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)

Atrial fibrillation is increasingly common with advancing age and is responsible for 10% of the half-million strokes that occur annually in the United States. When a patient presents with atrial fibrillation, the physician's first task is to use the history, physical examination, and electrocardiogram to determine whether hospitalization is necessary. Factors indicating a need for hospital care include evidence of infarction or ischemia, congestive heart failure, hypotension or hypoperfusion, excessive rate, or pre-excitation. In addition, if the episode began within 48 hours, consider early cardioversion, which also requires hospitalization. Next, the need for control of the ventricular rate should be assessed. A heart rate under 90 beats/min at rest and under 120 beats/min after 1 minute of step exercise is a reasonable goal. Dixogin usually controls the resting rate, but sometimes beta-blockers or calcium channel blockers are needed to control the exercise rate. The need for anticoagulation is determined by the presence of clinical risk factors such as valvular heart disease, previous thromboembolism, hypertension, age over 65 years, congestive heart failure, and left atrial enlargement. An echocardiogram is necessary to complete this assessment. Patients having one or more of these risk factors are most effectively treated with warfarin, as evident from several clinical trials. Although patients over age 65 demonstrate reduced thromboembolism with warfarin therapy, they also are more prone to cerebral hemorrhage, thus, their international normalization ratio (INR) should be kept at the lower end of the therapeutic range [2,3]. Other patients can be treated with aspirin, although stroke reduction in these patients may be more related to reduction of arterial thrombosis than thromboembolism. Patients under age 65 with no risk factors have a very low annual risk of stroke without therapy (approximately 1%). If symptoms persist or if this is a first episode in someone without left atrial enlargement, cardioversion can be considered after 3 weeks of warfarin therapy with INR in the therapeutic range. Otherwise, warfarin should be continued indefinitely. Prevention of recurrence with antiarrhythmic drugs is somewhat problematic because of incomplete efficacy (30% recurrence at 1 year) and the potential for inducing other, life-threatening arrhythmias.
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PMID:Management of atrial fibrillation: out-of-hospital approach. 1036 78

Sudden cardiac death due to ventricular arrhythmias remains a significant problem. In most studies about 50% of all death related to coronary artery disease and heart failure are sudden and unexpected and are caused by acute fatal ventricular tachycardia and fibrillation. Most of the patients suffering sudden cardiac death have some kind of structural heart disease but 80% of SCD events are associated with coronary artery disease, 10-15% with dilated and hypertrophic cardiomyopathy, and only small fraction with the less common disorders as valvular heart disease, ventricular dysplasia and cardiac involvement in sarcoidosis or amyloidosis. In some patients the anomaly responsible for sudden cardiac death is not structural but mainly electrical as in patients with the long QT syndrome, WPW syndrome or in patients with a proarrhythmic effect from antiarrhythmic drugs. In this review, data from clinical trials and other studies on on antiarrhythmic therapies have been evaluated in order to determine effective strategies for the prevention sudden cardiac death in high risk patients. Taken together with the mortality data routine prophylactic use of class I antiarrhythmic drugs in the patients survivors of acute myocardial infarction and patients with heart failure is associated with increased risk of death. Conversely beta-blockers are associated with significant reduction in nonfatal cardiac arrest in the short term trials and sudden cardiac death in long term trials. These benefits are likely due to relief ischemia, reduction of heart rate and maintenance favourable autonomic nervous system balance. Overall trial data on amiodarone suggests that this agent is effective in reducing the risk of death in survivors of cardiac arrest, post infarction patients, and patients with heart failure but the routine prophylactic use of amiodarone remains of uncertain efficacy. The physician who considers the use of antiarrhythmic medications in patients with ventricular arrhythmias must be aware of which arrhythmias are malignant or potentially malignant and which are benign and the decision to initiate antiarrhythmic therapy should be based on consideration of the patients absolute mortality risk.
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PMID:[Antiarrhythmic agents in the prevention of sudden cardiac death]. 1036 92

