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Myocardial
Terms modified by Myocardial Selected AbstractsImpaired contractile function and mitochondrial respiratory capacity in response to oxygen deprivation in a rat model of pre-diabetesACTA PHYSIOLOGICA, Issue 4 2009M. F. Essop Abstract Aim:, Obesity is a major contributor to the global burden of disease and is closely associated with the development of type 2 diabetes and cardiovascular diseases. This study tested the hypothesis that mitochondrial respiratory capacity of the pre-diabetic heart is decreased leading to impaired contractile function and tolerance to ischaemia/reperfusion. Methods:, Eight-week-old male Wistar rats were fed a high caloric diet for 16 weeks after which anthropometric, metabolic, cardiac and mitochondrial parameters were evaluated vs. age-matched lean controls. Cardiac function (working heart perfusions) and mitochondrial respiratory capacity were assessed at baseline and in response to acute oxygen deprivation. Results:, Rats fed the high caloric diet exhibited increased body weight and visceral fat vs. the control group. Heart weights of obese rats were also increased. Triglyceride, fasting plasma insulin and free fatty acid levels were elevated, while high-density lipoprotein cholesterol levels were reduced in the obese group. Contractile function was attenuated at baseline and further decreased after subjecting hearts to ischaemia-reperfusion. Myocardial infarct sizes were increased while ADP phosphorylation rates were diminished in obese rats. However, no differences were found for mtDNA levels and the degree of oxidative stress-induced damage. Conclusions:, These data show that decreased mitochondrial bioenergetic capacity in pre-diabetic rat hearts may impair respiratory capacity and reduce basal contractile function and tolerance to acute oxygen deprivation. [source] Hypertrophied hearts: what of sevoflurane cardioprotection?ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2009J. R. LARSEN Background: Recent studies have demonstrated that inhalation anaesthetics, like sevoflurane, confer cardioprotection both experimentally and clinically. However, coexisting cardiac disease might diminish anaesthetic cardioprotection and could partly explain why the clinical results of cardioprotection with anaesthetics remain controversial , in contrast to solid experimental evidence. Concomitant left ventricular hypertrophy is found in some cardiac surgery patients and could change cardioprotection efficacy. Hypertrophy could potentially render the heart less susceptible to sevoflurane cardioprotection and more susceptible to ischaemic injury. We investigated whether hypertrophy blocks sevoflurane cardioprotection, and whether tolerance to ischaemia is altered by left ventricular hypertrophy, in an established experimental animal model of ischaemia,reperfusion. Methods: Anaesthetized juvenile pigs (n=7,12/group) were subjected to 45 min distal coronary artery balloon occlusion, followed by 120 min of reperfusion. Controls were given pentobarbital, while sevoflurane cardioprotection was achieved by 3.2% inhalation throughout the experiment. Chronic banding of the ascending aorta resulted in left ventricular hypertrophy development in two further groups and these animals underwent identical ischaemia,reperfusion protocols, with or without sevoflurane cardioprotection. Myocardial infarct sizes were compared post-mortem. Results: The mean myocardial infarct size (% of area-at-risk) was reduced from mean 55.0 (13.6%) (±SD) in controls to 17.5 (13.2%) by sevoflurane (P=0.001). Sevoflurane reduced the infarct size in hypertrophied hearts to 14.6 (10.4%) (P=0.001); however, in hypertrophic controls, infarcts were reduced to 34.2 (10.2%) (P=0.001). Conclusion: Sevoflurane abrogated ischaemic injury to similar levels in both normal and left ventricular hypertrophied hearts. [source] Coronary and systemic hemodynamic effects of clevidipine, an ultra-short-acting calcium antagonist, for treatment of hypertension after coronary artery surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2000N. Kieler-Jensen Background: The aim was to evaluate the use of clevidipine, a new vascular selective, ultra-short-acting calcium antagonist for blood pressure control after coronary artery bypass grafting (CABG). Methods: The effects of clevidipine on central hemodynamics, myocardial blood flow and metabolism were studied at two different phases after CABG. In phase 1 (n=13), the hypertensive phase, the effects of clevidipine were compared to those of sodium nitroprusside (SNP) when used to control postoperative hypertension. In phase 2 (n=9), the normotensive phase, a clevidipine dose-response relationship was established. Results: At a target mean arterial pressure (MAP) of 75 mmHg, systemic vascular resistance (SVR) and heart rate (HR) were lower, preload, stroke volume (SV) and pulmonary vascular resistance (PVR) were higher, while there were no differences in myocardial lactate metabolism or oxygen extraction with clevidipine compared to SNP. In the normotensive phase, clevidipine induced a dose-dependent decrease in MAP (,19%), SVR (,27%) and PVR (,15%), accompanied by an increase in SV (10%), but no reflex increase in HR or changes in cardiac preload. Clevidipine caused a direct coronary vasodilation, as indicated by a decrease in myocardial oxygen extraction from 54% to 45%. Myocardial lactate metabolism was unaffected by clevidipine. The blood clearance of clevidipine was 0.05 l ,· ,min,1 ,· ,kg,1, the volume of distribution at steady state was 0.08 l ,· ,kg,1 and the initial and terminal half-lives were <1 min and 4 min, respectively. Conclusions: Clevidipine rapidly reduced MAP and induced a systemic, pulmonary and coronary vasodilation with no effect on venous capacitance vessels or HR. Clevidipine caused no adverse effects on myocardial lactate metabolism. Clevidipine thus appears suitable to control blood pressure after CABG. [source] In vivo Remote Delivery of DNA Encoding for Hypoxia-inducible Factor 1 Alpha Reduces Myocardial Infarct SizeCLINICAL AND TRANSLATIONAL SCIENCE, Issue 1 2009Gabor Czibik M.D. Abstract We tested if remote gene delivery of hypoxia-inducible factor 1 alpha (HIF-1,) protected hearts against induced ischemia, hypothesizing that gene delivery into skeletal muscle may lead to secretion of proteins with actions elsewhere. Murine