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Myocardial Function (myocardial + function)
Selected AbstractsTCAs and Myocardial FunctionACADEMIC EMERGENCY MEDICINE, Issue 7 2002Marc Bornstein DO No abstract is available for this article. [source] Cocaine and Ethanol: Combined Effects on Coronary Artery Blood Flow and Myocardial Function in DogsACADEMIC EMERGENCY MEDICINE, Issue 7 2009Lance D. Wilson MD Abstract Objectives:, In combination, cocaine and ethanol are more cardiotoxic than is either substance alone. These substances together constitute a drug abuse combination that commonly results in fatality. Previously the authors have demonstrated that cardiotoxicity of cocaine and ethanol is in part due to synergistic myocardial-depressant effects. However, it remains unclear whether this myocardial depression is associated with concomitant adverse effects on coronary blood flow in relation to these substances. The aim of this study was to investigate combined effects of cocaine and ethanol on myocardial blood flow, in relation to indices of myocardial function. Methods:, Anesthetized dogs were instrumented for hemodynamic monitoring with Doppler flow probes placed on the circumflex and left anterior descending (LAD) coronary arteries. Dogs were randomized to three groups (each n = 6): ethanol (E, 1.5 g/kg followed by placebo), cocaine (C, placebo followed by cocaine, 7.5 mg/kg IV), or cocaine plus ethanol (C + E). All measurements were made at control, after placebo or ethanol, and then at fixed time intervals after cocaine or placebo bolus over 3 hours. Results:, In both the C + E and the C groups, circumflex blood flow (CBF) decreased by 71% (95% confidence interval [CI] = 56% to 85%) and 57% (95% CI = 43% to 72%, both p < 0.04 vs. baseline) immediately after cocaine bolus. This was associated with transient depression of cardiac output, myocardial contractile function, and rate-pressure product (RPP), all indices of myocardial oxygen demand. A subsequent rebound increase of coronary sinus blood flow (CSBF) of 56% (95% CI = 26% to 137%, p < 0.03) compared to baseline occurred only in the C group and was associated with increases of myocardial contractile function and RPP. In the C + E group, 2 hours after drug administration, there was a decrease in CSBF of 49% (95% CI = 32% to 67%; p < 0.01) compared to baseline, which was associated with concomitant numerical decreases of the indices of myocardial oxygen demand and accumulation of cocaethylene. Conclusions:, Acute decreases in myocardial flow secondary to cocaine, and cocaine and ethanol in combination, were similar and temporally associated with cocaine's direct myocardial-depressant effects. Rebound increases in myocardial function and blood flow due to cocaine were attenuated by ethanol. Delayed myocardial depression and decreases in myocardial blood flow were observed only with coadministration of cocaine and ethanol. [source] Polyurethane Scaffolds Seeded With Genetically Engineered Skeletal Myoblasts: A Promising Tool to Regenerate Myocardial FunctionARTIFICIAL ORGANS, Issue 2 2010Britta Blumenthal Abstract In animal models, intramyocardial injection of primary skeletal myoblasts is supposed to promote tissue regeneration and to improve cardiac function after myocardial infarction. The usage of genetically engineered myoblasts overexpressing the paracrine factors involved in tissue repair is believed to enhance these effects. However, cell therapy via injection is always accompanied by a high death rate of the injected cells. Here, we describe the construction of a growth factor-producing myoblast-seeded scaffold to overcome this limitation. Skeletal myoblasts were isolated and expanded from newborn Lewis rats. Cells were seeded on polyurethane (PU) scaffolds (Artelon) and transfected with DNA of VEGF-A, HGF, SDF-1, or Akt1 using the lipid-based Metafectene Pro method. Overexpression was verified by ELISA, RT-PCR (VEGF-A, HGF, and SDF-1) and Western blot analysis (Akt1). The seeded scaffolds were transplanted onto damaged myocardium of Lewis rats 2 weeks after myocardial infarction. Six weeks later, their therapeutic potential in vivo was analyzed by measurement of infarction size and capillary density. Primary rat skeletal myoblasts seeded on PU scaffolds were efficiently transfected, achieving transfection rates of 20%. In vitro, we noted a significant increase in expression of VEGF-A, HGF, SDF-1, and Akt1 after transfection. In vivo, transplantation of growth factor-producing myoblast-seeded scaffolds resulted in enhanced angiogenesis (VEGF-A, HGF, and Akt1) or a reduced infarction zone (SDF-1 and Akt1) in the ischemically damaged myocardium. In summary, we constructed a growth factor-producing myoblast-seeded scaffold which combines the beneficial potential of stem cell transplantation with the promising effects of gene-therapeutic approaches. Because this matrix also allows us to circumvent previous cell application drawbacks, it may represent a promising tool for tissue regeneration and the re-establishment of cardiac function after myocardial infarction. [source] Reply to Statin Therapy Decreases Myocardial Function as Evaluated via Strain ImagingCLINICAL CARDIOLOGY, Issue 3 2010Jack Rubinstein MD No abstract is available for this article. [source] Effect of Chronic Sustained-Release Dipyridamole on Myocardial Blood Flow and Left Ventricular Function in Patients With Ischemic CardiomyopathyCONGESTIVE HEART FAILURE, Issue 3 2007Mateen Akhtar MD Dipyridamole increases adenosine levels and augments coronary collateralization in patients with coronary ischemia. This pilot study tested whether a 6-month course of sustained-release dipyridamole/aspirin improves coronary flow reserve and left ventricular systolic function in patients with ischemic cardiomyopathy. Six outpatients with coronary artery disease and left ventricular ejection fraction (LVEF) <40% were treated with sustained-release dipyridamole 200 mg/aspirin 25 mg twice daily for 6 months. Myocardial function and perfusion, including coronary sinus flow at rest and during intravenous dipyridamole-induced