Myocardial Fiber Hypertrophy Research Articles

Pathophysiology of the right ventricle in health and disease: an update.

The contribution of the right ventricle (RV) to cardiac output is negligible in normal resting conditions when pressures in the pulmonary circulation are low. However, the RV becomes relevant in healthy subjects during exercise and definitely so in patients with increased pulmonary artery pressures both at rest and during exercise. The adaptation of RV function to loading rests basically on an increased contractility. This is assessed by RV end-systolic elastance (Ees) to match afterload assessed by arterial elastance (Ea). The system has reserve as the Ees/Ea ratio or its imaging surrogate ejection fraction has to decrease by more than half, before the RV undergoes an increase in dimensions with eventual increase in filling pressures and systemic congestion. RV-arterial uncoupling is accompanied by an increase in diastolic elastance. Measurements of RV systolic function but also of diastolic function predict outcome in any cause pulmonary hypertension and heart failure with or without preserved left ventricular ejection fraction. Pathobiological changes in the overloaded RV include a combination of myocardial fibre hypertrophy, fibrosis and capillary rarefaction, a titin phosphorylation-related displacement of myofibril tension-length relationships to higher pressures, a metabolic shift from mitochondrial free fatty acid oxidation to cytoplasmic glycolysis, toxic lipid accumulation, and activation of apoptotic and inflammatory signalling pathways. Treatment of RV failure rests on the relief of excessive loading.

An alarming rise in the prevalence of deaths with methamphetamine involved in Tehran, Iran 2011-2018.

Methamphetamine is one of the most commonly abused illicit drugs in Iran. Despite this fact, there has been relatively little research on methamphetamine-associated deaths in Iran. The present study aimed to investigate the cause of death in methamphetamine positive cases based on forensic toxicology findings In this data base descriptive study, individuals with methamphetamine-associated deaths that were referred to the Legal Medicine Organization, Tehran, Iran (2011-2018) were assessed. Deaths including those from natural causes, toxicity, accident and suicides with positive forensic toxicology analyses for methamphetamine and its metabolite amphetamine in postmortem samples were investigated. All cases were examined to determine trends in methamphetamine-associated deaths, and in the manner and causes of deaths. During the eight year study there were 1389 methamphetamine-associated deaths. The mean age was 37.47±10.87 years, with a male/female ratio of 12.36:10. The methamphetamine-associated death rate increased significantly during the study period (2.05 vs. 21.93 per 106 Tehran province populations). The most common cause of death was cardiac arrest due to stimulant abuse with supportive histologic findings of acute myocardial infarction, myocardial fiber hypertrophy, aortic dissection and perivascular fibrosis (25%). Opioids (methadone, tramadol and morphine), tricyclic antidepressants and benzodiazepines were frequently present in postmortem samples of study cases. Methamphetamine-associated deaths significantly contribute to illicit drug-associated deaths in Tehran and represent a substantial clinical and public health problem.

Histopathological study of cardiac lesions in methamphetamine poisoning-related deaths

BackgroundMethamphetamine abuse is a worldwide health concern. Methamphetamine causes health hazards in many vital organs. It can cause damage to cardiac tissue via catecholamines release. Methamphetamine related deaths are becoming one of the most important problems in Iran. The purpose of the present study was to determine cardiac pathology in methamphetamine poisoning-related deaths.MethodsThe study included 100 cases of methamphetamine poisoning-related deaths and 100 cases as control group. Toxicology analysis of liver, gastric content, bile, urine, blood and vitreous humor were conducted to detect drugs, poisons and alcohols using thin layer chromatography, gas chromatography/mass spectrometry, and high performance liquid chromatography. Positive toxicology analysis results except for amphetamine and methamphetamine were excluded from the study in order to omit interfering factors. The most striking features of cardiac damage were observed by light microscopy.ResultsMethamphetamine and amphetamine were detected in either urine or gastric content samples. In all of the cases methamphetamine toxicity was determined to be a direct cause of death by forensic medicine practitioner. Cardiovascular pathology was noted in 68% of studied cases. The most common histopathologic features were myocardial fiber hypertrophy, mild, moderate to severe atherosclerosis and focal degeneration/necrosis.ConclusionThe results of the present study indicate that cardiotoxicity is one of the major contributing factors in methamphetamine poisoning related deaths. Overall, the current study highlights the fact that cardiotoxic effects of methamphetamine can explain increasing reports of heart failure and consequently death in young abusers.Trial registrationNot applicable.Graphical Histopathological study of cardiac lesions in methamphetamine poisoning-related deaths

