Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The major neuropathological lesions defining Alzheimer's disease (AD) include neurofibrillary tangles and amyloid plaques, which are mainly composed of abnormally phosphorylated tau and amyloid-beta (A beta), respectively. Numerous neuropathological and neuroimaging studies indicate that at least one-third of AD cases are complicated by some degree of vascular pathology, whereas in a similar proportion of patients clinically diagnosed with vascular dementia, AD pathology is also present. Many classical vascular risk factors such as hypertension, diabetes mellitus, and hypercholesterolemia have recently been shown also to increase the risk of AD. Growing evidence suggests that vascular pathology lowers the threshold for the clinical presentation of dementia at a given level of AD-related pathology and potentially directly promotes AD lesions such as A beta plaques. Cerebral ischemia, chronically up-regulates expression of the amyloid precursor protein (APP), which is the precursor to the amyloid beta peptide and damages the blood-brain barrier (BBB), affecting A beta peptide clearance from the brain. Recognition of the importance of these vascular risk factors for AD-related dementia and their treatment will be beneficial not only for preventing cardiac, cerebral, and peripheral complications of vascular disease, but also will likely have a direct impact on the occurrence of sporadic AD in older subjects. In this paper, we review some of the links between vascular risk factors and AD pathology and present data on the direct effect of ischemia on cognitive function and A beta deposition in a mouse model of AD.
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PMID:Links between the pathology of Alzheimer's disease and vascular dementia. 1517 82

Part 1: Technical and methodological issues. Contrast echocardiography is based on the use of gas microbubbles. The size, gas composition and shell structure of the microbubbles modify their stability, resistance to pressure and scattering behavior. A proposed classification of contrast agents is based on the modalities of production of microbubbles (galenic or industrial); the industrial agents are divided into three generations depending on their characteristics. Following venous administration, the industrial microbubbles behave as intravascular free-flowing tracers and this is fundamental for their use in perfusion studies. When insonated at a low acoustic pressure, microbubbles show a linear behavior and can be used for signal amplification. At intermediate acoustic pressures microbubbles resonate and produce a harmonic signal that is detectable by new scanners. Higher acoustic pressures cause microbubble disruption with emission of a transient acoustic signal. The available contrast agents behave differently in an ultrasound field. Part 2: Safety of contrast echocardiography. Galenic contrast agents were tested in many studies for intracoronary and intravenous injection and no clinically relevant side effects were detected. The intravenous injection of industrial contrast agents is safe in all conditions, even in acute coronary syndromes. The interaction between ultrasound and microbubbles produces energy with potential effects on tissue for inertial cavitation and acoustic current production. These effects seem particularly interesting for the therapeutic applications of contrast echocardiography, but they do not appear to have clinically relevant effects. Part 3: Experimental studies. Experimental studies in contrast echocardiography are designed to induce, in animal models, acute myocardial infarction and coronary artery stenosis and to evaluate the differences in blood flow. The risk area and infarct area are well visualized with serial contrast agent infusion. No-reflow after coronary occlusion is a well-known phenomenon and is detectable at contrast echocardiography. Different degrees of induced coronary stenosis cause differences in the regional flow rate. The results of contrast echocardiographic studies are comparable with those of other invasive flow measurements. Caution must be used to transfer the knowledge acquired from animal studies to the clinical arena, owing to both methodological and anatomical differences. Part 4: Enhancement of Doppler signal and coronary flow study. The anterior descending coronary artery flow is detectable in almost all patients, and the posterior descending coronary artery in about 70%. The coronary flow reserve can be measured by injection of a vasodilator agent (dipyridamole or preferably adenosine) with a success rate of almost 100 % for the anterior descending but only 50 % for the posterior descending coronary artery. Data from transthoracic studies are comparable with those of Doppler flow wire. The fields of application presently include the evaluation of acute myocardial infarction, the short- and long-term results of percutaneous coronary interventions and coronary grafts, and the study of the microcirculation in several clinical conditions where the coronary flow reserve may be reduced, such as in syndrome X, hypertension, hypercholesterolemia or diabetes. Part 5: Endocardial border enhancement. Opacification