Heart injuries

Although several potential therapeutic agents have been tested in animal models of ischemia/reperfusion heart injury with some success, nearly none of the specific antiapoptotic agents have reached the stage of clinical research [172]. The studies which have examined the effect of caspase inhibitors on ischemia/reperfusion models are summarized in Table 2. Broad-spectrum caspase inhibitors have been shown in many studies to reduce cardiomyo-cyte apoptosis, to reduce the size of MI, and to preserve heart function after MI [173-175, 178, 181]. The protective effect of caspase inhibitors can be seen when these agents are administered before or after the onset of ischemia but are most prominent when introduced before the onset of reperfusion [172, 175, 178]. Selective caspase inhibitors, on the other hand, have been reported to have varying effect they have been found to reduce cardiomyocytes apoptosis, but the infarct size remained unchanged [177, 178, 181],... 

We have previously shown [10,11] that following myocardial ischemia iron and copper are mobilized from the heart into the coronary flow, in an ischemia-duration-dependent manner, and that the level of the mobilized metals is well correlated with the degree of heart injury. Similar results were found by Cotin et al. [12] in patients with acute myocardial infarction treated by thrombolytic therapy. 

We have previously demonstrated that the extent of intracellular re-distribution and mobilization of iron, copper and proteins into the coronary flow depends on ischemic duration, and could serve as predictive criteria for the degree of heart injury [10,11]. The observed increase in iron and copper levels in the CFF ( free and bound states) resulted in the increase in free radicals production, which in turn could explain the post-ischemic heart damage. 

Smilkstein MJ. APAP-induced heart injury Maybe yes, maybe no. Next question. J Toxicol Clin Toxicol 1996 34 155-156. 

Granville, D.J., Gottlieb, R.A. Cytochromes P450 and ischemic heart injury Potential role for inhibitors in the treatment of myocardial infarction. Drug Discovery Today Technol. 2005, 2, 123-127. 

Toxicity oxycodone CR consists of a dual-polymer matrix, intended for oral use only. Abuse of the crushed tablet poses a hazard of overdose and death. This risk is increased with concurrent abuse of alcohol and other substances. With parenteral abuse, the tablet excipients, especially talc, can be expected to result in local tissue necrosis, infection, pulmonary granulomas, and increased risk of endocarditis and valvular heart injury. 

Surgical intervention in repeat sternotomy procedures requires sternal division with an oscillating saw. As there are often distinct adhesions between the posterior surface of the sternum and the heavily enlarged heart, injuries (especially of the right ventricle) are not unusual. Therefore, the surgeon has to be aware of that problem and should have experience in reoperative procedures. 

Isoflurane is a respiratory depressant (71). At concentrations which are associated with surgical levels of anesthesia, there is Htde or no depression of myocardial function. In experimental animals, isoflurane is the safest of the oral clinical agents (72). Cardiac output is maintained despite a decrease in stroke volume. This is usually because of an increase in heart rate. The decrease in blood pressure can be used to produce "deHberate hypotension" necessary for some intracranial procedures (73). This agent produces less sensitization of the human heart to epinephrine relative to the other inhaled anesthetics. Isoflurane potentiates the action of neuromuscular blockers and when used alone can produce sufficient muscle relaxation (74). Of all the inhaled agents currently in use, isoflurane is metabolized to the least extent (75). Unlike halothane, isoflurane does not appear to produce Hver injury and unlike methoxyflurane, isoflurane is not associated with renal toxicity. 

In the past, chloroform was used extensively as a surgical anesthetic, but this use was abandoned because exposure to narcotic concentrations often resulted in sudden death from effects on the heart and circulation or from severe injury to the Hver. In addition, chloroform for this and other consumer uses was harmed by FDA in 1976 with the discovery that it is carcinogenic in mice (38). When splashed into the eye, chloroform causes local pain and irritation, but serious injury is not expected. Skin contact for single, brief exposures ordinarily causes Htde or no local irritation. 

In most situations, adequate, usuaHy forced, ventilation is necessary to prevent excessive exposure. Persons who drink alcohol excessively or have Hver, kidney, or heart diseases should be excluded from any exposure to carbon tetrachloride. AH individuals regularly exposed to carbon tetrachloride should receive periodic examinations by a physician acquainted with the occupational hazard involved. These examinations should include special attention to the kidneys and the Hver. There is no known specific antidote for carbon tetrachloride poisoning. Treatment is symptomatic and supportive. Alcohol, oHs, fats, and epinephrine should not be given to any person who has been exposed to carbon tetrachloride. FoHowing exposure, the individual should be kept under observation long enough to permit the physician to determine whether Hver or kidney injury has occurred. Artificial dialysis may be necessary in cases of severe renal faHure. 

