franziska; Raasch, Walter; Bader, Michael; Dähnert, Ingo; Dhein, Stefan; Salameh, Aida

    2015-01-01

    Aim: Obesity is a risk factor for the development of cardiovascular diseases. Recently it was shown that overexpression of the Mas-receptor antagonist angiotensin(1-7) could prevent from diet-induced obesity. However, it remained unclear whether diet-induced obesity and angiotensin(1-7) overexpression might also have effects on the cardiovascular system in these rats. Methods:Twenty three male Sprague Dawley rats were fed with standard chow (SD+chow, n = 5) or a cafeteria diet (SD+CD, n = 6) for 5 months. To investigate the effect of angiotensin(1-7) transgenic rats, expressing an angiotensin(1-7)-producing fusion protein in testis were used. These transgenic rats also received a 5 month's feeding period with either chow (TGR+chow, n = 6) or cafeteria diet (TGR+CD, n = 6), respectively. Hemodynamic measurements (pressure-volume loops) were carried out to assess cardiac function and blood pressure. Subsequently, hearts were explanted and investigated according to the Langendorff technique. Furthermore, cardiac remodeling in these animals was investigated histologically. Results:After 5 months cafeteria diet feeding rats showed a significantly increased body weight, which could be prevented in transgenic rats. However, there was no effect on cardiac performance after cafeteria diet in non-transgenic and transgenic rats. Moreover, overexpression of angiotensin(1-7) deteriorated cardiac contractility as indicated by impaired dp/dt. Furthermore, histological analysis revealed that cafeteria diet led to myocardial fibrosis in both, control and transgenic rats and this was not inhibited by an overproduction of angiotensin(1-7). Conclusion:These results indicate that an overexpression of circulating angiotensin(1-7) prevents a cafeteria diet-induced increase in body weight, but does not affect cardiac performance in this experimental rat model of obesity. Furthermore, overexpression of angiotensin(1-7) alone resulted in an impairment of cardiac function. PMID:26733884

  16. Effect of acute exposure to ozone on heart rate and blood pressure of the conscious rat

    SciTech Connect

    Uchiyama, I.; Simomura, Y.; Yokoyama, E.

    1985-12-01

    Electrocardiogram and arterial blood pressure in conscious and unrestrained rats of various ages were recorded during a 3-hr exposure to filtered air or 1 ppm ozone (O/sub 3/). In general, heart rate and mean arterial blood pressure of rats significantly decreased during exposure to O/sub 3/, whereas these functional parameters remained almost stable during exposure to filtered air. Heart rate usually reached a plateau during the exposure to O/sub 3/. Additionally, PR interval and QRS complex significantly increased and premature atrial contraction and incomplete A-V block were frequently observed during the exposure to O/sub 3/. These circulatory effects of O/sub 3/ were more markedly manifested by rats 11 weeks old than either those 8 or 4 weeks old. On the other hand, no significant difference in the circulatory responses was observed between male and female rats. These circulatory effects of O/sub 3/ may be significant from the viewpoint of health effects, although its mechanisms remain unsolved.

  17. Voluntary exercise delays heart failure onset in rats with pulmonary artery hypertension.

    PubMed

    Natali, Antonio J; Fowler, Ewan D; Calaghan, Sarah C; White, Ed

    2015-08-01

    Increased physical activity is recommended for the general population and for patients with many diseases because of its health benefits but can be contraindicated if it is thought to be a risk for serious cardiovascular events. One such condition is pulmonary artery hypertension (PAH). PAH and right ventricular failure was induced in rats by a single injection of monocrotaline (MCT). MCT rats with voluntary access to a running wheel ran on average 2 km/day. The time for half the animals to develop heart failure signs (median survival time) was 28 days (exercise failure group), significantly longer than sedentary animals (sedentary failure group, 23 days). The contractility of single failing myocytes in response to increasing demand (stimulation frequency) was significantly impaired compared with that in both sedentary control and exercising control myocytes. However, myocytes from exercising MCT rats, tested at 23 days (exercise + MCT group), showed responses intermediate to the control (sedentary control and exercising control) and failing (sedentary failure and exercise failure) groups. We conclude that voluntary exercise is beneficial to rats with heart failure induced by PAH, and this is evidence to support the consideration of appropriate exercise regimes for potentially vulnerable groups.

  18. Lipotoxic heart disease in obese rats: Implications for human obesity

    PubMed Central

    Zhou, Yan-Ting; Grayburn, Paul; Karim, Asad; Shimabukuro, Michio; Higa, Moritake; Baetens, Dany; Orci, Lelio; Unger, Roger H.

    2000-01-01

    To determine the mechanism of the cardiac dilatation and reduced contractility of obese Zucker Diabetic Fatty rats, myocardial triacylglycerol (TG) was assayed chemically and morphologically. TG was high because of underexpression of fatty acid oxidative enzymes and their transcription factor, peroxisome proliferator-activated receptor-α. Levels of ceramide, a mediator of apoptosis, were 2–3 times those of controls and inducible nitric oxide synthase levels were 4 times greater than normal. Myocardial DNA laddering, an index of apoptosis, reached 20 times the normal level. Troglitazone therapy lowered myocardial TG and ceramide and completely prevented DNA laddering and loss of cardiac function. In this paper, we conclude that cardiac dysfunction in obesity is caused by lipoapoptosis and is prevented by reducing cardiac lipids. PMID:10677535

  19. Effect of hypothermia on baroreflex control of heart rate and renal sympathetic nerve activity in anaesthetized rats

    PubMed Central

    Sabharwal, R; Coote, J H; Johns, E J; Egginton, S

    2004-01-01

    The present study investigated the effect of acute hypothermia on baroreflex control of heart rate (HR) and renal sympathetic nerve activity (RSNA) by generating baroreflex logistic function curves, using bolus doses of phenylephrine and sodium nitroprusside, in anaesthetized male Wistar rats at a core temperature (Tb) of 37°C, during acute severe hypothermia at Tb= 25°C and on rewarming to 37°C. Comparisons were made between rats without (euthermic, n = 6) and with (acclimated, n = 7) prior exposure to lower ambient temperatures and shorter photoperiod, simulating adaptation to winter conditions. In both groups of rats, acute hypothermia to Tb= 25°C shifted the baroreflex-RSNA curve slightly leftwards and downwards with decreases in the setpoint pressure and maximal gain, whereas it markedly impaired the baroreflex-HR curve characterized by decreases in response range by ∼90% (P < 0.001), minimum response by ∼10% (P < 0.05) and maximum gain by ∼95% (P < 0.001), from that at Tb= 37°C. All parameters were restored to precooling levels on rewarming. Electrical stimulation of cardiac vagal efferents induced a voltage-related bradycardia, the magnitude of which was partially reduced during acute hypothermia, and there was a significant prolongation of the electrocardiogram intervals indicating a delay in cardiac conduction. Mild suppression of baroreflex control of RSNA could contribute to hypothermic hypotension and may primarily reflect an effect of Tb on central drive. The marked attenuation of the baroreflex control of HR during hypothermia was likely to be due to an impairment of both the central and peripheral components of the reflex arc. Baroreflex control of RSNA and HR was similar between both groups of rats, which implied that the control was non-adaptive on chronic cold exposure. PMID:14978202

  20. Exercise training attenuates the pressor response evoked by peripheral chemoreflex in rats with heart failure.

    PubMed

    Calegari, Leonardo; Mozzaquattro, Bruna B; Rossato, Douglas D; Quagliotto, Edson; Ferreira, Janaina B; Rasia-Filho, Alberto; Dal Lago, Pedro

    2016-09-01

    The effects of exercise training (ExT) on the pressor response elicited by potassium cyanide (KCN) in the rat model of ischemia-induced heart failure (HF) are unknown. We evaluated the effects of ExT on chemoreflex sensitivity and its interaction with baroreflex in rats with HF. Wistar rats were divided into four groups: trained HF (Tr-HF), sedentary HF (Sed-HF), trained sham (Tr-Sham), and sedentary sham (Sed-Sham). Trained animals underwent to a treadmill running protocol for 8 weeks (60 m/day, 5 days/week, 16 m/min). After ExT, arterial pressure (AP), baroreflex sensitivity (BRS), peripheral chemoreflex (KCN: 100 μg/kg body mass), and cardiac function were evaluated. The results demonstrate that ExT induces an improvement in BRS and attenuates the pressor response to KCN relative to the Sed-HF group (P < 0.05). The improvement in BRS was associated with a reduction in the pressor response following ExT in HF rats (P < 0.05). Moreover, ExT induced a reduction in left ventricular end-diastolic pressure and pulmonary congestion compared with the Sed-HF group (P < 0.05). The pressor response to KCN in the hypotensive state is decreased in sedentary HF rats. These results suggest that ExT improves cardiac function and BRS and attenuates the pressor response evoked by KCN in HF rats.

  1. 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.

  2. Comparison of ascorbate and glucose transport in the heart

    SciTech Connect

    Bassingthwaighte, J.B.; Kuikka, J.T.; Chan, I.S.; Arts, T.; Reneman, R.S.

    1985-07-01

    Multiple indicator-dilution experiments were done to compare the transcapillary exchange of tracer amounts of L-(/sup 14/C)ascorbate and D-(/sup 3/H)glucose (against an intravascular reference /sup 131/I-albumin) in Ringer-perfused (5 mM glucose) isolated rabbit hearts. The indicator-dilution curves for the two were virtually superimposed over the first 40-80 s. Estimates of the capillary permeability-surface area products, PSc, were the same, 2.3 +/- 0.7 (SD) ml X g-1 X min-1 (n = 18), in accord with the coincidence of their instantaneous extractions. The similarity of glucose and ascorbate permeabilities is explained by the similarity in molecular weights and passive diffusivity, their lipophobic nature, and the paucity of carrier-mediated endothelial transport for either molecule. The data were analyzed via a model composed of aggregates of spatially distributed capillary-tissue units (capillary blood, interstitium, myocytes) accounting for the heterogeneity of regional flows. The interstitial volumes in this preparation are enlarged, 0.30 +/- 0.04 ml/g. There is substantial entry into myocardial cells, the cell permeability-surface area products being approximately 2-3 ml X g-1 X min-1 for ascorbate and glucose. The estimated volumes of interstitial and intracellular space, 0.30 and 0.47 ml X g-1 X min-1, reflect interstitial edema and are very close to measured values, giving reassurance concerning the methods of modeling analysis.

  3. Low-dose copper infusion into the coronary circulation induces acute heart failure in diabetic rats: New mechanism of heart disease.

    PubMed

    Cheung, Carlos Chun Ho; Soon, Choong Yee; Chuang, Chia-Lin; Phillips, Anthony R J; Zhang, Shaoping; Cooper, Garth J S

    2015-09-01

    Diabetes impairs copper (Cu) regulation, causing elevated serum Cu and urinary Cu excretion in patients with established cardiovascular disease; it also causes cardiomyopathy and chronic cardiac impairment linked to defective Cu homeostasis in rats. However, the mechanisms that link impaired Cu regulation to cardiac dysfunction in diabetes are incompletely understood. Chronic treatment with triethylenetetramine (TETA), a Cu²⁺-selective chelator, improves cardiac function in diabetic patients, and in rats with heart disease; the latter displayed ∼3-fold elevations in free Cu²⁺ in the coronary effluent when TETA was infused into their coronary arteries. To further study the nature of defective cardiac Cu regulation in diabetes, we employed an isolated-perfused, working-heart model in which we infused micromolar doses of Cu²⁺ into the coronary arteries and measured acute effects on cardiac function in diabetic and non-diabetic-control rats. Infusion of CuCl₂ solutions caused acute dose-dependent cardiac dysfunction in normal hearts. Several measures of baseline cardiac function were impaired in diabetic hearts, and these defects were exacerbated by low-micromolar Cu²⁺ infusion. The response to infused Cu²⁺ was augmented in diabetic hearts, which became defective at lower infusion levels and underwent complete pump failure (cardiac output = 0 ml/min) more often (P < 0.0001) at concentrations that only moderately impaired function of control hearts. To our knowledge, this is the first report describing the acute effects on cardiac function of pathophysiological elevations in coronary Cu²⁺. The effects of Cu²⁺ infusion occur within minutes in both control and diabetic hearts, which suggests that they are not due to remodelling. Heightened sensitivity to the acute effects of small elevations in Cu²⁺ could contribute substantively to impaired cardiac function in patients with diabetes and is thus identified as a new mechanism of heart disease.

  4. Coping style and stress hormone responses in genetically heterogeneous rats: comparison with the Roman rat strains.

    PubMed

    Díaz-Morán, Sira; Palència, Marta; Mont-Cardona, Carme; Cañete, Toni; Blázquez, Gloria; Martínez-Membrives, Esther; López-Aumatell, Regina; Tobeña, Adolf; Fernández-Teruel, Alberto

    2012-03-01

    The purpose of the present study was to evaluate for the first time the stress-induced hypothalamus-pituitary-adrenal (HPA), adrenocorticotropic hormone (ACTH), corticosterone and prolactin responses of the National Institutes of Health genetically heterogeneous rat stock (N/Nih-HS rats) in comparison with responses of the relatively high and low stress-prone Roman Low- (RLA-I) and High-Avoidance (RHA-I) rat strains. The same rats were also compared (experiment 1) with respect to their levels of unconditioned anxiety (elevated zero-maze test), novelty-induced exploratory behavior, conditioned fear and two-way active avoidance acquisition. In experiment 2, naive rats from these three strains/stocks were evaluated for "depressive-like" behavior in the forced swimming test. N/Nih-HS and RLA-I rats showed significantly higher post-stress ACTH, corticosterone and prolactin levels than RHA-I rats. N/Nih-HS rats also presented the highest context-conditioned freezing responses, extremely poor two-way avoidance acquisition and very low novelty-induced exploratory behavior. Experiment 2 showed that, compared to RHA-I rats, N/Nih-HS and RLA-I rats displayed significantly less struggling (escape-directed) and increased immobility responses in the forced swimming test. Factor analysis of data from experiment 1 showed associations among behavioral and hormonal responses, with a first factor comprising high loadings of elevated zero-maze variables and lower loadings of conditioned fear, two-way avoidance acquisition and hormonal measures, while a second factor mainly grouped conditioned fear and two-way avoidance acquisition with novelty-induced exploration and post-stress prolactin. Thus, regarding their anxiety/fearfulness, passive coping style, "depressive-like" and stress-induced hormonal responses the N/Nih-HS rats resemble the phenotype profiles of the relatively high-anxious and stress-prone RLA-I rat strain.

  5. Propionate metabolism in the rat heart by 13C n.m.r. spectroscopy.

    PubMed Central

    Sherry, A D; Malloy, C R; Roby, R E; Rajagopal, A; Jeffrey, F M

    1988-01-01

    High-resolution 13C n.m.r. spectroscopy has been used to examine propionate metabolism in the perfused rat heart. A number of tricarboxylic acid (TCA) cycle intermediates are observable by 13C n.m.r. in hearts perfused with mixtures of pyruvate and propionate. When the enriched 13C-labelled nucleus originates with pyruvate, the resonances of the intermediates appear as multiplets due to formation of multiply-enriched 13C-labelled isotopomers, whereas when the 13C-labelled nucleus originates with propionate, these same intermediates appear as singlets in the 13C spectrum since entry of propionate into the TCA cycle occurs via succinyl-CoA. An analysis of the isotopomer populations in hearts perfused with [3-13C]pyruvate plus unlabelled propionate indicates that about 27% of the total pyruvate pool available to the heart is derived directly from unlabelled propionate. This was substantiated by perfusing a heart for 2 h with [3-13C]propionate as the only available exogenous substrate. Under these conditions, all of the propionate consumed by the heart, as measured by conventional chemical analysis, ultimately entered the oxidative pathway as [2-13C] or [3-13C]pyruvate. This is consistent with entry of propionate into the TCA cycle intermediate pools as succinyl-CoA and concomitant disposal of malate to pyruvate via the malic enzyme. 13C resonances arising from enriched methylmalonate and propionylcarnitine are also detected in hearts perfused with [3-13C] or [1-13C]propionate which suggests that 13C n.m.r. may be useful as a non-invasive probe in vivo of metabolic abnormalities involving the propionate pathway, such as methylmalonic aciduria or propionic acidaemia. PMID:3178775

  6. 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.

  7. Persistent effects after trigeminal nerve proprioceptive stimulation by mandibular extension on rat blood pressure, heart rate and pial microcirculation.

    PubMed

    Lapi, D; Colantuoni, A; Del Seppia, C; Ghione, S; Tonlorenzi, D; Brunelli, M; Scuri, R

    2013-03-01

    The trigemino-cardiac reflex is a brainstem reflex known to lead to a decrement in heart rate and blood pressure, whereas few data have been collected about its effects on the cerebral hemodynamic. In this study we assess the in vivo effects of trigeminal nerve peripheral stimulation by mandibular extension on pial microcirculation and systemic arterial blood pressure in rats. Experiments were performed in male Wistar rats subjected to mandibular extension obtained inserting an ad hoc developed retractor between the dental arches. Mean arterial blood pressure and heart rate were recorded and the pial arterioles were visualized by fluorescence microscopy to measure the vessel diameters before (15 minutes) during (5-15 minutes) and after (80 minutes) mandibular extension. While in control rats (sham-operated rats) and in rats subjected to the dissection of the trigeminal peripheral branches mean arterial blood pressure, heart rate and pial microcirculation did not change during the whole observation period (110 minutes), in rats submitted to mandibular extension, mean arterial blood pressure, heart rate and arteriolar diameter significantly decreased during stimulation. Afterward mean arterial blood pressure remained reduced as well as heart rate, while arteriolar diameter significantly increased evidencing a vasodilatation persisting for the whole remaining observation time. Therefore, trigeminal nerve proprioceptive stimulation appears to trigger specific mechanisms regulating systemic arterial blood pressure and pial microcirculation.

  8. A butter diet induces higher levels of n-3 PUFA and of n-3/n-6 PUFA ratio in rat serum and hearts than a safflower oil diet.

    PubMed

    Hirai, K; Ozeki, Y; Nakano, T; Takezoe, R; Nakanishi, M; Asano, Y; Higuchi, H

    2001-01-01

    The effects of a 47-week diet of butter or safflower oil as fat in combination with casein or soy protein as protein were observed for the serum concentrations of lipids and fatty acid compositions in rat serum and heart. Serum total cholesterol (Chol) did not differ among the four experimental diet groups. In the butter groups, significantly higher low-density lipoprotein (LDL)-Chol and lower high-density lipoprotein (HDL)-Chol were observed than in the safflower oil groups (p<0.005, respectively). Higher levels of α-tocopherol were found in the butter groups than in the safflower oil groups (p<0.05) and in the casein groups than in the soy protein groups (p<0.01). In comparison with the safflower oil groups, the butter groups showed higher n-3 polyunsaturated fatty acids (PUFA) contents and lower n-6 PUFA contents in serum and the hearts (p<0.005). The ratios of n-3/n-6 PUFA in the butter groups in serum, 0.26 and 0.18, and in the hearts, 0.37 and 0.36, (butter-casein diet and butter-soy protein diet, respectively) were higher than those of the safflower oil groups of under 0.01 in serum and 0.02 and 0.03 in the hearts (safflower oil-casein diet and safflower oil-soy protein diet, respectively) (p<0.005). In the soy protein groups, higher n-3 PUFA contents in the hearts were found than those of the casein groups (p<0.05). This study suggested that the butter diet induces higher levels of n-3 PUFA and a higher n-3/n-6 PUFA ratio than the safflower oil diet in rat serum and hearts over a long feeding period.

  9. Effects of Various Kynurenine Metabolites on Respiratory Parameters of Rat Brain, Liver and Heart Mitochondria

    PubMed Central

    Baran, Halina; Staniek, Katrin; Bertignol-Spörr, Melanie; Attam, Martin; Kronsteiner, Carina; Kepplinger, Berthold

    2016-01-01

    Previously, we demonstrated that the endogenous glutamate receptor antagonist kynurenic acid dose-dependently and significantly affected rat heart mitochondria. Now we have investigated the effects of L-tryptophan, L-kynurenine, 3-hydroxykynurenine and kynurenic, anthranilic, 3-hydroxyanthranilic, xanthurenic and quinolinic acids on respiratory parameters (ie, state 2, state 3), respiratory control index (RC) and ADP/oxygen ratio in brain, liver and heart mitochondria of adult rats. Mitochondria were incubated with glutamate/malate (5 mM) or succinate (10 mM) and in the presence of L-tryptophan metabolites (1 mM) or in the absence, as control. Kynurenic and anthranilic acids significantly reduced RC values of heart mitochondria in the presence of glutamate/malate. Xanthurenic acid significantly reduced RC values of brain mitochondria in the presence of glutamate/malate. Furthermore, 3-hydroxykynurenine and 3-hydroxyanthranilic acid decreased RC values of brain, liver and heart mitochondria using glutamate/malate. In the presence of succinate, 3-hydroxykynurenine and 3-hydroxyanthranilic acid affected RC values of brain mitochondria, whereas in liver and heart mitochondria only 3-hydroxykynurenine lowered RC values significantly. Furthermore, lowered ADP/oxygen ratios were observed in brain mitochondria in the presence of succinate with 3-hydroxykynurenine and 3-hydroxyanthranilic acid, and to a lesser extent with glutamate/malate. In addition, 3-hydroxyanthranilic acid significantly lowered the ADP/oxygen ratio in heart mitochondria exposed to glutamate/malate, while in the liver mitochondria only a mild reduction was found. Tests of the influence of L-tryptophan and its metabolites on complex I in liver mitochondria showed that only 3-hydroxykynurenine, 3-hydroxyanthranilic acid and L-kynurenine led to a significant acceleration of NADH-driven complex I activities. The data indicate that L-tryptophan metabolites had different effects on brain, liver and heart

  10. Enhanced functional preservation of cold-stored rat heart by a nucleoside transport inhibitor.

    PubMed

    Yang, X; Zhu, Q; Claydon, M A; Hicks, G L; Wang, T

    1994-07-15

    This study investigates the hypothesis that inhibition of nucleoside transport during hypothermic storage elevates tissue adenosine (ADO) content and improves the function of the isolated rat heart. The hearts, flushed with a cardioplegic solution containing varying concentrations (0-100 nM) of a nucleoside transport inhibitor, S-(4-nitrobenzyl)-6-thioinosine (NBTI), were immersion-stored at 0 degrees C for 9 hr. Function was assessed after 30 min of working reperfusion. Function of unstored fresh hearts served as controls and poststorage recovery is reported as percentage of control function. Poststorage heart rate in all groups returned to control level after reperfusion. Recovery of other functional parameters in the no-NBTI group was as follows: aortic flow (AF), 56.2 +/- 4.6%; coronary flow (CF), 53.9 +/- 3.2%; cardiac output (CO), 55.5 +/- 4.0%; systolic pressure, 81.6 +/- 2.5%; work, 47.0 +/- 4.2%; and coronary vascular resistance (CVR), 157.1 +/- 7.8% of control. NBTI improved functional recovery in a dose-dependent fashion; the maximal improvement was seen at a dose of 5 nM, in which the recovery was: AF, 78.1 +/- 3.4%; CF, 73.5 +/- 4.4%; CO, 76.7 +/- 3.6%; work, 70.7 +/- 5.0%; and CVR, 127.5 +/- 4.5% of control (P < 0.05 vs. no-NBTI). The ADO A1-receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (0.1 microM) blocked the effects of 5 nM NBTI; the recovery of AF, CF, CO, work, and CVR decreased to 62.8 +/- 8.0%, 58.3 +/- 5.0%, 61.5 +/- 3.9%, 54.4 +/- 4.5%, and 163.8 +/- 12.7% of control, respectively (P < 0.05 vs. 5 nM NBTI). Tissue ADO content in 5 nM NBTI hearts at the end of storage was 0.075 +/- 0.025 mumol/g dry wt, which was significantly elevated from 0.016 +/- 0.004 mumol/g dry wt in no-NBTI hearts. Purine release during initial reperfusion was delayed in 5 nM NBTI hearts, indicating the inhibition of nucleoside transport by NBTI. But NBTI treatment did not improve end-storage or end-reperfusion myocardial ATP. In conclusion, the addition of

  11. Low Frequency Electromagnetic Field Conditioning Protects against I/R Injury and Contractile Dysfunction in the Isolated Rat Heart.

    PubMed

    Bialy, Dariusz; Wawrzynska, Magdalena; Bil-Lula, Iwona; Krzywonos-Zawadzka, Anna; Wozniak, Mieczyslaw; Cadete, Virgilio J J; Sawicki, Grzegorz

    2015-01-01

    Low frequency electromagnetic field (LF-EMF) decreases the formation of reactive oxygen species, which are key mediators of ischemia/reperfusion (I/R) injury. Therefore, we hypothesized that the LF-EMF protects contractility of hearts subjected to I/R injury. Isolated rat hearts were subjected to 20 min of global no-flow ischemia, followed by 30 min reperfusion, in the presence or absence of LF-EMF. Coronary flow, heart rate, left ventricular developed pressure (LVDP), and rate pressure product (RPP) were determined for evaluation of heart mechanical function. The activity of cardiac matrix metalloproteinase-2 (MMP-2) and the contents of coronary effluent troponin I (TnI) and interleukin-6 (IL-6) were measured as markers of heart injury. LF-EMF prevented decreased RPP in I/R hearts, while having no effect on coronary flow. In addition, hearts subjected to I/R exhibited significantly increased LVDP when subjected to LF-EMF. Although TnI and IL-6 levels were increased in I/R hearts, their levels returned to baseline aerobic levels in I/R hearts subjected to LF-EMF. The reduced activity of MMP-2 in I/R hearts was reversed in hearts subjected to LF-EMF. The data presented here indicate that acute exposure to LF-EMF protects mechanical function of I/R hearts and reduces I/R injury.

  12. Low Frequency Electromagnetic Field Conditioning Protects against I/R Injury and Contractile Dysfunction in the Isolated Rat Heart

    PubMed Central

    Bialy, Dariusz; Wawrzynska, Magdalena; Bil-Lula, Iwona; Krzywonos-Zawadzka, Anna; Wozniak, Mieczyslaw; Cadete, Virgilio J. J.

    2015-01-01

    Low frequency electromagnetic field (LF-EMF) decreases the formation of reactive oxygen species, which are key mediators of ischemia/reperfusion (I/R) injury. Therefore, we hypothesized that the LF-EMF protects contractility of hearts subjected to I/R injury. Isolated rat hearts were subjected to 20 min of global no-flow ischemia, followed by 30 min reperfusion, in the presence or absence of LF-EMF. Coronary flow, heart rate, left ventricular developed pressure (LVDP), and rate pressure product (RPP) were determined for evaluation of heart mechanical function. The activity of cardiac matrix metalloproteinase-2 (MMP-2) and the contents of coronary effluent troponin I (TnI) and interleukin-6 (IL-6) were measured as markers of heart injury. LF-EMF prevented decreased RPP in I/R hearts, while having no effect on coronary flow. In addition, hearts subjected to I/R exhibited significantly increased LVDP when subjected to LF-EMF. Although TnI and IL-6 levels were increased in I/R hearts, their levels returned to baseline aerobic levels in I/R hearts subjected to LF-EMF. The reduced activity of MMP-2 in I/R hearts was reversed in hearts subjected to LF-EMF. The data presented here indicate that acute exposure to LF-EMF protects mechanical function of I/R hearts and reduces I/R injury. PMID:25961016

  13. 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

  14. Dietary linoleate preserves cardiolipin and attenuates mitochondrial dysfunction in the failing rat heart

    PubMed Central

    Mulligan, Christopher M.; Sparagna, Genevieve C.; Le, Catherine H.; De Mooy, Anthony B.; Routh, Melissa A.; Holmes, Michael G.; Hickson-Bick, Diane L.; Zarini, Simona; Murphy, Robert C.; Xu, Fred Y.; Hatch, Grant M.; McCune, Sylvia A.; Moore, Russell L.; Chicco, Adam J.

    2012-01-01

    Aims Cardiolipin (CL) is a tetra-acyl phospholipid that provides structural and functional support to several proteins in the inner mitochondrial membrane. The majority of CL in the healthy mammalian heart contains four linoleic acid acyl chains (L4CL). A selective loss of L4CL is associated with mitochondrial dysfunction and heart failure in humans and animal models. We examined whether supplementing the diet with linoleic acid would preserve cardiac L4CL and attenuate mitochondrial dysfunction and contractile failure in rats with hypertensive heart failure. Methods and results Male spontaneously hypertensive heart failure rats (21 months of age) were administered diets supplemented with high-linoleate safflower oil (HLSO) or lard (10% w/w; 28% kilocalorie fat) or without supplemental fat (control) for 4 weeks. HLSO preserved L4CL and total CL to 90% of non-failing levels (vs. 61–75% in control and lard groups), and attenuated 17–22% decreases in state 3 mitochondrial respiration observed in the control and lard groups (P < 0.05). Left ventricular fractional shortening was significantly higher in HLSO vs. control (33 ± 2 vs. 29 ± 2%, P < 0.05), while plasma insulin levels were lower (5.4 ± 1.1 vs. 9.1 ± 2.3 ng/mL; P < 0.05), with no significant effect of lard supplementation. HLSO also increased serum concentrations of several eicosanoid species compared with control and lard diets, but had no effect on plasma glucose or blood pressure. Conclusion Moderate consumption of HLSO preserves CL and mitochondrial function in the failing heart and may be a useful adjuvant therapy for this condition. PMID:22411972

  15. Rat Heterotopic Heart Transplantation Model to Investigate Unloading-Induced Myocardial Remodeling

    PubMed Central

    Fu, Xuebin; Segiser, Adrian; Carrel, Thierry P.; Tevaearai Stahel, Hendrik T.; Most, Henriette

    2016-01-01

    Unloading of the failing left ventricle in order to achieve myocardial reverse remodeling and improvement of contractile function has been developed as a strategy with the increasing frequency of implantation of left ventricular assist devices in clinical practice. But, reverse remodeling remains an elusive target, with high variability and exact mechanisms still largely unclear. The small animal model of heterotopic heart transplantation (hHTX) in rodents has been widely implemented to study the effects of complete and partial unloading on cardiac failing and non-failing tissue to better understand the structural and molecular changes that underlie myocardial recovery. We herein review the current knowledge on the effects of volume unloading the left ventricle via different methods of hHTX in rats, differentiating between changes that contribute to functional recovery and adverse effects observed in unloaded myocardium. We focus on methodological aspects of heterotopic transplantation, which increase the correlation between the animal model and the setting of the failing unloaded human heart. Last, but not least, we describe the late use of sophisticated techniques to acquire data, such as small animal MRI and catheterization, as well as ways to assess unloaded hearts under “reloaded” conditions. While giving regard to certain limitations, heterotopic rat heart transplantation certainly represents the crucial model to mimic unloading-induced changes in the heart and as such the intricacies and challenges deserve highest consideration. Careful translational research will further improve our knowledge of the reverse remodeling process and how to potentiate its effect in order to achieve recovery of contractile function in more patients. PMID:27807535

  16. 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.

  17. Cine-MRI versus two-dimensional echocardiography to measure in vivo left ventricular function in rat heart.

    PubMed

    Stuckey, Daniel J; Carr, Carolyn A; Tyler, Damian J; Clarke, Kieran

    2008-08-01

    Two-dimensional echocardiography is the most commonly used non-invasive method for measuring in vivo cardiac function in experimental animals. In humans, measurements of cardiac function made using cine-MRI compare favourably with those made using echocardiography. However, no rigorous comparison has been made in small animals. Here, standard short-axis two-dimensional (2D) echocardiography (2D-echo) and cine-MRI measurements were made in the same rats, both control and after chronic myocardial infarction. Correlations between the two techniques were found for end diastolic area, stroke area and ejection fraction, but cine-MRI measurements of ejection fraction were 12+/-6% higher than those made using 2D-echo, because of the 1.8-fold higher temporal resolution of the MRI technique (4.6 ms vs 8.3 ms). Repeated measurements on the same group of rats over several days showed that the cine-MRI technique was more reproducible than 2D-echo, in that 2D-echo would require five times more animals to find a statistically significant difference. In summary, caution should be exercised when comparing functional results acquired using short-axis 2D-echo vs cine-MRI. The accuracy of cine-MRI allows identification of alterations in heart function that may be missed when using 2D-echo.

  18. Neonatal rat heart cells cultured in simulated microgravity

    NASA Technical Reports Server (NTRS)

    Akins, Robert E.; Schroedl, Nancy A.; Gonda, Steve R.; Hartzell, Charles R.

    1994-01-01

    In vitro characteristics of cardiac cells cultured in simulated microgravity are reported. Tissue culture methods performed at unit gravity constrain cells to propagate, differentiate, and interact in a two dimensional (2D) plane. Neonatal rat cardiac cells in 2D culture organize predominantly as bundles of cardiomyocytes with the intervening areas filled by non-myocyte cell types. Such cardiac cell cultures respond predictably to the addition of exogenous compounds, and in many ways they represent an excellent in vitro model system. The gravity-induced 2D organization of the cells, however, does not accurately reflect the distribution of cells in the intact tissue. We have begun characterizations of a three-dimensional (3D) culturing system designed to mimic microgravity. The NASA designed High-Aspect-Ratio-Vessel (HARV) bioreactors provide a low shear environment which allows cells to be cultured in static suspension. HARV-3D cultures were prepared on microcarrier beads and compared to control-2D cultures using a combination of microscopic and biochemical techniques. Both systems were uniformly inoculated and medium exchanged at standard intervals. Cells in control cultures adhered to the polystyrene surface of the tissue culture dishes and exhibited typical 2D organization. Cells in cultured in HARV's adhered to microcarrier beads, the beads aggregated into defined clusters containing 8 to 15 beads per cluster, and the clusters exhibited distinct 3D layers: myocytes and fibroblasts appeared attached to the surfaces of beads and were overlaid by an outer cell type. In addition, cultures prepared in HARV's using alternative support matrices also displayed morphological formations not seen in control cultures. Generally, the cells prepared in HARV and control cultures were similar, however, the dramatic alterations in 3D organization recommend the HARV as an ideal vessel for the generation of tissue-like organizations of cardiac cells in simulated microgravity.

  19. Neonatal rat heart cells cultured in simulated microgravity

    NASA Technical Reports Server (NTRS)

    Akins, R. E.; Schroedl, N. A.; Gonda, S. R.; Hartzell, C. R.

    1997-01-01

    In vitro characteristics of cardiac cells cultured in simulated microgravity are reported. Tissue culture methods performed at unit gravity constrain cells to propagate, differentiate, and interact in a two-dimensional (2D) plane. Neonatal rat cardiac cells in 2D culture organize predominantly as bundles of cardiomyocytes with the intervening areas filled by nonmyocyte cell types. Such cardiac cell cultures respond predictably to the addition of exogenous compounds, and in many ways they represent an excellent in vitro model system. The gravity-induced 2D organization of the cells, however, does not accurately reflect the distribution of cells in the intact tissue. We have begun characterizations of a three-dimensional (3D) culturing system designed to mimic microgravity. The NASA-designed High-Aspect Ratio Vessel (HARV) bioreactors provide a low shear environment that allows cells to be cultured in static suspension. HARV-3D cultures were prepared on microcarrier beads and compared to control-2D cultures using a combination of microscopic and biochemical techniques. Both systems were uniformly inoculated and medium exchanged at standard intervals. Cells in control cultures adhered to the polystyrene surface of the tissue culture dishes and exhibited typical 2D organization. Cells cultured in HARVs adhered to microcarrier beads, the beads aggregated into defined clusters containing 8 to 15 beads per cluster, and the clusters exhibited distinct 3D layers: myocytes and fibroblasts appeared attached to the surfaces of beads and were overlaid by an outer cell type. In addition, cultures prepared in HARVs using alternative support matrices also displayed morphological formations not seen in control cultures. Generally, the cells prepared in HARV and control cultures were similar; however, the dramatic alterations in 3D organization recommend the HARV as an ideal vessel for the generation of tissuelike organization of cardiac cells in vitro.

  20. Effect of angiotensin II on rhythmic per2 expression in the suprachiasmatic nucleus and heart and daily rhythm of activity in Wistar rats.

    PubMed

    Herichová, Iveta; Šoltésová, Dorota; Szántóová, Kristína; Mravec, Boris; Neupauerová, Denisa; Veselá, Anna; Zeman, Michal

    2013-09-10

    Endogenous daily rhythms are generated by the hierarchically organized circadian system predominantly synchronized by the external light (L): dark (D) cycle. During recent years several humoral signals have been found to influence the generation and manifestation of daily rhythm. Since most studies have been performed under in vitro conditions, the mechanisms employed under in vivo conditions need to be investigated. Our study focused on angiotensin II (angII)-mediated regulation of Per2 expression in the suprachiasmatic nuclei (SCN) and heart and spontaneous locomotor activity in Wistar rats under synchronized conditions. Angiotensin II was infused (100ng/kg/min) via subcutaneously implanted osmotic minipumps for 7 or 28days. Samples were taken in 4-h intervals during a 24hcycle and after a light pulse applied in the first and second part of the dark phase. Gene expression was measured using real time PCR. Locomotor activity was monitored using an infrared camera with a remote control installed in the animal facility. Seven days of angII infusion caused an increase in blood pressure and heart/body weight index and 28days of angII infusion also increased water intake in comparison with controls. We observed a distinct daily rhythm in Per2 expression in the SCN and heart of control rats and infused rats. Seven days of angII infusion did not influence Per2 expression in the heart. 28days of angII treatment caused significant phase advance and a decrease in nighttime expression of Per2 and influenced expression of clock controlled genes Rev-erb alpha and Dbp in the heart compared to the control. Four weeks of angII infusion decreased the responsiveness of Per2 expression in the SCN to a light pulse at the end of the dark phase of the 24hcycle. Expression of mRNA coding angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) showed a daily rhythm in the heart of control rats. Four weeks of angII infusion caused a decrease in amplitude of rhythmic

  1. Effect of postnatal lead exposure on the development of sympathetic innervation of the heart. [Rats

    SciTech Connect

    Abreu, M.E.

    1983-01-01

    To determine possible mechanisms for this Pb-induced cardiotoxicity, several neutrochemical parameters indicative of cardiac sympathetic innervation were measured in developing rats. Presynaptic indices of nerve terminal development which were studied included steady-state levels of norepinephrine, neuronal uptake and vesicular storage of /sup 3/H-norepinephrine. Analysis of postsynaptic development was accomplished by quantitating the density of ..beta..-adrenergic receptors and by measuring the activity of adenylate cyclase. Rat pups were exposed to Pb from birth to weaning (21 days) via the milk of dams whose drinking water contained 0.2% Pb acetate. This method and level of Pb treatment had no effect on body or heart weight development, however, it did result in a seven-fold increase in the blood Pb content (70-75 ..mu..g/dl) of the treated pups during the period of exposure. Pb exposure accelerated the development of sympathetic innervation of the heart as detected by significant increases in the vesicular uptake of /sup 3/H-norepinephrine and the steady-state concentration of norepinephrine measured at postnatal day 4. On the other hand, ontogeny of the neutronal uptake of /sup 3/H-norepinephrine in the heart and in the forebrain was not affected by Pb treatment. The apparent premature development of sympathetic innervation induced by Pb treatment was not reflected in significant alterations in either the density or the affinity of ..beta..-adrenergic receptor sites determined by the binding kinetics of /sup 3/H-dihydroalprenolol.

  2. Changes in expression of a functional G sub i protein in cultured rat heart cells

    SciTech Connect

    Allen, I.S.; Gaa, S.T.; Rogers, T.B. )

    1988-07-01

    The muscarinic cholinergic agonist, carbachol, and pertussis toxin were used to examine the functional status of the guanine nucleotide-binding protein that inhibits adenylate cyclase (G{sub i}) in cultured neonatal rat heart myocytes. The isoproterenol stimulation of adenylate cyclase activity in myocyte membranes and adenosine 3{prime},5{prime}-cyclic monophosphate (cAMP) accumulation in intact cells (4 days in culture) were insensitive to carbachol. However, in cells cultured for 11 days, carbachol inhibited isoproterenol-stimulated cAMP accumulation by 30%. Angiotensin II (ANG II) was also found to inhibit isoproterenol-stimulated cAMP accumulation in day 11 cells in a dose-dependent manner. Pertussis toxin treatment reversed the inhibitory effects of both ANG II and carbachol, suggesting a role for G{sub i} in the process. Carbachol binding to membranes from day 4 cells was relatively insensitive to guanine nucleotides when compared with binding to membranes from day 11 or adult cells. Furthermore, pertussis toxin-mediated {sup 32}P incorporation into a 39- to 41-kDa substrate in day 11 membranes was increased 3.2-fold over that measured in day 4 membranes. These findings support the view that, although G{sub i} is expressed, it is nonfunctional in 4-day-old cultured neonatal rat heart myocytes and acquisition of functional G{sub i} is dependent on culture conditions. Furthermore, the ANG II receptor can couple to G{sub i} in heart.

  3. 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.

  4. Cardioprotective Effects of Astragalin against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart

    PubMed Central

    Qu, Daoxu; Ren, Huanhuan; Yang, Wenxiao; Zhang, Xinjie; Zheng, Qiusheng; Wang, Dong

    2016-01-01

    This study aims to evaluate the cardioprotective effects of astragalin against myocardial ischemia/reperfusion (I/R) injury in isolated rat heart. The cardioprotective effects of astragalin on myocardial I/R injury were investigated on Langendorff apparatus. Adult male Sprague-Dawley rats were randomly divided into five groups. The results showed that astragalin pretreatment improved myocardial function. Compared with I/R group, lactate dehydrogenase (LDH) and creatine kinase (CK) activities in coronary flow decreased in astragalin pretreatment groups, whereas superoxide dismutase (SOD) activity and glutathione/glutathione disulfide (GSH/GSSG) ratio significantly increased. The levels of malondialdehyde (MDA), intracellular reactive oxygen species (ROS), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) decreased in astragalin-treated groups. The infarct size (IS) and apoptosis rate in hearts from astragalin-treated groups were lower than those in hearts from the I/R group. Western blot analysis also revealed that astragalin preconditioning significantly reduced Bax level, whereas Bcl-2 was increased in the myocardium. Therefore, astragalin exhibited cardioprotective effects via its antioxidative, antiapoptotic, and anti-inflammatory activities. PMID:26788251

  5. Tl(+) induces both cationic and transition pore permeability in the inner membrane of rat heart mitochondria.

    PubMed

    Korotkov, Sergey M; Nesterov, Vladimir P; Brailovskaya, Irina V; Furaev, Viktor V; Novozhilov, Artemy V

    2013-12-01

    Effects of Tl(+) were studied in experiments with isolated rat heart mitochondria (RHM) injected into 400 mOsm medium containing TlNO3 and a nitrate salt (KNO3 or NH4NO3) or TlNO3 and sucrose. Tl(+) increased permeability of the inner membrane of the RHM to K(+) and H(+). This manifested as an increase of the non-energized RHM swelling, in the order of sucrose < K(+) < NH4 (+), respectively. After succinate administration, the swollen RHM contracted. The Tl(+)-induced opening of the mitochondrial permeability pore (MPTP) in Ca(2+)-loaded rat heart mitochondria increased both the swelling and the inner membrane potential dissipation, as well as decreased basal state and 2,4-dinitrophenol-stimulated respiration. These effects of Tl(+) were suppressed by the MPTP inhibitors (cyclosporine A, ADP, bongkrekic acid, and n-ethylmaleimide), activated in the presence of the MPTP inducer (carboxyatractyloside) or mitoKATP inhibitor (5-hydroxydecanoate), but were not altered in the presence of mitoKATP agonists (diazoxide or pinacidil). We suggest that the greater sensitivity of heart and striated muscles, versus liver, to thallium salts in vivo can result in more vigorous Tl(+) effects on muscle cell mitochondria.

  6. Long term effects of fetal undernutrition on rat heart. Role of hypertension and oxidative stress

    PubMed Central

    Rodríguez-Rodríguez, Pilar; López de Pablo, Angel L.; García-Prieto, Concha F.; Somoza, Beatriz; Quintana-Villamandos, Begoña; Gómez de Diego, José J.; Gutierrez-Arzapalo, Perla Y.; Ramiro-Cortijo, David; González, M. Carmen

    2017-01-01

    Background and aims Fetal undernutrition is a risk factor for heart disease in both genders, despite the protection of women against hypertension development. Using a rat model of maternal undernutrition (MUN) we aimed to assess possible sex differences in the development of cardiac alterations and the implication of hypertension and cardiac oxidative stress. Methods Male and female offspring from rats fed ad libitum (control) or with 50% of the normal daily intake during the second half of gestation (MUN) were used. Heart weight/body weight ratio (HW/BW), hemodynamic parameters (anaesthetized rats) and plasma brain natriuretic peptide (BNP, ELISA) were assessed in 21-day, 6-month and 22-month old rats. Plasma testosterone (ELISA) and cardiac protein expression of enzymes related to reactive oxygen species synthesis (p22phox, xanthine-oxidase) and degradation (catalase, Cu/Zn-SOD, Mn-SOD, Ec-SOD) were evaluated in 21-day and 6-month old rats (Western Blot). Heart structure and function was studied at the age of 22 months (echocardiography). Results At the age of 21 days MUN males exhibited significantly larger HW/BW and cardiac p22phox expression while females had reduced p22phox expression, compared to their respective sex-matched controls. At the age of 6-months, MUN males showed significantly larger blood pressure and cardiac xanthine-oxidase expression; MUN females were normotensive and had a lower cardiac expression of antioxidant enzymes, compared to their respective sex-matched controls. At the age of 22 months, both MUN males and females showed larger HW/BW and left ventricular mass and lower ejection fraction compared to sex-matched controls; only MUN males exhibited hypertension and a larger plasma BNP compared to aged male controls. Conclusions 1) During perinatal life females exposed to fetal undernutrition are protected from cardiac alterations, but in ageing they exhibit ventricular hypertrophy and functional loss, like MUN males; 2) cardiac oxidative

  7. Protection by the NO-Donor SNAP and BNP against Hypoxia/Reoxygenation in Rat Engineered Heart Tissue.

    PubMed

    Görbe, A; Eder, A; Varga, Z V; Pálóczi, J; Hansen, A; Ferdinandy, P; Eschenhagen, T

    2015-01-01

    In vitro assays could replace animal experiments in drug screening and disease modeling, but have shortcomings in terms of functional readout. Force-generating engineered heart tissues (EHT) provide simple automated measurements of contractile function. Here we evaluated the response of EHTs to hypoxia/reoxygenation (H/R) and the effect of known cardiocytoprotective molecules. EHTs from neonatal rat heart cells were incubated for 24 h in EHT medium. Then they were subjected to 180 min hypoxia (93% N2, 7% CO2) and 120 min reoxygenation (40% O2, 53% N2, 7% CO2), change of medium and additional follow-up of 48 h. Time-matched controls (40% O2, 53% N2, 7% CO2) were run for comparison. The following conditions were applied during H/R: fresh EHT medium (positive control), the NO-donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 10(-7), 10(-6), 10(-5) M) or the guanylate cyclase activator brain type natriuretic peptide (BNP, 10(-9), 10(-8), 10(-7) M). Frequency and force of contraction were repeatedly monitored over the entire experiment, pH, troponin I (cTnI), lactate dehydrogenase (LDH) and glucose concentrations measured in EHT medium. Beating activity of EHTs in 24 h-medium ceased during hypoxia, partially recovered during reoxygenation and reached time-control values during follow-up. H/R was accompanied by a small increase in LDH and non-significant increase in cTnI. In fresh medium, some EHTs continued beating during hypoxia and all EHTs recovered faster during reoxygenation. SNAP and BNP showed small but significant protective effects during reoxygenation. EHTs are applicable to test potential cardioprotective compounds in vitro, monitoring functional and biochemical endpoints, which otherwise could be only measured by using in vivo or ex vivo heart preparations. The sensitivity of the model needs improvement.

  8. Antidepressant treatment decreases daily salt intake and prevents heart dysfunction following subchronic aortic regurgitation in rats.

    PubMed

    De Gobbi, Juliana Irani Fratucci; Omoto, Ana Carolina Mieko; Siqueira, Tamires Ferreira; Matsubara, Luiz Shigueto; Roscani, Meliza Goi; Matsubara, Beatriz Bojikian

    2015-05-15

    Depression is a predictor of poor prognosis in patients with heart failure. Selective serotonin (5-HT) reuptake inhibitors (SSRIs) may improve these outcomes. Left ventricular volume overload induced hypertrophy that is associated with aortic regurgitation (AR) leads to ventricular dysfunction and heart failure. The aim of this study was to verify the effects of the SSRI paroxetine on cardiac function, as well as on fluid intake and excretion, in subchronic AR. Male Wistar rats (260 to 280g) received sham (SH) surgery or AR induced by retrograde puncture of the aortic valve leaflets. The presence of AR was confirmed by echocardiography (ECHO) exams. Four weeks after AR surgery, subcutaneous injections of paroxetine (PAR: 10mg/kg 3 times in a week) or saline were administered. The rats were randomly divided into the following 4 groups and treated for 4 weeks: AR-PAR, ARsaline, SH-PAR and SH-saline. At the end of the treatment period, fractional shortening was preserved in AR-PAR, compared to AR-saline (46.6±2.7% vs 38.3±2.2%, respectively). Daily 0.3 M NaCl intake was reduced in PAR-treated rats. Natriuresis was increased in weeks 2-3 after PAR treatment. Our results suggest that augmentation of central 5-HT neurotransmission has a beneficial effect on cardiovascular remodeling following volume overload. The mechanisms underlying this effect are unknown.

