Loss Of Myocardial Contractility Research Articles

Altered microRNA dynamics in acute coronary syndrome

IntroductionIn the course of acute myocardial infarction (AMI) cardiomyocyte injury, activation and destruction of endothelial cells together with inflammation lead to miRNA expression alterations.AimTo assess levels of circulating cardiac-specific (miR-1) and endothelial-specific (miR-126) miRNAs in the acute phase of AMI and after a follow-up period.Material and methodsSeventeen AMI patients (mean age: 64.24 ±13.83 years, mean left ventricle ejection fraction (LVEF): 42.6 ±9.65%), treated with primary percutaneous coronary intervention within the first 12 h, had plasma miRNAs isolated (quantitative real-time PCR, Exiqon) on admission and after 19.2 ±5.9 weeks. Measurements were also performed in a control group of healthy volunteers matched for age and sex.ResultsConcentrations of both miRNAs were significantly higher in AMI patients as compared to healthy controls: miR-1: 5.93 (3.15–14.92) vs. 1.46 (0.06–2.96), p = 0.04; miR-126: 4.5 (3.11–7.64) vs. 0.54 (0.36–0.99), p = 0.00003, respectively. Levels of both miRNAs significantly decreased after the follow-up period: miR-1: 5.93 (3.15–14.92) vs. 1.34 (0.04–2.34), p = 0.002; miR-126: 4.5 (3.11–7.64) vs. 1.18 (0.49–1.68), p = 0.0005). Moreover, miR-1 correlated positively with maximal troponin I concentration (r = 0.59, p = 0.02) and negatively with LVEF (r = –0.76, p = 0.0004).ConclusionsIn our study, miR-1 emerged as a marker of cardiomyocyte injury and loss of myocardial contractility, whereas dynamics of miR-126 concentration may reflect endothelial activation and damage in the most extreme stage of atherosclerosis, followed by angiogenesis in ischemic myocardium. However, to fully elucidate the role of miR-1 and miR-126 as biomarkers of AMI and future therapeutic targets, further research is required.

The role of multimodal imaging in the diagnostics of non-compaction cardiomyopathy (a clinical case)

Non-compaction cardiomyopathy is a rare heart disease of non-ischemic origin, which is characterized by increased myocardial trabecularity with deep intertrabecular recessions, which contributes to increased thrombogenicity, loss of myocardial contractility and heart failure manifestation. Despite of the increasing number of publications describing this pathology during last years, this form of cardiomyopathy remains underdiagnosed and little known for a wide range of physicians. The purpose of the study was to present the role of speckle tracking echocardiography and cardiac magnetic resonance tomography in the differential diagnosis of non-compaction cardiomyopathy. Results. It was described a clinical case of a 53-year old female with intact coronary arteries, who had been followed up for ten years with a diagnosis of dilated cardiomyopathy after the detection of a left bundle branch block. When performing standard echocardiography, a two-layer structure of the myocardium was found in the apical lateral segments of the left ventricle (LV) with the presence of hypertrabeculated internal layer and diffuse decrease in global LV contractility (three-dimensional ejection fraction 34 %). There was a decrease in LV global longitudinal strain up to 12 % measured by speckle-tracking echocardiography. Analysis of segmental myocardial deformation curves in conditions of left bundle branch block revealed the most prognostically unfavorable dyssynchrony pattern. Cardiac magnetic resonance imaging confirmed the presence of hypertrabecularity with compact to non-compact layer ratio of more than 1/2,5, which verified the diagnosis of non-compaction cardiomyopathy. Conclusions . The clinical manifestations of non-compaction cardiomyopathy are non-specific, therefore instrumental criteria play an important role in the diagnosis. Cardiac magnetic resonance imaging, three-dimensional and speckle-tracking echocardiography are reliable methods for diagnostics and prediction of this disease outcomes.

Assessment of Myocardial Viability: An Effective Gatekeeper for Coronary Revascularization?