of the left ventricle is the main indication to contrast echocardiography that, in this setting, is principally used to improve endocardial border delineation. This allows accurate evaluation of left ventricular volumes and function, increasing the role of echocardiography for the quantitative study of the left ventricle. Other indications for left ventricular opacification are the identification of intraventricular thrombosis, non-compaction of the left ventricle and heart rupture. In this respect, industrial second-generation contrast agents are more useful. The most appropriate patients for contrast echocardiography are those with a poor or suboptimal acoustic window, in whom a predictable diagnostic and prognostic usefulness of the procedure is expected. If appropriately used, contrast echocardiography is a cost-effective technique, although lack of reimbursement presently limits its use. Part 6: Use of contrast agents during stress echocardiography. Contrast agents during stress echocardiography may be used to improve the diagnostic accuracy of the test and to study myocardial perfusion. The diagnosis of ischemia in stress echo relies on the operator's visual assessment of changes in contractility during stress. Contrast agents must be considered an important tool that improve image quality especially in patients with an intermediate or poor acoustic window and their use has been reported to be cost-effective in the few studies designed to this end. The evaluation of myocardial perfusion during stress is certainly one of the most important goals of contrast echocardiography. Preliminary data are interesting but there is still a number of methodological problems that currently hamper clinical application. Part 7: Myocardial perfusion. Echocardiography has the potential of visualizing microbubbles in the microcirculation by detecting stimulated acoustic emission, produced by high-energy applied ultrasound, or by detecting the harmonic signal produced by resonance of the microbubbles in a low-energy ultrasound field. In the first case images are triggered at increasing end-systolic intervals (intermittent imaging), whereas in the second case entire cardiac cycles are analyzed (real-time imaging). Continuous infusion is the preferred method of maintaining a large and constant microbubble concentration inside the microcirculation. Analysis of the perfusion signal may be made in the qualitative, semi-quantitative or quantitative mode. Quantitative analysis is based on the construction of videointensity-time curves to study the refilling phase after complete microbubble destruction. There are not enough data in the literature showing the additional role of quantitative analysis for clinical purposes. Thus, at present, quantitative softwares should be considered as research tools. Conversely, there is a general consensus based on experimental and clinical studies on the use of myocardial contrast echo in patients with acute myocardial infarction by means of qualitative or semi-quantitative analysis. Important information on the infarct area extension, on the efficacy of reperfusion therapy, on the presence and extension of the no-reflow phenomenon and on the extent of residual tissue viability may be derived from the routine use of myocardial contrast echo. The reference technique still remains myocardial scintigraphy even though many theoretical problems are being discussed. Part 8: Implementing ultrasound contrast in the echocardiography laboratory. Contrast echocardiography should be considered an extension of the existing echocardiographic examination. Standard laboratory equipment is sufficient to run a contrast echocardiography program. However, cultural and technological upgrading is mandatory to obtain good results in contrast echocardiography. Intravenous infusion is easier during stress echocardiography than during rest study, because the time and cost for the venous line are comprised. In this setting, the cost-effectiveness for the addition of contrast agent is optimal, but patient selection is a critical point. The economic issue (contrast agent and personnel costs, and time needed) of contrast echocardiography determines the fact that without adequate reimbursement there is no incentive to perform the procedure.
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PMID:Italian Society of Cardiovascular Echography (SIEC) Consensus Conference on the state of the art of contrast echocardiography. 1518 94

A 62-year-old man with hypertension and hypercholesterolemia was referred to our unit for evaluation of chest pain. A very rare variant of single coronary artery, in which the anomalous right coronary artery originated as a separate branch from the left anterior descending artery, was incidentally found on his coronary angiography. The anomalous right coronary artery in our case appears to be unique in that it courses intraseptally rather than rightwards proximally and has obstructive atherosclerotic lesions resulting in inferior ischemia. Moreover, the acute angle made by the anomalous right coronary artery to turn toward the atrioventricular groove may have reduced the flow velocity and contributed to the development of inferior ischemia.