  9. Metformin prevents the development of chronic heart failure in the SHHF rat model.

    PubMed

    Cittadini, Antonio; Napoli, Raffaele; Monti, Maria Gaia; Rea, Domenica; Longobardi, Salvatore; Netti, Paolo Antonio; Walser, Marion; Samà, Mariateresa; Aimaretti, Gianluca; Isgaard, Jörgen; Saccà, Luigi

    2012-04-01

    Insulin resistance is a recently identified mechanism involved in the pathophysiology of chronic heart failure (CHF). We investigated the effects of two insulin-sensitizing drugs (metformin and rosiglitazone) in a genetic model of spontaneously hypertensive, insulin-resistant rats (SHHF). Thirty SHHF rats were randomized into three treatment groups as follows: 1) metformin (100 mg/kg per day), 2) rosiglitazone (2 mg/kg per day), and 3) no drug. Ten Sprague-Dawley rats served as normal controls. At the end of the treatment period (12 months), the cardiac phenotype was characterized by histology, echocardiography, and isolated perfused heart studies. Metformin attenuated left ventricular (LV) remodeling, as shown by reduced LV volumes, wall stress, perivascular fibrosis, and cardiac lipid accumulation. Metformin improved both systolic and diastolic indices as well as myocardial mechanical efficiency, as shown by improved ability to convert metabolic energy into mechanical work. Metformin induced a marked activation of AMP-activated protein kinase, endothelial nitric oxide synthase, and vascular endothelial growth factor and reduced tumor necrosis factor-α expression and myocyte apoptosis. Rosiglitazone did not affect LV remodeling, increased perivascular fibrosis, and promoted further cardiac lipid accumulation. In conclusion, long-term treatment with metformin, but not with rosiglitazone, prevents the development of severe CHF in the SHHF model by a wide-spectrum interaction that involves molecular, structural, functional, and metabolic-energetic mechanisms.

  10. Enhanced activation of RVLM-projecting PVN neurons in rats with chronic heart failure.

    PubMed

    Xu, Bo; Zheng, Hong; Patel, Kaushik P

    2012-04-15

    Previous studies have indicated that there is increased activation of the paraventricular nucleus (PVN) in rats with chronic heart failure (CHF); however, it is not clear if the preautonomic neurons within the PVN are specifically overactive. Also, it is not known if these neurons have altered responses to baroreceptor or osmotic challenges. Experiments were conducted in rats with CHF (6-8 wk after coronary artery ligation). Spontaneously active neurons were recorded in the PVN, of which 36% were antidromically activated from the rostral ventrolateral medulla (RVLM). The baseline discharge rate in RVLM-projecting PVN (PVN-RVLM) neurons from CHF rats was significantly greater than in sham-operated (sham) rats (6.0 ± 0.6 vs. 2.6 ± 0.3 spikes/s, P < 0.05). Picoinjection of the N-methyl-D-aspartate (NMDA) receptor antagonist D,L-2-amino-5-phosphonovaleric acid significantly decreased the basal discharge of PVN-RVLM neurons by 80% in CHF rats compared with 37% in sham rats. Fifty-two percent of spontaneously active PVN-RVLM neurons responded to changes in the mean arterial pressure (MAP). The changes in discharge rate in PVN-RVLM neurons after a reduction in MAP (+52 ± 7% vs. +184 ± 61%) or an increase in MAP (-42 ± 8% vs. -71 ± 6%) were significantly attenuated in rats with CHF compared with sham rats. Most PVN-RVLM neurons (63%), including all barosensitive PVN-RVLM neurons, were excited by an internal carotid artery injection of hypertonic NaCl (2.1 osmol/l), whereas a smaller number (7%) were inhibited. The increase in discharge rate in PVN-RVLM neurons to hypertonic stimulation was significantly enhanced in rats with CHF compared with sham rats (134 ± 15% vs. 92 ± 13%). Taken together, these data suggest that PVN-RVLM neurons are more active under basal conditions and this overactivation is mediated by an enhanced glutamatergic tone in rats with CHF. Furthermore, this enhanced activation of PVN-RVLM neurons may contribute to the altered responses to

  11. The Impact of Heart Irradiation on Dose-Volume Effects in the Rat Lung

    SciTech Connect

    Luijk, Peter van Faber, Hette; Meertens, Harm; Schippers, Jacobus M.; Langendijk, Johannes A.; Brandenburg, Sytze; Kampinga, Harm H.; Coppes, Robert P. Ph.D.

    2007-10-01

    Purpose: To test the hypothesis that heart irradiation increases the risk of a symptomatic radiation-induced loss of lung function (SRILF) and that this can be well-described as a modulation of the functional reserve of the lung. Methods and Materials: Rats were irradiated with 150-MeV protons. Dose-response curves were obtained for a significant increase in breathing frequency after irradiation of 100%, 75%, 50%, or 25% of the total lung volume, either including or excluding the heart from the irradiation field. A significant increase in the mean respiratory rate after 6-12 weeks compared with 0-4 weeks was defined as SRILF, based on biweekly measurements of the respiratory rate. The critical volume (CV) model was used to describe the risk of SRILF. Fits were done using a maximum likelihood method. Consistency between model and data was tested using a previously developed goodness-of-fit test. Results: The CV model could be fitted consistently to the data for lung irradiation only. However, this fitted model failed to predict the data that also included heart irradiation. Even refitting the model to all data resulted in a significant difference between model and data. These results imply that, although the CV model describes the risk of SRILF when the heart is spared, the model needs to be modified to account for the impact of dose to the heart on the risk of SRILF. Finally, a modified CV model is described that is consistent to all data. Conclusions: The detrimental effect of dose to the heart on the incidence of SRILF can be described by a dose dependent decrease in functional reserve of the lung.

  12. Ischemic preconditioning stimulates sodium and proton transport in isolated rat hearts.

    PubMed Central

    Ramasamy, R; Liu, H; Anderson, S; Lundmark, J; Schaefer, S

    1995-01-01

    One or more brief periods of ischemia, termed preconditioning, dramatically limits infarct size and reduces intracellular acidosis during subsequent ischemia, potentially via enhanced sarcolemmal proton efflux mechanisms. To test the hypothesis that preconditioning increases the functional activity of sodium-dependent proton efflux pathways, isolated rat hearts were subjected to 30 min of global ischemia with or without preconditioning. Intracellular sodium (Nai) was assessed using 23Na magnetic resonance spectroscopy, and the activity of the Na-H exchanger and Na-K-2Cl cotransporter was measured by transiently exposing the hearts to an acid load (NH4Cl washout). Creatine kinase release was reduced by greater than 60% in the preconditioned hearts (P < 0.05) and was associated with improved functional recovery on reperfusion. Preconditioning increased Nai by 6.24 +/- 2.04 U, resulting in a significantly higher level of Nai before ischemia than in the control hearts. Nai increased significantly at the onset of ischemia (8.48 +/- 1.21 vs. 2.57 +/- 0.81 U, preconditioned vs. control hearts; P < 0.01). Preconditioning did not reduce Nai accumulation during ischemia, but the decline in Nai during the first 5 min of reperfusion was significantly greater in the preconditioned than in the control hearts (13.48 +/- 1.73 vs. 2.54 +/- 0.41 U; P < 0.001). Exposure of preconditioned hearts to ethylisopropylamiloride or bumetanide in the last reperfusion period limited in the increase in Nai during ischemia and reduced the beneficial effects of preconditioning. After the NH4Cl prepulse, preconditioned hearts acidified significantly more than control hearts and had significantly more rapid recovery of pH (preconditioned, delta pH = 0.35 +/- 0.04 U over 5 min; control, delta pH = 0.15 +/- 0.02 U over 5 min). This rapid pH recovery was not affected by inhibition of the Na-K-2Cl cotransporter but was abolished by inhibition of the Na-H exchanger. These results demonstrate that

  13. Total and high molecular weight adiponectin levels in the rat model of post-myocardial infarction heart failure.

    PubMed

    Kalisz, M; Baranowska, B; Wolinska-Witort, E; Maczewski, M; Mackiewicz, U; Tulacz, D; Gora, M; Martynska, L; Bik, W

    2015-10-01

    Adiponectin is a protein secreted primarily by adipose tissue. It has been suggested that adiponectin plays a protective role in the early phase following myocardial infarction. Our primary aim was to investigate the effects of post-myocardial infarction heart failure well-characterized by left ventricular hemodynamic parameters on the total and high molecular weight adiponectin concentrations in plasma, fat and cardiac tissue. Eight weeks after myocardial infarction or sham operation, total and high molecular weight adiponectin concentrations in plasma, fat, and cardiac tissues were assayed in rats. In addition, hemodynamic parameters and expression of the genes encoding atrial natriuretic peptide and brain natriuretic peptide in left ventricle were evaluated. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels in left ventricle tissue were higher in rats with myocardial infarction-induced heart failure compared with the controls. Similarly, total adiponectin concentration was increased in left ventricle (but not in right ventricle) in rats with post-myocardial infarction heart failure. In contrast, adiponectin levels in plasma and cardiac adipose tissue in rats with post-myocardial infarction heart failure were lower than in sham-operated animals. Furthermore, there were no significant differences in levels of high molecular weight adiponectin in plasma, cardiac tissue or adipose tissue between these two groups. We conclude that in the rat model of post-myocardial infarction heart failure, adiponectin level is increased in left ventricle tissue. This is accompanied by decreased adiponectin levels in plasma and cardiac adipose tissue.

  14. Characteristic subcellular distribution, in brain, heart and lung, of biperiden, trihexyphenidyl, and (-)-quinuclidinyl benzylate in rats.

    PubMed

    Ishizaki, J; Yokogawa, K; Nakashima, E; Ohkuma, S; Ichimura, F

    1998-01-01

    The subcellular distribution of biperiden (BP), trihexyphenidyl (TP) and (-)-quinuclidinyl benzylate (QNB) in brain, heart and lung following high dose (3.2 mg/kg) i.v. administration was investigated in rats. The subcellular distribution of BP or TP used clinically conformed with that of QNB, a typical potent central muscarinic antagonist. The concentration-time courses of the brain subcellular fractions for these drugs were of two types which decreased slowly and in parallel to the plasma concentration. The subcellular distribution in the brain and heart was dependent on the protein amount of each fraction. The percent post-nuclear fraction (P2) of the total concentration in the lung was characteristically about 3-5 times larger than that in the heart. It was elucidated that the distribution in the lung differs from that in the brain and heart, with high affinity which is not dependent on the protein amount in the P2 fraction containing lysosomes. On the other hand, at a low dose (650 ng/kg) of 3H-QNB, each fraction as a percentage of the total concentration in the brain increased in synaptic membrane and synaptic vesicles and decreased in nuclei and cytosol as compared with the high dose. These results show that although the tissue concentration-time courses of anticholinergic drugs appear to decrease simply in parallel to plasma concentration, the subcellular distribution exhibits a variety of patterns among various tissues.

  15. Protective effects of benidipine on hydrogen peroxide-induced injury in rat isolated hearts.

    PubMed

    Yao, Kozo; Ina, Yasuhiro; Sonoda, Rie; Nagashima, Ken; Ohmori, Kenji; Ohno, Tetsuji

    2003-01-01

    We investigated the effects of benidipine (hydrochloride), a calcium antagonist, on hydrogen peroxide (H(2)O(2))-induced injury in Langendorff-perfused rat hearts. The hearts were aerobically perfused at a constant flow and exposed to H(2)O(2) (600 micromol L(-1)) for 4 min, resulting in the oxidative stress-induced myocardial dysfunction (e.g., decrease in the left ventricular developed pressure) and myocardial cell injury (e.g., increase in the release of lactate dehydrogenase). Pretreatment of the hearts with benidipine or nifedipine was performed for 20 min until the start of H(2)O(2) exposure. Benidipine at 1 nmol L(-1) and nifedipine at 10 nmol L(-1) decreased the myocardial contractility and perfusion pressure to a similar degree in the hearts under normal conditions. Benidipine (1 nmol L(-1)) significantly reduced the H(2)O(2)-induced myocardial damage. Nifedipine (10 nmol L(-1)) also tended to exhibit similar effects. Benidipine inhibited the increase in tissue lipid peroxidation induced by H(2)O(2). The results suggest that, in addition to the calcium antagonism, benidipine possesses other actions responsible for the cardioprotective effects, to which the antioxidant activity of benidipine may partly contribute.

  16. EFFECT OF PERILLA FRUTESCENS EXTRACTS AND ROSMARINIC ACID ON RAT HEART MITOCHONDRIAL FUNCTIONS.

    PubMed

    Raudone, Lina; Burdulis, Deividas; Raudonis, Raimondas; Janulis, Valdimaras; Jankauskiene, Laima; Viskelis, Pranas; Trumbeckaite, Sonata

    2016-01-01

    Perilla frutescens L. due to its aromatic, antibacterial, anti-inflammatory and antioxidant traits has been traditionally used as medicinal plant in Eastern Asia. Alterations of mitochondria are interconnected with many chronic diseases. Bioactives of herbal extracts can modulate mitochondrial effects and be beneficial in prevention of mitochondrial related chronic diseases. Direct effects of the red-leaf form P. frutescens extract (PFE) and the green-leaf form P. frutescens var. crispa f. viridis extract (PCE) were evaluated investigating activities on the oxidative phosphorylation and antioxidant activity in the rat heart mitochondria in vitro. HPLC-MS analysis was applied for the identification of phenolic compounds. Cell with a Clark-type oxygen electrode was used for mitochondrial respiration measurement. The generation of reactive oxygen species was estimated in isolated rat heart mitochondria and determined fluorimetrically. State 3 respiration rate was not affected by lower concentrations, however, it was inhibited at higher concentrations by 22-70% for PFE and by 45-55% for PCE. PFE containing anthocyanins induced the concentration-dependent stimulation (by 23-76%) of the State 4 respiration rate after addition of cytochrome c due to reducing properties. Significant reduction of H₂O₂ pro- duction was observed with investigated concentrations of rosmarinic acid and both perilla extracts. Our results demonstrate that the effect of PFE and PCE extracts on rat heart mitochondria depend on the qualitative characteristics of complex of biologically active compounds. Selective effects on mitochondrial function could enable the regulation of apoptosis or another mechanisms occurring in cells.

  17. Cordyceps sinensis protects against liver and heart injuries in a rat model of chronic kidney disease: a metabolomic analysis

    PubMed Central

    Liu, Xia; Zhong, Fang; Tang, Xu-long; Lian, Fu-lin; Zhou, Qiao; Guo, Shan-mai; Liu, Jia-fu; Sun, Peng; Hao, Xu; Lu, Ying; Wang, Wei-ming; Chen, Nan; Zhang, Nai-xia

    2014-01-01

    Aim: To test the hypothesis that the traditional Chinese medicine Cordyceps sinensis could improve the metabolic function of extrarenal organs to achieve its anti-chronic kidney disease (CKD) effects. Methods: Male SD rats were divided into CKD rats (with 5/6-nephrectomy), CKD rats treated with Cordyceps sinensis (4 mg•kg-1•d-1, po), and sham-operated rats. After an 8-week treatment, metabolites were extracted from the hearts and livers of the rats, and then subjected to 1H-NMR-based metabolomic analysis. Results: Oxidative stress, energy metabolism, amino acid and protein metabolism and choline metabolism were considered as links between CKD and extrarenal organ dysfunction. Within the experimental period of 8 weeks, the metabolic disorders in the liver were more pronounced than in the heart, suggesting that CKD-related extrarenal organ dysfunctions occurred sequentially rather than simultaneously. Oral administration of Cordyceps sinensis exerted statistically significant rescue effects on the liver and heart by reversely regulating levels of those metabolites that are typically perturbed in CKD. Conclusion: Oral administration of Cordyceps sinensis significantly attenuates the liver and heart injuries in CKD rats. The 1H NMR-based metabolomic approach has provided a systematic view for understanding of CKD and the drug treatment, which can also be used to elucidate the mechanisms of action of other traditional Chinese medicines. PMID:24632844

  18. Histopathological and immunohistochemical alterations in rat heart after thyroidectomy and the role of hemin and ketoconazole in treatment.

    PubMed

    Tousson, Ehab; Ali, Ehab M; Ibrahim, Wafaa; Ashraf, Rana M

    2012-12-01

    The heart is a major target organ for thyroid hormone action and marked changes occur in cardiac function in the case of hypo- or hyperthyroidism. Also, thyroid hormone has a significant regulatory effect on the rate of heme oxidation in the liver. Heme oxygenase (HO) is a heme-catabolizing enzyme that converts heme into biliverdin, iron and carbon monoxide. HO(-1) and its reaction products protect the heart and vasculature in pathological conditions. We studied the changes in the heart structure of thyroidectomized rat at the post-pubertal stage, in addition to the role of hemin as HO inducer and ketoconazole (KTZ) as HO inhibitor in treatment. 35 male Wistar rats were equally divided into seven groups; the first and second groups were the control and Sham-operated groups respectively while the 3rd and 4th groups were subjected to sham operation then treated with hemin (G(3)) and KTZ (G(4)). The 5th group (G(5)) was thyroidectomized group. The 6th and 7th groups were subjected to thyroidectomy then treated with hemin (G(5)) and KTZ (G(6)) respectively. Serum T(3) & TSH levels in thyroidectomized rats were significantly decreased and increased respectively when compared with the control group. Left ventricle section in the heart of thyroidectomized rats showed many of abnormalities as hydrophobic changes of myofibrillar structure with striations, myocardial atrophy and edema, focal haemorrhage when compared with that in control and sham groups. The iNOS label index was significantly decreased in thyroidectomized rat heart (grade 1) and their levels were significantly increased in treated thyroidectomized rats with hemin and KTZ (grades 3 & 2 respectively) when compared with control and sham rat groups (grade 4). Treatment of thyroidectomized rat with hemin improves the histopathological alternation and the intensity of iNOS immunoreactive cells demonstrating the recovery of some injury.

  19. The effects of interferon-alpha/beta in a model of rat heart transplantation

    NASA Technical Reports Server (NTRS)

    Slater, A. D.; Klein, J. B.; Sonnenfeld, G.; Ogden, L. L. 2nd; Gray, L. A. Jr

    1992-01-01

    Interferons have multiple immunologic effects. One such effect is the activation of expression of cell surface antigens. Interferon alpha/beta enhance expression of class I but not class II histocompatibility antigens. Contradictory information has been published regarding the effect of interferon-alpha/beta administration in patients with kidney transplantation. In a model of rat heart transplantation we demonstrated that administration of interferon-alpha/beta accelerated rejection in a dose-dependent fashion in the absence of maintenance cyclosporine. Animals treated with maintenance cyclosporine had evidence of increased rejection at 20 days that was resolved completely at 45 days with cyclosporine alone.

  20. Metabolic phenotyping of the diseased rat heart using 13C-substrates and ex vivo perfusion in the working mode.

    PubMed

    Vincent, Geneviève; Khairallah, Maya; Bouchard, Bertrand; Des Rosiers, Christine

    2003-01-01

    The objective of the present study was to compare energy substrate fluxes through metabolic pathways leading to mitochondrial citrate synthesis and release in normal and diseased rat hearts using 13C-substrates and mass isotopomer analysis by gas chromatography-mass spectrometry (GCMS). This study was prompted by our previous finding of a modulated citrate release by perfused rat hearts and by the possibility that a dysregulated myocardial citrate release represents a specific chronic alteration of energy metabolism in cardiac patients. The 15-week-old spontaneously hypertensive rat (SHR) was chosen as our animal model of disease and the Wistar-Kyoto (WKY) rat as its matched control. Ex vivo work-performing hearts were perfused with a semi-recirculating buffer containing physiological concentrations of unlabeled (glucose) and 13C-labeled ([U-13C3](lactate + pyruvate) and/or [1-(13)C]oleate) substrates. In parallel to the continuous monitoring of indices of the heart's functional and physiological status, the following metabolic parameters were documented: (i) citrate release rates and citric acid cycle intermediate tissue levels, (ii) the contribution of fatty acids as well as pyruvate decarboxylation and carboxylation to citrate synthesis, and (iii) lactate and pyruvate uptake and efflux rates. Working hearts from both rat species showed a similar percent contribution of carbohydrates for citrate synthesis through decarboxylation (70%) and carboxylation (10%). SHR hearts showed the following metabolic alterations: a higher citrate release rate, which was associated with a parallel increase in its tissue level, a lower contribution of oleate beta-oxidation to citrate synthesis, and an accelerated efflux rate of unlabeled lactate from glycolysis. These metabolic changes were not explained by differences in myocardial oxygen consumption, cardiac performance or efficiency, nor correlated with indices of tissue necrosis or ischemia. This study demonstrates how the

  1. Endomorphins decrease heart rate and blood pressure possibly by activating vagal afferents in anesthetized rats.

    PubMed

    Kwok, E H; Dun, N J

    1998-08-24

    Endomorphin 1 (10, 30, 100 nmol/kg) administered intravenously (i.v. ) to urethane-anesthetized rats consistently and dose-dependently lowered heart rate (HR) and mean arterial pressure (MAP); the decrease in blood pressure recovered faster as compared to the HR. The effects of endomorphin 2 were qualitatively similar. Naloxone (2 mg/kg, i.v.) completely antagonized the bradycardia and hypotension caused by endomorphin 1. Pretreatment of the rats with atropine methylnitrate, atropine sulfate (2 mg/kg, i.v.) or bilateral vagotomy nearly abolished the bradycardia and attenuated the hypotensive effect of endomorphin 1. Our studies suggest that the bradycardia effect following systemic administration of the new opioid peptide may be explained by activation of vagal afferents and the hypotensive effect may be secondary to a reduction of cardiac output and/or a direct vasodilation.

  2. Chronic heart failure modifies respiratory mechanics in rats: a randomized controlled trial

    PubMed Central

    Pacheco, Deise M.; Silveira, Viviane D.; Thomaz, Alex; Nunes, Ramiro B.; Elsner, Viviane R.; Dal Lago, Pedro

    2016-01-01

    ABSTRACT Objective To analyze respiratory mechanics and hemodynamic alterations in an experimental model of chronic heart failure (CHF) following myocardial infarction. Method Twenty-seven male adult Wistar rats were randomized to CHF group (n=12) or Sham group (n=15). Ten weeks after coronary ligation or sham surgery, the animals were anesthetized and submitted to respiratory mechanics and hemodynamic measurements. Pulmonary edema as well as cardiac remodeling were measured. Results The CHF rats showed pulmonary edema 26% higher than the Sham group. The respiratory system compliance (Crs) and the total lung capacity (TLC) were lower (40% and 27%, respectively) in the CHF rats when compared to the Sham group (P<0.01). There was also an increase in tissue resistance (Gti) and elastance (Hti) (28% and 45%, respectively) in the CHF group. Moreover, left ventricular end-diastolic pressure was higher (32 mmHg vs 4 mmHg, P<0.01), while the left ventricular systolic pressure was lower (118 mmHg vs 130 mmHg, P=0.02) in the CHF group when compared to the control. Pearson’s correlation coefficient showed a negative association between pulmonary edema and Crs (r=–0.70, P=0.0001) and between pulmonary edema and TLC (r=–0.67, P=0.0034). Pulmonary edema correlated positively with Gti (r=0.68, P=0.001) and Hti (r=0.68, P=0.001). Finally, there was a strong positive relationship between pulmonary edema and heart weight (r=0.80, P=0.001). Conclusion Rats with CHF present important changes in hemodynamic and respiratory mechanics, which may be associated with alterations in cardiopulmonary interactions. PMID:27556388

  3. The red wine antioxidant resveratrol protects isolated rat hearts from ischemia reperfusion injury.

    PubMed

    Ray, P S; Maulik, G; Cordis, G A; Bertelli, A A; Bertelli, A; Das, D K

    1999-07-01

    The consumption of red wine has been reported to impart a greater benefit in the prevention of coronary heart disease than the consumption of other alcoholic beverages. This beneficial effect is increasingly being attributed to certain antioxidants comprising the polyphenol fraction of red wine such as transresveratrol. In the present study, we investigated the potential cardioprotective effects of resveratrol in the face of ischemia reperfusion (I/R) injury. Isolated perfused working rat hearts after stabilization were perfused with Krebs-Henseleit Bicarbonate buffer (KHB) either in the presence or absence of transresveratrol (RVT) at a concentration of 10 microM for 15 min prior to subjecting them to 30 min of global ischemia followed by 2 h of reperfusion. Left ventricular functions were monitored at various timepoints throughout the reperfusion period to assess the extent of postischemic recovery in comparison with baseline values. Coronary perfusate samples were also collected to determine malonaldehyde (MDA) levels. The results demonstrated that RVT exhibited significant myocardial protection. This was evidenced by improved recovery of post-ischemic ventricular function including developed pressure and aortic flow as compared to the control group (KHB). Values for developed pressure in the RVT-treated group were significantly higher than those in the control group throughout the reperfusion period (71.09+/-4.88 mm Hg vs. 58.47+/-3.88 mm Hg, 68.87+/-5.07 mm Hg vs. 49.74+/-2.65 mm Hg and 51.67+/-3.95 mm Hg vs. 30.50+/-4.80 mm Hg at reperfusion timepoints R-15, R-60, and R-120, respectively). From R-30 onwards, aortic flow was markedly higher in the RVT treated group as compared with the control group, the differences being most significant at R-90 (32.45+/-2.19 ml/min vs. 19.83+/-1.62 ml/min) and R-120 (27.15+/-2.27 ml/min vs. 14.10+/-1.69 ml/min). In contrast to the KHB treated group, the RVT-treated group displayed significant reduction in MDA formation

  4. Lack of effect of thyroid hormone on diabetic rat heart function and biochemistry.

    PubMed

    Tahiliani, A G; McNeill, J H

    1984-06-01

    Cardiac functional abnormalities are frequently seen in diabetics and diabetes is also known to produce a state of mild hypothyroidism. To study the degree of involvement of diabetes-induced hypothyroidism on altered myocardial function, thyroid replacement therapy was carried out in streptozotocin-diabetic rats. Triiodothyronine (T3) treatment was initiated 3 days after the rats were made diabetic and was carried out for 6 weeks thereafter. Isolated perfused hearts from diabetic rats exhibited a depression in left ventricular developed pressure and positive and negative dP/dt at higher filling pressures as compared with controls. The depression could not be prevented by thyroid treatment. Calcium uptake activity in the cardiac sarcoplasmic reticulum (SR) was also depressed as a result of diabetes and this depression also was not prevented by thyroid treatment. Long chain acyl carnitine levels were found to be elevated in diabetic cardiac SR and could not be lowered by T3 treatment. The results indicate that the myocardial dysfunction observed in diabetic rats is due to factors other than the induced hypothyroidism.

  5. Protective Effects of Repetitive Injections of Radiographic Contrast Media on the Subsequent Tolerance to Ischemia in the Isolated Rat Heart

    SciTech Connect

    Falck, Geir; Bruvold, Morten; Schjott, Jan; Jynge, Per

    2000-11-15

    Purpose: Despite detailed knowledge of the effects of X-ray contrast media on cardiac function, no studies have examined the effect of contrast media injections on the subsequent tolerance to ischemia in the heart.Methods: Isolated perfused rat hearts were exposed to repetitive injections of iohexol, iodixanol, or ioxaglate before 30 min of global ischemia and 120 min of reperfusion. These groups were compared with control (no pretreatment) and ischemic preconditioning known to reduce infarct size. Physiologic variables and infarct size were measured. Results: Pretreatment with iodixanol reduced infarct size significantly compared with control and thus afforded protection against ischemia. Injections with iohexol and ioxaglate reduced infarct size, although not significantly, compared with control.Conclusion: Pretreatment of the isolated rat heart with commonly used contrast media enhances the cardiac tolerance to subsequent ischemia. The mechanism behind this protective effect could not be determined, but could involve stretching of the heart and/or generation of nitric oxide.

  6. Forskolin- and dihydroalprenolol (DHA) binding sites and adenylate cyclase activity in heart of rats fed diets containing different oils

    SciTech Connect

    Alam, S.Q.; Ren, Y.F.; Alam, B.S.

    1987-05-01

    The purpose of the present investigation was to determine if dietary lipids can induce changes in the adenylate cyclase system in rat heart. Three groups of male young Sprague-Dawley rats were fed for 6 weeks diets containing 10% corn oil (I), 8% coconut oil + 2% corn oil (II) or 10% menhaden oil (III). Adenylate cyclase activity (basal, fluoride-, isoproterenol-, and forskolin-stimulated) was higher in heart homogenates of rats in group III than in the other two groups. Concentration of the (/sup 3/H)-forskolin binding sites in the cardiac membranes were significantly higher in rats fed menhaden oil. The values (pmol/mg protein) were 4.8 +/- 0.2 (I), 4.5 +/- 0.7 (II) and 8.4 +/- 0.5 (III). There was no significant difference in the affinity of the forskolin binding sites among the 3 dietary groups. When measured at different concentrations of forskolin, the adenylate cyclase activity in cardiac membranes of rats fed menhaden oil was higher than in the other 2 groups. Concentrations of the (/sup 3/H)DHA binding sites were slightly higher but their affinity was lower in cardiac membranes of rats fed menhaden oil. The results suggest that diets containing fish oil increase the concentration of the forskolin binding sites and may also affect the characteristics of the ..beta..-adrenergic receptor in rat heart.

  7. Abnormalities of capillary microarchitecture in a rat model of coronary ischemic congestive heart failure.

    PubMed

    Chen, Jiqiu; Yaniz-Galende, Elisa; Kagan, Heather J; Liang, Lifan; Hekmaty, Saboor; Giannarelli, Chiara; Hajjar, Roger

    2015-04-15

    The aim of the present study is to explore the role of capillary disorder in coronary ischemic congestive heart failure (CHF). CHF was induced in rats by aortic banding plus ischemia-reperfusion followed by aortic debanding. Coronary arteries were perfused with plastic polymer containing fluorescent dye. Multiple fluorescent images of casted heart sections and scanning electric microscope of coronary vessels were obtained to characterize changes in the heart. Cardiac function was assessed by echocardiography and in vivo hemodynamics. Stenosis was found in all levels of the coronary arteries in CHF. Coronary vasculature volume and capillary density in remote myocardium were significantly increased in CHF compared with control. This occurred largely in microvessels with a diameter of ≤3 μm. Capillaries in CHF had a tortuous structure, while normal capillaries were linear. Capillaries in CHF had inconsistent diameters, with assortments of narrowed and bulged segments. Their surfaces appeared rough, potentially indicating endothelial dysfunction in CHF. Segments of main capillaries between bifurcations were significantly shorter in length in CHF than in control. Transiently increasing preload by injecting 50 μl of 30% NaCl demonstrated that the CHF heart had lower functional reserve; this may be associated with congestion in coronary microcirculation. Ischemic coronary vascular disorder is not limited to the main coronary arteries, as it occurs in arterioles and capillaries. Capillary disorder in CHF included stenosis, deformed structure, proliferation, and roughened surfaces. This disorder in the coronary artery architecture may contribute to the reduction in myocyte contractility in the setting of heart failure.

  8. [Quantitative estimation of connection of the heart rate rhythm with motor activity in rat fetuses].

    PubMed

    Vdovichenko, N D; Timofeeva, O P; Bursian, A V

    2014-01-01

    In rat fetuses at E17-20 with preserved placental circulation with use of mathematical analysis there were revealed value and character of connections of slow wave oscillations of the heart rhythm with motor activity for 30 min of observation. In the software "PowerGraph 3.3.8", normalization and filtration of the studied signals were performed at three frequency diapasons: D1 - 0.02-0.2 Hz (5-50 s), D2 - 0.0083-0.02 Hz (50 s-2 min), and D3 - 0.0017-0.0083 Hz (2-10 min). The EMG curves filtrated by diapasons or piezograms were compared with periodograms in the corresponding diapasons of the heart rhythm variations. In the software "Origin 8.0", quantitative estimation of the degree of intersystemic interrelations for each frequency diapason was performed by Pearson correlation of coefficient, by the correlation connection value, and by the time shift of maximum of cross-correlation function. It has been established that in the frequency D1, regardless of age, the connection of heart rhythm oscillations with motor activity is expressed weakly. In the frequency diapason D2, the connection in most cases is located in the zone of weak and moderate correlations. In the multiminute diapason (D3), the connection is more pronounced. The number of animals that have a significant value of the correlation connection rises. The fetal MA fires in the decasecond diapason in all age groups are accompanied by short-time decelerations of the heart rhythms. In the minute diapason, there is observed a transition from positive connections at E17 and E18 to the negative ones at E19-20. Results of the study are considered in association with age-related changes of ratios of positive and negative oscillations of the heart rhythm change depending on the character of motor activity.

  9. Rooibos (Aspalathus linearis) offers cardiac protection against ischaemia/reperfusion in the isolated perfused rat heart.

    PubMed

    Pantsi, W G; Marnewick, J L; Esterhuyse, A J; Rautenbach, F; van Rooyen, J

    2011-11-15

    Rooibos, a unique South African herbal tea, is known to be an important source of unique polyphenolic compounds. In the present study we have quantified the main polyphenolic compounds in both fermented/traditional and unfermented/"green" rooibos (Aspalathus linearis) and evaluated its cardioprotective effects against ischaemia/reperfusion injury. Male Wistar rats consumed aqueous rooibos and green tea (Camellia sinensis) extracts (2%, w/v) for 7 weeks before their hearts were rapidly excised and perfused in a working heart perfusion apparatus. The results showed that the rooibos supplemented hearts significantly improved aortic output recovery after reperfusion when compared to the green tea supplemented hearts. Additionally, we showed that the rooibos extracts, containing the highest amount of flavonols, significantly decreased the level of cleaved caspase-3 and PARP, both pro-apoptotic proteins, during reperfusion when compared to green tea. Green tea supplementation increased phosphorylation of total PKB/Akt, Akt (threonine 308) and Akt (serine 473). The rooibos extracts did not cause significant change in the levels of the pro-survival PKB/Akt (threonine 308 and serinet 473). The GSH/GSSG ratio in the hearts of the green tea supplemented group was significantly (p<0.05) lower when compared to RF (37.78±28.63), RU (33.20±4.13) and C (45.50±14.96). The results clearly demonstrate the cardio-protective properties of aqueous rooibos extracts via the inhibition of apoptosis which can possibly be related to the flavonol content of this unique South African herbal tea.

  10. Abnormalities of capillary microarchitecture in a rat model of coronary ischemic congestive heart failure

    PubMed Central

    Chen, Jiqiu; Yaniz-Galende, Elisa; Kagan, Heather J.; Liang, Lifan; Hekmaty, Saboor; Giannarelli, Chiara

    2015-01-01

    The aim of the present study is to explore the role of capillary disorder in coronary ischemic congestive heart failure (CHF). CHF was induced in rats by aortic banding plus ischemia-reperfusion followed by aortic debanding. Coronary arteries were perfused with plastic polymer containing fluorescent dye. Multiple fluorescent images of casted heart sections and scanning electric microscope of coronary vessels were obtained to characterize changes in the heart. Cardiac function was assessed by echocardiography and in vivo hemodynamics. Stenosis was found in all levels of the coronary arteries in CHF. Coronary vasculature volume and capillary density in remote myocardium were significantly increased in CHF compared with control. This occurred largely in microvessels with a diameter of ≤3 μm. Capillaries in CHF had a tortuous structure, while normal capillaries were linear. Capillaries in CHF had inconsistent diameters, with assortments of narrowed and bulged segments. Their surfaces appeared rough, potentially indicating endothelial dysfunction in CHF. Segments of main capillaries between bifurcations were significantly shorter in length in CHF than in control. Transiently increasing preload by injecting 50 μl of 30% NaCl demonstrated that the CHF heart had lower functional reserve; this may be associated with congestion in coronary microcirculation. Ischemic coronary vascular disorder is not limited to the main coronary arteries, as it occurs in arterioles and capillaries. Capillary disorder in CHF included stenosis, deformed structure, proliferation, and roughened surfaces. This disorder in the coronary artery architecture may contribute to the reduction in myocyte contractility in the setting of heart failure. PMID:25659485

  11. Effects of short- and long-term exposure to ozone on heart rate and blood pressure of emphysematous rats

    SciTech Connect

    Uchiyama, I.; Yokoyama, E.

    1989-02-01

    Electrocardiogram and arterial blood pressure of elastase-treated emphysematous rats (E rats) and saline-treated control rats (S rats) were recorded continuously during exposure to either 1 ppm ozone (O/sub 3/) for 3 hr or 0.5 ppm O/sub 3/ for 6 hr. The heart rates (HRs) of both groups decreased to about 50 and 65% of the initial levels at the end of 1 ppm and 0.5 ppm O/sub 3/ exposure, respectively. Mean arterial blood pressures (MAPs) also decreased to about 76 and 82%, respectively. There was no significant difference in these responses between E and S rats, although the levels of HRs and MAPs of the E rats were always a little lower than those of the S rats. Another group of E and S rats was continuously exposed to 0.2 ppm O/sub 3/ for 4 weeks. The HRs of both E and S groups decreased to about 81 and 88% of the initial levels on the first day, respectively, although they recovered completely by the third day. No significant difference in the variation of HRs during exposure was noted between E and S rats. However, the HR responses of these rats to a challenge exposure of 0.8 ppm O/sub 3/ for 1.5 hr appeared to be different. That is, S rats were more tolerant of the challenge exposure to O/sub 3/ for 1.5 hr than the E rats.

  12. Dipeptidyl Peptidase IV Inhibition Exerts Renoprotective Effects in Rats with Established Heart Failure

    PubMed Central

    Arruda-Junior, Daniel F.; Martins, Flavia L.; Dariolli, Rafael; Jensen, Leonardo; Antonio, Ednei L.; dos Santos, Leonardo; Tucci, Paulo J. F.; Girardi, Adriana C. C.

    2016-01-01

    Circulating dipeptidyl peptidase IV (DPPIV) activity is associated with worse cardiovascular outcomes in humans and experimental heart failure (HF) models, suggesting that DPPIV may play a role in the pathophysiology of this syndrome. Renal dysfunction is one of the key features of HF, but it remains to be determined whether DPPIV inhibitors are capable of improving cardiorenal function after the onset of HF. Therefore, the present study aimed to test the hypothesis that DPPIV inhibition by vildagliptin improves renal water and salt handling and exerts anti-proteinuric effects in rats with established HF. To this end, male Wistar rats were subjected to left ventricle (LV) radiofrequency ablation or sham operation. Six weeks after surgery, radiofrequency-ablated rats who developed HF were randomly divided into two groups and treated for 4 weeks with vildagliptin (120 mg/kg/day) or vehicle by oral gavage. Echocardiography was performed before (pretreatment) and at the end of treatment (post-treatment) to evaluate cardiac function. The fractional area change (FAC) increased (34 ± 5 vs. 45 ± 3%, p < 0.05), and the isovolumic relaxation time decreased (33 ± 2 vs. 27 ± 1 ms; p < 0.05) in HF rats treated with vildagliptin (post-treatment vs. pretreatment). On the other hand, cardiac dysfunction deteriorated further in vehicle-treated HF rats. Renal function was impaired in vehicle-treated HF rats as evidenced by fluid retention, low glomerular filtration rate (GFR) and high levels of urinary protein excretion. Vildagliptin treatment restored urinary flow, GFR, urinary sodium and urinary protein excretion to sham levels. Restoration of renal function in HF rats by DPPIV inhibition was associated with increased active glucagon-like peptide-1 (GLP-1) serum concentration, reduced DPPIV activity and increased activity of protein kinase A in the renal cortex. Furthermore, the anti-proteinuric effect of vildagliptin treatment in rats with established HF was associated with

  13. Functional study of TREK-1 potassium channels during rat heart development and cardiac ischemia using RNAi techniques.

    PubMed

    Yang, Xiaojuan; Guo, Peng; Li, Jiang; Wang, Weiping; Xu, Shaofeng; Wang, Ling; Wang, Xiaoliang

    2014-08-01

    To explore the physiological and pathological significance of the 2-pore domain potassium channel TWIK-related K(+) (TREK)-1 in rat heart, its expression and role during heart development and cardiac ischemia were investigated. In the former study, the ventricles of Sprague Dawley rats were collected from embryo day 19 to postnatal 18 months and examined for mRNA and protein expression of TREK-1. It was found that both increased during development, reached a maximum at postnatal day 28, and remained higher at postnatal day 3 through to postnatal 18 months. In the latter study, protein expression of TREK-1 was examined after initiation of acute heart ischemia by ligation of the left anterior descending coronary artery. TREK-1 expression was found to be increased in the endocardium but unchanged in the epicardium. In primary cultured rat neonatal ventricular myocytes subjected to hypoxia (oxygen-glucose deprivation), TREK-1 expression was increased. In cultured neonatal cardiomyocytes, silencing of the TREK-1 gene by lentivirus delivery of the short-hairpin RNAs, L-sh-492 and L-sh-605, was found to promote their viability and number. In addition, both short-hairpin RNA provided protection against hypoxia-induced injury to cardiomyocytes in vitro. These results suggest that TREK-1 plays an important role in neonatal rat heart development and downregulation of TREK-1 may provide protection against ischemic injury. It seems that TREK-1 is a potential drug target for treatment of acute heart ischemia.

  14. The small-molecule fast skeletal troponin activator, CK-2127107, improves exercise tolerance in a rat model of heart failure.

    PubMed

    Hwee, Darren T; Kennedy, Adam R; Hartman, James J; Ryans, Julie; Durham, Nickie; Malik, Fady I; Jasper, Jeffrey R

    2015-04-01

    Heart failure-mediated skeletal myopathy, which is characterized by muscle atrophy and muscle metabolism dysfunction, often manifests as dyspnea and limb muscle fatigue. We have previously demonstrated that increasing Ca(2+) sensitivity of the sarcomere by a small-molecule fast skeletal troponin activator improves skeletal muscle force and exercise performance in healthy rats and models of neuromuscular disease. The objective of this study was to investigate the effect of a novel fast skeletal troponin activator, CK-2127107 (2-aminoalkyl-5-N-heteroarylpyrimidine), on skeletal muscle function and exercise performance in rats exhibiting heart failure-mediated skeletal myopathy. Rats underwent a left anterior descending coronary artery ligation, resulting in myocardial infarction and a progressive decline in cardiac function [left anterior descending coronary artery heart failure (LAD-HF)]. Compared with sham-operated control rats, LAD-HF rat hindlimb and diaphragm muscles exhibited significant muscle atrophy. Fatigability was increased during repeated in situ isokinetic plantar flexor muscle contractions. CK-2127107 produced a leftward shift in the force-Ca(2+) relationship of skinned, single diaphragm, and extensor digitorum longus fibers. Exercise performance, which was assessed by rotarod running, was lower in vehicle-treated LAD-HF rats than in sham controls (116 ± 22 versus 193 ± 31 seconds, respectively; mean ± S.E.M.; P = 0.04). In the LAD-HF rats, a single oral dose of CK-2127107 (10 mg/kg p.o.) increased running time compared with vehicle treatment (283 ± 47 versus 116 ± 22 seconds; P = 0.0004). In summary, CK-2127107 substantially increases exercise performance in this heart failure model, suggesting that modulation of skeletal muscle function by a fast skeletal troponin activator may be a useful therapeutic in heart failure-associated exercise intolerance.

  15. [Effect of 17β-estradiol on bioenergetic processes in the heart mitochondria of ovariectomized rats with insulin resistance].

    PubMed

    Gorbenko, N I; Borikov, A Y; Ivanova, O V; Taran, E V; Zvyagina, T S

    2014-01-01

    Тhe bioenergetic processes in the heart mitochondria of Wistar rats with fructose-induced insulin resistance was investigated in female animals with different estrogen status. Respiration studies on isolated heart mitochondria by the polarographic method revealed that estrogen deficiency reduced complex IV activity, while its combination with high-fructose diet induced additional disturbances in the coupling of respiration and oxidative phosphorylation at the level of complex I of the electron transport chain. Exogenous 17b-estradiol inhibited the development of mitochondrial dysfunction in cardiomyocytes of ovariectomized rats with insulin resistance.

  16. Mitochondrial complex I dysfunction in rat heart with aging: critical role of reactive oxygen species and cardiolipin.

    PubMed

    Petrosillo, Giuseppe; Matera, Mariagiuseppa; Moro, Nicola; Ruggiero, Francesca M; Paradies, Giuseppe

    2009-01-01

    Reactive oxygen species (ROS) are considered a key factor in the heart aging process. Mitochondrial respiration is an important site of ROS generation and a potential contributor to heart functional changes with aging. We have examined the effects of aging on various parameters related to mitochondrial bioenergetics in rat heart, such as complex I activity, oxygen consumption, membrane potential, ROS production, and cardiolipin content and oxidation. A loss in complex I activity, state 3 respiration, and membrane potential was found in mitochondria with aging. The capacity of mitochondria to produce H(2)O(2) was significantly increased in aged rats. The mitochondrial content of cardiolipin, a phospholipid required for optimal activity of complex I, significantly decreased as a function of aging, whereas there was a significant increase in the level of oxidized cardiolipin. The lower complex I activity in mitochondria from aged rats could be almost completely restored to the level of young heart by exogenously added cardiolipin, but not by other phospholipids nor by peroxidized cardiolipin. It is proposed that aging causes heart mitochondrial complex I deficiency, which can be attributed to ROS-induced cardiolipin peroxidation. These results may prove useful in elucidating the mechanism underlying mitochondrial dysfunction associated with heart aging.

  17. Stimulation of phosphatidylglycerolphosphate phosphatase activity by unsaturated fatty acids in rat heart.

    PubMed

    Cao, S G; Hatch, G M

    1994-07-01

    Phosphatidylglycerolphosphate (PGP) synthase and PGP phosphatase catalyze the sequential synthesis of phosphatidylglycerol from cytidine-5'-diphosphate 1,2-diacyl-sn-glycerol (CDP-DG) and glycerol-3-phosphate. PGP synthase and PGP phosphatase activities were characterized in rat heart mitochondrial fractions, and the effect of fatty acids on the activity of these enzymes was determined. PGP synthase was observed to be a heat labile enzyme that exhibited apparent Km values for CDP-PG and glycerol-3-phosphate of 46 and 20 microM, respectively. The addition of exogenous oleic acid to the assay mixture did not affect PGP synthase activity. PGP phosphatase was observed to be a heat labile enzyme, and addition of oleic acid to the assay mixture caused a concentration-dependent stimulation of PGP phosphatase activity. Maximum stimulation (1.9-fold) of enzyme activity was observed in the presence of 0.5 mM oleic acid, but the stimulation was slightly attenuated by the presence of albumin in the assay. The presence of oleic acid in the assay mixture caused the inactivation of PGP phosphatase activity to be retarded at 55 degrees C. Stimulation of PGP phosphatase activity was also observed with arachidonic acid, whereas taurocholic, stearic and palmitic acids did not significantly affect PGP phosphatase activity. The activity of mitochondrial phosphatidic acid phosphohydrolase was not affected by inclusion of oleic acid in the incubation mixture. We postulate that unsaturated fatty acids stimulate PGP phosphatase activity in rat heart.

  18. Oleuropein attenuates the progression of heart failure in rats by antioxidant and antiinflammatory effects.

    PubMed

    Janahmadi, Zeinab; Nekooeian, Ali Akbar; Moaref, Ali Reza; Emamghoreishi, Masoomeh

    2017-03-01

    Much of the beneficial effects of olive products have been attributed to oleuropein. This study examined the effects of oleuropein in rats with heart failure induced by permanent ligation of left coronary arteries. Twenty-four hours after the operation, the rats were assigned to five groups including a sham assigned to receive vehicle (1 ml/day) and four coronary ligated groups assigned to receive vehicle or oleuropein at 5, 10, or 20 mg/kg/day. Five weeks later, echocardiographic and hemodynamic parameters, serum concentrations of oxidative stress, and inflammatory markers were determined. Myocardial infarction group receiving vehicle showed impaired hemodynamic and echocardiographic parameters as evidenced by decreased left ventricular systolic pressure, rate of rise and decrease of left ventricular pressure, stroke volume, ejection fraction, and cardiac output. In addition, significant reduction in superoxide dismutase and glutathione reductase was observed. Oleuropein treatment prevented the reduction of these variables. Moreover, the group had a significantly higher infarct size and serum malondialdehyde, interleukin-1β, and tumor necrosis factor-α than those of the sham group. Treatment with oleuropein prevented the increase of these variables. The results show that oleuropein attenuates the progression of heart failure, possibly by antioxidative and antiinflammatory effects.