Heart failure is an emerging worldwide epidemic. In the USA alone, there are an estimated 4.8 million Americans with heart failure, 10% of persons aged 70 years or greater and 400,000 new cases annually [1]. Heart failure is the most common diagnosis in hospitalized patients aged 65 years and older. There is an exceedingly high mortality rate associated with heart failure; approximately 50% of patients diagnosed with heart failure will be dead within 5 years. As the population ages, with more cardiac patients living longer with their disease, the opportunity for developing heart failure increases. The economic costs of heart failure are substantial with an estimated US$23.2 billion society costs per year in the USA. Coronary artery disease (CAD) is the most common cause of left ventricular (LV) systolic dysfunction leading to heart failure [2]. It was previously thought that loss of myocardial contractility after myocardial infarction was caused by the destruction of myocardium and the development of irreversible scarring. With the subsequent development of coronary artery bypass grafting (CABG), clinical observations showed that in some individuals, the function of hypo or akinetic segments could improve following revascularization [3]. The contractile regional dysfunction seen in patients may be either transient (stunning) or prolonged (hibernation). In reality, the spectrum of myocardial dysfunction is probably a continuum extending from myocardial ischemia to programmed cell death and apoptosis. A proportion of patients with heart failure will confer viability by symptomatic angina or ischemia demonstrated by myocardial perfusion imaging [4]. However, most patients with LV systolic dysfunction due to CAD have a heterogeneous mixture of stunned, hibernating and scarred myocardium in various proportions. Given many considerations, it is clear that patients with heart failure due to CAD should pursue treatment options to prevent future coronary events. These therapies include treatment of heart failure, myocardial ischemia, and myocardial stunning and hibernation. Standard treatment of patients with heart failure due to LV systolic dysfunction include angiotensin-converting enzyme (ACE) inhibitors, angiotensinreceptor blockers, β-blockers and aldosterone antagonists [5–8]. Many cardiologists, and some guidelines [9], recommend evaluating patients with CAD and heart failure to identify patients suitable for coronary revascularization, although this strategy is not evidence based. It is often believed that the presence of viable but dysfunctional myocardium is an indication for revascularization, although very few patients with heart failure undergo viability testing.

Part I: Pathogenetic Role of Peroxynitrite in the Development of Diabetes and Diabetic Vascular Complications: Studies With FP15, A Novel Potent Peroxynitrite Decomposition Catalyst

Peroxynitrite is a cytotoxic oxidant formed from nitric oxide (NO) and superoxide. Tyrosine nitration, a footprint of peroxynitrite, has been demonstrated in the pancreatic islets as well as in the cardiovascular system of diabetic subjects. Delineation of the pathogenetic role of peroxynitrite in disease conditions requires the use of potent, in vivo active peroxynitrite decomposition catalysts. The aim of the current work was to produce a potent peroxynitrite decomposition catalyst and to test its effects in rodent models of diabetes and its complications. FP15 was synthesized and analyzed using standard chemical methods. Diabetes was triggered by the administration of streptozotocin. Tyrosine nitration was measured immunohistochemically. Cardiovascular and vascular measurements were conducted according to standard physiologic methods. FP15, a potent porphyrinic peroxynitrite decomposition catalyst, potently inhibited tyrosine nitration and peroxynitrite-induced cytotoxicity in vitro and in vivo. FP15 treatment (3-10 mg/kg/d) dose dependently and reduced the incidence and severity of diabetes mellitus in rats subjected to multiple low doses of streptozotocin, as well as in nonobese mice developing spontaneous autoimmune diabetes. Furthermore, treatment with FP15 protected against the development of vascular dysfunction (loss of endothelium-dependent relaxations) and the cardiac dysfunction (loss of myocardial contractility) in diabetic mice. FP15 treatment reduced tyrosine nitration in the diabetic pancreatic islets. The current results demonstrate the importance of endogenous peroxynitrite generation in the pathogenesis of autoimmune diabetes and diabetic cardiovascular complications. Peroxynitrite decomposition catalysts may be of therapeutic utility in diabetes and other pathophysiologic conditions.

Hemodynamic effects of isoprostanes (8-iso-prostaglandin F2alpha and E2) in isolated guinea pig hearts.

Isoprostanes are a family of prostaglandin-related compounds formed from arachidonic acid in a cyclooxygenase-independent manner as products of free radical-initiated lipid peroxidation. To elucidate the biological activity of the F2-and E2-isoprostanes, 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) and 8-iso-prostaglandin E2 (8-iso-PGE2), we measured hemodynamic effects in isolated perfused guinea pig hearts after cumulative administration (3 x 10(-9)-10(-5) M) of these compounds into the coronary system. Coronary flow (CF), left ventricular pressure (LVP), maximal rate of pressure development (dP/dt(max)), and heart rate were determined continuously. Furthermore, net release of lactate into the coronary venous effluent and myocardial pyruvate consumption were measured. Comparative studies were performed with the known potent vasoconstrictor endothelin-1 (6 x 10(-12)-2 x 10(-9) M). Both 8-iso-PGF2alpha and 8-iso-PGE2 induced concentration-dependent decreases in CF, which declined maximally to approximately 50% of the baseline level. The potencies of the two compounds were almost identical. Alterations in CF were associated in both groups with parallel reductions of LVP and dP/dt(max); heart rate was not influenced. Furthermore, the diminished CF caused enhanced lactate release and a reduced pyruvate consumption. All isoprostane-induced hemodynamic changes were prevented by coapplication of the thromboxane A2-receptor antagonist SQ 29548 (1 microM). Endothelin-1 caused CF reductions associated with loss of myocardial contractility, just like the isoprostanes. We conclude that in isolated guinea pig hearts, 8-iso-PGF2alpha and 8-iso-PGE2 are potent vasoconstrictors. The action appears to be mediated by SQ 29548-responsive thromboxane receptors. The accompanying loss of contractility is a secondary phenomenon, elicited by infringed oxygen supply.