quadriceps muscles were transfected with DNA encoding for human HIF-1,, which resulted in a local, but lasting expression (mRNA and protein, where the latter had nuclear localization). Subjection of isolated hearts to global ischemia and reperfusion 1, 4, and 8 weeks after gene delivery resulted in infarct size reduction (p < 0.05). Supporting that this was due to paracrine effects, HL-1 cells treated with conditioned media from cells transfected with HIF-1, or serum from HIF-1,-treated mice were protected against H2O2 -induced cell death (p < 0.05, respectively). The latter protection was reduced when a heme oxygenase activity blocker was used. Taqman low-density array of 47 HIF-1,-regulated genes at the treatment site showed nine specific upregulations (p < 0.05). Of the corresponding proteins, PDGF-B and adrenomedullin were upregulated in the heart. HIF-1, treatment induced an increased vascularization of the heart and skeletal muscle. In conclusion, remote delivery of DNAfor HIF-1, was cardioprotective, represented by consistent infarct size reduction, which may be due to release of paracrine factors from the transfected muscle. [source] Acetylcholine- and ergonovine-induced coronary microvascular spasm reflected by increased coronary vascular resistance and myocardial lactate productionCLINICAL CARDIOLOGY, Issue 3 2000Masashi Horimoto M.D. Abstract Diagnosis of coronary microvascular spasm remains largely speculative because it has been mostly based on chest pain and electrocardiographic ST-segment shift with slow filling of contrast medium into the coronary artery. A patient with resting chest pain and normal coronary angiograms underwent provocative tests with intracoronary acetylcholine (ACh) and ergonovine. During the tests, coronary diameter and flow velocity in the left anterior descending (LAD) coronary artery were measured with quantitative coronary angiography and intracoronary Doppler guide wire, respectively. Vascular resistance of the LAD and lactate production were determined separately. With injections of 100 ,g of ACh and 20 ,g of ergonovine, chest pain occurred with ST-segment elevation in the precordial leads in the absence of epicardial coronary spasm. Coronary vascular resistance increased by 2.2- and 1.6-fold of the baseline value with ACh and ergonovine, respectively. Myocardial lactate production was noted during the ST-segment elevation. Coronary microvascular spasm was verified by the increment in coronary vascular resistance and myocardial lactate production with concomitant ST-segment elevation in the presence of normal coronary angiograms. [source] Cardioprotection of bradykinin at reperfusion involves transactivation of the epidermal growth factor receptor via matrix metalloproteinase-8ACTA PHYSIOLOGICA, Issue 4 2009C. Methner Abstract Aim:, The endogenous autacoid bradykinin (BK) reportedly reduces myocardial infarct size when given exogenously at reperfusion. Muscarinic and opioid G-protein-coupled receptors are equally protective and have been shown to couple through a matrix metalloproteinase (MMP)-dependent transactivation of the epidermal growth factor receptor (EGFR). Here we test whether BK protects the rat heart through the EGFR by an MMP-dependent pathway. Methods:, Infarct size was measured in isolated perfused rat hearts undergoing 30 min regional ischaemia followed by 120 min reperfusion. In additional studies HL-1 cardiomyocytes were loaded with tetramethylrhodamine ethyl to measure their mitochondrial membrane potential (,m). Adding the calcium ionophore calcimycin, causes ,m-collapse presumably due to calcium-induced mitochondrial permeability transition. Results:, As expected, BK (100 nmol L,1) started 5 min prior to reperfusion reduced infarct size from 38.9 ± 2.0% of the ischaemic zone in control hearts to 22.2 ± 3.3% (P < 0.001). Co-infusing the EGFR inhibitor AG1478, the broad-spectrum MMP-inhibitor GM6001, or a highly selective MMP-8 inhibitor abolished BK's protection, thus suggesting an MMP-8-dependent EGFR transactivation in the signalling. Eighty minutes of exposure to calcimycin reduced the mean cell fluorescence to 37.4 ± 1.8% of untreated cells while BK could partly preserve the fluorescence and, hence, protect the cells (50.5 ± 2.3%, P < 0.001). The BK-induced mitochondrial protection could again be blocked by AG1478, GM6001 and MMP-8 inhibitor. Finally, Western blotting revealed that BK's protection was correlated with increased phosphorylation of EGFR and its downstream target Akt. Conclusion:, These results indicate that BK at reperfusion triggers its protective signalling pathway through MMP-8-dependent transactivation of the EGFR. [source] MR imaging in assessing cardiovascular interventions and myocardial injuryCONTRAST MEDIA & MOLECULAR IMAGING, Issue 1 2007Alexis Jacquier Abstract Performing an MR-guided endovascular intervention requires (1) real-time tracking and guidance of catheters/guide wires to the target, (2) high-resolution images of the target and its surroundings in order to define the extent of the target, (3) performing a therapeutic procedure (delivery of stent or injection of gene or cells) and (4) evaluating the outcome of the therapeutic procedure. The combination of X-ray and MR imaging (XMR) in a single suite was designed for new interventional procedures. MR contrast media can be used to delineate myocardial infarcts and microvascular obstruction, thereby defining the target for local delivery of therapeutic agents under MR-guidance. Iron particles, or gadolinium- or dysprosium-chelates are mixed with the soluble injectates or stem cells in order to track intramyocardial delivery and distribution. Preliminary results show that genes encoded for vascular endothelial and fibroblast growth factor and cells are effective in promoting angiogenesis, arteriogenesis, perfusion and LV function. Angiogenic growth factors, genes and cells administered under MR-guided minimally invasive catheter-based procedures will open up new avenues in treating end-stage ischemic heart disease. The optimum dose of the therapeutic agents, delivery devices and real-time imaging techniques to guide the delivery are currently the subject of ongoing research. The aim of this review is to (1) provide an updated review of experiences using MR imaging to guide transcatheter therapy, (2) address the potential of cardiovascular magnetic resonance (MR) imaging and MR contrast