Induction Of Myocardial Ischemia Research Articles

Morphine timing-dependent modulation of TRPV1 phosphorylation correlates with differential morphine effects on myocardial ischemia/reperfusion injury

Opioids are used for pain relief in patients suffering from acute myocardial ischemia or infarction. Clinical and laboratory studies demonstrate that morphine treated patients or the experimental animal model suffering acute myocardial ischemia and reperfusion, may worsen myocardial viability. As transient receptor potential vanilloid 1 (TRPV1) plays important roles in pain sensation and cardio-protection, we query whether opioids may exacerbate myocardial viability via interaction with TRPV1 activity in the pain relief. We found the co-expressions of TRPV1 and opioid μ, δ and κ receptors in adult rat cardiomyocytes. Intravenous injection of morphine (0.3 mg/kg) at 20 min after induction of myocardial ischemia, in the rat model of acute myocardial ischemia and reperfusion, induced significant reduction of phosphorylated TRPV1 (p-TRPV1) in the ventricular myocardium and increase in serum cardiac troponin I (cTnI), compared with the ischemia/reperfusion controls (all P < 0.05). The effects of morphine were completely reversed by selective opioid μ, δ and κ receptor antagonists. While significant upregulation of p-TRPV1 (P < 0.05) and improvement of ±dP/dt max (all P < 0.05) were detected in the animals giving the same dose of morphine before induction of myocardial ischemia. The changes in p-TRPV1 correlate with the alterations of cTnI (r = −0.5840, P = 0.0283) and ±dP/dt max (r = 0.8084, P = 0.0005 and r = −0.8133, P = 0.0004, respectively). The findings of this study may indicate that potentiation and attenuation of TRPV1 sensitivity correlate with the improvement of the cardiac performance and the aggravation of myocardial viability, respectively, by giving morphine before and during myocardial ischemia and reperfusion.

Effect of lazaroid U-74389G and Sildenafil, alone or in combination, on pulmonary function during ischamia-reperfusion injury of myocardium: An exploratory study

Background: This experimental study was designed to evaluate the effects of the pharmaceutical substances U-74389G (Lazaroid) and Sildenafil, administered separately or in combination, during anaesthesia in relation to pulmonary function, in a myocardial ischaemia-reperfusion procedure. Methods: We sought to determine the effect of sildenafil and lazaroid U-74389G maleate, alone or in combination, on systemic and pulmonary tissue inflammation and oxidative stress in a pig model of myocardial ischaemia-reperfusion injury. A total of 56 pigs were divided into seven groups according to the use of sildenafil, lazaroid, or their combination, and the time of administration (prior to the induction of myocardial ischaemia or after reperfusion). Results: Both sildenafil and lazaroid U-74389G maleate, administered either 10 minutes before the induction of myocardial ischaemia or immediately after the start of reperfusion, resulted in a significant effect on several markers of systemic inflammation (p&lt;0.05). In addition, a significant reduction in lung tissue expression of tumour necrosis factor-alpha (TNF-a) (p&lt;0.05) was observed with sildenafil, lazaroid U-74389G maleate, and their combination, when administered either before the induction of myocardial ischaemia or after the induction of reperfusion. However, no effect on tissue oxidative stress was demonstrated. Conclusion: Sildenafil, lazaroid U-74389G maleate, and their combination led to a significant amelioration of both systemic and pulmonary tissue-specific inflammatory responses. Notably, they did not exert any significant effect against tissue oxidative stress in this model. Human mechanistic studies are required to confirm these observations.

Relation Between Coronary Plaque Composition Assessed by Intravascular Ultrasound Virtual Histology and Myocardial Ischemia Assessed by Quantitative Flow Ratio

