Myocardial Malfunction Research Articles

A Review on Cardiac Biomarkers Detection for Heart Failure Prognosis

Nowadays, problems in healthcare sector seem to be more crucial than ever. Among these, cardiovascular diseases (CVDs) play an important role, being for years a major threat to human health. In a bid to reduce the number of deaths due to heart diseases by taking precautions, science has turned to the development of devices able to offer early diagnosis of a heart failure. Recently, many biosensors have been developed based on cardiac biomarkers that can be detected in blood and predict the risk of heart failure. Of these, cardiac troponin is the best known, while C-reactive protein and myoglobin have also been used. Troponin is a complex of proteins found in the thin filaments of striated muscles and consists of three protein subunits, I, C and T. In case of myocardial malfunction, troponin is released into the blood. Consequently, the detection of elevated troponin levels at an early stage in human serum, is an indication of high risk of cardiovascular event enabling early medical intervention and treatment. In the present work, after the analysis of heart diseases, medical tests, troponin and its role in controlling myocardial health, there is an overview of the available biosensor platforms for cardiac biomarkers detection.

A molecular explanation of cardiovascular protection through abnormal cannabidiol: Involving the dysfunctional β-adrenergic and ATP-sensitive K+ channel activity in cardiovascular compromised preterm infants.

Growing cannabis efficacy, usage frequency, legal supply, and declining awareness of danger recently led to expanded United States cannabis exposure. In turn, cannabis use among elderly people over 50 has more than tripled in a decade and has contributed toward a positive association of cannabis use with pathological conditions, which include type II diabetes, metabolic syndrome, neurovascular and cardiovascular disease. Remarkably, all these outcome results are mediated by the involvement of the ATP-sensitive K+ channel. Cardiovascular compromise is a common syndrome in preterm infants that leads to incidence and death and has been distinguished by poor systemic flow or hypotension. Conditions of cardiovascular compromise include vasodysregulation and myocardial malfunction through dysfunctional β-adrenergic activity. To avoid organ hypoperfusion progressing to tissue hypoxia-ischemia, inotropic drugs are used. Many premature children, however, respond insufficiently to inotropic activity with adrenergic agonists. The clinical disturbance including myocardial dysfunction through the activation of the ATP-sensitive K+ channel is often involved and the comparative efficacy of the nonpsychotropic cannabinoid, abnormal cannabidiol(Abn-CBD) is not yet known. Therefore, our primary aim was to investigate the molecular exploration of the cannabinoid system specifically Abn-CBD in cardiovascular protection involving dysregulated KATP.

New thoughts in mechanism research of acupuncture for myocardial stunning from κ-opioid receptor signaling pathway

By reviewing the literature regarding the development mechanism of myocardial stunning, effects of acupuncture on myocardial ischemic injury, and correlation between acupuncture and κ-opioid receptor, it was suggested that acupuncture was highly likely to act on κ-opioid receptor in myocardial cells, and directly treated myocardial malfunction induced by myocardial stunning through κ-opioid receptor and its signaling pathway. In addition, acupuncture could inhabit the signaling pathway of adrenoceptor β1, one of the main functional receptors, to indirectly improve myocardial ischemic injury. From κ-opioid receptor signaling pathway, the action mechanism of acupuncture for prevention and treatment of myocardial stunning was discussed in this paper, hoping to provide new ideas for possible mechanism of acupuncture for myocardial ischemic injury.

Assessment of Myofilament Ca2+ Sensitivity Underlying Cardiac Excitation-contraction Coupling.