media in assessing myocardial injury at a molecular level and labeling cells and (3) illustrate the applicability of the non-invasive MR imaging in the field of angiogenic therapies through recent clinical and experimental publications. Copyright © 2007 John Wiley & Sons, Ltd. [source] Cocaine- and amphetamine-regulated transcript (CART) peptide as an in vivo regulator of cardiac function in Rana ridibunda frogEXPERIMENTAL PHYSIOLOGY, Issue 6 2007Iliyana V. Ivanova The aim of this study was to investigate the effect of CART peptide on cardiac performance and on the physiological signalling pathways involved using Rana ridibunda frog heart preparations in vivo. The CART peptide, when injected into the venous sinus, significantly and reproducibly increased the force of frog heart contractions by up to 33.0 ± 6.4% during the first 15 min after its application but did not influence the chronotropic activity of the frog heart. The positive inotropic effect was entirely blocked by prazosin, pertussis toxin, Rp -adenosine 3,,5,-cyclic monophosphorothioate, autosauvagine 30 or metyrapone, as well as by extirpation of the pituitary gland, functional elimination of the inter-renal glands and long-lasting starvation, and was not observed on isolated heart preparations. Propranolol and double pithing were without significant effect on this phenomenon. It was concluded that: (i) CART peptide, administered to frogs in vivo, increases the force of heart contractions; (ii) this effect of the peptide is exerted via activation of the hypothalamic,pituitary,inter-renal gland axis through a corticoliberin-sensitive mechanism; (iii) CART augments the pumping function of the heart via a corticosteroid-dependent potentiation of myocardial ,1 -adrenoreceptors signalling; and (iv) prolonged food deprivation abolishes the positive inotropic effect of CART, suggesting the participation of endogenous CART in the physiological adaptation of the circulatory system to limitations of energy consumption. [source] Cardioprotection of cariporide evaluated by plasma myoglobin and troponin I in myocardial infarction in pigsFUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 2 2006Robert Létienne Abstract The cardioprotective effects of cariporide were investigated against myoglobin and troponin I elevation in a model of myocardial infarction in pig, and the possible relationship between these markers and myocardial infarct size. The left circumflex coronary artery was ligated for 60-min and then reperfused for 48-h. Plasma levels of myoglobin and troponin I were quantified during reperfusion. Vehicle or cariporide (2.5 mg/kg) were administered i.v. before ischaemia and infused throughout ischaemia and for the beginning of reperfusion. In vehicle-treated pigs, the infarct size represented 26% ± 3% of the area at risk. Cariporide significantly decreased the infarct size by 66% ± 9%, and significantly reduced plasma levels of myoglobin and troponin I. A strongly correlated linear relationship between myocardial necrosis and plasma levels of myoglobin (R = 0.966, P < 0.0001) or troponin I (R = 0.855, P < 0.0001) was clearly identified. In conclusion, in our porcine model of myocardial infarction, even with small infarcts (in the presence of cariporide), plasma levels of myoglobin and troponin I are predictive of the presence of necrosis and its extent. [source] Elucidation of the molecular mechanism of platelet activation: Dense granule secretion is regulated by small guanosine triphosphate-binding protein Rab27 and its effector Munc13-4GERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 4 2006Hisanori Horiuchi Cardiovascular diseases such as myocardial and cerebral infarction are common critical diseases occurring more frequently in the elderly. The trigger of the diseases is platelet activation following plaque rupture or erosion. Investigation of the molecular mechanism in platelet activation has been exclusively performed pharmacologically. We have succeeded in establishing the granule secretion and aggregation assays using permeabilized platelets. These systems enabled us to examine the molecular mechanism in platelet activation with molecular biological and biochemical methods. Using these assay systems, we have been investigating the molecular mechanism of platelet activation. With a support grant from the Novartis Foundation for Gerontological Research, we found several molecules involved in the regulation. In this report, I present the progress in the research of the granule secretion mechanism in activated platelets, which was reported in the Japanese Geriatric Society Meeting in 2005. [source] Infusion of hypertonic saline/starch during cardiopulmonary bypass reduces fluid overload and may impact cardiac functionACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2010V. L. KVALHEIM Objective: Peri-operative fluid accumulation resulting in myocardial and pulmonary tissue edema is one possible mechanism behind post-operative cardiopulmonary dysfunction. This study aimed to confirm an improvement of cardiopulmonary function by reducing fluid loading during an open-heart surgery. Materials and methods: Forty-nine elective CABG patients were randomized to an intraoperative infusion of hypertonic saline/hydroxyethyl starch (HSH group) or Ringer's solution (CT group). Both groups received 1 ml/kg/h of the study solution for 4 h after baseline values were obtained (PICCO® transpulmonary thermodilution technique). Net fluid balance (NFB), hemodynamic and laboratory parameters were measured. Results: NFB was four times higher in the CT group compared with the HSH group during the first 6 h post-operatively. The total fluid gain until the next morning was lower in the HSH group, 2993.9 (938.6) ml, compared with the CT group, 4298.7 (1059.3) ml (P<0.001). Normalized values (i.e., %-changes from the baseline) of the cardiac index and the global end diastolic volume index increased post-operatively in both groups. Both parameters were significantly higher at 6 h in the HSH group compared with CT group (P=0.002 and 0.005, respectively). Normalized values of the intrathoracic blood volume index were lower in the HSH group at 6 h post-operatively when compared with the CT group. The PaO2/FiO2 ratio decreased similarly in both groups early post-operatively, but recovery tended to be more rapid in the HSH group. Although serum-sodium and serum-chloride levels were