Coronary plaque composition may play an important role in the induction of myocardial ischemia. Our objective was to further clarify the relation between coronary plaque composition and myocardial ischemia in patients with chest pain symptoms. The study population consisted of 103 patients who presented to the outpatient clinic or emergency department with chest pain symptoms and were referred for diagnostic invasive coronary angiography. Intravascular ultrasound virtual histology was used for the assessment of coronary plaque composition. A noncalcified plaque was defined as a combination of necrotic core and fibrofatty tissue. Quantitative flow ratio (QFR), which is a coronary angiography-based technique used to calculate fractional flow reserve without the need for hyperemia induction or for a pressure wire, was used as the reference standard for the evaluation of myocardial ischemia. Coronary artery plaques with QFR of ≤0.80 were considered abnormal-that is, ischemia-generating. In total, 149 coronary plaques were analyzed, 21 of which (14%) were considered abnormal according to QFR. The percentage of noncalcified tissue was significantly higher in plaques with abnormal QFR (38.2 ± 6.5% vs 33.1 ± 9.0%, p=0.014). After univariable analysis, both plaque load (odds ratio [OR] per 1% increase 1.081, p <0.001) and the percentage of noncalcified tissue (OR per 1% increase 1.070, p=0.020) were significantly associated with reduced QFR. However, after multivariable analysis, only plaque load remained significantly associated with abnormal QFR (OR per 1% increase 1.072, p <0.001). In conclusion, the noncalcified plaque area was significantly higher in hemodynamically significant coronary lesions than in nonsignificant lesions. Although an increase in the noncalcified plaque area was significantly associated with a reduced QFR, this association lost significance after adjustment for localized plaque load.

Dexmedetomidine protects against myocardial ischaemia/reperfusion-induced renal damage in rats

BackgroundMyocardial ischaemia/reperfusion (MI/R) may induce renal damage. Our aim was to investigate the effects of dexmedetomidine (DEX) administration at two different timings either before or after ischaemia on renal damage induced by MI/R.MethodsMI/R injury was induced in a rat model. we ligated the left anterior descending coronary artery for 30min (ischaemic period), then reperfusion occurred for 2h (reperfusion period). A single dose of DEX (100µg/kg) was given intraperitoneally, either 30min before myocardial ischaemia or 5min after reperfusion. With the end of reperfusion period, rats were sacrificed, then we collected the blood and removed both kidneys quickly for biochemical and histopathological analysis.ResultsMI/R caused an elevation in serum urea and creatinine, significant elevation in malondialdehyde (MDA) release and decrease in superoxide dismutase (SOD) activity in the rat kidney. There were also higher levels of serum tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β). Treatment with dexmedetomidine, 30min before induction of myocardial ischaemia, succeeded to improve all the tested parameters. The valuable changes in these biochemical parameters were linked with similar enhancement in the histopathological appearance of the kidney. Meanwhile, DEX given 5min after reperfusion improved serum urea and creatinine only.ConclusionThese findings imply that MI/R plays a fundamental role in kidney damage through increased production of oxygen radicals or deficiency in antioxidants, and DEX given before ischaemia exerts reno-protective effects probably by its radical scavenging antioxidant activity and anti-inflammatory mechanism.

Myocardial and Peripheral Ischemia Causes an Increase in Circulating Pregnancy-Associated Plasma Protein-A in Non-atherosclerotic, Non-heparinized Pigs.

The usefulness of circulating pregnancy-associated plasma protein-A (PAPP-A) as a biomarker for acute coronary syndrome (ACS) is widely debated. We used the pig as a model to assess PAPP-A dynamics in the setting of myocardial ischemia. Induction of myocardial ischemia by ligation of the left anterior descending (LAD) coronary artery caused a systemic rise in PAPP-A. However, the ischemic myocardium was excluded as the source of PAPP-A. Interestingly, induction of ischemia in peripheral tissues by ligation of the left femoral artery caused a systemic rise in PAPP-A originating from the left hind limb. This is the first study to demonstrate PAPP-A elevations in the absence of atherosclerosis or heparin during myocardial ischemia. Our findings thus add to the current discussion of the usefulness of PAPP-A as a biomarker for ACS.

The effect of levosimendan on lung damage after myocardial ischemia reperfusion in rats in which experimental diabetes was induced

