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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The etiology of sudden-death ischemic heart disease (SDIHD) remains an enigma. Data will be presented which suggest that SDIHD may be due to hypomagnesemia in and around the coronary arterial and arteriolar vessels. We have found that blood vessels (especially arteries and arterioles) deficient with respect to Mg can undergo constriction and spasm; the greater the reduction in Mg2+, the greater the magnitude of the spontaneous contractile responses. The higher the Ca2+:Mg2+ ratio, the greater are the magnitudes of these contractile responses. A severe deficit in surface membrane Mg2+, in particular, results in intense vasospasm. Using direct in situ high resolution microscopy (3000 x), we have found that a lowering of Mg2+ around perfused arterioles (15--20 microns i.d.) will also result in spontaneous vasoconstriction and, in addition, increased arteriolar resistance, tissue ischemia and reduced venous outflow. We have also found that the constrictor actions of certain circulating vasoconstrictor hormones (i.e., angiotensin, serotonin, acetylcholine) are enhanced when [Mg2+] is lowered below the levels normally found in plasma. Other direct studies, from our laboratory, indicate that [Mg2+]o regulates calcium exchange and content of vascular smooth muscle. In summary, the concept to be presented suggests that a deficiency in dietary Mg2+ is a key factor in the high incidence of mortality noted in SDIHD in nations of the Western world. The hypomagnesemia produces progressive vasoconstriction, vasospasm and ischemia, which, given time, will lead to SDIHD.
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PMID:Sudden-death ischemic heart disease and dietary magnesium intake: is the target site coronary vascular smooth muscle? 39 Mar 30

The pathogenesis of primary Raynaud's phenomenon remains an enigma. Most evidence favors a local abnormality in the digital arteries as opposed to an increased activity of the sympathetic nervous system. The local fault may involve the alpha 2-adrenergic receptors, which are most important in reflex sympathetic vasoconstriction. Cooling blood vessels increase the sensitivity of alpha 2-adrenergic receptors, increased levels of alpha 2-adrenergic receptors are present in primary Raynaud's disease, and patients show an increased sensitivity to alpha 2-adrenergic receptor agonists on finger blood flow. Serotonin has also been implicated, but the evidence is not compelling. In secondary Raynaud's phenomenon, vasospastic attacks can often be explained by a low arterial distending pressure, a thickened vessel wall, or absence of beta-adrenergic receptor activity. Diagnosis of primary Raynaud's disease relies on a typical history and normal physical examination, laboratory studies, and nailfold capillaroscopy. Finger systolic blood pressures during local cooling with ischemia may be helpful to document vasospastic attacks but does not distinguish primary from secondary Raynaud's phenomenon. The treatment of Raynaud's phenomenon is usually conservative. Pavlovian conditioning or biofeedback may be beneficial. When drug therapy is necessary, the calcium channel entry blocker nifedipine or sympatholytic agents have been shown to decrease the frequency and duration of vasospastic attacks in about two thirds of patients, although subjective improvement does not usually correlate with objective testing. Direct-acting vasodilators have not been shown to be of definite benefit. New therapies include prostaglandins, captopril, and the serotonergic antagonist ketanserin. Surgical sympathectomy has not been beneficial.
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PMID:Raynaud's phenomenon. An update. 202 4

Acute renal failure after contrast media injection has been recognized for at least 35 years but the exact mechanism responsible for the renal injury remains an enigma. The clinical characteristics of contrast-induced nephropathy (CAN) are well-known although more recently the nonoliguric presentation has occurred at an increased frequency--in 70 to 90% of cases. For nonoliguric presentation of CAN, one can expect an asymptomatic increase in serum creatinine, the mean peak occurring at 4.2 days. If oliguric, the fractional excretion of sodium will be less than 1% and resistant to either fluid challenge or loop diuretics. Preexisting renal insufficiency, with or without diabetes mellitus, increases the risk of CAN 6- to 10-fold but recovery is expected, with less than 10% of all patients requiring dialytic support. Despite the growing body of published reports, the lack of a suitable animal model to evaluate various proposed mechanisms of renal injury has compromised our ability to devise a technique for preventing CAN. A popular scheme has been proposed to describe the possible sequence by which ischemia or nephrotoxins, or both, induce acute renal failure. In particular, a vascular mechanism (i.e., ischemia), is an appealing explanation for CAN since acute changes in renal hemodynamics after contrast media injection have been confirmed by several animal experiments. Unlike other vascular beds in which contrast media induce acute vasoconstriction followed by vasodilatation, the initial effect on the renal circulation is acute vasodilatation, followed by progressive vasoconstriction, increasing renal vascular resistance and a concomitant decrease in both renal blood flow and glomerular filtration rate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Experimental contrast-associated nephropathy and its clinical implications. 223 94

