Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002962 (angina)
 21,142 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aortic and coronary sinus platelet aggregation, thromboxane A2 (TXA2) and prostacyclin (PG12) levels were studied in fourteen patients of stable angina (SA), six of vasopastic angina (VA) and six control subjects (C). Patients of SA were studied at rest and during incremental atrial pacing and patients with VA were studied at rest and during various stages of vasospasm. Platelet aggregation was studied with different working concentrations of ADP, epinephrine and collagen. TX A2 and PGI2 concentrations were estimated by measuring levels of their stable metabolites viz. thromboxane B2 (TXB2) and 6-keto prostaglandin F1 alpha (PGF1 alpha) respectively. Platelet aggregation was increased in SA and VA patients (p < 0.01) and further increase was seen during vasospasm (p < 0.001). However, it failed to increase on incremental atrial pacing. Similarly, TXB2 and PGF1 alpha levels were raised in SA and VA patients. While TXB2 further increased during vasospasm but not during atrial pacing. PGF1 infinity failed to rise with either. Thus platelets are in an activated state in SA and VA. This activated state is a cause and not an effect in SA and VA. An imbalance in the levels of TXA2 and PG12 could account for the vasospasm.
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PMID:A study of platelet aggregation, thromboxane A2 and prostacyclin in central aortic and coronary sinus blood in ischemic heart disease. 787 1

Fifteen 3-alkyl-, four 3-cycloalkyl-N-nitroso-5-sydnone imines and five 3-alkyl-N-nitro-5-sydnone imines were synthesized and their ability to inhibit platelet aggregation induced by collagen (Born-test) was studied in vitro. Dependent on the chemical structure, the IC50-values for the inhibition of platelet aggregation were in the range of 0.2-140 mumol/L. It is suggested that this scale reflects different binding properties of the nitrosimines with respect to the platelet membrane. Highest activities were observed for the 3-hexyl (2f) and the 3-cyclohexyl (2p) derivative. Three nitrimines (3e, 3f, 3i) also showed IC50 values below 10 mumol/L. For the nitrosimines 2a, 2f, and 2m antithrombotic activity was demonstrated in vivo. They inhibited laser induced arterial thrombosis in anesthetized rats up to 70% two h after oral administration. In conscious renal-hypertensive dogs, the decrease in systolic blood pressure and left ventricular enddiastolic pressure suggests an antianginal activity of the compound 2a similar to that of molsidomine (M). The smoother onset and the longer duration of action of the new compound as compared to M could be a significant advantage of 2a in the therapy of angina pectoris.
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PMID:New NO-donors with antithrombotic and vasodilating activities, II: 3-alkyl-N-nitroso-5-sydnone imines. 826 14

Adult polycystic kidney disease is frequently associated with gastrointestinal and cardiovascular abnormalities. These include hypertension, mitral valve prolapse, mild dilation of the aortic root, abdominal aneurysms, and predisposition to aortic, mitral, and tricuspidal valve regurgitation reminiscent of Marfan's syndrome. Although the exact molecular mechanisms of adult polycystic kidney disease are not well established, a generalized defect of collagen structure is hypothesized. The most severe vascular problems, however, are typical intracranial aneurysms with a high incidence of subarachnoid hemorrhage and a high mortality rate. We report a case of dilated coronary arteries found incidentally in a patient with adult polycystic kidney disease and stress-induced angina pectoris. The typical angina pectoris of the patient is explained by left ventricular hypertrophy and coronary heart disease. Multiple liver cysts, mitral valve prolapse, and the coronary aneurysms in this patient with adult polycystic kidney disease appear to reflect the manifestation of a generalized connective tissue disorder in this syndrome.
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PMID:Aneurysms of coronary arteries in a patient with adult polycystic kidney disease: arteriosclerosis or involvement by the primary disease? 846 27

