Independency of myocardial stunning of endothelial stunning?

Background and objective Vascular endothelial cells play an important role in the control of vascular tone. The reasons for coronary endothelial dysfunction are complex and may involve ischemia/reperfusion injury. We investigated whether endothelial, smooth muscle, and myocardial dysfunction are independent phenomena. Methods Rabbit hearts were rapidly excised without intermittent ischemia, connected to a modified Langendorff apparatus, and perfused with a modified Krebs-Henseleit solution containing bovine erythrocytes. Normoxic control hearts (n = 16) were perfused for 125 min. Postischemic hearts (n = 15) were perfused for 45 min, submitted to global ischemia (20 min) and reperfused (60 min). Both the normoxic and the postischemic hearts were divided into three groups that received either 0.9% NaCl (placebo), or 3-morpholinosydnonimine (SIN-1; 100 μM),or substance P (SP; 5 nM). Results After SIN-1, CBF in the normoxic hearts was increased by maximum 63% and after SP by 62%. 60 min after the onset of reperfusion, the postischemic hearts of both groups had recovered to 95% LVP_max. In the postischemic hearts, SIN-1 increased CBF still by 58%, while the endothelium-dependent vasomotion was impaired: SP improved CBF by only 9%. Summary and conclusions The particular protocol permitted differentiation between myocardial and vascular stunning. The results show that, while myocardial function has already recovered, endothelial cells are more severely impaired than smooth muscle cells, and that this injury persists beyond myocardial stunning. Thus, endothelial-dependent dysfunction can still impair vasodilatation while ventricular dysfunction has already resolved.     

Clinical relevance of myocardial “stunning”

Summary Experimental studies have demonstrated that myocardium reperfused after reversible ischemia exhibits prolonged depression of contractile function (stunning). Despite the multiplicity of clinical situations in which myocardial stunning would be expected to occur, investigation of this phenomenon in humans has been hindered by several major problems, including the limited accuracy of the methods available to measure regional left ventricular function, the inability to quantify regional myocardial blood flow during acute ischemia, the difficulty in establishing with certainty the beginning and end of an ischemic episode, and the uncontrolled influence of variables (such as preload, afterload, adrenergic tone, and inotropic therapy) that have a major impact on postischemic dysfunction. The main problem is to discern whether a reversible defect of contractility is caused by stunning, silent ischemia, or hibernation (i.e., chronic ischemia). This differential diagnosis requires the simultaneous measurement of regional myocardial function and flow, which thus far has not been generally possible. Despite these limitations, however, numerous clinical observations suggest that stunning does occur in various settings in which the myocardium is exposed to transient ischemia, including coronary angioplasty, exercise-induced angina, angina at rest (unstable or variant), acute myocardial infarction with early reperfusion, open-heart surgery, and cardiac transplantation. Recognition of this entity is important, amongst other reasons, because it is likely to cause significant morbidity and because it is potentially correctable with inotropic therapy or even preventable with antioxidant therapy. In addition, the appreciation of the phenomenon of myocardial stunning should allow the clinician to assess the efficacy of reperfusion therapy with greater accuracy and to recognize that patients should not be denied mechanical revascularization solely because of an abnormal left ventricular wall motion. Perhaps the most intriguing clinical implication of the concept of myocardial stunning is the possibility that in patients who exhibit frequent episodes of ischemia in the same territory, the myocardium may not be able to fully recover between episodes and thus may remain reversibly depressed for prolonged periods of time, or even chronically, which could account for some cases of ischemic cardiomyopathy. Our understanding of myocardial stunning in humans is still relatively crude and will not significantly improve until studies are performed that measure simultaneously regional myocardial perfusion and function (so that stunning can be differentiated from silent ischemia and hibernation). Future important areas of research should also include the elucidation of whether stunning can become chronic and the evaluation of therapies (such as antioxidant treatments) designed to prevent this contractile abnormality. Further knowledge regarding the clinical significance of myocardial stunning will be essential to improve our understanding of the pathophysiology of coronary artery disease and our management of the adverse manifestations associated with this disorder.     