  19. Mitigation Effect of Proanthocyanidin on Secondary Heart Injury in Rats Caused by Mechanical Trauma

    PubMed Central

    Ma, Shuo; Chen, Chong; Cao, Tingting; Bi, Yue; Zhou, Jicheng; Li, Xintao; Yu, Deqin; Li, Shuzhuang

    2017-01-01

    Multiple organ dysfunctional syndrome secondary to mechanical trauma (MT) has attracted considerable research attention. The heart is one of the most important organs of the body, and secondary cardiac insufficiency caused by MT seriously affects the quality of life. This study aims to investigate whether proanthocyanidin can alleviate myocardial injury and improve heart function in the process of MT leading to secondary cardiac insufficiency. Noble-Collip drum wasused to prepare MT model in rats. And myocardial apoptosis index was calculated after TUNEL staining. Ventricular intubation was employed to detect heart function. Changes in myocardial ultrastructure were observed using an electron microscope. ELISA was used to detect the content of TNF-α and reactive oxygen species generated from monocytes and cardiomyocytes. The changes in Ca2+ concentration in cardiomyocyte were observed by confocal microscope. Compared with trauma group, the administration group had a decreased apoptosis index of cardiomyocytes, and increased ±dp/dtmax. Meanwhile, proanthocyanidin can inhibit monocytes’ TNF-α production, and reduce plasma TNF-α concentration. Moreover, proanthocyanidin can attenuate the excessive oxidative stress reaction of cardiomyocyte, and inhibit calcium overload in cardiomyocytes. In conclusion, proanthocyanidin can effectively ease myocardial damage and improve cardiac function, through anti-inflammatory and antioxidant effects in secondary cardiac insufficiency caused by MT. PMID:28294148

  20. Multiple Mass Isotopomer Tracing of Acetyl-CoA Metabolism in Langendorff-perfused Rat Hearts

    PubMed Central

    Li, Qingling; Deng, Shuang; Ibarra, Rafael A.; Anderson, Vernon E.; Brunengraber, Henri; Zhang, Guo-Fang

    2015-01-01

    We developed an isotopic technique to assess mitochondrial acetyl-CoA turnover (≈citric acid flux) in perfused rat hearts. Hearts are perfused with buffer containing tracer [13C2,2H3]acetate, which forms M5 + M4 + M3 acetyl-CoA. The buffer may also contain one or two labeled substrates, which generate M2 acetyl-CoA (e.g. [13C6]glucose or [1,2-13C2]palmitate) or/and M1 acetyl-CoA (e.g. [1-13C]octanoate). The total acetyl-CoA turnover and the contributions of fuels to acetyl-CoA are calculated from the uptake of the acetate tracer and the mass isotopomer distribution of acetyl-CoA. The method was applied to measurements of acetyl-CoA turnover under different conditions (glucose ± palmitate ± insulin ± dichloroacetate). The data revealed (i) substrate cycling between glycogen and glucose-6-P and between glucose-6-P and triose phosphates, (ii) the release of small excess acetyl groups as acetylcarnitine and ketone bodies, and (iii) the channeling of mitochondrial acetyl-CoA from pyruvate dehydrogenase to carnitine acetyltransferase. Because of this channeling, the labeling of acetylcarnitine and ketone bodies released by the heart are not proxies of the labeling of mitochondrial acetyl-CoA. PMID:25645937

  1. Upregulation of the alpha1-adrenoceptor-induced phosphoinositide and inotropic response in hypothyroid rat heart.

    PubMed

    Jalali, Shahrzad; Durston, Melanie; Panagia, Vincenzo; Mesaeli, Nasrin

    2006-02-01

    In this study, we examined changes in the biochemical and inotropic events of the alpha(1)-adrenoceptor signaling pathway in hypothyroid rat hearts. Hypothyroidism was induced by treating experimental animals with 0.05% 6-n-propyl-2-thiouracil (PTU) in drinking water for 7 weeks. A significant decrease of beta- and an increase in alpha(1)-adrenoceptor density as well as an increase in the basal activity of the phosphoinositide (4,5) bisphosphate hydrolyzing phospholipase C was observed in sarcolemmal membranes purified from hypothyroid hearts as compared to age-matched euthyroid controls. Following stimulation with 10 microM phenylephrine (in the presence of 10 microM atenolol), the increase of contractile parameters over baseline values was significantly higher in hypo- than euthyroid hearts, while the opposite occurred under beta-stimulation with 0.1 microM isoproterenol. Interestingly, the increase in phenylephrine-mediated positive inotropy was accompanied by a significant increase in the sarcolemmal phospholipase C activity and in the inositol 1,4,5-trisphosphate content in hypothyroid as compared to euthyroid controls. Our results suggest that cardiac alpha(1)-adrenoceptor and its associated phosphoinositide signaling pathway may act as a reserve for catecholamine inotropic response in hypothyroidism, where the beta-adrenoceptors are compromised.

  2. Morphological and biochemical examination of Cosmos 1887 rat heart tissue. Part 1: Ultrastructure

    NASA Technical Reports Server (NTRS)

    Philpott, D. E.; Popova, I. A.; Kato, K.; Stevenson, J.; Miquel, J.; Sapp, W.

    1990-01-01

    Morphological changes were observed in the left ventricle of rat heart tissue from animals flown on the Cosmos 1887 biosatellite for 12.5 days. These tissues were compared to the synchronous and vivarium control hearts. While many normal myofibrils were observed, others exhibited ultrastructural alterations, i.e., damaged and irregular-shaped mitochondria and generalized myofibrillar edema. Analysis of variance (ANOVA) of the volume density data revealed a statistically significant increase in glycogen and a significant decrease in mitochondria compared to the synchronous and vivarium controls. Point counting indicated an increase in lipid and myeloid bodies and a decrease in microtubules, but these changes were not statistically significant. In addition, the flight animals exhibited some patchy loss of protofibrils (actin and myosin filaments) and some abnormal supercontracted myofibrils that were not seen in the controls. This study was undertaken to gain insight into the mechanistic aspects of cardiac changes in both animals and human beings as a consequence of space travel. Cardiac hypotrophy and fluid shifts have been observed after actual or simulated weightlessness and raise concerns about the functioning of the heart and circulatory system during and after travel in space.

  3. Amino acid- and lipid-induced insulin resistance in rat heart: molecular mechanisms.

    PubMed

    Terruzzi, Ileana; Allibardi, Sonia; Bendinelli, Paola; Maroni, Paola; Piccoletti, Roberta; Vesco, Flavio; Samaja, Michele; Luzi, Livio

    2002-04-25

    Lipids compete with glucose for utilization by the myocardium. Amino acids are an important energetic substrate in the heart but it is unknown whether they reduce glucose disposal. The molecular mechanisms by which lipids and amino acids impair insulin-mediated glucose disposal in the myocardium are unknown. We evaluated the effect of lipids and amino acids on the insulin stimulated glucose uptake in the isolated rat heart and explored the involved target proteins. The hearts were perfused with 16 mM glucose alone or with 6% lipid or 10% amino acid solutions at the rate of 15 ml/min. After 1 h of perfusion (basal period), insulin (240 nmol/l) was added and maintained for an additional hour. Both lipids and amino acids blocked the insulin effect on glucose uptake (P<0.01) and reduced the activity of the IRSs/PI 3-kinase/Akt/GSK3 axis leading to the activation of glucose transport and glycogen synthesis. Amino acids, but not lipids, increased the activity of the p70 S6 kinase leading to the stimulation of protein synthesis. Amino acids induce myocardial insulin resistance recruiting the same molecular mechanisms as lipids. Amino acids retain an insulin-like stimulatory effect on p70 S6 kinase, which is independent from the PI 3-Kinase downstream effectors.

  4. Control of the heart rate of rat embryos during the organogenic period

    PubMed Central

    Ritchie, Helen E; Ragnerstam, Carolina; Gustafsson, Elin; Jonsson, Johanna M; Webster, William S

    2016-01-01

    The aim of this study was to gain insight into whether the first trimester embryo could control its own heart rate (HR) in response to hypoxia. The gestational day 13 rat embryo is a good model for the human embryo at 5–6 weeks gestation, as the heart is comparable in development and, like the human embryo, has no functional autonomic nerve supply at this stage. Utilizing a whole-embryo culture technique, we examined the effects of different pharmacological agents on HR under normoxic (95% oxygen) and hypoxic (20% oxygen) conditions. Oxygen concentrations ≤60% caused a concentration-dependent decrease in HR from normal levels of ~210 bpm. An adenosine agonist, AMP-activated protein kinase (AMPK) activator and KATP channel opener all caused bradycardia in normoxic conditions; however, putative antagonists for these systems failed to prevent or ameliorate hypoxia-induced bradycardia. This suggests that the activation of one or more of these systems is not the primary cause of the observed hypoxia-induced bradycardia. Inhibition of oxidative phosphorylation also decreased HR in normoxic conditions, highlighting the importance of ATP levels. The β-blocker metoprolol caused a concentration-dependent reduction in HR supporting reports that β1-adrenergic receptors are present in the early rat embryonic heart. The cAMP inducer colforsin induced a positive chronotropic effect in both normoxic and hypoxic conditions. Overall, the embryonic HR at this stage of development is responsive to the level of oxygenation, probably as a consequence of its influence on ATP production. PMID:27878135

  5. Influence of starvation on heart contractility and corticosterone level in rats.

    PubMed

    Lee, Sung Ryul; Ko, Tae Hee; Kim, Hyoung Kyu; Marquez, Jubert; Ko, Kyung Soo; Rhee, Byoung Doo; Han, Jin

    2015-11-01

    The physiological changes, including cardiac modification, that occur during starvation are not yet completely understood. The purpose of this study is to examine the effects of a 2-week starvation period on heart contractility, muscle mass, and irisin and corticosterone levels in rats. Rats in the starved group showed a significant reduction in the body, heart, kidney, and muscle weight (n = 23, p < 0.05). Blood glucose, total protein, and albumin showed a 44, 17.5, and 10.3 % reduction, respectively (p < 0.05). Lipid reserves, such as total lipid, triglyceride, and free fatty acid, were also comparably reduced (p < 0.05). However, the bilirubin, creatinine, blood urea nitrogen, and creatine kinase levels were higher than in the control group (p < 0.05). The blood irisin level was unchanged, but the stress-related corticosterone level was significantly higher in the starved group. The differences observed in M-mode echocardiography were further compared with the body-weight-matched control group. Starvation reduced the left ventricle mass; however, this difference was not significant compared with the body-weight-matched group (p > 0.05). In the starvation group, the impairment of cardiac output was dependent on the reduction in stroke volume and heart rate. Starvation induced a severe reduction in ejection fraction and fractional shortening when compared with the body-weight-matched control group (p < 0.05). In summary, prolonged starvation, which leads to a deficiency of available nutrition, increases the stress-related corticosterone level, impairs the cardiac output, and is associated with changes in cardiac morphogeometry.

  6. Cardioprotective effects of silver fir (Abies alba) extract in ischemic-reperfused isolated rat hearts

    PubMed Central

    Drevenšek, Gorazd; Lunder, Mojca; Benković, Eva Tavčar; Štrukelj, Borut; Kreft, Samo

    2016-01-01

    Background Silver fir trunk extract (SFTE) is a complex mixture of antioxidative polyphenols (lignans and phenolic acids) from the trunks of silver fir trees (Abies alba, lignum). In our previous study, we have shown that SFTE exerts strong antioxidative and protective effects against atherogenic, diet-induced arterial wall damage. Objective The aim of the present study was to test the potential protective effects of SFTE and its compounds, two phenolic acids (p-coumaric and protocatechuic acids) in ischemia–reperfusion injury of isolated rat hearts. Design Isolated hearts of Wistar rats aged 4–8 weeks were exposed to perfusion, ischemia, and reperfusion periods. The experiments were performed using the following five groups: control, SFTE (10 µg/L), SFTE (100 µg/L), protocatechuic acid, and p-coumaric. Aortas were isolated to measure vascular responses in the presence of Nω-Nitro-L-arginine. Results SFTE dose-dependently reduced ischemic-reperfusion heart damage, which was indicated as the decrease in the lactate dehydrogenase (LDH) release rate and arrhythmias duration by 80% and an increase in coronary flow rate during the reperfusion period. Two tested compounds (p-coumaric and protocatechuic acids) acted less cardioprotective, since they decreased the duration of arrhythmias only by 40 and 45%, respectively, and did not decrease LDH release rates during the reperfusion period. Only p-coumaric acid increased coronary flow rates, whereas protocatechuic acid did not. Conclusions We conclude that the SFTE exerted the strongest cardioprotective effect, whereas its constituents (the p-coumaric and protocatechuic acids) were less effective in inducing cardioprotection. PMID:27756448

  7. Ischemic postconditioning influences electron transport chain protein turnover in Langendorff-perfused rat hearts

    PubMed Central

    Cao, Song; Liu, Yun; Wang, Haiying; Mao, Xiaowen; Chen, Jincong; Liu, Jiming; Xia, Zhengyuan; Zhang, Lin; Liu, Xingkui

    2016-01-01

    Ischemia postconditioning (IPo) is a promising strategy in reducing myocardial ischemia reperfusion (I/R) injury (MIRI), but its specific molecular mechanism is incompletely understood. Langendorff-perfused isolated rat hearts were subjected to global I/R and received IPo in the absence or presence of the mitochondrial ATP-sensitive potassium channel (mitoKATP) blocker 5-hydroxydecanoate (5-HD). Myocardial mitochondria were extracted and mitochondrial comparative proteomics was analyzed. IPo significantly reduces post-ischemic myocardial infarction and improved cardiac function in I/R rat hearts, while 5-HD basically cancelled IPo’s myocardial protective effect. Joint application of two-dimensional polyacrylamide gel electrophoresis (2DE) and MALDI-TOF MS identified eight differentially expressed proteins between groups. Expression of cardiac succinate dehydrogenase (ubiquinone) flavoprotein subunit (SDHA) increased more than two-fold after I/R, while IPo led to overexpression of dihydrolipoyl dehydrogenase (DLD), NADH dehydrogenase (ubiquinone) flavoprotein 1 and isoform CRA_b (NDUFV1). When the mitoKATP was blocked, MICOS complex subunit Mic60 (IMMT) and Stress-70 protein (Grp75) were over expressed, while DLDH, ATPase subunit A (ATPA) and rCG44606 were decreased. Seven of the differential proteins belong to electron transport chain (ETC) or metabolism regulating proteins, and five of them were induced by closing mitoKATP in I/R hearts. We thus conclude that IPo’s myocardial protective effect relies on energy homeostasis regulation. DLD, SDHA, NDUFV1, Grp75, ATPA and rCG44606 may contribute to IPo’s cardial protective effect. PMID:26925330

  8. Early alterations in myocardia and vessels of the diabetic rat heart: an FTIR microspectroscopic study.

    PubMed

    Toyran, Neslihan; Lasch, Peter; Naumann, Dieter; Turan, Belma; Severcan, Feride

    2006-08-01

    Diabetes mellitus is associated with a high incidence and poor prognosis of cardiovascular disease. The aim of the present study was to examine the effect of relatively short-term (5 weeks) Type I diabetes on the left ventricle, the right ventricle and the vessel (vein) on the left ventricle of the myocardium at molecular level by FTIR (Fourier-transform infrared) microspectroscopy. The rats were categorized into two groups: control group (for the left ventricle myocardium, n=8; for the right ventricle myocardium, n=9; for the vein, n=9) and streptozotocin-induced diabetic group (for the left ventricle myocardium, n=7; for the right ventricle myocardium, n=9; for the vein, n=8). Two adjacent cross-sections of 9 microm thickness were taken from the ventricles of the hearts in two groups of rats by using a cryotome. The first sections were used for FTIR microspectroscopy measurements. The second serial sections were stained by haematoxylin/eosin for comparative purposes. Diabetes caused an increase in the content of lipids, an alteration in protein profile with a decrease in alpha-helix and an increase in beta-sheet structure as well as an increase in glycogen and glycolipid contents in both ventricles and the vein. Additionally, the collagen content was found to be increased in the vein of the diabetic group. The present study demonstrated that diabetes-induced alterations in the rat heart can be detected by correlating the IR spectral changes with biochemical profiles in detail. The present study for the first time demonstrated the diabetes-induced alterations at molecular level in both ventricle myocardia and the veins in relatively short-term diabetes.

  9. Protective effects of hydroalcoholic extract from rhizomes of Cynodon dactylon (L.) Pers. on compensated right heart failure in rats

    PubMed Central

    Garjani, Alireza; Afrooziyan, Arash; Nazemiyeh, Hossein; Najafi, Moslem; Kharazmkia, Ali; Maleki-Dizaji, Nasrin

    2009-01-01

    Background The rhizomes of Cynodon dactylon are used for the treatment of heart failure in folk medicine. In the present study, we investigated the effects of hydroalcoholic extract of C. dactylon rhizomes on cardiac contractility in normal hearts and on cardiac functions in right-heart failure in rats. Methods Right-heart failure was induced by intraperitoneal injection of monocrotaline (50 mg/kg). Two weeks later, the animals were treated orally with different doses of the extract for fifteen days. At the end of the experiments cardiac functions and markers of myocardial hypertrophy were measured. Results The treated rats showed very less signs of fatigue, peripheral cyanosis and dyspnea. The survival rate was high in the extract treated groups (90%). Administration of C. dactylon in monocrotaline-injected rats led to profound improvement in cardiac functions as demonstrated by decreased right ventricular end diastolic pressure (RVEDP) and elevated mean arterial pressure. RVdP/dtmax, and RVdP/dt/P as indices of myocardial contractility were also markedly (p < 0.001; using one way ANOVA) increased by the extract. The extract reduced heart and lung congestion by decreasing tissue wet/dry and wet/body weight ratios (p < 0.01). In the isolated rat hearts, the extract produced a remarkable (P < 0.001) positive inotropic effect concomitant with a parallel decrease in LVEDP. Conclusion The results of this study indicated that C. dactylon exerted a strong protective effect on right heart failure, in part by positive inotropic action and improving cardiac functions. PMID:19653918

  10. Dietary nitrate increases arginine availability and protects mitochondrial complex I and energetics in the hypoxic rat heart

    PubMed Central

    Ashmore, Tom; Fernandez, Bernadette O; Branco-Price, Cristina; West, James A; Cowburn, Andrew S; Heather, Lisa C; Griffin, Julian L; Johnson, Randall S; Feelisch, Martin; Murray, Andrew J

    2014-01-01

    Hypoxic exposure is associated with impaired cardiac energetics in humans and altered mitochondrial function, with suppressed complex I-supported respiration, in rat heart. This response might limit reactive oxygen species generation, but at the cost of impaired electron transport chain (ETC) activity. Dietary nitrate supplementation improves mitochondrial efficiency and can promote tissue oxygenation by enhancing blood flow. We therefore hypothesised that ETC dysfunction, impaired energetics and oxidative damage in the hearts of rats exposed to chronic hypoxia could be alleviated by sustained administration of a moderate dose of dietary nitrate. Male Wistar rats (n = 40) were given water supplemented with 0.7 mmol l−1 NaCl (as control) or 0.7 mmol l−1 NaNO3, elevating plasma nitrate levels by 80%, and were exposed to 13% O2 (hypoxia) or normoxia (n = 10 per group) for 14 days. Respiration rates, ETC protein levels, mitochondrial density, ATP content and protein carbonylation were measured in cardiac muscle. Complex I respiration rates and protein levels were 33% lower in hypoxic/NaCl rats compared with normoxic/NaCl controls. Protein carbonylation was 65% higher in hearts of hypoxic rats compared with controls, indicating increased oxidative stress, whilst ATP levels were 62% lower. Respiration rates, complex I protein and activity, protein carbonylation and ATP levels were all fully protected in the hearts of nitrate-supplemented hypoxic rats. Both in normoxia and hypoxia, dietary nitrate suppressed cardiac arginase expression and activity and markedly elevated cardiac l-arginine concentrations, unmasking a novel mechanism of action by which nitrate enhances tissue NO bioavailability. Dietary nitrate therefore alleviates metabolic abnormalities in the hypoxic heart, improving myocardial energetics. PMID:25172947

  11. Oxymatrine attenuated isoproterenol-induced heart failure in rats via regulation of COX-2/PGI2 pathway.

    PubMed

    Zhou, Ru; Xu, Qingbin; Xu, Yehua; Xiong, Aiqin; Wang, Yang; Ma, Ping

    2016-12-01

    Oxymatrine (OMT) is an active constituent of traditional Chinese herb Sophora japonica Ait which has been shown to exert potent anti-inflammatory,anti-oxidant and anti-fibrosis properties. Our previous studies have demonstrated that OMT has protective effects on isoproterenol-induced heart failure in rats through regulation of DDAH/ADMA metabolism pathway.In this study,we further investigated whether OMT could attenuate isoproterenol-induced heart failure through the regulation of COX-2/PGI2 pathway. Heart failure was induced in Sprague-Dawley rats by 5mg/kg isoproterenol subcutaneous injection for 7days. The rats were maintained on normal diet and randomly divided into five groups: control, isoproterenol, isoproterenol with OMT (50, 100mg/kg), and OMT alone groups (n=12 in each group). Serum brain natruretic peptide (BNP, a heart failure biomarker), histopathological variables, expression of Cytosolic phospholipase A2 (cPLA2), cyclooxygenase-1 (COX-1), cyclooxygenase-2 (COX-2) and Prostacyclin synthase (PGIS) were analysed. Administration of OMT significantly reduced the increased BNP in plasm of isoproterenol-induced rats, attenuated cardiac fibrosis,suppressed overexpression of myocardial COX-1 expression, up-regulated COX-2 and PGIS expression, but had no effects on isoproterenol-induced elevated protein cPLA2. And compared with control group, any indexes in sham rats treated with OMT (100mg/kg) alone were unaltered. These results demonstrated that OMT has cardioprotective effects on isoproterenol-induced heart failure in rats by regulating COX-2/PGI2 pathway.

  12. Comparative proteomic analysis of 2-MCPD- and 3-MCPD-induced heart toxicity in the rat.

    PubMed

    Schultrich, Katharina; Frenzel, Falko; Oberemm, Axel; Buhrke, Thorsten; Braeuning, Albert; Lampen, Alfonso

    2017-01-30

    The chlorinated propanols 2- and 3-monochloropropanediol (MCPD), and their fatty acid esters have gained public attention due to their frequent occurrence as heat-induced food contaminants. Toxic properties of 3-MCPD in kidney and testis have extensively been characterized. Other 3-MCPD target organs include heart and liver, while 2-MCPD toxicity has been observed in striated muscle, heart, kidney, and liver. Inhibition of glycolysis appears to be important in 3-MCPD toxicity, whereas mechanisms of 2-MCPD toxicity are still unknown. It is thus not clear whether toxicity by the two isomeric compounds is dependent on similar or dissimilar modes of action. A 28-day oral feeding study in rats was conducted using daily non-toxic doses of 2-MCPD or 3-MCPD [10 mg/kg body weight], or an equimolar (53 mg/kg body weight) or a lower (13.3 mg/kg body weight) dose of 2-MCPD dipalmitate. Comprehensive comparative proteomic analyses of substance-induced alterations in the common target organ heart revealed striking similarities between effects induced by 2-MCPD and its dipalmitate ester, whereas the degree of effect overlap between 2-MCPD and 3-MCPD was much less. The present data demonstrate that even if exerting effects in the same organ and targeting similar metabolic networks, profound differences between molecular effects of 2-MCPD and 3-MCPD exist thus warranting the necessity of separate risk assessment for the two substances. This study for the first time provides molecular insight into molecular details of 2-MCPD toxicity. Furthermore, for the first time, molecular data on 3-MCPD toxicity in the heart are presented.

  13. In vivo creatine kinase reaction kinetics at rest and stress in type II diabetic rat heart

    PubMed Central

    Bashir, Adil; Coggan, Andrew R.; Gropler, Robert J.

    2015-01-01

    Abstract The effects of type II diabetes on cardiac creatine kinase (CK) enzyme activity and/or flux are unknown. We therefore measured steady‐state phosphocreatine (PCr) and adenosine triphosphate (ATP) content and forward CK reaction kinetic parameters in Zucker Diabetic Fatty (ZDF) rat hearts, a type II diabetes research model. At baseline the PCr to ATP ratio (PCr/ATP) was significantly lower in diabetic heart when compared with matched controls (1.71 ± 0.21 vs. 2.26 ± 0.24, P < 0.01). Furthermore, the forward CK reaction rate constant (kf) was higher in diabetic animals (0.52 ± 0.09 s−1 vs. 0.35 ± 0.06 s−1, P < 0.01) and CK flux calculated as a product of PCr concentration ([PCr]) and kf was similar between two groups (4.32 ± 1.05 μmol/g/s vs. 4.94 ± 1.23 μmol/g/s, P = 0.20). Dobutamine administration resulted in similar increases in heart rate (~38%) and kf (~0.12 s−1) in both groups. No significant change in PCr and ATP content was observed with dobutamine. In summary, our data showed reduced PCr/ATP in diabetic myocardium as an indicator of cardiac energy deficit. The forward CK reaction rate constant is elevated at baseline which might reflect a compensatory mechanics to support energy flux through the CK shuttle and maintain constant ATP supply. When hearts were stimulated similar increase in kf was observed in both groups thus it seems that CK shuttle does not limit ATP supply for the range of workload studied. PMID:25626865

  14. 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.

  15. Differential modulation of citrate synthesis and release by fatty acids in perfused working rat hearts.

    PubMed

    Vincent, Genevieve; Bouchard, Bertrand; Khairallah, Maya; Des Rosiers, Christine

    2004-01-01

    The objective of this study was to test the effect of increasing fatty acid concentrations on substrate fluxes through pathways leading to citrate synthesis and release in the heart. This was accomplished using semirecirculating work-performing rat hearts perfused with substrate mixtures mimicking the in situ milieu (5.5 mM glucose, 8 nM insulin, 1 mM lactate, 0.2 mM pyruvate, and 0.4 mM oleate-albumin) and 13C methods. Raising the fatty acid concentration from 0.4 to 1 mM with long-chain oleate or medium-chain octanoate resulted in a lowering ( approximately 20%) of cardiac output and efficiency with unaltered O2 consumption. At the metabolic level, beyond the expected effects of high fatty acid levels on the contribution of pyruvate decarboxylation (reduced >3-fold) and beta-oxidation (enhanced approximately 3-fold) to citrate synthesis, there was also a 2.4-fold lowering of anaplerotic pyruvate carboxylation. Despite the dual inhibitory effect of high fatty acids on pyruvate decarboxylation and carboxylation, tissue citrate levels were twofold higher, but citrate release rates remained unchanged at 11-14 nmol/min, representing <0.5% of citric acid cycle flux. A similar trend was observed for most metabolic parameters after oleate or octanoate addition. Together, these results emphasize a differential modulation of anaplerotic pyruvate carboxylation and citrate release in the heart by fatty acids. We interpret the lack of effects of high fatty acid concentrations on citrate release rates as suggesting that, under physiological conditions, this process is maximal, probably limited by the activity of its mitochondrial or plasma membrane transporter. Limited citrate release at high fatty acid concentrations may have important consequences for the heart's fuel metabolism and function.

  16. Effect of antihypertensive agents - captopril and nifedipine - on the functional properties of rat heart mitochondria

    PubMed Central

    Kancirová, Ivana; Jašová, Magdaléna; Waczulíková, Iveta; Ravingerová, Táňa; Ziegelhöffer, Attila; Ferko, Miroslav

    2016-01-01

    Objective(s): Investigation of acute effect on cellular bioenergetics provides the opportunity to characterize the possible adverse effects of drugs more comprehensively. This study aimed to investigate the changes in biochemical and biophysical properties of heart mitochondria induced by captopril and nifedipine antihypertensive treatment. Materials and Methods: Male, 12-week-old Wistar rats in two experimental models (in vivo and in vitro) were used. In four groups, the effects of escalating doses of captopril, nifedipine and combination of captopril + nifedipine added to the incubation medium (in vitro) or administered per os to rat (in vivo) on mitochondrial ATP synthase activity and membrane fluidity were monitored. Results: In the in vitro model we observed a significant inhibitory effect of treatment on the ATP synthase activity (P<0.05) with nonsignificant differences in membrane fluidity. Decrease in the value of maximum reaction rate Vmax (P<0.05) without any change in the value of Michaelis-Menten constant Km, indicative of a noncompetitive inhibition, was presented. At the in vivo level, we did not demonstrate any significant changes in the ATP synthase activity and the membrane fluidity in rats receiving captopril, nifedipine, and combined therapy. Conclusion: In vitro kinetics study revealed that antihypertensive drugs (captopril and nifedipine) directly interact with mitochondrial ATP synthase. In vivo experiment did not prove any acute effect on myocardial bioenergetics and suggest that drugs do not enter cardiomyocyte and have no direct effect on mitochondria. PMID:27482342

  17. Tonic glutamatergic input in the rostral ventrolateral medulla is increased in rats with chronic heart failure.

    PubMed

    Wang, Wei-Zhong; Gao, Lie; Wang, Han-Jun; Zucker, Irving H; Wang, Wei

    2009-02-01

    Chronic heart failure (CHF) is characterized by increased sympathetic tone. The glutamatergic input in the rostral ventrolateral medulla (RVLM), which is a key region involved in sympathetic outflow, seems not to be involved in the generation of sympathetic tone in the normal state. The aim of this study was to determine the role of the RVLM glutamate receptors in the generation of sympathetic tone in CHF. CHF was produced by coronary artery ligation. Bilateral microinjection of the glutamate receptor antagonist kynurenic acid, the N-methyl-d-aspartate (NMDA) receptor antagonist D-2-amino-5-phosphonopentanoate, or the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione into the RVLM dose-dependently reduced resting blood pressure and renal sympathetic nerve activity in CHF but not in sham rats. Picoinjection of kynurenic acid (100 pmol in 5 nL) significantly decreased the basal discharge by 47% in 25 RVLM presympathetic neurons in CHF rats. In contrast, kynurenic acid had no effect on the discharge in all 22 of the RVLM presympathetic neurons tested in sham rats. These data suggest that upregulated glutamate receptors, including NMDA and non-NMDA, in the RVLM are involved in tonic control of elevated sympathetic tone in CHF.

  18. The influence of low-level laser therapy on parameters of oxidative stress and DNA damage on muscle and plasma in rats with heart failure.

    PubMed

    Biasibetti, Micheli; Rojas, Denise B; Hentschke, Vítor S; Moura, Dinara Jaqueline; Karsten, Marlus; Wannmacher, Clóvis M D; Saffi, Jenifer; Dal Lago, Pedro

    2014-11-01

    In heart failure (HF), there is an imbalance between the production of reactive oxygen species and the synthesis of antioxidant enzymes, causing damage to the cardiovascular function and increased susceptibility to DNA damage. The aim of this study was to evaluate the influence of low-level laser therapy (LLLT) on parameters of oxidative stress and DNA damage in skeletal muscle and plasma of rats with HF. Wistar rats were allocated into six groups: "placebo" HF rats (P-HF, n = 9), "placebo" Sham rats (P-sham, n = 8), HF rats at a dose 3 J/cm(2) of LLLT (3 J/cm(2)-HF, n = 8), sham rats at a dose 3 J/cm(2) of LLLT (3 J/cm(2)-sham, n = 8), HF rats at a dose 21 J/cm(2) of LLLT (21 J/cm(2)-HF, n = 8) and sham rats at a dose 21 J/cm(2) of LLLT (21 J/cm(2)-sham, n = 8). Animals were submitted to a LLLT protocol for 10 days at the right gastrocnemius muscle. Comparison between groups showed a significant reduction in superoxide dismutase (SOD) activity in the 3 J/cm(2)-HF group (p = 0.03) and the 21 J/cm(2)-HF group (p = 0.01) compared to the P-HF group. 2',7'-Dihydrodichlorofluorescein (DCFH) oxidation levels showed a decrease when comparing 3 J/cm(2)-sham to P-sham (p = 0.02). The DNA damage index had a significant increase either in 21 J/cm(2)-HF or 21 J/cm(2)-sham in comparison to P-HF (p = 0.004) and P-sham (p = 0.001) and to 3 J/cm(2)-HF (p = 0.007) and 3 J/cm(2)-sham (p = 0.037), respectively. Based on this, laser therapy appears to reduce SOD activity and DCFH oxidation levels, changing the oxidative balance in the skeletal muscle of HF rats. Otherwise, high doses of LLLT seem to increase DNA damage.

  19. Reduced nitric oxide in the rostral ventrolateral medulla enhances cardiac sympathetic afferent reflex in rats with chronic heart failure.

    PubMed

    Zhu, Guo-Qing; Gao, Xing-Ya; Zhang, Feng; Wang, Wei

    2004-02-25

    The purpose of this study was to determine the effect of nitric oxide (NO) in the rostral ventrolateral medulla (RVLM) on the central integration of the cardiac sympathetic afferent reflex (CSAR) in normal rats and in rats with coronary ligation-induced chronic heart failure (CHF). Under alpha-chloralose and urethane anesthesia, mean arterial pressure, heart rate and renal sympathetic nerve activity (RSNA) were recorded at baseline and during elicitation of the CSAR evoked by electrical stimulation of the cardiac afferent sympathetic nerves in sino-aortic denervated and cervical vagotomized rats. A cannula was inserted into the left RVLM for microinjection of NO synthase inhibitor, S-methyl-L-thiocitruline (MeTC) or NO donor, S-nitroso-N-acetyl-penicillamine (SNAP). The CSAR was tested by electrical stimulation (5, 10, 20 and 30 Hz at 10 V for 1 ms) of the afferent cardiac sympathetic nerves. It was observed that (1) the responses of RSNA to stimulation were enhanced in rats with CHF; (2) MeTC (80 nmol) potentiated the responses of RSNA to stimulation in sham rats but not in rats with CHF; (3) SNAP (50 nmol) depressed the enhanced RSNA response to stimulation in CHF rats but had no effect in sham rats; and (4) MeTC increased the baseline RSNA and MAP only in sham rats, but SNAP inhibited the baseline RSNA and MAP in both sham and CHF rats. These results indicate that reductance of NO in the RVLM is involved in the augmentation of CSAR in CHF rats.

  20. Influence of doxazosin on biosynthesis of S100A6 and atrial natriuretic factor peptides in the heart of spontaneously hypertensive rats

    PubMed Central

    Piotrowska, Żaneta; Filipek, Anna; Majewski, Mariusz

    2016-01-01

    Hypertension frequently results in severe complications in cardiovascular system and histopathological changes in the heart. To better understand the cellular processes and signaling pathways responsible for the proper functioning of the heart, we decided to check whether doxazosin affects the density of structures containing S100A6 and atrial natriuretic factor in the heart of spontaneously hypertensive rats. The aim of this study is to find differences in the density of the structures containing S100A6 and atrial natriuretic factor in the heart of spontaneously hypertensive rats treated with doxazosin compared to untreated animals. Fragments of heart were collected from five spontaneously hypertensive rats and five spontaneously hypertensive rats receiving doxazosin for six weeks (dose 0.1 mg per 1 kg of body weight). On the paraffin sections S100A6 and atrial natriuretic factor peptides were localized in the heart using immunohistochemistry. Positive immunohistochemical reaction for S100A6 was observed in atrial and ventricular cardiomyocytes and in the coronary vasculature. In the heart of hypertensive rats treated with doxazosin the S100A6 immunoreactivity was significantly lower compared to untreated animals. Immunodetection of atrial natriuretic factor in the heart of rats confirmed presence of peptide in atrial myocardium. Delicate atrial natriuretic factor-immunoreactivity was observed also in few ventricular cardiomyocytes. The atrial natriuretic factor-immunosignal was significantly weaker in hearts of hypertensive rats receiving doxazosin compared to spontaneously hypertensive rats untreated. Since we found that doxazosin reduces the levels of S100A6 and atrial natriuretic factor peptides in the heart of spontaneously hypertensive rats, it can be assumed that cardiovascular disorders that occur in hypertension may be associated with disturbances of cellular processes and signaling pathways. PMID:26515144

  1. Diesel Exhaust-Induced Cardiac Dysfunction Is Mediated by Sympathetic Dominance in Heart Failure-Prone Rats

    EPA Science Inventory

    Short-term exposure to vehicular emissions is associated with adverse cardiac events. Diesel exhaust (DE) may provoke cardiac events through defective co-ordination of the two main autonomic nervous system (ANS) branches. We exposed heart failure-prone rats once to DE (500 g/m3 ...

  2. Disparate Effects of Stilbenoid Polyphenols on Hypertrophic Cardiomyocytes In Vitro vs. in the Spontaneously Hypertensive Heart Failure Rat.

    PubMed

    Akinwumi, Bolanle C; Raj, Pema; Lee, Danielle I; Acosta, Crystal; Yu, Liping; Thomas, Samuel M; Nagabhushanam, Kalyanam; Majeed, Muhammed; Davies, Neal M; Netticadan, Thomas; Anderson, Hope D

    2017-02-01

    Stilbenoids are bioactive polyphenols, and resveratrol (trans-3,5,40-trihydroxystilbene) is a representative stilbenoid that reportedly exerts cardioprotective actions. As resveratrol exhibits low oral bioavailability, we turned our attention to other stilbenoid compounds with a history of medicinal use and/or improved bioavailability. We determined the effects of gnetol (trans-3,5,20,60-tetrahydroxystilbene) and pterostilbene (trans-3,5-dimethoxy-40-hydroxystilbene) on cardiac hypertrophy. In vitro, gnetol and pterostilbene prevented endothelin-1-induced indicators of cardiomyocyte hypertrophy including cell enlargement and protein synthesis. Gnetol and pterostilbene stimulated AMP-activated protein kinase (AMPK), and inhibition of AMPK, using compound C or shRNA knockdown,abolished these anti-hypertrophiceffects. In contrast,resveratrol, gnetol, nor pterostilbene reduced blood pressure or hypertrophy in the spontaneously hypertensive heart failure (SHHF) rat. In fact, AMPK levels were similar between Sprague-Dawley and SHHF rats whether treated by stilbenoids or not. These data suggest that the anti-hypertrophic actions of resveratrol (and other stilbenoids?) do not extend to the SHHF rat, which models heart failure superimposed on hypertension. Notably, SHHF rat hearts exhibited prolonged isovolumic relaxationtime(an indicator of diastolicdys function),and this was improved by stilbenoid treatment.In conclusion, stilbenoid-based treatment as a viable strategy to prevent pathological cardiac hypertrophy,a major risk factor for heart failure,may be context-dependent and requires furtherstudy.

  3. EFFECTS OF INSTILLED EMISSION PARTICULATE MATTER ON ELECTROCARDIOGRAPHIC INDICES AND HEART RATE VARIABILITY (HRV) IN SPONTANEOUSLY HYPERTENSIVE RATS

    EPA Science Inventory

    EFFECTS OF INSTILLED EMISSION PARTICULATE MATTER (EPM) ON ELECTROCARDIOGRAPHIC INDICES AND HEART RATE VARIABILITY (HRV) IN SPONTANEOUSLY HYPERTENSIVE (SH) RATS. L.B. Wichers1, J.P. Nolan2, W.H. Rowan2, M.J. Campen3, T.P. Jenkins4, D.L. Costa2, and W.P. Watkinson2. 1UNC SPH, Chap...

  4. Fatty Acid Chain Elongation in Palmitate-perfused Working Rat Heart

    PubMed Central

    Kerner, Janos; Minkler, Paul E.; Lesnefsky, Edward J.; Hoppel, Charles L.

    2014-01-01

    Rat hearts were perfused with [1,2,3,4-13C4]palmitic acid (M+4), and the isotopic patterns of myocardial acylcarnitines and acyl-CoAs were analyzed using ultra-HPLC-MS/MS. The 91.2% 13C enrichment in palmitoylcarnitine shows that little endogenous (M+0) palmitate contributed to its formation. The presence of M+2 myristoylcarnitine (95.7%) and M+2 acetylcarnitine (19.4%) is evidence for β-oxidation of perfused M+4 palmitic acid. Identical enrichment data were obtained in the respective acyl-CoAs. The relative 13C enrichment in M+4 (84.7%, 69.9%) and M+6 (16.2%, 17.8%) stearoyl- and arachidylcarnitine, respectively, clearly shows that the perfused palmitate is chain-elongated. The observed enrichment of 13C in acetylcarnitine (19%), M+6 stearoylcarnitine (16.2%), and M+6 arachidylcarnitine (17.8%) suggests that the majority of two-carbon units for chain elongation are derived from β-oxidation of [1,2,3,4-13C4]palmitic acid. These data are explained by conversion of the M+2 acetyl-CoA to M+2 malonyl-CoA, which serves as the acceptor for M+4 palmitoyl-CoA in chain elongation. Indeed, the 13C enrichment in mitochondrial acetyl-CoA (18.9%) and malonyl-CoA (19.9%) are identical. No 13C enrichment was found in acylcarnitine species with carbon chain lengths between 4 and 12, arguing against the simple reversal of fatty acid β-oxidation. Furthermore, isolated, intact rat heart mitochondria 1) synthesize malonyl-CoA with simultaneous inhibition of carnitine palmitoyltransferase 1b and 2) catalyze the palmitoyl-CoA-dependent incorporation of 14C from [2-14C]malonyl-CoA into lipid-soluble products. In conclusion, rat heart has the capability to chain-elongate fatty acids using mitochondria-derived two-carbon chain extenders. The data suggest that the chain elongation process is localized on the outer surface of the mitochondrial outer membrane. PMID:24558043

  5. Early development of intracellular calcium cycling defects in intact hearts of spontaneously hypertensive rats

    PubMed Central

    Kapur, Sunil; Aistrup, Gary L.; Sharma, Rohan; Kelly, James E.; Arora, Rishi; Zheng, Jiabo; Veramasuneni, Mitra; Kadish, Alan H.; Balke, C. William

    2010-01-01

    Defects in excitation-contraction coupling have been reported in failing hearts, but little is known about the relationship between these defects and the development of heart failure (HF). We compared the early changes in intracellular Ca2+ cycling to those that underlie overt pump dysfunction and arrhythmogenesis found later in HF. Laser-scanning confocal microscopy was used to measure Ca2+ transients in myocytes of intact hearts in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs) at different ages. Early compensatory mechanisms include a positive inotropic effect in SHRs at 7.5–9 mo compared with 6 mo. Ca2+ transient duration increased at 9 mo in SHRs, indicating changes in Ca2+ reuptake during decompensation. Cell-to-cell variability in Ca2+ transient duration increased at 7.5 mo, decreased at 9 mo, and increased again at 22 mo (overt HF), indicating extensive intercellular variability in Ca2+ transient kinetics during disease progression. Vulnerability to intercellular concordant Ca2+ alternans increased at 9–22 mo in SHRs and was mirrored by a slowing in Ca2+ transient restitution, suggesting that repolarization alternans and the resulting repolarization gradients might promote reentrant arrhythmias early in disease development. Intercellular discordant and subcellular Ca2+ alternans increased as early as 7.5 mo in SHRs and may also promote arrhythmias during the compensated phase. The incidence of spontaneous and triggered Ca2+ waves was increased in SHRs at all ages, suggesting a higher likelihood of triggered arrhythmias in SHRs compared with WKY rats well before HF develops. Thus serious and progressive defects in Ca2+ cycling develop in SHRs long before symptoms of HF occur. Defective Ca2+ cycling develops early and affects a small number of myocytes, and this number grows with age and causes the transition from asymptomatic to overt HF. These defects may also underlie the progressive susceptibility to Ca2+ alternans and Ca2+ wave

  6. [CA²⁺ ACCUMULATION IN ISOLATED RAT HEART MITOCHONDRIA UNDER MAINTENANCE OF MITOCHONDRIAL POTENTIAL].

    PubMed

    Budko, A Yu; Strutynska, N A; Okhay, I Yu; Semenykhina, O M; Sagach, V F

    2015-01-01

    It is known that mitochondria can accumulate calcium, which regulates energy metabolism and cell death. About 90% of energy of cardiomyocytes is synthesized in mitochondria. Heart cells are also affected by the rapid changes in the Ca²⁺ concentration in the cytoplasm. Therefore, mitochondrial Ca²⁺-accumulation ability is crucial. The aim of our work was to study the accumulation of Ca²⁺ in isolated rat heart mitochondria in the presence of mitochondrial potential and different extramitochondrial Ca²⁺ concentrations. Isolated organelles were loaded with fluorescent dye Fluo-4 AM (2.5 μmol/l) at a temperature of 26°C for 30 min. It has been revealed that under these conditions high mitochondrial potential was maintained sufficiently, which is necessary for the functioning of the calcium transporting system in organelles. We established that mitochondria have a limited ability to store ionized calcium, as addition of Ca²⁺ ion in concentrations of 10, 20, 50 µmol/l ensures a certain level of accumulation in organelles with further fluorescent signal growth cessation. Addition of 100 µmol/Ca²⁺ to isolated mitochondria resulted in a significant increase in fluorescence intensity (46% in the fifth minute, compared to the fluorescence when 20 µmol/l Ca²⁺ was added) and likely to activation of cation release. It was shown that ruthenium red (10⁻⁵ mol/l), an inhibitor of Ca²⁺-uniporter, prevented accumulation of calcium ions in organelles by 89%, in the presence of 100 µmol/ Ca²⁺. It was clearly seen that heart mitochondria require Mg²⁺-ATP complex (3 mmol/l) to accumulate Ca²⁺, likely to maintain the inner membrane potential, activity of Ca²⁺ uniporter and energetic processes in organelles. Thus, the process of Ca²⁺ accumulation in rat heart mitochondria requires the maintenance of mitochondrial potential, activity of Ca²⁺-uniporter, depends on extramitochondrial Ca²⁺ concentration and presence of Mg²⁺-ATP complex.

  7. Nuclear pore rearrangements and nuclear trafficking in cardiomyocytes from rat and human failing hearts

    PubMed Central

    Chahine, Mirna N.; Mioulane, Maxime; Sikkel, Markus B.; O'Gara, Peter; Dos Remedios, Cristobal G.; Pierce, Grant N.; Lyon, Alexander R.; Földes, Gábor; Harding, Sian E.

    2015-01-01

    Aims During cardiac hypertrophy, cardiomyocytes (CMs) increase in the size and expression of cytoskeletal proteins while reactivating a foetal gene programme. The process is proposed to be dependent on increased nuclear export and, since nuclear pore trafficking has limited capacity, a linked decrease in import. Our objective was to investigate the role of nuclear import and export in control of hypertrophy in rat and human heart failure (HF). Methods and results In myocardial tissue and isolated CMs from patients with dilated cardiomyopathy, nuclear size was increased; Nucleoporin p62, cytoplasmic RanBP1, and nuclear translocation of importins (α and β) were decreased while Exportin-1 was increased. CM from a rat HF model 16 weeks after myocardial infarction (MI) reproduced these nuclear changes. Nuclear import, determined by the rate of uptake of nuclear localization sequence (NLS)-tagged fluorescent substrate, was also decreased and this change was observed from 4 weeks after MI, before HF has developed. Treatment of isolated rat CMs with phenylephrine (PE) for 48 h produced similar cell and nuclear size increases, nuclear import and export protein rearrangement, and NLS substrate uptake decrease through p38 MAPK and HDAC-dependent pathways. The change in NLS substrate uptake occurred within 15 min of PE exposure. Inhibition of nuclear export with leptomycin B reversed established nuclear changes in PE-treated rat CMs and decreased NLS substrate uptake and cell/nuclear size in human CMs. Conclusions Nuclear transport changes related to increased export and decreased import are an early event in hypertrophic development. Hypertrophy can be prevented, or even reversed, by targeting import/export, which may open new therapeutic opportunities. PMID:25341891

  8. Long-term caloric restriction reduces metabolic rate and heart rate under cool and thermoneutral conditions in FBNF1 rats.

    PubMed

    Knight, W David; Witte, M M; Parsons, A D; Gierach, M; Overton, J Michael

    2011-05-01

    The long-term metabolic and cardiovascular responses to caloric restriction (CR) are poorly understood. We examined the responses to one year of CR in FBNF1 rats housed in cool (COOL; T(a)=15 °C) or thermoneutral (TMN; T(a)=30 °C) conditions. Rats were acclimated to COOL or TMN for 2 months, instrumented for cardiovascular telemetry and studied in calorimeters. Baseline caloric intake, oxygen consumption (VO(2)), mean arterial blood pressure (MAP), and heart rate (HR) were determined prior to assignment to ad lib (AL) or CR groups (30-40% CR) within each T(a) (n = 8). Groups of rats were studied after 10 weeks CR, one year CR, and after 4 days of re-feeding. Both 10 weeks and one year of CR reduced HR and VO(2) irrespective of T(a). Evaluation of the relationship between metabolic organ mass (liver, heart, brain, and kidney mass) and energy expenditure revealed a clear shift induced by CR to reduce expenditure per unit metabolic mass in both COOL and TMN groups. Re-feeding resulted in prompt elevations of HR and VO(2) to levels observed in control rats. These findings are consistent with the hypothesis that long term CR produces sustained reductions in metabolic rate and heart rate in rats.

  9. Contribution of depressed reuptake to the depletion of norepinephrine from rat heart and spleen during endotoxin shock

    SciTech Connect

    Pardini, B.J.; Jones, S.B.; Filkins, J.P.