Cardiovascular aspects in renal disease

The majority of hemodialysis patients die from cardiovascular disease. However, the contribution of myocardial infarction to mortality is relatively minor, despite the fact that coronary artery disease is common in uremic patients. Hypertension seems to be the major risk factor for the development of atherosclerosis in hemodialysis patients, although abnormalities of the lipid spectrum, characterized by an increase in triglycerides and very low density lipoprotein levels and a decrease in high-density lipoprotein levels, are frequent in hemodialysis patients. The existence of left ventricular (LV) hypertrophy is a serious risk factor for morbidity and mortality in hemodialysis patients. LV hypertrophy can present as a dilated cardiomyopathy or as concentric or asymmetric septal hypertrophy. Loss of myocardial contractility by coronary artery disease or carnitine deficiency can lead to systolic LV dysfunction with a compensatory dilated cardiomyopathy. Furthermore, the presence of a hypercirculation in uremic patients, resulting from anemia, the arteriovenous fistula, or fluid overload, can also lead to a dilated cardiomyopathy. Systolic LV dysfunction occurs when the increase in LV wall thickness is inadequate for the increase in LV radius, which might be caused by increased levels of parathyroid hormone. LV diastolic dysfunction, resulting from an increase in LV mass due to the effects of hypertension or to uremic interstitial fibrosis, can both lead to pulmonary edema and hypotensive periods during hemodialysis and is a severe risk factor for mortality in hemodialysis patients. Therefore, in uremic patients, anemia should be corrected and hypertension adequately treated early in the development of renal failure. Chronic fluid overload should be prevented by adequate estimation of optimal dry weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of ibopamine in the treatment of heart failure

Loss of myocardial contractility, reflexly enhanced vasoconstriction, and neuroendocrine excitation are the pathophysiologic hallmarks of low-output heart failure. Drugs that counter both consequences afford considerable therapeutic potential in retarding and perhaps even in staying the consequences of the syndrome. Ibopamine possesses such potential through its unique ability to stimulate both dopaminergic- and β-adrenoreceptors in the heart and circulatory system. Stimulation of dopaminergic- receptors and β 2-adrenoreceptors results in vasodilatation in all regional vascular territories. β 2-Adrenoreceptor agonist activity also affords mild positive inotropic activity in the heart, whereas stimulation of presynaptic dopaminergic- receptors (DA 2) attenuates the Increased sympathetic neural outflow. The drug also suppresses the renin-angiotensin-aldosterone system in addition to having a direct natriuretic activity. The pharmacodynamic effects of ibopamine, exerted through its metabolite epinine, are transiated into measurable therapeutic benefits in patients with chronic heart failure. The increase in peripheral blood flow induced in all regional vascular territories, including the kidneys, is associated with increased cardiac output and stroke volume and reduction in left ventricular pressure work, wall stress, and myocardial oxygen consumption. Plasma norepinephrine, angiotensin, and aldosterone are also reduced, and renal sodium excretion is enhanced. These hemodynamic and neuroendocrine activities, which are not subject to tolerance during sustained administration of the drug, are accompanied by clinically significant improvement in symptoms, exercise tolerance, and the New York Heart Association classification of disability. More important, no proarrhythmic effects have been observed during sustained treatment, and the minimal side effects observed during long-term treatment enhance the safety profile of the drug. Results of survival studies are awaited, but open studies hold substantial promise for the efficacy of ibopamine in this respect.

The Ischemic Myocardium: Mechanism of Early Pump Failure

The rapid loss of myocardial contractility that occurs after coronary occlusion may result from the absence of some critical substrate for cellular metabolism or from accumulation of toxic metabolites. In any event, for a few hours the portion of the myocardium affected by the interruption of blood flow retains its viability. Research into the mechanisms operating during this early period may open the way to reversal of the cellular changes.