BackgroundIt is known that diabetic complications and lipid peroxidation are closely associated. During ischemia and reperfusion (IR), injury may occur in distant organs, as well as in tissues next to the region exposed to the ischemia, and the lungs can be one of the most affected of these organs. Therefore, this study investigated the effects of levosimendan on lung tissue and the oxidant–antioxidant system in diabetic rats. Materials and methodsThe study was conducted in 24 Wistar albino rats that were separated into four groups (C, control; DC, diabetic control; DIR, diabetic IR; and DIRL, diabetic IR levosimendan). Diabetes was induced in 18 rats using streptozotocin (55 mg/kg), and the animals were randomly separated into three groups after the effects of the diabetes became apparent. After a left thoracotomy, ischemia was performed on the myocardial muscle with the left main coronary artery (LAD) for 30 min in the DIR and DIRL groups. After ischemia, the LAD ligation was removed, and reperfusion was applied for 120 min. Single-dose intraperitoneal 12 μg/kg levosimendan was administered to group DIRL before the ischemia. Group DC was evaluated as the diabetic control group, and six rats were considered to be the control group (group C), in which thoracotomy was performed and then closed with no induction of myocardial ischemia. We measured the levels of malondialdehyde, as a lipid peroxidation end product, as well as catalase and glutathione S-transferase activities, as antioxidant enzymes in the lung tissue. Tissue samples were also examined histopathologically. ResultsNeutrophil infiltration or aggregation in lung tissue was significantly higher in the DIR group compared with the C, DC, and DIRL groups (P = 0.003, P = 0.026, and P = 0.026, respectively). Alveolar wall thickening in lung tissue was significantly higher in the DIR group compared with the C, DC, and DIRL groups (P = 0.002, P = 0.002, and P = 0.006, respectively). In addition, the lung tissue damage score was significantly higher in the DIR group compared with the C, DC, and DIRL groups (P = 0.001, P = 0.004, and P = 0.007, respectively). Finally, catalase and glutathione S-transferase activity levels were significantly higher in the DIR group compared with those observed in the C, DC, and DIRL groups. ConclusionsAlthough diabetes increases lipid peroxidation, it suppresses antioxidant activity. Our results showed that levosimendan had a protective effect against lung damage secondary to IR in the rats with induced diabetes. We recommend that experimental and clinical studies be conducted to examine the effects of levosimendan at different doses and different IR durations on various organs for clinical use.

Release kinetics of early ischaemic biomarkers in a clinical model of acute myocardial infarction

ObjectiveTo determine the release kinetics of different biomarkers with potential as novel early ischaemic biomarkers in patients with acute coronary syndrome (ACS); it is difficult to establish the detailed release...

Impaired post-infarction cardiac remodeling in chronic kidney disease is due to excessive renin release

The complex pathophysiological interactions between heart and kidney diseases are collectively known as cardiorenal syndrome. The renin–angiotensin system (RAS) may have a pivotal role in the development of cardiorenal syndrome. The aim of this study was to elucidate the RAS activity responsible for adverse post-infarction remodeling and prognosis in mice with renal failure. To establish the type IV cardiorenal syndrome model, 5/6 nephrectomy (NTX) was performed in a surgical procedure, followed by the induction of myocardial ischemia (MI) by a coronary artery ligation 4 weeks later. NTX and MI resulted in deteriorated left ventricular remodeling and RAS activation, which was improved by an aliskiren that appeared to be independent of renal function and blood pressure (BP). Moreover, MI induced in renin and angiotensinogen double-transgenic (Tg) mice showed comparable effects to MI plus NTX mice, including advanced ventricular remodeling and enhancement of RAS, oxidative stress, and monocytes chemoattractant protein (MCP)-1. Aliskiren suppressed these changes in the MI-induced Tg mice. In in vitro study, Nox2 expression was elevated by the stimulation of plasma from NTX mice in isolated neonatal cardiomyocytes. However, Nox2 upregulation was negated when we administered plasma from aliskiren-treated-NTX mice or isolated cardiomyocytes from AT1-deficient mice. Primary mononuclear cells also showed an upregulation in the expression of Nox2 and MCP-1 by stimulation with plasma from NTX mice. Our data suggest that renal disorder results in ventricular dysfunction and deteriorates remodeling after MI through excessive RAS activation. Moreover, renin inhibition improved the changes caused by cardiorenal syndrome.