    1982-01-01

    Norepinephrine content (microgram/g) was depressed in hearts and spleens of fasted male Holtzman rats treated intravenously with Salmonella enteritidis lipopolysaccharide (14-17 mg/kg). To investigate the mechanism of norepinephrine depletion during endotoxicosis, in vivo norepinephrine reuptake was evaluated in control and severely shocked rats using the incorporation of /sup 3/H-norepinephrine into hearts and spleens. Incorporation of /sup 3/H-norepinephrine into spleens of endotoxic rats was reduced 88%. In contrast, cardiac tissue incorporation of /sup 3/H-norepinephrine was not significantly impaired. In vitro analysis of total norepinephrine retained in cardiac and splenic tissue slices incubated with /sup 3/H-norepinephrine yielded results consistent with in vivo experiments: Splenic norepinephrine reuptake was significantly decreased on the order of 50% in preparations from endotoxic rats, while myocardial norepinephrine reuptake was the same in both groups. The results indicate that depression of norepinephrine reuptake is a mechanism of norepinephrine depletion in spleens but not hearts of endotoxic rats.

  10. Training differentially regulates elastin level and proteolysis in skeletal and heart muscles and aorta in healthy rats

    PubMed Central

    Gilbert, Anna; Wyczalkowska-Tomasik, Aleksandra; Zendzian-Piotrowska, Malgorzata; Czarkowska-Paczek, Bozena

    2016-01-01

    ABSTRACT Exercise induces changes in muscle fibers and the extracellular matrix that may depend on elastin content and the activity of proteolytic enzymes. We investigated the influence of endurance training on the gene expression and protein content and/or activity of elastin, elastase, cathepsin K, and plasmin in skeletal and heart muscles and in the aorta. Healthy rats were randomly divided into untrained (n=10) and trained (n=10; 6 weeks of endurance training with increasing load) groups. Gene expression was evaluated via qRT-PCR. Elastin content was measured via enzyme-linked immunosorbent assay and enzyme activity was measured fluorometrically. Elastin content was significantly higher in skeletal (P=0.0014) and heart muscle (P=0.000022) from trained rats versus untrained rats, but not in the aorta. Although mRNA levels in skeletal muscle did not differ between groups, the activities of elastase (P=0.0434), cathepsin K (P=0.0343) and plasmin (P=0.000046) were higher in trained rats. The levels of cathepsin K (P=0.0288) and plasminogen (P=0.0005) mRNA were higher in heart muscle from trained rats, but enzyme activity was not. Enzyme activity in the aorta did not differ between groups. Increased elastin content in muscles may result in better adaption to exercise, as may remodeling of the extracellular matrix in skeletal muscle. PMID:27069251

  11. Effects of High Intensity Interval Training on Pregnant Rats, and the Placenta, Heart and Liver of Their Fetuses

    PubMed Central

    Hafstad, Anne Dragøy; Basnet, Purusotam; Ytrehus, Kirsti; Acharya, Ganesh

    2015-01-01

    Objective To investigate the effects of high intensity interval training (HIIT) on the maternal heart, fetuses and placentas of pregnant rats. Methods Female Sprague-Dawley rats were randomly assigned to HIIT or sedentary control groups. The HIIT group was trained for 6 weeks with 10 bouts of high intensity uphill running on a treadmill for four minutes (at 85–90% of maximal oxygen consumption) for five days/week. After three weeks of HIIT, rats were mated. After six weeks (gestational day 20 in pregnant rats), echocardiography was performed to evaluate maternal cardiac function. Real-time PCR was performed for the quantification of gene expression, and oxidative stress and total antioxidant capacity was assessed in the tissue samples. Results Maternal heart weight and systolic function were not affected by HIIT or pregnancy. In the maternal heart, expression of 11 of 22 genes related to cardiac remodeling was influenced by pregnancy but none by HIIT. Litter size, fetal weight and placental weight were not affected by HIIT. Total antioxidant capacity, malondialdehyde content, peroxidase and superoxide dismutase activity measured in the placenta, fetal heart and liver were not influenced by HIIT. HIIT reduced the expression of eNOS (p = 0.03), hypoxia-inducible factor 1α (p = 0.04) and glutathione peroxidase 4.2 (p = 0.02) in the fetal liver and increased the expression of vascular endothelial growth factor-β (p = 0.014), superoxide dismutase 1 (p = 0.001) and tissue inhibitor of metallopeptidase 3 (p = 0.049) in the fetal heart. Conclusions Maternal cardiac function and gene expression was not affected by HIIT. Although HIIT did not affect fetal growth, level of oxidative stress and total antioxidant capacity in the fetal tissues, some genes related to oxidative stress were altered in the fetal heart and liver indicating that protective mechanisms may be activated. PMID:26566220

  12. Endurance training induces fiber type-specific revascularization in hindlimb skeletal muscles of rats with chronic heart failure

    PubMed Central

    Ranjbar, Kamal; Ardakanizade, Malihe; Nazem, Farzad

    2017-01-01

    Objective(s): Previous studies showed that skeletal muscle microcirculation was reduced in chronic heart failure. The aim of this study was to investigate the effects of endurance training on capillary and arteriolar density of fast and slow twitch muscles in rats with chronic heart failure. Materials and Methods: Four weeks after surgeries (left anterior descending (LAD) artery occlusion), chronic heart failure rats were divided into 3 groups: Sham (Sham, n=10); Sedentary (Sed, n=10); Exercise training (Ex, n=10). Ex group rats were subjected to endurance training in the form of treadmill running with moderate intensity for 10 weeks. Results: Exercise training significantly increased capillary density and capillary to fiber ratio (P<0.05) in slow twitch muscle, but didn’t change fast twitch muscle capillary density and capillary to fiber ratio. Furthermore, arteriolar density in fast twitch muscle increased remarkably (P<0.05) in response to training, but slow twitch muscle arteriolar density did not change in response to exercise in chronic heart failure rats. HIF-1 increased (P<0.01) but VEGF and FGF-2 mRNA did not change in slow twitch muscle after training. In fast twitch muscle, HIF-1 mRNA increased (P<0.05), and VEGF and angiostatin decreased (P<0.01) significantly after training. Conclusion: Endurance training ameliorates fast and slow twitch muscle revascularization non-uniformly in chronic heart failure rats by increasing capillary density in slow twitch muscle and arteriolar density in fast twitch muscle. The difference in revascularization at slow and fast twitch muscles may be induced by the difference in angiogenic and angiostatic gene expression response to endurance training. PMID:28133530

  13. Beneficial effect of zinc chloride and zinc ionophore pyrithione on attenuated cardioprotective potential of preconditioning phenomenon in STZ-induced diabetic rat heart.

    PubMed

    Jamwal, Sumit; Kumar, Kushal; Reddy, B V Krishna

    2016-05-01

    Ischemic preconditioning (IPC) is well demonstrated to produce cardioprotection by phosphorylation and subsequent inactivation of glycogen synthase kinase-3β (GSk-3β) in the normal rat heart, but its effect is attenuated in the diabetic rat heart. This study was designed to investigate the effect of zinc chloride and zinc ionophore pyrithione (ZIP) on the attenuated cardioprotective potential of IPC in the diabetic rat heart. Diabetes mellitus (DM) was induced by a single intraperitoneal administration of streptozotocin (STZ) (50 mg/kg; i.p). The isolated perfused rat heart was subjected to 30 minutes of ischemia followed by 120 minutes of reperfusion. Myocardial infarct size was estimated by triphenyltetrazolium chloride (TTC) staining and cardiac injury was measured by estimating lactate dehydrogenase (LDH) and creatine kinase-MB (CK-MB) in the coronary effluent. Also, GSK-3β was measured and neutrophil accumulation was measured by estimating myeloperoxidase (MPO) levels. IPC significantly decreased the myocardial infarct size, the release of LDH and CK-MB, the GSK-3β levels and the MPO levels in the normal rat heart. Pre- and post-ischemic treatment with zinc chloride and zinc ionophore pyrithione (ZIP) in the normal and diabetic rat hearts significantly decreased the myocardial infarct size, the level of CK-MB and LDH in the coronary effluent and GSK-3β and MPO levels. Our results suggest that pharmacological preconditioning with zinc chloride and ZIP significantly restored the attenuated cardioprotective potential of IPC in the diabetic rat heart.

  14. 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.

  15. Mass isotopomer study of anaplerosis from propionate in the perfused rat heart

    PubMed Central

    Kasumov, Takhar; Cendrowski, Andrea V.; David, France; Jobbins, Kathryn A.; Anderson, Vernon E.; Brunengraber, Henri

    2007-01-01

    Anaplerosis from propionate was investigated in rat hearts perfused with 0–2 mM [13C3]propionate and physiological concentrations of glucose, lactate and pyruvate. The data show that when the concentration of [13C3]propionate was raised from 0 to 2 mM, total anaplerosis increases from 5 to 16% of the turnover of citric acid cycle intermediates. Then, [13C3]propionate abolished anaplerosis from endogenous substrates, glucose, lactate and pyruvate. Also, while the contents of propionyl-CoA and methylmalonyl-CoA increased with [13C3]propionate concentration, the content of succinyl-CoA decreased, presumably via activation of succinyl-CoA hydrolysis by a decrease in free CoA. Under our conditions, [13C3]propionate was a purely anaplerotic substrate since there was no labeling of mitochondrial acetyl-CoA, reflected by the labeling of the acetyl moiety of citrate. PMID:17418801

  16. Acute and nongenomic effects of testosterone on isolated and perfused rat heart.

    PubMed

    Ceballos, G; Figueroa, L; Rubio, I; Gallo, G; Garcia, A; Martinez, A; Yañez, R; Perez, J; Morato, T; Chamorro, G

    1999-05-01

    Gonadal steroid hormones influence vascular tone and the development of hypertension. There are sex differences in the incidence of cardiovascular diseases, and great attention has been placed on the study of estrogen cardiovascular effects. However, there are only a few reports on the effects of testosterone on the vasculature. It is commonly accepted that the mechanism of the action of steroid hormones on target tissues is mediated through the binding of hormones to cytoplasmic or nuclear receptors. However, some studies indicate that steroid action can be extremely rapid and therefore unlikely to be through a genomic mechanism. The purpose of this study was to assess the effect of intravascularly confined testosterone on an isolated rat heart to demonstrate acute and possibly nongenomic effects of the steroid. Our results show that testosterone blocked the adenosine vasodilator effect and increased vascular resistance, even when its presence was restricted to the coronary vascular lumen. These effects were exerted rapidly and possibly through nongenomic mechanisms.

  17. Diesel Exhaust Inhalation Increases Cardiac Output, Bradyarrhythmias, and Parasympathetic Tone in Aged Heart Failure–Prone Rats

    PubMed Central

    Farraj, Aimen K.

    2013-01-01

    Acute air pollutant inhalation is linked to adverse cardiac events and death, and hospitalizations for heart failure. Diesel engine exhaust (DE) is a major air pollutant suspected to exacerbate preexisting cardiac conditions, in part, through autonomic and electrophysiologic disturbance of normal cardiac function. To explore this putative mechanism, we examined cardiophysiologic responses to DE inhalation in a model of aged heart failure–prone rats without signs or symptoms of overt heart failure. We hypothesized that acute DE exposure would alter heart rhythm, cardiac electrophysiology, and ventricular performance and dimensions consistent with autonomic imbalance while increasing biochemical markers of toxicity. Spontaneously hypertensive heart failure rats (16 months) were exposed once to whole DE (4h, target PM2.5 concentration: 500 µg/m3) or filtered air. DE increased multiple heart rate variability (HRV) parameters during exposure. In the 4h after exposure, DE increased cardiac output, left ventricular volume (end diastolic and systolic), stroke volume, HRV, and atrioventricular block arrhythmias while increasing electrocardiographic measures of ventricular repolarization (i.e., ST and T amplitudes, ST area, T-peak to T-end duration). DE did not affect heart rate relative to air. Changes in HRV positively correlated with postexposure changes in bradyarrhythmia frequency, repolarization, and echocardiographic parameters. At 24h postexposure, DE-exposed rats had increased serum C-reactive protein and pulmonary eosinophils. This study demonstrates that cardiac effects of DE inhalation are likely to occur through changes in autonomic balance associated with modulation of cardiac electrophysiology and mechanical function and may offer insights into the adverse health effects of traffic-related air pollutants. PMID:23047911

  18. Continuous Monitoring of Intracellular Volumes in Isolated Rat Hearts during Normothermic Perfusion and Ischemia

    NASA Astrophysics Data System (ADS)

    Askenasy, Nadir; Navon, Gil

    1997-01-01

    The present study describes an experimental setup that enables continuous measurement of cellular volumes in isolated organs. The procedure is a modification of a recently reported method that uses multinuclear NMR measured by59Co NMR of cobalticyanide and1H NMR of water in isolated rat hearts at normothermia. The new apparatus contains a background flow which is shown to improve the rate of exchange of the marker between the interstitium and the external solution and allows detection of cellular shrinkage during no-flow ischemia. A series of experiments of marker loading and wash-out were performed to validate the method. In the Langendorff preparation, intracellular volumes (in units of milliliters per gram dry weight) of hearts perfused with Krebs-Henseleit solution oscillated around a mean value of 2.50 ± 0.06 ml/gdw. During 30 min of ischemia the cells swelled to 2.88 ± 0.08 ml/gdw and residual edema was observed after 30 min of reperfusion (2.62 ± 0.08 ml/gdw). A hypoosmotic shock was used to assess changes in membrane permeability at different time points of ischemia and reperfusion. Water influx induced by the hypoosmotic shock at the end of ischemia was similar to that elicited in perfused hearts. After 15 and 30 min of reperfusion, the magnitude of the response to hypoosmolarity decreased by 9 and 37%, respectively, indicating a gradual permeabilization of the membranes, presumably to ions. The experimental setup was also used to monitor intracellular volumes as a function of time in anisoosmotic conditions. Cellular swelling/shrinkage were delayed for periods of 5 and 8 min at osmolarities of ±50 and ±100 mosmol/liter, suggesting a limited capability of the heart to absorb an anisoosmotic shock. The variation in cellular volumes was proportional to the deviation of the conditions from isoosmolarity, and activation of volume-regulatory mechanisms was demonstrated. The noninvasive technique presented in this study is capable of providing quantitative

  19. 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.

  20. 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.

  1. Protective effect of Co-enzyme Q10 On doxorubicin-induced cardiomyopathy of rat hearts.

    PubMed

    Chen, Pei-Yu; Hou, Chien-Wen; Shibu, Marthandam Asokan; Day, Cecilia Hsuan; Pai, Peiying; Liu, Zhao-Rong; Lin, Tze-Yi; Viswanadha, Vijaya Padma; Kuo, Chia-Hua; Huang, Chih-Yang

    2017-02-01

    Q10 is a powerful antioxidant often used in medical nutritional supplements for cancer treatment. This study determined whether Q10 could effectively prevent cardio-toxicity caused by doxorubicin treatment. Four week old SD rats were segregated into groups namely control, doxorubicin group (challenged with doxorubicin), Dox + Q10 group (with doxorubicin challenge and oral Q10 treatment), and Q10 group (with oral Q10 treatment). Doxorubicin groups received IP doxorubicin (2.5 mg/kg) every 3 days and Q10 groups received Q10 (10 mg/kg) every day. Three weeks of doxorubicin challenge caused significant reduction in heart weight, disarray in cardiomyocyte arrangement, elevation of collagen accumulation, enhancement of fibrosis and cell death associated proteins, and inhibition of survival proteins. However, Q10 effectively protected cardiomyocytes and ameliorated fibrosis and cell death induced by doxorubicin. Q10 is, therefore, evidently a potential drug to prevent heart damage caused by doxorubicin. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 679-689, 2017.

  2. Uptake of perfusion imaging agents by transplanted hearts: an experimental study in rats

    SciTech Connect

    Bergsland, J.; Carr, E.A. Jr.; Carroll, M.; Feldman, M.J.; Kung, H.; Wright, J.R.

    1989-02-01

    There is a need for a reliable noninvasive marker of rejection in transplanted hearts. Endomyocardial biopsy is now the universally accepted diagnostic method of choice, but the invasiveness of the procedure and the limited size of the sample obtained makes this method far from ideal. As coronary blood flow may be expected to decrease during acute rejection, there has been interest in thallium-201 chloride (T1), a perfusion marker, as an imaging agent for diagnosing cardiac rejection. Hexakis(t-butylisonitrile)-technetium (Tc-TBI) is a representative of a new class of radiopharmaceuticals proposed as perfusion markers. We have compared the uptake of these imaging agents in a rat model of cardiac transplantation. Uptake of Tc-TBI as well as of T1 was significantly lower in rejecting than in nonrejecting hearts. This change was found in both left (LV) and right (RV) ventricles. Allografts in animals treated with cyclosporine (CyA) showed less severe rejection and higher uptakes of both imaging agents as compared to unmodified rejection. Our results suggest that perfusion imaging with these radionuclides is a potentially useful approach to the problem of detecting allograft rejection.

  3. Reduction of calcium channel antagonist binding sites by oxygen free radicals in rat heart.

    PubMed

    Kaneko, M; Lee, S L; Wolf, C M; Dhalla, N S

    1989-09-01

    In view of the importance of Ca2+-channels in controlling the entry of Ca2+ into the myocardium, this study was undertaken to examine the effects of oxygen free radicals on the binding of Ca2+-channel antagonists in rat heart by employing [3H]-nitrendipine as a ligand. Isolated heart membranes were incubated with xanthine + xanthine oxidase (a superoxide anion radicals generating system), hydrogen peroxide (an activated species of oxygen), or hydrogen peroxide + Fe2+ (a hydroxyl radicals generating system). The assay of the [3H]-nitrendipine binding activity revealed that the maximal number of binding sites (Bmax) were reduced in a time-dependent manner by superoxide radicals without any changes in the binding constant (Kd); a significant reduction of Bmax was seen after incubating membranes with xanthine + xanthine oxidase for a 10-min-period. Superoxide dismutase showed a protective effect on the superoxide radicals induced reduction in Bmax. Both hydrogen peroxide and hydroxyl radicals also depressed the Bmax for [3H]-nitrendipine binding without any significant change in Kd; catalase and mannitol showed protective effects on hydrogen peroxide or hydroxyl radicals induced depression in Bmax, respectively. These results indicate that oxygen free radicals may reduce the number of Ca2+-channels in the cell membrane and this change may contribute towards decreasing the voltage-dependent Ca2+ influx in the cardiac cell.

  4. Loss of microvascular negative charges accompanied by interstitial edema in septic rats' heart.

    PubMed

    Gotloib, L; Shostak, A; Galdi, P; Jaichenko, J; Fudin, R

    1992-01-01

    We studied the effect of Gram-negative sepsis on negative charges of heart capillaries and myocardial cells. We used a rat model of multiorgan failure, with ruthenium red (RR) and polyethyleneimine (PEI) as cationic binding tracers. Twenty-four hours after induction of sepsis, negative charges had decreased in glycocalyx and basement membrane of myocardial capillary endothelial cells. There were substantial amounts of interstitial edema. Density of anionic charges in the sarcolemmal glycocalyx complex of cardiac cells was markedly reduced. Myocardial cells' mitochondria consistently showed morphologic changes, whose severity ranged between stages II and IV C of Trump. Thirteen days after induction of sepsis, capillary endothelial and myocardial cells had recovered almost completely and showed no intracellular edema. Gram-negative sepsis caused a significant reduction in negative charges normally present in the microvascular wall as well as on myocardial cells. Consequently, several membranes limiting the various compartments of heart tissue lost their structural integrity. This morphometric data could explain the development of protein-rich interstitial edema and defective cell volume regulation observed in cardiac muscle of endotoxin-shocked animals. This myocardial edema may be at the origin of the cardiac dysfunction observed in both experimental and human septic shock.

  5. Age-associated changes in basal c-fos transcription factor binding activity in rat hearts.

    PubMed

    Tsou, H; Azhar, G; Lu, X G; Kovacs, S; Peacocke, M; Wei, J Y

    1996-12-15

    The early response proto-oncogene c-fos is expressed at very low levels in the mammalian heart at baseline. To further investigate the mechanism of altered c-fos expression with age, we studied in the basal state the binding of five transcription proteins to their cognate sites in the c-fos promoter/enhancer region, in adult and old F344 rats. Our results show a reduced binding of E2F and AP1 proteins to the c-fos promoter in aging hearts. The major calcium/cyclic AMP response element (CRE) and SP1 binding was unchanged. The only increase seen with age was in the serum response element (SRE) binding proteins. SRE is the point of convergence of different signal transduction pathways (via MAP kinases and the Rho family of GTPases) at the c-fos promoter. Increased SRE binding may reflect a compensation for a decreased binding of other transcription proteins to the c-fos promoter, alteration in the phosphorylation status of SRF, or a change in the ternary complex factors Elk 1 or SAP 1. Other possibilities include defects in the signal transduction pathways with aging, which combine to produce an overall negative balance in the function of the c-fos promoter despite the increased SRE binding activity. Both in vitro and in vivo experiments have shown decreased c-fos expression with age. This may be due partly to alterations in the basal levels of transcription factor binding.

  6. Some factors affecting phosphate transport in a perfused rat heart preparation.

    PubMed Central

    Medina, G; Illingworth, J

    1980-01-01

    Pi uptake by a perfused rat heart preparation did not require the presence of any other permeant anion, but was markedly dependent on the extracellular Na+ concentration and accelerated when tissue oxygenation was inadequate. Pi efflux was also independent of other permeant anions, but apparently varied with the intracellular Na+ concentration. Cardiac Pi efflux was not sensitive to a number of inhibitors that clock Cl- movement in heart and other tissues. Both uptake and efflux apparently proceed via a reversible electroneutral co-transport system linked to the transmembrane Na+ gradient. Pi uptake was independent of cardiac work load, but the efflux rate was sharply accelerated after an increase in aortic pressure development, with a slow return towards basal values during sustained periods of high work output. An inverted biphasic effect on the efflux rate was observed after a reduction in cardiac work load. Mild hypoxia and respiratory and metabolic acidosis each resulted in a transient acceleration of Pi efflux followed by a return towards basal values during prolonged exposure to the stimulus, whereas respiratory and metabolic alkalosis produced a similar but inverted response. The origin of these phasic effects on Pi efflux remains to be identified at present. PMID:7396864

  7. Mitochondrial function in heart and kidney of spontaneously hypertensive rats: influence of captopril treatment.

    PubMed

    Mujkosová, Jana; Ulicná, Olga; Waczulíková, Iveta; Vlkovicová, Jana; Vancová, Ol'ga; Ferko, Miroslav; Polák, Stefan; Ziegelhöffer, Attila

    2010-06-01

    Effect of captopril treatment on capability of heart and kidney mitochondria to produce ATP was investigated in spontaneously hypertensive rats (SHR). Heart mitochondria from SHR responded to hypertension with tendency to compensate the elevated energy demands of cardiac cells by moderate increase in mitochondrial Mg2+-ATPase activity, membrane fluidity (MF) and in majority of functional parameters of the mitochondria (p>0.05). Significant increase exhibited only the oxygen consumption (QO2; p<0.01-0.001) and oxidative phosphorylation rate (OPR; p<0.003) with glutamate+malate (GLUT+MAL) as substrates. Lowering the blood pressure (p<0.02) captopril also eliminated the above compensatory response and impaired the oxidative ATP production by decreasing OPR (p<0.001). Kidney mitochondria of SHR experienced serious disarrangement in parameters of oxidative ATP production: increase in Mg2+-ATPase activity (p<0.05) but, also scattered QO2 values (p<0.03-0.01) leading to decrease in OPR and the ADP:O (p<0.05-0.01) values with both GLUT+MAL and succinate as substrates. Captopril treatment does not alleviated but even worsened the above alterations. Mg2+-ATPase became also decreased and the depression of ADP:O became aggravated (p<0.0001).

  8. Chronic arteriovenous shunt: evaluation of a model for heart failure in rat.

    PubMed

    Flaim, S F; Minteer, W J; Nellis, S H; Clark, D P

    1979-05-01

    A model for high output heart failure (HCO) was developed in male, Sprague-Dawley rats using an abdominal aortocaval shunt equal to 50% of total cardiac output (CO) with 2 mo of postsurgical recovery. The model was evaluated by analysis of hemodynamics, peripheral blood flows (BF) (radioactive microspheres), and plasma catecholamine levels as well as mass and fluid content of organs. In HCO, CO and left ventricular end-diastolic pressure were increased with significant left and right ventricular hypertrophy. Mean blood pressure (BP) was unchanged, but pulse BP was increased in HCO. BF to skeletal muscle, cutaneous, and some splanchnic regions was reduced to HCO, whereas BF to the cerebral, coronary, and renal beds was protected. Plasma epinephrine and norepinephrine levels were significantly elevated in HCO suggesting enhanced sympathetic as well as adrenal catecholamine release. Tissue analysis indicated altered circulatory status secondary to HCO in liver, kidney, spleen, and lung. The results indicate that this model will be a relevant tool for studies of the circulatory effects of heart failure.

  9. Pregnancy Differentially Regulates the Collagens Types I and III in Left Ventricle from Rat Heart

    PubMed Central

    Limon-Miranda, Sarai; Salazar-Enriquez, Diana G.; Muñiz, Jesus; Ramirez-Archila, Mario V.; Sanchez-Pastor, Enrique A.; Andrade, Felipa; Soñanez-Organis, Jose G.; Moran-Palacio, Edgar F.; Virgen-Ortiz, Adolfo

    2014-01-01

    The pathologic cardiac remodeling has been widely documented; however, the physiological cardiac remodeling induced by pregnancy and its reversion in postpartum are poorly understood. In the present study we investigated the changes in collagen I (Col I) and collagen III (Col III) mRNA and protein levels in left ventricle from rat heart during pregnancy and postpartum. Col I and Col III mRNA expression in left ventricle samples during pregnancy and postpartum were analyzed by using quantitative PCR. Data obtained from gene expression show that Col I and Col III in left ventricle are upregulated during pregnancy with reversion in postpartum. In contrast to gene expression, the protein expression evaluated by western blot showed that Col I is downregulated and Col III is upregulated in left ventricle during pregnancy. In conclusion, the pregnancy differentially regulates collagens types I and III in heart; this finding could be an important molecular mechanism that regulates the ventricular stiffness in response to blood volume overload present during pregnancy which is reversed in postpartum. PMID:25147829

  10. Pregnancy differentially regulates the collagens types I and III in left ventricle from rat heart.

    PubMed

    Limon-Miranda, Sarai; Salazar-Enriquez, Diana G; Muñiz, Jesus; Ramirez-Archila, Mario V; Sanchez-Pastor, Enrique A; Andrade, Felipa; Soñanez-Organis, Jose G; Moran-Palacio, Edgar F; Virgen-Ortiz, Adolfo

    2014-01-01

    The pathologic cardiac remodeling has been widely documented; however, the physiological cardiac remodeling induced by pregnancy and its reversion in postpartum are poorly understood. In the present study we investigated the changes in collagen I (Col I) and collagen III (Col III) mRNA and protein levels in left ventricle from rat heart during pregnancy and postpartum. Col I and Col III mRNA expression in left ventricle samples during pregnancy and postpartum were analyzed by using quantitative PCR. Data obtained from gene expression show that Col I and Col III in left ventricle are upregulated during pregnancy with reversion in postpartum. In contrast to gene expression, the protein expression evaluated by western blot showed that Col I is downregulated and Col III is upregulated in left ventricle during pregnancy. In conclusion, the pregnancy differentially regulates collagens types I and III in heart; this finding could be an important molecular mechanism that regulates the ventricular stiffness in response to blood volume overload present during pregnancy which is reversed in postpartum.

  11. Label-free detection of myocardial ischaemia in the perfused rat heart by spontaneous Raman spectroscopy

    PubMed Central

    Ohira, Suguru; Tanaka, Hideo; Harada, Yoshinori; Minamikawa, Takeo; Kumamoto, Yasuaki; Matoba, Satoaki; Yaku, Hitoshi; Takamatsu, Tetsuro

    2017-01-01

    Raman spectroscopy, which identifies intrinsic molecular constituents, has a potential for determining myocardial viability under label-free conditions. However, its suitability for evaluating myocardial ischaemia is undetermined. Focusing on cytochromes, i.e., representative molecules reflecting mitochondrial activity, we tested whether Raman spectroscopy is applicable for evaluating myocardial ischaemia especially during early ischaemic phase. We obtained spontaneous Raman spectra of the subepicardial myocardium in the Langendorff-perfused rat heart upon 532-nm excitation before and during the “stopped-flow,” global ischaemia. Semi-quantitative values of the peak intensities at 750 and 1127 cm−1, which reflect reduced cytochromes c and b, increased immediately and progressively after induction of the stopped flow, indicating progressive reduction of the mitochondrial respiration. Such spectral changes emerged before the loss of 1) mitochondrial membrane potentials measured by the fluorescence intensity of tetramethyl rhodamine ethyl ester or 2) staining of the triphenyl tetrazolium chloride dye in the myocardium. The progressive increases in the Raman peaks by stopped flow were significantly retarded by ischaemic preconditioning. Sequential measurements of the peak intensities at 750 and 1127 cm−1 enabled early detection of the myocardial ischaemia based on the mitochondrial functions. These data suggest that Raman spectroscopy offers the potential to evaluate acute ischaemic heart under label-free conditions. PMID:28186163

  12. Effect of graded hypoxia on retention of technetium-99m-nitroheterocycle in perfused rat heart

    SciTech Connect

    Rumsey, W.L.; Patel, B.; Linder, K.E.

    1995-04-01

    The purpose of this investigation was to determine the effects of graded hypoxia on the retention of a {sup 99m}Tc-labeled nitroimidazole. Rat hearts were perfused retrogradely with Krebs-Henseleit buffer at 37{degrees}C and paced at 5 Hz. After a 20-min stabilization period, coronary flow was maintained at 8 ml/min/g wet wt and the hearts were perfused with media equilibrated with gas mixtures containing 5% CO{sub 2} and various levels of O{sub 2}, from 544 to 29 Torr. Technetium-99m-O(PnAO-1-(2-nitroimidazole)), BMS-181321, was infused for 20 min into a side port of the aortic cannula. Perfusion continued for an additional 40 min to allow for compound clearance. Each decrease of perfusate PO{sub 2} brought about an increase in the retention of BMS-181321, resulting in a good correlation between its retention and perfusate PO{sub 2} (r=0.97). Myocardial oxygen consumption was independent of oxygen delivery when the perfusate oxygen pressure was greater than 350 Torr. Below this value, oxygen consumption declined markedly as influent PO{sub 2}. A good correlation was obtained between retention of the nitroheterocycle and the cytosolic lactate/pyruvate ratio (r=0.98). When glucose was omitted from the perfusate (PO{sub 2}=27 Torr), retention of the nitroheterocycle was increased by about 25% as compared to hearts perfused in the presence of this substrate. These results indicate that myocardial retention of BMS-181321 is coupled to the level of tissue oxygenation and that hypoxic retention may be affected by substrate input. 24 refs., 3 figs., 1 tab.

  13. Metabolic context affects hemodynamic response to bupivacaine in the isolated rat heart.

    PubMed

    Edelman, Lucas B; Ripper, Richard; Kelly, Kemba; Di Gregorio, Guido; Weinberg, Guy L

    2008-03-10

    Previous studies have demonstrated that the local anesthetic bupivacaine selectively inhibits oxidative metabolism of fatty acids in isolated cardiac mitochondria. In the present investigation, we compare the development of bupivacaine cardiotoxicity during fatty acid and carbohydrate metabolism. Hearts from adult male Sprague-Dawley rats were excised and retrograde perfused with a solution containing fatty acid (oleate or octanoate) or carbohydrate substrates for cardiac metabolism. An infusion of bupivacaine was initiated and sustained until asystole, after which full cardiac recovery was allowed. During fatty acid metabolism, substantially lower bupivacaine doses induced both arrhythmia (60.4+/-11.5 microg oleate and 106.8+/-14.8 octanoate versus 153.4+/-21.4 carbohydrate; P<0.05) and asystole (121.0+/-30.1 microg and 171.5+/-20.2 versus 344.7+/-34.6; P<0.001). Dose-response analysis revealed significantly increased sensitivity to bupivacaine toxicity during fatty acid metabolism, indicated by lower V50 doses for both heart rate (70.6+/-5.6 microg oleate and 122.3+/-6.2 octanoate versus 152.6+/-8.6) and rate-pressure product (63.4+/-5.1 microg and 133.7+/-7.9 versus 165.1+/-12.2). Time to recovery following bupivacaine exposure was elevated in the fatty acid group (24.3+/-2.0 s versus 15.8+/-3.1; P<0.04). Fatty acid metabolism was shown to predispose the isolated heart to bupivacaine toxicity, confirming that the local anesthetic exerts specific effects on lipid processes in cardiomyocytes.

  14. Functional improvement and maturation of rat and human engineered heart tissue by chronic electrical stimulation.

    PubMed

    Hirt, Marc N; Boeddinghaus, Jasper; Mitchell, Alice; Schaaf, Sebastian; Börnchen, Christian; Müller, Christian; Schulz, Herbert; Hubner, Norbert; Stenzig, Justus; Stoehr, Andrea; Neuber, Christiane; Eder, Alexandra; Luther, Pradeep K; Hansen, Arne; Eschenhagen, Thomas

    2014-09-01

    Spontaneously beating engineered heart tissue (EHT) represents an advanced in vitro model for drug testing and disease modeling, but cardiomyocytes in EHTs are less mature and generate lower forces than in the adult heart. We devised a novel pacing system integrated in a setup for videooptical recording of EHT contractile function over time and investigated whether sustained electrical field stimulation improved EHT properties. EHTs were generated from neonatal rat heart cells (rEHT, n=96) or human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (hEHT, n=19). Pacing with biphasic pulses was initiated on day 4 of culture. REHT continuously paced for 16-18 days at 0.5Hz developed 2.2× higher forces than nonstimulated rEHT. This was reflected by higher cardiomyocyte density in the center of EHTs, increased connexin-43 abundance as investigated by two-photon microscopy and remarkably improved sarcomere ultrastructure including regular M-bands. Further signs of tissue maturation include a rightward shift (to more physiological values) of the Ca(2+)-response curve, increased force response to isoprenaline and decreased spontaneous beating activity. Human EHTs stimulated at 2Hz in the first week and 1.5Hz thereafter developed 1.5× higher forces than nonstimulated hEHT on day 14, an ameliorated muscular network of longitudinally oriented cardiomyocytes and a higher cytoplasm-to-nucleus ratio. Taken together, continuous pacing improved structural and functional properties of rEHTs and hEHTs to an unprecedented level. Electrical stimulation appears to be an important step toward the generation of fully mature EHT.

  15. Suppression of T cells results in long-term survival of mouse heart xenografts in C6-deficient rats.

    PubMed

    Wu, G; Korsgren, O; van Rooijen, N; Tibell, A

    2001-11-01

    The present study aimed to investigate the role of cellular immune response in the absence of membrane attack complex (MAC) formation in the concordant mouse-to-rat heart xenografting. Hearts from BALB/c mice were transplanted into the neck vessels of C6-competent (C6(+)) and C6-deficient (C6(-)) PVG rats. Liposome-encapsulated dichloro-methylene diphosphonate (Lip-Cl2MDP) was administered at a dose of 10 ml/kg 2 days before transplantation and every 5 days thereafter. Cyclosporine (CsA) was administered intramuscularly (i.m.) at a dose of 15 mg/kg per day. The heart xenografts were harvested for immuno-histological analysis at the time of rejection and the functioning grafts were removed at 70 days after transplantation. In untreated C6(+) rats, xeno-grafts survived for 2.3 +/- 0.5 days. Treatment with CsA or Lip-Cl(2)MDP in C6(+) rats did not significantly affect graft survival (2.5 +/- 0.6 and 2.3 +/- 0.4 days, respectively). In untreated C6(-) rats, xenografts survived for 5.0 +/- 0.6 days. However, Lip-Cl(2)MDP in C6(-) rats resulted in a prolongation of graft survival to 11 +/- 2.3 days (P < 0.05 vs. untreated C6(-) rats), while treatment with CsA alone in these rats led to more than 70 days' survival in four out of six grafts (61 +/- 16 days). In untreated C6(+) rats, immunohistology showed a severe myocardial necrosis and thrombosis with a scarce cellular infiltrate in the rejected xenografts. By contrast, in untreated C6(-) rats, xenografts were heavily infiltrated by macrophages and T cells. The number of macrophages, but not T cells, was markedly reduced in Lip-Cl(2)MDP-treated rats. In CsA-treated C6(-) rats, the grafts harvested at 70 days after transplantation had a normal morphology, with a minimal cellular infiltrate. Our data indicate that MAC-mediated injury plays an essential role in concordant xenograft rejection. Once this mechanism has been prevented, suppression of T cells allows for long-term xenograft survival.

  16. Tributyltin impairs the coronary vasodilation induced by 17β-estradiol in isolated rat heart.

    PubMed

    dos Santos, Roger Lyrio; Podratz, Priscila Lang; Sena, Gabriela Cavati; Filho, Vicente Sathler Delgado; Lopes, Pedro Francisco Iguatemy; Gonçalves, Washington Luiz Silva; Alves, Leandro Miranda; Samoto, Vivian Yochiko; Takiya, Christina Maeda; de Castro Miguel, Emilio; Moysés, Margareth Ribeiro; Graceli, Jones Bernardes

    2012-01-01

    Triorganotins, such as tributyltin (TBT), are environmental contaminants that are commonly used as antifouling agents for boats. However, TBT is also known to alter mammalian reproductive functions. Although the female sex hormones are primarily involved in the regulation of reproductive functions, 17β-estradiol also protects against cardiovascular diseases, in that this hormone reduces the incidence of coronary artery disease via coronary vasodilation. The aim of this study was to examine the influence of 100 ng/kg TBT administered daily by oral gavage for 15 d on coronary functions in female Wistar rats. Findings were correlated with changes in sex steroids concentrations. Tributyltin significantly increased the baseline coronary perfusion pressure and impaired vasodilation induced by 17β-estradiol. In addition, TBT markedly decreased serum 17β-estradiol levels accompanied by a significant rise in serum progesterone levels. Tributyltin elevated collagen deposition in the heart interstitium and number of mast cells proximate to the cardiac vessels. There was a positive correlation between the increase in coronary perfusion pressure and incidence of cardiac hypertrophy. In addition, TBT induced endothelium denudation (scanning electron microscopy) and accumulation of platelets. Moreover, TBT impaired coronary vascular reactivity to estradiol (at least in part), resulting in endothelial denudation, enhanced collagen deposition and elevated number of mast cells. Taken together, the present results demonstrate that TBT exposure may be a potential risk factor for cardiovascular disorders in rats.

  17. Effects of allitridum on the transient outward potassium current in rats with heart failure

    PubMed Central

    Zhao, Xiao-Jing; Lin, Kun; Zhang, Yu; Xu, Bin; Liu, Li; Fu, Yi-Cheng; Chen, Xi; Cai, Zhong-Qi; Wu, Zhi-Juan; Huang, Yun; Li, Yang

    2016-01-01

    Objective To study the effect of allitridum on the transient outward potassium current (Ito) of ventricular myocytes in heart failure (HF). Methods The dual enzymatic method was used to separate single ventricular myocytes from Sprague Dawley rats. Patch-clamping was used to record Ito and analyze the effect of allitridum on the current. Results The Ito current had a significant decrease in the HF group, compared with the control group. The density of Ito in the HF group was increased after treatment of allitridum (30 µmol/L). The peak current densities of Ito were enhanced in the HF group from 6.01 ± 0.30 pA/pF to 8.41 ± 0.54 pA/pF (P < 0.01) at +50 mV after treatment with allitridum (30 µmol/L). We also determined the effect of allitridum on the gating mechanism of the Ito in the HF group. Conclusions We found that allitridum increased the Ito by accelerating the activation of channels and shortened the time constants of inactivation, and allitridum decreased the remodeling of Ito in ventricular myocytes of rats with HF. PMID:27899943

  18. Resveratrol improves survival, hemodynamics and energetics in a rat model of hypertension leading to heart failure.

    PubMed

    Rimbaud, Stéphanie; Ruiz, Matthieu; Piquereau, Jérôme; Mateo, Philippe; Fortin, Dominique; Veksler, Vladimir; Garnier, Anne; Ventura-Clapier, Renée

    2011-01-01

    Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001), and prevented the 25% reduction in body weight in HS-NT (P<0.001). Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening -34% in HS-NT) as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium-dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF.

  19. Resveratrol Improves Survival, Hemodynamics and Energetics in a Rat Model of Hypertension Leading to Heart Failure

    PubMed Central

    Rimbaud, Stéphanie; Ruiz, Matthieu; Piquereau, Jérôme; Mateo, Philippe; Fortin, Dominique; Veksler, Vladimir; Garnier, Anne; Ventura-Clapier, Renée

    2011-01-01

    Heart failure (HF) is characterized by contractile dysfunction associated with altered energy metabolism. This study was aimed at determining whether resveratrol, a polyphenol known to activate energy metabolism, could be beneficial as a metabolic therapy of HF. Survival, ventricular and vascular function as well as cardiac and skeletal muscle energy metabolism were assessed in a hypertensive model of HF, the Dahl salt-sensitive rat fed with a high-salt diet (HS-NT). Resveratrol (18 mg/kg/day; HS-RSV) was given for 8 weeks after hypertension and cardiac hypertrophy were established (which occurred 3 weeks after salt addition). Resveratrol treatment improved survival (64% in HS-RSV versus 15% in HS-NT, p<0.001), and prevented the 25% reduction in body weight in HS-NT (P<0.001). Moreover, RSV counteracted the development of cardiac dysfunction (fractional shortening −34% in HS-NT) as evaluated by echocardiography, which occurred without regression of hypertension or hypertrophy. Moreover, aortic endothelial dysfunction present in HS-NT was prevented in resveratrol-treated rats. Resveratrol treatment tended to preserve mitochondrial mass and biogenesis and completely protected mitochondrial fatty acid oxidation and PPARα (peroxisome proliferator-activated receptor α) expression. We conclude that resveratrol treatment exerts beneficial protective effects on survival, endothelium–dependent smooth muscle relaxation and cardiac contractile and mitochondrial function, suggesting that resveratrol or metabolic activators could be a relevant therapy in hypertension-induced HF. PMID:22028869

  20. Nerve Growth Factor Decreases in Sympathetic and Sensory Nerves of Rats with Chronic Heart Failure

    PubMed Central

    Lu, Jian

    2014-01-01

    Nerve growth factor (NGF) plays a critical role in the maintenance and survival of both sympathetic and sensory nerves. Also, NGF can regulate receptor expression and neuronal activity in the sympathetic and sensory neurons. Abnormalities in NGF regulation are observed in patients and animals with heart failure (HF). Nevertheless, the effects of chronic HF on the levels of NGF within the sympathetic and sensory nerves are not known. Thus, the ELISA method was used to assess the levels of NGF in the stellate ganglion (SG) and dorsal root ganglion (DRG) neurons of control rats and rats with chronic HF induced by myocardial infarction. Our data show for the first time that the levels of NGF were significantly decreased (P < 0.05) in the SG and DRG neurons 6–20 weeks after ligation of the coronary artery. In addition, a close relation was observed between the NGF levels and the left ventricular function. In conclusion, chronic HF impairs the expression of NGF in the sympathetic and sensory nerves. Given that sensory afferent nerves are engaged in the sympathetic nervous responses to somatic stimulation (i.e. muscle activity during exercise) via a reflex mechanism, our data indicate that NGF is likely responsible for the development of muscle reflex-mediated abnormal sympathetic responsiveness observed in chronic HF. PMID:24913185

  1. Heart rate variability and electrocardiogram waveform as predictors of morbidity during hypothermia and rewarming in rats.

    PubMed

    Matthew, C B; Bastille, A M; Gonzalez, R R; Sils, I V

    2002-09-01

    This study examined electrocardiogram (ECG) waveform, heart rate (HR), mean blood pressure (BP), and HR variability as potential autonomic signatures of hypothermia and rewarming. Adult male Sprague-Dawley rats had telemetry transmitters surgically implanted, and 2 weeks were allowed for recovery prior to induction of hypothermia. Rats were lightly anesthetized (sodium pentobarbital, 35 mg/kg i.p.) and placed in a coil of copper tubing through which temperature-controlled water was circulated. Animals were cooled to a core temperature (Tc) of 20 degrees C, maintained there for 30 min, and then rewarmed. Data (Tc, BP, HR from ECG, and 10-s strips of ECG waveforms) were collected every 5 min throughout hypothermia and rewarming. Both HR and BP declined after initial increases with the drop in HR starting at a higher Tc than the drop in BP (29.6 +/- 2.4 degrees C vs. 27.1 +/- 3.3 degrees C, p < 0.05). Animals that were not successfully rewarmed exhibited a significant (p < 0.05) increase in the normalized standard deviation of interbeat intervals (IBI) throughout cooling compared with animals that were successfully rewarmed. The T wave of the ECG increased in amplitude and area with decreasing Tc. T-wave amplitude and IBI variability show potential as predictors of survival in hypothermic victims.

  2. Relaxin protects against myocardial injury caused by ischemia and reperfusion in rat heart.

    PubMed Central

    Bani, D.; Masini, E.; Bello, M. G.; Bigazzi, M.; Sacchi, T. B.

    1998-01-01

    Myocardial injury caused by ischemia and reperfusion comes from multiple pathogenic events, including endothelial damage, neutrophil extravasation into tissue, platelet and mast cell activation, and peroxidation of cell membrane lipids, which are followed by myocardial cell alterations resulting eventually in cell necrosis. The current study was designed to test the possible cardioprotective effect of the hormone relaxin, which has been found to cause coronary vessel dilation and to inhibit platelet and mast cell activation. Ischemia (for 30 minutes) was induced in rat hearts in vivo by ligature of the left anterior descending coronary artery; reperfusion (for 60 minutes or less if the rats died before this predetermined time) was induced by removal of the ligature. Relaxin (100 ng) was given intravenously 30 minutes before ischemia. The results obtained showed that relaxin strongly reduces 1) the extension of the myocardial areas affected by ischemia-reperfusion-induced damage, 2) ventricular arrhythmias, 3) mortality, 4) myocardial neutrophil number, 5) myeloperoxidase activity, a marker of neutrophil accumulation, 6) production of malonyldialdehyde, an end product of lipid peroxidation, 7) mast cell granule release, 8) calcium overload, and 9) morphological signs of myocardial cell injury. This study shows that relaxin can be regarded as an agent with a marked cardioprotective action against ischemia-reperfusion-induced myocardial injury. Images Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 PMID:9588905

  3. Contribution of central nervous system endothelial nitric oxide synthase to neurohumoral activation in heart failure rats.

    PubMed

    Biancardi, Vinicia C; Son, Sook J; Sonner, Patrick M; Zheng, Hong; Patel, Kaushik P; Stern, Javier E

    2011-09-01

    Neurohumoral activation, a hallmark in heart failure (HF), is linked to the progression and mortality of HF patients. Thus, elucidating its precise underlying mechanisms is of critical importance. Other than its classic peripheral vasodilatory actions, the gas NO is a pivotal neurotransmitter in the central nervous system control of the circulation. While accumulating evidence supports a contribution of blunted NO function to neurohumoral activation in HF, the precise cellular sources, and NO synthase (NOS) isoforms involved, remain unknown. Here, we used a multidisciplinary approach to study the expression, cellular distribution, and functional relevance of the endothelial NOS isoform within the hypothalamic paraventricular nucleus in sham and HF rats. Our results show high expression of endothelial NOS in the paraventricular nucleus (mostly confined to astroglial cells), which contributes to constitutive NO bioavailability, as well as tonic inhibition of presympathetic neuronal activity and sympathoexcitatory outflow from the paraventricular nucleus. A diminished endothelial NOS expression and endothelial NOS-derived NO availability were found in the paraventricular nucleus of HF rats, resulting, in turn, in blunted NO inhibitory actions on neuronal activity and sympathoexcitatory outflow. Taken together, our study supports blunted central nervous system endothelial NOS-derived NO as a pathophysiological mechanism underlying neurohumoral activation in HF.

  4. Effects of methanol in blood pressure and heart rate in the rat

    PubMed Central

    Jahan, Kausar; Mahmood, D.; Fahim, M.