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PMID:Single coronary artery with anomalous origin of the right coronary artery from the left anterior descending artery with a unique proximal course. 1524 Sep 72

Different types of ATP-sensitive K+ (K(ATP)) channels have been identified in cardiomyocytes, vascular smooth muscle cells, pancreatic beta-cells, neurons and mitochondria. Years before the discovery of the K(ATP) channel in cardiomyocytes, pharmacological openers of this channel had been developed for the treatment of angina pectoris and hypertension. The K(ATP) channel plays an important role not only in coronary blood flow regulation but also in protection of cardiovascular cells from ischemia/reperfusion injury. In animal models of myocardial ischemia/reperfusion, activation of the mitochondrial K(ATP) channels by their pharmacological openers has been shown to attenuate endothelial dysfunction and to reduce myocardial necrosis. Conversely, blockade of the K(ATP) channel aggravates microvascular necrosis and the no-reflow phenomenon after ischemia/reperfusion, resulting in augmentation of post-infarct ventricular dysfunction. Recent clinical studies have shown that a combination of coronary reperfusion therapy and infusion of nicorandil, a hybrid of K(ATP) channel opener and nitrate, improved left ventricular function in patients with acute myocardial infarction. Furthermore, chronic treatment with nicorandil has been shown to significantly improve prognosis of patients with high-risk stable angina pectoris. Both of these clinical benefits cannot be attributed to the nitrate property of nicorandil. However, a recent basic investigation has suggested that the protective function of K(ATP) channel openers is compromised by concurrent hypercholesterolemia and administration of sulfonylureas for diabetes mellitus. These interferences in the beneficial action of K(ATP) channel openers by concurrent illness and pharmacological agents need to be further investigated to allow a more effective use of K(ATP) channel openers in patients with coronary artery diseases.
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PMID:ATP-sensitive K+ channel openers: old drugs with new clinical benefits for the heart. 1532 Apr 72

It is widely, but mistakenly, believed that ischemic heart disease (IsHD) and its complications are the sole and direct result of reduced coronary blood flow by obstructive coronary artery disease (CAD). However, cardiac angina, acute myocardial infarction (AMI), and sudden cardiac death (SCD) occur in 15%-20% of patients with anatomically unobstructed and grossly normal coronaries. Moreover, severe obstructive coronary disease often occurs without associated pathologic myocardiopathy or prior symptoms, ie, unexpected sudden death, silent myocardial infarction, or the insidious appearance of congestive heart failure (CHF). The fact that catecholamines explosively augment oxidative metabolism much more than cardiac work is generally underappreciated. Thus, adrenergic actions alone are likely to be more prone to cause cardiac ischemia than reduced coronary blood flow per se. The autonomic etiology of IsHD raises contradictions to the traditional concept of anatomically obstructive CAD as the lone cause of cardiac ischemia and AMI. Actually, all the signs and symptoms of IsHD reflect autonomic nervous system imbalance, particularly adrenergic hyperactivity, which may by itself cause ischemia as in rest angina. Adrenergic activity causing ischemia signals cardiac pain to pain centers via sympathetic efferent pathways and tend to induce arrhythmogenic and necrotizing ischemic actions on the cardiovascular system. This may result in ischemia induced metabolic myocardiopathy not unlike that caused by anatomic or spasmogenic coronary obstruction. The clinical study and review presented herein suggest that adrenergic hyperactivity alone without CAD can be a primary cause of IsHD. Thus, adrenergic heart disease (AdHD), or actually adrenergic cardiovascular heart disease (ACVHD), appears to be a distinct entity, most commonly but not necessarily occurring in parallel with CAD. CAD certainly contributes to vulnerability as well as the