hyperemia, were measured using velocity-encoded cine magnetic resonance stress perfusion studies at baseline, 3 months, and 6 months. There was no change in heart failure or angina class at 6 months. LVEF increased by 39%±64% (31.0%±13.3% at baseline vs 38.3%±10.7% at 6 months; P=.01), hyperemic coronary sinus flow increased more than 2-fold (219.6±121.3 mL/min vs 509.4±349.3 mL/min; P=.01), and stress-induced relative myocardial perfusion increased by 35%±13% (9.4%±3.4% vs 13.9%±8.5%; P=.004). Sustained-release dipyridamole improved hyperemic myocardial blood flow and left ventricular systolic function in patients with ischemic cardiomyopathy. [source] Myocardial perfusion defects in Bartter and Gitelman syndromesEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2008R. Scognamiglio ABSTRACT Background, Normotensive hypokalaemic tubulopathies (Bartter and Gitelman syndromes (BS/GS)) are genetic diseases that are considered benign. However, QT prolongation, left ventricular dysfunction and reduction of cardiac index upon exercise leading to arrhythmias and sudden cardiac death have been reported in these patients. Hence, we aimed to verifying whether an isometric exercise could represent a useful tool for the identification of patients at risk for future cardiac events. Patients and methods, Myocardial function (MF) and perfusion, evaluated as myocardial blood flow (MBF) of 10 BS/GS patients and 10 healthy controls, were investigated at rest and during isometric exercise. MF and MBF were evaluated using quantitative two-dimensional and myocardial contrast echocardiography. Results, BS/GS patients had normal baseline MF and MBF. During exercise in BS/GS patients, corrected QT (QTc) was prolonged to peak value of 494 ± 9·1 ms (P < 0·001). In controls, MF increased from resting to peak exercise (left ventricular ejection fraction: 65 ± 4% to 78 ± 5%, P < 0·003) while in seven BS/GS patients (Group 1) it declined (64 ± 5% to 43 ± 9%, P < 0·001). Myocardial perfusion increased upon exercise in controls as shown by changes of its markers: , (a measure of myocardial flow velocity; 0·89 ± 0·12 vs. 0·99 ± 0·12, P < 0·001) and myocardial blood volume (14·4 ± 2 vs. 20·2 ± 0·25, P < 0·001), while in Group 1 BS/GS it decreased (0·87 ± 0·15 vs. 0·67 ± 0·15, P < 0·001; and 14·5 ± 1·9 vs. 8·3 ± 0·22, P < 0·001, respectively). Conclusions, Our results document for the first time that exercise induce coronary microvascular and myocardial defects in BS/GS patients. Therefore, this may challenge the idea that BS/GS are benign diseases. In addition, the diagnostic approach to these syndromes should include an in-depth cardiac assessment in order to identify patients at higher risk. [source] Effects of intra-abdominal CO2 -insufflation on normal and impaired myocardial function: an experimental studyACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2003C. A. Greim Background:, Intra-abdominal pressure (IAP) elevation during CO2 -pneumoperitoneum increases cardiac afterload and may enhance dysfunction of the already compromized heart. This study focused on the effects of acute IAP increases on left and right ventricular loadings and contractility in the heart with impaired global function. Methods:, Impairment of myocardial function (IMF) was pharmacologically induced in 16 pigs by administration of halothane and propranolol, while baseline arterial pressure was maintained by intravenous phenylephrine. Intra-abdominal pressure was gradually increased by 10 mmHg up to 30 mmHg in the supine position (IMF group 1, n = 8) or in a head-down tilted position (IMF group 2, n = 8). In two control groups with normal myocardial function, IAP was also increased in the supine position or the head-down tilted position. Cardiac function in all groups was assessed by epicardial echocardiography, intraventricular pressure measurements and pulmonary artery catheterization. Results:, The increase in IAP was accompanied by a transient rise in LV end-systolic wall stress and reduced cardiac output significantly by 16,24% in all groups. In the IMF groups, LV end-diastolic transmural pressure increased by 34,60% to peak values of 24 mmHg, while cross-sectional LV end-diastolic areas remained unchanged. Increases in right ventricular end-diastolic volume and decreases in right ventricular ejection fraction as well as in cardiac output were most pronounced at IAP 20 mmHg and significantly stronger in both IMF groups than in the control groups (P < 0.001). Conclusion:, Following the acute elevation of IAP, the right ventricular volume load shifted more extensively in the IMF groups than in the animals with normal myocardial function. Myocardial function in the impaired heart may worsen during IAP elevation due to right ventricular load alterations rather than a LV afterload increase. [source] Myocardial Perfusion As Assessed by Positron Emission Tomography During Long-Term Mechanical Circulatory SupportCONGESTIVE HEART FAILURE, Issue 2 2006George V. Letsou MD Although mechanical circulatory support (MCS) can improve myocardial function in patients with advanced heart failure, its effects on relative myocardial perfusion are unclear. Using positron emission tomographic imaging techniques, the authors assessed relative myocardial perfusion in patients with ischemic or idiopathic cardiomyopathy who were receiving chronic MCS with a left ventricular assist device (pulsatile HeartMate [n=2] [Thoratec Corporation, Pleasanton, CA] or nonpulsatile Jarvik 2000 [n=4] [Jarvik Heart, Inc., New York, NY]). Relative myocardial perfusion was compared at lower and higher levels of MCS (50 vs. 100,110 ejections/min for the HeartMate and 8000 vs. 12,000 rpm for the Jarvik 2000). The size and severity of perfusion defects at rest and after dipyridamole stress were measured objectively and subjectively by computer algorithms and visual inspection, respectively. Relative myocardial perfusion increased >5% from baseline in only one of six patients when MCS was increased. No change in relative myocardial perfusion of >5% was seen in any of the other five patients, even after subsequent dipyridamole