    2015-01-01

    Introduction: Methanol ingestion is an uncommon form of poisoning that can cause severe metabolic disturbances, blindness, permanent neurologic dysfunction and death. While methanol itself may be harmless, it converts, in vivo, to highly toxic formic acid. Methanol intoxication clinically manifests as ocular toxicity. The present study investigated the cardiovascular effects of methanol. Materials and Methods: On the day of the experiment, Wistar rats were anesthetized with urethane. The femoral artery on one side was exposed, and a polyethylene catheter was inserted into the artery for recording arterial blood pressure (ABP). The catheter was attached to a pressure transducer (Statham - P23D). Systolic blood pressure (BP), mean ABP, and heart rate were recorded on a power-lab data acquisition system with a computerized analysis program. Rats were administered with different dilutions (9.5%, 19.0%, 28.5%, 38.0%, 47.5%, 57.0%, 66.5%, 76%) of methanol (95% v/v, i.v.). Results: Of all dilutions of methanol, 66.5% dilution showed maximum decrease of diastolic BP from 124.64 ± 5.39 to 62.30 ± 11.90 mmHg; 76.0% dilution showed maximum decrease of systolic BP from 165.70 ± 5.57 to 112.11 ± 12.0 mmHg, and mean ABP from 160.61 ± 12.45 to 86.14 ± 4.11 mmHg. The heart rate increased (from 250 beats/s to near about 275 beats/s) following administration of methanol dilution from 19.0% till 76.0%. Conclusion: The present study is consistent with previous studies suggesting that methanol ingestion leads to severe hypotension as observed from decrease in diastolic BP, systolic BP, and mean ABP. However, severe increase of heart rate suggests activation of a compensatory mechanism to offset hypotension that eventually leads to death in methanol poisoning. Hence, this study emphasizes the need to monitor all the hemodynamic parameters in accidental methanol poisoning. PMID:25709339

  5. Changes in citric acid cycle flux and anaplerosis antedate the functional decline in isolated rat hearts utilizing acetoacetate.

    PubMed Central

    Russell, R R; Taegtmeyer, H

    1991-01-01

    To determine the temporal relationship between changes in contractile performance and flux through the citric acid cycle in hearts oxidizing acetoacetate, we perfused isolated working rat hearts with either glucose or acetoacetate (both 5 mM) and freeze-clamped the tissue at defined times. After 60 min of perfusion, hearts utilizing acetoacetate exhibited lower systolic and diastolic pressures and lower cardiac outputs. The oxidation of acetoacetate increased the tissue content of 2-oxoglutarate and glutamate and decreased the content of succinyl-CoA suggesting inhibition of citric acid cycle flux through 2-oxoglutarate dehydrogenase. Whereas hearts perfused with either acetoacetate or glucose were similar with respect to their function for the first 20 min, changes in tissue metabolites were already observed within 5 min of perfusion at near-physiological workloads. The addition of lactate or propionate, but not acetate, to hearts oxidizing acetoacetate improved contractile performance, although inhibition of 2-oxoglutarate dehydrogenase was probably not diminished. If lactate or propionate were added, malate and citrate accumulated indicating utilization of anaplerotic pathways for the citric acid cycle. We conclude that a decreased rate of flux through 2-oxoglutarate dehydrogenase in hearts oxidizing acetoacetate precedes, and may be responsible for, contractile failure and is not the result of decreased cardiac work. Further, anaplerosis play an important role in the maintenance of contractile function in hearts utilizing acetoacetate. Images PMID:1671390

  6. Effect of superoxide anion scavenger on rat hearts with chronic intermittent hypoxia.

    PubMed

    Pai, Peiying; Lai, Ching Jung; Lin, Ching-Yuang; Liou, Yi-Fan; Huang, Chih-Yang; Lee, Shin-Da

    2016-04-15

    Only very limited information regarding the protective effects of the superoxide anion scavenger on chronic intermittent hypoxia-induced cardiac apoptosis is available. The purpose of this study is to evaluate the effects of the superoxide anion scavenger on cardiac apoptotic and prosurvival pathways in rats with sleep apnea. Forty-two Sprague-Dawley rats were divided into three groups, rats with normoxic exposure (Control, 21% O2, 1 mo), rats with chronic intermittent hypoxia exposure (Hypoxia, 3-7% O2vs. 21% O2per 40 s cycle, 8 h per day, 1 mo), and rats with pretreatment of the superoxide anion scavenger and chronic intermittent hypoxia exposure (Hypoxia-O2 (-)-Scavenger, MnTMPyP pentachloride, 1 mg/kg ip per day; 3-7% O2vs. 21% O2per 40 s cycle, 8 h per day, 1 mo) at 5-6 mo of age. After 1 mo, the protein levels and apoptotic cells of excised hearts from three groups were measured by Western blotting and terminal deoxynucleotide transferase-mediated dUTP nick end labeling (TUNEL) assay. The superoxide anion scavenger decreased hypoxia-induced myocardial architecture abnormalities, left ventricular hypertrophy, and TUNEL-positive apoptosis. The superoxide anion scavenger decreased hypoxia-induced Fas ligand, Fas death receptors, Fas-associated death domain (FADD), activated caspase-8, and activated caspase-3 (Fas-dependent apoptotic pathway) as well as Bad, activated caspase-9 and activated caspase-3 (mitochondria-dependent apoptotic pathway), endonuclease G (EndoG), apoptosis-inducing factor (AIF), and TUNEL-positive apoptosis. The superoxide anion scavenger increased IGF-1, IGF-1R, p-PI3k, p-Akt, p-Bad, Bcl-2, and Bcl-xL (survival pathway). Our findings imply that the superoxide anion scavenger might prevent cardiac Fas-mediated and mitochondrial-mediated apoptosis and enhance the IGF-1-related survival pathway in chronic intermittent hypoxia. The superoxide anion scavenger may prevent chronic sleep apnea-enhanced cardiac apoptotic pathways and enhances

  7. Influence of renovascular hypertension on the distribution of vasoactive intestinal peptide in the stomach and heart of rats.

    PubMed

    Kasacka, Irena; Piotrowska, Żaneta; Janiuk, Izabela

    2015-11-01

    Arterial hypertension is associated with serious dysfunction of the cardiovascular system and digestive system. Given the relevant role of vasoactive intestinal peptide (VIP) in the regulation of digestion process, control of blood pressure and heart rate as well as cardio- and gastro-protective character of the peptide, it appeared worthwhile to undertake the research aimed at immunohistochemical identification and evaluation of VIP-positive structures in the pylorus and heart of hypertensive rats. Up to now, this issue has not been investigated. The experimental model of hypertension in rats according to Goldblatt (two-kidney one clip model of hypertension) was used in the study. The experimental material (pylorus and heart) was collected in the sixth week of the study. VIP-containing structures were evaluated using immunohistochemical and morphometric methods. The analysis of the results showed a significant increase in the number of immunoreactive VIP structures and in the intensity of immunohistochemical staining in the stomach and in the heart of hypertensive rats. Our findings indicate that VIP is an important regulator of cardiovascular and digestive system in physiological and pathological conditions. However, to better understand the exact role of VIP in hypertension further studies need to be carried out.

  8. Modifications in nitric oxide and superoxide anion metabolism induced by fructose overload in rat heart are prevented by (-)-epicatechin.

    PubMed

    Calabró, Valeria; Piotrkowski, Barbara; Fischerman, Laura; Vazquez Prieto, Marcela A; Galleano, Monica; Fraga, Cesar G

    2016-04-01

    Fructose overload promotes functional and metabolic derangements in humans and in animal experimental models. Evidence suggests that dietary flavonoids have the ability to prevent/attenuate the development of metabolic diseases. In this work we investigated the effects of (-)-epicatechin on the modifications induced by fructose overload in the rat heart in terms of nitric oxide and superoxide metabolism. Male Sprague Dawley rats received 10% (w/v) fructose in the drinking water for 8 weeks, with or without (-)-epicatechin (20 mg per kg body weight per day) in the rat chow diet. These conditions of fructose overload did not lead to overt manifestations of heart hypertrophy or tissue remodeling. However, biochemical and molecular changes were observed and could represent the onset of functional alterations. (-)-Epicatechin prevented a compromised NO bioavailability and the development of oxidative stress produced by fructose overload essentially acting on superoxide anion metabolism. In this line, the increase in superoxide anion production, the overexpression of NOX2 subunit p47phox and of NOX4, the decrease in superoxide dismutase activity, and the higher oxidized/reduced glutathione ratio installed by fructose overload were absent in the rats receiving (-)-epicatechin. These results support the hypothesis that diets rich in (-)-epicatechin could prevent the onset and progression of heart dysfunctions associated with metabolic alterations.

  9. Superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase in the heart of hypergravity-treated and aging rats

    NASA Astrophysics Data System (ADS)

    Utko, Natalie

    2005-08-01

    Activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GP), and glutathione reductase (GR) were determined in the heart of young and old control and hypergravity (HG) treated male Wistar rats. Relatively small and insignificant changes were observed when comparing enzyme activities in the heart of young and old control rats, whereas HG induced significant decline of SOD and GP in the group of old rats and GR in young animals. Statistically highly significant positive correlation found for SOD and downstream acting catalase in young (r=0.72; P<0.00001) and old rats (r=0,86; P<0.00001) was preserved in HG- treated young animals as well (r=0.66; P<0.02), assuming that SOD-catalase pair could remain functionally related in both aging and HG. However, three-dimensional (3D) non- linear plotting and cluster analysis revealed significant alterations in enzyme relations in the heart of both aging and HG-treated animals.

  10. Expression and location of HSP60 and HSP10 in the heart tissue of heat-stressed rats

    PubMed Central

    Cheng, Yanfen; Sun, Jiarui; Chen, Hongbo; Adam, Abdelnasir; Tang, Shu; Kemper, Nicole; Hartung, Jörg; Bao, Endong

    2016-01-01

    The present study aimed to analyze the expression levels and localizations of heat shock protein (HSP) 60 and HSP10 in the heart tissue of rats subjected to heat stress (42°C) for 0, 20, 80 and 100 min. Histopathological injuries and increased serum activities of serum lactate dehydrogenase and creatine kinase isoenzyme MB were detected in the heated rat myocardial cells. These results suggested that heat stress-induced acute degeneration may be sufficient to cause sudden death in animals by disrupting the function and permeability of the myocardial cell membrane. In addition, the expression levels of HSP60 were significantly increased following 20 min heat stress, whereas the expression levels of its cofactor HSP10 were not. Furthermore, the location of HSP60, but not of HSP10, was significantly altered during periods of heat stress. These results suggested that HSP60 in myocardial tissue may be more susceptive to the effects of heat stress as compared with HSP10, and that HSP10 is constitutively expressed in the heart of rats. The expression levels and localizations of HSP60 and HSP10 at the different time points of heat stress were not similar, which suggested that HSP60 and HSP10 may not form a complex in the heart tissue of heat-stressed rats. PMID:27698781

  11. 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

  12. Effect of in vivo heart irradiation on the development of antioxidant defenses and cardiac functions in the rat

    SciTech Connect

    Benderitter, M.; Assem, M.; Maupoil, V.

    1995-10-01

    During radiotherapy of thoracic tumors, the heart is often included in the primary treatment volume, and chronic impairment of myocardial function occurs. The cellular biomolecules are altered directly by radiation or damaged indirectly by free radical production. The purpose of this investigation was to evaluate the biochemical and functional response of the rat heart to a single high dose of radiation. The effect of 20 Gy local X irradiation was determined in the heart of Wistar rats under general anesthesia. Mechanical performances were measured in vitro using an isolated perfused working heart model, and cardiac antioxidant defenses were also evaluated. Hearts were studied at 1 and 4 months after irradiation. This single dose of radiation induced a marked drop in the mechanical activity of the rat heart: aortic output was significantly reduced (18% less than control values) at 1 month postirradiation and remained depressed for the rest of the experimental period (21% less than control 4 months after treatment). This suggests the development of myocardial failure after irradiation. The decline of functional parameters was associated with changes in antioxidant defenses. The decrease in cardiac levels of vitamin E (-30%) was associated with an increase in the levels of Mn-SOD and glustathione peroxidase (+45.5% and +32%, respectively, at 4 months postirradiation). However, cardiac vitamin C and catalase levels remained constant. Since these antioxidant defenses were activated relatively long after irradiation, it is suggested that this was probable due to the production of free radical species associated with the development of inflammation. 49 refs., 8 figs., 1 tab.

  13. Alternative Splicing Generates a Novel Truncated Cav1.2 Channel in Neonatal Rat Heart*

    PubMed Central

    Liao, Ping; Yu, Dejie; Hu, Zhenyu; Liang, Mui Cheng; Wang, Jue Jin; Yu, Chye Yun; Ng, Gandi; Yong, Tan Fong; Soon, Jia Lin; Chua, Yeow Leng; Soong, Tuck Wah

    2015-01-01

    L-type Cav1.2 Ca2+ channel undergoes extensive alternative splicing, generating functionally different channels. Alternatively spliced Cav1.2 Ca2+ channels have been found to be expressed in a tissue-specific manner or under pathological conditions. To provide a more comprehensive understanding of alternative splicing in Cav1.2 channel, we systematically investigated the splicing patterns in the neonatal and adult rat hearts. The neonatal heart expresses a novel 104-bp exon 33L at the IVS3-4 linker that is generated by the use of an alternative acceptor site. Inclusion of exon 33L causes frameshift and C-terminal truncation. Whole-cell electrophysiological recordings of Cav1.233L channels expressed in HEK 293 cells did not detect any current. However, when co-expressed with wild type Cav1.2 channels, Cav1.233L channels reduced the current density and altered the electrophysiological properties of the wild type Cav1.2 channels. Interestingly, the truncated 3.5-domain Cav1.233L channels also yielded a dominant negative effect on Cav1.3 channels, but not on Cav3.2 channels, suggesting that Cavβ subunits is required for Cav1.233L regulation. A biochemical study provided evidence that Cav1.233L channels enhanced protein degradation of wild type channels via the ubiquitin-proteasome system. Although the physiological significance of the Cav1.233L channels in neonatal heart is still unknown, our report demonstrates the ability of this novel truncated channel to modulate the activity of the functional Cav1.2 channels. Moreover, the human Cav1.2 channel also contains exon 33L that is developmentally regulated in heart. Unexpectedly, human exon 33L has a one-nucleotide insertion that allowed in-frame translation of a full Cav1.2 channel. An electrophysiological study showed that human Cav1.233L channel is a functional channel but conducts Ca2+ ions at a much lower level. PMID:25694430

  14. Cumene hydroperoxide, an agent inducing lipid peroxidation, and 4-hydroxy-2,3-nonenal, a peroxidation product, cause coronary vasodilatation in perfused rat hearts by a cyclic nucleotide independent mechanism.

    PubMed

    van der Kraaij, A M; de Jonge, H R; Esterbauer, H; de Vente, J; Steinbusch, H W; Koster, J F

    1990-02-01

    STUDY OBJECTIVE - The aim of the study was to determine whether cumene hydroperoxide, a substance known to induce lipid peroxidation through free radical action, and 4-hydroxy-2,3-nonenal (4-hydroxynonenal), a major aldehyde formed during lipid peroxidation, induce coronary vasodilatation by changing cyclic nucleotide levels. DESIGN - The study involved Langendorff perfused rat hearts, using different concentrations of cumene hydroperoxide and 4-hydroxynonenal, with sodium nitroprusside for comparison. Coronary flow was measured indirectly as retrograde aortic flow, with constant perfusion pressure. Information about the precise localisation of cyclic guanosine monophosphate (cGMP) in the heart was obtained by immunocytochemistry, using a new cGMP antiserum. EXPERIMENTAL MATERIAL - Hearts were from male Wistar rats, body weight 200-250 g. MEASUREMENTS and RESULTS - Both cumene hydroperoxide and 4-hydroxynonenal caused a dose dependent and reversible increase in coronary flow comparable with sodium nitroprusside. With sodium nitroprusside there was a good correlation between extent of vasodilatation and total heart cGMP concentration. Vasodilatation induced by cumene hydroperoxide or 4-hydroxynonenal was not accompanied by increase in total heart cGMP or cAMP (cyclic adenosine monophosphate) concentration. Isoprenaline was used as a positive control for cAMP. cGMP immunostaining was found in coronary vascular smooth muscle after vasodilatation with sodium nitroprusside, but no immunostaining was found in vascular smooth muscle after vasodilatation with cumene hydroperoxide or 4-hydroxynonenal. CONCLUSIONS - Cumene hydroperoxide and 4-hydroxynonenal can provoke reversible coronary vasodilatation in isolated perfused rat hearts by a cyclic nucleotide independent mechanism.

  15. The Impact of Different Plasma Glucose Levels on Heart Rate in Experimental Rats With Acute Myocardial Infarction

    PubMed Central

    Pan, Guo-Zhong; Xie, Jing; Tian, Xiao-Fang; Yang, Shi-Wei; Zhou, Yu-Jie

    2016-01-01

    Background The aim of the study was to evaluate the impact of different plasma glucose levels on heart rate (HR) in experimental rats with acute myocardial infarction (AMI). Methods One hundred and twenty-one male Wistar rats were randomly divided into AMI group (n = 70) and sham-operation group (n = 51). Both groups had low, normal and high glucose levels, respectively. In the former group, hypertonic glucose was injected into the rats to make their blood glucose levels above 16 mmol/L and insulin below 3.3 mmol/L; then, the left anterior descending artery was ligated. In the later group, the models of different blood glucose levels were the same as the former ones, but false operations, thread without ligating, were given to the rats. Electrocardiogram and troponin I (TnI) confirmed that the models were prepared successfully. Electrocardiogram expression of AMI was the formation of Q-wave in over three adjacent leads and abnormal elevation of TnI. Results The HR of the rats in the hypoglycemic group is higher than that of the hyperglycemic group and normal blood glucose group before AMI (P < 0.05). The HR of the hyperglycemic rats is higher than that of the hypoglycemic group and normal blood glucose group after AMI (P < 0.05). In the hypoglycemic group, the HR of the rats who suffered from AMI was lower than that of the rats of the sham group (P < 0.05). Conclusion Hypoglycemia allows faster HR and the HR in the rats with hyperglycemia is higher than that in the rats with hypoglycemia among the AMI rats. PMID:28197283

  16. Influence of ethanol extract of Ginkgo biloba leaves on the isolated rat heart work and mitochondria functions.

    PubMed

    Baliutyte, Giedre; Baniene, Rasa; Gendviliene, Vida; Martisiene, Irma; Trumbeckaite, Sonata; Borutaite, Vilmante; Toleikis, Adolfas

    2012-05-01

    In this study, we attempted to elucidate whether the effects of ethanol extract of Ginkgo biloba leaves (GBE) observed previously on isolated rat heart mitochondria may be realized in situ (in case of isolated heart perfused under normal conditions and under ischemia-reperfusion). We found that GBE at low concentrations (0.01, 0.05, and 0.1 μL/mL) does not affect the heart rate and parameters of electrocardiogram (ECG) but produces a small increase in the coronary flow. Higher concentration of GBE (0.2 and 0.3 μL/mL) diminished the heart rate, decreased the coronary flow, and tended to enhance the parameters of ECG. The contractility of isolated rat heart and mitochondrial nicotinamide adenine dinucleotide reduced form fluorescence decreased in a GBE concentration-dependent manner. Mitochondria isolated from hearts pre-perfused with GBE (0.05 μL/mL) for 20 minutes before nonflow global ischemia-reperfusion (45 min/15 min) showed higher respiratory rates with pyruvate + malate in state 2 and state 3, higher respiratory control index, and diminished H₂O₂ generation compared with untreated group. Higher GBE concentration, 0.4 μL/mL, had no effect on H2O2 generation and did not prevent the ischemia-reperfusion-induced decrease of pyruvate + malate oxidation in state 3 but even enhanced it. However, in the case of nonischemic perfusions, this GBE concentration had no significant effect on these parameters of respiratory functions of isolated heart mitochondria.

  17. Effects of a protocol of ischemic postconditioning and/or captopril in hearts of normotensive and hypertensive rats.

    PubMed

    Penna, Claudia; Tullio, Francesca; Moro, Francesca; Folino, Anna; Merlino, Annalisa; Pagliaro, Pasquale

    2010-03-01

    Brief periods (a few seconds) of cyclic coronary occlusions applied early in reperfusion induce a cardioprotection against infarct size, called postconditioning (PostC) in which B(2)-bradykinin receptors play a pivotal role. Since angiotensin-converting enzyme (ACE) inhibitors reduce degradation of kinins, we studied the effects of PostC on infarct size and postischemic myocardial dysfunction in both normotensive (WKY) and spontaneously hypertensive rats (SHR) acutely or chronically treated with the ACE inhibitor Captopril. Isolated hearts from SHR and WKY rats were subjected to the following protocols: (a) ischemia for 30- and 120-min reperfusion (I/R); (b) I/R + PostC protocol (5-cycles 10-s I/R); (c) pretreatment with Captopril for 4-weeks before to subject the hearts to I/R with or without PostC maneuvers. Some SHR hearts were treated with Captopril during the 20- or 40-min early reperfusion with or without PostC maneuvers. Cardiac function was assessed in vivo with echocardiography. Left ventricular pressure and infarct size were measured ex vivo. Chronic Captopril significantly reduced left ventricular hypertrophy in SHR, and reduced infarct size in both WKY and SHR hearts. PostC maneuvers significantly reduced infarct size in WKY, but not in SHR hearts. Yet, PostC slightly improved postischemic systolic function in untreated SHR. Captopril given in reperfusion was unable to limit I/R injury in SHR hearts. Data show that PostC protection against infarct size is blunted in SHR and that PostC is unable to add its protective effect to those of chronic Captopril, which per se reduces cardiac hypertrophy and heart susceptibility to I/R insult.

  18. Localization of atrial natriuretic peptide mRNA and immunoreactivity in the rat heart and human atrial appendage

    SciTech Connect

    Hamid, Q.; Wharton, J.; Terenghi, G.; Hassall, C.J.S.; Aimi, J.; Taylor, K.M.; Nakazato, H.; Dixon, J.E.; Burnstock, G.; Polak, J.M.

    1987-10-01

    The localization of mRNA encoding preproatrial natriuretic peptide was investigated in tissue sections and cultures of rat heart and in sections of human right atrial appendage using the technique of in situ hybridization with /sup 32/P- and /sup 35/S-labeled RNA probes. Rat atrial natriuretic peptide (ANP) transcripts were demonstrated in numerous atrial myocytes and, to a lesser extent, in ventricular myocytes in both tissue sections and newborn rat heart cultures. These findings are consistent with those obtained by RNA blot analysis of rat heart total RNA, indicating that a single prepro-ANP transcript of approx. 900 nucleotides was present in the ventricles as well as the atria. Using a /sup 35/S-labeled RNA probe for human ANP mRNA, ANP transcripts were also localized to the majority of myocytes in the human right atrial appendage. Only background levels of autoradiographic labeling were obtained when RNA probes identical to the coding sequence of rat or human ANP mRNA were used. A close correlation was found between the distribution of ANP immunoreactivity and prepro-ANP mRNA in these preparations. These results provide unequivocal evidence for the expression of the ANP gene in the rat ventricles, as well as the atria, because myocytes in these tissues have been established as the sites of both ANP localization and precursor biosynthesis. The combined use of cardiac cultures and in situ hybridization may be of value in future studies investigating the regulation of ANP synthesis in cardiac myocytes.

  19. Comparison of magnetic field and electric potential produced by frog heart muscle

    NASA Astrophysics Data System (ADS)

    Burstein, Deborah; Cohen, David

    1985-04-01

    A comparison is made here between the magnetic field and electric potential produced by a thin strip of frog heart muscle. An experimental test is made of the theory which states that the wave front of a single fiber (or parallel bundle of fibers as in this strip) can be represented, for both the magnetic field and electric potential, by the same single-current dipole. First, an experimental measurement is made of the ratio of magnetic field/electric potential produced by an actual current dipole in an electrolytic tank. Then the dipole is replaced by the muscle strip and a measurement is again made of the ratio; this is done for three muscle strips at eight different source-to-detector distances ranging from 1 to 5 cm. It is found, in all cases, that the muscle ratios are equal to those of the actual dipole to within the experimental uncertainty of ±10%. Therefore, to this extent the theory is verified for this case of a thin strip of frog heart tissue.

  20. Comparison of macroscopic models of excitation and force propagation in the heart.

    PubMed

    Sachse, F B; Blümcke, L G; Mohr, M; Glänzel, K; Häfner, J; Riedel, C; Seemann, G; Skipa, O; Werner, C D; Dössel, O

    2002-01-01

    Computer aided simulations of the heart provide knowledge of phenomena, which are commonly neither visible nor measurable with current techniques. This knowledge can be applied e.g. in cardiologic diagnosis and therapy. A variety of models was created to reconstruct cardiac processes, e.g. electrical propagation and force development. In this work different macroscopic models were compared, i.e. models based on excitation-diffusion equations and cellular automata. The comparison was carried out concerning reconstruct-ability of cardiac phenomena, mathematical and biophysical foundation as well as computational expense. Particularly, the reconstruct-ability of electromechanic feedback mechanisms was examined. Perspectives for further developments and improvements of models were given.

  1. Total lymphoid irradiation in rat heart albgrafts: dose, fractionation, and combination with cyclosporin-A. [X-ray

    SciTech Connect

    Rynasiewicz, J.J.; Sutherland, D.E.R.; Kawahara, K.; Kim, T.; Najarian, J.S.

    1981-03-01

    The survival or organ allografts is prolonged in mice and rats treated with fractionated, high-dose total lymphoid irradiation (TLI). We have studied the effect of TLI, alone or in combination with donor bone marrow or pharmacologic immunosuppression (cyclosporin-A: CY-A), on the survival of heterotopic rat heart allografts. Specifically, we evaluated the generalized immunosuppressive effect of TLI as a function of accumulated dose and fractionation schedule. In addition, TLI and CY-A were used individually in schedules that by themselves gave only moderate graft prolongation and then subsequently in sequential combination.

  2. Time course of ubiquitin-proteasome and macroautophagy-lysosome pathways in skeletal muscle in rats with heart failure.

    PubMed

    Fujita, Naoto; Fujino, Hidemi; Sakamoto, Hiroki; Takegaki, Jyunya; Deie, Masataka

    2015-01-01

    Patients with heart failure have limited exercise capacity due to not only the myocardial dysfunction but also skeletal muscle atrophy. However, the mechanisms and time course of protein degradation in skeletal muscle during heart failure remain unclear, and there is no established standard treatment. The purpose of the present study was to investigate the time course of major protein degradation pathways in skeletal muscle during heart failure. Four-week-old male Wistar rats were randomly assigned to heart failure induced by monocrotaline or control groups. At 14 and 21 days after monocrotaline injection, the lungs, heart, and gastrocnemius and soleus muscles were removed and analyzed. There was no significant difference in body weight between the groups at 14 days after monocrotaline injection. Although there were no morphological changes in the skeletal muscle of the monocrotaline group at this time point, ubiquitin-proteasome and macroautophagylysosome pathways were activated in the monocrotaline group. Additionally, the pathways were less strongly activated in the soleus muscle than in the gastrocnemius muscle. These results suggest that physical exercise that shifts to slow muscle characteristics should begin when there is no indication of skeletal muscle atrophy to prevent exercise intolerance with heart failure.

  3. Global changes in the rat heart proteome induced by prolonged morphine treatment and withdrawal.

    PubMed

    Drastichova, Zdenka; Skrabalova, Jitka; Jedelsky, Petr; Neckar, Jan; Kolar, Frantisek; Novotny, Jiri

    2012-01-01

    Morphine belongs among the most commonly used opioids in medical practice due to its strong analgesic effects. However, sustained administration of morphine leads to the development of tolerance and dependence and may cause long-lasting alterations in nervous tissue. Although proteomic approaches enabled to reveal changes in multiple gene expression in the brain as a consequence of morphine treatment, there is lack of information about the effect of this drug on heart tissue. Here we studied the effect of 10-day morphine exposure and subsequent drug withdrawal (3 or 6 days) on the rat heart proteome. Using the iTRAQ technique, we identified 541 proteins in the cytosol, 595 proteins in the plasma membrane-enriched fraction and 538 proteins in the mitochondria-enriched fraction derived from the left ventricles. Altogether, the expression levels of 237 proteins were altered by morphine treatment or withdrawal. The majority of changes (58 proteins) occurred in the cytosol after a 3-day abstinence period. Significant alterations were found in the expression of heat shock proteins (HSP27, α-B crystallin, HSP70, HSP10 and HSP60), whose levels were markedly up-regulated after morphine treatment or withdrawal. Besides that morphine exposure up-regulated MAPK p38 (isoform CRA_b) which is a well-known up-stream mediator of phosphorylation and activation of HSP27 and α-B crystallin. Whereas there were no alterations in the levels of proteins involved in oxidative stress, several changes were determined in the levels of pro- and anti-apoptotic proteins. These data provide a complex view on quantitative changes in the cardiac proteome induced by morphine treatment or withdrawal and demonstrate great sensitivity of this organ to morphine.

  4. Global Changes in the Rat Heart Proteome Induced by Prolonged Morphine Treatment and Withdrawal

    PubMed Central

    Drastichova, Zdenka; Skrabalova, Jitka; Jedelsky, Petr; Neckar, Jan; Kolar, Frantisek; Novotny, Jiri

    2012-01-01

    Morphine belongs among the most commonly used opioids in medical practice due to its strong analgesic effects. However, sustained administration of morphine leads to the development of tolerance and dependence and may cause long-lasting alterations in nervous tissue. Although proteomic approaches enabled to reveal changes in multiple gene expression in the brain as a consequence of morphine treatment, there is lack of information about the effect of this drug on heart tissue. Here we studied the effect of 10-day morphine exposure and subsequent drug withdrawal (3 or 6 days) on the rat heart proteome. Using the iTRAQ technique, we identified 541 proteins in the cytosol, 595 proteins in the plasma membrane-enriched fraction and 538 proteins in the mitochondria-enriched fraction derived from the left ventricles. Altogether, the expression levels of 237 proteins were altered by morphine treatment or withdrawal. The majority of changes (58 proteins) occurred in the cytosol after a 3-day abstinence period. Significant alterations were found in the expression of heat shock proteins (HSP27, α-B crystallin, HSP70, HSP10 and HSP60), whose levels were markedly up-regulated after morphine treatment or withdrawal. Besides that morphine exposure up-regulated MAPK p38 (isoform CRA_b) which is a well-known up-stream mediator of phosphorylation and activation of HSP27 and α-B crystallin. Whereas there were no alterations in the levels of proteins involved in oxidative stress, several changes were determined in the levels of pro- and anti-apoptotic proteins. These data provide a complex view on quantitative changes in the cardiac proteome induced by morphine treatment or withdrawal and demonstrate great sensitivity of this organ to morphine. PMID:23056601

  5. Metformin induces cardioprotection against ischaemia/reperfusion injury in the rat heart 24 hours after administration.

    PubMed

    Solskov, Lasse; Løfgren, Bo; Kristiansen, Steen B; Jessen, Niels; Pold, Rasmus; Nielsen, Torsten T; Bøtker, Hans Erik; Schmitz, Ole; Lund, Sten

    2008-07-01

    The UK Prospective Diabetes Study demonstrated that the hypoglycaemic drug metformin is associated with a reduction in cardiovascular events in a group of obese type 2 diabetes patients. The energy sensing enzyme AMP-activated protein kinase (AMPK) has been indicated to play an important protective role in the ischaemic heart and is activated by metformin. The aim of this study was to determine whether a single dose of metformin protects the myocardium against experimentally induced ischaemia 24 hr after the administration, and furthermore to determine whether a single dose of metformin results in an acute increase in myocardial AMPK activity. Wistar rats were given either a single oral dose of metformin (250 mg/kg body weight), or a single oral dose of saline. After 24 hr, the hearts were Langendorff-perfused and subjected to 45 min. of coronary artery occlusion. Infarct size was determined by staining with triphenyltetrazoliumchloride (TTC) and Evans Blue and expressed as a percentage of the risk zone (IS/AAR %). Isoform specific AMPK activity was measured 2 hr after administration of metformin or saline. Infarct size was significantly reduced in the metformin treated (I/R: 19.9 +/- 3.9%versus 36.7 +/- 3.6%, P < 0.01, n = 8-14) compared to the control group. A single oral dose of metformin resulted in an approximately ~2-fold increase in AMPK-alpha2 activity 2 hr after administration (P < 0.015, n = 10). In conclusion, a single dose of metformin results in an acute increase in myocardial AMPK activity measured 2 hr after administration and induces a significant reduction in myocardial infarct size 24 hr after metformin administration. Increased AMPK activity may be an important signal mediator involved in the mechanisms behind the cardioprotective effects afforded by metformin.

  6. miRNA-146a induces vascular smooth muscle cell apoptosis in a rat model of coronary heart disease via NF-κB pathway.

    PubMed

    Wu, Z W; Liu, Y F; Wang, S; Li, B

    2015-12-29

    The aim of this study was to investigate the role of miRNA-146a in modulating the function of vascular smooth muscle cells in a rat model of coronary heart disease. Vascular smooth muscle cells were isolated and cultured from the rat coronary heart disease model and normal rats (controls). miRNA-146a levels were measured in vascular smooth muscle cells obtained from rats with coronary heart disease and control rats. The proliferation, growth, apoptosis, and activation of the NF-κB pathway in the vascular smooth muscle cells were detected using the MTT assay and flow cytometry, respectively. The role of the NF-κB pathway in modulating the apoptosis of vascular smooth muscle cells was investigated by measuring the reactivity of the cells to an NF-κB pathway inhibitor (TPCA-1). Vascular smooth muscle cells from the disease model exhibited higher levels of miRNA-146a than that by the normal controls (P = 0.0024). The vascular smooth muscle cells obtained from rats with coronary heart disease showed decreased proliferation and growth and increased apoptosis. miRNA-146a overexpression elevated the rate of cell apoptosis. The NF-κB pathway was activated in vascular smooth muscle cells obtained from rats with coronary heart disease. Inhibition of the NF- κB pathway significantly decreased the rate of vascular smooth muscle cell apoptosis in coronary heart disease rats (P = 0.0038). In conclusion, miRNA- 146a was found to induce vascular smooth muscle cell apoptosis in rats with coronary heart disease via the activation of the NF-κB signal pathway.

  7. Decreased long-chain fatty acid oxidation impairs postischemic recovery of the insulin-resistant rat heart.

    PubMed

    Harmancey, Romain; Vasquez, Hernan G; Guthrie, Patrick H; Taegtmeyer, Heinrich

    2013-10-01

    Diabetic patients with acute myocardial infarction are more likely to die than nondiabetic patients. In the present study we examined the effect of insulin resistance on myocardial ischemia tolerance. Hearts of rats, rendered insulin resistant by high-sucrose feeding, were subjected to ischemia/reperfusion ex vivo. Cardiac power of control hearts from chow-fed rats recovered to 93%, while insulin-resistant hearts recovered only to 80% (P<0.001 vs. control). Unexpectedly, impaired contractile recovery did not result from an impairment of glucose oxidation (576±36 vs. 593±42 nmol/min/g dry weight; not significant), but from a failure to increase and to sustain oxidation of the long-chain fatty acid oleate on reperfusion (1878±56 vs. 2070±67 nmol/min/g dry weight; P<0.05). This phenomenon was due to a reduced ability to transport oleate into mitochondria and associated with a 38-58% decrease in the mitochondrial uncoupling protein 3 (UCP3) levels. Contractile function was rescued by replacing oleate with a medium-chain fatty acid or by restoring UCP3 levels with 24 h of food withdrawal. Lastly, the knockdown of UCP3 in rat L6 myocytes also decreased oleate oxidation by 13-18% following ischemia. Together the results expose UCP3 as a critical regulator of long-chain fatty acid oxidation in the stressed heart postischemia and identify octanoate as an intervention by which myocardial metabolism can be manipulated to improve function of the insulin-resistant heart.

  8. Visualization and quantification of whole rat heart laminar structure using high-spatial resolution contrast-enhanced MRI

    PubMed Central

    Benoist, David; Benson, Alan P.; White, Ed; Tanner, Steven F.; Holden, Arun V.; Dobrzynski, Halina; Bernus, Olivier; Radjenovic, Aleksandra

    2012-01-01

    It has been shown by histology that cardiac myocytes are organized into laminae and this structure is important in function, both influencing the spread of electrical activation and enabling myocardial thickening in systole by laminar sliding. We have carried out high-spatial resolution three-dimensional MRI of the ventricular myolaminae of the entire volume of the isolated rat heart after contrast perfusion [dimeglumine gadopentate (Gd-DTPA)]. Four ex vivo rat hearts were perfused with Gd-DTPA and fixative and high-spatial resolution MRI was performed on a 9.4T MRI system. After MRI, cryosectioning followed by histology was performed. Images from MRI and histology were aligned, described, and quantitatively compared. In the three-dimensional MR images we directly show the presence of laminae and demonstrate that these are highly branching and are absent from much of the subepicardium. We visualized these MRI volumes to demonstrate laminar architecture and quantitatively demonstrated that the structural features observed are similar to those imaged in histology. We showed qualitatively and quantitatively that laminar architecture is similar in the four hearts. MRI can be used to image the laminar architecture of ex vivo hearts in three dimensions, and the images produced are qualitatively and quantitatively comparable with histology. We have demonstrated in the rat that: 1) laminar architecture is consistent between hearts; 2) myolaminae are absent from much of the subepicardium; and 3) although localized orthotropy is present throughout the myocardium, tracked myolaminae are branching structures and do not have a discrete identity. PMID:22021329

  9. Pre-treatment with a DPP-4 inhibitor is infarct sparing in hearts from obese, pre-diabetic rats.

    PubMed

    Huisamen, Barbara; Genis, Amanda; Marais, Erna; Lochner, Amanda

    2011-02-01

    Cardiovascular risk is closely associated with insulin resistance and type 2 diabetes. Therapy based on the actions of GLP-1 is currently seen as a novel approach to treat this disease. The aims of this study was therefore to use an animal model to determine whether (i) pre-treatment of obese, insulin resistant but pre-diabetic rats with a DPP4 inhibitor, PFK275-055, could protect the heart from ischaemia/reperfusion injury and (ii) the possible mechanisms involved in such protection. Obese, pre-diabetic rats (DIO) were treated for 4 weeks with 10 mg/kg/day of the DPP4 inhibitor PFK275-055. Ex vivo perfusion was used to subject hearts to ischaemia/reperfusion to determine infarct size, functional recovery and post-ischaemic activation of proteins associated with cardiac protection. Adult ventricular cardiomyocytes were isolated to determine insulin sensitivity. Other assessments included body weight, intra-peritoneal fat weight, insulin and GLP-1 levels as well as histological evaluation of the pancreata. Results showed that DIO animals had higher body mass and intra-peritoneal fat mass than chow-fed animals. They presented with elevated plasma insulin levels and lower GLP-1 levels. Treatment with the DPP4 inhibitor resulted in smaller infarct size development in hearts from DIO rats after ischaemia/reperfusion accompanied by activation of cardioprotective kinases. GLP-1 levels were elevated and plasma insulin levels lower after treatment. In addition, the beta-cell to alpha-cell ratio of the pancreas was improved. We conclude that treatment with PFK275-055 for 4 weeks protected the heart against ischaemia/reperfusion injury, elevated GLP-1 levels and improved metabolic control in obese, pre-diabetic rats.

  10. S100A1 transgenic treatment of acute heart failure causes proteomic changes in rats

    PubMed Central

    Guo, Yichen; Cui, Lianqun; Jiang, Shiliang; Wang, Dongmei; Jiang, Shu; Xie, Chen; Jia, Yanping

    2016-01-01

    S100 Ca2+-binding protein A1 (S100A1) is an important regulator of myocardial contractility. The aim of the present study was to identify the underlying mechanisms of S100A1 activity via profiling the protein expression in rats administered with an S100A1 adenovirus (Ad-S100A1-EGFP) following acute myocardial infarction (AMI). LTQ OrbiTrap mass spectrometry was used to profile the protein expression in the Ad-S100A1-EGFP and control groups post-AMI. Using Protein Analysis Through Evolutionary Relationships (PANTHER) analysis, 134 energy metabolism-associated proteins, which comprised 20 carbohydrate metabolism-associated and 27 lipid metabolism associated proteins, were identified as differentially expressed in the Ad-S100A1-EGFP hearts compared with controls. The majority of the differentially expressed proteins identified were important enzymes involved in energy metabolism. The present study identified 12 Ca2+-binding proteins and 22 cytoskeletal proteins. The majority of the proteins expressed in the Ad-S100A1-EGFP group were upregulated compared with the control group. These results were further validated using western blot analysis. Following AMI, Ca2+ is crucial for the recovery of myocardial function in S100A1 transgenic rats as indicated by the upregulation of proteins associated with energy metabolism and Ca2+-binding. Thus, the current study ascertained that energy production and contractile ability were enhanced after AMI in the ventricular myocardium of the Ad-S100A1-EGFP group. PMID:27357314

  11. Ozone protects rat heart against ischemia-reperfusion injury: A role for oxidative preconditioning in attenuating mitochondrial injury.

    PubMed

    Meng, Weixin; Xu, Ying; Li, Dandan; Zhu, Erjun; Deng, Li; Liu, Zonghong; Zhang, Guowei; Liu, Hongyu

    2017-04-01

    Ischemia-reperfusion injury (IRI) is a major cause of cardiac dysfunction during cardiovascular surgery, heart transplantation and cardiopulmonary bypass procedures. The purpose of the present study was to explore, firstly, whether ozone induces oxidative preconditioning by activation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and, secondly, whether ozone oxidative preconditioning (OzoneOP) can protect the heart against IRI by attenuating mitochondrial damage. Rats were subjected to 30min of cardiac ischemia followed by 2h of reperfusion, with or without prior OzoneOP (100μg/kg/day) for 5 days. Antioxidant capacity, myocardial apoptosis and mitochondrial damage were evaluated and compared at the end of reperfusion. OzoneOP was found to increase antioxidant capacity and to protect the myocardium against IRI by attenuating mitochondrial damage and myocardial apoptosis. The study suggests a potential role for OzoneOP in protecting the heart against IRI during cardiovascular surgery, cardiopulmonary bypass procedures or transplantation.

  12. Renoprotective effect of vasopressin v2 receptor antagonist tolvaptan in Dahl rats with end-stage heart failure.

    PubMed

    Ishikawa, Mayuko; Kobayashi, Naohiko; Sugiyama, Fumihiro; Onoda, Sho; Ishimitsu, Toshihiko

    2013-01-01

    Tolvaptan is a highly selective and orally effective arginine vasopressin V2 receptor antagonist, and is potentially useful for the treatment of heart failure (HF) patients. However, the renoprotective effect of long-term tolvaptan therapy and its underlying mechanisms remain unknown. We evaluated the effects of chronic treatment with tolvaptan on renal dysfunction, podocyte injury, inflammation, oxidative stress, Rho-kinase, epithelial-mesenchymal transition (EMT), and the extracellular signal-regulated protein kinase (ERK1/2) pathway in the renal cortex of Dahl salt-sensitive hypertensive (DS) rats with end-stage severe HF. DS and Dahl salt-resistant rats were fed a high-salt diet at 6 weeks of age. DS rats were treated with vehicle and tolvaptan (0.05% concentration in diet) from the age of 11 to 18 weeks. Vehicle-treated DS rats developed proteinuria, renal dysfunction, glomerulosclerosis, and interstitial fibrosis, which were ameliorated by tolvaptan without changing blood pressure. Decreased expression of nephrin and podocin and increased desmin-positive area in failing rats were restored by tolvaptan. Upregulation of NAD(P)H oxidase p22(phox), p47(phox), and gp91(phox), EMT markers such as transforming growth factor-β1, vimentin, and fibronectin expression, and Rho-kinase and ERK1/2 phosphorylation in DS rats were significantly suppressed by tolvaptan. Tolvaptan administration resulted in significant inhibition of tumor necrosis factor-α and monocyte chemoattractant protein-1 expression, and nuclear factor-κB phosphorylation. We concluded that long-term tolvaptan therapy may improve renal dysfunction, glomerulosclerosis, podocyte injury, and inflammation associated with oxidative stress, as well as EMT, ERK, and the Rho-kinase pathway in the failing heart of DS rats. Thus, tolvaptan may be a therapeutic strategy for end-stage severe HF.

  13. Effects of perfusion pressure and insulin on (/sup 3/H) cytochalasin B (CB) binding to control and diabetic rat hearts

    SciTech Connect

    Pleta, M.; Chan, T.

    1987-05-01

    Using (/sup 3/H) CB, they attempted to quantitate the changes in the amount of glucose transporters in the plasma membrane (PM) and intracellular membranes (HSP) prepared from rat hearts perfused with insulin, under low and high pressure. Membranes isolated from non-perfused hearts showed a PM/HSP ratio of (0.593). Hearts perfused with low pressure showed a lower ratio of (0.474). Perfusion with insulin increased the ratio to (1.8), almost a 3-4 fold increase from low perfusion pressure. These data correlate with insulin effects in glucose transport and CB binding in the fat cells. High pressure perfusion increased the PM/HSP ratio by 1-2 fold. (/sup 3/H) 2-DG transport indicates a comparable increase in glucose uptake with high pressure, but with insulin only a 1.5 fold increase was observed. Initial data obtained from streptozotocin (STZ) injected diabetic rats indicate low CB binding in the PM fraction. Only insulin, but not high perfusion pressure increased PM/HSP ratio in the STZ-diabetic hearts. Their data imply that while both caused apparent translocation of glucose transporters, influences on cardiac glucose metabolism by work load are different. Furthermore, STZ induced diabetes affected only the high perfusion pressure-induced and not the insulin-stimulated change in CB binding.

  14. The safety assessment of saffron (Crocus sativus L.) on sympathovagal balance and heart rate variability; a comparison with amiodarone.

    PubMed

    Joukar, Siyavash; Dehesh, Mohammad-Moein

    2015-12-01

    Dry stigmas of the Crocus sativus L. (Saffron) are well known in world as a popular flavouring and therapeutic agent. The anxiolytic, antidepressant, anticonvulsant and antiarrhythmic effects of saffron suggest that it may affect the autonomic control of the heart. This study assessed its safety on cardiac sympathovagal balance and heart rate variability in rat. Experimental groups were control, Saf50, Saf100, Saf200 (received saffron at dosages of 50 and 100 and 200 mg/kg/d, orally, respectively) and Amio (received 30 mg/mL/kg/d of amiodarone, orally, for 7 days) groups. On day 8, the frequency domain and time domain indices of animals' electrocardiograms were calculated. The heart rate decreased and RR interval increased in Saf200 and Amio groups (P<.05 vs other groups). Square root of the mean squared differences of successive RR intervals enhanced in all treated groups, however, was only significant in Amio group (P<.05). The SD1/SD2 ratio was higher in Saf200 and Amio groups. Both low-frequency (LF) and high-frequency (HF) parameters were higher, and the LF/HF ratio was non-significantly lower in treated groups. The findings suggest that saffron not only has no harmful effect on activity of cardiac autonomic nervous system, but it may improve the stability of heart sympathovagal balance in normal rat.

  15. Comparison of the effects of three different (-)-hydroxycitric acid preparations on food intake in rats: response

    PubMed Central

    Preuss, Harry G; Bagchi, Manashi; Bagchi, Debasis

    2006-01-01

    A response to Louter-van de Haar J, Wielinga PY, Scheurink AJ, Nieuwenhuizen AG: Comparison of the effects of three different (-)-hydroxycitric acid preparations on food intake in rats. Nutr Metabol 2005, 2:23 PMID:16846513

  16. [Expression of UCP3 and the sensitivity of mitochondrial permeability transition pore opening to Ca2+ in old rat heart under activation of biosynthesis of coenzyme Q].

    PubMed

    Strutyns'ka, N A; Timoshchuk, S V; Vavilova, H L; Kotsiuruba, A V; Sahach, V F

    2009-01-01

    The expression of mitochondrial uncoupling protein 3 (UCP3), as well as the sensitivity of mitochondrial permeability transition pore opening (MPTP) to Ca2+ (10(-4) mol/l) in old rat heart under activation in vivo of ubiquinone synthesis--coenzyme Q, (CoQ) via administration of the precursors (4-hydroxybenzoic acid, aminoacid methionine and modulator vitamin E) were studied. It was shown that the expression level of UCP3 decreased by 63% in old rats compared to adult rats and this was accompanied by an increased sensitivity of the MPT to calcium. Under activation of endogenous synthesis of CoQ it was observed almost complete restoration of UCP3 expression in old rat heart and a decrease in the sensitivity of the MPTP opening to Ca2+. In mitochondria from old rat hearts we noted an increased content of the superoxide (O2) and hydroxyl (OH) radicals and of the stable metabolite of active oxygen species hydrogen peroxide (H2O2), as compared to those in adult animals. Following activation of endogenous synthesis of CoQ in old rat heart mitochondria it was observed a decreased content of H2O2, and the tendency for decreasing the levels of the radicals O2 and MOH. The results obtained allowed to conclude that the CoQ-dependent restoration of the UCP3 levels in old rat heart and antioxidant/cardioprotective effects of CoQ related to the MPTP opening inhibition can reduce the oxidative stress and thus prevent the manifestation of mitochondrial dysfunction in aging heart. We suggest that UCP3 is not involved in the increase of the passive H-conductance through the inner mitochondrial membrane in the aging heart, and that CoQ as a factor of respiratory chain could be an important endogenous regulator of the uncoupling proteins, in particular UCP3, in the heart.

  17. 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.