Appetite suppressants, such as dexfenfluramine (dex), are associated with primary pulmonary hypertension, valvular heart disease, and systemic vascular complications, such as coronary, cerebral, or mesenteric ischemia. These drugs suppress appetite by enhancing release and inhibiting reuptake of serotonin in the central nervous system. The effects of dex on the systemic circulation have not been studied. K(+) channels regulate vascular tone in most vascular beds. We hypothesized that dex is a systemic vasoconstrictor acting primarily by inhibiting K(+) channels, independent of effects on serotonin. The effects of clinically relevant concentrations of dex (10(-6) to 10(-4) M) on outward K(+) current and membrane potential were studied with whole-cell patch clamping in freshly isolated smooth muscle cells from rat renal, carotid, and basilar arteries. Tone was measured in tissue baths. Blood pressure, cardiac output, and left ventricular end diastolic pressure were assessed in open- and closed-chest anesthetized rats. At 10(-4) M, dex inhibits outward K(+) current (50%) and increases membrane potential (by >35 mV), an effect comparable with 4-aminopyridine (5 mM). Furthermore, dex constricts rings and acutely elevates systemic pressure (+17 +/- 3 mm Hg) and systemic vascular resistance in the presence of ketanserin. Dex vasoconstriction is dose-dependent (threshold dose 10(-6) M; 156 microg/ml) and enhanced in L-NAME-fed rats. We conclude that dex causes acute systemic vasoconstriction, at least in part by inhibition of voltage-gated K(+) channels, independent of effects on serotonin. To our knowledge, this is the first time that a commonly prescribed drug with voltage-gated K(+) channel-blocking properties is shown to have significant hemodynamic effects in vivo.
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PMID:Dexfenfluramine elevates systemic blood pressure by inhibiting potassium currents in vascular smooth muscle cells. 1056 35

Primary diastolic failure is typically seen in patients with hypertensive or valvular heart disease as well as in hypertrophic or restrictive cardiomyopathy but can also occur in a variety of clinical disorders, especially tachycardia and ischemia. Diastolic dysfunction has a particularly high prevalence in elderly patients and is generally associated, with low mortality but high morbidity. The pathophysiology of diastolic dysfunction includes delayed relaxation, impaired LV filling and/or increased stiffness. These conditions result typically in an upward displacement of the diastolic pressure-volume relationship with increased end-diastolic, left atrial and pulmo-capillary wedge pressure leading to symptoms of pulmonary congestion. Diagnosis of diastolic heart failure requires three conditions: (1) presence of signs or symptoms of heart failure; (2) presence of normal or slightly reduced LV ejection fraction (EF > 50%) and (3) presence of increased diastolic filling pressure. Assessment of diastolic function can be performed with several non-invasive (2D- and Doppler-echocardiography, color Doppler M-mode, Doppler tissue imaging, MR-myocardial tagging, radionuclide ventriculography) and invasive techniques (micromanometry, angiography, conductance method). Doppler-echocardiography is the most useful tool to routinely measure diastolic function. Different techniques can be used alone or in combination to assess LV diastolic function, but most of them are dependent on heart rate, pre- and afterload. The transmitral flow pattern remains the starting point, since it is easy to acquire and rapidly categorizes patients into normal (E > A), delayed relaxation (E < A), and restrictive (E >> A) filling patterns. Invasive assessment of diastolic function allows determination of the time constant of relaxation from the exponential pressure decay during isovolumic relaxation, and the evaluation of the passive elastic properties from the slope of the diastolic pressure-volume (= constant of chamber stiffness) and stress-strain relationship (= constant of myocardial stiffness). The prognosis of diastolic heart failure is usually better than for systolic dysfunction. Diastolic heart failure is associated with a lower annual mortality rate of approximately 8% as compared to annual mortality of 19% in heart failure with systolic dysfunction, however, morbidity rate can be substantial. Thus, diastolic heart failure is an important clinical disorder mainly seen in the elderly patients with hypertensive heart disease. Early recognition and appropriate therapy of diastolic dysfunction is advisable to prevent further progression to diastolic heart failure and death. There is no specific therapy to improve LV diastolic function directly. Medical therapy of diastolic dysfunction is often empirical and lacks clear-cut pathophysiologic concepts. Nevertheless, there is growing evidence that calcium channel blockers, beta-blockers, ACE-inhibitors and AT2-blockers as well as nitric oxide donors can be beneficial. Treatment of the underlying disease is currently the most important therapeutic approach.
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PMID:Diastolic heart failure. 1072 7

Although heart failure is a common clinical syndrome, especially in the elderly, its diagnosis is often missed. A detailed clinical history is crucial and should address not only current signs and symptoms of heart failure but also signs and symptoms that point to a specific cause of the syndrome, such as coronary artery disease, hypertension or valvular heart disease. It is important to determine whether the patient has had a previous cardiac event, in particular a myocardial infarction. The physical examination should include Valsalva's maneuver, a test that is highly specific and sensitive for the detection of left ventricular systolic and diastolic dysfunction in patients with heart failure. An electrocardiograph and a chest radiograph should also be obtained. Two-dimensional echocardiography of the heart helps differentiate systolic from diastolic dysfunction. Coronary angiography is indicated in patients with heart failure and anginal chest pain and should be strongly considered in patients with an electrocardiogram suggestive of ischemia or myocardial infarction.
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PMID:Essentials of the diagnosis of heart failure. 1073 40