In general, arterial thrombi are platelet-rich ( white clots ) and form at ruptured atherosclerotic plaques, leading to intraluminal occlusion of arteries that can result in end-organ injury (e.g., myocardial infarction, stroke). In contrast, venous thrombi consist mainly of fibrin and red blood cells ( red clots ), and usually form in low-flow veins of the limbs, producing deep vein thrombosis (DVT) the major threat to life results when lower extremity (and, occasionally, upper extremity) venous thrombi embolize via the right heart chambers into the pulmonary arteries, i.e., pulmonary embolism (PE). 

Acute over-activation of NHE1 results in a marked elevation in intracellular sodium concentration with a subsequent increase in intracellular calcium, via the Na +/Ca++ exchanger. This in turn triggers a cascade of injurious events that can culminate in tissue dysfunction and ultimately apoptosis and necrosis. This is commonly seen in organs such as the heart, brain and kidneys as a consequence of ischemia-reperfusion. 

Mitochondria KATP channels Cardiac KATP channel opening has a role in myocardial preconditioning, a paradoxical form of cardioprotection wherein brief ischemic episodes can protect the heart from subsequent lethal ischemic injury. Openers including BMS-180448 and BMS-191095 have been reported to possess preferential cardioprotective effects over vasorelaxant effects by activating mitochondria KAXP channels. 

Polycystic kidney disease (Polycyst in-1 activates canonical Wnt signaling pathway) Injury-induced renal fibrosis Heart failure Ulcerative colitis Osteoporosis-Pseudoglioma Syndrome (genetic syndrome of defective bone formation) Ulcerative colitis Familial Alzheimer s disease (through interaction with Presenilin-1) Familial Alzheimer s disease (through interaction with Presenilin-1)... 

Histamine is a substance present in various tissues of die body, such as die heart, lungs, gastric mucosa, and skin (Pig. 36-1). The highest concentration of histamine is found in die basophil (a type of white blood cell) and mast cells diat are found near capillaries. Histamine is produced in response to injury. It acts on areas such as die vascular system and smooth muscle, producing dilatation of arterioles and an increased permeability of capillaries and venules. Dilatation of die arterioles results in localized redness. An increase in die permeability of... 

Based upon theoretical considerations of the mechanisms of hypothermic-induced cellular injury, we developed the University of Wisconsin organ preservation solution (UW solution) that has had a widespread and dramatic effect on organ preservation (Table 2). Prior to the development of this solution, the liver and pancreas could be preserved for only four to six hours. Thus, there was a large time constraint on liver and pancreas transplantation and many cadaveric organs were wasted. However, the UW solution increased preservation duration to 48 to 72 hours, and dramatically increased the quality and numbers of these organs transplanted. Furthermore, this solution appears effective for the preservation of the kidney for three days and the heart for at least 15 hours. 

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]. 

Not all toxic organophosphoms compounds have uses beneficial to humans. Sarin is an extremely toxic nerve gas that is lethal to humans. In March 1995 this substance was released in a terrorist attack on a Japanese subway, resulting in several deaths and many serious injuries. Sarin and related nerve gases bind an amino acid in the enzyme responsible for muscle action. When this enzyme is deactivated, muscles contract but cannot relax. Even a small dose can be lethal if the nerve gas reaches the muscles of the heart. 

In these 500 cases, there were 26 culture failures, an Incidence of about 5% Nine women of this group underwent a second aminocentesls, and successful cultures were obtained The other 17, or 3 4% of the total, did not obtain any results, either because of spontaneous abortions prior to the time a second amniocentesis could be performed (In four) or because the family elected not to proceed There were no Instances of severe or significant fetal Injury, although small linear "scars" were noted on four fetuses Three fetuses had abnormalities which were not related to the procedure Itself, Including spina bifida, osteogenesis Imperfecta, and congenital heart disease ... 

Crompton, M. and Costi, A. (1990). A heart mitochondrial Ca -dependent pore of possible relevance to re-perfusion-induced injury. Biochem. J. 266, 33-39. 

Misra, H.P., Weglicki, W.B., Abdulla, R- and McCay, P.B. (1984). Identification of a carbon centered free radical during reperfusion injury in ischemic rat heart. Circulation II, 260 (abstract). 

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