significantly higher in the HSH group, the acid,base parameters remained similar and within the normal range. Conclusions: An intraoperative infusion of HSH during cardiac surgery contributes to reduced fluid loading and an improvement in the post-operative cardiac performance. No adverse effects of the HSH infusion were observed. [source] Remifentanil post-conditioning attenuates cardiac ischemia,reperfusion injury via , or , opioid receptor activationACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2010G. T. C. WONG Background: Ischemic pre- or post-conditioning of the heart has been shown to involve opioid receptors. Remifentanil, an ultra-short-acting selective , opioid receptor agonist in clinical use, pre-conditions the rat heart against ischemia,reperfusion injury. This study investigates whether remifentanil post-conditioning is also cardioprotective. Methods: Remifentanil post-conditioning (5-min infusion at 1, 5, 10 or 20 ,g/kg/min) or ischemic post-conditioning (three cycles of a 10 s reperfusion interspersed with a 10 s ischemia) was induced in an open-chest rat heart model of ischemia and reperfusion injury, in the presence or absence of nor-binaltorphimine, naltrindole or CTOP, specific ,, , and , opioid receptor antagonists, respectively. The same sequence of experiments was repeated in the isolated heart model using the maximal protective dose of remifentanil from the dose,response studies. Results: Both ischemic and remifentanil post-conditioning reduced the myocardial infarct size relative to the control group in both models. This cardioprotective effect for both post-conditioning regimes was prevented by the prior administration of nor-binaltorphimine and naltrindole but not CTOP. The sole administration of the antagonists had no effect on the size of myocardial infarction. Conclusions: These results indicate that remifentanil post-conditioning protects the heart from ischemia,reperfusion injury to a similar extent as of ischemic post-conditioning. This protection involves , and , but not , opioid receptor activation. This drug has great potential as a clinical post-conditioning modality as it can be given in large doses without prolonged opioid-related side effects. [source] Levosimendan cardioprotection in acutely ,-1 adrenergic receptor blocked open chest pigsACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2010C. METZSCH Background: Levosimendan and volatile anesthetics have myocardial pre-conditioning effects. ,-1 adrenergic receptor antagonists may inhibit the protective effect of volatile anesthetics. No information exists as to whether this also applies to the pre-conditioning effect of levosimendan. We therefore investigated whether levosimendan added to metoprolol would demonstrate a cardioprotective effect. Methods: Three groups of anesthetized open chest pigs underwent 30 min of myocardial ischemia and 90 min of reperfusion by temporary occlusion of the largest side branch from the circumflex artery or the left anterior descending artery. One group (CTRL) served as a control, in another group (BETA), a metoprolol-loading dose was intravenously injected 30 min before ischemia, and in a third group (BETA+L), a levosimendan infusion was added to metoprolol. Myocardial tissue concentrations of glucose, glycerol, and lactate/pyruvate ratio as the primary end-points were investigated with microdialysis in ischemic and non-ischemic tissues. Results: At the end of the ischemic period, statistically significant differences were only found between CTRL and BETA+L in the ischemic myocardium, with a lower lactate/pyruvate ratio, lower glycerol, and higher glucose concentrations in BETA+L as compared with CTRL. There were no differences in non-ischemic myocardium. From 10 to 90 min of reperfusion, no more differences were found between groups. Conclusion: The cardioprotective effect of levosimendan on ischemic metabolism with a reduction in the myocardial lactate/pyruvate ratio, less glycerol accumulation, and better preserved glucose concentration does not seem to be prevented by ,-1 adrenergic receptor antagonism with metoprolol. [source] Timing of Depolarization and Contraction in the Paced Canine Left Ventricle:JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 2003Experiment, Model Introduction: For efficient pump function, contraction of the heart should be as synchronous as possible. Ventricular pacing induces asynchrony of depolarization and contraction. The degree of asynchrony depends on the position of the pacing electrode. The aim of this study was to extend an existing numerical model of electromechanics in the left ventricle (LV) to the application of ventricular pacing. With the model, the relation between pacing site and patterns of depolarization and contraction was investigated. Methods and Results: The LV was approximated by a thick-walled ellipsoid with a realistic myofiber orientation. Propagation of the depolarization wave was described by the eikonal-diffusion equation, in which five parameters play a role: myocardial and subendocardial velocity of wave propagation along the myofiber cm and ce; myocardial and subendocardial anisotropy am and ae; and parameter k, describing the influence of wave curvature on wave velocity. Parameters cm, ae, and k were taken from literature. Parameters am and ce were estimated by fitting the model to experimental data, obtained by pacing the canine left ventricular free wall (LVFW). The best fit was found with cm= 0.75 m/s, ce= 1.3 m/s, am= 2.5, ae= 1.5, and k= 2.1 × 10,4 m2/s. With these parameter settings, for right ventricular apex (RVA) pacing, the depolarization times were realistically simulated as also shown by the wavefronts and the time needed to activate the LVFW. The moment of depolarization was used to initiate myofiber contraction in a model of LV mechanics. For both pacing situations, mid-wall circumferential strains and onset of myofiber shortening were obtained. Conclusion: With a relatively simple model setup, simulated depolarization timing patterns agreed with measurements for pacing at the LVFW and RVA in an LV. Myocardial cross-fiber wave velocity is estimated to be 0.40 times the velocity along the myofiber direction (0.75 m/s). Subendocardial wave velocity is about 1.7 times faster than in the rest of the myocardium, but about 3 times slower than as found in Purkinje fibers. Furthermore, model and experiment agreed in