Myocyte necrosis

Cardiac MRI may have a role in risk stratification for SCD due to its ability to detect myocardial scar. The use of gadolinium, which accumulates in infarcted tissue, has allowed delayed enhancement MRI to detect scar burden. Early experiments in dog models performed by coronary artery occlusion compared acute and chronic infarcts to pathologic specimens of the dog heart postmortem (89,90). Delayed enhancement MRI was remarkably accurate in imaging the infarcted tissue in comparison to the pathologic specimen. The spatial extent of hyperenhancement was the same as the spatial extent of myocyte necrosis at every stage post-MI. Reversible ischemia did not show delayed gadolinium uptake. Thus, delayed enhancement MRI can distinguish between reversible and irreversible injury, and... 

HHMM, and HMMM, respectively (Markert, Shaklee, and Whitt 1975). The widespread tissue distribution of LDH differs with the various species (Garbus et al. 1967 Cornish, Barth, and Dodson 1970 Karlsson and Larsson 1971 Schultze et al. 1994). Some additional isoenzymes of LDH have been described, and some LDH isoenzymes may complex with drugs—for example, streptokinase (Podlasek and McPherson 1989). Because LD is a cytoplasmic enzyme, it is increased in serum during hepatocyte or myocyte necrosis and conditions that are toxic to hepatocytes or myocytes. However, it lacks specificity and sensitivity when compared to other enzymes for detection of specific organ injury. In laboratory animals, the primary use for LD has been the detection of experimentally induced myocardial injury (see Chapter 7). 

Pre-treatment with the reactive oxygen scavenger N-(2-mercaptopropionyl)-glycine completely inhibited monocyte chemotactic protein-1 induction by dog cardiac venules in reperfused infarcts (Lakshminarayanan et al. 2001). In situ hybridisation localised monocyte chemotactic protein-1 message to small venular endothelium in ischaemic areas without myocyte necrosis. Immunohisto-chemical staining demonstrated reperfusion-dependent nuclear translocation of c-Jun and NF-xB (p65) in small venular endothelium, only in the... 

The key to managing rejection is early diagnosis, before myocyte necrosis and stimulation of vascular endothelial cell proliferation. Rapid diagnosis allows immediate modification of the recipient s immunosuppressive therapy. 

Troponins T or I Proteins found predominantly in cardiac muscle that regulate calcium-mediated interaction of actin and myosin troponins I and T are released into the blood from myocytes at the time of myocardial cell necrosis after infarction. These biochemical markers become elevated and are used in the diagnosis of myocardial infarction. 

NSTEMI differs from UA in that ischemia is severe enough to produce myocardial necrosis, resulting in release of detectable amounts of biochemical markers, primarily troponin I or T and creatine kinase myocardial band (CK-MB) from the necrotic myocytes into the bloodstream. 

In a myocardial infarction (MI), myocytes swell as the membrane potential collapses and the I cell gets leaky. Enzymes are released from the damaged tissue, and lactic acidosis contributes to protein precipitation and coagulation necrosis. 

Nakamura, K., Fushimi, K., Kouchi, H., Mihara, K., Miyazaki, M., Ohe, T., and Namba, M. 1998. Inhibitory effects of antioxidants on neonatal rat cardiac myocyte hypertrophy induced by tumor necrosis factor-oc and angiotensin II. Circulation 98 794-799. 

Studies in various animal models and in human hearts suggest that apoptosis does occur in ischemia/reperfusion injury of the heart, though the relative contribution of apoptosis in comparison with necrosis to cell loss in ischemia/ reperfusion injury is still controversial. Cardiomyocyte apoptosis was first reported by Gottlieb et al. [107], who studied the ischemia/reperfusion in rabbit hearts and found the hallmark of apoptosis in ischemic/reperfused hearts but not in the normal or ischemic-only rabbit hearts. Identification of apoptosis was based on the presence of fragmented DNA in electrophoretic gels, on in situ nick end-labeling assays, and on electron microscopy. They concluded that apoptosis may be a specific feature of reperfusion injury in cardiac myocytes. Subsequent studies have shown that apoptosis probably occurs both in ischemia and reperfusion [108], It appears that apoptosis is more prominent after ischemia followed by reperfusion than after ischemia alone [109, 110],... 

A number of potential mechanisms have been suggested to explain the beneficial effects of /3-blockers in heart failure patients. Although not clearly elucidated, it seems likely that the mechanisms of benefit include antiarrhythmic effects, slowing or reversing the detrimental ventricular remodeling caused by sympathetic stimulation, decreased myocyte death from catecholamine-induced necrosis or apoptosis, and prevention of fetal gene expression and the other detrimental effects of SNS activation described earlier. ... 

In this experiment it was found that the hearts from monkeys fed high fat diets do not develop the myocardial necrosis and fibrosis that were found in male rats. As described in Table XXXIX, two types of lesions were observed. The ( ) or trace lesion was a myocardial lesion consisting of focal interstitial collections of inflammatory cells, occasional focal scars, or groups of swollen interstitial fibroblasts. The authors concluded that these heart lesions were not diet related. The (+) myocardial lesion consisted of multiple small foci of fibroblasts, mononuclear cells, and Antischkow s myocytes. As shown in Table XXXIX this lesion was but rarely observed and then only in male monkeys fed the soybean oil diet. 

Yokoyama, T., Nakano, M., Bednarczyk, J.L., McIntyre, B.W., Entman, M., Mann, D.L. (1997). Tumor necrosis factor-alpha provokes a hypertrophic growth response in adult cardiac myocytes. Circulation. 95(5) 1247-1252. 

The tools available to identify and monitor drug-induced muscle injury (defined as myocyte degeneration and necrosis) both in preclinical and in clinical drug development are very limited. In preclinical studies, histopathology is the primary method used to routinely identify muscle injury. Numerous enzymatic assays have routinely been used as... 

It has been known since the work of Rona et al. (1959) that sympathomimetic amines at dose levels, which would be lethal for humans produce extensive necrosis in the rat myocardium. The lesions and those produced in the same species by hypoxia have morphological features in common (Niles et al. 1968). A proteolipid binding H-isoprenaline was localized in the plasma membrane of the feline heart ventricular myocytes (Ochoa et al. 1972). Exposing myocytes to catecholamines lead to down-regulation of the number of receptors within minutes (Linden et al. 1984). 

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