Heart failure and cardiac arrhythmias are the leading causes of mortality and morbidity worldwide. However, the mechanism of pathogenesis and myocardial malfunction in the diseased heart remains to be fully clarified. Recent compelling evidence demonstrates that changes in the myofilament Ca(2+) sensitivity affect intracellular Ca(2+) homeostasis and ion channel activities in cardiac myocytes, the essential mechanisms responsible for the cardiac action potential and contraction in healthy and diseased hearts. Indeed, activities of ion channels and transporters underlying cardiac action potentials (e.g., Na(+), Ca(2+) and K(+) channels and the Na(+)-Ca(2+) exchanger) and intracellular Ca(2+) handling proteins (e.g., ryanodine receptors and Ca(2+)-ATPase in sarcoplasmic reticulum (SERCA2a) or phospholamban and its phosphorylation) are conventionally measured to evaluate the fundamental mechanisms of cardiac excitation-contraction (E-C) coupling. Both electrical activities in the membrane and intracellular Ca(2+) changes are the trigger signals of E-C coupling, whereas myofilament is the functional unit of contraction and relaxation, and myofilament Ca(2+) sensitivity is imperative in the implementation of myofibril performance. Nevertheless, few studies incorporate myofilament Ca(2+) sensitivity into the functional analysis of the myocardium unless it is the focus of the study. Here, we describe a protocol that measures sarcomere shortening/re-lengthening and the intracellular Ca(2+) level using Fura-2 AM (ratiometric detection) and evaluate the changes of myofilament Ca(2+) sensitivity in cardiac myocytes from rat hearts. The main aim is to emphasize that myofilament Ca(2+) sensitivity should be taken into consideration in E-C coupling for mechanistic analysis. Comprehensive investigation of ion channels, ion transporters, intracellular Ca(2+) handling, and myofilament Ca(2+) sensitivity that underlie myocyte contractility in healthy and diseased hearts will provide valuable information for designing more effective strategies of translational and therapeutic value.

A Central Role for Monocyte-Platelet Interactions in Heart Failure.

Heart failure (HF) is an increasingly prevalent and costly multifactorial syndrome with high morbidity and mortality rates. The exact pathophysiological mechanisms leading to the development of HF are not completely understood. Several emerging paradigms implicate cardiometabolic risk factors, inflammation, endothelial dysfunction, myocardial fibrosis, and myocyte dysfunction as key factors in the gradual progression from a healthy state to HF. Inflammation is now a recognized factor in disease progression in HF and a therapeutic target. Furthermore, the monocyte-platelet interaction has been highlighted as an important pathophysiological link between inflammation, thrombosis, endothelial activation, and myocardial malfunction. The contribution of monocytes and platelets to acute cardiovascular injury and acute HF is well established. However, their role and interaction in the pathogenesis of chronic HF are not well understood. In particular, the cross talk between monocytes and platelets in the peripheral circulation and in the vicinity of the vascular wall in the form of monocyte-platelet complexes (MPCs) may be a crucial element, which influences the pathophysiology and progression of chronic heart disease and HF. In this review, we discuss the role of monocytes and platelets as key mediators of cardiovascular inflammation in HF, the mechanisms of cell activation, and the importance of monocyte-platelet interaction and complexes in HF pathogenesis. Finally, we summarize recent information on pharmacological inhibition of inflammation and studies of antithrombotic strategies in the setting of HF that can inform opportunities for future work. We discuss recent data on monocyte-platelet interactions and the potential benefits of therapy directed at MPCs, particularly in the setting of HF with preserved ejection fraction.

Pediatric cardiogenic shock: Current perspectives

Cardiogenic shock is a pathophysiologic state where an abnormality of cardiac function is responsible for the failure of the cardiovascular system to meet the metabolic needs of the body tissues.Though it is less common than hypovolemia as the primary etiology in paediatric shock, eventually myocardial function is affected because of reduced perfusion in all forms of shock. Myocardial malfunction, in other forms of shock, is secondary to ischemia, acidosis, drugs, toxins or inflammation. Cardiogenic shock is a low output state characterized by elevated filling pressures, neurohormonal activation with the evidence of end-organ hypoperfusion. The management is challenging and consists of a combination of conventional cardio-respiratory support, vasoactive medications with correction of the anatomic cardiac defects. Treatment options like Extracorporeal membrane oxygenation and Ventricular assist devices provide a bridge to recovery, surgery or transplant. As cardiogenic shock in children carries a high risk of morbidity and mortality, emphasis should be placed on expedient management to arrest the pathophysiological cascade and avoid hypotension.This article aims to review the aetio-pathophysiological basis of pediatric cardiogenic shock, diagnostic options, recent advances in management modalities and outcome.