Experimental observation on the histopathological and ultrastructural pathology of Great Gerbils (Rhombomys opimus) in the Junggar Basin by subcutaneous injecting of Yersinia pestis

Objective: To understand the histopathological and ultrastructural pathology changes of great gerbils in the Junggar Basin to Yersinia pestis infection. Methods: Forty captured great gerbils from the Junggar Basin that tested negative for anti-F1 antibodies were infected. The Y. pestis strain 2504, isolated from a live great gerbil in the natural plague foci of the Junggar Basin in 2005 with a median lethal dose (LD(50)) of <10 CFU/ml, was used in this study. Forty great gerbils were divided into seven infection groups and were subcutaneously infected with 7.4×10(5), 7.4×10(6), 7.4×10(7), 7.4×10(8), 7.4×10(9), 7.4×10(10), or 3.0×10(11) CFU/ml of 2504. One milliliter of physiological saline was injected in the noninfected group as a control. We collected the liver, spleen, heart, and lung from all animals for histopathologic and ultrastructural pathology examination. Results: Great gerbils in the 7.4×10(8)-3.0×10(11) CFU/ml groups did not survive and exhibited pathological changes and altered ultrastructural pathology. The liver tissue of infected great gerbils showed spotty necrosis and fatty degeneration, intranuclear canaliculi with increased hepatocytes, and uneven distribution of organelles. Additionally, reactive proliferation of lymphoid tissue in the spleen, blood sinusoid lacunae with neutrophil infiltration, and phagocytosed bacteria in phagocyte cells were observed. Myocardial fiber hypertrophy and interstitial indistinction, nuclear matrices decreased in cardiac myocytes, and loose arrangement of myogenic fibers in myocardial cells were also observed. Angiectasia, capillary congestion, and tissue necrosis were found in the lung. No significant difference in histopathological and ultrastructural pathology in the parenchymal organ was observed between the 7.4×10(5)-7.4×10(7) CFU/ml groups and the 7.4×10(8)-3.0×10(11) CFU/ml groups, and no specific death caused by Y. pestis infection was apparent in the 7.4×10(5)-7.4×10(7) CFU/ml groups. Conclusion:Y. pestis infection altered tissue and ultrastructural pathology in the parenchyma apparatus of great gerbils. In particular, the liver and spleen appeared to be the primary site of Y. pestis infection in great gerbils.

A study of the pathology and pathogenesis of the myocardial lesions in gousiekte, a plant-induced cardiotoxicosis of ruminants

Myocardial lesions were studied in sheep in which gousiekte was induced by experimental dosage of Pachystigma pygmaeum, Fadogia homblei or Pavetta harborii. The single most consistent diagnostic histological feature in 33 animals was hypertrophy of myocardial fibres in the subendocardial region. Fibrosis in the subendocardial region of the apex or left ventricular wall was often scarce or absent in animals with a short latent period, and was not always prominent even in sheep with an intermediate or long latent period. The presence or absence of fibrosis cannot therefore be used to confirm or exclude gousiekte, particularly in cases with shorter latent periods. Light microscopical and ultrastructural lesions in sheep with gousiekte correspond to a large extent to changes reported in humans with dilated cardiomyopathy of unknown cause. It appears that the myocardial lesions in gousiekte represent a final common pathway of cellular damage rather than a manifestation of a specific type of heart disease. The predilection for hypertrophy of myofibres in the subendocardial region is probably related to diminished perfusion that potentiates the primary myocardial dysfunction.