  18. Phosphorylation of low-molecular-weight proteins in preparations of rat heart sarcolemma and sarcoplasmic reticulum.

    PubMed

    Lamers, J M; Stinis, J T

    1982-01-01

    Two substrate proteins for cAMP-dependent protein kinase detected in a rat heart sarcolemma preparation displayed molecular weights of 24,000 and 9000 in sodium dodecyl sulfate gels and were shown to be interconvertible. The 9000-dalton protein could readily be separated from other low molecular weight phosphoproteins (mol. wt. 14,000 and 7000) by the use of 15% polyacrylamide gels. In addition to an endogenous cAMP-dependent protein kinase the membrane preparation also contained a protein-phosphorylation system that required Ca2+ and calmodulin. It appeared that both 24,000- and 55,000-dalton proteins were substrates for the endogenous Ca2+- and calmodulin-dependent protein kinase. Contaminating sarcoplasmic reticulum vesicles, first loaded with calcium oxalate, could be separated from the enriched sarcolemma preparation by sucrose gradient centrifugation. The separation was confirmed by comparative analysis of 5'-nucleotidase, Na+ -Ca2+ antiporter, and (Ca2+ + Mg2+)-dependent ATPase activities and by determination of gel electrophoretic (phospho)protein composition, sialic acid, cholesterol, and phospholipid contents. The 24,000-dalton phosphoprotein complex was equally distributed between sarcolemmal and sarcoplasmic reticulum fractions, whereas the 55,000- and 7000-dalton proteins were predominantly found in the sarcolemmal fraction. The 24,000-dalton protein was most likely phospholamban, because no other phosphoprotein was found in the 20,000 molecular weight range.

  19. Endogenous adenosine release is involved in the control of heart rate in rats.

    PubMed

    Jammes, Yves; Joulia, Fabrice; Steinberg, Jean Guillaume; Ravailhe, Sylvie; Delpierre, Stéphane; Condo, Jocelyne; Guieu, Regis; Delliaux, Stéphane

    2015-08-01

    Intravenous (i.v.) injections of adenosine exert marked effects on heart rate (HR) and arterial blood pressure (BP), but the role of an endogenous adenosine release by vagal stimulation has not been evaluated. In anaesthetized rats, we examined HR and BP changes induced by 1 min electrical vagal stimulation in the control condition, and then after i.v. injections of (i) atropine, (ii) propranolol, (iii) caffeine, (iv) 8 cyclopentyl-1,3-dipropylxanthine (DPCPX), or (v) dipyridamole to increase the plasma concentration of adenosine (APC). APC was measured by chromatography in the arterial blood before and at the end of vagal stimulation. The decrease in HR in the controls during vagal stimulation was markedly attenuated, but persisted after i.v. injections of atropine and propranolol. When first administered, DPCPX modestly but significantly reduced the HR response to vagal stimulation, but this disappeared after i.v. caffeine administration. Both the HR and BP responses were significantly accentuated after i.v. injection of dipyridamole. Vagal stimulation induced a significant increase in APC, proportional to the magnitude of HR decrease. Our data suggest that the inhibitory effects of electrical vagal stimulations on HR and BP were partly mediated through the activation of A1 and A2 receptors by an endogenous adenosine release. Our experimental data could help to understand the effects of ischemic preconditioning, which are partially mediated by adenosine.

  20. Quantitation of cytosolic [Ca2+] in whole perfused rat hearts using Indo-1 fluorometry.

    PubMed Central

    Brandes, R; Figueredo, V M; Camacho, S A; Baker, A J; Weiner, M W

    1993-01-01

    Fluorometric determination of cytosolic calcium, [Ca2+]c, using Indo-1 in intact tissue, is limited by problems in obtaining calibration parameters for Indo-1 in vivo. Therefore, the goal of this study was to calibrate Indo-1 using in vitro constants, obtained from protein-containing reference solutions designed to produce similar Indo-1 spectral properties to those in vivo. Due to wavelength-dependent tissue light absorbance, the in vitro constants had to be absorbance-corrected using a novel method. The correction factor was calculated from the relationship between the Indo-1 fluorescence intensities at the two detection wavelengths. A mixture of proteins at approximately 28 mg/ml had a similar Indo-1 isosbestic wavelength (430 nm) to that found in vivo (427 nm), and a similar fluorescence ratio maximum with saturating Ca2+ to that found in vivo (after absorbance correction). Using calibration constants from this protein mixture, calculated [Ca2+]c in a Langendorf perfused rat heart was 187 nM during diastole, and 464 nM in systole. This new calibration method circumvented the considerable experimental problems of previous methods which required measurements with the cytosol fully depleted and fully saturated with Ca2+. PMID:8298027

  1. Fatty acid uptake by isolated rat heart myocytes represents a carrier-mediated transport process.

    PubMed Central

    Stremmel, W

    1988-01-01

    The mechanism by which fatty acids enter cardiomyocytes is unclear. Therefore, the influx kinetics of [3H]oleate into isolated rat heart myocytes were examined. Cells were incubated at 37 degrees C with [3H]oleate bound to albumin in various molar ratios and the initial rate of uptake (V0) was determined as a function of the unbound oleate concentration in the medium. V0 was saturable with increasing oleate concentrations incubated (Km 78 nM; Vmax 1.9 nmol X min-1 per 10(6) cells) and temperature dependent with an optimum at 37 degrees C. Furthermore, binding of [3H]oleate to isolated plasma membranes of cardiomyocytes was saturable, revealing a KD of 42 nM, and was inhibited by heat denaturation or trypsin pretreatment of the membranes. From these membranes a single 40-kD protein with high affinity for a variety of long chain fatty acids was isolated. With a monospecific antibody to this membrane protein, binding as well as cellular influx of [3H]oleate was selectively inhibited. These data indicate that at least a portion of myocardial fatty acid uptake is mediated by a specific membrane protein. Images PMID:3343344

  2. Tricarboxylic acid cycle metabolites during ischemia in isolated perfused rat heart.

    PubMed

    Peuhkurinen, K J; Takala, T E; Nuutinen, E M; Hassinen, I E

    1983-02-01

    Isolated rat hearts were, after a retrograde perfusion by the Langendorff procedure, rendered ischemic by lowering the aortic pressure to zero. The rate of proteolysis and temporal patterns of the changes in the concentrations of the metabolites of the tricarboxylic acid cycle, related amino acids, ammonia, and breakdown products of the adenine nucleotides were determined. The most significant change in the amino acid metabolism was a decrease of the proteolysis to one-tenth and a large accumulation of alanine, which was almost stoichiometric to the degradation of aspartate plus asparagine. The accumulation of malate and succinate was small compared with the metabolic net fluxes of aspartate and alanine. The metabolic balance sheet suggests that aspartate was converted to alanine. A prerequisite for this would be a feed in of carbon of aspartate to the tricarboxylic acid cycle as oxalacetate, reversal of the malate dehydrogenase, and production of pyruvate by the malic enzyme reaction. Alanine accumulating during ischemia is not glycolytic in origin but occurs through a concerted operation of anaplerotic reactions and tricarboxylic acid cycle metabolite disposal. The data also suggest that the potentially energy-yielding reduction of fumarate to succinate is not significant in the ischemic myocardium.

  3. Effects of moderate heart failure and functional overload on rat plantaris muscle

    NASA Technical Reports Server (NTRS)

    Spangenburg, Espen E.; Lees, Simon J.; Otis, Jeff S.; Musch, Timothy I.; Talmadge, Robert J.; Williams, Jay H.

    2002-01-01

    It is thought that changes in sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) of skeletal muscle contribute to alterations in skeletal muscle function during congestive heart failure (CHF). It is well established that exercise training can improve muscle function. However, it is unclear whether similar adaptations will result from exercise training in a CHF patient. Therefore, the purpose of this study was to determine whether skeletal muscle during moderate CHF adapts to increased activity, utilizing the functional overload (FO) model. Significant increases in plantaris mass of the CHF-FO and sham-FO groups compared with the CHF and control (sham) groups were observed. Ca(2+) uptake rates were significantly elevated in the CHF group compared with all other groups. No differences were detected in Ca(2+) uptake rates between the CHF-FO, sham, and sham-FO groups. Increases in Ca(2+) uptake rates in moderate-CHF rats were not due to changes in SERCA isoform proportions; however, FO may have attenuated the CHF-induced increases through alterations in SERCA isoform expression. Therefore, changes in skeletal muscle Ca(2+) handling during moderate CHF may be due to alterations in regulatory mechanisms, which exercise may override, by possibly altering SERCA isoform expression.

  4. Hemidesmus indicus and Hibiscus rosa-sinensis Affect Ischemia Reperfusion Injury in Isolated Rat Hearts

    PubMed Central

    Khandelwal, Vinoth Kumar Megraj; Balaraman, R.; Pancza, Dezider; Ravingerová, Táňa

    2011-01-01

    Hemidesmus indicus (L.) R. Br. (HI) and Hibiscus rosa-sinensis L. (HRS) are widely used traditional medicine. We investigated cardioprotective effects of these plants applied for 15 min at concentrations of 90, 180, and 360 μg/mL in Langendorff-perfused rat hearts prior to 25-min global ischemia/120-min reperfusion (I/R). Functional recovery (left ventricular developed pressure—LVDP, and rate of development of pressure), reperfusion arrhythmias, and infarct size (TTC staining) served as the endpoints. A transient increase in LVDP (32%–75%) occurred at all concentrations of HI, while coronary flow (CF) was significantly increased after HI 180 and 360. Only a moderate increase in LVDP (21% and 55%) and a tendency to increase CF was observed at HRS 180 and 360. HI and HRS at 180 and 360 significantly improved postischemic recovery of LVDP. Both the drugs dose-dependently reduced the numbers of ectopic beats and duration of ventricular tachycardia. The size of infarction was significantly decreased by HI 360, while HRS significantly reduced the infarct size at all concentrations in a dose-dependent manner. Thus, it can be concluded that HI might cause vasodilation, positive inotropic effect, and cardioprotection, while HRS might cause these effects at higher concentrations. However, further study is needed to elucidate the exact mechanism of their actions. PMID:20953394

  5. Stromal cell derived factor-1 (SDF-1) targeting reperfusion reduces myocardial infarction in isolated rat hearts.

    PubMed

    Jang, Young-Ho; Kim, June-Hong; Ban, Changill; Ahn, Kyohan; Cheong, Jae-Hun; Kim, Hyung-Hoi; Kim, Jung-Soo; Park, Yong-Hyun; Kim, Jun; Chun, Kook-Jin; Lee, Gyeong-Ho; Kim, Miju; Kim, Cheolmin; Xu, Zhelong

    2012-10-01

    Recent studies have shown that stromal cell derived factor-1 (SDF-1), first known as a cytokine involved in recruiting stem cells into injured organs, confers myocardial protection in myocardial infarction, which is not dependent on stem cell recruitment but related with modulation of ischemia-reperfusion (I/R) injury. However, the effect of SDF has been studied only in a preischemic exposure model, which is not clinically relevant if SDF is to be used as a therapeutic agent. Our study was aimed at evaluating whether or not SDF-1 confers cardioprotection during the reperfusion period. Hearts from SD rats were isolated and perfused with the Langendorff system. Proximal left coronary artery ligation, reperfusion, and SDF perfusion in KH buffer was done according to study protocol. Area of necrosis (AN) relative to area at risk (AR) was the primary endpoint of the study. Significant reduction of AN/AR by SDF in an almost dose-dependent manner was noted during both the preischemic exposure and reperfusion periods. In particular, infusion of a high concentration of SDF (25 nM/L) resulted in a dramatic reduction of infarct size, which was greater than that achieved with ischemic pre- or postconditioning. SDF perfusion during reperfusion was associated with a similar significant reduction of infarct size as preischemic SDF exposure. Further studies are warranted to assess the potential of SDF as a therapeutic agent for reducing I/R injury in clinical practice.

  6. Purinergic component in the coronary vasodilatation to acetylcholine after ischemia-reperfusion in perfused rat hearts.

    PubMed

    García-Villalón, Ángel Luis; Granado, Miriam; Monge, Luis; Fernández, Nuria; Carreño-Tarragona, Gonzalo; Amor, Sara

    2014-01-01

    To determine the involvement of purinergic receptors in coronary endothelium-dependent relaxation, the response to acetylcholine (1 × 10(-8) to 3 × 10(-7)M) was recorded in isolated rat hearts perfused according to the Langendorff procedure before and after 30 min of ischemia and 15 min of reperfusion and after the inhibition of nitric oxide synthesis with L-NAME (10(-4)M), in the absence and presence of the antagonist of purinergic P2X receptors, PPADS (3 × 10(-6)M), and of the antagonist of purinergic P2Y receptors, Reactive Blue 2 (3 × 10(-7)M). In control conditions, the relaxation to acetylcholine was not altered by PPADS or Reactive Blue 2. The relaxation to acetylcholine was reduced after ischemia-reperfusion, and, in this condition, it was further reduced by treatment with PPADS or Reactive Blue 2. Likewise, the relaxation to acetylcholine was reduced by L-NAME, and reduced further by Reactive Blue 2 but not by PPADS. These results suggest that the relaxation to acetylcholine may be partly mediated by purinergic receptors after ischemia-reperfusion, due to the reduction of nitric oxide release in this condition.

  7. Comparison of biomaterial delivery vehicles for improving acute retention of stem cells in the infarcted heart.

    PubMed

    Roche, Ellen T; Hastings, Conn L; Lewin, Sarah A; Shvartsman, Dmitry E; Brudno, Yevgeny; Vasilyev, Nikolay V; O'Brien, Fergal J; Walsh, Conor J; Duffy, Garry P; Mooney, David J

    2014-08-01

    Cell delivery to the infarcted heart has emerged as a promising therapy, but is limited by very low acute retention and engraftment of cells. The objective of this study was to compare a panel of biomaterials to evaluate if acute retention can be improved with a biomaterial carrier. Cells were quantified post-implantation in a rat myocardial infarct model in five groups (n = 7-8); saline injection (current clinical standard), two injectable hydrogels (alginate, chitosan/β-glycerophosphate (chitosan/ß-GP)) and two epicardial patches (alginate, collagen). Human mesenchymal stem cells (hMSCs) were delivered to the infarct border zone with each biomaterial. At 24 h, retained cells were quantified by fluorescence. All biomaterials produced superior fluorescence to saline control, with approximately 8- and 14-fold increases with alginate and chitosan/β-GP injectables, and 47 and 59-fold increases achieved with collagen and alginate patches, respectively. Immunohistochemical analysis qualitatively confirmed these findings. All four biomaterials retained 50-60% of cells that were present immediately following transplantation, compared to 10% for the saline control. In conclusion, all four biomaterials were demonstrated to more efficiently deliver and retain cells when compared to a saline control. Biomaterial-based delivery approaches show promise for future development of efficient in vivo delivery techniques.

  8. Central command dysfunction in rats with heart failure is mediated by brain oxidative stress and normalized by exercise training.

    PubMed

    Koba, Satoshi; Hisatome, Ichiro; Watanabe, Tatsuo

    2014-09-01

    Sympathoexcitation elicited by central command, a parallel activation of the motor and autonomic neural circuits in the brain, has been shown to become exaggerated in chronic heart failure (CHF). The present study tested the hypotheses that oxidative stress in the medulla in CHF plays a role in exaggerating central command-elicited sympathoexcitation, and that exercise training in CHF suppresses central command-elicited sympathoexcitation through its antioxidant effects in the medulla. In decerebrate rats, central command was activated by electrically stimulating the mesencephalic locomotor region (MLR) after neuromuscular blockade. The MLR stimulation at a current intensity greater than locomotion threshold in rats with CHF after myocardial infarction (MI) evoked larger (P < 0.05) increases in renal sympathetic nerve activity and arterial pressure than in sham-operated healthy rats (Sham) and rats with CHF that had completed longterm (8–12 weeks) exercise training (MI + TR). In the Sham and MI + TR rats, bilateral microinjection of a superoxide dismutase (SOD) mimetic Tempol into the rostral ventrolateral medulla (RVLM) had no effects on MLR stimulation-elicited responses. By contrast, in MI rats, Tempol treatment significantly reduced MLR stimulation-elicited responses. In a subset of MI rats, treatment with Tiron, another SOD mimetic, within the RVLM also reduced responses. Superoxide generation in the RVLM, as evaluated by dihydroethidium staining, was enhanced in MI rats compared with that in Sham and MI + TR rats. Collectively, these results support the study hypotheses. We suggest that oxidative stress in the medulla in CHF mediates central command dysfunction, and that exercise training in CHF is capable of normalizing central command dysfunction through its antioxidant effects in the medulla.

  9. Altered essential fatty acid metabolism and composition in rat liver, plasma, heart and brain after microalgal DHA addition to the diet.

    PubMed

    Lin, Yu Hong; Shah, Samit; Salem, Norman

    2011-08-01

    To investigate the effect of docosahexaenoic acid (DHA) without other highly unsaturated fatty acids (HUFA) on n-3 and n-6 essential fatty acid (EFA) metabolism and fatty acid composition in mammals, a stable isotope tracer technique was used in adult rats fed diets with or without 1.3% of algal DHA in a base diet containing 15% of linoleic acid and 3% of alpha-linolenic acid over 8 weeks. The rats were administered orally a mixed oil containing 48 mg/kg body weight of deuterated linoleic and alpha-linolenic acids and euthanized at 4, 8, 24, 96, 168, 240, 360 and 600 h after administration of the isotopes. Fatty acid compositions and the concentrations of deuterated precursors and their respective metabolites were determined in rat liver, plasma, heart and brain as a function of time. DHA, docosapentaenoic acid and eicosapentaenoic acid in the n-3 EFA family were significantly increased in all organs tested in the DHA-fed group, ranging from 5% to 200% greater in comparison with the control group. The accumulation of the metabolites, deuterated-DHA and deuterated-docosapentaenoic acid n-6 was greatly decreased by 1.5- to 2.5-fold in the dietary DHA group. In summary, feeding preformed DHA led to a marked increase in n-3 HUFA content of rat organs at the expense of n-6 HUFA and also prevented the accumulation of newly synthesized deuterated end products. This is the first study which has isolated the effects of DHA on the de novo metabolism on both the n-6 and n-3 EFA pathways.

  10. Effects of treppe and calcium on intracellular calcium and function in the failing heart from the spontaneously hypertensive rat.

    PubMed

    Brooks, W W; Bing, O H; Litwin, S E; Conrad, C H; Morgan, J P

    1994-09-01

    We studied functional and intracellular calcium responses to treppe and extracellular calcium in spontaneously hypertensive rat (SHR) hearts during the transition from compensated pressure overload to failure. Intracellular calcium was measured using aequorin, a bioluminescent Ca2+ indicator. Experiments were performed with intact, isovolumically contracting, buffer-perfused hearts from three rat groups: (1) aging SHR with evidence of heart failure (SHR-F), (2) age-matched SHR with no evidence of heart failure (SHR-NF), and (3) age-matched normotensive Wistar-Kyoto (WKY) rats. In each experiment, left ventricular pressure and intracellular calcium transients were simultaneously recorded. Hearts were studied at 30 degrees C and paced at a rate of 1.6 Hz while being perfused with oxygenated Krebs-Henseleit solution (95% O2/5% CO2) at 100 mm Hg. At the baseline state, peak systolic pressure was greatest in the SHR-NF group and lowest in the SHR-F group. Peak and resting [Ca2+]i were not significantly different among groups; however, the calcium transient was prolonged in the SHR-NF and SHR-F groups. With increasing perfusate [Ca2+]o from 0.5 to 3.0 mmol/L, the relative increases in peak [Ca2+]i and peak systolic pressure were similar among groups. When stimulation rate was increased from 1.6 to 2.0, 2.4, 2.8, and 3.2 Hz, peak [Ca2+]i, peak systolic pressure, and +/- dP/dt fell in SHR-F hearts. Peak systolic pressure decreased in the SHR-NF group at rates above 2.4 Hz but did not decline in the WKY group. Peak [Ca2+]i increased in the WKY and SHR-NF groups with increasing heart rates. Peak systolic pressure did not fall significantly in the WKY group at any heart rate. Elevation of diastolic [Ca2+]i and/or calcium transient and pressure alternans were present in 8 of 13 SHR-F hearts at the highest stimulation rate, findings that were absent in both the WKY and SHR-NF hearts. We conclude the following: (1) Under baseline conditions, depressed contractile function of

  11. Protective Effect of Antenatal Antioxidant on Nicotine-Induced Heart Ischemia-Sensitive Phenotype in Rat Offspring.

    PubMed

    Xiao, DaLiao; Wang, Lei; Huang, Xiaohui; Li, Yong; Dasgupta, Chiranjib; Zhang, Lubo

    2016-01-01

    Fetal nicotine exposure increased risk of developing cardiovascular disease later in life. The present study tested the hypothesis that perinatal nicotine-induced programming of heart ischemia-sensitive phenotype is mediated by enhanced reactive oxygen species (ROS) in offspring. Nicotine was administered to pregnant rats via subcutaneous osmotic minipumps from day 4 of gestation to day 10 after birth, in the absence or presence of a ROS inhibitor, N-acetyl-cysteine (NAC) in drinking water. Experiments were conducted in 8 month old age male offspring. Isolated hearts were perfused in a Langendorff preparation. Perinatal nicotine treatment significantly increased ischemia and reperfusion-induced left ventricular injury, and decreased post-ischemic recovery of left ventricular function and coronary flow rate. In addition, nicotine enhanced cardiac ROS production and significantly attenuated protein kinase Cε (PKCε) protein abundance in the heart. Although nicotine had no effect on total cardiac glycogen synthase kinase-3β (GSK3β) protein expression, it significantly increased the phosphorylation of GSK3β at serine 9 residue in the heart. NAC inhibited nicotine-mediated increase in ROS production, recovered PKCε gene expression and abrogated increased phosphorylation of GSK3β. Of importance, NAC blocked perinatal nicotine-induced increase in ischemia and reperfusion injury in the heart. These findings provide novel evidence that increased oxidative stress plays a causal role in perinatal nicotine-induced developmental programming of ischemic sensitive phenotype in the heart, and suggest potential therapeutic targets of anti-oxidative stress in the treatment of ischemic heart disease.

  12. The role of transient outward K+ current in electrical remodelling induced by voluntary exercise in female rat hearts.

    PubMed

    Stones, Rachel; Billeter, Rudolf; Zhang, Henggui; Harrison, Simon; White, Ed

    2009-11-01

    Regular exercise can lead to electrical remodelling of the heart. The cellular mechanisms associated with these changes are not well understood, and are difficult to study in human tissue but are important given that exercise is recommended to the general population. We have investigated the role played by the transient outward K+ current (I(to)) in the changes in electrical activity seen in response to voluntary exercise training in rats. Female rats undertook 6 weeks of voluntary wheel running exercise (TRN) or were sedentary controls (SED). Monophasic action potentials (MAPs) were recorded from the surface of whole hearts. Whole cell patch clamp recordings of I(to); mRNA and protein levels of selected targets in sub-epicardial (EPI) and sub-endocardial myocardium of SED and TRN hearts were compared. In TRN rats, heart weight:body weight was significantly increased and epicardial MAPs significantly prolonged. I(to) density was reduced in TRN EPI myocytes, such that the transmural gradient of I(to) was significantly reduced (P < 0.05). Computer modelling of these changes in I(to) predicted the observed changes in action potential profile. However, transmural gradients in mRNA and protein expression for Kv4.2 or mRNA levels of the Kv4.2 regulators; KChIP2 and Irx-5 were not significantly altered by voluntary exercise. We conclude that voluntary exercise electrical remodelling is caused, at least in part, by a decrease in EPI I(to), possibly because of fewer functional channels in the membrane, which results in a fall in the transmural action potential duration gradient.

  13. Short-term melatonin consumption protects the heart of obese rats independent of body weight change and visceral adiposity.

    PubMed

    Nduhirabandi, Frederic; Huisamen, Barbara; Strijdom, Hans; Blackhurst, Dee; Lochner, Amanda

    2014-10-01

    Chronic melatonin treatment has been shown to prevent the harmful effects of diet-induced obesity and reduce myocardial susceptibility to ischaemia-reperfusion injury (IRI). However, the exact mechanism whereby it exerts its beneficial actions on the heart in obesity/insulin resistance remains unknown. Herein, we investigated the effects of relatively short-term melatonin treatment on the heart in a rat model of diet-induced obesity. Control and diet-induced obese Wistar rats (fed a high calorie diet for 20 wk) were each subdivided into three groups receiving drinking water with or without melatonin (4 mg/kg/day) for the last 6 or 3 wk of experimentation. A number of isolated hearts were perfused in the working mode, subjected to regional or global ischaemia-reperfusion; others were nonperfused. Metabolic parameters, myocardial infarct sizes (IFS), baseline and postischaemic activation of PKB/Akt, ERK42/44, GSK-3β and STAT-3 were determined. Diet-induced obesity caused increases in body weight gain, visceral adiposity, fasting blood glucose, serum insulin and triglyceride (TG) levels with a concomitant cardiac hypertrophy, large postischaemic myocardial IFSs and a reduced cardiac output. Melatonin treatment (3 and 6 wk) decreased serum insulin levels and the HOMA index (P < 0.05) with no effect on weight gain (after 3 wk), visceral adiposity, serum TG and glucose levels. It increased serum adiponectin levels, reduced myocardial IFSs in both groups and activated baseline myocardial STAT-3 and PKB/Akt, ERK42/44 and GSK-3β during reperfusion. Overall, short-term melatonin administration to obese/insulin resistant rats reduced insulin resistance and protected the heart against ex vivo myocardial IRI independently of body weight change and visceral adiposity.

  14. Erythroblast transformation-specific 2 correlates with vascular smooth muscle cell apoptosis in rat heterotopic heart transplantation model

    PubMed Central

    Liu, Xiaojuan; Yan, Daliang; Li, Yangcheng; Sha, Xilin; Wu, Kunpeng; Zhao, Jianhua; Yang, Chen; Zhang, Chao

    2016-01-01

    Background Cardiac allograft vasculopathy (CAV) decreases the long-term survival of heart transplantation recipients. Vascular smooth muscle cell (VSMC) apoptosis is an important pathological feature of CAV. Erythroblast transformation-specific 2 (Ets-2), as a transcription factor, participates in cell apoptosis and plays an important role in organ transplantation. Methods Hearts from Wistar-Furth (WF:RT1u) rats were heterotopically transplanted into Lewis (Lew:RT1l) rats without immunosuppression. Additional syngeneic heterotopic cardiac transplantations were performed in Lewis rats. HE staining was used to identify CAV. Ets-2 expression was examined by western blot. Ets-2 tissue location was examined by immunohistochemical assay and double immunostaining. Cleaved caspase 3 expression was detected by western blot. Co-localization of Ets-2 and cleaved caspase 3 was detected by double immunostaining. Ets-2, p53, cleaved caspase 3 and Bcl-xl expression in rat VSMC line A7R5 was examined after Ets-2 siRNA transfection. TUNEL assay was applied to detect A7R5 apoptosis with or without ETS-2 siRNA transfection. Immunoprecipitation was performed to explore the interaction between Ets-2 and p53. Results Ets-2 expression decreased in the allograft group but had no obvious change in the isograft group. Meanwhile, the phenomenon of CAV was observed in the allograft group and there is neointima formation in the isograft group which is not obvious compared with allograft group. Additionally, Ets-2 expression was opposite to VSMC apoptosis in the allograft group. In vitro, Ets-2 siRNA transfection in A7R5cells resulted in enhanced cell apoptosis. Finally, Ets-2 interacted with p53. Conclusions Ets-2 might inhibit VSMC apoptosis via p53 pathway. The results further elucidate the molecular mechanism of VSMC apoptosis after heart transplantation during CAV and provide theoretical basis for seeking new specific drug targets for CAV prevention and treatment. PMID:27621856

  15. Effect of static magnetic field and/or cadmium in the antioxidant enzymes activity in rat heart and skeletal muscle.

    PubMed

    Amara, Salem; Garrel, Catherine; Favier, Alain; Ben Rhouma, Khémais; Sakly, Mohsen; Abdelmelek, Hafedh

    2009-12-01

    Currently, environmental and industrial pollution along with increase and causes multiple stress conditions, the combined exposure to magnetic field and other toxic agents is recognised as an important research area, with a view to better protecting human health against their probable unfavourable effects. In the present study, we investigated the effect of co-exposure to static magnetic field (SMF) and cadmium (Cd) on the antioxidant enzymes activity and the malondialdehyde (MDA) concentration in rat skeletal and cardiac muscles. The exposure of rats to SMF (128 mT, 1 h/day during 30 consecutive days) decreased the activities of glutathione peroxidase (GPx) and the superoxide dismutase (CuZn-SOD) in heart muscle. Sub-chronic exposure to SMF increased the MDA concentration in rat cardiac muscle. Cd treatment (CdCl2, 40 mg/l, per os) during 4 weeks decreased the activities of catalase (CAT) in skeletal muscle and the CuZn-SOD in the heart. Moreover, Cd administration increased MDA concentration in the both structures. The combined effect of SMF (128 mT, 1 h/day during 30 consecutive days) and Cd (40 mg/l, per os) disrupt the antioxidant enzymes activity in rat skeletal and cardiac muscles. Moreover, we noted a huge increase in MDA concentration in the heart and skeletal muscle compared to control group. Thus it is possible that the SMF- and/or Cd-induced depletion of antioxidant enzymes activity in muscle tissues might, like the enhanced lipid peroxidation, importantly contribute to oxidative damage. The combined effect of SMF and Cd altered significantly the antioxidant enzymatic capacity and induced lipid peroxidation in both skeletal and cardiac muscle.

  16. Respiratory muscle training improves hemodynamics, autonomic function, baroreceptor sensitivity, and respiratory mechanics in rats with heart failure.

    PubMed

    Jaenisch, Rodrigo B; Hentschke, Vítor S; Quagliotto, Edson; Cavinato, Paulo R; Schmeing, Letiane A; Xavier, Léder L; Dal Lago, Pedro

    2011-12-01

    Respiratory muscle training (RMT) improves functional capacity in chronic heart-failure (HF) patients, but the basis for this improvement remains unclear. We evaluate the effects of RMT on the hemodynamic and autonomic function, arterial baroreflex sensitivity (BRS), and respiratory mechanics in rats with HF. Rats were assigned to one of four groups: sedentary sham (n = 8), trained sham (n = 8), sedentary HF (n = 8), or trained HF (n = 8). Trained animals underwent a RMT protocol (30 min/day, 5 day/wk, 6 wk of breathing through a resistor), whereas sedentary animals did not. In HF rats, RMT had significant effects on several parameters. It reduced left ventricular (LV) end-diastolic pressure (P < 0.01), increased LV systolic pressure (P < 0.01), and reduced right ventricular hypertrophy (P < 0.01) and pulmonary (P < 0.001) and hepatic (P < 0.001) congestion. It also decreased resting heart rate (HR; P < 0.05), indicating a decrease in the sympathetic and an increase in the vagal modulation of HR. There was also an increase in baroreflex gain (P < 0.05). The respiratory system resistance was reduced (P < 0.001), which was associated with the reduction in tissue resistance after RMT (P < 0.01). The respiratory system and tissue elastance (Est) were also reduced by RMT (P < 0.01 and P < 0.05, respectively). Additionally, the quasistatic Est was reduced after RMT (P < 0.01). These findings show that a 6-wk RMT protocol in HF rats promotes an improvement in hemodynamic function, sympathetic and vagal heart modulation, arterial BRS, and respiratory mechanics, all of which are benefits associated with improvements in cardiopulmonary interaction.

  17. Attenuation of Ca2+ homeostasis, oxidative stress, and mitochondrial dysfunctions in diabetic rat heart: insulin therapy or aerobic exercise?

    PubMed

    da Silva, Márcia F; Natali, Antônio J; da Silva, Edson; Gomes, Gilton J; Teodoro, Bruno G; Cunha, Daise N Q; Drummond, Lucas R; Drummond, Filipe R; Moura, Anselmo G; Belfort, Felipe G; de Oliveira, Alessandro; Maldonado, Izabel R S C; Alberici, Luciane C

    2015-07-15

    We tested the effects of swimming training and insulin therapy, either alone or in combination, on the intracellular calcium ([Ca(2+)]i) homeostasis, oxidative stress, and mitochondrial functions in diabetic rat hearts. Male Wistar rats were separated into control, diabetic, or diabetic plus insulin groups. Type 1 diabetes mellitus was induced by streptozotocin (STZ). Insulin-treated groups received 1 to 4 UI of insulin daily for 8 wk. Each group was divided into sedentary or exercised rats. Trained groups were submitted to swimming (90 min/day, 5 days/wk, 8 wk). [Ca(2+)]i transient in left ventricular myocytes (LVM), oxidative stress in LV tissue, and mitochondrial functions in the heart were assessed. Diabetes reduced the amplitude and prolonged the times to peak and to half decay of the [Ca(2+)]i transient in LVM, increased NADPH oxidase-4 (Nox-4) expression, decreased superoxide dismutase (SOD), and increased carbonyl protein contents in LV tissue. In isolated mitochondria, diabetes increased Ca(2+) uptake, susceptibility to permeability transition pore (MPTP) opening, uncoupling protein-2 (UCP-2) expression, and oxygen consumption but reduced H2O2 release. Swimming training corrected the time course of the [Ca(2+)]i transient, UCP-2 expression, and mitochondrial Ca(2+) uptake. Insulin replacement further normalized [Ca(2+)]i transient amplitude, Nox-4 expression, and carbonyl content. Alongside these benefits, the combination of both therapies restored the LV tissue SOD and mitochondrial O2 consumption, H2O2 release, and MPTP opening. In conclusion, the combination of swimming training with insulin replacement was more effective in attenuating intracellular Ca(2+) disruptions, oxidative stress, and mitochondrial dysfunctions in STZ-induced diabetic rat hearts.

  18. Enhanced incorporation of docosahexaenoic acid in serum, heart, and brain of rats given microemulsions of fish oil.

    PubMed

    Sugasini, D; Lokesh, B R

    2013-10-01

    Long-chain n-3 fatty acids are essential for the development of cognitive functions and reducing the risk factor for cardiovascular diseases. The present study was undertaken to prepare fish oil (FO) microemulsion and explore the possibility of enhancing the enrichment of long-chain n-3 PUFA in the heart and brain lipids. The bioavailability of encapsulated FO was compared with that of native oil in rats by utilizing the intestinal sac method and by an in vivo study giving microemulsions of FO through intubation for a period of 30 days. Microemulsions were prepared using chitosan, gum acacia, whey protein, and lipoid. The bioavailability of eicosapentaenoic acid and docosahexaenoic acid (DHA) from FO encapsulated in chitosan, gum acacia, whey protein, and lipoid was increased by 7, 9, 23, and 68%, respectively, as compared to oil given without encapsulation in the everted intestinal sacs model. The DHA levels in serum lipids when FO was given as lipoid emulsion to rats were found to be 56 μg/ml, while rats given FO without encapsulation had a DHA level of 22 μg/ml. In the heart and brain lipids, the DHA levels were increased by 77 and 41%, respectively, in rats given FO encapsulated with lipoid compared to those given native oil. These studies indicated that DHA from FO was taken up in a more efficient manner when given in an encapsulated form with lipoid. Thus, phospholipid-based binding materials such as Lipoid provide a good delivery system for FO and significantly enhance DHA levels in the serum, liver, heart, and brain tissues.

  19. Comparison of Traditional and Alternative Fitness Teaching Formats on Heart Rate Intensity and Perceived Enjoyment.

    ERIC Educational Resources Information Center

    Ha, Amy Sau-ching; Heung-Sang Wong, Stephen

    2002-01-01

    Compared a traditional and an alternative (skill-fitness- music) fitness teaching format to determine whether there would be differences on Hong Kong middle school students' heart rate intensity and perceived enjoyment. Data from heart rate monitors and student surveys indicated that the two formats did not produce differences in heart rates.…

  20. Bromide-dependent toxicity of eosinophil peroxidase for endothelium and isolated working rat hearts: a model for eosinophilic endocarditis.

    PubMed

    Slungaard, A; Mahoney, J R

    1991-01-01

    Eosinophilic endocarditis is a potentially lethal complication of chronic peripheral blood hypereosinophilia. We hypothesized that eosinophil peroxidase (EPO), an abundant eosinophil (EO) cationic granule protein, promotes eosinophilic endocarditis by binding to negatively charged endocardium, and there generating cytotoxic oxidants. Using an immunocytochemical technique, we demonstrated endocardial deposition of EPO in the heart of a patient with hypereosinophilic heart disease. Because EPO preferentially oxidizes Br- to hypobromous acid (HOBr) rather than Cl- to hypochlorous acid (HOCl) at physiologic halide concentrations, we characterized the Br(-)-dependent toxicity of both activated EOs and purified human EPO towards several types of endothelial cells and isolated working rat hearts. In RPMI supplemented with 100 microM Br-, phorbol myristate acetate-activated EOs, but not polymorphonuclear leukocytes, caused 1.8-3.6 times as much 51Cr release from four types of endothelial cell monolayers as in RPMI alone. H2O2 and purified human EPO, especially when bound to cell surfaces, mediated extraordinarily potent, completely Br(-)-dependent cytolysis of endothelial cells that was reversed by peroxidase inhibitors, HOBr scavengers, and competitive substrates. We further modeled eosinophilic endocarditis by instilling EPO into the left ventricles of isolated rat hearts, flushing unbound EPO, then perfusing them with a buffer containing 100 microM Br- and 1 microM H2O2. Acute congestive heart failure (evidenced by a precipitous decrement in rate pressure product, stroke volume work, aortic output, and MVO2 to 0-33% of control values) ensued over 20 min, which deletion of EPO, Br-, or H2O2 completely abrogated. These findings raise the possibility that EPO bound to endocardial cells might utilize H2O2 generated either by overlying phagocytes or endogenous cardiac metabolism along with the virtually inexhaustible supply of Br- from flowing blood to fuel HOBr

  1. Bromide-dependent toxicity of eosinophil peroxidase for endothelium and isolated working rat hearts: a model for eosinophilic endocarditis

    PubMed Central

    1991-01-01

    Eosinophilic endocarditis is a potentially lethal complication of chronic peripheral blood hypereosinophilia. We hypothesized that eosinophil peroxidase (EPO), an abundant eosinophil (EO) cationic granule protein, promotes eosinophilic endocarditis by binding to negatively charged endocardium, and there generating cytotoxic oxidants. Using an immunocytochemical technique, we demonstrated endocardial deposition of EPO in the heart of a patient with hypereosinophilic heart disease. Because EPO preferentially oxidizes Br- to hypobromous acid (HOBr) rather than Cl- to hypochlorous acid (HOCl) at physiologic halide concentrations, we characterized the Br(-)- dependent toxicity of both activated EOs and purified human EPO towards several types of endothelial cells and isolated working rat hearts. In RPMI supplemented with 100 microM Br-, phorbol myristate acetate- activated EOs, but not polymorphonuclear leukocytes, caused 1.8-3.6 times as much 51Cr release from four types of endothelial cell monolayers as in RPMI alone. H2O2 and purified human EPO, especially when bound to cell surfaces, mediated extraordinarily potent, completely Br(-)-dependent cytolysis of endothelial cells that was reversed by peroxidase inhibitors, HOBr scavengers, and competitive substrates. We further modeled eosinophilic endocarditis by instilling EPO into the left ventricles of isolated rat hearts, flushing unbound EPO, then perfusing them with a buffer containing 100 microM Br- and 1 microM H2O2. Acute congestive heart failure (evidenced by a precipitous decrement in rate pressure product, stroke volume work, aortic output, and MVO2 to 0-33% of control values) ensued over 20 min, which deletion of EPO, Br-, or H2O2 completely abrogated. These findings raise the possibility that EPO bound to endocardial cells might utilize H2O2 generated either by overlying phagocytes or endogenous cardiac metabolism along with the virtually inexhaustible supply of Br- from flowing blood to fuel HOBr

  2. Effects of wire-bottom caging on heart rate, activity and body temperature in telemetry-implanted rats.

    PubMed

    Giral, Marta; García-Olmo, Dolores C; Kramer, Klaas

    2011-10-01

    Some experimental procedures are associated with placement of animals in wire-bottom cages. The goal of this study was to evaluate stress-related physiological parameters (heart rate [HR], body temperature [BT], locomotor activity [LA], body weight [BW] and food consumption) in rats under two housing conditions, namely in wire-bottom cages and in bedding-bottom cages. Telemetry devices were surgically implanted in male Sprague-Dawley rats. HR, BT and LA were recorded at 5 min intervals. Analysis under each housing condition was performed from 16:00 to 08:00 h of the following day (4 h light, 12 h dark). During almost all of the light phase, the HR of rats housed in wire-bottom cages remained high (371 ± 35 bpm; mean ± SD; n = 6) and was significantly different from that of rats housed in bedding-bottom cages (340 ± 29 bpm; n = 6; P < 0.001; Student's t-test). In general, BT was similar under the two housing conditions. However, when rats were in wire-bottom cages, BT tended to fluctuate more widely during the dark phase. LA decreased when animals were housed in wire-bottom cages, in particular during the dark phase. Moreover, there was a significant difference with respect to the gain in BW: BW of rats housed in bedding-bottom cages increased 12 ± 2 g, whereas that of rats in wire-bottom cages decreased by 2 ± 3 g (P < 0.001). Our results demonstrate that housing rats in wire-bottom cages overnight leads to immediate alterations of HR, BW and LA, which might be related to a stress response.

  3. 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.

  4. Diabetes and the control of pyruvate dehydrogenase in rat heart mitochondria by concentration ratios of adenosine triphosphate/adenosine diphosphate, of reduced/oxidized nicotinamide-adenine dinucleotide and of acetyl-coenzyme A/coenzyme A.

    PubMed Central

    Kerbey, A L; Radcliffe, P M; Randle, P J

    1977-01-01

    1. The proportion of active (dephosphorylated) pyruvate dehydrogenase in rat heart mitochondria was correlated with total concentration ratios of ATP/ADP, NADH/NAD+ and acetyl-CoA/CoA. These metabolites were measured with ATP-dependent and NADH-dependent luciferases. 2. Increase in the concentration ratio of NADH/NAD+ at constant [ATP]/[ADP] and [acetyl-CoA]/[CoA] was associated with increased phosphorylation and inactivation of pyruvate dehydrogenase. This was based on comparison between mitochondria incubated with 0.4mM- or 1mM-succinate and mitochondria incubated with 0.4mM-succinate+/-rotenone. 3. Increase in the concentration ratio acetyl-CoA/CoA at constant [ATP]/[ADP] and [NADH][NAD+] was associated with increased phosphorylation and inactivation of pyruvate dehydrogenase. This was based on comparison between incubations in 50 micrometer-palmitotoyl-L-carnitine and in 250 micrometer-2-oxoglutarate +50 micrometer-L-malate. 4. These findings are consistent with activation of the pyruvate dehydrogenase kinase reaction by high ratios of [NADH]/[NAD+] and of [acetyl-CoA]/[CoA]. 5. Comparison between mitochondria from hearts of diabetic and non-diabetic rats shows that phosphorylation and inactivation of pyruvate dehydrogenase is enhanced in alloxan-diabetes by some factor other than concentration ratios of ATP/ADP, NADH/NAD+ or acetyl-CoA/CoA. PMID:196589

  5. Putative M2 muscarinic receptors of rat heart have high affinity for organophosphorus anticholinesterases

    SciTech Connect

    Silveira, C.L.; Eldefrawi, A.T.; Eldefrawi, M.E. )

    1990-05-01

    The M2 subtype of muscarinic receptor is predominant in heart, and such receptors were reported to be located in muscles as well as in presynaptic cholinergic and adrenergic nerve terminals. Muscarinic receptors of rat heart were identified by the high affinity binding of the agonist (+)-(3H)cis-methyldioxolane ((3H)CD), which has been used to label a high affinity population of M2 receptors. A single population of sites was detected and (3H)CD binding was sensitive to the M2 antagonist himbacine but much less so to pirenzepine, the M1 antagonist. These cardiac receptors had different sensitivities to NiCl2 and N-ethylmaleimide from brain muscarinic receptors, that were also labeled with (3H)CD and considered to be of the M2 subtype. Up to 70% of the (3H)CD-labeled cardiac receptors had high affinities for several organophosphate (OP) anticholinesterases. (3H)CD binding was inhibited by the nerve agents soman, VX, sarin, and tabun, with K0.5 values of 0.8, 2, 20, and 50 nM, respectively. It was also inhibited by echothiophate and paraoxon with K0.5 values of 100 and 300 nM, respectively. The apparent competitive nature of inhibition of (3H)CD binding by both sarin and paraoxon suggests that the OPs bind to the acetylcholine binding site of the muscarinic receptor. Other OP insecticides had lower potencies, inhibiting less than 50% of 5 nM (3H)CD binding by 1 microM of EPN, coumaphos, dioxathion, dichlorvos, or chlorpyriphos. There was poor correlation between the potencies of the OPs in reversibly inhibiting (3H)CD binding, and their anticholinesterase activities and toxicities. Acetylcholinesterases are the primary targets for these OP compounds because of the irreversible nature of their inhibition, which results in building of acetylcholine concentrations that activate muscarinic and nicotinic receptors and desensitize them, thereby inhibiting respiration.

  6. 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

  7. Metformin improves cardiac function in a nondiabetic rat model of post-MI heart failure.

    PubMed

    Yin, Meimei; van der Horst, Iwan C C; van Melle, Joost P; Qian, Cheng; van Gilst, Wiek H; Silljé, Herman H W; de Boer, Rudolf A

    2011-08-01

    Metformin is the first choice drug for the treatment of patients with diabetes, but its use is debated in patients with advanced cardiorenal disease. Epidemiological data suggest that metformin may reduce cardiac events, in patients both with and without heart failure. Experimental evidence suggests that metformin reduces cardiac ischemia-reperfusion injury. It is unknown whether metformin improves cardiac function (remodeling) in a long-term post-MI remodeling model. We therefore studied male, nondiabetic, Sprague-Dawley rats that were subjected to either myocardial infarction (MI) or sham operation. Animals were randomly allocated to treatment with normal water or metformin-containing water (250 mg·kg(-1)·day(-1)). At baseline, 6 wk, and 12 wk, metabolic parameters were analyzed and oral glucose tolerance tests (OGTT) were performed. Echocardiography and hemodynamic parameters were assessed 12 wk after MI. In the MI model, infarct size was significantly smaller after 12-wk metformin treatment (29.6 ± 3.2 vs. 38.0 ± 2.2%, P < 0.05). Moreover, metformin resulted in less left ventricular dilatation (6.0 ± 0.4 vs. 7.6 ± 0.6 mm, P < 0.05) and preservation of left ventricular ejection fraction (65.8 ± 3.7% vs. 48.6 ± 5.6%, P < 0.05) compared with MI control. The improved cardiac function was associated with decreased atrial natriuretic peptide mRNA levels in the metformin-treated group (50% reduction compared with MI, P < 0.05). Insulin resistance did not occur during cardiac remodeling (as indicated by normal OGTT) and fasting glucose levels and the pattern of the OGTT were not affected by metformin. Molecular analyses suggested that altered AMP kinase phosphorylation status and low insulin levels mediate the salutary effects of metformin. Altogether our results indicate that metformin may have potential to attenuate heart failure development after myocardial infarction, in the absence of diabetes and independent of systemic glucose levels.

  8. Effect of dietary polyunsaturated fatty acids on contractile function of hearts isolated from sedentary and trained rats.

    PubMed

    Demaison, L; Blet, J; Sergiel, J P; Gregoire, S; Argaud, D

    2000-01-01

    Moderate physical training induced a decrease in arterial blood pressure in fish oil-fed rats as compared to sunflower seed oil-fed rats. The purpose of this study was to determine if these changes were due to modifications of the left ventricular function of the heart. Forty rats were fed a semi-purified diet containing either 10% sunflower seed oil or 10% fish oil (EPAX 3000TG, Pronova). Each dietary group was assigned to two sub-groups, one being constituted by sedentary animals and the other by trained animals. Training was achieved by daily running for 60 minutes at moderate intensity for three weeks. At the end of the training period, the animals were sacrificed and their hearts were immediately perfused according to the working mode. The phospholipid fatty acid composition and parameters of the left ventricular function were determined. Feeding fish oil markedly reduced the proportion of n-6 polyunsaturated fatty acids (PUFA, 18:2 n-6, 20:4 n-6, 22:4 n-6 and 22:5 n-6) in cardiac phospholipids. The n-6 PUFA were replaced by n-3 PUFA (mainly docosahexaenoic acid). In sedentary animals, the fluid dynamic (aortic and coronary flow, cardiac output) was not modified by the diet. The heart rate was reduced (-10%) in n-3 PUFA-rich hearts. Physical training did not markedly alter the polyunsaturated fatty acid profile of cardiac phospholipids. Conversely, it reduced the heart rate, aortic flow and cardiac output (-11, -21 and -14%, respectively) at a similar extent in the two dietary groups. In a second set of experiments, the training period was repeated in animals fed a commercially available diet (A103, UAR) which simultaneously provided n-6 and n-3 fatty acids. In these dietary conditions, neither the aortic flow nor the heart rate was decreased by physical exercise. These results suggest that both n-6 and n-3 PUFA in the diet are necessary to ensure a good cardiac adaptation to moderate physical training. Furthermore, the fish oil-induced decrease in arterial

  9. Transmural stretch-dependent regulation of contractile properties in rat heart and its alteration after myocardial infarction.