Regulation of Hepatic Cell Mobilization in Experimental Myocardial Ischemia

Myocardial ischemia induces cardiomyocyte injury and death, resulting in impairment of cardiac function. The adult cardiomyocytes possess a limited capacity of protection in myocardial ischemia, and nonmyocytic cells can be activated to support myocardial protection. We recently demonstrated that hepatic cells were able to upregulate genes encoding secreted proteins and were mobilized to the circulatory system, potentially contributing to myocardial protection against ischemic injury. In this investigation, we tested the potential mechanisms by which hepatic cells were mobilized in experimental myocardial ischemia. Following the induction of myocardial ischemia, hepatic cells, including hepatocytes and biliary epithelial cells, were mobilized to the circulatory system with a peak population 1.9 ± 0.4% at day 5. The cytokine IL-6 was upregulated in the ischemic myocardium as well as the serum. IL-6 promoted leukocyte retention in the liver as demonstrated by an increase in liver-retained leukocytes in myocardial ischemia in wild type mice, reduced leukocytes in IL-6−/− mice, and restoration of leukocyte retention in response to IL-6 administration to IL-6−/− mice. Liver-retained leukocytes exhibited upregulation of MMP-2, which in turn mediated hepatic cell mobilization by degrading extracellular matrix. These observations suggest that IL-6-stimulated leukocytes mediate the mobilization of hepatic cells via releasing MMP-2 in myocardial ischemia.

PI3K/Akt signaling pathway involved in cardioprotection of preconditioning with high mobility group box 1 protein during myocardial ischemia and reperfusion

Fifty-four male Sprague–Dawley (SD) rats (250–300 g) were randomly assigned into 5 groups receiving the following treatments: Group 1: Sham-operated control (SO) (n=6): rats were treated with phosphate bufferedsaline (PBS) before 24 h and then subjected to surgical manipulation without the induction of myocardial ischemia. Group 2: Ischemia and reperfusion (I/R) (n=12): rats were treated with phosphate buffer (PBS) before 24 h and then subjected to the left anterior descending coronary artery occlusion for 30 min followed by reperfusion for 4 h. Group 3: High mobility group box 1 protein (HMGB1)+I/R (HMGB1−I/R) (n=12): rats were treated with HMGB1 (200 μg/kg, ip, Sigma, USA) 24 h before ischemia, and then ischemia 30 min followed by a 4 h reperfusion, HMGB1 was dissolved in PBS. Group 4: HMGB1+LY294002+I/R (HMGB1−LY−I/R) (n=12): after rats treated with HMGB1 24 h (200 μg/kg, ip) before ischemia, LY294002 (0.3 mg/kg, a PI3K inhibitor, iv, Sigma, USA) was injected 10 min before ischemia, and then ischemia 30 min followed by a 4 h reperfusion, LY294002 was dissolved in dimethyl sulfoxide (DMSO). Group 5: LY+I/R (LY−I/R) (n=12): LY294002 (0.3 mg/kg, iv) was injected 10 min before ischemia, and then ischemia 30 min followed by a 4 h reperfusion.

Cardioprotective effect of MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one) during acute ischemia-reperfusion injury in rats

MCI-186 (3-methyl-1-phenyl-2-pyrazolin-5-one), a free radical scavenger, has the ability to stimulate prostacyclin release and to inhibit the lipoxygenase pathway in the arachidonic acid cascade. The authors investigated the cytoprotective effect of MCI-86 in a reperfusion model of myocardial ischemia. Rats were subjected to occlusion of the left coronary artery for ten minutes followed by reperfusion for twenty-four hours. The loss of myocardial creatine kinase activity (CK) from the left ventricular free wall (LVFW) twenty-four hours after the induction of myocardial ischemia was used as an index of ischemic damage. Administration of MCI-186 (3 mg/kg IV) significantly blunted the depletion of LVFW-CK activity when compared with vehicle (MCI-186 vs vehicle, 31.5 ± 1.1 vs 26.5 ± 1.2 U/mg protein, respectively,p<0.01). In another group of rats that underwent coronary artery occlusion—reperfusion, infarct size was measured by planimetry on histologic sections of serial slices of the left ventricle and was found to be 20.0 ± 1.3% of the left ventricle in vehicle-treated rats and 10.7 ± 1.3% in MCI-186 (3 mg/kg)-treated rats (p<0.01). These results indicate the potential usefulness of MCI-186 in myocardial ischemia-reperfusion injury.