progression of IsHD. This vicious cycle, which explains the frequent parallel occurrence of arteriosclerosis and IHD, an association that appears to be linked by the same cause, comprises a common vulnerability to deleterious adrenergic actions on the myocardium, lipid metabolism, and vascular system alike, rather than viewing CAD and IsHD as having a putative cause and effect relationship as commonly thought. Adrenergic actions can also cause the abnormal lipid metabolism that is associated with CAD and IsHD by catecholamine-induced metabolic actions on lipid mobilization by activation of phospholipases. This may also be part of toxic catecholamine hypermetabolic actions by enhancing deleterious cholesterol and lipid actions in damaging coronary vessels by plaque formation as well as inducing obstructive coronary spasm and platelet aggregation. This may also cause direct toxic necrosis on the myocardium as well as atherosclerosis in blood vessels. In fact, drugs that inhibit adrenergic actions like propranolol, reserpine, and guanethidine all inhibit arteriosclerosis induced by hypercholesterolemia in experimental animals and prevent carotid vascular disease (associated with stroke) in humans. The concomitant development of myocardiopathy and coronary vascular lesions or coronary and carotid artery intimal medial thickening by catecholamine toxicity is reflected by the frequent primary presentation of patients with catecholamine-secreting pheochromocytoma with cardiovascular disease, ie, hypertension arrhythmias, AMI, SCD, CHF, and vascular disease, which represents a clear example of the primary deleterious impact of catecholamines on the entire cardiovascular system causing adrenergic cardiovascular disease. Thus, like myocardiopathy, CAD and atherosclerosis in general may be the consequences of or a complication of catecholamine actions rather than its putative cause. This report shows how prophylactic bretylium not only prevents arrhythmias but prevents myocardial necrosis, shock, CHF, maintains or restores normal contractility, and lowers mortality in AMI patients by inducing adrenergic blockade.
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PMID:Prevention of ventricular fibrillation, acute myocardial infarction (myocardial necrosis), heart failure, and mortality by bretylium: is ischemic heart disease primarily adrenergic cardiovascular disease? 1535 32

Although NO donors have been shown to confer late preconditioning (PC) against myocardial ischemia/reperfusion injury in healthy rabbits, it is unknown whether concurrent systemic disorders affect NO donor-induced cardioprotection. Since many patients with coronary artery disease have hypercholesterolemia (HC), we examined the effect of this condition on late PC induced by the NO donor diethylenetriamine/nitric oxide (DETA/ NO). Chronically instrumented rabbits were fed a normal diet (normocholesterolemia, NC) or a diet enriched with 1% cholesterol (HC) for 4 weeks. Plasma cholesterol levels were significantly elevated and the arterial pressure response to the endothelium-dependent vasodilator bradykinin was blunted in cholesterol diet-fed rabbits. Conscious rabbits underwent a 30-minute coronary occlusion followed by 3 days of reperfusion. When NC rabbits were pretreated with DETA/NO (0.1 mg/kg, i. v. x 4, group II, n = 7) 24 hours before the 30-minute occlusion, infarct size was reduced by 52% (29.7 +/- 3.4% versus 62.4 +/- 4.0% of the region at risk in NC controls [group I, n = 5], P < 0.05), indicating that DETA/NO induced a late PC effect against myocardial infarction. In contrast, when HC rabbits were pretreated with the same dose of DETA/NO (group IV, n = 6), infarct size was not significantly reduced (61.0 +/- 5.7% versus 68.1 +/- 4.5% of the region at risk in HC [group III, n = 5], P = NS), suggesting that DETA/NO failed to induce a delayed cardioprotective effect. These data demonstrate, for the first time, that HC blunts NO donor-induced late PC against myocardial infarction, implying that the inhibitory effects of HC on ischemia-induced and NO donor-induced late PC are caused by disruption of biochemical pathways distal to the generation of NO that triggers these adaptations.