Andrographolide Attenuates LPS-Induced Cardiac Malfunctions Through Inhibition of IκB Phosphorylation and Apoptosis in Mice

Background/Aims: Cardiac malfunction is a common complication in sepsis and significantly increases the mortality of patients in septic shock. However, no studies have examined whether andrographolide (And) reduces LPS-induced myocardial malfunction. Methods: Left ventricular systolic and diastolic functions were examined using echocardiography. TNF-a and IL-1ß protein levels were detected by an enzyme-linked immunosorbent assay (ELISA). NO oxidation products were determined using Griess reagent. Protein expression levels of inhibitors of NF-κBa (IκB) and phospho-IκB were determined via Western blot. Oxidative injury was determined by measuring myocardial lipid peroxidation and superoxide dismutase activity. Cardiac apoptosis was examined by terminal deoxynucleotidyl transferase-mediated dUTP nickend-labeling (TUNEL) and cardiac caspase 3/7 activity. Results: And blunted LPS-induced myocardial malfunctions in mice. LPS induced TNF-a, IL-1ß, and NO production as well as I-κB phosphorylation. Cardiac apoptosis was attenuated via incubation with And, but the extent of oxidative injury remained unaffected. Conclusion: And prevents LPS-induced cardiac malfunctions in mice by inhibiting TNF-a, IL-1ß, and NO production, IκB phosphorylation, and cardiac apoptosis, indicating that And may be a potential agent for preventing myocardial malfunction during sepsis.

βARKct: A Therapeutic Approach for Improved Adrenergic Signaling and Function in Heart Disease

One of the most powerful regulators of cardiovascular function is catecholamine-stimulated adrenergic receptor (AR) signaling. The failing heart is characterized by desensitization and impaired beta-AR responsiveness as a result of upregulated G protein-coupled receptor kinase-2 (GRK2) present in injured myocardium. Deterioration of cardiac function is progressively enhanced by chronic adrenergic over-stimulation due to increased levels of circulating catecholamines. Increased GRK2 activity contributes to this pathological cycle of over-stimulation but lowered responsiveness. Over the past two decades the GRK2 inhibitory peptide betaARKct has been identified as a potential therapy that is able to break this vicious cycle of self-perpetuating deregulation of the beta-AR system and subsequent myocardial malfunction, thus halting development of cardiac failure. The betaARKct has been shown to interfere with GRK2 binding to the betagamma subunits of the heterotrimeric G protein, therefore inhibiting its recruitment to the plasma membrane that normally leads to phosphorylation and internalization of the receptor. In this article we summarize the current data on the therapeutic effects of betaARKct in cardiovascular disease and report on recent and ongoing studies that may pave the way for this peptide towards therapeutic application in heart failure and other states of cardiovascular disease.

Cardiovascular Effects of Fine and Ultrafine Particles

Epidemiological studies of the past decades have provided a strong body of evidence that elevated levels of ambient particulate air pollution (PM) are associated with increased cardiovascular and respiratory morbidity and mortality. Exacerbations of ischemic and/or arrhythmic cardiac diseases have been linked to PM exposure. At a workshop held at the GSF- National Center for Environment and Health in November 2003, relevant epidemiological and toxicological data of the past 5 years were compiled and potential biological pathways discussed. Available clinical and experimental evidence lends support to the following mechanisms mediating cardiovascular effects of inhaled ambient particles: (i) pulmonary and/or systemic inflammatory responses inducing endothelial dysfunction, a pro-coagulatory state and promotion of atherosclerotic lesions, (ii) dysfunction of the autonomic nervous system in response to direct reflexes from receptors in the lungs and/or to local or systemic inflammatory stimuli, and (iii) cardiac malfunction due to ischemic responses in the myocardium and/or altered ion-channel functions in myocardial cells. While an increasing number of studies addressing these questions support the notion that PM exposure is associated with cardiovascular effects, these studies at present provide only a fragmentary and at times inconclusive picture of the complex biological pathways involved. The available data are consistent with the occurrence of a systemic inflammatory response and an alteration of autonomic cardiac control, but evidence on endothelial dysfunction, pro-coagulatory states, and PM-related myocardial malfunction is as yet scarce. Further studies are therefore needed to substantiate our current understanding of the pathophysiological links between PM exposure and adverse cardiovascular outcomes.