Electromagnetic Field at 15.95–16 Hz is Cardio Protective Following Acute Myocardial Infarction

Previous studies have shown that pre-exposure of the heart to weak magnetic field reduces infarct size shortly after induction of myocardial ischemia. To investigate the role of AC magnetic field with a frequency of 15.95-16 Hz and 80 mT on left ventricular (LV) remodeling following chronic coronary occlusion and a short episode of ischemia followed by reperfusion (I/R). LV dimension and function were measured using echocardiography. Femur bone marrow was isolated and cells were phenotyped for endothelial linage and immuno stained for endothelial cells. The area at risk was measured using triphenyltetrazolium chloride staining. A significant reduction of 27% in shortening fraction (SF) was measured following acute myocardial infarction (AMI) compared with a 7% decrease in animals exposed to magnetic field (p < 0.04). A significantly higher number of colony forming units and endothelial progenitor cells were counted within the treated groups subjected to magnetic field (p < 0.02). Exposing the heart to magnetic field prior to reperfusion did not show any preservation either on SF or on infarct size. Magnetic field was protective in the AMI but not in the I/R model. The mechanisms underlying cardiac protection induced by AC magnetic field following chronic injury deserves further investigation.

Focus on ivabradine: a new heart rate-controlling drug

Angina pectoris is a cardiac condition characterized by an insufficient perfusion to meet myocardial metabolic demand. A high heart rate represents an important factor in the induction of myocardial ischemia and subsequent angina. β-blocker drugs are effective at reducing angina pectoris by decreasing the heart rate and are usually preferred as initial therapy in the absence of contraindication or intolerance. Ivabradine, a new oral drug for the symptomatic treatment of chronic stable angina pectoris, decreases the resting heart rate of patients with normal sinus rhythm. In many clinical trials, ivabradine has been directly compared with placebo, β-blocker drugs (e.g., atenolol and propranolol) and calcium channel blockers (e.g., amlodipine). These studies have demonstrated ivabradine, given in doses of 5–10 mg twice daily, to be more effective than placebo for increasing time to angina onset and noninferior to atenolol 50–100 mg daily and amlodipine 10 mg daily for increasing total exercise duration in patients with chronic stable angina. Visual symptoms, a transient, enhanced brightness in a limited area of the visual field known as luminous phenomena or phosphenes, were the most common adverse effects in clinical trials. This article aims to provide a research update regarding this new drug, based on a literature search.

Does Induction of Myocardial Ischaemia by Dipyridamole Mimic Physiological Stress?

Does Induction of Myocardial Ischaemia by Dipyridamole Mimic Physiological Stress?

Reducing the Risk of Myocardial Revascularization: Relevance of Multimodal Brain Monitoring

Perioperative neurologic events in heart surgery are the most devastating complications. Although myocardial revascularization without cardiopulmonary bypass (CPB) has reduced the incidence of cerebrovascular accidents, they still remain a reality that the cardiothoracic surgeon is unable to completely eliminate. The events leading to a neurologic complication are related to hemodynamic instability and embolization of aortic debris at the time a side-biting clamp is applied. Combined events may eventually impact the brain to varying degrees, ranging from a temporary confusional state to a full-blown stroke from which meaningful recovery may be impossible. This report describes the interventions necessary to maintain hemodynamic stability, the role of brain monitoring required, and how to safely achieve complete off-CPB myocardial revascularization and minimize the incidence of neurologic complications. Cardiac interventions include maintaining sinus rhythm, providing adequate blood supply to all vital organs, and avoiding induction of myocardial ischemia, which may induce supraventricular, ventricular arrhythmias, or both. These interventions depend upon an experienced surgical team (anesthesiologist, cardiologist, surgeon, and operating room and intensive care unit recovery nurses). Anticipation of myocardial ischemia may require loading the patient with antiarrhythmic drugs, and placement of intracoronary shunts and intraaortic balloon pump support. Patience from the surgeon is often required to allow time for the specific intervention to act. In addition to interventions to maintain a balance between the demand and supply of oxygen, we frequently rely on "intermittent hypotensive anesthesia'' while performing the distal and proximal coronary anastomoses. Hypotension may lead to inadequate oxygen supply to the brain, so multimodal brain monitoring becomes mandatory. We use a combination of transcranial brain oximetry and electroencephalographic compressed spectral array. This combined monitoring results in a safer surgical procedure, allowing the hemodynamic interventions to be performed rationally and without interruption of the surgical procedure.

18F-labelled annexin V: a PET tracer for apoptosis imaging.