the following respects. (1) Ventricular pacing decreased both systolic pressure and ejection fraction relative to natural sinus rhythm. (2) In early depolarized regions, early shortening was observed in the isovolumic contraction phase; in late depolarized regions, myofibers were stretched in this phase. Maps showing timing of onset of shortening were similar to previously measured maps in which wave velocity of contraction appeared similar to that of depolarization. (J Cardiovasc Electrophysiol, Vol. 14, pp. S188-S195, October 2003, Suppl.) [source] Xanthine oxidase inhibitor allopurinol attenuates the development of diabetic cardiomyopathyJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 8b 2009Mohanraj Rajesh Abstract In this study, we investigated the effect of the xanthine oxidase (XO) inhibitor, allopurinol (ALP), on cardiac dysfunction, oxidative-nitrosative stress, apoptosis, poly(ADP-ribose) polymerase (PARP) activity and fibrosis associated with diabetic cardiomyopathy in mice. Diabetes was induced in C57/BL6 mice by injection of streptozotocin. Control and diabetic animals were treated with ALP or placebo. Left ventricular systolic and diastolic functions were measured by pressure,volume system 10 weeks after established diabetes. Myocardial XO, p22phox, p40phox, p47phox, gp91phox, iNOS, eNOS mRNA and/or protein levels, ROS and nitrotyrosine (NT) formation, caspase3/7 and PARP activity, chromatin fragmentation and various markers of fibrosis (collagen-1, TGF-,, CTGF, fibronectin) were measured using molecular biology and biochemistry methods or immunohistochemistry. Diabetes was characterized by increased myocardial, liver and serum XO activity (but not expression), increased myocardial ROS generation, p22phox, p40phox, p47phox, p91phox mRNA expression, iNOS (but not eNOS) expression, NT generation, caspase 3/7 and PARP activity/expression, chromatin fragmentation and fibrosis (enhanced accumulation of collagen, TGF-,, CTGF and fibronectin), and declined systolic and diastolic myocardial performance. ALP attenuated the diabetes-induced increased myocardial, liver and serum XO activity, myocardial ROS, NT generation, iNOS expression, apoptosis, PARP activity and fibrosis, which were accompanied by improved systolic (measured by the evaluation of both load-dependent and independent indices of myocardial contractility) and diastolic performance of the hearts of treated diabetic animals. Thus, XO inhibition with ALP improves type 1 diabetes-induced cardiac dysfunction by decreasing oxidative/nitrosative stress and fibrosis, which may have important clinical implications for the treatment and prevention of diabetic cardiomyopathy and vascular dysfunction. [source] Increased VEGFR2 expression during human late endothelial progenitor cells expansion enhances in vitro angiogenesis with up-regulation of integrin ,6JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 5 2007David M. Smadja Abstract In vitro expansion of late endothelial progenitor cells (EPCs) might yield a cell therapy product useful for myocardial and leg ischaemia, but the influence of EPC expansion on the angiogenic properties of these cells is unknown. In the present study, we investigated the effect of in vitro EPC expansion on vascular endothelial growth factor (VEGF) receptor expression. EPCs were obtained from CD34+ cord blood cells and expanded for up to 5 weeks. Real-time quantitative reverse-transcription polymerase chain reaction (RT-PCR) showed that VEGFR2 expression, contrary to VEGFR1 and VEGFR3 expression, was significantly higher on expanded EPCs than on freshly isolated CD34+ cells or on human umbilical vein endothelial cells (HUVECs). Quantitative flow cytometry confirmed that VEGFR2 density on EPCs increased during the expansion process and was significantly higher than on HUVECs. The impact of VEGFR2 increase was studied on the three theoretical steps of angiogenesis, i.e., EPC proliferation, migration and differentiation. VEGFR2 up-regulation had no effect on VEGF-induced cell proliferation, but significantly enhanced EPC migration and pseudotubes formation dependent on integrin ,6 subunit overexpression. In vitro expansion of late EPCs increases the expression of VEGFR2, the main VEGF receptor, with possible implications for EPC-based angiogenic therapy. [source] Anesthetic preconditioning in a normal and a hypertrophic porcine myocardium: the effects of sevoflurane volatile anesthetic preconditioning on myocardial infarct size in a closed-chest ischemia,reperfusion modelACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2009J. K. R. Larsen No abstract is available for this article. [source] Synthesis of (R)- and (S)-[O-methyl - 11C]N -[2-[3-(2-cyano-phenoxy)-2-hydroxy-propylamino]-ethyl]- N,-(4-methoxy-phenyl)-urea as candidate high affinity ,1 -adrenoceptor PET radioligandsJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 10 2005Stefan Wagner Abstract Molecular imaging and quantification of myocardial ,1 -adrenoceptor (AR) rather than total , -AR density is of great clinical interest since cardiac biopsy studies suggest that myocardial ,1 -AR density is reduced in patients with chronic heart failure whereas cardiac ,2 -AR density may vary. Positron emission tomography (PET), with appropriate radioligands, offers the possibility to assess , -AR density non-invasively in humans. However, no PET radioligand for the selective imaging of cardiac ,1 -ARs is clinically available. Here some derivatives of the well characterized ,1 -AR selective antagonist, ICI 89,406, namely the enantiomers of N -[2-[3-(2-cyano-phenoxy)-2-hydroxy-propylamino]-ethyl]- N,-(4-hydroxy-phenyl)-urea (5a and 5b) were synthesized and evaluated in vitro. The (R)-isomer 5a was more ,1 -selective but has lower affinity than its (S)-enantiomer 5b (,1 -AR selectivity: 6100 vs 1240; ,1 -affinity: K1 = 0.288 nM vs K1 = 0.067 nM). Etherification of the analogous desmethyl precursors, 5e and 5f, respectively, with [11C]iodomethane gave 11C-labelled versions of 5a and 5b, namely 5g and 5h, in 44 ± 5% radiochemical yield (decay-corrected) and 97.4 ± 1.3% radiochemical purity with specific radioactivities of 26.4 ± 9.4 GBq/µmol within 41.2 ± 3.4 min from the end of bombardment (n = 14). 