    PubMed

    Cazorla, Olivier; Szilagyi, Szabolcs; Le Guennec, Jean-Yves; Vassort, Guy; Lacampagne, Alain

    2005-01-01

    The "stretch-sensitization" response is essential to the regulation of heart contractility. An increase in diastolic volume improves systolic contraction. The cellular mechanisms of this modulation, the Frank-Starling law, are still uncertain. Moreover, their alterations in heart failure remains controversial. Here, using left ventricular skinned rat myocytes, we show a nonuniform stretch-sensitization of myofilament activation across the ventricular wall. Stretch-dependent Ca2+ sensitization of myofilaments increases from sub-epicardium to sub-endocardium and is correlated with an increase in passive tension. This passive tension-dependent component of myofibrillar activation is not associated with expression of titin isoforms, changes in troponin I level, and phosphorylation status. Instead, we observe that stretch induces phosphorylation of ventricular myosin light chain 2 isoform (VLC2b) in sub-endocardium specifically. Thus, VLC2b phosphorylation could act as a stretch-dependent modulator of activation tuned within normal heart. Moreover, in postmyocardial infarcted rat, the gradient of stretch-dependent Ca2+ sensitization disappears associated with a lack of VLC2b phosphorylation in sub-endocardium. In conclusion, nonuniformity is a major characteristic of the normal adult left ventricle (LV). The heterogeneous myocardial deformation pattern might be caused not only by the morphological heterogeneity of the tissue in the LV wall, but also by the nonuniform contractile properties of the myocytes across the wall. The loss of a contractile transmural gradient after myocardial infarction should contribute to the impaired LV function.

  10. Phosphorus-31 NMR magnetization transfer measurements of metabolic reaction rates in the rat heart and kidney in vivo

    SciTech Connect

    Koretsky, A.P.

    1984-08-01

    This dissertation is concerned with the measurement of the rates of ATP synthesis in the rat kidney and of the creatine kinase catalyzed reaction in the rat heart in situ. Chronically implanted detection coils, employing a balanced matching configuration of capacitors in the tuned circuit, were used to obtain /sup 31/P NMR spectra from heart, kidney, and liver in situ. Gated spectra of heart obtained at systole and diastole and the effects of fructose on kidney and liver were studied. The ability to observe other nuclei using implanted coils is illustrated with /sup 39/K NMR spectra from kidney and muscle. The theoretical considerations of applying magnetization transfer techniques to intact organs are discussed with emphasis on the problems associated with multiple exchange reactions and compartmentation of reactants. Experimental measurements of the ATP synthesis rate (13 ..mu..mol/min/gm tissue) were compared to whole kidney oxygen consumption and Na/sup +/ reabsorption rates to derive ATP/O (0.8 to 1.7) and Na/sup +//ATP (4 to 10) values. The problems associated with ATP synthesis rate measurements in kidney, e.g., the heterogeneity of the inorganic phosphate resonance, are discussed and experiments to overcome these problems proposed.

  11. Long-term low dose dietary resveratrol supplement reduces cardiovascular structural and functional deterioration in chronic heart failure in rats.

    PubMed

    Ahmet, Ismayil; Tae, Hyun-Jin; Lakatta, Edward G; Talan, Mark

    2017-03-01

    A short-term exposure to resveratrol at high dosages exerts a remarkable cardioprotective effect. Whether a long-term exposure to resveratrol at low dosages that can be obtained through consumption of a resveratrol-rich diet is beneficial to heart diseases is unknown. We tested the effects of a resveratrol-enriched diet on cardiovascular remodeling of chronic heart failure (CHF) in rats resulting from permanent ligation of left coronary artery. Two weeks after surgery, rats were started on either a resveratrol-enriched (R; 5 mg/kg per day; n = 23) or normal (Control; n = 23) diet for next 10 months. Serial echocardiography in Control showed a significant decline in LV ejection fraction, increases in LV end-systolic and end-diastolic volumes, and expansion in myocardial infarct from pre-treatment values. In R, compared with Control, there were substantial improvements in those parameters. End-point LV pressure-volume loop analysis showed a significantly improved LV systolic function and AV-coupling, an index of energy transfer efficacy between the heart and aortic tree, in R compared with Control (p < 0.05). Aortic pulse wave velocity, a measure of arterial stiffness, was significantly lower in R (389 ± 15 cm/s; p < 0.05) compared with Control (489 ± 38 cm/s). These results demonstrated that long-term dietary resveratrol supplement reduces cardiovascular structural and functional deterioration in CHF.

  12. The effect of Ginkgo biloba extract on mitochondrial oxidative phosphorylation in the normal and ischemic rat heart.

    PubMed

    Bernatoniene, Jurga; Majiene, Daiva; Peciura, Rimantas; Laukeviciene, Ale; Bernatoniene, Ruta; Mekas, Tauras; Kasauskas, Arturas; Kopustinskiene, Dalia

    2011-07-01

    Free radical-induced myocardial damage and impairment of vascular endothelium-dependent relaxation are amongst the most important mechanisms responsible for ischemic heart injury. Ginkgo biloba leaf extract (GE) has been reported to improve blood circulation in the brain and have a beneficial impact on the cardiovascular system but its cardioprotective effects have not been elucidated yet. Therefore, this study investigated the influence of GE in 70% ethanol (1:5) administered orally to rats on the functions of isolated heart mitochondria under normal and ischemic conditions. Wistar rats were given GE or ethanol (solvent control) at a dosage of 0.32 mL/kg in drinking water for 10 and 18 days, while the control animals received untreated drinking water. Mitochondrial respiration rates were determined oxygraphically. Pyruvate and malate, succinate or palmitoyl-L-carnitine and malate were used as substrates. The GE treatment partially uncoupled mitochondrial oxidation from phosphorylation, reduced the generation of free radicals in the mitochondria, diminished the ischemia-induced V₃ decrease and the degree of respiration stimulation by exogenous cytochrome c. Thus, these results indicate that GE exerts cardioprotective effects reducing ischemia-caused impairment of the functions of heart mitochondria.

  13. Simultaneous determination of creatine phosphate, creatine and 12 nucleotides in rat heart by LC-MS/MS.

    PubMed

    Wang, Jun-mei; Chu, Yang; Li, Wei; Wang, Xiang-yang; Guo, Jia-hua; Yan, Lu-lu; Ma, Xiao-hui; Ma, Ying-li; Yin, Qi-hui; Liu, Chang-xiao

    2014-05-01

    A simple, rapid and sensitive LC-MS/MS method was developed and validated for simultaneous determination of creatine phosphate (CP), creatine (Cr) and 12 nucleotides in rat heart. The analytes, ATP, ADP, AMP, GTP, GDP, GMP, CTP, CDP, CMP, UTP, UDP, UMP, CP, Cr, were extracted from heart tissue with pre-cooled (0°C) methanol/water (1:1, v/v) and separated on a Hypersil Gold AQ C18 column (150mm×4.6mm, 3μm) using an isocratic elution with a mobile phase consisting of 2mmol/L ammonium acetate in water (pH 10.0, adjusted with ammonia). The detection was performed by negative ion electrospray ionization in selective reaction monitoring mode (SRM). In the assay, all the analytes showed good linearity over the investigated concentration range (r>0.99). The accuracy was between 80.7% and 120.6% and the precision expressed in RSD was less than 15.6%. This method was successfully applied to measure the concentrations of the 12 nucleotides, creatine phosphate and creatine in rat heart for the first time.

  14. Proteomic analysis reveals perturbed energy metabolism and elevated oxidative stress in hearts of rats with inborn low aerobic capacity

    PubMed Central

    Burniston, Jatin G.; Kenyani, Jenna; Wastling, Jonathan M.; Burant, Charles F.; Qi, Nathan R.; Koch, Lauren G.; Britton, Steven L.

    2012-01-01

    Selection on running capacity has created rat phenotypes of high capacity runners (HCR) that have enhanced cardiac function and low capacity runners (LCR) that exhibit risk factors of metabolic syndrome. We analysed hearts of HCR and LCR from generation 22 of selection using DIGE and identified proteins from MS database searches. The running capacity of HCR was 6-fold greater than LCR. DIGE resolved 957 spots and proteins were unambiguously identified in 369 spots. Protein expression profiling detected 67 statistically significant (P<0.05; false discovery rate <10 %, calculated using q-values) differences between HCR and LCR. Hearts of HCR rats exhibited robust increases in the abundance of each enzyme of the beta-oxidation pathway. In contrast, LCR hearts were characterised by the modulation of enzymes associated with ketone body or amino acid metabolism. LCR also exhibited enhanced expression of antioxidant enzymes such as catalase and greater phosphorylation of alpha B-crystallin at serine 59, which is a common point of convergence in cardiac stress signalling. Thus proteomic analysis revealed selection on low running capacity is associated with perturbations in cardiac energy metabolism and provided the first evidence that the LCR cardiac proteome is exposed to greater oxidative stress. PMID:21751351

  15. Luteolin improves cardiac dysfunction in heart failure rats by regulating sarcoplasmic reticulum Ca2+-ATPase 2a

    PubMed Central

    Hu, Wenjing; Xu, Tongda; Wu, Pei; Pan, Defeng; Chen, Junhong; Chen, Jing; Zhang, Buchun; Zhu, Hong; Li, Dongye

    2017-01-01

    We previously found that luteolin (Lut) appeared to improve the contractility of cardiomyocytes during ischemia/reperfusion in rats. The enhancement was associated with the alteration in sarcoplasmic reticulum Ca2+-ATPase 2a (SERCA2a). This finding prompted us to consider if the mechanism worked in heart failure (HF). We studied the regulation of SERCA2a by Lut in failing cardiomyocytes and intact heart of rats. Improvement of contractility and the mechanisms centered on SERCA2a were studied in isolated cardiomyocytes and intact heart. We found that Lut significantly improved contractility and Ca2+ transients, ameliorated expression, activity and stability of SERCA2a and upregulated expression of small ubiquitin-related modifier (SUMO) 1, which is a newfound SERCA2a regulator. Lut also increased phosphorylation of protein kinase B (Akt), phospholaban (PLB) and sumoylation of SERCA2a, specificity protein 1 (Sp1). Transcriptions of SUMO1 and SERCA2a were concurrently increased. Inhibition of posphatidylinositol 3 kinase/Akt (PI3K/Akt) pathway and SERCA2a activity both markedly abolished Lut-induced benefits in vitro and in vivo. Lut upregulated the expression ratio of Bcl-2/Bax, caspase-3/cleaved-Caspase3. Meanwhile, Lut ameliorated the myocardium fibrosis of HF. These discoveries provide an important potential therapeutic strategy that Lut targeted SERCA2a SUMOylation related to PI3K/Akt-mediated regulations on rescuing the dysfunction of HF. PMID:28112209

  16. Mechanisms for cardiac depression induced by phorbol myristate acetate in working rat hearts.

    PubMed Central

    Karmazyn, M.; Watson, J. E.; Moffat, M. P.

    1990-01-01

    1. The effects of the phorbol ester, phorbol myristate acetate (PMA) were examined on function and energy metabolism in the isolated working heart of the rat. 2. At a concentration of 10(-9) M PMA produced a rapid loss in cardiac function in terms of aortic flow rate (AFR) and coronary flow rates (CFR) whereas a similar concentration of 4 alpha-phorbol 12,13-didecanoate was ineffective. At a concentration of 10(-10) M, the PMA-induced depression was more gradual but nevertheless very pronounced with an almost total loss in AFR after 30 min perfusion. The reduction in CFR was more moderate than that observed with respect to AFR. 3. The protein kinase C (PKC) inhibitor (+/-)-1-O-hexadecyl-2-O-acylglycerol significantly attenuated the loss in AFR and CFR following addition of PMA. 4. Two inhibitors of Na+/H+ exchange, amiloride and quinacrine, totally prevented the reduction in AFR. Although the PMA-induced depression in CFR was also attenuated by both amiloride and quinacrine, these effects were not significant, probably reflecting the less pronounced effect of PMA on this parameter. 5. Nifedipine, a dihydropyridine calcium channel blocker reduced PMA toxicity to a similar degree as Na+/N+ exchange inhibition whereas the calcium channel agonist Bay K 8644 was without effect. 6. Tissue content of energy metabolites including high energy phosphates, total adenine nucleotides or lactate were not significantly affected by PMA perfusion. 7. We conclude that PKC activation is necessary for phorbol ester-induced cardiac dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2207502

  17. Expression and localization of caveolins during postnatal development in rat heart: implication of thyroid hormone.

    PubMed

    Ratajczak, Philippe; Oliviéro, Patricia; Marotte, Françoise; Kolar, Frantisek; Ostadal, Bohuslav; Samuel, Jane-Lise

    2005-07-01

    Caveolins modulate signaling pathways involved in cardiac development. Caveolin-1 exists in two isoforms: the beta-isoform derivates from an alternative translational start site that creates a protein truncated by 31 amino acids, mainly expressed in endothelial cells, whereas caveolin-3 is present in muscle cells. Our aim was to define caveolin distribution and expression during cardiac postnatal development using immunofluorescence and Western blotting. Caveolin-3 sarcolemmal labeling appeared as dotted lines from days 1 to 5 and as continuous lines after 14 days of age. Caveolin-3 expression, low at birth, increased (4-fold) to reach a maximum (P < 0.05) by day 5 and then decreased to stabilize in adults. Total caveolin-1 and its alpha-isoform were codistributed at birth in endothelial and smooth muscle cells; afterward, only the caveolin-1alpha labeling became limited to endothelium. Quantitative analysis indicated a similar temporal pattern of both total caveolin-1 and caveolin-1alpha expression, suggesting that caveolin-1alpha and -1beta are coregulated; the caveolin-1alpha levels increased fourfold by day 5 to reach a maximum by day 14 (P < 0.05). Tyrosine-14-caveolin-1 phosphorylation, low at birth, increased suddenly around day 14 (8-fold vs. day 1) and returning afterward to basal level. Because the T3/T4 level is maximal by day 14, caveolin-1 expression/phosphorylation profiles were analyzed in hypothyroid heart. The levels of caveolin-1alpha and consequently tyrosine-14-caveolin-1 phosphorylation, but not that of caveolin-3, decreased (50%) in hypothyroid 14-day-old rats. Our data demonstrate that, during postnatal cardiac growth, 1) caveolins are distinctly regulated, and 2) thyroid hormones are involved in caveolin-1alpha expression.

  18. A new apex-ejecting perfused rat heart preparation: relation between coronary flow and loading conditions.

    PubMed

    Wikman-Coffelt, J; Coffelt, R J; Rapcsak, M; Sievers, R; Rouleau, J L; Parmley, W W

    1983-12-01

    The isolated perfused rat heart is an important experimental preparation for both mechanical and biochemical studies. In order to define better the relationship between coronary flow and loading conditions, a new preparation was developed in which the left ventricle ejected through the apex, while the aortic perfusion pressure could be separately controlled at a higher level than the apex afterload. Results were compared with a standard aortic perfused and ejecting preparation. All analyses were made at low calcium concentration (1.6 mmol X litre-1) for reducing cardiac performance. Coronary flow was related to perfusion pressure in the aortic ejecting preparation when the aortic afterload chamber was between 6.0 and 9.3 kPa (45 and 70 mmHg). Coronary autoregulation was demonstrable in the apex ejecting preparation irrespective of the height of the apex afterload chamber and the aortic ejecting preparation when the aortic chamber was between 11.0 and 16.0 kPa (83 and 120 mmHg). Following the addition of 10(-6) mol X litre-1 adenosine, there was significant coronary vasodilatation, and flow became pressure dependent in all cases. In the apex-ejecting preparation, with a high aortic pressure, coronary flow remained at relatively fixed level, and increases in oxygen demand were met by increasing oxygen extraction. Thus, in this preparation oxygen extraction was directly related to workload. With abrupt increases in afterload, going from 6.0 to 9.3 kPa (45 to 70 mmHg) to a higher level, there was evidence of transient hypoxia with the aortic ejecting but not the apex ejecting preparation.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Paeonol Protects Rat Heart by Improving Regional Blood Perfusion during No-Reflow

    PubMed Central

    Ma, Lina; Chuang, Chia-Chen; Weng, Weiliang; Zhao, Le; Zheng, Yongqiu; Zhang, Jinyan; Zuo, Li

    2016-01-01

    No-reflow phenomenon, defined as inadequate perfusion of myocardium without evident artery obstruction, occurs at a high incidence after coronary revascularization. The mechanisms underlying no-reflow is only partially understood. It is commonly caused by the swelling of endothelial cells, neutrophil accumulation, and vasoconstriction, which are all related to acute inflammation. Persistent no-reflow can lead to hospitalization and mortality. However, an effective preventive intervention has not yet been established. We have previously found that paeonol, an active extraction from the root of Paeonia suffruticosa, can benefit the heart function by inhibiting tissue damage after ischemia, reducing inflammation, and inducing vasodilatation. To further investigate the potential cardioprotective action of paeonol on no-reflow, healthy male Wistar rats were randomly divided into four groups: sham, ischemia-reperfusion (I/R) injury (left anterior descending coronary artery was ligated for 4 h followed by reperfusion for 8 h), and I/R injury pretreated with paeonol at two different doses. Real-time myocardial contrast echocardiography was used to monitor regional blood perfusion and cardiac functions. Our data indicated that paeonol treatment significantly reduces myocardial infarct area and no-reflow area (n = 8; p < 0.05). Regional myocardial perfusion (A·β) and cardiac functions such as ejection fraction, stroke volume, and fractional shortening were elevated by paeonol (n = 8; p < 0.05). Paeonol also lowered the serum levels of lactate dehydrogenase, creatine kinase, cardiac troponin T, and C-reactive protein, as indices of myocardial injury. Paeonol exerts beneficial effects on attenuating I/R-associated no-reflow injuries, and may be considered as a potential preventive treatment for cardiac diseases or post-coronary revascularization in which no-reflow often occurs. PMID:27493631

  20. Aerobic exercise training rescues cardiac protein quality control and blunts endoplasmic reticulum stress in heart failure rats.

    PubMed

    Bozi, Luiz H M; Jannig, Paulo R; Rolim, Natale; Voltarelli, Vanessa A; Dourado, Paulo M M; Wisløff, Ulrik; Brum, Patricia C

    2016-11-01

    Cardiac endoplasmic reticulum (ER) stress through accumulation of misfolded proteins plays a pivotal role in cardiovascular diseases. In an attempt to reestablish ER homoeostasis, the unfolded protein response (UPR) is activated. However, if ER stress persists, sustained UPR activation leads to apoptosis. There is no available therapy for ER stress relief. Considering that aerobic exercise training (AET) attenuates oxidative stress, mitochondrial dysfunction and calcium imbalance, it may be a potential strategy to reestablish cardiac ER homoeostasis. We test the hypothesis that AET would attenuate impaired cardiac ER stress after myocardial infarction (MI). Wistar rats underwent to either MI or sham surgeries. Four weeks later, rats underwent to 8 weeks of moderate-intensity AET. Myocardial infarction rats displayed cardiac dysfunction and lung oedema, suggesting heart failure. Cardiac dysfunction in MI rats was paralleled by increased protein levels of UPR markers (GRP78, DERLIN-1 and CHOP), accumulation of misfolded and polyubiquitinated proteins, and reduced chymotrypsin-like proteasome activity. These results suggest an impaired cardiac protein quality control. Aerobic exercise training improved exercise capacity and cardiac function of MI animals. Interestingly, AET blunted MI-induced ER stress by reducing protein levels of UPR markers, and accumulation of both misfolded and polyubiquinated proteins, which was associated with restored proteasome activity. Taken together, our study provide evidence for AET attenuation of ER stress through the reestablishment of cardiac protein quality control, which contributes to better cardiac function in post-MI heart failure rats. These results reinforce the importance of AET as primary non-pharmacological therapy to cardiovascular disease.

  1. 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.

  2. Effect of intracerebroventricular and intravenous administration of nitric oxide donors on blood pressure and heart rate in anaesthetized rats.

    PubMed Central

    Nurminen, M. L.; Vapaatalo, H.

    1996-01-01

    1. The effects of nitric oxide (NO) releasing substances, sodium nitroprusside, 3-morpholino sydnonimine (SIN-1) and a novel oxatriazole derivative, GEA 3162, on blood pressure and heart rate were studied after peripheral or central administration in anaesthetized normotensive Wistar rats. 2. Given as cumulative intravenous injections, both nitroprusside and GEA 3162 (24-188 nmol kg-1) induced short-lasting and dose-dependent decreases in mean arterial pressure, while SIN-1 decreased blood pressure only slightly even after larger doses (94-3000 nmol kg-1). Heart rate increased concomitantly with the hypotensive effect of the NO-releasing substances. 3. Cumulative intracerebroventricular administration of GEA 3162 (24-188 nmol kg-1) induced a dose-dependent hypotension with slight but insignificant increases in heart rate. In contrast, intracerebroventricular nitroprusside induced little change in blood pressure, while a large dose of SIN-1 (3000 nmol kg-1, i.c.v.) slightly increased mean arterial pressure. However, intracerebroventricular nitroprusside and SIN-1 increased heart rate at doses that did not significantly affect blood pressure. 4. To determine whether the cardiovascular effects of GEA 3162 were attributable to an elevation of cyclic GMP levels, pretreatments with methylene blue, a putative guanylate cyclase inhibitor, were performed. This substance failed to attenuate the cardiovascular effects of peripherally or centrally administered GEA 3162, suggesting that the effects were independent of guanylate cyclase. 5. In conclusion, the centrally administered NO-donor, GEA 3162, induced a dose-dependent. hypotensive response without significant changes in heart rate. Furthermore, intracerebroventricular injections of nitroprusside and SIN-1 increased heart rate without affecting blood pressure. These results suggest that NO released by these drugs may affect central mechanisms involved in cardiovascular regulation independently of cyclic GMP. PMID:8968551

  3. Effect of Flos carthami on stress-activated protein kinase activity in the isolated reperfused rat heart.

    PubMed

    Siow, Y L; Choy, P C; Leung, W M; O, K

    2000-04-01

    The apoptotic death of cardiomyocytes due to ischemia/reperfusion is one of the major complications of heart disease. Ischemia/reperfusion has been shown to lead to the activation of the stress-activated protein (SAP) kinases and the p38/reactivating kinase (p38/RK). In this study, the direct effect of an aqueous Flos carthami (FC) extract on SAP kinases was investigated. When isolated rat hearts were perfused by Langendorff mode with media containing FC extract prior to the induction of global ischemia and the subsequent reperfusion, SAP kinase activity was inhibited 95%. Untreated ischemic/reperfused hearts showed a 57% elevation in the activity of SAP kinase. The in vitro effect of these FC extracts on SAP kinase was also tested. At a concentration of 10 microg/ml, the aqueous FC extract resulted in 50% inhibition of SAP kinase activity in ischemic heart tissue. Our results showed that FC affected both the interaction of SAP kinase with c-jun as well as the phosphotransferase reaction. These results clearly demonstrate that extracts from Flos carthami exerted inhibitory effects on SAP kinase. The administration of the FC extract may lead to a modulation of the apoptotic effect of SAP kinase activation induced during ischemia/reperfusion.

  4. Effect of exogenous adenosine and monensin on glycolytic flux in isolated perfused normoxic rat hearts: role of pyruvate kinase.

    PubMed

    Peltier, S; Burelle, Y; Novel-Chate, V; Demaison, L; Verdys, M; Saks, V; Keriel, C; Leverve, X M

    2005-09-01

    We studied the effect of exogenous adenosine in isolated perfused normoxic rat hearts on glycolytic flux through pyruvate kinase (PK). We compared its effect with that of myxothiazol, an inhibitor of mitochondrial ATP production. Moreover, we tested whether an increase of membrane ionic flux with monensin is linked to a stimulation of glycolytic flux through PK. After a 20-min stabilization period adenosine, myxothiazol or monensin were administrated to the perfusate continuously at various concentrations during 10 min. The contraction was monitored and the lactate production in coronary effluents evaluated. The amount of adenine nucleotides and phosphoenolpyruvate was measured in the frozen hearts. Myxothiazol induced a decrease of the left ventricular developed pressure (LVDP : -40%) together with a stimulation of glycolytic flux secondary to PK activation. In contrast, adenosine primarily reduced heart rate (HR: -30%) with only marginal effects on LVDP. This was associated with an inhibition of glycolysis at the level of PK. The Na+ ionophore monensin affected HR (+14%) and LVDP (+25%). This effect was associated with a stimulation of glycolysis secondary to the stimulation of PK. These results provide new information of action of adenosine in the heart and support the concept of a direct coupling between glycolysis and process regulating sarcolemmal ionic fluxes.

  5. Roselle Polyphenols Exert Potent Negative Inotropic Effects via Modulation of Intracellular Calcium Regulatory Channels in Isolated Rat Heart.

    PubMed

    Lim, Yi-Cheng; Budin, Siti Balkis; Othman, Faizah; Latip, Jalifah; Zainalabidin, Satirah

    2016-07-11

    Roselle (Hibiscus sabdariffa Linn.) calyces have demonstrated propitious cardioprotective effects in animal and clinical studies; however, little is known about its action on cardiac mechanical function. This study was undertaken to investigate direct action of roselle polyphenols (RP) on cardiac function in Langendorff-perfused rat hearts. We utilized RP extract which consists of 12 flavonoids and seven phenolic acids (as shown by HPLC profiling) and has a safe concentration range between 125 and 500 μg/ml in this study. Direct perfusion of RP in concentration-dependent manner lowered systolic function of the heart as shown by lowered LVDP and dP/dt max, suggesting a negative inotropic effect. RP also reduced heart rate (negative chronotropic action) while simultaneously increasing maximal velocity of relaxation (positive lusitropic action). Conversely, RP perfusion increased coronary pressure, an indicator for improvement in coronary blood flow. Inotropic responses elicited by pharmacological agonists for L-type Ca(2+) channel [(±)-Bay K 8644], ryanodine receptor (4-chloro-m-cresol), β-adrenergic receptor (isoproterenol) and SERCA blocker (thapsigargin) were all abolished by RP. In conclusion, RP elicits negative inotropic, negative chronotropic and positive lusitropic responses by possibly modulating calcium entry, release and reuptake in the heart. Our findings have shown the potential use of RP as a therapeutic agent to treat conditions like arrhythmia.

  6. Time course of changes in heart rate and blood pressure variability in rats with myocardial infarction

    PubMed Central

    Aires, R.; Pimentel, E.B.; Forechi, L.; Dantas, E.M.; Mill, J.G.

    2017-01-01

    Our aim was to determine the time course of changes in autonomic balance in the acute (1 and 3 days), sub-acute (7 days) and chronic (28 days) phases of myocardial infarction (MI) in rats. Autonomic balance was assessed by temporal and spectral analyses of blood pressure variability (BPV) and heart rate variability (HRV). Pulsatile blood pressure (BP) recordings (30 min) were obtained in awake and unrestrained male Wistar rats (N = 77; 8-10 weeks old) with MI (coronary ligature) or sham operation (SO). Data are reported as means±SE. The high frequency (HF) component (n.u.) of HRV was significantly lower in MI-1- (P<0.01) and MI-3-day rats (P<0.05) than in their time-control groups (SO-1=68±4 vs MI-1=35.3±4.3; SO-3=71±5.8 vs MI-3=45.2±3.8), without differences thereafter (SO-7=69.2±4.8 vs MI-7=56±5.8; SO-28=73±4 vs MI-28=66±6.6). A sharp reduction (P<0.05) of BPV (mmHg2) was observed in the first week after MI (SO-1=8.55±0.80; SO-3=9.11±1.08; SO-7=7.92±1.10 vs MI-1=5.63±0.73; MI-3=5.93±0.30; MI-7=5.30±0.25). Normal BPV, however, was observed 4 weeks after MI (SO-28=8.60±0.66 vs MI-28=8.43±0.56 mmHg2; P>0.05). This reduction was mainly due to attenuation of the low frequency (LF) band of BPV in absolute and normalized units (SO-1=39.3±7%; SO-3=55±4.5%; SO-7=46.8±4.5%; SO-28=45.7±5%; MI-1=13±3.5%; MI-3=35±4.7%; MI-7=25±2.8%; MI-28=21.4±2.8%). The results suggest that the reduction in HRV was associated with decrease of the HF component of HRV suggesting recovery of the vagal control of heartbeats along the post-infarction healing period. The depression of BPV was more dependent on the attenuation of the LF component, which is linked to the baroreflex modulation of the autonomic balance. PMID:28076450

  7. High-fat diet-induced obesity Rat model: a comparison between Wistar and Sprague-Dawley Rat

    PubMed Central

    Marques, Cláudia; Meireles, Manuela; Norberto, Sónia; Leite, Joana; Freitas, Joana; Pestana, Diogo; Faria, Ana; Calhau, Conceição

    2016-01-01

    ABSTRACT In the past decades, obesity and associated metabolic complications have reached epidemic proportions. For the study of these pathologies, a number of animal models have been developed. However, a direct comparison between Wistar and Sprague-Dawley (SD) Rat as models of high-fat (HF) diet-induced obesity has not been adequately evaluated so far. Wistar and SD rats were assigned for 2 experimental groups for 17 weeks: standard (St) and high-fat (HF) diet groups. To assess some of the features of the metabolic syndrome, oral glucose tolerance tests, systolic blood pressure measurements and blood biochemical analysis were performed throughout the study. The gut microbiota composition of the animals of each group was evaluated at the end of the study by real-time PCR. HF diet increased weight gain, body fat mass, mesenteric adipocyte's size, adiponectin and leptin plasma levels and decreased oral glucose tolerance in both Wistar and SD rats. However, the majority of these effects were more pronounced or earlier detected in Wistar rats. The gut microbiota of SD rats was less abundant in Bacteroides and Prevotella but richer in Bifidobacterium and Lactobacillus comparatively to the gut microbiota of Wistar rats. Nevertheless, the modulation of the gut microbiota by HF diet was similar in both strains, except for Clostridium leptum that was only reduced in Wistar rats fed with HF diet. In conclusion, both Wistar and SD Rat can be used as models of HF diet-induced obesity although the metabolic effects caused by HF diet seemed to be more pronounced in Wistar Rat. Differences in the gut microbial ecology may account for the worsened metabolic scenario observed in Wistar Rat. PMID:27144092

  8. 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.

  9. Lippia alba, Melissa officinalis and Cymbopogon citratus: effects of the aqueous extracts on the isolated hearts of rats.

    PubMed

    Gazola, Ruth; Machado, Denise; Ruggiero, Campos; Singi, Glenan; Macedo Alexandre, Mariângela

    2004-11-01

    1. This research was developed to evaluate the actions of the aqueous extracts of leaves of Lippia alba, Melissa officinalis and Cymbopogon citratus upon contractile force (CF) and cardiac rate (CR). 2. For the experiments in isolated heart, 21 male adult rats were used. The hearts were perfused according to Langendorff's method. The records of CF and CR were obtained in control and after application of the extracts. The extracts were utilized in doses: 0.038, 0.38, 3.8 and 38 mg. Results obtained were compared by statistic analyses. 3. The aqueous extracts provoked significant CR reduction and did not alter the CF. The negative CR effect may have occurred by cardiac muscarinics receptors stimulation.

  10. Comparison of the Performance of the Warfarin Pharmacogenetics Algorithms in Patients with Surgery of Heart Valve Replacement and Heart Valvuloplasty.

    PubMed

    Xu, Hang; Su, Shi; Tang, Wuji; Wei, Meng; Wang, Tao; Wang, Dongjin; Ge, Weihong

    2015-09-01

    A large number of warfarin pharmacogenetics algorithms have been published. Our research was aimed to evaluate the performance of the selected pharmacogenetic algorithms in patients with surgery of heart valve replacement and heart valvuloplasty during the phase of initial and stable anticoagulation treatment. 10 pharmacogenetic algorithms were selected by searching PubMed. We compared the performance of the selected algorithms in a cohort of 193 patients during the phase of initial and stable anticoagulation therapy. Predicted dose was compared to therapeutic dose by using a predicted dose percentage that falls within 20% threshold of the actual dose (percentage within 20%) and mean absolute error (MAE). The average warfarin dose for patients was 3.05±1.23mg/day for initial treatment and 3.45±1.18mg/day for stable treatment. The percentages of the predicted dose within 20% of the therapeutic dose were 44.0±8.8% and 44.6±9.7% for the initial and stable phases, respectively. The MAEs of the selected algorithms were 0.85±0.18mg/day and 0.93±0.19mg/day, respectively. All algorithms had better performance in the ideal group than in the low dose and high dose groups. The only exception is the Wadelius et al. algorithm, which had better performance in the high dose group. The algorithms had similar performance except for the Wadelius et al. and Miao et al. algorithms, which had poor accuracy in our study cohort. The Gage et al. algorithm had better performance in both phases of initial and stable treatment. Algorithms had relatively higher accuracy in the >50years group of patients on the stable phase.

  11. Prevention and Treatment of Functional and Structural Radiation Injury in the Rat Heart by Pentoxifylline and Alpha-Tocopherol

    SciTech Connect

    Boerma, Marjan Roberto, Kerrey A.; Hauer-Jensen, Martin

    2008-09-01

    Purpose: Radiation-induced heart disease (RIHD) is a severe side effect of thoracic radiotherapy. This study examined the effects of pentoxifylline (PTX) and {alpha}-tocopherol on cardiac injury in a rat model of RIHD. Methods and Materials: Male Sprague-Dawley rats received fractionated local heart irradiation with a daily dose of 9 Gy for 5 days and were observed for 6 months after irradiation. Rats were treated with a combination of PTX, 100 mg/kg/day, and {alpha}-tocopherol (20 IU/kg/day) and received these compounds either from 1 week before until 6 months after irradiation or starting 3 months after irradiation, a time point at which histopathologic changes become apparent in our model of RIHD. Results: Radiation-induced increases in left ventricular diastolic pressure (in mm Hg: 35 {+-} 6 after sham-irradiation, 82 {+-} 11 after irradiation) were significantly reduced by PTX and {alpha}-tocopherol (early treatment: 48 {+-} 7; late treatment: 53 {+-} 6). PTX and {alpha}-tocopherol significantly reduced deposition of collagen types I (radiation only: 3.5 {+-} 0.2 {mu}m{sup 2} per 100 {mu}m{sup 2}; early treatment: 2.7 {+-} 0.8; late treatment: 2.2 {+-} 0.2) and III (radiation only: 13.9 {+-} 0.8; early treatment: 11.0 {+-} 1.2; late treatment: 10.6 {+-} 0.8). On the other hand, radiation-induced alterations in heart/body weight ratios, myocardial degeneration, left ventricular mast cell densities, and most echocardiographic parameters were not significantly altered by PTX and {alpha}-tocopherol. Conclusions: Treatment with PTX and {alpha}-tocopherol may have beneficial effects on radiation-induced myocardial fibrosis and left ventricular function, both when started before irradiation and when started later during the process of RIHD.

  12. Cobalt protoporphyrin accelerates TFEB activation and lysosome reformation during LPS-induced septic insults in the rat heart.

    PubMed

    Unuma, Kana; Aki, Toshihiko; Funakoshi, Takeshi; Yoshida, Ken-ichi; Uemura, Koichi

    2013-01-01

    Lipopolysaccharide (LPS)-induced myocardial dysfunction is caused, at least in part, by mitochondrial dysfunction. Mitochondrial dysfunction and the oxidative damage associated with it are scavenged through various cellular defense systems such as autophagy to prevent harmful effects. Our recent study has demonstrated that cobalt protoporphyrin IX (CoPPIX), a potent inducer of heme oxygenase-1 (HO-1), ameliorates septic liver injuries by enhancing mitochondrial autophagy in rats. In our current study, we show that CoPPIX (5 mg/kg s.c.) not only accelerates the autophagic response but also promotes lysosome reformation in the rat heart treated with LPS (15 mg/kg i.p.). Lysosomal membrane-associated protein-2 (LAMP2), which is essential to the maintenance of lysosomal functions in the heart, is depleted transiently but restored rapidly during LPS administration in the rat. Activation of transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, was also observed, indicating a hyper consumption and subsequent reformation of the lysosome to meet the increased demand for autophagosome cleaning. CoPPIX was found to promote these processes and tended to restore the LPS-induced suppression of cardiac performances whilst chloroquine (CQ; 20 mg/kg i.p.), an inhibitor of lysosomes and autophagic protein degradation, abrogates these beneficial effects. The cardioprotective effect of CoPPIX against LPS toxicity was also observed via decreased levels of cardiac releasing enzymes in the plasma. Taken together, our current data indicate that lysosome reformation mediated by TFEB may be involved in cardioprotection against LPS-induced septic insults, and serve as a novel mechanism by which CoPPIX protects the heart against oxidative stress.

  13. Histamine H3-receptor stimulation is unable to modulate noradrenaline release by the isolated rat heart during ischaemia-reperfusion.

    PubMed

    Mazenot, C; Durand, A; Ribuot, C; Demenge, P; Godin-Ribuot, D

    1999-01-01

    The aim of this study was to evaluate the ability of H3-histaminergic prejunctional receptors to modulate the noradrenaline release induced by myocardial ischaemia in the rat, and the effects of an eventual modulation on haemodynamic, biochemical and electrophysiological parameters. Isolated rat hearts were perfused according to the Langendorff technique. Control hearts (n = 13) were not treated; two groups were treated with the H3-agonist R-alpha-methyl-histamine at 0.3 microM (n = 14) and 1 microM (n = 11) and one group, used as positive control, was treated with the selective alpha 2-agonist Mivazerol at 0.5 microM (n = 14) added to the perfusion medium. Noradrenaline, lactate and transaminase output in the coronary effluent, as well as various haemodynamic and electrophysiological parameters, were measured during global and total ischaemia (30 min) and reperfusion (30 min). alpha 2-receptor stimulation increased ischaemia-induced noradrenaline release during reperfusion (195 +/- 13 vs. 145 +/- 12 pmol.g-1 in control group, P < 0.05). In contrast, R-alpha-methyl-histamine, at both doses, did not significantly modify these parameters. Both treatments did not affect ischaemia- and reperfusion-induced haemodynamic (decrease in heart rate or in left ventricular developed pressure), biochemical (lactate and GOT release) and electrophysiological (arrhythmias or increase in action potential duration) alterations. Unlike other species, the rat appears to be insensitive to H3-histaminergic receptor modulation of ischaemia-induced noradrenaline release, although a modulation can be seen with other prejunctional receptor agonists.

  14. Effects of electromagnetic radiation from 3G mobile phone on heart rate, blood pressure and ECG parameters in rats.

    PubMed

    Colak, Cengiz; Parlakpinar, Hakan; Ermis, Necip; Tagluk, Mehmet Emin; Colak, Cemil; Sarihan, Ediz; Dilek, Omer Faruk; Turan, Bahadir; Bakir, Sevtap; Acet, Ahmet

    2012-08-01

    Effects of electromagnetic energy radiated from mobile phones (MPs) on heart is one of the research interests. The current study was designed to investigate the effects of electromagnetic radiation (EMR) from third-generation (3G) MP on the heart rate (HR), blood pressure (BP) and ECG parameters and also to investigate whether exogenous melatonin can exert any protective effect on these parameters. In this study 36 rats were randomized and evenly categorized into 4 groups: group 1 (3G-EMR exposed); group 2 (3G-EMR exposed + melatonin); group 3 (control) and group 4 (control + melatonin). The rats in groups 1 and 2 were exposed to 3G-specific MP's EMR for 20 days (40 min/day; 20 min active (speech position) and 20 min passive (listening position)). Group 2 was also administered with melatonin for 20 days (5 mg/kg daily during the experimental period). ECG signals were recorded from cannulated carotid artery both before and after the experiment, and BP and HR were calculated on 1st, 3rd and 5th min of recordings. ECG signals were processed and statistically evaluated. In our experience, the obtained results did not show significant differences in the BP, HR and ECG parameters among the groups both before and after the experiment. Melatonin, also, did not exhibit any additional effects, neither beneficial nor hazardous, on the heart hemodynamics of rats. Therefore, the strategy (noncontact) of using a 3G MP could be the reason for ineffectiveness; and use of 3G MP, in this perspective, seems to be safer compared to the ones used in close contact with the head. However, further study is needed for standardization of such an assumption.

  15. Short-Term Thyroid Hormone Excess Affects the Heart but Does not Affect Adrenal Activity in Rats

    PubMed Central

    Szkudlarek, Ariani Cavazzani; Aldenucci, Bruno; Miyagui, Nelson Itiro; Silva, Ilana Kassouf; Moraes, Rosana Nogueira; Ramos, Helton Estrela; Fogaça, Rosalva Tadeu Hochmuller

    2014-01-01

    Background Hyperthyroidism (Hy) exerts a broad range of influences on a variety of physiological parameters. Its disruptive effect on cardiovascular system is one of its most remarkable impacts. Moreover, Hy has been clinically associated with stress - induced hyperactivation of the hypothalamic-pituitary-adrenal axis. Objective Evaluate the impact of short-term Hy on cardiac performance and adrenal activity of rats. Methods Induction of Hy in Wistar rats through injections of T3 (150 µg/kg) for 10 days (hyperthyroid group - HG) or vehicle (control group). The cardiovascular performance was evaluated by: echocardiography (ECHO); heart weight/body weight (mg/gr) ratio; contractility of isolated papillary muscles (IPM) and direct measurement of blood pressures. Adrenal activity was evaluated by adrenal weight/body weight (mg/gr) ratio and 24-hour fecal corticosterone (FC) levels on the, 5th and 10th days of T3 treatment. Results In HG, the ECHO showed reduction of the End Systolic and End Diastolic Volumes, Ejection, Total Diastolic and Isovolumic Relaxation Times, Diastolic and Systolic Areas and E/A ratio. Heart Rate, Ejection Fraction and Cardiac Output increased. The heart weight/body weight ratio was higher. Similarly, in IPM, the maximum rate of force decay during relaxation was higher in all extracellular calcium concentrations. Systolic blood pressure (SBP) levels were higher. (p ≤ 0.05). On the other hand, there was no difference in the adrenal weight/body weight ratio or in the 24-hour FC levels. Conclusions Hy induces positive inotropic, chronotropic and lusitropic effects on the heart by direct effects of T3 and increases SBP. Those alterations are not correlated with changes in the adrenal activity. PMID:24676225

  16. Maximal oxygen uptake and exercise tolerance are improved in rats with heart failure subjected to low-level laser therapy associated with resistance training.

    PubMed

    Hentschke, Vítor Scotta; Capalonga, Lucas; Rossato, Douglas Dalcin; Perini, Júlia Luíza; Alves, Jadson Pereira; Stefani, Giuseppe Potrick; Karsten, Marlus; Pontes, Mauro; Lago, Pedro Dal

    2017-01-01

    Exercise tolerance and maximal oxygen uptake (VO2max) are reduced in heart failure (HF). The influence of combined resistance training (RT) and low-level laser therapy (LLLT) on exercise tolerance and VO2max in HF has not yet been explored. The aim of this study was to evaluate the influence of combined RT and LLLT on VO2max and exercise tolerance in rats with HF induced by myocardial infarction (MI). Rats were allocated to sedentary sham (Sed-Sham, n = 12), sedentary heart failure (Sed-HF, n = 9), RT heart failure (RT-HF, n = 7) and RT associated with LLLT heart failure (RT + LLLT-HF, n = 7) groups. After MI or sham surgery, rats underwent a RT and LLLT protocol (applied immediately after RT) for 8 weeks. VO2max and exercise tolerance were evaluated at the end of protocol. HF rats subjected to LLLT combined with RT showed higher VO2basal (41 %), VO2max (40 %), VO2reserve (39 %), run distance (46 %), time to exhaustion (30 %) and maximal velocity (22 %) compared with HF rats that underwent RT alone. LLLT associated with RT improved oxygen uptake and exercise tolerance compared with RT alone in HF rats.

  17. Aerobic training prior to myocardial infarction increases cardiac GLUT4 and partially preserves heart function in spontaneously hypertensive rats.

    PubMed

    Schaun, Maximiliano Isoppo; Marschner, Rafael Aguiar; Peres, Thiago Rodrigues; Markoski, Melissa Medeiros; Lehnen, Alexandre Machado

    2017-03-01

    We assessed cardiac function (echocardiographic) and glucose transporter 4 (GLUT4) expression (Western blot) in response to 10 weeks of aerobic training (treadmill) prior to acute myocardial infarction (AMI) by ligation of the left coronary artery in spontaneously hypertensive rats. Animals were allocated to sedentary+sham, sedentary+AMI, training+sham, and training+AMI. Aerobic training prior to AMI partially preserves heart function. AMI and/or aerobic training increased GLUT4 expression. However, those animals trained prior to AMI showed a greater increase in GLUT4 in cardiomyocytes.

  18. Role of Opioid Receptors Signaling in Remote Electrostimulation - Induced Protection against Ischemia/Reperfusion Injury in Rat Hearts

    PubMed Central

    Tsai, Hsin-Ju; Huang, Shiang-Suo; Tsou, Meng-Ting; Wang, Hsiao-Ting; Chiu, Jen-Hwey

    2015-01-01

    Aims Our previous studies demonstrated that remote electro-stimulation (RES) increased myocardial GSK3 phosphorylation and attenuated ischemia/ reperfusion (I/R) injury in rat hearts. However, the role of various opioid receptors (OR) subtypes in preconditioned RES-induced myocardial protection remains unknown. We investigated the role of OR subtype signaling in RES-induced cardioprotection against I/R injury of the rat heart. Methods & Results Male Spraque-Dawley rats were used. RES was performed on median nerves area with/without pretreatment with various receptors antagonists such as opioid receptor (OR) subtype receptors (KOR, DOR, and MOR). The expressions of Akt, GSK3, and PKCε expression were analyzed by Western blotting. When RES was preconditioned before the I/R model, the rat's hemodynamic index, infarction size, mortality and serum CK-MB were evaluated. Our results showed that Akt, GSK3 and PKCε expression levels were significantly increased in the RES group compared to the sham group, which were blocked by pretreatment with specific antagonists targeting KOR and DOR, but not MOR subtype. Using the I/R model, the duration of arrhythmia and infarct size were both significantly attenuated in RES group. The mortality rates of the sham RES group, the RES group, RES group + KOR antagonist, RES group + DOR/MOR antagonists (KOR left), RES group + DOR antagonist, and RES group + KOR/MOR antagonists (DOR left) were 50%, 20%, 67%, 13%, 50% and 55%, respectively. Conclusion The mechanism of RES-induced myocardial protection against I/R injury seems to involve multiple target pathways such as Akt, KOR and/or DOR signaling. PMID:26430750

  19. Melatonin ameliorates metabolic risk factors, modulates apoptotic proteins, and protects the rat heart against diabetes-induced apoptosis.

    PubMed

    Amin, Ali H; El-Missiry, Mohamed A; Othman, Azza I

    2015-01-15

    The present study investigated the ability of melatonin in reducing metabolic risk factors and cardiac apoptosis induced by diabetes. Streptozotocin (60 mg/kg, i.p.) was injected into male rats, and after diabetic induction melatonin (10mg/kg i.g.) was administered orally for 21 days. Diabetic hearts showed increased number of apoptotic cells with downregulation of Bcl-2 and activation of p53 and CD95 as well as the caspases 9, 8 and 3. In addition, there was a significant decrease in insulin level, hyperglycemia, elevated HOMA-IR, glycosylated hemoglobin (HbA1c), total lipids, triglycerides, total cholesterol, low and very low-density lipoprotein and decreased high-density lipoprotein. These changes were coupled with a significant increase in the activities of creatin kinase-MB (CK-MB) and lactate dehydrogenase (LDH) in the serum of the diabetic rats indicating myocardium injury. Oral administration of melatonin for 3 weeks after diabetes induction ameliorated the levels of hyperglycemia, insulin, HbA1c, lipids profile and HOMA-IR. The oral melatonin treatment of diabetic rats significantly decreased the number of apoptotic cells in the heart compared to diabetic rats. It enhanced Bcl-2 expression and blocked the activation of CD95 as well as caspases 9, 8 and 3. These changes were accompanied with significant improvement of CK-MB and LDH in the serum indicating the ameliorative effect of melatonin on myocardium injury. Melatonin effectively ameliorated diabetic myocardium injury, apoptosis, reduced the metabolic risk factors and modulated important steps in both extrinsic and intrinsic pathways of apoptosis. Thus, melatonin may be a promising pharmacological agent for ameliorating potential cardiomyopathy associated with diabetes.

  20. Sodium tungstate administration ameliorated diabetes-induced electrical and contractile remodeling of rat heart without normalization of hyperglycemia.