Behcet's disease is a generalized chronic inflammatory disease characterized by genital, ocular, and cardiovascular involvement. Recently, left ventricular diastolic dysfunction, ventricular arrhythmia and sudden cardiac death have been documented in Behcet's disease. From January 1996 to May 1998, we investigated left ventricular systolic and diastolic function, valvular heart disease, ischemic heart disease and repolarization dispersion in 71 cases, 40 men and 31 women (mean age, 36.8+/-10.3 years) with Behcet's disease. All of the results were compared with the control group of 33 men and 22 women (mean age, 37.9+/-9.6 years). Exercise stress test or myocardial perfusion scintigraphy was performed for the documentation of ischemia. All the patients and the controls were recorded by M-mode, 2-D and Doppler echocardiography. Ventricular wall thickness, valvular apparatus, left ventricular systolic and diastolic parameters were evaluated. Repolarization dispersion parameters were calculated as the difference between maximal and minimal values of QT from 12-lead electrocardiogram recording at baseline, immediate and end of recovery from the exercise stress tests. The measured parameters were compared with the control group by using statistical methods. In the Behcet's group of 22 patients (31%) E/A ratio was <1. In the control group of five cases (10%) E/A ratio was <1 (P=0.003). In the Behcet's group isovolumic relaxation time (IRT) and mitral deceleration time (MDT) were longer than the control group (P=0.002, P=0.041, respectively). A mean QT of 368+/-30 ms and mean QT dispersion of 73+/-14 ms in the patient group compared with a mean QT of 395+/-39 ms and mean QT dispersion of 38+/-12 ms in the controls. There was no statistical difference between the mean QT values of the patient and control groups however, ventricular dispersion parameters in the Behcet's patients were longer than in the controls (P<0.001). There was also statistical significance for the QT dispersion between the Behcet's patients with and without diastolic dysfunction (P<0.01). In conclusion, the study reveals that the patients with Behcet's disease have a high incidence of increased diastolic dysfunction and repolarization dispersion. A positive correlation may exist between diastolic dysfunction and QT dispersion.
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PMID:Evaluation of diastolic dysfunction and repolarization dispersion in Behcet's disease. 1081 52

The echocardiographic examination is generally performed in patients with heart failure and it often gives a significant contribution to the differential diagnosis. Firstly, the evaluation of left ventricular pump function by measuring the ejection fraction (EF) can distinguish patients with heart failure into two different groups, with depressed or preserved EF. The most frequent causes of heart failure and depressed EF are coronary artery disease, idiopathic dilated cardiomyopathy (DCM) and hypertensive heart disease. Although the echocardiographic features of coronary artery disease versus idiopathic DCM may be similar, the demonstration of inducible ischemia at dobutamine echocardiographic test suggests the presence of significant coronary artery disease and may be useful in the selection of cases for coronary arteriography. The association of left ventricular hypertrophy, hypokinesis and, sometimes, significant dilation is compatible with hypertensive heart disease or end-stage hypertrophic cardiomyopathy. No useful echocardiographic findings can identify the patients with genetic DCM or affected by myocarditis from other cases with idiopathic DCM. Some advanced cases of right ventricular dysplasia/cardiomyopathy may show a biventricular involvement and mimic DCM; these patients are usually characterized at echo by predominant right ventricular dilation and multiple a-dyskinetic bulges in the absence of pulmonary hypertension. Very difficult to manage are the patients with significant left ventricular dysfunction and severe valvular heart disease (such as aortic stenosis or mitral regurgitation). According to the literature, the left ventricular systolic function is relatively preserved (EF > 40%) in 30-40% of patients with heart failure. In these cases a diastolic dysfunction may be hypothesized. Echo-Doppler evaluation can be helpful in the recognition of signs of increased left ventricular stiffness ("restrictive filling pattern") and of increased filling pressures. In the differential diagnosis one must first consider the most frequent heart disorders that may present with this clinical syndrome, coronary artery disease and hypertensive heart disease. Furthermore, other less common diseases characterized by heart failure due to predominant diastolic dysfunction are the following: hypertrophic and restrictive cardiomyopathies, infiltrative heart diseases, such as amyloidosis, and constrictive pericarditis. Restrictive cardiomyopathy is characterized by heart failure and preserved left ventricular EF in the absence of significant ventricular dilation and hypertrophy; typical, although not pathognomonic, echocardiographic features are atrial enlargement ad restrictive filling pattern. In distinguishing constrictive pericarditis from restrictive cardiomyopathy useful Doppler signs are the wide respiratory variability in flow velocities at mitral and tricuspid levels, due to increased ventricular interdependence caused by the presence of an abnormally rigid pericardium.
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PMID:[Contribution of echocardiography to the diagnosis of patients with chronic heart failure]. 1106 13