Myocardial Strain Imaging Based on Two-Dimensional Displacement Vector Measurement

The abnormalities of myocardial wall motion caused by changes in wall stiffness often appear in the early stage of ischemic heart disease. Since the myocardium exhibits complex and large motion, a two-dimensional (2D) or three-dimensional (3D) assessment of stiffness distribution is required for accurate diagnosis. Although a 3D assessment is ultimately required, as a stepped approach for practical use, we propose novel methods for tracking the 2D motion using a one-dimensional (1D) phased array and for assessing myocardial malfunction by visualizing the invariant of a strain tensor. The feasibilities of the proposed methods were evaluated by numerically simulating the short-axis imaging of a 3D myocardial model. This model includes a hard infarction located between 1 and 3 o'clock, which is difficult to detect by conventional tissue Doppler and strain rate imaging, and the motions of the model were assigned by referring to actual myocardial motion. These results revealed that the proposed imaging methods clearly depicted the hard infarction area which conventional imaging could not detect.

Choc initial du brûlé. Physiopathologie : principes thérapeutiques

Widespread destruction of the skin induces a large necrotic mass and a break of the skin barrier. It also leads to an intense inflammatory reaction. This activates keratinocytes, endothelial cells and neutrophils. Certain mediators (e.g. endothelin, histamine, bradykinin, serotonin, catecholamines, vasopressin, prostaglandins, cytokines and nitrogen monoxide) are thus released in large quantities and act both at the site of the burns and at a distance. The abnormally high level of albumin in the capillary wall and the increased capacity of absorption of the interstitial areas around the burns are the main abnormalities observed. This results in a hypovolemia associated with a hemoconcentration, hyponatremia, hypoalbuminemia, systemic vasoconstriction and myocardial malfunction, which is difficult to evidence. During the initial phase, the major risk is the appearance of hypovolemic shock, which is rapidly irreversible if early treatment is not administered. Vascular filling with iso- or hyper-osmolar sodium crystalloids, associated with buffer solutions, is the first line. There is still debate regarding the best moment at which to give albumin. A hyperkinetic shock may occur after several hours and despite the filling. The symptoms are tachycardia, increased heart rate and a dramatic decrease in systemic vascular resistance. This may lead to metabolic acidosis and multi-organ failure. Study of the hemodynamic profile of the patient allows the rational use of pressor amines and haemodialysis.

Myocardial malfunction in chronic alcoholism during controlled abstinence.

Cardiac malfunction has been described in chronic alcoholics in the absence of clinical manifestations.In an unselected group of 25 chronic alcoholics, a low ejection time index was found as expected, but this index remained low after 2 weeks of abstinence. Since the ejection time index is primarily related to stroke volume, this observation could be explained on the basis of persistently depressed myocardial function.

Studies on advanced rheumatic mitral insufficiency: clinical aspects and circulatory dynamics with special reference to their correlations.

