			Home About us Contact

Ischemic Myocardium (ischemic + myocardium)

Distribution by Scientific Domains

Medical Sciences	86%
Life Sciences	13%

Selected Abstracts

Myocardial Gene Expression of Angiogenic Factors in Human Chronic Ischemic Myocardium: Influence of Acute Ischemia/Cardioplegia and Reperfusion

MICROCIRCULATION, Issue 3 2006
YONGZHONG WANG
ABSTRACT Objective: Angiogenic therapies in animals have demonstrated the development of new blood vessels within ischemic myocardium. However, results from clinical protein and gene angiogenic trials have been less impressive. The present study aimed to investigate the expression of angiogenic genes in human chronic ischemic myocardium and the influence of acute ischemia/cardioplegia and reperfusion on their expression. Methods: Myocardial biopsies were taken from chronic ischemic and nonischemic myocardium in 15 patients with stable angina pectoris during coronary bypass surgery. Tissue samples were evaluated by oligonucleotide microarray and quantitative real-time PCR for the expression of angiogenic factors. Results: There was identical baseline expression of VEGF-A and VEGF-C mRNA in chronic ischemic myocardium compared with nonischemic myocardium. Reperfusion increased the gene expression of VEGF-A and VEGF-C mRNA both in nonischemic and ischemic myocardium. VEGF-A protein was detected mainly in the extracellular matrix around the cardiomyocytes in ischemic myocardium. Conclusion: These data suggest that the nonconclusive VEGF gene therapy trials chronic coronary artery disease was not due to a preexisting upregulation of VEGF in chronic ischemic myocardium. There might be room for further therapeutic angiogenesis in chronic ischemic myocardium. [source]

Coronary Arteries Angiogenesis in Ischemic Myocardium: Biocompatibility and Biodegradability of Various Hydrogels

ARTIFICIAL ORGANS, Issue 10 2009
Xiaodong Shen
Abstract To evaluate the biocompatibility and biodegradability of various hydrogels and choose suitable hydrogels for the coronary arteries angiogenesis in ischemic myocardium, we synthesized six kinds of hyaluronan hydrogels, fibrin hydrogel, poly(vinyl alcohol)-chitosan hydrogel, and obtained elastin hydrogels. We examined their degradation rates and cytotoxicity in vitro. Then, hydrogels were implanted into rat adductor muscles for 1, 2, or 4 weeks. Hydrogels and surrounding tissues were resected, followed by hematoxylin and eosin staining, Masson's trichrome staining, and immunohistochemical staining for measurements of degradation, immune response, and angiogenesis. 2-Iminothiolane grafted hyaluronan hydrogel and periodate oxidated hyaluronan hydrogel presented rapid degradation rates, low quantity of inflammation-mediating cells (12 ± 3 and 12 ± 4 per 2.5 × 10,3 mm2, respectively, at week 2), thin fibrous capsules (scores were 3.8 ± 0.1 and 4.0 ± 0.3 per 0.33 mm2, respectively, at week 2) with dense blood vessels in the areas surrounding the implanted hydrogels. 2-Iminothiolane grafted hyaluronan and periodate oxidated hyaluronan hydrogels with appropriate degradation rates and low immune responses were suitable for coronary arteries angiogenesis in ischemic myocardium. [source]

Complement and its implications in cardiac ischemia/reperfusion: strategies to inhibit complement

FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 5 2001
Tiphaine Monsinjon
Although reperfusion of the ischemic myocardium is an absolute necessity to salvage tissue from eventual death, it is also associated with pathologic changes that represent either an acceleration of processes initiated during ischemia or new pathophysiological changes that were initiated after reperfusion. This so-called ,reperfusion injury' is accompanied by a marked inflammatory reaction, which contributes to tissue injury. In addition to the well known role of oxygen free radicals and white blood cells, activation of the complement system probably represents one of the major contributors of the inflammatory reaction upon reperfusion. The complement may be activated through three different pathways: the classical, the alternative, and the lectin pathway. During reperfusion, complement may be activated by exposure to intracellular components such as mitochondrial membranes or intermediate filaments. Two elements of the activated complement contribute directly or indirectly to damages: anaphylatoxins (C3a and C5a) and the membrane attack complex (MAC). C5a, the most potent chemotactic anaphylatoxin, may attract neutrophils to the site of inflammation, leading to superoxide production, while MAC is deposited over endothelial cells and smooth vessel cells, leading to cell injury. Experimental evidence suggests that tissue salvage may be achieved by inhibition of the complement pathway. As the complement is composed of a cascade of proteins, it provides numerous sites for pharmacological interventions during acute myocardial infarction. Although various strategies aimed at modulating the complement system have been tested, the ideal approach probably consists of maintaining the activity of C3 (a central protein of the complement cascade) and inhibiting the later events implicated in ischemia/reperfusion and also in targeting inhibition in a tissue-specific manner. [source]