Annexin V can be used to detect apoptotic cells in vitro and in vivo, based on its ability to identify extracellular phosphatidylserine, which arises during apoptosis. In the present study, we examined the synthesis of fluorine-18 labelled annexin V as a positron emission tomography tracer for apoptosis imaging. The distribution of [18F]annexin V and technetium-99m labelled annexin V, a well-characterised SPET tracer for apoptosis imaging, was compared. [18F]annexin V was synthesised using N-succinimidyl 4-[18F]fluorobenzoate as an 18F labelling reagent. Synthesised and purified [18F]annexin V was confirmed by SDS-PAGE. In an ex vivo imaging experiment, [18F]annexin V was intravenously injected into rats 24 h after the induction of myocardial ischaemia, and accumulation in the left ventricle was examined. [18F]annexin V accumulated in the infarct area of the left ventricle, where apoptotic cells were observed. In separate experiments, [18F]annexin V or [(99m)Tc]annexin V was intravenously injected into ischaemic or normal animals, and the distribution of the tracers was compared. In ischaemic animals, accumulation of [18F]annexin V and [(99m)Tc]annexin V in the infarct area was about threefold higher than in the non-infarct area. Furthermore, the ratio of accumulation in the normal heart to the blood radioactivity was not significantly different between the tracers. In normal animals, however, the uptake of [18F]annexin V in the liver, spleen and kidney was much lower than that of [(99m)Tc]annexin V. The low uptake of [18F]annexin V in these organs might represent an advantage over [(99m)Tc]annexin V.

Terrorism and the heart: implications for arrhythmogenesis and coronary artery disease.

The destruction of the World Trade Center and associated terrorist activities of September 11, 2001 have spurred interest in understanding the medical consequences of terrorist activity. Currently, there is a paucity of data regarding this subject. Potential effects, however, can be garnered by studying the medical effects of other acute stressors, such as earthquakes, missile attacks, and the like. None of these stressors have been studied extensively, but there is enough data available concerning earthquakes to indicate that in some instances, the effects of the earthquake may last at least a period of weeks, if not months, following the earthquake. Since the World Trade Center attack was associated with a rise in post-traumatic stress syndrome and affective disorders afterwards, there is accordingly interest in both the acute and more prolonged health effects that could be engendered following terrorist attacks. Known pathophysiological effects of acute stress, whether produced in a laboratory environment or by studying naturally occurring acute stressors, include: the induction or potentiation of cardiac arrhythmias; the induction of myocardial ischemia in susceptible patients with underlying coronary artery disease; acute increases in arterial blood pressure with its ability to cause shear stress; the precipitation of worsening endothelial function and/or endothelial injury; coagulation abnormalities; and hemoconcentration. These all represent important areas for study following the occurrence of future terrorist activity. Based on existing epidemiological and pathophysiological data concerning the cardiac effects of acute life stressors, it would behoove physicians to closely monitor high-risk cardiac patients following future terrorist events. In addition, physician-scientists should be well prepared to use new epidemiological markers which could provide rapid information following future events, such as the evaluation of patients using pre-versus post-event serum markers or tracing records available among patients fitted with implantable cardiovertor-defibrillators.

Therapeutic Potential of Ex Vivo Expanded Endothelial Progenitor Cells for Myocardial Ischemia

We investigated the therapeutic potential of ex vivo expanded endothelial progenitor cells (EPCs) for myocardial neovascularization. Peripheral blood mononuclear cells obtained from healthy human adults were cultured in EPC medium and harvested 7 days later. Myocardial ischemia was induced by ligating the left anterior descending coronary artery in male Hsd:RH-rnu (athymic nude) rats. A total of 10(6) EPCs labeled with 1,1'-dioctadecyl-1 to 3,3,3',3'-tetramethylindocarbocyanine perchlorate were injected intravenously 3 hours after the induction of myocardial ischemia. Seven days later, fluorescence-conjugated Bandeiraea simplicifolia lectin I was administered intravenously, and the rats were immediately killed. Fluorescence microscopy revealed that transplanted EPCs accumulated in the ischemic area and incorporated into foci of myocardial neovascularization. To determine the impact on left ventricular function, 5 rats (EPC group) were injected intravenously with 10(6) EPCs 3 hours after ischemia; 5 other rats (control group) received culture media. Echocardiography, performed just before and 28 days after ischemia, disclosed ventricular dimensions that were significantly smaller and fractional shortening that was significantly greater in the EPC group than in the control group by day 28. Regional wall motion was better preserved in the EPC group. After euthanization on day 28, necropsy examination disclosed that capillary density was significantly greater in the EPC group than in the control group. Moreover, the extent of left ventricular scarring was significantly less in rats receiving EPCs than in controls. Immunohistochemistry revealed capillaries that were positive for human-specific endothelial cells. Ex vivo expanded EPCs incorporate into foci of myocardial neovascularization and have a favorable impact on the preservation of left ventricular function.