stress positron emission tomographic imaging. These pilot study findings suggest that the decreased metabolic requirements induced by ventricular unloading correspondingly decreased blood flow requirements to physiologically inactive myocardium. [source] Mechanical Bridging to Improvement in Severe Acute ,Nonischemic, Nonmyocarditis' Heart FailureCONGESTIVE HEART FAILURE, Issue 2 2004O.H. Frazier MD Improved myocardial function has been observed in patients with acute myocarditis who have had short-term support with a ventricular assist system. Additionally, a limited number of patients with nonischemic cardiomyopathy have undergone successful device explantation after their myocardial function improved during ventricular assist system support. The authors present their experience with four patients who had acute, severe heart failure without coronary artery disease or biopsy-proven myocarditis. After receiving prolonged ventricular assist system support, all four patients had significantly improved left ventricular function, returning to New York Heart Association functional class I without inotropic therapy. In each case, dobutamine stress echocardiography and invasive hemodynamic tests were performed to confirm improvement of cardiac function before device explantation was undertaken. In all four cases, device explantation was followed by early successful maintenance of left ventricular function. These cases reveal a unique clinical syndrome that may be successfully treated with early institution of ventricular assist system support followed by explantation after myocardial recovery. [source] Role of ß Blockers in Congestive Heart FailureCONGESTIVE HEART FAILURE, Issue 6 2000MPhil, Nazim Uddin Azam Khan MD Prolonged activation of the adrenergic nervous system has adverse consequences on the cardiovascular system in patients with congestive heart failure. , adrenergic receptor,blocker therapy modifies these deleterious effects. , blockers have been shown to improve myocardial function and survival when used in conjunction with conventional treatment with diuretics, angiotensinconverting enzyme inhibitors, and digoxin. , blocker therapy in mild-to-moderate heart failure should not be delayed because it causes some reversal of both neurohormonal compensatory mechanisms and the deletorious myocardial remodeling process. This paper reviews the beneficial effects of , adrenergic receptor-blocker therapy on the pathophysiology, symptoms, left ventricular function, morbidity, and mortality in patients with congestive heart failure. [source] Comparative Overview of Cardiac Output Measurement Methods: Has Impedance Cardiography Come of Age?CONGESTIVE HEART FAILURE, Issue 2 2000Anthony N. De Maria MD Cardiac output, usually expressed as liters of blood ejected by the left ventricle per minute, is a fundamental measure of the adequacy of myocardial function to meet the perfusion needs of tissue at any time. Decreases in cardiac output over time (when cardiac output is measured under similar conditions) may signal myocardial functional deterioration and the onset or progression of heart failure. Conversely, improvements in cardiac output may indicate a positive response to medical therapy. However, most methods for evaluating cardiac output are technically demanding, require specialized training and specialized environments for measurement, and are costly. Therefore, most measurement techniques are impractical for routine evaluation of disease progression and/or response to treatment in the prevention and/or management of heart failure. This paper provides a comparative overview of commonly employed cardiac output measurement strategies with emphasis on developments in impedance cardiography which suggest that impedance cardiography has the potential to make routine assessment and trending of cardiac output a viable alternative to assist in the management of both chronically and acutely ill patients, including those with heart failure. [source] Clinical Value of the Tissue Doppler S Wave to Characterize Left Ventricular Hypertrophy as Defined by EchocardiographyECHOCARDIOGRAPHY, Issue 4 2010Demian Chejtman M.D. Left ventricular hypertrophy (LVH) may be a physiological finding and may also be associated with different disease entities and hence, with different outcomes. Regional myocardial function can be assessed with color Doppler tissue imaging, specifically by the waveform of the isovolumic contraction (IC) period and the regional systolic wave ("s"). Methods and Results: We studied five groups (G): healthy, sedentary young volunteers (G1, n:10); healthy sedentary adult volunteers (G2, n:8); and subjects with LVH (left ventricular mass index >125 g/m2) including: high performance athletes (G3, n:21), subjects with hypertension (G4, n:21), subjects with hypertrophic cardiomyopathy (HCM) (G5, n:18). We measured peak "s" wave velocity (cm/sec) at the basal and mid septum, the IC/s ratio, and basal to mid-septal velocity difference (BMVD) of the "s" wave. Regional "s" wave values (cm/sec) were G1 = 5.6 ± 1; G2 = 5.4 ± 0.8; G3 = 5.7 ± 0.6; G4 = 5.3 ± 1.1; G5 = 4.2 ± 1.1 (P < 0.0001). The IC/s ratio was G1 = 0.28 ± 0.18; G2 = 0.39 ± 0.21; G3 = 0.23 ± 0.10; G4 = 0.42 ± 0.15; G5 = 0.64 ± 0.15 (P < 0.0001). The BMVD (cm/sec) was G1 = 2 ± 0.51; G2 = 1.71 ± 0.29; G3 = 1.78 ± 0.44; G4 = 1.26 ± 0.96; G5 = 0.45 ± 0.4 (P < 0.0001). IC/s < 0.38 discriminated physiological from pathological forms of hypertrophy (sensitivity 90%; specificity 88%). Peak "s" wave velocity discriminated HCM from other causes of hypertrophy, with a cutoff value of 4.46 cm/sec (sensitivity 72%; specificity 90%). BMVD <0.98 cm/sec detected HCM with 89% sensitivity and 86% specificity. Conclusions: Peak "s" wave velocity and two indices: IC/s and BMDV are novel parameters that may allow to discriminate physiological from pathological forms of hypertrophy as well as different subtypes of hypertrophy. (ECHOCARDIOGRAPHY 2010;27:370-377) [source] Two-dimensional, Non-Doppler Strain Imaging during Anesthesia and Cardiac SurgeryECHOCARDIOGRAPHY, Issue 3 2009F.A.S.E., Nikolaos J. Skubas