Levosimendan cardioprotection in acutely ,-1 adrenergic receptor blocked open chest pigs

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 1 2010
C. 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]

Temporary Epicardial Ventricular Stimulation in Patients with Atrial Fibrillation: Acute Effects of Ventricular Pacing Site on Bypass Graft Flows

JOURNAL OF CARDIAC SURGERY, Issue 4 2009
Navid Madershahian M.D.
This study aimed to evaluate the optimal epicardial ventricular pacing site in patients with AF following coronary artery bypass surgery (CABG). Methods: In 23 consecutive patients (mean age = 69.2 ± 1.9 years, gender = 62% male, ejection fraction [EF]= 50.4 ± 2.1%) monoventricular stimulations (VVI) were tested with a constant pacing rate of 100 bpm. The impact of ventricular pacing on bypass graft flow (transit-time flow probe) and pulsatility index (PI) were measured after lead placement on the mid paraseptal region of the right (RVPS) and the left (LVPS) ventricle, on the right inferior wall (RVIW), and on the right ventricular outflow tract (RVOT). In addition, hemodynamic parameters were measured. Patients served as their own control. Results: Comparison of all tested pacing locations revealed that RVOT stimulation provided the highest bypass grafts flows (59.9 ± 6.1 mL/min) and PI (2.2 ± 0.1) when compared with RVPS (51.3 ± 4.7 mL/min, PI = 2.6 ± 0.2), RVIW (54.0 ± 5.1 mL/m; PI = 2.4 ± 0.2), and LVPS (53.1 ± 4.5 mL/min; PI = 2.3 ± 0.1), respectively (p < 0.05). When analyzing patients according to their preoperative LV function (group I = EF > 50%; group II = EF < 50%), higher bypass graft flows were observed with RVOT pacing in patients with lower EF (p = n.s.). Conclusions: Temporary RVOT pacing facilitates optimal bypass graft flows when compared with other ventricular pacing sites and should be the preferred method of temporary pacing in cardiac surgery patients with AF. Especially in patients with low EF following CABG, RVOT pacing may improve myocardial oxygen conditions for the ischemic myocardium and enhance graft patency in the early postoperative period. [source]

Metabolic responses in ischemic myocardium after inhalation of carbon monoxide

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2009
K. AHLSTRÖM
Background: To clarify the mechanisms of carbon monoxide (CO) tissue-protective effects, we studied energy metabolism in an animal model of acute coronary occlusion and pre-treatment with CO. Methods: In anesthetized pigs, a coronary snare and microdialysis probes were placed. CO (carboxyhemoglobin 5%) was inhaled for 200 min in test animals, followed by 40 min of coronary occlusion. Microdialysate was analyzed for lactate and glucose, and myocardial tissue samples were analyzed for adenosine tri-phosphate, adenosine di-phosphate, and adenosine mono-phosphate. Results: Lactate during coronary occlusion was approximately half as high in CO pre-treated animals and glucose levels decreased to a much lesser degree during ischemia. Energy charge was no different between groups. Conclusions: CO in the low-doses tested in this model results in a more favorable energy metabolic condition in that glycolysis is decreased in spite of maintained energy charge. Further work is warranted to clarify the possible mechanistic role of energy metabolism for CO protection. [source]

Active site inhibited factor VIIa attenuates myocardial ischemia/reperfusion injury in mice

JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 2 2009
S. T. B. G. LOUBELE
Summary.,Background:,Inhibition of specific coagulation pathways such as the factor VIIa-tissue factor complex has been shown to attenuate ischemia/reperfusion (I/R) injury, but the cellular mechanisms have not been explored. Objectives:,To determine the cellular mechanisms involved in the working mechanism of active site inhibited factor VIIa (ASIS) in the protection against myocardial I/R injury. Methods:,We investigated the effects of a specific mouse recombinant in a mouse model of myocardial I/R injury. One hour of ischemia was followed by 2, 6 or 24 h of reperfusion. Mouse ASIS or placebo was administered before and after induction of reperfusion. Results:,ASIS administration reduced myocardial I/R injury by more than 40% at three reperfusion times. Multiplex ligation dependent probe amplification (MLPA) analysis showed reduced mRNA expression in the ischemic myocardium of CD14, TLR-4, interleukin-1 (IL-1) receptor-associated kinase (IRAK) and I,B, upon ASIS administration, indicative of inhibition of toll-like receptor-4 (TLR-4) and subsequent nuclear factor-,B (NF-,B) mediated cell signaling. Levels of nuclear activated NF-,B and proteins influenced by the NF-,B pathway including tissue factor (TF) and IL-6 that were increased after I/R, were attenuated upon ASIS administration. After 6 and 24 h of reperfusion, neutrophil infiltration into the area of infarction was decreased upon ASIS administration. There was, however, no evidence of an effect of ASIS on apoptosis (Tunel staining and MLPA analysis). Conclusions:,We conclude that the diminished amount of myocardial I/R injury after ASIS administration is primarily due to attenuated inflammation-related lethal I/R injury, probably mediated through the NF-,B mechanism. [source]

Myocardial Gene Expression of Angiogenic Factors in Human Chronic Ischemic Myocardium: Influence of Acute Ischemia/Cardioplegia and Reperfusion

Noninvasive Imaging of Angiogenesis Inhibition Following Nitric Oxide Synthase Blockade in the Ischemic Rat Heart in Vivo

MICROCIRCULATION, Issue 4 2005
CHRISTIANE WALLER MD
ABSTRACT Objective: Nitric oxide synthase inhibition has anti-angiogenic properties. Magnetic resonance (MR) imaging was used to image the functional significance of these microvascular changes in a rat model of chronic ischemic myocardium in vivo. Methods: The authors quantitatively determined myocardial perfusion and regional blood volume, left ventricular geometry, and function using MR imaging. Animals received either L-NAME + hydralazine or no treatment and were investigated 1 and 2 weeks after induction of coronary artery stenosis or sham operation at rest and during vasodilatation. Double-labeling immunohistochemistry was used to visualize angiogenesis and to compare with data obtained by MR imaging. Results: Left ventricular mass and end-diastolic volumes were comparable in both groups 2 weeks after treatment. However, basal and maximum perfusion in animals with L -NAME + hydralazine treatment were reduced compared to animals not treated (p < .05). Basal regional blood volume remained constant in all groups, whereas maximum regional blood volume was reduced by L -NAME + hydralazine (p < .05). Endothelial cell proliferation, a direct marker for angiogenesis, was reduced by L -NAME + hydralazine (p < .01). Conclusions: MR imaging allows noninvasive quantification of functional microcirculation and angiogenesis in the rat heart in vivo. Nitric oxide synthase blockade results in changes in functional microcirculation and in an inhibition of angiogenesis in both ischemic and nonischemic myocardial tissue. [source]

Stem cell implantation in ischemic mouse heart: a high-resolution magnetic resonance imaging investigation,

NMR IN BIOMEDICINE, Issue 6 2005
Ekkehard Küstermann
Abstract Advances in the biology of stem cells have evoked great interest in cell replacement therapies for the regeneration of heart tissue after myocardial infarction. However, results from human trials are controversial, since the destination of the injected cells, their engraftment and their long-term fate have remained unclear. Here we investigate whether transplanted cells can be identified in the intact and lesioned murine myocardium employing high-resolution MRI. Cardiac progenitor cells, expressing the enhanced green fluorescent protein (EGFP), were labeled with ultra-small paramagnetic iron-oxide (USPIO) nanoparticles and transplanted into the intact or injured myocardium of mice. Their precise location was determined with high-resolution MRI and compared with histological tissue sections, stained with Prussian blue for iron content. These experiments showed that iron nanoparticle-loaded cells could be identified at high resolution in the mouse heart. However, ischemic myocardium (after cryoinjury or left coronary artery ligation) was characterized by a signal attenuation similar to that induced by USPIO-labeled cells in T -weighted MR images, making detection of labeled stem cells in this area by T -sensitive contrast rather difficult. In animals with myocardial injury only, the signal attenuated areas were of the same size in proton density- and T -weighted MR images. In injured animals also receiving labeled cells the lesioned area appeared larger in T - than in proton density-weighted MR images. This sequence-dependent lesion size change is due to the increased signal loss caused by the iron oxide nanoparticles, most sensitively detectable in the T -sensitive images. Thus, using the novel combination of these two parameter weightings, USPIO-labeled cells can be detected at high resolution in ischemic myocardium. Copyright © 2005 John Wiley & Sons, Ltd. [source]