Tuberculous aortitis with coronary ostial and left ventricular outflow obstruction: Unusual cause of sudden unexpected death

Tuberculous aortitis is a distinct, but uncommon, cause of thoracic and abdominal aortic aneurysms. We report an unusual case of tuberculous aortitis in a 12-year-old girl that resulted in her sudden death. The patient suffered from undiagnosed primary pulmonary tuberculosis affecting the apical region of her right lower lobe, with regional hilar lymphadenopathy. The granulomatous inflammatory process spread from the hilar lymph nodes to the aortic root, leading to tuberculous aortitis and the formation of an intraluminal tuberculoma just superior to the aortic valve. The tuberculoma also involved the ostia and proximal portions of both coronary arteries, resulting in obstruction of the coronary arteries in addition to the left ventricular outflow tract. The consequent myocardial fiber hypertrophy and interstitial fibrosis predisposed the patient to the development of fatal arrhythmias that most probably accounted for her sudden death.

Nonreentrant Mechanisms Underlying Spontaneous Ventricular Arrhythmias in a Model of Nonischemic Heart Failure in Rabbits

The goal of this study was to define the mechanisms of spontaneously occurring ventricular arrhythmias in the setting of nonischemic heart failure. Three-dimensional cardiac mapping from 232 intramural sites was performed in four rabbits with heart failure induced by combined aortic regurgitation and aortic stenosis and in four control rabbits. During the development of heart failure, serial echocardiographic examination demonstrated a progressive increase in left ventricular (LV) chamber dimensions and a decrease in LV systolic function over 19 +/- 2 months. Serial Holter monitoring demonstrated spontaneously occurring premature ventricular complexes (PVCs) (up to 13,000 per day) and couplets in all four rabbits with heart failure, and runs of nonsustained ventricular tachycardia (VT) up to 26 beats long in three. Mapping of spontaneous rhythm was performed for up to 60 minutes. None of the control rabbits demonstrated spontaneous arrhythmias during mapping. Three rabbits with heart failure demonstrated isolated PVCs, and two demonstrated couplets and runs of nonsustained VT up to 4 beats long. The three-dimensional activation sequence of 50 sinus beats (42 from rabbits with heart failure; 8 from control rabbits), 19 PVCs, and 37 beats of couplets and nonsustained VT was determined and the mechanism of arrhythmia defined for all ventricular ectopic beats analyzed. Normal sinus beats from the failing rabbits activated rapidly, with a total activation time of 28 +/- 1 ms (P = .18 versus sinus beats from control hearts, 26 +/- 1 ms). Sinus beats preceding PVCs in the rabbits with heart failure activated in a similar fashion, with a total activation time of 26 +/- 1 ms. In each case, these PVCs initiated in the subendocardium by a nonreentrant mechanism based on the absence of intervening electrical activity between the termination of the preceding beat and the initiation of the next (225 +/- 7 ms), despite the presence of multiple intervening electrode recording sites. Couplets and monomorphic and polymorphic VTs were due to repetitive nonreentrant activation at the same or different subendocardial sites. Total activation time of beats of VT averaged 44 +/- 1 ms and did not differ from that of isolated PVCs (43 +/- 2 ms, P = .65). Pathological analysis of tissue demonstrated myocardial fiber hypertrophy, degenerative changes, and interstitial fibrosis throughout the failing hearts. Spontaneously occurring PVCs, couplets, and VT in a model of nonischemic heart failure are due to nonreentrant mechanisms such as triggered activity or abnormal automaticity. Approaches to the treatment of spontaneously occurring ventricular arrhythmias in patients with nonischemic heart failure should be directed at nonreentrant mechanisms.