M.D. Transesophageal echochardiography (TEE) has become an essential intraoperative monitor during general anesthesia for cardiac surgical procedures. In clinical practice, ventricular function is visually evaluated using gray scale and Doppler modes, despite the fact that subjective interpretation is influenced by level of experience and training. Echocardiographic strain imaging measures cardiac deformation and provides objective quantification of regional myocardial function. Non-Doppler strain, which is derived by tracking speckles from two-dimensional (2D) images, bypasses the limitations of Doppler-based strain measurements and evaluates the complex myocardial deformation along three dimensions. As a result, longitudinal shortening, circumferential thinning and radial thickening can be quantified using standard midesophageal and transgastric views, being acquired during a comprehensive TEE examination. Once non-Doppler strain becomes available on "real time," it will have the potential to become a valuable tool for detection of ischemia on the regional level and objective quantification of global ventricular function. [source] Viable Myocardium: How Much Is Enough?ECHOCARDIOGRAPHY, Issue 1 2005A Comparison of Viability by Comparative Imaging Techniques to Assess the Quantity, Functionality of Ischemic Myocardium Left ventricular systolic dysfunction is mainly a result of coronary artery disease (CAD). Decrease in myocardial contractility results as a response to a chronic hypoperfusion state that produces a change in cardiac myocyte metabolism, resulting in a perfusion-contraction mismatch in which function is sacrificed for survival. If revascularization is performed in a timely fashion, metabolism can be restored leading to recovery of function. Through the use of noninvasive imaging modalities, assessing myocardial viability can be easily performed and will aid in selecting those patients who will benefit from revascularization. Viable myocardium can be identified by nuclear modalities that have a high sensitivity but a lower specificity, such as thallium-201 single photon emission computed tomography and positron emission tomography (PET); or by the use of dobutamine stress echocardiogram (DSE), which has a decreased sensitivity but a better specificity. A modality that is increasingly being used with an overall good sensitivity and specificity is contrast-enhanced magnetic resonance imaging. The purpose of this review is to explore the amount of myocardial viability that is relevant to pursue revascularization, since as myocardial function improves there is a decrease in morbidity and mortality from heart failure and arrhythmias. [source] Cardiac and coronary function in the Langendorff-perfused mouse heart modelEXPERIMENTAL PHYSIOLOGY, Issue 1 2009Melissa E. Reichelt The Langendorff mouse heart model is widely employed in studies of myocardial function and responses to injury (e.g. ischaemia). Nonetheless, marked variability exists in its preparation and functional properties. We examined the impact of early growth (8, 16, 20 and 24 weeks), sex, perfusion fluid [Ca2+] and pacing rate on contractile function and responses to 20 min ischaemia followed by 45 min reperfusion. We also assessed the impact of strain, and tested the utility of the model in studying coronary function. Under normoxic conditions, hearts from 8-week-old male C57BL/6 mice (2 mm free perfusate [Ca2+], 420 beats min,1) exhibited 145 ± 2 mmHg left ventricular developed pressure (LVDP). Force development declined by ,15% (126 ± 5 mmHg) with a reduction in free [Ca2+] to 1.35 mm, and by 25% (108 ± 3 mmHg) with increased pacing to 600 beats min,1. While elevated heart rate failed to modify ischaemic outcome, the lower [Ca2+] significantly improved contractile recovery (by >30%). We detected minimal sex-dependent differences in normoxic function between 8 and 24 weeks, although age modified contractile function in males (increased LVDP at 24 versus 8 weeks) but not females. Both male and female hearts exhibited age-related reductions in ischaemic tolerance, with a significant decline in recovery evident at 16 weeks in males and later, at 20,24 weeks, in females (versus recoveries in hearts at 8 weeks). Strain also modified tolerance to ischaemia, with similar responses in hearts from C57BL/6, 129/sv, Quackenbush Swiss and FVBN mice, but substantially greater tolerance in BALB/c hearts. In terms of vascular function, baseline coronary flow (20,25 ml min,1 g,1) was 50,60% of maximally dilated flows, and coronary reactive and functional hyperaemic responses were pronounced (up to 4-fold elevations in flow in hearts lacking ventricular balloons). These data indicate that attention to age (and sex) of mice will reduce variability in contractile function and ischaemic responses. Even small differences in perfusion fluid [Ca2+] also significantly modify tolerance to ischaemia (whereas modest shifts in heart rate do not impact). Ischaemic responses are additionally strain dependent, with BALB/c hearts displaying greatest intrinsic tolerance. Finally, the model is applicable to the study of vascular reactivity, providing large responses and excellent reproducibility. [source] The emerging role of neuronal nitric oxide synthase in the regulation of myocardial functionEXPERIMENTAL PHYSIOLOGY, Issue 6 2006Barbara Casadei The recent discovery of a NOS1 gene product (i.e. a neuronal-like isoform of nitric oxide synthase or nNOS) in the mammalian left ventricular (LV) myocardium has provided a new key for the interpretation of the complex experimental evidence supporting a role for myocardial constitutive nitric oxide (NO) production in the regulation of basal and ,-badrenergic cardiac function. Importantly, nNOS gene deletion has been associated with more severe LV remodelling and functional deterioration in murine models of myocardial infarction, suggesting that nNOS-derived NO may also be involved in the myocardial response to injury. To date, the mechanisms by which nNOS influences myocardial pathophysiology remain incompletely understood. In particular, it seems over