Myocardial injury

With regard to epinephrines potential adverse cardiac effects, it is important to remember that in anaphylaxis, the heart is a target organ. Mast cells located between myocardial fibers, in perivascular tissue, and in the arterial intima are activated through IgE and other mechanisms to release chemical mediators of inflammation, including histamine, leukotriene C4, and prostaglandin D2. Coronary artery spasm, myocardial injury, and cardiac dysrhythmias have been documented in some patients before epinephrine has been injected for treatment of anaphylaxis, as well as in patients with anaphylaxis who have not been treated with epinephrine [11, 12]. 

Following massive crush injury, myoglobin released from damaged muscle fibers colors the urine dark red. Myoglobin can be detected in plasma following a myocardial infarction, but assay of serum enzymes (see Chapter 7) provides a more sensitive index of myocardial injury. 

Ay H, Koroshetz WJ, Benner T, Vangel MG, Melinosky C, Arsava EM, Ayata C, Zhu M, Schwamm LH, Sorensen AG. Neuroanatomic correlates of stroke-related myocardial injury. Neurology 2006 66(9) 1325-1329. 

Vandeplassche, G., Bernier, M., Thone, F., Borgers, M., Kusama, Y. and Hearse, D.J. (1990). Singlet oxygen and myocardial injury ultrastructural, cytochemical and electrocardiographic consequences of photoactivation of rose bengal. J. Mol. Cell. Cardiol. 22, 287-301. 

Lauver DA, Lockwood SF, and Lucchesi BR. 2005. Disodium disuccinate astaxanthin (Cardax) attenuates complement activation and reduces myocardial injury following ischemia/reperfusion. Journal of Pharmacology and Experimental Therapeutics 314(2) 686-692. 

High antioxidative activity carvedilol has been shown in isolated rat heart mitochondria [297] and in the protection against myocardial injury in postischemic rat hearts [281]. Carvedilol also preserved tissue GSL content and diminished peroxynitrite-induced tissue injury in hypercholesterolemic rabbits [298]. Habon et al. [299] showed that carvedilol significantly decreased the ischemia-reperfusion-stimulated free radical formation and lipid peroxidation in rat hearts. Very small I50 values have been obtained for the metabolite of carvedilol SB 211475 in the iron-ascorbate-initiated lipid peroxidation of brain homogenate (0.28 pmol D1), mouse macrophage-stimulated LDL oxidation (0.043 pmol I 1), the hydroxyl-initiated lipid peroxidation of bovine pulmonary artery endothelial cells (0.15 pmol U1), the cell damage measured by LDL release (0.16 pmol l-1), and the promotion of cell survival (0.13 pmol l-1) [300]. SB 211475 also inhibited superoxide production by PMA-stimulated human neutrophils. 

As cardiac function decreases after myocardial injury, the heart relies on the following compensatory mechanisms (1) tachycardia and increased contractility through sympathetic nervous system activation (2) the Frank-Starling mechanism, whereby increased preload increases stroke volume (3) vasoconstriction and (4) ventricular hypertrophy and remodeling. Although these compensatory mechanisms initially maintain cardiac function, they are responsible for the symptoms of HF and contribute to disease progression. 

Myocardial injury was reported in guinea pigs exposed to 26-52 ppm for 41 days, and rabbits exhibited qualitatively similar but less severe effects after 88 days of similar exposure (Deichmann et al. 1944). 

The injury was characterized by myocardial inflammation, degeneration, and necrosis, interstitial fibrosis, and lymphocyte infiltration. Since only a range was given for the exposure level (26-52 ppm), the exact level of phenol in air that resulted in myocardial injury was not established and may be as low as 26 ppm or as high as 52 ppm. Interpretation of this study is further complicated by an apparent lack of controls. However, the heart pathology was so severe that it is difficult to ascribe the effects to any... 

Despite the advances in pharmacological therapy, cardiovascular surgery and cardiology, more than half of the patients with clinically evident heart failure die within 5 years of the initial diagnosis. The myocardial injury is usually irreversible because healing pathways are only expressed for a short time (Penn et al., 2004). 

In a proof-of-concept study in which Saito et al. [60] intravenously injected LacZ reporter gene-transfected MSCs into healthy rats, the MSCs preferentially engrafted in the bone marrow. When injected into rats subjected to repetitive periods of ischemia/reperfusion, however, the MSCs engrafted in the infarcted regions of the heart, where they participated in angiogenesis and expressed cardio-myocyte-specific proteins. When injected into rats 10 days after myocardial injury, MSCs preferentially homed to damaged myocardium. 

Siminiak T, Kalawski R, Fiszer D, Jerzykowska O, Rzezniczak J, Rozwadowska N, Kurpisz M. Autologous skeletal myoblast transplantation for the treatment of postinfarction myocardial injury phase I clinical study with 12 months of follow-up. Am Heart J 2004 148 531-537. 

Many pathological conditions, including ischemia/reperfusion, inflammation, and sepsis may induce tissues to simultaneously produce both superoxide and nitric oxide. For example, ischemia allows intracellular calcium to accumulate in endothelium (Fig. 20). If the tissue is reperfused, the readmission of oxygen will allow nitric oxide as well as superoxide to be produced (Beckman, 1990). For each 10-fold increase in the concentration of nitric oxide and superoxide, the rate of peroxynitrite formation will increase by 100-fold. Sepsis causes the induction of a second nitric oxide synthase in many tissues, which can produce a thousand times more nitric oxide than the normal levels of the constitutive enzyme (Moncada et al., 1991). Nitric oxide and indirectly peroxynitrite have been implicated in several important disease states. Blockade of nitric oxide synthesis with N-methyl or N-nitroarginine reduces glutamate-induced neuronal degeneration in primary cortical cultures (Dawson et al., 1991). Nitroarginine also decreases cortical infarct volume by 70% in mice subjected to middle cerebral artery occlusion (Nowicki et al., 1991). Myocardial injury from a combined hy-... 