Sudden Death Caused by Unsuspected Pulmonary Arterial Hypertension, 10 Years After Surgery for Extrahepatic Biliary Atresia

SummaryA case of extrahepatic biliary atresia presenting with an acute respiratory episode and rapid deterioration, 10 years after a successful portoenterostomy and a very active life, was the setting of unsuspected severe pulmonary arterial hypertension leading to sudden death. The pulmonary arteries showed widespread plexiform lesions, thickening of the muscular media, and subendothe‐lial proliferation. Occasionally, eccentric arterial obstructive lesions and fibrinous thrombi were observed. There was marked reduction of preacinar arterioles with a consequent increase in the alveolar/arterial ratio. The pulmonary veins showed arterialization of their walls. There was marked hypertrophy of myocardial fibres in the right ventricle together with foci of myocardial degeneration and fibrosis. Areas of endocardial thickening were observed in both ventricles. The absence of clinical indicators of pulmonary arterial hypertension at any but the terminal stages of the disease precluded any form of conservative management. Lung‐heart and presumably liver transplantation might have been the only option. Prospective assessment of pulmonary function and haemodynamic studies should be considered in cirrhotic patients with portal hypertension.

Sudden Death Caused by Unsuspected Pulmonary Arterial Hypertension, 10 Years After Surgery for Extrahepatic Biliary Atresia

A case of extrahepatic biliary atresia presenting with an acute respiratory episode and rapid deterioration, 10 years after a successful portoenterostomy and a very active life, was the setting of unsuspected severe pulmonary arterial hypertension leading to sudden death. The pulmonary arteries showed widespread plexiform lesions, thickening of the muscular media, and subendothelial proliferation. Occasionally, eccentric arterial obstructive lesions and fibrinous thrombi were observed. There was marked reduction of preacinar arterioles with a consequent increase in the alveolar/arterial ratio. The pulmonary veins showed arterialization of their walls. There was marked hypertrophy of myocardial fibres in the right ventricle together with foci of myocardial degeneration and fibrosis. Areas of endocardial thickening were observed in both ventricles. The absence of clinical indicators of pulmonary arterial hypertension at any but the terminal stages of the disease precluded any form of conservative management. Lung-heart and presumably liver transplantation might have been the only option. Prospective assessment of pulmonary function and haemodynamic studies should be considered in cirrhotic patients with portal hypertension.

Myocardial structure in volume-overloaded hearts before and after valve replacement.

The purpose of this study was to evaluate the histological characteristics of left ventricular muscle in volume-overloaded hearts. A preoperative biopsy was obtained in 31 patients: 14 with mitral regurgitation, 14 with aortic regurgitation and 3 with mitral regurgitation and aortic regurgitation. Postoperative tissue samples were available in 15 patients. Histological findings were correlated with echocardiographic and angiographic data before (preop) and one year after (postop) operation. Myocardial cell diameter was correlated with both the end-diastolic (r = 0.77, p less than 0.01) and end-systolic (r = 0.78, p less than 0.01) dimensions of the left ventricle, but was inversely correlated with the end-diastolic wall thickness-to-radius (h/R) ratio (r = -0.71, p less than 0.01). Percent fibrosis increased proportionally to the diameter (r = 0.42, p less than 0.05). For one year after operation, echocardiographic left ventricular dimensions and angiographic left ventricular volumes were significantly reduced (p less than 0.05), but in some patients postoperative values remained greater than normal. With regard to left ventricular morphology, myocardial cell diameter and interstitial fibrosis decreased significantly after valve replacement (p less than 0.05). However, the myocardial fiber remained hypertrophied and interstitial fibrosis remained above normal after surgery. Thus, postoperative ventricular dilatation was dependent upon the degree of myocardial fiber hypertrophy and interstitial fibrosis.

Anatomic and light microscopic characterisation of hypertrophic obstructive and non-obstructive cardiomyopathy.

