Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the behavior of circulating endothelin and atrial natriuretic peptide (ANP) during coronary artery bypass graft (CABG) surgery, blood samples from patients with coronary artery disease (n = 8) were investigated before, during and after operation. Plasma levels of endothelin and ANP were determined using the radioimmunoassay method. Baseline plasma levels were compared to those of normal volunteers (n = 6). Left ventricular function at rest and as a response to isometric exercise was evaluated using radionuclide ventriculography before and after coronary bypass surgery. The mean endothelin value was found to be within normal limits, however the mean ANP value was slightly higher than control. Patients had significantly improved left ventricular systolic and diastolic function after surgery. The mean endothelin level was higher than initial values immediately after extra-corporeal circulation and returned to initial values in two hours. However, ANP values were increased and remained higher than initial values. Baseline endothelin values were negatively correlated with systolic function parameters, whereas endothelin and heart rate had a positive correlation before extra-corporeal circulation. Coronary artery bypass graft surgery may cause an increase in the circulating endothelin level either due to endothelial injury or due to myocardial ischemia and hypothermia. Following surgery, increased endothelin levels returned to normal values immediately.
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PMID:Changes in the circulating endothelin and atrial natriuretic peptide levels during coronary artery bypass surgery. 816 37

We assessed the activation of p38-MAPK (mitogen-activated protein kinase) by osmotic and thermal stresses in the isolated perfused amphibian (Rana ridibunda) heart. Hyperosmotic stress induced the rapid activation of the kinase. In particular, in the presence of 0.5 mol l(-1) sorbitol, p38-MAPK was maximally phosphorylated (by approximately twelvefold) at 15 min, while excess of NaCl (206 mmol l(-1) final concentration) or KCl (16 mmol l(-1) final concentration) stimulated a less potent activation, maximised (by approximately eightfold and fourfold) within 2 min and 30 s, respectively, relative to control values. The effect of all three compounds examined was reversible, since the kinase phosphorylation levels decreased upon reperfusion of the heart with normal bicarbonate-buffered saline. Conversely, hypotonicity did not induce any p38-MAPK activation. Furthermore, both hypothermia and hyperthermia induced considerable phosphorylation of the kinase, by four- and 7.5-fold, respectively, relative to control values. Immunohistochemical studies elucidated the localisation pattern of phospho-p38-MAPK and also revealed enhanced atrial natriuretic peptide (ANP) immunoreactivity in osmotically stressed hearts. Interestingly, SB 203580 (1 micromol l(-1)) not only completely blocked the activation of p38-MAPK by all these interventions, but also abolished the enhanced ANP immunoreactivity induced by 0.5 mol l(-1) sorbitol. These findings indicate the possible involvement of ANP in the mechanisms regulating responses under such stressful conditions.
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PMID:Hyperosmotic and thermal stresses activate p38-MAPK in the perfused amphibian heart. 1189 58

The National Heart, Lung, and Blood Institute convened a Workshop on September 20-21, 2010, "New Horizons in Cardioprotection," to identify future research directions for cardioprotection against ischemia and reperfusion injury. Since the early 1970s, there has been evidence that the size of a myocardial infarction could be altered by various interventions. Early coronary artery reperfusion has been an intervention that consistently reduces myocardial infarct size in animal models as well as humans. Most cardiologists agree that the best way to treat acute ST-segment elevation myocardial infarction is to reperfuse the infarct artery as soon as possible and to keep the infarct artery patent. In general, stenting is superior to angioplasty, which is superior to thrombolysis. There is no accepted adjunctive therapy to acutely limit myocardial infarct size along with reperfusion that is routinely used in clinical practice. In the Kloner experimental laboratory, some adjunctive therapies have reproducibly limited infarct size (regional hypothermia, preconditioning, cariporide, combinations of the above, remote preconditioning, certain adenosine agonists, and late sodium current blockade). In clinical trials, a host of pharmacologic adjunctive therapies have failed to either reduce infarct size or improve clinical outcome. Potential reasons for the failure of these trials are discussed. However, some adjunctive therapies have shown promise in data subanalyses or subpopulations of clinical trials (adenosine, therapeutic hypothermia, and hyperoxemic reperfusion) or in small clinical trials (atrial natriuretic peptide, ischemic postconditioning, and cyclosporine, the mitochondrial permeability transition pore inhibitor). A recent clinical trial with remote conditioning induced by repetitive inflation of a brachial artery cuff begun prior to hospitalization showed promise in improving myocardial salvage and there are several reports in the cardiothoracic literature, suggesting that remote preconditioning protects hearts during surgery. Thus, in 2011, there is hope that applying some of the body's own conditioning mechanisms may provide protection against ischemic damage.
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PMID:State of the science of cardioprotection: Challenges and opportunities--proceedings of the 2010 NHLBI Workshop on Cardioprotection. 2182 20