Properties of labetalol,a combined α-and β-blocking agent,relevant to the treatment of myocardial ischemia

Summary Labetalol, a combined --adrenergic antagonist, is one of the new group of -adrenergic blockers reduces peripheral and coronary vascular resistances while preserving cardiac output. Unlike -adrenergic blockers, labetalol tends to reduce heart rate during rest and exercise. The drug is a potent antihypertensive agent which has been used by mouth and by vein to treat mild, moderate, and severe hypertension, including hypertensive emergencies. Labetalol has a hemodynamic profile which makes it an attractive agent for treating myocardial ischemia. The drug reduces blood pressure, left ventricular wall tension, heart rate, and contractility while preserving or even augmenting coronary blood flow. Studies with labetalol in hypertensive patients with angina have shown it to be more effective than placebo in reducing angina attacks and blood pressure while improving exercise tolerance. The drug appears to have antianginal and antihypertensive effects comparable to atenolol and propranolol. Side effects of treatment are observed and most are related to - and -adrenergic blockade. Labetalol also appears to be effective for treatment of normotensive patients with angina and for silent myocardial ischemia. It has no apparent effects on serum lipids and lipoproteins. Labetalol appears to be a useful drug for treating the hypertensive heart and its many complications.     

Effects of Dangua recipe on myocardial ATP,PPAR-α,GLUT-4,and morphology in diabetic rats

<正>Objective To observe the effects of Dangua Recipe(DGR) on myocardial adenosine triphosphate (ATP),peroxisome proliferator-activated receptor-α(PPAR-α),glucose transporter type 4 (GLUT-4) and other related energy metabolism indicators and myocardial morphology in diabetic rats,and to provide reference for preventing     

Short-term effects of air pollution on acute myocardial infarctions in Shanghai, China, 2013–2014

Background Although particulate matter, with diameters < 2.5 μm (PM_2.5) and < 10 μm (PM₁₀), and other pollutants have been associated with cardiovascular morbidity and mortality, the effect of pollutants on acute myocardial infarctions (AMIs) has rarely been investigated in Asia, especially in Shanghai, China. Methods Between 1 November 2013 and 27 April 2014, 972 patients from the Pudong District, Shanghai City, were assessed by the Emergency Medical Service. A case-crossover design was used to analyze exposure to air pollution and the AMI risk. Exposures to PM_2.5, PM₁₀, nitrogen dioxide (NO₂), sulphurdioxide (SO₂), and carbon monoxide (CO) were based on the mean urban background levels. The associations among AMI admissions, the included pollutants, temperature, and relative humidity were analyzed using correlation and logistic regression. Results The urban background levels of PM_2.5, PM₁₀ and CO were associated with an increased risk of AMI, unlike NO₂ and SO₂ levels. The OR (95% CI) for AMI were 1.16 (1.03–1.29), 1.05 (1.01–1.16), 0.82 (0.75–1.02), 0.87 (0.63–1.95), and 1.08 (1.02-1.21) for PM_2.5, PM₁₀, NO₂, SO₂, and CO, respectively. Increases in the air quality index (AQI) were associated with more AMI occurrences. There was no correlation between fluctuations in temperature and relative humidity with AMI hospital admissions. Conclusions Short-term exposure to moderate-serious pollution levels is associated with increased risk of AMI. Increased PM_2.5, PM₁₀ and CO levels are related to increased AMI admissions.     

Recognition of an additional mechanism leading to myocardial abnormalities

See related article,pages 83-89.A growing body of evidence explicitly suggests thesignificant role of inflammatory processes in the develop-ment and progressive deterioration of vascular diseasesand cardiomyopathies.~(1-3)In recent years,a large varietyof infections have been reported to be associated with thedevelopment of cardiomyopathy;the pathogenic factors     

Roles of different types of collagens in cardiac repair after myocardial infarction

Background The cardiac extracellular matrix(ECM) undergoes ongoing modification following myocardial infarction(MI), driving the inflammation and repair response. Collagens, the major component of ECM, regulate the healing process uniquely after MI, where they are synthesized and accumulated to form scars in the infarcted area.Various types of collagens affect the repair response in different ways. Knowing the exact processes of collagen regulation can facilitate the development of new therapeut...     