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PMID:Hypercholesterolemia blunts NO donor-induced late preconditioning against myocardial infarction in conscious rabbits. 1537 83

Peripheral arterial disease (PAD) may be asymptomatic, may be associated with intermittent claudication, or may be associated with critical limb ischemia. Coronary artery disease (CAD) and other atherosclerotic vascular disorders may coexist with PAD. Persons with PAD are at increased risk for all-cause mortality, cardiovascular mortality, and mortality from CAD. Modifiable risk factors such as cessation of cigarette smoking and control of dyslipidemia, hypertension, and diabetes should be treated. Statins reduce the incidence of intermittent claudication and improve exercise duration until the onset of intermittent claudication in persons with PAD and hypercholesterolemia. Antiplatelet drugs such as aspirin or clopidogrel, especially clopidogrel, and angiotensin-converting enzyme inhibitors should be given to all persons with PAD. beta-Blockers should be given if CAD is present. Exercise rehabilitation programs and cilostazol improve exercise time until intermittent claudication. Indications for lower-extremity angioplasty, preferably with stenting, or bypass surgery are 1) incapacitating claudication in persons interfering with work or lifestyle; 2) limb salvage in persons with limb-threatening ischemia as manifested by rest pain, nonhealing ulcers, and/or infection or gangrene; and 3) vasculogenic impotence. However, amputation should be performed if tissue loss has progressed beyond the point of salvage, if surgery is too risky, if life expectancy is very low, or if functional limitations diminish the benefit of limb salvage.
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PMID:Management of peripheral arterial disease. 1570 52

Although hypercholesterolemia is a strong risk factor for cardiovascular disease, it has in some instances paradoxically been associated with reduced infarct size and preserved contractile function in isolated hearts after ischemia and reperfusion. To elucidate potential cellular protective mechanisms, myocytes of hypercholesterolemic apolipoprotein E-deficient (ApoE-/-) and wild-type mice were subjected to hypoxic metabolic inhibition (I) with subsequent reoxygenation (R). Intracellular Ca2+ concentration ([Ca2+]i) and pH (pHi) were monitored as well as cell length and arrhythmic events. Force measurements in papillary muscles were also recorded, and myocardial expression of Na+/H+ exchanger 1 (NHE1) and three Ca2+ handling proteins [sarco(endo)plasmic reticulum Ca2+-ATPase, Na+/Ca2+ exchanger, and plasma membrane Ca2+-ATPase] was quantified. After 30 min of I and 35 min of R, Ca2+ overload was more pronounced in wild-type cells (P < 0.05). In these myocytes, pHi also dropped faster and remained below those values determined in ApoE-/- cells (P < 0.05). Furthermore, more wild-type myocytes remained in a contracted state (P < 0.05). This group also showed a higher incidence of arrhythmic events during R (P < 0.05). No group difference was found in the expression of the Ca2+ handling proteins. However, NHE1 protein was downregulated in hearts of ApoE-/- mice (P < 0.05). Histological results depict hyperplasia in ApoE-/- hearts without atherosclerosis of the coronaries. Contractile dysfunction was not observed in papillary muscles from ApoE-/- hearts. Our results suggest that downregulated myocardial NHE1 expression in hypercholesterolemic ApoE-/- mice could have contributed to increased tolerance to I/R. It remains to be elucidated whether NHE1 downregulation is a unique feature of these genetically altered animals.