5g and 5h are now being evaluated as candidate radioligands for myocardial ,1 -ARs. Copyright © 2005 John Wiley & Sons, Ltd. [source] Simultaneous myocardial and fat suppression in magnetic resonance myocardial delayed enhancement imaging,JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 4 2007Thomas K.F. Foo PhD Abstract Purpose To develop a method for fat suppression in myocardial delayed enhancement (MDE) studies that achieves effective signal intensity reduction in fat but does not perturb myocardial signal suppression. Materials and Methods A new approach to fat suppression that uses a spectrally-selective inversion-recovery (SPEC-IR) tip-up radio frequency (RF) pulse following the conventional nonselective IR RF pulse together with a second SPEC-IR RF pulse is proposed. The tip-up pulse restores the fat longitudinal magnetization after the nonselective IR pulse and allows the fat magnetization to recover more fully toward its equilibrium value, providing for better fat suppression by the second SPEC-IR RF pulse. This new approach was validated in phantom studies and in five patients. Results Effective fat suppression was achieved using the proposed technique with minimal impact on normal myocardial signal suppression. Mean fat suppression achieved using this approach was 67% ± 8%, as measured in the chest wall immediately opposite the heart. Conclusion The results indicate this modular-type approach optimizes fat suppression in myocardial delayed enhancement studies but does not perturb the basic IR pulse sequence or change basic acquisition parameters. J. Magn. Reson. Imaging 2007;26:927,933. © 2007 Wiley-Liss, Inc. [source] Magnetic resonance imaging of acute myocardial infarction in dextrocardia with situs solitus (dextroversion)JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 5 2005JC Salanitri Summary The case report of an 88-year-old woman with dextroversion and acute anterior wall myocardial infarction is presented. The patient, who had been diagnosed with dextrocardia 3 years prior to this admission, presented with right-sided chest pain. Coronary angiography demonstrated an 80% proximal left anterior descending artery stenosis which was successfully stented. A cardiac MRI was performed to exclude a left atrial thrombus after an inconclusive echocardiogram. The MRI demonstrated findings consistent with dextroversion, with delayed contrast-enhanced viability sequences confirming a near transmural anterior wall myocardial infarct. To our knowledge, this is the first report illustrating the cardiac MRI findings in such a case. [source] FR183998, a Na+/H+ exchange inhibitor, suppresses both IL-8 content and myocardial infarct size in a cardiac ischaemia-reperfusion model in ratsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 2 2002F. Ohara The aim of this study was to determine the effect of FR183998 (5-(2,5-dichlorothiophen-3-yl)-3-[(2-dimethylaminoethyl)carbamoyl]benzoylguanidine dihydrochloride), an Na+/H+ exchange inhibitor, on myocardial interleukin-8 (IL-8) content and myocardial infarct size in a rat ischaemia and reperfusion model. Rats underwent30 min of ischaemia followed by 1 to 24 h of reperfusion. IL-8 content rapidly increased in reperfused rat hearts. The maximum increase in IL-8 was obtained after 3 h of reperfusion. Intravenous administration of FR183998 at 1 and 3.2 mg kg,1, 5 min before ischaemia, significantly reduced the IL-8 level after 3 h of reperfusion (122 ± 16 and 149 ± 23 pg mg,1 protein, respectively), compared with that of the saline-treated group (258 ± 27 pg mg,1 protein). Myeloperoxidase activity after 3 h of reperfusion was also reduced by FR183998 (from 0.83 ± 0.19 unit g,1 weight of tissue in the saline-treated group to 0.36 ± 0.09 and 0.33 ± 0.06 unit g,1 weight of tissue in FR183998-treated groups at 1.0 and 3.2 mg kg,1, respectively). Myocardial infarction induced by 30 min of ischaemia and 24 h of reperfusion was significantly suppressed by the same doses of FR183998 (14.0 ± 1.5,13.5 ± 1.9% at 1.0 and 3.2 mg kg,1), compared with 22.2 ± 2.7% in the saline-treated group. These results suggest that IL-8 may contribute to the generation of myocardial infarction in an ischaemia and reperfusion model in rats. [source] Ischaemic heart disease in the dog: a review of 65 casesJOURNAL OF SMALL ANIMAL PRACTICE, Issue 3 2000T. Falk Sixty-five dogs are reviewed with histopathologically confirmed intramural arteriosclerosis. Clinical data (clinical signs, electrocardiographic findings and ultrasound parameters) on these animals were collected from nine small animal clinics in Sweden: 16 dogs had died suddenly, with few or no previous clinical signs; 13 dogs died or were euthanased during or shortly after general anaesthesia or sedation; 30 dogs developed acute (14) or chronic (16) congestive heart failure; and six dogs died or were euthanased for causes unrelated to cardiac disease. Electrocardiography of 23 of the dogs revealed several types of arrhythmias, with atrial fibrillation and sinus tachycardia being most commonly detected. Ultrasonographic examinations of 24 dogs found a relatively high number (19) with decreased indices of contractility. Dogs that had died suddenly and in relation to general anaesthesia or sedation had a higher incidence (25 of 29) of purely arteriosclerotic changes in the myocardial vessels, whereas just over half the dogs with congestive heart failure (16 of 30) had other concomitant heart lesions (in most cases endocardiosis). The incidence of myocardial infarcts was high (51 of 65 cases). It is postulated that arteriosclerosis in the dog may be an important reason for sudden death and death during general anaesthesia. Coronary arterial disease should also be a consideration in the clinical evaluation of dilated cardiomyopathy and may contribute to the decreased myocardial contractility when it is present in dogs with mitral regurgitation. [source] The use of vasopressin for treating vasodilatory shock and cardiopulmonary arrestJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 2 2009DACVIM, Richard D. Scroggin Jr. Abstract Objective , To discuss 3 potential mechanisms for loss of peripheral vasomotor tone during vasodilatory shock; review vasopressin physiology; review the available animal experimental and human clinical studies of vasopressin in vasodilatory shock and cardiopulmonary arrest; and make recommendations based on review of the data for the use of vasopressin in vasodilatory shock and cardiopulmonary arrest. Data Sources , Human clinical studies, veterinary experimental studies, forum proceedings, book