Effects of rosuvastatin on ADMA,rhokinase, NADPH oxidase,caveolin-1, hsp 90 and NFkB levels in a rat model of myocardial ischaemia–reperfusion

Ischaemic heart disease remains among the major causes of morbidity and mortality worldwide. The most common form is reduction in blood flow in the coronary arteries supplying blood to the myocardium due to atherosclerotic plaques or vasospasm.1 After ischaemia, reperfusion of the tissue is of great importance for maintenance of the viability of the ischaemic tissue. However reperfusion may paradoxically lead to some morphological changes, enzyme destruction and even death of the still-viable tissue that may be rescued.2Ischaemia–reperfusion (I/R) injury is the mainstay of myocardial infarction, cerebral ischaemia, stroke, haemorrhagic shock and surgical interventions such as organ transplantation, cardiac surgery, coronary angioplasty and thrombolytic treatment-related pathophysiology.3 Endothelial dysfunction, oxidative stress and inflammation are among the most common mechanisms of I/R injury.4,5Asymmetrical dimethyl arginine (ADMA) is an endogenous nitric oxide synthase (eNOS) inhibitor. Its importance is becoming more recognised and further studies are required to determine its use in clinical diagnosis. Available evidence indicates that oxidative stress leads to changes in the activity of enzymes involved in the production and degradation of ADMA.4,5 High levels of ADMA and low levels of nitric oxide (NO) in the coronary arteries of patients with vasospastic angina have been reported.6In the cardiovascular system, NADPH oxidase accounts for the production of reactive oxygen species (ROS), which is produced not only during I/R injury but also under physiological conditions.7 The pro-oxidative NADPH oxidase is present in the plasma membranes of neutrophils, which are an important source of free radical formation and I/R injury.8 Additionally, the rhokinase pathway, which has an important role in regulation of vascular smooth muscle tone, has been shown to be involved in I/R injury, thus making its inhibition a potential target for limiting I/R injury.9It has been reported that inflammatory NFkB expression increased in the I/R-related infarct area; inflammation was suppressed when NFkB expression was inhibited, and cardiac preservation was provided.10 In this context, caveolin-1 was shown to regulate eNOS activation consistently with other signalling molecules such as hsp 90.11 Interaction of hsp 90 with eNOS increases eNOS activity, and consequently, NO production increases.12,13 Myocardial caveolin-1 content is reported to decrease following ischaemia–reperfusion.14 Caveolin-1 deficiency was noted to aggravate cardiac dysfunction and reduce the survival rate in mice that had experienced myocardial infarction (MI).15Rosuvastatin is a synthetic hydrophilic statin widely used in the treatment of dyslipidaemia, as it increases levels of highdensity lipoprotein (HDL) cholesterol, and reduces low-density lipoprotein (LDL) cholesterol and triglyceride levels. Statins have been reported to have anti-inflammatory, antiproliferative, antithrombotic, anti-atherogenic and antihypertensive effects in addition to their cholesterol-lowering effects.8,16-18 Recent studies indicate that rosuvastatin decreases levels of ADMA in hypercholesterolaemia,19 levels of caveolin,20 and also NFkB levels21 in subaracnoid bleeding.To our knowledge, the effects of rosuvastatin on ADMA, rhokinase, caveolin-1, hsp 90 and NFkB levels are not known in cardiac I/R injury. In this study, we aimed to investigate the influence of rosuvastatin on oxidative stress-related rhokinase, NADPH oxidase, ADMA, caveolin-1 and hsp 90 levels in a rat model of I/R injury.     

Inferoseptal myocardial infarction: Another cause of precordial ST-segment depression in transmural inferior wall myocardial infarction?

Electrocardiographic ST-segment depression in the anterior precordial leads is a frequent observation during the initial hospital phase of acute transmural inferior myocardial infarction (MI), but is of uncertain significance. No available clinical studies have examined the prevalence of inferoseptal necrosis complicating inferior MI. Therefore, the clinical course, electrocardiographic features, radionuclide angiograms and cardiac enzyme changes in 57 patients with transmural inferior MI who did not have prior anterior or concomitant "true posterior" MI, associated anterior or posterolateral asynergy by radionuclide ventriculography, or left or right bundle branch block were reviewed retrospectively. Patients were categorized according to the presence (group A) or absence (group B) of precordial ST-segment depression and according to the presence (group I) or absence (group II) of radionuclide septal wall motion abnormalities. There were no significant differences in global left ventricular ejection fraction (group A, 49 +/- 8, group B, 52 +/- 41; group I, 51 +/- 7, group II, 51 +/- 6), right ventricular ejection fraction (group A, 45 +/- 9, group B, 42 +/- 7; group I, 43 +/- 8, group II, 41 +/- 8), or clinical outcome in the hospital. However, chi-square analysis revealed a significant (p less than 0.05) association between the presence or absence of septal asynergy and the presence or absence of precordial ST depression. In addition, average peak creatine kinase elevation (group I, 761 +/- 164 IU; group II, 698 +/- 178 IU) attained marginal significance by paired t test (p = 0.06). Precordial ST-segment depression during transmural inferior MI is frequently associated with septal asynergy by gated radionuclide angiography (15 of 26 patients, 58%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Relation between NT-proBNP levels, iron overload, and early stage of myocardial dysfunction in β-thalassemia major patients