Macroscopically asymmetric hypertrophy of the interventricular septum is the characteristic change, though mild degrees can be seen in normal hearts and in combination with congenital or acquired heart disease. If asymmetric hypertrophy is severe, this alone characterises the condition. Concentric forms have, however, been described. At light microscopic level disarray and often extreme hypertrophy of myocardial fibres together with degenerative changes and interstitial fibrosis are typical. Overlap of individual features with 'ordinary' hypertrophy exists but if all criteria are considered in combination a high degree of diagnostic reliability can be achieved, frequently aided by severe accumulation of glycogen. In support semiquantitative studies will also be presented. The patterns of abnormal fibre arrangement differ in the two clinical types. In cases with obstruction the abnormal fibres are predominantly confined to the interventricular septum, whereas in cases without obstruction they are scattered focally throughout the ventricular walls. Unfortunately, these disturbances are not always present. Subdivisions based on histological changes by other workers will be mentioned. Brief reference will be made to experimental work that has shown that a possible endogenous mechanism may be operative in some of the patients with hypertrophic cardiomyopathy. It is concluded that the morphology of hypertrophic cardiomyopathy is sufficiently characteristic to separate it as a distinct entity and to ensure reliable diagnosis.

Biventricular hypoplasia with myocardial fiber hypertrophy and disarray

A 25 year old woman with effort intolerance and systemic venous congestion since childhood, and restrictive ventricular filling and severe atrioventricular (A-V) valve regurgitation at cardiac catheterization died after valve replacement surgery. At autopsy, the atria were enlarged and thickened; both ventricles were small. In some areas the right ventricular wall was only a few myofibers thick. The myofibers of both ventricles were hypertrophied, and there was widespread fiber disarray in the left ventricular free wall, the interventricular septum and, focally, the right ventricular free wall. Because the ventricles were not enlarged or thickened despite myocardial fiber hypertrophy and severe chronic A-V valve regurgitation, and the myofiber disarray was widespread, this is a very unusual case of biventricular hypoplasia and dysplasia.

Quantitation of left ventricular myocardial fiber hypertrophy and interstitial tissue in human hearts with chronically increased volume and pressure overload.

Using new techniques, we quantitated left ventricular myocardial fiber hypertrophy and interstitial tissue in four groups of autopsied hearts free of coronary disease: 1) 22 normal hearts, 2) 20 hearts from patients with mitral incompetence (NYHA Class II-III) who died early after mitral valve replacement from causes other than cardiac failure, 3) 22 hearts from patients with mitral incompetence (NYHA Class III-IV) who died early after mitral valve replacement from cardiac failure with low cardiac output syndrome, and 4) 22 hearts from patients with hypertensive heart disease (NYHA Class II-III). Myocardial fiber hypertrophy was quantitated by measuring cross-sectional myocardial fiber diameter; the proportion of interstitial tissue was quantitated by using a computerized, high-resolution video image-digitizing system. Myocardial fiber average diameter in groups 2, 3 and 4 was significantly higher than group 1. The proportion of interstitial tissue was significantly increased in group 3. In chronic mitral incompetence an increase in left ventricular interstitial tissue may play a role in the development of severe cardiac failure.

Quantitation of left ventricular myocardial fiber hypertrophy and interstitial tissue following mitral valve replacement for mitral incompetence

Quantitation of left ventricular myocardial fiber hypertrophy and interstitial tissue following mitral valve replacement for mitral incompetence

The Electrocardiogram in Muscular Subaortic Stenosis

The electrocardiograms of four patients with muscular subaortic stenosis, in whom there was angiographic evidence of ventricular septal hypertrophy (confirmed at surgery in three), revealed pathological Q waves in the limb leads (except aV R ) and the left precordial leads, as well as tall R waves in the right precordial leads. Three patients underwent surgical correction of the stenosis. The left anterior septal ventriculomyotomy abolished the Q waves and diminished the right precordial R waves while at the same time producing left axis deviation believed to be due to severing of the anterior division(s) of the left bundle branch. In the fourth patient the left precordial and limb lead Q waves and right precordial R waves increased following spontaneous development of complete right bundle-branch block. These observations support the belief that the Q-wave and R-wave abnormalities in the electrocardiogram in patients with muscular subaortic stenosis are the result of septal depolarization commencing at the left septal surface and may be related to the overall hypertrophy of the septum, the bizarre myocardial fiber hypertrophy or premature activation of the base of the septum, or all three.