Coronary heart disease (CHD) is the leading cause of death and disability in Europe. For patients presenting with an acute ST-segment elevation myocardial infarction (STEMI), timely myocardial reperfusion using either thrombolytic therapy or primary percutaneous coronary intervention (PPCI) is the most effective therapy for limiting myocardial infarct (MI) size, preserving left-ventricular systolic function and reducing the onset of heart failure. Despite this, the morbidity and mortality of STEMI patients remain significant, and novel therapeutic interventions are required to improve clinical outcomes in this patient group. Paradoxically, the process of myocardial reperfusion can itself induce cardiomyocyte death-a phenomenon which has been termed 'myocardial reperfusion injury' (RI), the irreversible consequences of which include microvascular obstruction and myocardial infarction. Unfortunately, there is currently no effective therapy for preventing myocardial RI in STEMI patients making it an important residual target for cardioprotection. Previous attempts to translate cardioprotective therapies (antioxidants, calcium-channel blockers, and anti-inflammatory agents) for reducing RI into the clinic, have been unsuccessful. An improved understanding of the pathophysiological mechanisms underlying RI has resulted in the identification of several promising mechanical (ischaemic post-conditioning, remote ischaemic pre-conditioning, therapeutic hypothermia, and hyperoxaemia), and pharmacological (atrial natriuretic peptide, cyclosporin-A, and exenatide) therapeutic strategies, for preventing myocardial RI, many of which have shown promise in initial proof-of-principle clinical studies. In this article, we review the pathophysiology underlying myocardial RI, and highlight the potential therapeutic interventions which may be used in the future to prevent RI and improve clinical outcomes in patients with CHD.
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PMID:Myocardial reperfusion injury: looking beyond primary PCI. 2353 10

Despite major advances in mechanical and pharmacological reperfusion strategies to improve acute myocardial infarction (MI) injury, substantial mortality, morbidity, and socioeconomic burden still exists. To further reduce infarct size and thus ameliorate clinical outcome, the focus has also shifted towards early detection of MI with high-sensitive troponin assays, imaging, cardioprotection against pathophysiological targets of myocardial reperfusion injury with mechanical (ischaemic post-conditioning, remote ischaemic pre-conditioning, therapeutic hypothermia, and hypoxemia) and newer pharmacological interventions (atrial natriuretic peptide, cyclosporine A, and exenatide). Evidence from animal models of myocardial ischaemia and reperfusion also demonstrated promising results on more selective anti-inflammatory compounds that require additional validation in humans. Cardiac stem cell treatment also hold promise to reduce infarct size and negative remodelling of the left ventricle that may further improves symptoms and prognosis in these patients. This review focuses on the pathophysiology, detection, and reperfusion strategies of ST-segment elevation MI as well as current and future challenges to reduce ischaemia/reperfusion injury and infarct size that may result in a further improved outcome in these patients.
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PMID:Pathophysiology of ST-segment elevation myocardial infarction: novel mechanisms and treatments. 2654 47