    PubMed

    Aydemir, Mustafa; Ozturk, Nihal; Dogan, Serdar; Aslan, Mutay; Olgar, Yusuf; Ozdemir, Semir

    2012-08-01

    Recently, sodium tungstate was suggested to improve cardiac performance of diabetic rats in perfused hearts based on its insulinomimetic activity. In this study, we aimed to investigate the cellular and molecular mechanisms underlying this beneficial effect of sodium tungstate. Tungstate was administered (100 mg/kg/day) to diabetic and control rats intragastrically for 6 weeks. Blood glucose levels increased, whereas body weight, heart weight and plasma insulin levels decreased significantly in diabetic animals. Interestingly, none of these parameters was changed by tungstate treatment. On the other hand, fractional shortening and accompanying intracellular Ca(2+) [Ca(2+)](i) transients of isolated ventricular myocytes were measured, and sodium tungstate was found to improve the peak shortening and the amplitude of [Ca(2+)](i) transients in diabetic cardiomyocytes. Potassium and L-type Ca(2+) currents were also recorded in isolated ventricular cells. Significant restoration of suppressed I (to) and I (ss) was achieved by tungstate administration. Nevertheless, L-type calcium currents did not change either in untreated or treated diabetic rats. Tissue biochemical parameters including TBARS, protein carbonyl content, xanthine oxidase (XO) and xanthine dehydogenase (XDH) were also determined, and diabetes revealed a marked increase in TBARS and carbonyl content which were decreased significantly by tungstate treatment. Conversely, although XO and XDH activities didn't change in untreated diabetic rats, a remarkable but insignificant decrease was detected in treated animals. In conclusion, tungstate treatment improved diabetes-induced contractile abnormalities via restoration of dysregulated [Ca(2+)](i) and altered ionic currents. This beneficial effect is due to antioxidant property of sodium tungstate rather than normalization of hyperglycemia.

  1. Possible involvement of phosphorylated heat-shock factor-1 in changes in heat shock protein 72 induction in the failing rat heart following myocardial infarction.

    PubMed

    Marunouchi, Tetsuro; Murata, Mao; Takagi, Norio; Tanonaka, Kouichi

    2013-01-01

    It is supposed that an increase in the level of heat shock protein 72 (HSP72) in the failing heart would be beneficial for reducing the myocardial damage. However, the induction of HSP72 after an exposure to heat shock is blunted in the failing rat heart following myocardial infarction. In this study, to clarify the possible mechanisms underlying this reduction in the ability for HSP72 induction in the failing heart, the possible involvement of heat-shock factor-1 (HSF1), an HSP transcription factor, in this reduction was examined. When hemodynamic parameters of rats with myocardial infarction 8 weeks after coronary artery ligation were measured, the animals showed the signs of chronic heart failure. The HSF1 content was increased in the viable myocardium in the failing heart. The ability to induce cardiac HSP72 was reduced after an exposure to hyperthermia. The level of HSF1 in the cytosolic fraction from the failing heart with or without exposure to hyperthermia was increased, whereas that of HSF1 in the nuclear fraction was reduced. In the failing heart, the level of HSF1 on its serine 303 (Ser303) residue, which phosphorylation represses HSF1, was increased. These findings suggest that HSF1 translocation from the cytosol into the nucleus was attenuated after an exposure to hyperthermia and that an increase in the phosphorylation of HSF1 Ser303 was involved in the impairment of heat shock-induced HSP72 induction in the failing heart following myocardial infarction.

  2. Oral administration of eicosapentaenoic acid or docosahexaenoic acid modifies cardiac function and ameliorates congestive heart failure in male rats.

    PubMed

    Yamanushi, Tomoko T; Kabuto, Hideaki; Hirakawa, Eiichiro; Janjua, Najma; Takayama, Fusako; Mankura, Mitsumasa

    2014-04-01

    This study assessed the effects of eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) on normal cardiac function (part 1) and congestive heart failure (CHF) (part 2) through electrocardiogram analysis and determination of EPA, DHA, and arachidonic acid (AA) concentrations in rat hearts. In part 2, pathologic assessments were also performed. For part 1 of this study, 4-wk-old male rats were divided into a control group and 2 experimental groups. The rats daily were orally administered (1 g/kg body weight) saline, EPA-ethyl ester (EPA-Et; E group), or DHA-ethyl ester (DHA-Et; D group), respectively, for 28 d. ECGs revealed that QT intervals were significantly shorter for groups E and D compared with the control group (P ≤ 0.05). Relative to the control group, the concentration of EPA was higher in the E group and concentrations of EPA and DHA were higher in the D group, although AA concentrations were lower (P ≤ 0.05). In part 2, CHF was produced by subcutaneous injection of monocrotaline into 5-wk-old rats. At 3 d before monocrotaline injection, rats were administered either saline, EPA-Et, or DHA-Et as mentioned above and then killed at 21 d. The study groups were as follows: normal + saline (control), CHF + saline (H group), CHF + EPA-Et (HE group), and CHF + DHA-Et (HD group). QT intervals were significantly shorter (P ≤ 0.05) in the control and HD groups compared with the H and HE groups. Relative to the H group, concentrations of EPA were higher in the HE group and those of DHA were higher in the control and HD groups (P ≤ 0.05). There was less mononuclear cell infiltration in the myocytes of the HD group than in the H group (P = 0.06). The right ventricles in the H, HE, and HD groups showed significantly increased weights (P ≤ 0.05) compared with controls. The administration of EPA-Et or DHA-Et may affect cardiac function by modification of heart fatty acid composition, and the administration of DHA-Et may ameliorate CHF.

  3. Electrical stimulation of the aortic depressor nerve in conscious rats overcomes the attenuation of the baroreflex in chronic heart failure.

    PubMed

    Pinto, Tomás O C Teixeira; Lataro, Renata M; Castania, Jaci A; Durand, Marina T; Silva, Carlos A A; Patel, Kaushik P; Fazan, Rubens; Salgado, Helio C

    2016-04-01

    Chronic heart failure (CHF) is characterized by autonomic dysfunction combined with baroreflex attenuation. The hypotensive and bradycardic responses produced by electrical stimulation of the aortic depressor nerve (ADN) were examined in conscious CHF and control male Wistar rats (12-13 wk old). Furthermore, the role of parasympathetic and sympathetic nervous system in mediating the cardiovascular responses to baroreflex activation was evaluated by selective β1-adrenergic and muscarinic receptor antagonists. CHF was induced by myocardial infarction. After 6 wk, the subjects were implanted with electrodes for ADN stimulation. Twenty-four hours later, electrical stimulation of the ADN was applied for 20 s using five different frequencies (5, 15, 30, 60, and 90 Hz), while the arterial pressure was recorded by a catheter implanted into the femoral artery. Electrical stimulation of the ADN elicited progressive and similar hypotensive and bradycardic responses in control (n = 12) and CHF (n = 11) rats, while the hypotensive response was not affected by methylatropine. Nevertheless, the reflex bradycardia was attenuated by methylatropine in control, but not in CHF rats. Atenolol did not affect the hypotensive or bradycardic response in either group. The ADN function was examined under anesthesia through electroneurographic recordings. The arterial pressure-ADN activity relationship was attenuated in CHF rats. In conclusion, despite the attenuation of baroreceptor function in CHF rats, the electrical stimulation of the ADN elicited a stimulus-dependent hypotension and bradycardia of similar magnitude as observed in control rats. Therefore, electrical activation of the aortic baroreflex overcomes both the attenuation of parasympathetic function and the sympathetic overdrive.

  4. Merits of Non-Invasive Rat Models of Left Ventricular Heart Failure

    EPA Science Inventory

    Heart failure (HF) is defined primarily by the impairment of cardiac function and consequent inability of the heart to supply tissues with ample oxygen. To study HF etiology, investigators have applied many different techniques to elicit this condition in animals, with varying de...

  5. Cardiovascular effects of native and non-native urotensin II and urotensin II-related peptide on rat and salmon hearts.

    PubMed

    Prosser, H C G; Leprince, J; Vaudry, H; Richards, A M; Forster, M E; Pemberton, C J

    2006-12-01

    Urotensin II (UII) was first discovered in the urophyses of goby fish and later identified in mammals, while urotensin II-related peptide (URP) was recently isolated from rat brain. We studied the effects of UII on isolated heart preparations of Chinook salmon and Sprague-Dawley rats. Native rat UII caused potent and sustained, dose-dependent dilation of the coronary arteries in the rat, whereas non-native UII (human and trout UII) showed attenuated vasodilation. Rat URP dilated rat coronary arteries, with 10-fold less potency compared with rUII. In salmon, native trout UII caused sustained dilation of the coronary arteries, while rat UII and URP caused significant constriction. Nomega-nitro-(l)-arginine methyl (l-NAME) and indomethacin significantly attenuated the URP and rat UII-induced vasodilation in the rat heart. We conclude that UII is a coronary vasodilator, an action that is species form specific. We also provide the first evidence for cardiac actions of URP, possibly via mechanisms common with UII.

  6. Comparison of rat and rabbit embryo-fetal developmental ...

    EPA Pesticide Factsheets

    Regulatory non-clinical safety testing of human pharmaceutical compounds typically requires embryo fetal developmental toxicity (EFDT) testing in two species, (one rodent and one non-rodent, usually the rat and the rabbit). The question has been raised whether under some conditions EFDT testing could be limited to one species, or whether the need for testing in a second species could be decided on a case by case basis. As part of an RIVM/CBG-MEB/HESI/US EPA consortium initiative, we built and queried a database of 379 EFDT studies conducted for marketed and non-marketed pharmaceutical compounds. The animal models (rat and rabbit) were assessed for their potential for adverse developmental and maternal outcomes. The database was analyzed for the prevalence of EFDT incidence and the nature and severity of adverse findings in the two species. Some manifestation of EFDT in either one or both species (rat and rabbit) was demonstrated for 282 compounds (74%), and EFDT was detected in only one species (rat or rabbit) in almost a third (31%, 118 compounds), with approximately 58% rat and 42% rabbit studies identifying an EFDT signal among the 379 compounds tested. For 24 compounds (6%), fetal malformations were observed in one species (rat or rabbit) in the absence of any EFDT in the second species. In general, growth retardation, fetal variations, and malformations were more prominent in the rat, whereas embryo-fetal death was observed more often in the rabbit. Discor

  7. Mechanism of passive Ca2+ permeability of vesicular sarcolemmal preparations from rat hearts.

    PubMed

    Kupriyanov, V V; Preobrazhensky, A N; Saks, V A

    1983-02-01

    Vesicular sarcolemmal preparations isolated from rat hearts were characterized by high total ATPase (4.32 +/- 0.57 mumol/min per mg), adenylate cyclase (121 +/- 11 pmol/min per mg) and creatine kinase (1.73 +/- 0.35 mumol/min per mg) activities as well as Na-Ca exchange specific to sodium. ATPase activity was inhibited with digitoxigenin by 50-70% and was not changed by ouabain, ionophore A23187 or oligomycin. Sarcolemmal vesicles bound [3H]digitoxigenin and [3H]ouabain in isotonic medium in the presence of Pi and Mg2+. The number of binding sites for hydrophobic digitoxigenin (N = 237 pmol/mg) was several-times higher than that for hydrophilic ouabain (N = 32.7 pmol/mg). These data show that sarcolemmal preparations were not significantly contaminated by mitochondria and sarcoplasmic reticulum and consisted mostly of inside-out vesicles. Incubation of these vesicles with 45Ca2+ (0.5-10 mM) led to penetration of the latter into the vesicles with the following binding characteristics: number of binding sites (N = 20.5 +/- 4.6 nmol/mg, Kd approximately equal to 2.0 mM). Ca2+ binding to the inner surface of vesicles was proved by the following facts: (1) Ca2+ ionophore A23187 increased slightly total intravesicular Ca2+ content but markedly accelerated Ca2+ efflux along its concentration gradient; (2) gramicidin and osmotic shock showed a similar accelerating effect. Ca2+ efflux from the vesicles along its concentration gradient ([Ca2+]i/[Ca2+]e = 2.0 mM/0.1 microM) was inhibited by Mn2+, Co2+, and verapamil when they acted inside the vesicles. The rate of Ca2+ efflux was hyperbolically dependent on intravesicular Ca2+ concentration (Km approximately equal to 2.9 mM). These data reveal that Ca2+ efflux from sarcolemmal vesicles is controlled by Ca2+ binding to the sarcolemmal membrane. Ca2+ efflux from the vesicles was stimulated 1.7--times after incubation of vesicles with 0.2 mM MgATP or MgADP and 15-times after treatment with 0.2 mM adenylyl beta, gamma

  8. Comparison of body composition, heart rate variability, aerobic and anaerobic performance between competitive cyclists and triathletes

    PubMed Central

    Arslan, Erşan; Aras, Dicle

    2016-01-01

    [Purpose] The aim of this study was to compare the body composition, heart rate variability, and aerobic and anaerobic performance between competitive cyclists and triathletes. [Subjects] Six cyclists and eight triathletes with experience in competitions voluntarily participated in this study. [Methods] The subjects’ body composition was measured with an anthropometric tape and skinfold caliper. Maximal oxygen consumption and maximum heart rate were determined using the incremental treadmill test. Heart rate variability was measured by 7 min electrocardiographic recording. The Wingate test was conducted to determine anaerobic physical performance. [Results] There were significant differences in minimum power and relative minimum power between the triathletes and cyclists. Anthropometric characteristics and heart rate variability responses were similar among the triathletes and cyclists. However, triathletes had higher maximal oxygen consumption and lower resting heart rates. This study demonstrated that athletes in both sports have similar body composition and aerobic performance characteristics. PMID:27190476

  9. Effects of dichloroacetate on the metabolism of glucose, pyruvate, acetate, 3-hydroxybutyrate and palmitate in rat diaphragm and heart muscle in vitro and on extraction of glucose, lactate, pyruvate and free fatty acids by dog heart in vivo

    PubMed Central

    McAllister, Anthony; Allison, S. P.; Randle, Philip J.

    1973-01-01

    1. The extractions of glucose, lactate, pyruvate and free fatty acids by dog heart in vivo were calculated from measurements of their arterial and coronary sinus blood concentration. Elevation of plasma free fatty acid concentrations by infusion of intralipid and heparin resulted in increased extraction of free fatty acids and diminished extractions of glucose, lactate and pyruvate by the heart. It is suggested that metabolism of free fatty acids by the heart in vivo, as in vitro, may impair utilization of these substrates. These effects of elevated plasma free fatty acid concentrations on extractions by the heart in vivo were reversed by injection of dichloroacetate, which also improved extraction of lactate and pyruvate by the heart in vivo in alloxan diabetes. 2. Sodium dichloroacetate increased glucose oxidation and pyruvate oxidation in hearts from fed normal or alloxan-diabetic rats perfused with glucose and insulin. Dichloroacetate inhibited oxidation of acetate and 3-hydroxybutyrate and partially reversed inhibitory effects of these substrates on the oxidation of glucose. In rat diaphragm muscle dichloroacetate inhibited oxidation of acetate, 3-hydroxybutyrate and palmitate and increased glucose oxidation and pyruvate oxidation in diaphragms from alloxan-diabetic rats. Dichloroacetate increased the rate of glycolysis in hearts perfused with glucose, insulin and acetate and evidence is given that this results from a lowering of the citrate concentration within the cell, with a consequent activation of phosphofructokinase. 3. In hearts from normal rats perfused with glucose and insulin, dichloroacetate increased cell concentrations of acetyl-CoA, acetylcarnitine and glutamate and lowered those of aspartate and malate. In perfusions with glucose, insulin and acetate, dichloroacetate lowered the cell citrate concentration without lowering the acetyl-CoA or acetylcarnitine concentrations. Measurements of specific radioactivities of acetyl-CoA, acetylcarnitine

  10. Expression of inducible stress protein 70 in rat heart myogenic cells confers protection against simulated ischemia-induced injury.

    PubMed Central

    Mestril, R; Chi, S H; Sayen, M R; O'Reilly, K; Dillmann, W H

    1994-01-01

    Myocardial ischemia markedly increases the expression of several members of the stress/heat shock protein (HSP) family, especially the inducible HSP70 isoforms. Increased expression of HSP70 has been shown to exert a protective effect against a lethal heat shock. We have examined the possibility of using this resistance to a lethal heat shock as a protective effect against an ischemic-like stress in vitro using a rat embryonic heart-derived cell line H9c2 (2-1). Myogenic cells in which the heat shock proteins have been induced by a previous heat shock are found to become resistant to a subsequent simulated ischemic stress. In addition, to address the question of how much does the presence of the HSP70 contribute to this protective effect, we have generated stably transfected cell lines overexpressing the human-inducible HSP70. Embryonal rat heart-derived H9c2(2-1) cells were used for this purpose. This stably transfected cell line was found to be significantly more resistant to an ischemic-like stress than control myogenic cells only expressing the selectable marker (neomycin) or the parental cell line H9c2(2-1). This finding implicates the inducible HSP70 protein as playing a major role in protecting cardiac cells against ischemic injury. Images PMID:8113409

  11. Phosphorus-31 NMR magnetization transfer measurements of metabolic reaction rates in the rat heart and kidney in vivo

    SciTech Connect

    Koretsky, A.P.

    1984-01-01

    /sup 31/P NMR is a unique tool to study bioenergetics in living cells. The application of magnetization transfer techniques to the measurement of steady-state enzyme reaction rates provides a new approach to understanding the regulation of high energy phosphate metabolism. This dissertation is concerned with the measurement of the rates of ATP synthesis in the rat kidney and of the creatine kinase catalyzed reaction in the rat heart in situ. The theoretical considerations of applying magnetization transfer techniques to intact organs are discussed with emphasis on the problems associated with multiple exchange reactions and compartmentation of reactants. Experimental measurements of the ATP synthesis rate were compared to whole kidney oxygen consumption and Na/sup +/ reabsorption rates to derive ATP/O values. The problems associated with ATP synthesis rate measurements in kidney, e.g. the heterogeneity of the inorganic phosphate resonance, are discussed and experiments to overcome these problems proposed. In heart, the forward rate through creatine kinase was measured to be larger than the reverse rate. To account for the difference in forward and reverse rates a model is proposed based on the compartmentation of a small pool of ATP.

  12. Longitudinal Evaluation of Fatty Acid Metabolism in Normal and Spontaneously Hypertensive Rat Hearts with Dynamic MicroSPECT Imaging

    DOE PAGES

    Reutter, Bryan W.; Huesman, Ronald H.; Brennan, Kathleen M.; ...

    2011-01-01

    The goal of this project is to develop radionuclide molecular imaging technologies using a clinical pinhole SPECT/CT scanner to quantify changes in cardiac metabolism using the spontaneously hypertensive rat (SHR) as a model of hypertensive-related pathophysiology. This paper quantitatively compares fatty acid metabolism in hearts of SHR and Wistar-Kyoto normal rats as a function of age and thereby tracks physiological changes associated with the onset and progression of heart failure in the SHR model. The fatty acid analog, 123 I-labeled BMIPP, was used in longitudinal metabolic pinhole SPECT imaging studies performed every seven months for 21 months. The uniquenessmore » of this project is the development of techniques for estimating the blood input function from projection data acquired by a slowly rotating camera that is imaging fast circulation and the quantification of the kinetics of 123 I-BMIPP by fitting compartmental models to the blood and tissue time-activity curves.« less

  13. Perinatal and Postnatal Expression of Cav1.3 α1D Ca2+ Channel in the Rat Heart

    PubMed Central

    Qu, Yongxia; Karnabi, Eddy; Ramadan, Omar; Yue, Yuankun; Chahine, Mohamed; Boutjdir, Mohamed

    2011-01-01

    The novel Cav1.3 (α1D) L-type Ca2+ channel plays a significant role in sino-atrial, atrioventricular nodes function and in atrial fibrillation. However, the characterization of α1D Ca2+ channel during heart development is very limited. We used real-time RT-PCR, Western blotting and indirect immunostaining to characterize the developmental expression and localization of α1D Ca2+ channel in rat hearts. Both protein and mRNA levels of α1D Ca2+ channel decreased postnatally. Two forms of α1D Ca2+ channel protein (250 kD and 190 kD) were observed, with the full length (250kD) channel protein being predominant in the prenatal stages. Both Western blots and confocal imaging demonstrated that α1D Ca2+ channel protein was expressed in both atria and ventricles at fetal and neonatal stages but was absent in the adult ventricles. Interestingly, α1D Ca2+ channel was also found at the nucleus/perinucleus of immature, but not adult atrial cells. Furthermore, the nuclear staining was reproduced in adult atrial cell line, HL-1 cells, which possess immature properties. The data are first to show that α1D Ca2+ channel has unique age-dependent expression profile and subcellular localization in the heart, suggesting a developmental stage dependent specific function. PMID:21378599

  14. Hypokinesia of myocardium of perfused rat heart at different oxygenation of myoglobin and redox state of cytochrome

    NASA Astrophysics Data System (ADS)

    Frank, Klaus H.; Zuendorf, J.; Tauschek, D.; Kessler, Manfred D.

    2002-06-01

    Questions about development of hypo-kinetic zones in myocardium of patients suffering from severe coronary heart disease are discussed controversially among heart surgeons. We established a model for isolated and hemoglobin free perfusion of rat heart in which sufficient flow was established within all capillaries and thus existence of ischemic capillaries could be excluded. A definite diagnosis of tissue anoxia is only possible by optical measurements of the oxidation and the reduction (redox state) of the cytochrome oxidase of intact myocytes. Therefore, we used an EMPHO for this kind of measurements. Intracellular oxygenation of myoglobin oxygenation (MbO2) and redox state of cytochrome aa3, b and c were recorded in the outer wall of working, hypo-kinetic and a-kinetic myocardium. As a result of our investigations we were able to prove that by lowering at the venous end of capillaries tissue pO2 and myoglobin oxygenation stepwise below 5 mmHg and 50% of saturation respectively, a continuous decrease of myocardial contractility could be achieved.

  15. Evidence of Reversible Bradycardia and Arrhythmias Caused by Immunogenic Proteins Secreted by T. cruzi in Isolated Rat Hearts

    PubMed Central

    Rodríguez-Angulo, Héctor O.; Toro-Mendoza, Jhoan; Marques, Juan A.; Concepción, Juan L.; Bonfante-Cabarcas, Rafael; Higuerey, Yoliver; Thomas, Luz E.; Balzano-Nogueira, Leandro; López, José R.; Mijares, Alfredo

    2015-01-01

    Rationale Chagas cardiomyopathy, caused by the protozoan Trypanosoma cruzi, is characterized by alterations in intracellular ion, heart failure and arrhythmias. Arrhythmias have been related to sudden death, even in asymptomatic patients, and their molecular mechanisms have not been fully elucidated. Objective The aim of this study is to demonstrate the effect of proteins secreted by T. cruzi on healthy, isolated beating rat heart model under a non-damage-inducing protocol. Methods and Results We established a non-damage-inducing recirculation-reoxygenation model where ultrafiltrate fractions of conditioned medium control or conditioned infected medium were perfused at a standard flow rate and under partial oxygenation. Western blotting with chagasic patient serum was performed to determine the antigenicity of the conditioned infected medium fractions. We observed bradycardia, ventricular fibrillation and complete atrioventricular block in hearts during perfusion with >50 kDa conditioned infected culture medium. The preincubation of conditioned infected medium with chagasic serum abolished the bradycardia and arrhythmias. The proteins present in the conditioned infected culture medium of >50 kDa fractions were recognized by the chagasic patient sera associated with arrhythmias. Conclusions These results suggest that proteins secreted by T. cruzi are involved in Chagas disease arrhythmias and may be a potential biomarker in chagasic patients. PMID:25647069

  16. The effects of homocysteine-related compounds on cardiac contractility, coronary flow, and oxidative stress markers in isolated rat heart.

    PubMed

    Zivkovic, Vladimir; Jakovljevic, Vladimir; Djordjevic, Dusica; Vuletic, Milena; Barudzic, Nevena; Djuric, Dragan

    2012-11-01

    Research on the effects of homocysteine on the vascular wall, especially in endothelial and smooth muscle cells, has indicated that increased homocysteine levels lead to cellular stress and cell damage. Considering the adverse effects of homocysteine on vascular function and the role of oxidative stress in these mechanisms, the aim of this study was to estimate the influence of different homocysteine isoforms on cardiac contractility, coronary flow, and oxidative stress markers in isolated rat heart. The hearts of male Wistar albino rats (n = 36, age 8 weeks, body mass 180-200 g), were excised and retrogradely perfused according to the Langendorff technique at a constant perfusion pressure (70 cmH(2)O) and administered with three isoforms of 10 μM homocysteine [DL-Hcy, DL-Hcy thiolactone-hydrochloride (TLHC) and L-Hcy TLHC). After the insertion and placement of the sensor in the left ventricle, the parameters of heart function: maximum rate of pressure development in the left ventricle (dP/dt max), minimum rate of pressure development in the left ventricle (dP/dt min), systolic left ventricular pressure (SLVP), diastolic left ventricular pressure (DLVP), mean blood pressure (MBP) and heart rate (HR)] were continuously registered. Flowmetry was used to evaluate the coronary flow. Markers of oxidative stress: index of lipid peroxidation measured as TBARS, nitric oxide measured through nitrites (NO(2)(-)), superoxide anion radical (O(2)(-)), and hydrogen peroxide (H(2)O(2)) in the coronary venous effluent were assessed spectrophotometrically. Our results showed that administration of Hcy compounds in concentration of 10 μM induced depression of cardiac contractility, manifested by a decrease in dp/dt max after administration of any Hcy compound, decrease in dp/dt min after administration of L-Hcy TLHC, decrease in SLVP after administration of DL-Hcy TLHC and DL-Hcy, and the drop in CF after administration of any Hcy compound. Regarding the effects of Hcy on

  17. Seasonal superoxide overproduction and endothelial activation in guinea-pig heart; seasonal oxidative stress in rats and humans.

    PubMed

    Konior, Anna; Klemenska, Emilia; Brudek, Magdalena; Podolecka, Ewa; Czarnowska, Elżbieta; Beręsewicz, Andrzej

    2011-04-01

    Seasonality in endothelial dysfunction and oxidative stress was noted in humans and rats, suggesting it is a common phenomenon of a potential clinical relevance. We aimed at studying (i) seasonal variations in cardiac superoxide (O(2)(-)) production in rodents and in 8-isoprostane urinary excretion in humans, (ii) the mechanism of cardiac O(2)(-) overproduction occurring in late spring/summer months in rodents, (iii) whether this seasonal O(2)(-)-overproduction is associated with a pro-inflammatory endothelial activation, and (iv) how the summer-associated changes compare to those caused by diabetes, a classical cardiovascular risk factor. Langendorff-perfused guinea-pig and rat hearts generated ~100% more O(2)(-), and human subjects excreted 65% more 8-isoprostane in the summer vs. other seasons. Inhibitors of NADPH oxidase, xanthine oxidase, and NO synthase inhibited the seasonal O(2)(-)-overproduction. In the summer vs. other seasons, cardiac NADPH oxidase and xanthine oxidase activity, and protein expression were increased, the endothelial NO synthase and superoxide dismutases were downregulated, and, in guinea-pig hearts, adhesion molecules upregulation and the endothelial glycocalyx destruction associated these changes. In guinea-pig hearts, the summer and a streptozotocin-induced diabetes mediated similar changes, yet, more severe endothelial activation associated the diabetes. These findings suggest that the seasonal oxidative stress is a common phenomenon, associated, at least in guinea-pigs, with the endothelial activation. Nonetheless, its biological meaning (regulatory vs. deleterious) remains unclear. Upregulated NADPH oxidase and xanthine oxidase and uncoupled NO synthase are the sources of the seasonal O(2)(-)-overproduction.

  18. [Effect of different concentrations liposomal emoxipine on coronary flow, contractive and pump function of the isolated rat heart after normotermic ischema and further reperfusion].

    PubMed

    Toropova, Ia G; Mukhamadiiarov, R A; Golovkin, A S

    2013-07-01

    In the experiments on the isolated perfused rat heart we studied the effects of liposomes containing different concentrations (0.25 and 0.1 mg/ml) of emoxipine on coronary flow, contractive and pump function of the isolated heart, which was effected by total normothermical ischemia and reperfusion. The parameters of the contractile activity of hearts, coronary flow and pump function of the hearts were assessed. It was detected that the introduction of the liposomal emoxipine during ischemia provides a protective effect against ischemic and reperfusion myocardial damage and smaller concentration of the emoxipin (0.1 mg/ml) in composition with the liposomes promote the best recovery of contractile activity and the pumping function of the ischemic heart in the period of the reperfusion.

  19. Comparison of two surgical techniques for creating an acute myocardial infarct in rats

    PubMed Central

    Capriglione, Luiz Guilherme Achcar; Barchiki, Fabiane; Ottoboni, Gabriel Sales; Miyague, Nelson Itiro; Suss, Paula Hansen; Rebelatto, Carmen Lúcia Kuniyoshi; Pimpão, Cláudia Turra; Senegaglia, Alexandra Cristina; Brofman, Paulo Roberto

    2014-01-01

    Objective To perform a comparative assessment of two surgical techniques that are used creating an acute myocardial infarc by occluding the left anterior descending coronary artery in order to generate rats with a left ventricular ejection fraction of less than 40%. Methods The study was completely randomized and comprised 89 halothane-anaesthetised rats, which were divided into three groups. The control group (SHAM) comprised fourteen rats, whose left anterior descending coronary artery was not occluded. Group 1 (G1): comprised by 35 endotracheally intubated and mechanically ventilated rats, whose left anterior descending coronary artery was occluded. Group 2 (G2): comprised 40 rats being manually ventilated using a nasal respirator whose left anterior descending coronary artery was occluded. Other differences between the two techniques include the method of performing the thoracotomy and removing the pericardium in order to expose the heart, and the use of different methods and suture types for closing the thorax. Seven days after surgery, the cardiac function of all surviving rats was determined by echocardiography. Results No rats SHAM group had progressed to death or had left ventricular ejection fraction less than 40%. Nine of the 16 surviving G1 rats (56.3%) and six of the 20 surviving G2 rats (30%) had a left ventricular ejection fraction of less than 40%. Conclusion The results indicate a tendency of the technique used in G1 to be better than in G2. This improvement is probably due to the greater duration of the open thorax, which reduces the pressure over time from the surgeon, allowing occlusion of left anterior descending coronary artery with higher accuracy. PMID:25714202

  20. ACUTE EXPOSURE TO PARTICULATE MATTER IN A RAT MODEL OF HEART FAILURE

    EPA Science Inventory

    Human exposure to ambient particulate matter (PM) has been linked to cardiovascular morbidity and mortality. This association strengthens in people with preexisting cardiopulmonary diseases—especially heart failure (HF). To better characterize the cardiovascular effects of PM, we...

  1. A comparison of different feature extraction methods for diagnosis of valvular heart diseases using PCG signals.

    PubMed

    Rouhani, M; Abdoli, R

    2012-01-01

    This article presents a novel method for diagnosis of valvular heart disease (VHD) based on phonocardiography (PCG) signals. Application of the pattern classification and feature selection and reduction methods in analysing normal and pathological heart sound was investigated. After signal preprocessing using independent component analysis (ICA), 32 features are extracted. Those include carefully selected linear and nonlinear time domain, wavelet and entropy features. By examining different feature selection and feature reduction methods such as principal component analysis (PCA), genetic algorithms (GA), genetic programming (GP) and generalized discriminant analysis (GDA), the four most informative features are extracted. Furthermore, support vector machines (SVM) and neural network classifiers are compared for diagnosis of pathological heart sounds. Three valvular heart diseases are considered: aortic stenosis (AS), mitral stenosis (MS) and mitral regurgitation (MR). An overall accuracy of 99.47% was achieved by proposed algorithm.

  2. Orthotopic heart transplant versus left ventricular assist device: A national comparison of cost and survival

    PubMed Central

    Mulloy, Daniel P.; Bhamidipati, Castigliano M.; Stone, Matthew L.; Ailawadi, Gorav; Kron, Irving L.; Kern, John A.

    2012-01-01

    Objectives Orthotopic heart transplantation is the standard of care for end-stage heart disease. Left ventricular assist device implantation offers an alternative treatment approach. Left ventricular assist device practice has changed dramatically since the 2008 Food and Drug Administration approval of the HeartMate II (Thoratec, Pleasanton, Calif), but at what societal cost? The present study examined the cost and efficacy of both treatments over time. Methods All patients who underwent either orthotopic heart transplantation (n = 9369) or placement of an implantable left ventricular assist device (n = 6414) from 2005 to 2009 in the Nationwide Inpatient Sample were selected. The trends in treatment use, mortality, and cost were analyzed. Results The incidence of orthotopic heart transplantation increased marginally within a 5-year period. In contrast, the annual left ventricular assist device implantation rates nearly tripled. In-hospital mortality from left ventricular assist device implantation decreased precipitously, from 42% to 17%. In-hospital mortality for orthotopic heart transplantation remained relatively stable (range, 3.8%–6.5%). The mean cost per patient increased for both orthotopic heart transplantation and left ventricular assist device placement (40% and 17%, respectively). With the observed increase in both device usage and cost per patient, the cumulative Left ventricular assist device cost increased 232% within 5 years (from $143 million to $479 million). By 2009, Medicare and Medicaid were the primary payers for nearly one half of all patients (orthotopic heart transplantation, 45%; left ventricular assist device, 51%). Conclusions Since Food and Drug Administration approval of the HeartMate II, mortality after left ventricular assist device implantation has decreased rapidly, yet has remained greater than that after orthotopic heart transplantation. The left ventricular assist device costs have continued to increase and have been

  3. Pharmacological induction of transforming growth factor-beta1 in rat models enhances radiation injury in the intestine and the heart.

    PubMed

    Boerma, Marjan; Wang, Junru; Sridharan, Vijayalakshmi; Herbert, Jean-Marc; Hauer-Jensen, Martin

    2013-01-01

    Radiation therapy in the treatment of cancer is dose limited by radiation injury in normal tissues such as the intestine and the heart. To identify the mechanistic involvement of transforming growth factor-beta 1 (TGF-β1) in intestinal and cardiac radiation injury, we studied the influence of pharmacological induction of TGF-β1 with xaliproden (SR 57746A) in rat models of radiation enteropathy and radiation-induced heart disease (RIHD). Because it was uncertain to what extent TGF-β induction may enhance radiation injury in heart and intestine, animals were exposed to irradiation schedules that cause mild to moderate (acute) radiation injury. In the radiation enteropathy model, male Sprague-Dawley rats received local irradiation of a 4-cm loop of rat ileum with 7 once-daily fractions of 5.6 Gy, and intestinal injury was assessed at 2 weeks and 12 weeks after irradiation. In the RIHD model, male Sprague-Dawley rats received local heart irradiation with a single dose of 18 Gy and were followed for 6 months after irradiation. Rats were treated orally with xaliproden starting 3 days before irradiation until the end of the experiments. Treatment with xaliproden increased circulating TGF-β1 levels by 300% and significantly induced expression of TGF-β1 and TGF-β1 target genes in the irradiated intestine and heart. Various radiation-induced structural changes in the intestine at 2 and 12 weeks were significantly enhanced with TGF-β1 induction. Similarly, in the RIHD model induction of TGF-β1 augmented radiation-induced changes in cardiac function and myocardial fibrosis. These results lend further support for the direct involvement of TGF-β1 in biological mechanisms of radiation-induced adverse remodeling in the intestine and the heart.

  4. The determination of presynaptic KA values of methacholine and pilocarpine and of a presynaptic receptor reserve in the rat perfused heart.

    PubMed Central

    Fuchs, P.; Fuder, H.

    1985-01-01

    Rat isolated perfused hearts with the right sympathetic nerves attached were loaded with [3H]-noradrenaline. The nerves were stimulated with up to 11 trains of 10 pulses at 0.1 Hz. The evoked increases of [3H]-noradrenaline overflow into the perfusate were measured in the presence of cocaine, corticosterone and propranolol. Activation of presynaptic muscarinic receptors by methacholine or pilocarpine inhibited the evoked transmitter release in a reversible and concentration-dependent manner. Preperfusion with phenoxybenzamine (5 microM) for 15 min (followed by a washout of 35 min) changed neither resting nor evoked overflow of [3H]-noradrenaline. The concentration-response curve of methacholine was shifted to the right after exposure of the hearts to phenoxybenzamine (1 microM) without depression of the maximum effect. Pretreatment with phenoxybenzamine (5 microM) reduced the maximum inhibition of release by about 50%. Analysis of the data gave a dissociation constant for the agonist-receptor complex (KA) of 4.0 microM and a receptor reserve of roughly 70%. Half-maximal inhibition of [3H]-noradrenaline release occurred when about 2% of the total receptor population was occupied. Comparison of the concentration-response data for methacholine and pilocarpine revealed a relative efficacy (methacholine/pilocarpine) of 16, a KA of 10 microM for pilocarpine and no receptor reserve for this agonist. The results show that KA values for methacholine and pilocarpine obtained at presynaptic receptors are similar to those obtained at postsynaptic muscarinic receptors. This is in agreement with the idea that muscarinic receptors located on postganglionic adrenergic nerves are not different from those located on effector sites of non-neuronal tissue. PMID:2983804

  5. Rats' Memory for Time and Relational Responding in the Duration-Comparison Procedure

    ERIC Educational Resources Information Center

    Santi, Angelo; Hoover, Claire; Simmons, Sabrina

    2011-01-01

    Rats were trained in a duration-comparison task to press one lever if the comparison duration ("c") was 1.2-s shorter than a standard duration ("s"), and another lever if c was 1.2-s longer than s. The interval between s and c duration was 1 s. The 10 duration pairs used during training controlled for the absolute duration of "c" and the total…

  6. RNASeq-derived transcriptome comparisons reveal neuromodulatory deficiency in the CO2 insensitive brown Norway rat.

    PubMed

    Puissant, Madeleine M; Echert, Ashley E; Yang, Chun; Mouradian, Gary C; Novotny, Tyler; Liu, Pengyuan; Liang, Mingyu; Hodges, Matthew R

    2014-11-10

    Raphé-derived serotonin (5-HT) and thyrotropin-releasing hormone (TRH) play important roles in fundamental, homeostatic control systems such as breathing and specifically the ventilatory CO2 chemoreflex. Brown Norway (BN) rats exhibit an inherent and severe ventilatory insensitivity to hypercapnia but also exhibit relatively normal ventilation at rest and during other conditions, similar to multiple genetic models of 5-HT system dysfunction in mice. Herein, we tested the hypothesis that the ventilatory insensitivity to hypercapnia in BN rats is due to altered raphé gene expression and the consequent deficiencies in raphé-derived neuromodulators such as TRH. Medullary raphé transcriptome comparisons revealed lower expression of multiple 5-HT neuron-specific genes in BN compared to control Dahl salt-sensitive rats, predictive of reduced central nervous system monoamines by bioinformatics analyses and confirmed by high-performance liquid chromatography measurements. In particular, raphé Trh mRNA and peptide levels were significantly reduced in BN rats, and injections of the stable TRH analogue Taltirelin (TAL) stimulated breathing dose-dependently, with greater effects in BN versus control Sprague-Dawley rats. Importantly, TAL also effectively normalized the ventilatory CO2 chemoreflex in BN rats, but TAL did not affect CO2 sensitivity in control Sprague-Dawley rats. These data establish a molecular basis of the neuromodulatory deficiency in BN rats, and further suggest an important functional role for TRH signalling in the mammalian CO2 chemoreflex.

  7. RNASeq-derived transcriptome comparisons reveal neuromodulatory deficiency in the CO2 insensitive brown Norway rat.

    PubMed

    Puissant, Madeleine M; Echert, Ashley E; Yang, Chun; Mouradian, Gary C; Novotny, Tyler; Liu, Pengyuan; Liang, Mingyu; Hodges, Matthew R

    2015-01-15

    Raphé-derived serotonin (5-HT) and thyrotropin-releasing hormone (TRH) play important roles in fundamental, homeostatic control systems such as breathing and specifically the ventilatory CO2 chemoreflex. Brown Norway (BN) rats exhibit an inherent and severe ventilatory insensitivity to hypercapnia but also exhibit relatively normal ventilation at rest and during other conditions, similar to multiple genetic models of 5-HT system dysfunction in mice. Herein, we tested the hypothesis that the ventilatory insensitivity to hypercapnia in BN rats is due to altered raphé gene expression and the consequent deficiencies in raphé-derived neuromodulators such as TRH. Medullary raphé transcriptome comparisons revealed lower expression of multiple 5-HT neuron-specific genes in BN compared to control Dahl salt-sensitive rats, predictive of reduced central nervous system monoamines by bioinformatics analyses and confirmed by high-performance liquid chromatography measurements. In particular, raphé Trh mRNA and peptide levels were significantly reduced in BN rats, and injections of the stable TRH analogue Taltirelin (TAL) stimulated breathing dose-dependently, with greater effects in BN versus control Sprague-Dawley rats. Importantly, TAL also effectively normalized the ventilatory CO2 chemoreflex in BN rats, but TAL did not affect CO2 sensitivity in control Sprague-Dawley rats. These data establish a molecular basis of the neuromodulatory deficiency in BN rats, and further suggest an important functional role for TRH signalling in the mammalian CO2 chemoreflex.

  8. Effects of broad band electromagnetic fields on HSP70 expression and ischemia-reperfusion in rat hearts.

    PubMed

    Ronchi, Raffaella; Marano, Lidia; Braidotti, Paola; Bianciardi, Paola; Calamia, Mario; Fiorentini, Cesare; Samaja, Michele

    2004-09-03

    Although exposure to broad band (0.2-20 MHz) electromagnetic fields (EMF) is part of the treatment of several diseases, little is known as to their effects on myocardial protein expression and resistance to ischemia-reperfusion (I/R). We exposed Sprague-Dawley rats to either high (H, 10 min/day at 200 V/m, 36.1 microT) or low (L, 2 min/day at 30 V/m, 11.4 microT) intensity broad band EMF for 15 days. At the end of the treatment, myocardial HSP70 was 32 +/- 8% (mean +/- SEM) higher in L (P = 0.01) than in control (C), whereas in H it remained the same as in C. Electron microscopy revealed sporadic ruptures of mitochondrial cristae in H hearts, with no differences in other parameters. Malondialdehyde was increased in treated hearts (P < 0.05), but especially in H (P = 0.008). To assess the protective role of HSP70 during I/R, hearts were Langendorff-perfused with Krebs-Henseleit. After I/R, C hearts displayed depressed rate. pressure (-13 +/- 7%) and increased end-diastolic (+9.2 +/- 2.8 mmHg) and perfusion pressures (+30 +/- 10 mmHg). In H and L, rate. pressure recovery was similar to C (-2 +/- 21% and -12 +/- 16%, respectively, P = NS). In contrast, both end-diastolic and perfusion pressures were higher in L than in H (30.8 +/- 5.4 vs 18.2 +/- 3.5, P = 0.01, and 54 +/- 8 vs 21 +/- 8 mmHg, P = 0.01, respectively) indicating diastolic derangement in L. In conclusion, the effects of broad band EMF on HSP70 appear to be biphasic, and HSP70 overexpression might not be directly related to improved protection against I/R.

  9. Competition for transport of amino acids into rat heart: effect of competitors on protein synthesis and degradation.

    PubMed

    Tovar, A R; Tews, J K; Torres, N; Madsen, D C; Harper, A E

    1992-09-01

    Transport of the neutral amino acids, 2-(methylamino)isobutyrate (MeAIB) and Phe, was examined in isolated rat hearts perfused by the Langendorff method. Hearts were perfused by recirculating for various time periods buffer containing [14C]-MeAIB or [14C]-Phe plus desired additions. Uptake of MeAIB was linear for approximately 30 minutes; Phe uptake was linear for a maximum of 5 minutes, and reached a steady state after 15 minutes. Km and Vmax for MeAIB were 1.1 +/- 0.03 mmol/L and 37.7 +/- 0.4 pmol/microL intracellular fluid (ICF)/min; values for Phe were 1.8 +/- 0.02 mmol/L and 364 +/- 5 pmol/microL ICF/minute. Uptake of MeAIB (0.2 mmol/L) was reduced 95% in the presence of Ser (10 mmol/L), and less severely by large neutral amino acids ([LNAA], 10 mmol/L) such as Phe and Leu (by 46% and 54%, respectively). Uptake of Phe (0.2 mmol/L) was reduced by LNAA such as Val, Leu, and Ile (by 51%, 78%, and 81%, respectively), or by commercial preparations used in parenteral nutrition, eg, Travasol or Travasol plus extra branched-chain amino acids (BCAA) (Branchamin); Ser had little effect (8% reduction). Insulin in the perfusion medium increased the fractional rate of protein synthesis. Individual BCAA at physiological concentrations (0.2 mmol/L) did not alter the rate of protein synthesis. Branchamin or Travasol plus Branchamin also had no effect on the rate of protein synthesis in heart, but did depress the rate of degradation. These studies suggest that amino acid transport into heart may be affected by normal levels of plasma amino acids, whereas protein synthesis is not.

  10. Changes in Myocardial Composition and Conduction Properties in Rat Heart Failure Model Induced by Chronic Volume Overload

    PubMed Central

    Sedmera, David; Neckar, Jan; Benes, Jiri; Pospisilova, Jana; Petrak, Jiri; Sedlacek, Kamil; Melenovsky, Vojtech

    2016-01-01

    Volume overload leads to development of eccentric cardiac hypertrophy and heart failure. In our previous report, we have shown myocyte hypertrophy with no fibrosis and decrease in gap junctional coupling via connexin43 in a rat model of aorto-caval fistula at 21 weeks. Here we set to analyze the electrophysiological and protein expression changes in the left ventricle and correlate them with phenotypic severity based upon ventricles to body weight ratio. ECG analysis showed increased amplitude and duration of the P wave, prolongation of PR and QRS interval, ST segment elevation and decreased T wave amplitude in the fistula group. Optical mapping showed a prolongation of action potential duration in the hypertrophied hearts. Minimal conduction velocity (CV) showed a bell-shaped curve, with a significant increase in the mild cases and there was a negative correlation of both minimal and maximal CV with heart to body weight ratio. Since the CV is influenced by gap junctional coupling as well as the autonomic nervous system, we measured the amounts of tyrosine hydroxylase (TH) and choline acetyl transferase (ChAT) as a proxy for sympathetic and parasympathetic innervation, respectively. At the protein level, we confirmed a significant decrease in total and phosphorylated connexin43 that was proportional to the level of hypertrophy, and similarly decreased levels of TH and ChAT. Even at a single time-point, severity of morphological phenotype correlates with progression of molecular and electrophysiological changes, with the most hypertrophied hearts showing the most severe changes that might be related to arrhythmogenesis. PMID:27610087

  11. Juniperus communis Linn oil decreases oxidative stress and increases antioxidant enzymes in the heart of rats administered a diet rich in cholesterol.

    PubMed

    Gumral, Nurhan; Kumbul, Duygu Doguc; Aylak, Firdevs; Saygin, Mustafa; Savik, Emin

    2015-01-01

    It has been asserted that consumption of dietary cholesterol (Chol) raises atherosclerotic cardiovascular diseases and that Chol causes an increase in free radical production. Hypercholesterolemic diet has also been reported to cause changes in the antioxidant system. In our study, different doses of Juniperus communis Linn (JCL) oil, a tree species growing in Mediterranean and Isparta regions and having aromatic characteristics, were administered to rats; and the levels of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and thiobarbituric acid reactive substances assay (TBARS) were examined in the heart tissue of rats. In this study, 35 Wistar Albino male adult rats weighing approximately 250-300 g were used. The rats were divided into five groups of seven each. The control group was administered normal pellet chow, and the Chol group was administered pellet chow including 2% Chol, while 50 JCL, 100 JCL, and 200 JCL groups were administered 50, 100, and 200 mg/kg JCL oil dissolved in 0.5% sodium carboxy methyl cellulose, respectively, in addition to the pellet chow containing 2% Chol, by gavage. After 30 days, the experiment was terminated and the antioxidant enzyme activities were examined in the heart tissue of rats. While consumption of dietary Chol decreases the activities of SOD, GSH-Px, and CAT in heart tissue of rats (not significant), administeration of 200 mg/kg JCL oil in addition to Chol led to a significant increase in the activity of antioxidant enzymes. Administering Chol led to a significant increase in TBARS level. Administering 100 and 200 mg/kg JCL oil together with Chol prevented significantly the increase in lipid peroxides. As a result of the study, JCL oil showed oxidant-antioxidant effect in the heart tissue of rats.

  12. COMPARISON OF DETOXIFICATION AND BIOACTIVATION PATHWAYS FOR BROMODICHLOROMETHANE IN THE RAT

    EPA Science Inventory

    Comparison of Detoxification and Bioactivation pathways FOR Bromodichloromethane in the Rat
    M.K. Ross1, C.R. Eklund2, and R.A. Pegram2
    1Curriculum in Toxicology, UNC-CH, Chapel Hill, NC
    2ETD, NHEERL/ORD, USEPA, Research Triangle Park, NC

    Bromodichloromethane (BDCM...

  13. STRAIN COMPARISON OF ENDOCRINE RESPONSE IN RATS TO BROMODICHLOROMETHANE (BDCM) DURING PREGNANCY

    EPA Science Inventory

    STRAIN COMPARISON OF ENDOCRINE RESPONSE IN RATS TO BROMODICHLOROMETHANE (BDCM) DURING PREGNANCY.

    S. R. Bielmeier1, D. S. Best2 and M. G. Narotsky2

    1 Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC, USA
    2 Reproductive Toxicology Division, NHEERL...

  14. Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with resting rats

    EPA Science Inventory

    Dose and effect of inhaled ozone in resting versus exercising human subjects: comparison with