simplistic to assume that all aspects of the myocardial phenotype of nNOS knockout (nNOS,/,) mice are a direct consequence of lack of NO production from this source. Emerging data showing co-localisation of xanthine oxidoreductase (XOR) and nNOS in the sarcoplasmic reticulum of rodents, and increased XOR activity in the nNOS,/, myocardium, suggest that nNOS gene deletion may have wider implications on the myocardial redox state. Similarly, the mechanisms regulating the targeting of myocardial nNOS to different subcellular compartments and the functional consequences of intracellular nNOS trafficking have not been fully established. Whether this information could be translated into a better understanding and management of human heart failure remains the most important challenge for future investigations. [source] Twenty-Four Hours Postoperative Results After Orthotopic Cardiac Transplantation in SwineJOURNAL OF CARDIAC SURGERY, Issue 4 2007Matthias Siepe M.D. However, there is no functional data available for a longer time period after transplantation. We have established a pig model to investigate myocardial function 24 hours after orthotopic transplantation.Materials and Methods: Orthotopic cardiac transplantations (HTx) in pigs were performed with a postoperative observation period of 24 hours (n = 6). To analyze myocardial function after transplantation, hemodynamical parameters (Swan-Ganz- and impedance-catheter data) as well as tissue and blood samples were obtained. Regional myocardial blood flow (RMBF) was assessed using fluorescent microspheres. Results: The impedance-catheter parameters demonstrated a preserved contractility in both ventricles 24 hours post-transplantation. In contrast, cardiac output 24 hours after HTx was diminished by 50% as compared to the preoperative value. Conversely, pulmonary vascular resistance increased significantly. The RMBF was increased in both ventricles. Metabolic and histological analyses indicate myocardial recovery 24 hours after HTx with no irreversible damage. Conclusions: For the first time, we were able to establish a porcine model to investigate myocardial function 24 hours after heart transplantation. While the contractility of the transplanted hearts was well-preserved, impaired cardiac output was going along with an increase in pulmonary vascular resistance. Using this clinical relevant model, improvements of human cardiac transplantation and post-transplant contractile dysfunction, especially, could be investigated. [source] Distinct mechanisms of cardiomyocyte apoptosis induced by doxorubicin and hypoxia converge on mitochondria and are inhibited by Bcl-xLJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2007Janice LV Reeve Abstract Hypoxia and doxorubicin can cause cardiotoxicity and loss of myocardial function. These effects are due, in part, to an induction of apoptosis. Herein we identify the apoptotic pathways activated in H9c2 cells in response to hypoxia (O2/N2/CO2, 0.5:94.5:5) and doxorubicin (0.5 ,M). Although the apoptosis induced was accompanied by induction of Fas and Fas ligand, the death receptor pathway was not critical for caspase activation by either stimulus. Hypoxia induced the expression of endoplasmic reticulum (ER) stress mediators and processed ER-resident pro-caspase-12 whereas doxorubicin did not induce an ER stress response. Most importantly, both stimuli converged on mitochondria to promote apoptosis. Accumulation of cytochrome c in the cytosol coincided with the processing of pro-caspase-9 and -3. Increasing the expression of the anti-apoptotic protein Bcl-xL, either by dexamethasone or adenovirus-mediated transduction, protected H9c2 cells from doxorubicin- and hypoxia-induced apoptosis. Bcl-xL attenuated mitochondrial cytochrome crelease and reduced downstream pro-caspase processing and apoptosis. These data demonstrate that two distinct cardiomyocyte-damaging stimuli converge on mitochondria thus presenting this organelle as a potentially important therapeutic target for anti-apoptotic strategies for cardiovascular diseases. [source] AMP-activated protein kinase deficiency exacerbates aging-induced myocardial contractile dysfunctionAGING CELL, Issue 4 2010Subat Turdi Summary Aging is associated with myocardial dysfunction although the underlying mechanism is unclear. AMPK, a key cellular fuel sensor for energy metabolism, is compromised with aging. This study examined the role of AMPK deficiency in aging-associated myocardial dysfunction. Young or old wild-type (WT) and transgenic mice with overexpression of a mutant AMPK ,2 subunit (kinase dead, KD) were used. AMPK , isoform activity, myocardial function and morphology were examined. DCF and JC-1 fluorescence probes were employed to quantify reactive oxygen species (ROS) and mitochondrial membrane potential (,,m), respectively. KD mice displayed significantly reduced ,2 but not ,1 AMPK isoform activity at both ages with a greater effect at old age. Aging itself decreased ,1 isoform activity. Cardiomyocyte contractile function, intracellular Ca2+ handling, and SERCA2a levels were compromised with aging, the effects of which were exacerbated by AMPK deficiency. H&E staining revealed cardiomyocyte hypertrophy with aging, which was more pronounced in KD mice. TEM micrographs displayed severe disruption of mitochondrial ultrastructure characterized by swollen, irregular shape and disrupted cristae in aged KD compared with WT mice. Aging enhanced ROS production and reduced ,,m, the effects of which were accentuated by AMPK deficiency. Immunoblotting data depicted unchanged Akt phosphorylation and a significant decrease in mitochondrial biogenesis cofactor PGC-1, in aged groups. AMPK deficiency but not aging decreased the phosphorylation of ACC and eNOS. Expression of membrane Glut4 and HSP90 was decreased in aged KD mice. Moreover, treatment of the AMPK activator metformin attenuated aging-induced cardiomyocyte contractile defects. Collectively, our data suggest a role for AMPK deficiency in aging-induced cardiac dysfunction possibly through disrupted mitochondrial function and ROS production. [source] High thoracic epidural analgesia improves left ventricular function in patients with ischemic heartACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2009C.