Nonexercise stress transthoracic echocardiography: transesophageal atrial pacing versus dobutamine stress

ObjectivesTo compare transesophageal atrial pacing stress echocardiography with dobutamine stress echocardiography for feasibility, safety, duration, patient acceptance and concordance in inducing wall motion abnormalities.BackgroundTransesophageal atrial pacing is an effective method of increasing heart rate and has been used in the assessment of coronary artery disease.MethodsBoth tests were performed in sequence on the same patients in random order. Transesophageal atrial pacing stress echocardiography began at a heart rate of 10 beats/min above the baseline value and was increased by 20 beats/min every two min until 85% of the age-predicted maximum heart rate or another end point was reached. Dobutamine echocardiography was performed using three-min stages and a maximum dose of 40 μg/kg per min. Atropine (total dose ≤2 mg) was administered at the start of the 40 μg/kg per min stage if needed to augment heart rate or during pacing if Wenckebach heart block occurred.ResultsTransesophageal atrial pacing stress echocardiography was feasible in 100 of 104 patients (96%); the duration (8.6 ± 3.6 min) was significantly shorter than that of dobutamine stress echocardiography (15.1 ± 3.9 min) (p = 0.0001). With transesophageal atrial pacing stress echocardiography, the recovery period was shorter, symptoms and dysrhythmias were fewer, hypertension and hypotension were less common and target heart rate was more frequently achieved. No complications occurred with either test. Patient acceptance was satisfactory. Agreement between results of both tests was good for segmental wall motion scoring with a 16-segment model, scores 1 to 5 (kappa: rest, 0.79; peak, 0.57) and test interpretation (normal, ischemia, infarction or resting wall motion abnormality with ischemia) (kappa: 0.77).ConclusionsTransesophageal atrial pacing stress echocardiography is a feasible, well-tolerated alternative to dobutamine stress echocardiography. It can be performed rapidly and shows good agreement with dobutamine stress echocardiography in the induction of myocardial ischemia.

Inhibition of nitric oxide synthesis aggravates myocardial ischemia in hemorrhagic shock in constant pressure model.

In hemorrhagic shock (HS), nitric oxide synthase (NOS) inhibitor is known to increase blood pressure and prolong survival time. On the other hand, NOS inhibitor decreases coronary flow and worsens myocardial ischemia. Therefore, we hypothesized that the beneficial effect of NOS inhibitor is attributable to the increased coronary perfusion pressure and that it outcompetes the coronary vasodilating effects of nitric oxide. To investigate the direct effect of NOS inhibitor on the regulation of coronary circulation and the induction of myocardial ischemia in HS, we used a canine model at a constant aortic pressure of 40 mmHg with an aortic reservoir. In seven dogs, intravenous administration of Nomega-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg) at 10 min after induction of HS increased both systemic and coronary vascular resistances and further increased the serum catecholamine concentration at 10 min after L-NAME. In another 14 dogs, the beating hearts were rapidly cross-sectioned (120 ms) and freeze clamped (-190 degrees C) by a specially developed sampling device after 10 min of HS. Transmurally distributed myocardial ischemia was visualized by the enhanced reduced nicotinamide adenine dinucleotide fluorescence, which was significantly increased with L-NAME (n=7). Chemical analysis revealed a decrease in the myocardial ATP concentration with L-NAME in the subendocardial ischemic region in HS. In conclusion, with the use of an aortic reservoir to keep the aortic pressure constant in HS, NOS blockade significantly worsened myocardial ischemia by decreasing coronary flow and augmenting the serum catecholamine concentration.