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PMID:Increased tolerance to hypoxic metabolic inhibition and reoxygenation of cardiomyocytes from apolipoprotein E-deficient mice. 1573 85

Percutaneous transluminal intervention for atherosclerotic iliac occlusive disease is now commonplace. We examine the long-term outcomes of TransAtlantic Inter-Society Consensus (TASC) A and B lesions. We performed a retrospective anonymous analysis of records from patients who underwent iliac artery angioplasty with or without stenting between January 1990 and June 1999. Indications for intervention were symptomatic claudication (77%) or critical ischemia (23%). Altogether, 276 patients (all men; average age 64 +/- 11 years range 32-87 years) underwent 394 interventions. Co-morbidities included hypertension (61%), hypercholesterolemia (45%), diabetes (28%), and chronic renal insufficiency (26%). A total of the 62% of the lesions were TASC category A, and the remainder were category B. Of the 394 primary interventions, 51% included placement of stents. Technical success (defined by < 30% residual stenosis) was achieved in 98% of treated vessels. The procedure-related mortality rate was 1.8% at 30 days and 4.7% at 90 days; the procedure-related complication rate was 7%. Hemodynamic success (defined as a rise in the ankle/branchial index > 0.15) was achieved in 82%. The average Society for Vascular Surgery symptom score was 3.4 +/- 0.9 before intervention, which improved to 1.9 +/- 0.8 following intervention. Within 3 months, 84% of patients demonstrated clinical improvement. Patient survival by life-table analysis was 38% at 10 years. The cumulative assisted patency rate was 71 +/- 7% at 10 years. The presence of two-vessel femoral runoff, two or more patent tibial vessels, or both was associated with improved patency. Limb salvage was 95 +/- 2% and 87 +/- 9% at 5 and 10 years, respectively. Using Cox proportional hazards analysis, the presence of hypertension, hypercholesterolemia, or chronic renal insufficiency was associated with the occurrence of primary failure, whereas increased patency intervals were associated with the presence of immediate hemodynamic improvement. Use of a stent did not influence outcome. Endoluminal iliac intervention for TASC A and B lesions is a safe, durable intervention in patients with good femoral and tibial runoff. The presence of hypertension, hypercholesterolemia, or poor tibial runoff is associated with failure.
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PMID:Percutaneous transluminal revascularization for iliac occlusive disease: long-term outcomes in TransAtlantic Inter-Society Consensus A and B lesions. 1581 61

Recent studies suggest that postnatal neovascularization relies not exclusively on sprouting of preexisting vessels ("angiogenesis"), but also involves the contribution of bone marrow-derived circulating endothelial progenitor cells (EPCs). EPCs can be isolated from peripheral blood or bone marrow mononuclear cells, CD34(+) or CD133(+) hematopoietic progenitors. Infusion of EPCs was shown to promote postnatal neovascularization of ischemic tissue after myocardial infarction in animal models and initial clinical trials. Moreover, circulating endothelial precursor cells can home to denuded arteries after balloon injury and contribute to endothelial regeneration, thereby limiting the development of restenosis. Thus, circulating endothelial cells may exert an important function as endogenous repair mechanism to maintain the integrity of the endothelial monolayer and to promote ischemia-induced neovascularization. However, risk factors for coronary artery disease, such as diabetes, hypercholesterolemia, and hypertension are associated with impaired number and function of EPC in patients with coronary artery disease. Therapeutically, the reduction of EPC number and the decreased functional activity in patients with coronary artery disease was counteracted by 3-hydroxy-3-methylglutaryl coenzymeA (HMG-CoA) reductase inhibitors (statins), vascular endothelial growth factor (VEGF), estrogen, or exercise. At the molecular level, these factors are well established to activate the phosphatidyl-inositol-3-kinase (PI3K)-Akt-dependent activation of the endothelial nitric oxide synthase (eNOS), suggesting that the PI3K-Akt-eNOS signaling pathway may be involved in the transduction of atheroprotective factors. Taken together, the balance of atheroprotective and proatherosclerotic factors may influence EPC levels and their functional capacity to improve neovascularization and endothelial regeneration.
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PMID:Risk factors for coronary artery disease, circulating endothelial progenitor cells, and the role of HMG-CoA reductase inhibitors. 1584 10


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