-J. JAKOBSEN Background: In patients with ischemic heart disease, high thoracic epidural analgesia (HTEA) has been proposed to improve myocardial function. Tissue Doppler Imaging (TDI) is a tool for quantitative determination of myocardial systolic and diastolic velocities and a derivative of TDI is tissue tracking (TT), which allows quantitative assessment of myocardial systolic longitudinal displacement during systole. The purpose of this study was to evaluate the effect of thoracic epidural analgesia on left ventricular (LV) systolic and diastolic function by means of two-dimensional (2D) echocardiography and TDI in patients with ischemic heart disease. Methods: The effect of a high epidural block (at least Th1,Th5) on myocardial function in patients (N=15) with ischemic heart disease was evaluated. Simpson's 2D volumetric method was used to quantify LV volume and ejection fraction. Systolic longitudinal displacement was assessed by the TT score index and the diastolic function was evaluated from changes in early (E,) and atrial (A,) peak velocities during diastole. Results: After HTEA, 2D measures of left ventricle function improved significantly together with the mean TT score index [from 5.87 ± 1.53 to 6.86 ± 1.38 (P<0.0003)], reflecting an increase in LV global systolic function and longitudinal systolic displacement. The E,/A, ratio increased from 0.75 ± 0.27 to 1.09 ± 0.32 (P=0.0026), indicating improved relaxation. Conclusion: A 2D-echocardiography in combination with TDI indicates both improved systolic and diastolic function after HTEA in patients with ischemic heart disease. [source] Synthesis and activity of four (N,N -dimethylamino)benzamide nonsteroidal anti-inflammatory drugs based on thiazole and thiazolineJOURNAL OF HETEROCYCLIC CHEMISTRY, Issue 1 2006Daniel E. Lynch Four compounds derived from 2-aminothiazole and 2-amino-2-thiazoline were prepared by coupling the respective bases with the acid chlorides of either 3- or 4-(N,N -dimethylamino)benzoic acid. Products were identified using infrared spectroscopy, 1H NMR spectroscopy and electrospray mass spectroscopy and in two cases by single-crystal X-ray diffraction. Of the four, N -(thiazol-2-yl)-3-(N,N -dimethylamino)-benzamide (1), N -(thiazolin-2-yl)-4-(N,N -dimethylamino)benzamide (2), N -(thiazolin-2-yl)-3-(N,N -dimethylamino) benzamide (3) and N -(thiazolin-2-yl)-4-(N,N -dimethylamino)benzamide (4), the hydrochloride salts of compounds 3 and 4 showed anti-inflammatory activity across a concentration range of 10,2,5 × 10,4M while 3 (at a concentration of 10,5M) was found to have no adverse effect on myocardial function. The X-ray crystal structure of 2 and the 1:1 adduct structure of 3 with 3-(N,N -dimethylamino)benzoic acid are reported. [source] Catheter-Based Transendocardial Myocardial Gene TransferJOURNAL OF INTERVENTIONAL CARDIOLOGY, Issue 1 2002CHRISTER SYLVÉNM.D. Ph.D. Background and Aim: Local modulation of myocardial function by gene transfer or cell depositions constitutes a potential method of cardiac treatment. This study tested the morphology of myocardial plasmid gene transfer by catheter-based transendocardial injection (NOGA). Methods: Left ventricular morphology and electrical and mechanical characteristics were mapped in three dimensions. In two pigs, 0.10 mL oftoluidine blue was injected at ten sites. In seven pigs, seven to ten injections of 0.10 mL saline containing 0.10 mg pCMV-LacZ expressing the enzyme ,-galactosidase and 0.10 mg phVEGF-A165 were given. The pigs were sacrificed after 3 days and gene expression was determined. Results: Macroscopically on the endocardial surface, all identified spots were located in the target area. However, along the transmyocardial axis, injections with color and plasmid were located randomly throughout the left ventricular wall from the endocardium to the epicardium. In each detected spot, gene expression of ,-galactosidase was observed in an approximate myocardial volume of 5 × 5 × 5 mm. Microscopically, the transfected cells were located typically at the tip of the injection scar. As a rule, 10 to 20 transfected cells were located at the end of the injection scar. In sections where expression of both transcripts was observed, 42% of the cells expressed both ,-galactosidase and vascular endothelial growth factors (VEGF), 32% only ,-galactosidase, and 26% only VEGF. Conclusions: Myocardial gene transfer following magnetic guidance can be located precisely on the left ventricular inner surface. Within the myocardium, gene expression is local around the distal tip of the injection scar and is located randomly at every level of depth of the left ventricular wall. [source] Tissue Doppler and Strain Imaging in Dogs with Myxomatous Mitral Valve Disease in Different Stages of Congestive Heart FailureJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 6 2009A. Tidholm Background: Tissue Doppler imaging (TDI) including strain and strain rate (SR) assess systolic and diastolic myocardial function. Hypothesis: TDI, strain, and SR variables of the left ventricle (LV) and the interventricular septum (IVS) differ significantly between dogs with myxomatous mitral valve disease (MMVD) with and without congestive heart failure (CHF). Animals: Sixty-one dogs with MMVD with and without CHF. Ten healthy control dogs. Methods: Prospective observational study. Results: Radial motion: None of the systolic variables were altered and 3 of the diastolic velocities were significantly increased in dogs with CHF compared with dogs without CHF and control dogs. Longitudinal motion: 2 systolic velocities and 3 diastolic velocities were significantly increased in dogs with CHF compared with dogs without CHF and control dogs. Difference in systolic velocity time-to-peak between LV and IVS was significantly increased in dogs with MMVD with and without CHF compared with control dogs. In total, 11 (23%) of 48 TDI and strain variables differed significantly between groups. Left