STUDIES ON THE CORONARY CIRCULATION. VII. THE REMARKABLE RESERVE POWER OF THE HEART

Article1 September 1949STUDIES ON THE CORONARY CIRCULATION. VII. THE REMARKABLE RESERVE POWER OF THE HEARTELIOT CORDAY, M.D., RAMON SPRITZLER, M.D., MYRON PRINZMETAL, M.D.ELIOT CORDAY, M.D.Search for more papers by this author, RAMON SPRITZLER, M.D.Search for more papers by this author, MYRON PRINZMETAL, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-31-3-450 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptLittle is known about the reserve contractile power of the heart. This is in marked contrast to the extensive knowledge available in regard to the reserve power of other vital organs. Thus, it is known that animals can continue to live with 25 per cent of one kidney,140 per cent of one lung,220 per cent of the liver,316 per cent of the adrenal cortex,4and 6 per cent of the small intestine.5In the case of these organs, the method of investigation is technically easy. In serial experiments upon the same or successive animals, increasing portions of...Bibliography1. WRIGHT S: Applied physiology, ed. 8, 1945, Oxford Medical Publications, New York, p. 879. Google Scholar2. GOLDMAN A: Personal communication. Google Scholar3. WRIGHT S: Applied physiology, ed. 8, 1945, Oxford Medical Publications, New York, p. 746. Google Scholar4. BESTTAYLOR CHNB: Physiological basis for medical practice, ed. 4, 1945, Williams and Wilkins, Baltimore, p. 692. Google Scholar5. GERMANBROWNFOSTERGRISSEL JKHMRTTL: Massive resection of the intestine, Jr. Am. Med. Assoc., 1947, cxxxv, 918. Google Scholar6. PRINZMETAL M: Studies on the coronary circulation. VI. Loss of myocardial contractility after coronary artery occlusion, Ann. Int. Med., 1949, xxxi, 429-449. Google Scholar7. PRINZMETAL M: Studies on the coronary circulation. III. Collateral circulation of beating human and dog hearts with coronary occlusion, Am. Heart Jr., 1948, xxxv, 689. CrossrefGoogle Scholar8. PRINZMETAL M: Studies on the coronary circulation. IV. The effect of shock on the heart and its treatment, Am. Heart Jr., to be published. Google Scholar9. THOMASGARLAND SFLH: Roentgen cardiac diagnosis, Calif. Med., 1948, lxviii, 126. Google Scholar10. LEARYWEARN TJT: Two cases of complete occlusion of both coronary orifices, Am. Heart Jr., 1929, v, 412. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Los Angeles, California*Read before: The III Interamerican Cardiological Congress, Chicago, June 17, 1948; The American Heart Association, Chicago, June 19, 1948.Motion pictures of these experiments were shown before: The III Interamerican Cardiological Congress, Chicago, June 17, 1948; The American Heart Association, Chicago, June 19, 1948; The American College of Physicians, San Francisco, April 23, 1948.From the Institute for Medical Research, Cedars of Lebanon Hospital, Los Angeles, California.Aided by grants from the Blanche May and Beaumont Trust Funds. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byEffects of reperfusion on the regional contraction of ischemic and nonischemic myocardium following partial coronary obstruction.Haemodynamische Kompensationsmechanismen der Kontraktionsst�rungen bei der chronischen KoronarskleroseTemporal sequence of dynamic contractile characteristics in ischemic and nonischemic myocardium after acute coronary ligationLimitations of myocardial revascularization in restoration of regional contraction abnormalities produced by coronary occlusionReevaluation of the Treatment of Shock Secondary to Cardiac InfarctionSPONTANEOUS, HEREDITARY MYOCARDIAL DEGENERATION AND CONGESTIVE HEART FAILURE IN A STRAIN OF SYRIAN HAMSTERSTHE HEART MUSCLE IN MUSCULAR DYSTROPHY WITH SPECIAL REFERENCE TO INVOLVEMENT OF THE CARDIOVASCULAR SYSTEM IN THE HEREDITARY MYOPATHY OF THE HAMSTER*Myocardial infarct and sudden coronary heart death in relation to coronary occlusion and collateral circulationAcute coronary occlusion as a cause of myocardial infarct and sudden coronary heart deathSelection and management of anaesthesia in those suffering from diseases and disorders of the heartExperimental production of chronic cardiac aneurysm and congestive heart failure in the ratPathophysiologie der HerzinsuffizienzDie Coronarerkrankungen. Coronarinsuffizienz, Angina pectoris und HerzinfarktVentriculoplasty for cardiac aneurysmEXPERIMENTAL METHODS FOR DETECTION OF CHANGES OF BLOOD SUPPLY TO THE HEARTIntra-arterial infusion in the treatment of shock resulting from coronary occlusionCARDIOSTATHORRHAPHY—SPLINTING THE FLACCID MYOCARDIUM OF CORONARY OCCLUSION BY SURGICAL PROCEDURESSymptomatik Und Pathogenese Des Akuten HerzversagensElectrokymographic studies of abnormal left ventricular pulsations 1 September 1949Volume 31, Issue 3Page: 450-455KeywordsHeartLiver Issue Published: 1 September 1949 PDF downloadLoading ...