chapters, and American Heart Association guidelines. Human and Veterinary Data Synthesis , Septic shock is the most common form of vasodilatory shock. The exogenous administration of vasopressin in animal models of fluid-resuscitated septic and hemorrhagic shock significantly increases mean arterial pressure and improves survival. The effect of vasopressin on return to spontaneous circulation, initial cardiac rhythm, and survival compared with epinephrine is mixed. Improved survival in human patients with ventricular fibrillation, pulseless ventricular tachycardia, and nonspecific cardiopulmonary arrest has been observed in 4 small studies of vasopressin versus epinephrine. Three large studies, though, did not find a significant difference between vasopressin and epinephrine in patients with cardiopulmonary arrest regardless of initial cardiac rhythm. No veterinary clinical trials have been performed using vasopressin in cardiopulmonary arrest. Conclusion , Vasopressin (0.01,0.04 U/min, IV) should be considered in small animal veterinary patients with vasodilatory shock that is unresponsive to fluid resuscitation and catecholamine (dobutamine, dopamine, and norepinephrine) administration. Vasopressin (0.2,0.8 U/kg, IV once) administration during cardiopulmonary resuscitation in small animal veterinary patients with pulseless electrical activity or ventricular asystole may be beneficial for myocardial and cerebral blood flow. [source] Quantitative Assessment of Regional Right Ventricular Myocardial Velocities in Awake Dogs by Doppler Tissue Imaging: Repeatability, Reproducibility, Effect of Body Weight and Breed, and Comparison with Left Ventricular Myocardial VelocitiesJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 6 2005Valérie Chetboul Right ventricular myocardial (RVM) motion is poorly documented. The objective of this study was to determine the variability of RVM velocities by tissue Doppler imaging (TDI) in healthy dogs (study 1), to analyze RVM motion in a large healthy canine population (study 2), and to compare the results with those obtained for the left ventricular free wall. Six healthy Beagle Dogs were monitored in study 1, and 64 healthy dogs of 14 different breeds were monitored in study 2. Velocities were recorded in 2 segments (basal and apical) of the right and left myocardial walls. In study 1, 36 TDI examinations were performed for 4 days, whereas a single TDI examination was performed on each dog in study 2. All velocity profiles included 1 positive systolic wave and 2 negative diastolic waves. The lowest intraday and interday coefficient of variation values of the right TDI variables were observed at the base (3.5,16.1%). The variability of the right apical velocities was much higher, with most coefficient of variation values >15%. RVM velocities were higher in the basal than in the apical segments (P < .001) and were higher than the left velocities of the corresponding segment (P < .01). Body weight and breed had an effect on only a few right and left TDI variables. TDI provides a repeatable and reproducible method for evaluating basal RV function in the dog. These data also demonstrate the heterogeneity of the myocardial velocities between the left and the right ventricles and between the base and the apex. [source] Fat-water separated delayed hyperenhanced myocardial infarct imagingMAGNETIC RESONANCE IN MEDICINE, Issue 3 2008James W. Goldfarb Abstract Fat deposition associated with myocardial infarction (MI) has been reported as a commonly occurring phenomenon. Magnetic resonance imaging (MRI) has the ability to efficiently detect MI using T1 -sensitive contrast-enhanced sequences and fat via its resonant frequency shift. In this work, the feasibility of fat-water separation applied to the conventional delayed hyperenhanced (DHE) MI imaging technique is demonstrated. A three-point Dixon acquisition and reconstruction was combined with an inversion recovery gradient-echo pulse sequence. This allowed fat-water separation along with T1 sensitive imaging after injection of a gadolinium contrast agent. The technique is demonstrated in phantom experiments and three subjects with chronic MI. Areas of infarction were well defined as conventional hyperenhancement in water images. In two cases, fatty deposition was detected in fat images and confirmed by precontrast opposed-phase imaging. Magn Reson Med 60:503,509, 2008. © 2008 Wiley-Liss, Inc. [source] T1 -weighted magnetic resonance imaging shows fatty deposition after myocardial infarctionMAGNETIC RESONANCE IN MEDICINE, Issue 5 2007James W. Goldfarb Abstract Pathologic studies have shown an increased lipid content in areas of myocardial infarction (MI). We sought to show the ability of precontrast T1 -weighted MRI to noninvasively detect fat deposition in MI and show its association with infarct age. Thirty-two patients with MI were studied. Precontrast inversion-recovery (IR) cine steady-state free precession (SSFP) imaging was used to generate both fat- and muscle-nulled images to locate areas of fat deposition in the left ventricular (LV) myocardium. Postcontrast delayed hyperenhanced (DHE) imaging was also performed. Image contrast in regions of MI on precontrast images and postcontrast DHE images was measured. The association of image contrast with infarct age was determined by means of correlations and Student's t -test. We found a significant association between infarct age and image contrast in both fat- and muscle-nulled images. Precontrast T1 -weighted MRI is a promising method for detecting myocardial fat deposition in chronic MI, and can be used to assess myocardial infarct age. Magn Reson Med 57:828,834, 2007. © 2007 Wiley-Liss, Inc. [source] Two-component diffusion tensor MRI of isolated perfused heartsMAGNETIC RESONANCE IN MEDICINE, Issue 6 2001Edward W. Hsu Abstract Nonmonoexponential MR diffusion decay behavior has been observed at high diffusion-weighting strengths for cell aggregates and tissues, including the myocardium; however, implications for myocardial MR diffusion tensor imaging are largely unknown. In this study, a slow-exchange-limit, two-component diffusion tensor model was fitted to diffusion-weighted images obtained in isolated, perfused rat hearts. Results indicate that there are at least two distinct components of anisotropic diffusion, characterized by a "fast" component whose principal diffusivity is comparable to that of