Improved cardiac function in infarcted mice after treatment with pluripotent embryonic stem cells

THE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 11 2006
Timothy J. Nelson
Abstract Because pluripotent embryonic stem cells (ESCs) are able to differentiate into any tissue, they are attractive agents for tissue regeneration. Although improvement of cardiac function has been observed after transplantation of pluripotent ESCs, the extent to which these effects reflect ESC-mediated remuscularization, revascularization, or paracrine mechanisms is unknown. Moreover, because ESCs may generate teratomas, the ability to predict the outcome of cellular differentiation, especially when transplanting pluripotent ESCs, is essential; conversely, a requirement to use predifferentiated ESCs would limit their application to highly characterized subsets that are available in limited numbers. In the experiments reported here, we transplanted low numbers of two murine ESC lines, respectively engineered to express a ,-galactosidase gene from either a constitutive (elongation factor) or a cardiac-specific (,-myosin heavy chain) promoter, into infarcted mouse myocardium. Although ESC-derived tumors formed within the pericardial space in 21% of injected hearts, lacZ histochemistry revealed that engraftment of ESC was restricted to the ischemic myocardium. Echocardiographic monitoring of ESC-injected hearts that did not form tumors revealed functional improvements by 4 weeks postinfarction, including significant increases in ejection fraction, circumferential fiber shortening velocity, and peak mitral blood flow velocity. These experiments indicate that the infarcted myocardial environment can support engraftment and cardiomyogenic differentiation of pluripotent ESCs, concomitant with partial functional recovery. Anat Rec Part A, 288A:1216,1224, 2006. © 2006 Wiley-Liss, Inc. [source]

Combining angiogenic gene and stem cell therapies for myocardial infarction

THE JOURNAL OF GENE MEDICINE, Issue 9 2009
Jennifer Pons
Abstract Background Transplantation of stem cells from various sources into infarcted hearts has the potential to promote myocardial regeneration. However, the regenerative capacity is limited partly as a result of the low survival rate of the transplanted cells in the ischemic myocardium. In the present study, we tested the hypothesis that combining cell and angiogenic gene therapies would provide additive therapeutic effects via co-injection of bone marrow-derived mesenchymal stem cells (MSCs) with an adeno-associated viral vector (AAV), MLCVEGF, which expresses vascular endothelial growth factor (VEGF) in a cardiac-specific and hypoxia-inducible manner. Methods MSCs isolated from transgenic mice expressing green fluorescent protein and MLCVEGF packaged in AAV serotype 1 capsid were injected into mouse hearts at the border of ischemic area, immediately after occlusion of the left anterior descending coronary, individually or together. Engrafted cells were detected and quantified by real-time polymerase chain reaction and immunostaining. Angiogenesis and infarct size were analyzed on histological and immunohistochemical stained sections. Cardiac function was analyzed by echocardiography. Results We found that co-injection of AAV1-MLCVEGF with MSCs reduced cell loss. Although injection of MSCs and AAV1-MLCVEGF individually improved cardiac function and reduced infarct size, co-injection of MSC and AAV1-MLCVEGF resulted in the best improvement in cardiac function as well as the smallest infarct among all groups. Moreover, injection of AAV1-MLCVEGF induced neovasculatures. Nonetheless, injection of MSCs attracted endogenous stem cell homing and increased scar thickness. Conclusions Co-injection of MLCVEGF and MSCs in ischemic hearts can result in better cardiac function and MSC survival, compared to their individual injections, as a result of the additive effects of each therapy. Copyright © 2009 John Wiley & Sons, Ltd. [source]

Coronary Arteries Angiogenesis in Ischemic Myocardium: Biocompatibility and Biodegradability of Various Hydrogels

Spontaneous coronary artery dissection

CLINICAL CARDIOLOGY, Issue 7 2004
Francis Q. Almeda M.D.
Abstract Spontaneous coronary artery dissection (SCAD) is an unusual cause of acute myocardial ischemia with complex pathophysiology. This paper reviews the major diagnostic and therapeutic issues of this rare but important disease. The diagnosis of SCAD should be strongly considered in any patient who presents with symptoms suggestive of acute myocardial ischemia, particularly in young subjects without traditional risk factors for coronary artery disease (especially in young women during the peripartum period or in association with oral contraceptive use). Urgent coronary angiography is indicated to establish the diagnosis and to determine the appropriate therapeutic approach. The decision to pursue medical management, percutaneous coronary intervention, or surgical revascularization is based primarily on the clinical presentation, extent of dissection, and amount of ischemic myocardium at risk. [source]