atrial to aortic ratio was positively correlated to early diastolic velocities, percentage increase in left ventricular internal diameter in systole was positively correlated to systolic and diastolic velocities, and mitral E wave to peak early diastolic velocity in the LV basal segment (E/Em) was positively correlated to radial strain and SR. Conclusions and Clinical Importance: Few TDI and strain variables were changed in dogs with MMVD with and without CHF. Intraventricular dyssynchrony may be an early sign of MMVD or may be an age-related finding. [source] Complementary displacement-encoded MRI for contrast-enhanced infarct detection and quantification of myocardial function in miceMAGNETIC RESONANCE IN MEDICINE, Issue 4 2004Wesley D. Gilson Abstract MRI is emerging as an important modality for assessing myocardial function in transgenic and knockout mouse models of cardiovascular disease, including myocardial infarction (MI). Displacement encoding with stimulated echoes (DENSE) measures myocardial motion at high spatial resolution using phase-reconstructed images. The current DENSE technique uses inversion recovery (IR) to suppress T1 -relaxation artifacts; however, IR is ill-suited for contrast-enhanced infarct imaging in the heart, where multiple T1 values are observed. We have developed a modified DENSE method employing complementary acquisitions for T1 -independent artifact suppression. With this technique, displacement and strain are measured in phase-reconstructed images, and contrast-enhanced regions of infarction are depicted in perfectly coregistered magnitude-reconstructed images. The displacement measurements and T1 -weighted image contrast were validated with the use of a rotating phantom. Modified DENSE was performed in mice (N = 9) before and after MI. Circumferential (Ecc) and radial (Err) strain were measured, and contrast-enhanced infarcted myocardium was detected by DENSE. At baseline, Ecc was ,0.16 ± 0.01 and Err was 0.39 ± 0.07. After MI, Ecc was 0.04 ± 0.02 and Err was 0.03 ± 0.04 in infarcted regions, whereas Ecc was ,0.12 ± 0.02 and Err was 0.38 ± 0.09 in noninfarcted regions. In vivo Ecc as determined by DENSE correlated well with Ecc obtained by conventional tag analysis (R = 0.90). Magn Reson Med 51:744,752, 2004. © 2004 Wiley-Liss, Inc. [source] Assessment of regional systolic and diastolic dysfunction in familial hypertrophic cardiomyopathy using MR tagging,MAGNETIC RESONANCE IN MEDICINE, Issue 3 2003Daniel B. Ennis Abstract Diastolic and systolic left ventricular (LV) dysfunction often significantly contribute to disabling symptoms in familial hypertrophic cardiomyopathy (FHC). This study compares regional LV function (midwall circumferential strain) during systole and diastole in eight FHC patients and six normal volunteers (NVs) using MR tagging. A prospectively-gated fast gradient-echo sequence with an echo-train readout was modified to support complementary spatial modulation of magnetization (CSPAMM) tagging and full cardiac cycle data acquisition using the cardiac phase to order reconstruction (CAPTOR), thus providing tag persistence and data acquisition during the entire cardiac cycle. Total systolic strains in FHC patients were significantly reduced in septal and inferior regions (both P < 0.01). Early-diastolic strain rates were reduced in all regions of the FHC group (all P < 0.03). The combination of CSPAMM and CAPTOR allows regional indices of myocardial function to be quantified throughout the cardiac cycle. This technique reveals regional differences in systolic and diastolic impairment in FHC patients. Magn Reson Med 50:638,642, 2003. Published 2003 Wiley-Liss, Inc. [source] Effects of intra-abdominal CO2 -insufflation on normal and impaired myocardial function: an experimental studyACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2003C. A. Greim Background:, Intra-abdominal pressure (IAP) elevation during CO2 -pneumoperitoneum increases cardiac afterload and may enhance dysfunction of the already compromized heart. This study focused on the effects of acute IAP increases on left and right ventricular loadings and contractility in the heart with impaired global function. Methods:, Impairment of myocardial function (IMF) was pharmacologically induced in 16 pigs by administration of halothane and propranolol, while baseline arterial pressure was maintained by intravenous phenylephrine. Intra-abdominal pressure was gradually increased by 10 mmHg up to 30 mmHg in the supine position (IMF group 1, n = 8) or in a head-down tilted position (IMF group 2, n = 8). In two control groups with normal myocardial function, IAP was also increased in the supine position or the head-down tilted position. Cardiac function in all groups was assessed by epicardial echocardiography, intraventricular pressure measurements and pulmonary artery catheterization. Results:, The increase in IAP was accompanied by a transient rise in LV end-systolic wall stress and reduced cardiac output significantly by 16,24% in all groups. In the IMF groups, LV end-diastolic transmural pressure increased by 34,60% to peak values of 24 mmHg, while cross-sectional LV end-diastolic areas remained unchanged. Increases in right ventricular end-diastolic volume and decreases in right ventricular ejection fraction as well as in cardiac output were most pronounced at IAP 20 mmHg and significantly stronger in both IMF groups than in the control groups (P < 0.001). Conclusion:, Following the acute elevation of IAP, the right ventricular volume load shifted more extensively in the IMF groups than in the animals with normal myocardial function. Myocardial function in the impaired heart may worsen during IAP elevation due to right ventricular load alterations rather than a LV afterload increase. [source] In ovo non-invasive quantification of the myocardial function and mass of chick embryos using magnetic resonance imagingNMR IN BIOMEDICINE, Issue 7 2009William M. Holmes Abstract Magnetic resonance imaging (MRI) has evolved as one of the major non-invasive tools to study healthy and diseased hearts in animal models, especially rodent