Background: Heart failure (HF) secondary to myocardial iron loading remains the leading cause of death in β‐thalassemia major (β‐TM) patients. The early diagnosis and treatment of HF in these patients is related to survival. We aimed to evaluate myocardial performance using conventional and tissue Doppler echocardiography and its relation to plasma NT‐proBNP levels and iron overload indices in β‐TM patients with preserved systolic function. Methods: The study population included 49 β‐TM patients (24.0 ± 4.2 years) and 48 age‐matched healthy controls. Doppler‐echocardiographic study was performed and blood samples for NT‐proBNP measurements were drawn on the third day following blood transfusion. Patients were divided as group‐1, without diastolic dysfunction: E/E′ ratio < 9 and group‐2, with suspected diastolic dysfunction: E/E′ ratio ≥ 9. Results: NT‐proBNP levels and E/E′ ratio were increased in patients compared with controls (P < 0.001 and P < 0.001) but did not correlate with each other. A strong positive correlation was detected between NT‐proBNP levels and mean ferritin levels in β‐TM patients (r_s= 0.939; P < 0.001). Median NT‐proBNP levels were significantly higher in group‐1 in comparison to controls [51.2 (41.51–113.5) vs 30.1 (17.97–68.16) ng/mL, P < 0.01]. NT‐proBNP levels were also increased in group‐2 in comparison to group‐1 but this increase was not statistically significant. Conclusion: NT‐proBNP secretion begins in the early phase of the disease before the increase in diastolic pressure becomes overt. While there was a strong correlation between the plasma NT‐proBNP levels and iron overload, there was no correlation between NT‐proBNP levels and diastolic dysfunction parameters in patients in the third decade of life. (Echocardiography 2012;29:318‐325)     

Impact of advanced age on myocardial perfusion, distal embolization, and mortality patients with ST-segment elevation myocardial infarction treated by primary angioplasty and glycoprotein IIb–IIIa inhibitors

Despite mechanical reperfusion, the outcome is still unsatisfactory in elderly patients with ST-segment elevation myocardial infarction (STEMI). The vast majority of studies have been conducted without extensive use of glycoprotein (Gp) IIb–IIIa inhibitors, which have been associated with improved perfusion and survival. Thus the aim of the current study was to evaluate the impact of age on the angiographic and clinical outcome patients with STEMI undergoing primary angioplasty with Gp IIb–IIIa inhibitors. Our population is represented by a total of 1,662 patients undergoing primary angioplasty for STEMI included in 11 randomized trials comparing early versus late administration of Gp IIb–IIIa inhibitors. Myocardial perfusion was evaluated by myocardial blush grade and ST-segment resolution. Follow-up data were collected between 30 days and 1 year after primary angioplasty. A total of 231 (13.9 %) patients were older than 75 years. Elderly patients showed a larger prevalence of female gender, hypertension, and diabetes, more advanced Killip class at presentation and longer time to treatment, but a smaller prevalence of smoking. All patients were treated with GP IIb–IIIa inhibitors. Elderly patients showed a significantly impaired postprocedural thrombolysis in myocardial infarction (TIMI) flow (TIMI 0–2: 17.7 vs 10.3 %, P = 0.002) and myocardial perfusion (myocardial blush grade 0–1: 38.3 vs 26.5 %, P = 0.001), and higher prevalence of distal embolization (19.2 vs 9.8 %, P < 0.001), whereas no difference was observed in terms of ST-segment resolution. At follow-up, elderly patients showed a significantly higher mortality (3.2 vs 11.0 %, hazard ratio (HR) (95 % confidence interval (CI)) = 3.78 (2.31–6.16), P < 0.001), which was confirmed after adjustment for baseline confounding factors (HR (95 % CI) = 5.01 (2.63–9.55), P < 0.0001). This study showed that among patients with STEMI undergoing primary angioplasty, advanced age is an independent predictor of mortality after primary angioplasty. Higher rates of distal embolization and poor myocardial perfusion, in addition to the worse risk profile, contribute toward explaining the impact of aging on mortality.