the perfusate, and a highly anisotropic "slow" component. It is speculated that the two components correspond to tissue compartments and have a general agreement with the orientations of anisotropy, or fiber orientations, in the myocardium. Moreover, consideration of previous studies of myocardial diffusion suggests that the presently observed fast component may likely be dominated by diffusion in the vascular space, whereas the slow component may include the intracellular and interstitial compartments. The implications of the results for myocardial fiber orientation mapping and limitations of the current two-component model used are also discussed. Magn Reson Med 45:1039,1045, 2001. © 2001 Wiley-Liss, Inc. [source] The Cardio-Protective Properties of Ncx-6550, a Nitric Oxide Donating Pravastatin, in the MouseMICROCIRCULATION, Issue 6 2010CLARA DI FILIPPO Please cite this paper as: Di Filippo, Monopoli, Ongini, Perretti and D'Amico (2010). The Cardio-Protective Properties of Ncx-6550, a Nitric Oxide Donating Pravastatin, in the Mouse. Microcirculation17(6), 417,426. Abstract Objective:, Determine the cardio-protective properties of a nitric oxide-releasing pravastatin (Ncx-6550), in comparison to pravastatin. Methods:, A mouse model of myocardial infarct was used assessing tissue damage both at 2 and 24 hour post-reperfusion, administering compounds both prophylactically and therapeutically. Results:, Ncx-6550 induced a significant dose-dependent (2.24,22.4 ,mol/kg i.p.) cardioprotection in the two hour reperfusion protocol. In vehicle-treated mice, infarct size (expressed as fraction of area at risk; IS/AR) was 41.2 ± 1%, and it was reduced to 22.2 ± 0.9% and 32.6 ± 0.9% following 22.4 and 6.72 ,mol/kg Ncx-6550 (p < 0.05). 22.4 ,mol/kg Ncx-6550 also increased cardiac levels of the enzyme heme oxygenase-1. Treatment of mice with pravastatin induced significant reduction of myocardial injury only at 22.4 ,mol/kg (IS/AR value: 33.7 ± 0.9%). In a 24 hour reperfusion protocol, Ncx-6550 and pravastatin were tested only at 22.4 ,mol/kg i.p. being given either one hour prior to ischemia (prophylactic protocol) or one hour into reperfusion (therapeutic protocol). With either treatment scheme, Ncx-6550 produced higher cardioprotection compared to pravastatin, as reflected also by a reduction in the incidence of lethality as well as in circulating troponin I and interleukin-1, levels. Conclusions:, These results indicate Ncx-6550 as a novel therapeutic agent with a potential for the treatment of myocardial infarct. [source] Coronary and systemic hemodynamic effects of clevidipine, an ultra-short-acting calcium antagonist, for treatment of hypertension after coronary artery surgeryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2000N. Kieler-Jensen Background: The aim was to evaluate the use of clevidipine, a new vascular selective, ultra-short-acting calcium antagonist for blood pressure control after coronary artery bypass grafting (CABG). Methods: The effects of clevidipine on central hemodynamics, myocardial blood flow and metabolism were studied at two different phases after CABG. In phase 1 (n=13), the hypertensive phase, the effects of clevidipine were compared to those of sodium nitroprusside (SNP) when used to control postoperative hypertension. In phase 2 (n=9), the normotensive phase, a clevidipine dose-response relationship was established. Results: At a target mean arterial pressure (MAP) of 75 mmHg, systemic vascular resistance (SVR) and heart rate (HR) were lower, preload, stroke volume (SV) and pulmonary vascular resistance (PVR) were higher, while there were no differences in myocardial lactate metabolism or oxygen extraction with clevidipine compared to SNP. In the normotensive phase, clevidipine induced a dose-dependent decrease in MAP (,19%), SVR (,27%) and PVR (,15%), accompanied by an increase in SV (10%), but no reflex increase in HR or changes in cardiac preload. Clevidipine caused a direct coronary vasodilation, as indicated by a decrease in myocardial oxygen extraction from 54% to 45%. Myocardial lactate metabolism was unaffected by clevidipine. The blood clearance of clevidipine was 0.05 l ,· ,min,1 ,· ,kg,1, the volume of distribution at steady state was 0.08 l ,· ,kg,1 and the initial and terminal half-lives were <1 min and 4 min, respectively. Conclusions: Clevidipine rapidly reduced MAP and induced a systemic, pulmonary and coronary vasodilation with no effect on venous capacitance vessels or HR. Clevidipine caused no adverse effects on myocardial lactate metabolism. Clevidipine thus appears suitable to control blood pressure after CABG. [source] Side-to-side linking of myocardial cells in hypertrophic cardiomyopathy: Whole heart microscopic observation with tangential sectionsPATHOLOGY INTERNATIONAL, Issue 11 2005Hirotake Masuda By cross-section or longitudinal section, it is difficult to investigate longitudinal features of myocardial cells in the whole heart. Here, introducing the use of tangential sections to obtain longitudinal aspect of myocardial cells in any part of myocardium, the authors evaluated myocardium in the left ventricle in 10 normal hearts and four hearts with hypertrophic cardiomyopathy (HCM). Tangential sections were obtained by peeling the superficial layer of myocardium. After peeling the whole surface, secondary deep layer was peeled. These procedures were repeated more than five times through the wall. Intercalated discs (ICD) were observed immunohistochemically with anti-N-cadherin and antidesmoplakin. In normal hearts, myocardial cells were cut longitudinally and ran parallel in tangential sections. They linked end-to-end with simple and regular ICD with average lengths of 120,130 µm and average sarcomere numbers of 56,65. In HCM hearts, many myocardial cells were cut almost longitudinally running approximately parallel in tangential sections. Myocardial cells frequently showed side-to-side linking characterized by skewed ICD, indistinct ICD counterparts, and longitudinally arranged ICD. Two young HCM hearts had circle-shaped ICD and vacuole-like structures highlighted by immunostaining for N-cadherin, which were actually extracellular structures comparable with irregular side-to-side linking. It is considered that side-to-side linking of myocardial cells is a characteristic microscopic feature in HCM rather than myocardial disarray. [source] | ||||||||||||||||||||||||||||||||||