The anthracycline antibiotics, which include doxorubicin, daunorubicin, bleomycin, and mitomycin C, inhibit DNA and RNA synthesis. Doxorubicin also interfers with topoisomerase II (a DNA gyrase), the activity of which is markedly increased in proliferating cells. Structurally related to doxorubicin are epirubicin and mitozantrone. The cytotoxic antibiotics are used to treat leukaemias and lymphomas and also for solid tumours in the breast, lung, thyroid and ovary. Cardiotoxicity is the major dose-limiting factor, with arrhythmias and myocardial depression (Bacon and Nuzzo 1993). The chronic phase of cardiotoxicity is a dose-dependent cardiomyopathy that leads to congestive heart failure in 2-10% of patients. Myocardial injury is the result of oxygen free radical formation. Children are particularly sensitive to these cardiotoxic reactions and may require a heart transplant in their later years. Epirubicin is less cardiotoxic than doxorubicin. 

The term, arrhythmogenic substrate, became a matter of interest to many researchers. The arrhythmogenic substrate means the pathologic and anatomic preconditions for the initiation of tachyarrhythmias such as myocardial fibrosis, aneurysm, the border zone between normal and ischemic or infarcted tissue, scars, diffuse myocardial injury in cardiomyopathy or the chronic alterations induced by myocarditis, and furthermore, accessory pathways or variations in the specific cardiac conduction system. These anatomic or pathologic altera-... 

Tracey WR, Magee WP, Oleynek JJ, Hill RJ, Smith AH, Flynn DM, Knight DR (2003) Novel N6-substituted adenosine 5 -N-methyluronamides with high selectivity for human adenosine A3 receptors reduce ischemic myocardial injury. Am J Physiol-Heart Circ Physiol... 

Tracey WR, Magee W, Masamune H, Kennedy SP, Knight DR, Buchholz RA, Hill RJ (1997) Selective adenosine A3 receptor stimulation reduces ischemic myocardial injury in the rabbit heart. Cardiovasc Res 33(2) 410-415... 

Tracey WR, Magee W, Masamune H, Oleynek JJ, Hill RJ (1998) Selective activation of adenosine A3 receptors with N6-(3-chlorobenzyl)-5 -N-methylcarboxamidoadenosine (CB-MECA) provides cardioprotection via KATp channel activation. Cardiovasc Res 40(1) 138—145 Tracey WR, Magee WP, Oleynek JJ, Hill RJ, Smith AH, Flynn DM, Knight DR (2003) Novel N6-substituted adenosine 5 -N-methyluronamides with high selectivity for human adenosine A3 receptors reduce ischemic myocardial injury. Am J Physiol Heart Circ Physiol 285(6) H2780-H2787... 

Tilley SL, Tsai M, Williams CM, Wang ZS, Erikson CJ, Galli SJ, Roller BH (2003) Identification of A3 receptor- and mast cell-dependent and -independent components of adenosine-mediated airway responsiveness in mice. J Immunol 171(1) 331—337 Toledo-Pereyra LH, Toledo AH, Walsh J, Lopez-Neblina F (2004) Molecular signaling pathways in ischemia/reperfusion. Exp Clin Transplant 2(1) 174-177 Tracey WR, Magee W, Masamune H, Kennedy SP, Knight DR, Buchholz RA, Hill RJ (1997) Selective adenosine A3 receptor stimulation reduces ischemic myocardial injury in the rabbit heart. Cardiovasc Res 33(2) 410-415... 

Gupta MS, Singh H, Gupta BK, et al. 1995b. Acute myocardial injury in aluminum phosphide poisoning. J Assoc Physicians India 43 58. 

Byun, J. H., Huh, J. E., Park, S. J. et al. (2000). Myocardial injury-induced fibroblast proliferation facilitates retroviral-mediated gene transfer to the rat heart in vivo. J. Gene Med. 2(1), 2-10. 

Herrmann J. Peri-procedural myocardial injury 2005 update. Eur Heart J 2005 26 2493-2519. 

Selvanayagam JB, Porto I, Channon K, et al, Troponin elevation after percutaneous coronary intervention directly represents the extent of irreversible myocardial injury insights from cardiovascular magnetic resonance imaging, Circulation 2005 ... 

The continuum of myocardial injury that is initiated by a coronary ischemic event and perpetuated by reperfusion [ischemia/reperfusion (l/R) injury] may be clinically manifested in patients undergoing thrombolytic therapy following an... 

In the past 15 years, an extensive amount of preclinical data has been on the reparative potential of cell transplantation in acute and chronic myocardial injury. Since the first preclinical report of functional repair after the injection of autologous skeletal myoblasts into the injured heart in 1998 (7), a variety of cell types or combinations (Table I) have been proposed for transplantation during different stages of CVD (19). Preclinical data has been promising, and in at least one study, the amount of repair achieved with cell transplantation in HF is additive to current medical treatment (20). With the first cardiac clinical application in 2001 (8), the field rapidly moved from bench to bedside, and at present, we are gaining valuable information about the questions to ask and the early answers from both animal and human studies. To date, 19 clinical trials either in AMI (Table 2) or chronic HF have been published (21) (Table 3), including 13, where BM... 

In the context of acute myocardial injury where the maximal restoration of blood flow to the ischemic/hibernating... 

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