Several workers have used histochemical, enzymatic, and fluorescent methods to diagnose early myocardial ischemia, but the problem of unequivocal detection of early ischemia still remains an enigma to pathologists. In the present study, the left coronary artery was ligated in an animal model, rat, in order to produce myocardial ischemia at different time intervals, from five minutes to six hours. Fluorescent techniques and tetrazolium staining of myocardial succinic dehydrogenases have been used to detect onset of ischemia with the purpose of identifying a sensitive technique for use in routine pathologic specimens. Nitroso-blue tetrazolium and triphenyl tetrazolium chloride staining of myocardium showed loss of dehydrogenases within five to twenty minutes of ligation of the coronary artery. This loss was consistent and progressively increased at longer time intervals, the mean ischemic area mapped being 25.74 mm2 and 66.87 mm2 at five to twenty minutes and six hours respectively. Such comparison of ischemic area of myocardium at different time intervals has not been reported earlier. Autofluorescence in formalin-fixed, hematoxylin and eosin-stained sections showed positive fluorescence only after fifty to seventy-five minutes of ischemia and was patchy in distribution in the left ventricular wall even up to six hours of ligation. Examination of myocardium under fluorescent light after acridine orange staining proved to be more sensitive than autofluorescence for detecting ischemia. At five to twenty minutes, the mean ischemic area was 18.67 mm2 and by six hours it increased to 27.48 mm2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Histochemical and fluorescent techniques for detection of early myocardial ischemia following experimental coronary artery occlusion: a comparative and quantitative study. 245 Apr 89

Motility disorders of the gut in children have become a matter of increasing concern for the pediatric surgeon. Infantile hypertrophic pyloric stenosis is the most common disease requiring surgery in early infancy. While this entity was first described as early as 1888 by Hirschsprung, its etiology and pathogenesis are still an enigma. Fortunately, its surgical treatment is simple and safe, which cannot be said of all other motility disorders of the infantile gut. Dysmotility in small bowel atresia and in gastroschisis is related to damaged smooth muscle cells caused by concomitant ischemia of the bowel wall. In contrast, the temporarily adynamic bowel of the prematurely born child, as well as Hirschsprung's disease and related disorders, is the result of anomalies of the intestinal innervation. The pathogenesis of congenital malformations of the enteric nervous system is still a mystery to surgeons and physicians alike. With his pressure studies of the colon, Swenson first recognized Hirschsprung's disease for what it was. This led to the resection of the manometrically diagnosed abnormal colon, which was found to be aganglionic. Histological investigation of the bowel wall became the decisive tool, replacing manometry, in the diagnosis of Hirschsprung's disease. Histochemical investigation of the bowel wall is not conclusive in other malformations of the enteric nervous system, since the presence or absence of enteric neurons is not the definitive factor discriminating between normally and abnormally functioning bowel. Monoclonal antibodies raised against neuron-specific markers may become important tools for differentiation within the spectrum of congenital malformations of the enteric nervous system. The immunocytochemical technique, however, does not provide sufficient information to explain the cause of innervation disorders of the gut in infancy and childhood. Primary migration disturbances or selective disappearance of enteric neurons following ischemia are highly unlikely to cause aganglionosis of the gut. With respect to the pathogenesis and etiology of Hirschsprung's disease, current research is focused on the embryonic bowel (target organ) in plexus formation. The enteric nervous system is still an enigma, although its origin is known, at least in birds. Why neural crest cells travel, along what paths, how they reach their destination, and what may go wrong during the migratory process, are questions that must be answered. There is increasing knowledge concerning the way in which neural crest cells aggregate and form plexuses in the gut. It is largely unknown why neural crest cells settle, in the bowel, at the sites of the myenteric and submucous plexus.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Diagnosis of innervation-related motility disorders of the gut and basic aspects of enteric nervous system development. 251 2

A short period of ischemia followed by reperfusion produces a state of affairs in which the cells' potential for surviving longer ischemia is enhanced. This is called ischemic preconditioning. The effects of preconditioning are also related to the reperfusion damage which ensues upon tissue oxygenation. The role of the cellular energy state in reperfusion damage remains an enigma, although ischemic preconditioning is known to trigger mechanisms which contribute to the prevention of unnecessary ATP waste. In some species up to 80% of ATP hydrolysis in ischemia can be attributed to mitochondrial F1-F0-ATPase (ATP synthase), and a role for its inhibitor protein (IF1) in ATP preservation has been proposed. Although originally regarded as limited to large animals with a slow heart beat, inhibition by IF1 is probably a universal phenomenon. Coincidentally with ATPase inhibition, the decline in cellular ATP slows down, but even so the difference in ATP concentration between preconditioned and non-conditioned hearts is still small at the final stages of a long ischemia, when the beneficial effect of preconditioning is observable, although the energy state during reperfusion remains low in hearts which do not recover.
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PMID:Role of cellular energetics in ischemia-reperfusion and ischemic preconditioning of myocardium. 974 33