The clinical and pathophysiological features of 41 patients with advanced pure mitral insufficiency of rheumatic origin, were investigated and statistical analysis of the hemodynamic parameters was made with special reference to their correlations. 1. A history compatible with acute rheumatic fever was obtained in 31 patients (75.6 per cent). The average age at the time of initial attack was 13.1 years and the asymptomatic intervals averaged 6.8 years. 2. Exertional dyspnea (95 per cent), palpitation (78 per cent) and excess fatigability (76 per cent) were the early and most common symptoms of the patients. 3. In addition to the loud apical pansystolic murmur constantly present, a middiastolic murmur was heard in 33 patients (.81 per cent). A third sound or diastolic gallop sound was present in over a half of the patients (56 per cent). 4. Auricular fibrillation was found in over two-thirds of the patients (68 per cent). Patients with auricular fibrillation was older and had longer duration of the disease in comparison with those of sinus rhythm. The average period since first attack of rheumatic fever or equivalents was 15 years in patients with auricular fibrillation. The majority of patients revealed electrocardiographic evidence of combined ventricular hyper-trophy (54 per cent) and right ventricular hypertrophy alone was observed in 5 per cent of patients. 5. The cardiac size as expressed by cardio-thoracic ratio ranged from 0.52 to 0.87 with an average of 0.70 and marked cardiomegaly (cardio-thoracic ratio exceeding 0.81) was noted in 7.5 per cent of the patients. Giant left atrium was present in 1 2.8 per cent of the cases. 6. The cardiac index ranged from 2.0 to 4.5 L/min/M2 BSA with an average of 3.1 and low cardiac index (less than 2.6 L/min/M2 BSA) was encountered in 37 per cent of patients. 7. The peak systolic pressure in the pulmonary artery ranged from 25 to 105 mmHg, averaging 55; the mean pressure varied from 14 to 65 with an average of 37. Moderately severe to severe pulmonary hypertension (pulmonary-systemic peak systolic ratio of over 0.7) was observed in 17 per cent of patients. The total pulmonary resistance ranged from 286 to 2, 329 dynes sec. cm-5 with an average of 81 5. The values in excess of 1, 300 dynes sec. cm-5 was noted in 17 per cent of patients. 8. The various hemodynamic parameters were analysed in relation to duration of the disease and degree of the mitral insufficiency, and factors influencing pulmonary vascular reactivity were assessed in addition. The pressure-volume relationships of the left side of the heart in rheumatic mitral insufficiency were complex. Myocardial malfunction secondary to the under-lying rheumatic process as well as to increased myocardial burden because of the presence of mitral insufficiency, size and compliance of the left atrium and presence or absence of auricular fibrillation might greatly influence and shape the total cardiac dynamics. The possible interrelationships between mitral regurgitant flow and pulmonary vascular reactivity were also discuss-ed. 9. The most reliable method for estimating the severity of mitral insufficiency was selective left ventriculography. With no exception, the severity could be graded as 3 plus or greater in a total of 30 patients in whom the diagnosis was confirmed at surgery. 10. Selected pathological findings obtained at surgery were reported and the status of rheumatic fever as well as the prevalence of cardiac involvement in this subtropical or tropical zone was sepculated.

Cardiomyopathy.

When confronted with a 400-page book dealing with cardiomyopathy, most clinicians respond with two questions: Is that much known about cardiomyopathy? If so, do I want to know that much about it? Volume 4 of the Cardiovascular Clinics Series is profusely illustrated, carefully edited, and sells for $12. It justifies an affirmative answer to both questions. Furthermore, it is a real bargain at current prices. Eighteen separate chapters are written by 22 contributing authors who are world authorities in their respective fields. Only by listing the chapter headings can the magnitude of this text be indicated: "Pathology of Cardiomyopathy," "Physiology of Idiopathic Cardiomyopathies," "Diagnosis of the Myocardial Diseases," "Electrocardiographic and Vectorcardiographic Patterns in Cardiomyopathy," "Myocardial Malfunction of Unknown Cause," "Hypertrophic Obstructive Cardiomyopathy of the Left Ventricle," "Infectious Myocarditis," "Alcoholic Cardiomyopathy," "Ischemic Cardiomyopathy: Diagnostic, Pathophysiologic, and Therapeutic Considerations," "Nutritional Heart Disease," "Toxic Agents and Cardiomyopathies," "Postpartal Cardiomyopathy," "Cardiomyopathy Associated with Systemic

Left Ventricular Function in Children Studied by Increasing Peripheral Resistance with Angiotensin

Response to angiotensin infusion was evaluated in 11 normal children and 24 patients with suspected left ventricular dysfunction. This included 12 patients with endocardial fibroelastosis, three with idiopathic myocardial hypertrophy, one with cardiac glycogenosis, and eight with the Hunter-Hurler syndrome. In 20 of these 24 patients, cardiac catheterization findings confirmed the clinical suspicion of decreased left ventricular function. In 11 instances left ventricular dysfunction was diagnosed by an elevation of resting left ventricular end-diastolic pressure. In eight instances this was ascertained by a decrease in resting left ventricular stroke work when compared to the expected range, derived by using a linear regression formula based on 24 normal subjects. In only four instances were both abnormal; that is, the resting left ventricular stroke work was decreased and the left ventricular end-diastolic pressure was increased. In five of these 20 patients, abnormal left ventricular function was elicited only on infusion of angiotensin. Thus this test is a significant adjunct in our ability to determine myocardial malfunction at cardiac catheterization.