models. Even though, the chick embryo has long been used as a model for cardiovascular research, MRI has not yet been used for in vivo cardiac studies. Part of the reason for this is the difficulty in monitoring the ECG and respiration of the chick embryo in the magnet for gating purposes. To overcome this complication, this paper presents the use of retrospective Cine MRI to measure the cardiac function of chick embryos in ovo for the first time, without the need for respiratory or cardiac gating. The resulting left ventricular functional parameters, from six chick embryos at 20 days of incubation, were (mean,±,SD) EDV 69,±,15,µL, ESV 31,±,7,µL, SV 38,±,9,µL and EF 54.5,±,2%. The use of retrospective Cine MRI at earlier stages of development is also discussed and difficulties have been highlighted. Copyright © 2009 John Wiley & Sons, Ltd. [source] Late cardiotoxicity after bolus versus infusion anthracycline therapy for childhood cancersPEDIATRIC BLOOD & CANCER, Issue 6 2003Monesha Gupta MBBS Abstract Objective To compare the long-term myocardial function of patients who had been treated with infusion anthracycline therapy (administered continuously over >24 hr, IG) versus bolus therapy (administered over <30 min, BG). Methods We selected 25 patients (BG) and 19 patients (IG) who had three or more years of disease free survival. We evaluated the echocardiograms for left ventricular shortening fraction (SF) obtained at baseline, within one year after the end of therapy (early follow-up), and on long-term follow-up. Results The mean anthracycline dose in the BG was 385 mg/m2 and in the IG was 345 mg/m2 (P,=,0.07). During therapy, one patient in BG and none in IG developed diminished SF. During early follow-up, five of the 22 patients in BG and one of the 17 patients in IG developed diminished SF (P,=,0.2). Of these five patients with diminished SF, three patients in BG and none in IG continued to have abnormally low SF long-term. At mean of 7 years, five of the 25 patients in BG and two of the 19 in IG had diminished SF on (P,=,0.7). Late left ventricular dilatation was seen in 8% in BG and 5% in IG (P,=,1.0). Conclusions At mean of 7 years after end of therapy, diminished cardiac function was seen in 20% of the patient who had received bolus anthracycline compared to 11% of patients who had received it via infusion. This difference did not prove to be statistically significant. Med Pediatr Oncol 2003;40:343,347. © 2003 Wiley-Liss, Inc. [source] Sex influence on myocardial function with exercise in adolescentsAMERICAN JOURNAL OF HUMAN BIOLOGY, Issue 5 2010Thomas Rowland Objectives: Ventricular systolic functional response to exercise has been reported to be superior in adult men compared to women. This study explored myocardial responses to maximal upright progressive exercise in late pubertal males and females. Methods: Doppler echocardiographic techniques were utilized to estimate myocardial function response to a bout of progressive cycle exercise. Results: Systolic functional capacity, as indicated by ejection rate (12.5 ± 2.8 and 13.1 ± 1.0 [×10,2] ml s,1 cm,2 for boys and girls, respectively) and peak aortic velocity (208 ± 45 and 196 ± 12 cm s,1, respectively) at maximal exercise, did not differ between the two groups. Similarly, peak values as well as increases in transmitral pressure gradient (mitral E flow velocity), ventricular relaxation (tissue Doppler imaging E,), and left ventricular filling pressure (E/E, ratio) as estimates of diastolic function were similar in males and females. Conclusions: This study failed to reveal qualitative or quantitative differences between adolescent boys and girls in ventricular systolic or diastolic functional responses to maximal cycle exercise. Am. J. Hum. Biol. 22:680,682, 2010. © 2010 Wiley-Liss, Inc. [source] Direct evidence of nitric oxide release from neuronal nitric oxide synthase activation in the left ventricle as a result of cervical vagus nerve stimulationTHE JOURNAL OF PHYSIOLOGY, Issue 12 2009Kieran E. Brack Information regarding vagal innervation in the cardiac ventricle is limited and the direct effect of vagal stimulation on ventricular myocardial function is controversial. We have recently provided indirect evidence that the anti-fibrillatory effect of vagus nerve stimulation on the ventricle is mediated by nitric oxide (NO). The aim of this study was to provide direct evidence for the release of nitric oxide in the cardiac ventricle during stimulation of the efferent parasympathetic fibres of the cervical vagus nerve. The isolated innervated rabbit heart was employed with the use of the NO fluorescent indicator 4,5-diaminofluorescein diacetate (DAF-2 DA) during stimulation of the cervical vagus nerves and acetylcholine perfusion in the absence and presence of the non-specific NO synthase inhibitor NG -nito- l- arginine (l- NNA) and the neuronal NO synthase selective inhibitor 1-(2-trifluormethylphenyl)imidazole (TRIM). Using the novel fluorescence method in the beating heart, we have shown that NO-dependent fluorescence is increased by 0.92 ± 0.26, 1.20 ± 0.30 and 1.91 ± 0.27% (during low, medium and high frequency, respectively) in the ventricle in a stimulation frequency-dependent manner during vagus nerve stimulation, with comparable increases seen during separate stimulation of the left and right cervical vagus nerves. Background fluorescence is reduced during perfusion with l- NNA and the increase in fluorescence during high frequency vagal stimulation is inhibited during perfusion with both l- NNA (1.97 ± 0.35% increase before l- NNA, 0.00 ± 0.02% during l- NNA) and TRIM (1.78 ± 0.18% increase before TRIM, ,0.11 ± 0.08% during TRIM). Perfusion with 0.1 ,m acetylcholine increased NO fluorescence by 0.76 ± 0.09% which was blocked by l- NNA (change of 0.00 ± 0.03%) but not TRIM (increase of 0.82 ± 0.21%). Activation of cardiac parasympathetic efferent nerve fibres by stimulation of the cervical vagus is associated with NO production and release in the ventricle of the rabbit, via the neuronal isoform of nitric oxide synthase. [source] | ||||||||||||||||||||||||||||