The transitory memory disturbance known as transient global amnesia (TGA) remains an enigma from a pathogenic point of view. In spite of its typical benign prognosis, TGA is a frightening experience for patients and their relatives. Moreover, a TGA episode usually leads to extensive investigation of patients in search of organic alterations that might be responsible for the event. Finally, TGA generates queries about therapeutic choices. In this review, we critically re-evaluate the evidence in support of and against the three main pathogenic hypotheses (i.e. ischemia, seizure discharge, and migraine), and we conclude that none of these appears completely convincing. Given the good prognosis and the lack of association with organic and instrumental abnormalities, we advance the hypothesis that TGA may be related to psychological disturbances causing transient alteration in brain metabolism and, consequently, amnesia. Our conclusion has relevant consequences in the evaluation of patients with TGA.
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PMID:Transient global amnesia: a review emphasizing pathogenic aspects. 1108 3

Eales disease, first described by Henry Eales in 1880, remains an enigma. The disease, observed more commonly in the Indian subcontinent than in the rest of the world, occurs in young healthy adult males, initially presenting as retinal periphlebitis and later as retinal ischemia that may lead to vascular alterations and neovascularization. Recurrent vitreous hemorrhage with or without retinal detachment is the common sequelae. In recent years, immunological, molecular biological, and biochemical studies have indicated the role of human leukocyte antigen, retinal autoimmunity, mycobacterium tuberculosis genome, and free radical mediated damage in the etiopathogenesis of this disease. However, its etiology appears to be multifactorial. The management depends on the stage of the disease and consists of medical treatment with oral corticosteroids in the active inflammatory stage and laser photocoagulation in the advanced retinal ischemia and neovascularization stages. The results of vitreoretinal surgery have been found to be satisfactory in case of vitreous hemorrhage with or without retinal detachment.
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PMID:Eales disease--an update. 1205 8

More than 10 years after its discovery, the function of cyclooxygenase-2 (COX-2) in the cardiovascular system remains largely an enigma. Many scholars have assumed that the allegedly detrimental effects of COX-2 in other systems (e.g. proinflammatory actions and tumorigenesis) signify a detrimental role of this protein in cardiovascular homeostasis as well. This view, however, is ill-founded. Recent studies have demonstrated that ischemic preconditioning (PC) upregulates the expression and activity of COX-2 in the heart, and that this increase in COX-2 activity mediates the protective effects of the late phase of PC against both myocardial stunning and myocardial infarction. An obligatory role of COX-2 has been observed in the setting of late PC induced not only by ischemia but also by delta-opioid agonists and physical exercise, supporting the view that the recruitment of this protein is a central mechanism whereby the heart protects itself from ischemia. The beneficial actions of COX-2 appear to be mediated by the synthesis of PGE(2) and/or PGI(2). Since inhibition of iNOS in preconditioned myocardium blocks COX-2 activity whereas inhibition of COX-2 does not affect iNOS activity, COX-2 appears to be downstream of iNOS in the protective pathway of late PC. The results of these studies challenge the widely accepted paradigm that views COX-2 activity as detrimental. The discovery that COX-2 plays an indispensable role in the anti-stunning and anti-infarct effects of late PC demonstrates that the recruitment of this protein is a fundamental mechanism whereby the heart adapts to stress, thereby revealing a novel, hitherto unappreciated cardioprotective function of COX-2. From a practical standpoint, the recognition that COX-2 is an obligatory co-mediator (together with iNOS) of the protection afforded by late PC has implications for the clinical use of COX-2 selective inhibitors as well as nonselective COX inhibitors. For example, the possibility that inhibition of COX-2 activity may augment myocardial cell death by obliterating the innate defensive response of the heart against ischemia/reperfusion injury needs to be considered and is the object of much current debate. Furthermore, the concept that the COX-2 byproducts, PGE(2) and/or PGI(2), play a necessary role in late PC provides a basis for novel therapeutic strategies designed to enhance the biosynthesis of these cytoprotective prostanoids in the ischemic myocardium. From a conceptual standpoint, the COX-2 hypothesis of late PC expands our understanding of the function of this enzyme in the cardiovascular system and impels a critical reassessment of current thinking regarding the biologic significance of COX-2.
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PMID:Discovery of a new function of cyclooxygenase (COX)-2: COX-2 is a cardioprotective protein that alleviates ischemia/reperfusion injury and mediates the late phase of preconditioning. 1216 Sep 47

Review of the published literature on adenosine and cardioprotection could lead one to paraphrase the famous words of Sir Winston Churchill (Radio broadcast, 1 October 1939 (in reference to Russia)) and conclude: 'I cannot forecast to you the action of adenosine. It is a riddle wrapped in a mystery inside an enigma'. That is, although it is well-established that adenosine can render cardiomyocytes resistant to lethal ischemia/reperfusion-induced injury, new and intriguing insights continue to emerge as to the mechanisms by which adenosine might limit myocardial infarct size.
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PMID:Cardioprotection with adenosine: 'a riddle wrapped in a mystery'. 1589 4


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