The results of trials that study patients with defined lesions (atrial fibrillation without valvular heart disease, various severities of carotid artery stenosis in the neck, intracranial artery stenosis) are very helpful for clinicians caring for patients with those conditions. On the other hand, trials that group all patients with brain ischemia together are not very helpful. Modern technology now makes it possible to define quickly and safely: (1) the location, nature, and severity of causative cerebrovascular, cardiac, and aortic lesions; (2) blood constituents and coagulability; and, (3) the presence, location, and severity of ischemic brain damage. As in all medicine, treatment should be aimed at the cause of disease, not the time course and severity of present damage. Clearly, more trials are needed in patients who have been studied thoroughly using modern technology. Until then, clinicians must understand the context of the trial data to determine if the results are applicable to Mr. or Ms. Jones, and the patients sitting before them in the office or in the hospital bed.
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PMID:Evidence-based treatment of patients with ischemic cerebrovascular disease. 1147 69

Anorectic drugs are widely used for the treatment of obesity. They are thought to decrease appetite through their effects on catecholamine or 5-hydroxytryptamine (5-HT) levels in the brain. Their use has been associated with epidemics of pulmonary hypertension and the development of valvular heart disease, hypertension, stroke and digital or mesenteric ischemia. Understanding the mechanism of the cardiovascular toxicity of anorectic drugs is important because of the modern epidemic of obesity and the resulting plethora of new anorexigens, many of which share similar mechanisms with those that have previously caused cardiovascular disease. In addition, the mechanism by which anorexigens cause vascular disease has relevance to the etiology and treatment of pulmonary and systemic hypertension. Recent discoveries have clarified how the anorexigens cause vasoconstriction and hypertension. Most anorexigens directly inhibit voltage-gated K+ (KV) channels in vascular smooth muscle cells (SMCs). This reduced K+ efflux leads to depolarization, the opening of voltage-sensitive Ca2+ channels, an increase in intracellular Ca2+ and vasoconstriction. Endothelial dysfunction appears to be a predisposing factor for the development of anorectic-induced vascular complications. Vasoconstriction is weak at clinically relevant doses of anorectic drugs. However, when nitric oxide synthase is inhibited, vasoconstriction is significantly enhanced. Anorexigens are the only drugs in widespread clinical use that have KV-channel-blocking properties and it is probable that much of their cardiovascular toxicity relates to this mechanism. Investigators need to examine new anorexigens and other therapeutic molecules for inhibitory effects on KV channels, as this effect may be a marker of drugs that will elicit vascular complications.
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PMID:Anorectic drugs and vascular disease: the role of voltage-gated K+ channels. 1237 23

Cardiotrophin-1 (CT-1), a member of the IL-6 family of cytokines, has been shown to be elevated in the serum of patients with ischemic heart disease and valvular heart disease, and induces cardiomyocyte hypertrophy in vitro. We investigated expression of CT-1 in post-MI rat heart and the effect of CT-1 on cultured primary adult rat cardiac fibroblasts. Elevated CT-1 expression was observed in the infarct zone at 24 h and continued through 2, 4 and 8 weeks post-MI, compared to sham-operated animals. CT-1 induced rapid phosphorylation of Jak, Jak2, STAT1, STAT3, p42/44 MAPK and Akt in cultured adult cardiac fibroblasts. CT-1 induced cardiac fibroblast protein synthesis and proliferation. Protein and DNA synthesis were dependent on activation of Jak/STAT, MEK1/2, PI3K and Src pathways as evidenced by decreased 3H-leucine and 3H-thymidine incorporation after pretreatment with AG490, PD98059, LY294002 and genistein respectively. Furthermore, CT-1 treatment increased procollagen-1-carboxypropeptide (PICP) synthesis, a marker of mature collagen synthesis. CT-1 induced cell migration of rat cardiac fibroblasts. Our results suggest that CT-1, as expressed in post-MI heart, may play an important role in infarct scar formation and ongoing remodeling of the scar. CT-1 was able to initiate each of the processes considered important in the formation of infarct scar including cardiac fibroblast migration as well as fibroblast proliferation and collagen synthesis. Further work is required to determine factors that induce CT-1 expression and interplay with other mediators of cardiac infarct wound healing in the setting of acute cardiac ischemia and chronic post-MI heart failure.
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PMID:Cardiotrophin-1: expression in experimental myocardial infarction and potential role in post-MI wound healing. 1467 4


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