Myocardial ischemia necrosis

Although troponin elevation suggests necrosis, biomarkers of myocardial ischemia are equally important. Ischemia-modified albumin was reported to be highly sensitive for a diagnosis of ischemia in patients with chest pain presenting to the emergency room (12). Further study needs to be done on this sensitive biomarker for myocardial ischemia. 

The authors reasoned that the myocardial ischemia did not proceed to necrosis or a dysrhythmia because the amount of drug exposure was low. 

The authors concluded that even if beta2-adrenoceptor agonists can cause myocardial ischemia in pregnant women by further increasing oxygen consumption, acute myocardial necrosis is rare however, in this case... 

Takashi E, AshrafM (2000) Pathologic assessment of myocardial cell necrosis and apoptosis after ischemia and reperfusion with molecular and morphological markers. J Mol Cell Cardiol 32 209-224... 

Myocardial ischemia is associated with an inflammatory response that further contributes to myocardial injury and ultimately leads to myocardial healing and scar formation. Myocardial necrosis has been associated with complement activation and free radical generation that trigger cytokine cascades and upregulate chemokines expression. Mononuclear cell chemoattractants, such as the CC chemokines CCL2/Monocyte... 

P.S. Ray, J.L. Martin, E.A. Swanson, H. Otani, W.H. Dillmann and D.K. Das, Transgene overexpression of alphaB crystallin confers simultaneous protection against cardiomyocyte apoptosis and necrosis during myocardial ischemia and reperfusion, FASEBJ. 15(2), 393-402 (2001). 

Various aspects of myocardial ischemia are highlighted in Chapter 1. Reperfusion, generally a pre-requisite for tissue survival may increase injury over and above that sustained during ischemia. In this context, the role of apoptosis is appreciated. Mitochondrion seems to be the site of life or death . This organelle that provides ATP to sustain cell life is converted to an instrument of programmed cell death or necrosis upon stress depending on the severity of the insult. 

Calcium overload as a pathogenic mechanism of cell injury has been incriminated in various disorders of cardiac and skeletal muscle including catecholamine-induced cardiac necrosis (8, 13), myocardial ischemia (8, 13), myopathies (9, 17), and malignant hyperthermia (18). Of interest is that in the majority of these pathophysiological entities calcium antagonists effectively suppress calcium accumulation and cell necrosis (8, 13, 18). 

Cyclophosphamide (279 Da) Acute HF with pericardial effusion, myocardial hemorrfiagic necrosis, interstitial edema, fibrin deposits, microvascular thrombi, ischemia, ECG changes... 

Erosion and rupture of vulnerable atherosclerotic plaque is the cause of most acute coronary syndromes [32, 33]. Plaque mpture leads to the formation of an intracoronary thrombus, which produces an obstruction that acutely limits coronary artery blood flow, resulting in myocardial ischemia or necrosis. Multiple clinical and autopsy studies have confirmed the pathogenic role of coronary thrombus in cases of acute MI, unstable angina and sudden cardiac death [33, 34]. The lesions that harbor vulnerable plaques are often mildly stenotic on angiographic examination and, consequently, their stability cannot be assessed. The stability of atherosclerotic plaques is related to histological composition Figure 17.2. Unstable plaques typically comprise thin (<65 pm) fibrous caps infiltrated with macrophages that encapsulate lipid-rich necrotic cores with adjacent microcalcification [33, 34]. 

Although Fig. 13.2 describes a hypothetical situation, there is ample experimental evidence to suggest that both apoptosis and necrosis occur in a wide variety of disease conditions. A prominent example of this is the condition of ischemia-reperfusion injury in cardiovascular disease. Prolonged regional myocardial ischemia without reperfusion causes myocyte cell death. However, reperfusion after even a brief period of ischemia can also lead to cellular death even though restoration of blood flow is necessary to salvage the myocardium. 

Reduced blood flow through orre or more coronary arteries causes myocardial ischemia and necrosis. 

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. 

Alternatives to FDG for detecting viable myocardium are based on myocardial leak of creatine phos-phokinase, inosine, inorganic phosphate [100-103] due to impaired cell membrane function induced by ischemia and/or necrosis. Therefore, the use of a potassium analogue reflecting myocardial cellular membrane function and the myocardial potassium space represents an alternative for a quantitative assessment of... 

Myocardial infarction. An area of coagulation necrosis in a tissue resulting from local ischemia in the heart. 

G10. Gurevitch, J., Frolkis, I., Yuhas, Y., Lifschitz-Mercer, B., Berger, E., Paz, Y., Matsa, M., Kramer A., and Mohr, R., Anti-tumor necrosis factor-alpha improves myocardial recovery after ischemia and reperfusion. J. Am. Coll. Cardiol. 30, 1554-1561 (1997). 

Several disease states can result from abnormal blood clots. For example, strokes were mentioned previously. However, the most common and deadliest thrombotic disease is myocardial infarction (MI). Atherosclerosis has long been associated with reduced cardiac function and elevated mortality due to rupture of atherosclerotic plaques. The rupture of an atherosclerotic plaque usually results not only in blockage due to the plaque itself but also in the immediate formation of an occlusive blood clot, which results in an MI. Immediately after the initiation of an MI, a zone of necrosis begins to develop around the area as ischemia proceeds. It is during this early phase of ischemia (several hours) that therapeutic intervention not only can be life-saving but also can minimize the amount of necrotic heart tissue formed. 

Based on a retrospective study of 344 patients with cocaine-associated chest pain, it has been suggested that patients who do not have evidence of ischemia or cardiovascular complications over 9-12 hours in a chest-pain observation unit have a very low risk of death or myocardial infarction during the 30 days after discharge (59). Nevertheless, patients with cocaine-associated chest pain should be evaluated for potential acute coronary syndromes those who do not have recurrent symptoms, increased concentrations of markers of myocardial necrosis, or dysrhythmias can be safely discharged after 9-12 hours of observation. A protocol of this sort should incorporate strategies for treating substance abuse, since there is an increased likelihood of non-fatal myocardial infarction in patients who continue to use cocaine. 

Protein kinase signal transduction pathways have been extensively studied and characterized in the myocardium. Ischemic preconditioning (IP) and the role of individual kinases involved is where much of the research efforts have been focused. IP is the reduction in susceptibility to myocardial infarction that follows brief periods of sublefhal ischemia (Murry et al, 1986). This reduction can manifest itself as a 4-fold reduction in infarct size, this being secondary to a delay in the onset and rate of cell necrosis during the subsequent lethal ischemia (Marber et al., 1994). 

---