The patency of aorto-coronary bypasses is greatly influenced by platelet aggregability, and there is an associated risk of thrombosis which may occur very early during surgery. It is in this context that aspirin has been the subject of successful clinical studies. When administering aspirin, it is preferable to choose formulations that are well tolerated by the gastro-intestinal tract. This was the reason for carrying out the present randomised single-centre double-blind parallel-group study aimed at confirming the platelet anti-aggregant effect and tolerability of calcium carbasalate administered during the immediate postoperative period. The dose prescribed was equivalent to aspirin 325 mg daily, and was given as a single dose 6 hours after the end of the operation and repeated for 7 days, versus placebo, in 56 patients undergoing aorto-coronary bypass grafts. A clinical assessment, ECG, platelet count and measurements of CPK and CPK-MB were carried out daily for the 7 days of the study. Tests of platelet aggregation (to arachidonic acid, ADP and collagen), assays of serum thromboxane B2, MDA and PDF, and urinary assays for beta-thromboglobulin and 6-keto-PGF-1 were carried out before treatment, then 1 and 7 days after the start of treatment. Fifty males (89%) and 6 females, mean age 58.3 years, received treatment with either calcium carbasalate (group C, n = 28) or placebo (group P, n = 28). The atheromatous lesions present in most cases represented triple-vessel disease (37 cases), and most operations were triple bypasses (23 cases) or double bypasses (20 cases). A significant reduction in platelet aggregation to arachidonic acid and collagen on D1 (p = 0.05) and D7 (p < 0.001), and to ADP on D7 (p < 0.01) was observed in group C as compared with group P. Group C also showed significant reductions as compared with group P in respect of serum thromboxane B2 levels on D1 (p < 0.01) and D7 (p < 0.001) and MDA levels on D1 and D7 (p < 0.001). No significant difference was demonstrated between the two groups in respect of urinary 6-keto-PFG-1 excretion. The number of patients showing a rise in CPK was lower in group C but this difference did not reach statistical significance. ST segments change were comparable in the two groups, and no patient complained of anginal pain during the study. These results show that calcium carbasalate administered at a dose equivalent to 325 mg aspirin daily caused very early inhibition of platelet aggregation, specifically inhibiting platelet production of thromboxane B2 without altering prostacyclin levels. In addition, calcium carbasalate was found to be well tolerated. This study confirms the value of early administration of aspirin at a dose of 325 mg daily during the hours immediately following aorto-coronary bypass graft surgery.
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PMID:[Antiaggregant effect and tolerance of calcium carbasalate administrated immediately after aorto-coronary bypass. Results of a double-blind versus placebo study]. 897 14

Within a few seconds after a sudden reduction of coronary blood flow regional contractile dysfunction ensues. The mechanisms responsible for the rapid reduction in contractile function during acute myocardial ischemia remain unclear, but may involve a rise in inorganic phosphate. When severe ischemia, such as resulting from a sudden and complete coronary artery occlusion, is prolonged for more than 20-40 min, myocardial infarction develops, and there is irreversible loss of contractile function. When myocardial ischemia is less severe but nevertheless prolonged, the myocardium is dysfunctional but can remain viable. In such ischemic and dysfunctional myocardium, contractile function is reduced in proportion to the reduction in regional myocardial blood flow; i.e. a state of "perfusion-contraction matching" exists. The metabolic status of such myocardium improves over the first few hours, as myocardial lactate production is attenuated and creatine phosphate, after an initial reduction, returns towards control values. Ischemic myocardium, characterized by perfusion-contraction matching, metabolic recovery and lack of necrosis, has been termed "short-term hibernating myocardium". Short-term hibernating myocardium can respond to an inotropic stimulation with increased contractile function, however, at the expense of a renewed worsening of the metabolic status. This situation of an increased regional contractile function at the expense of metabolic recovery during inotropic stimulation can be used to identify short-term hibernating myocardium. When inotropic stimulation is prolonged, the development of short-term hibernation is impaired and myocardial infarction develops. The mechanisms responsible for the development of short-term myocardial hibernation remain unclear at present; a significant involvement of adenosine and of activation of ATP-dependent potassium channels has been excluded. Whereas short-term hibernation is well characterized in animal experiments, the existence of hibernation over weeks or months (long-term hibernation) can only be inferred from clinical studies. Hibernation, as defined by Rahimtoola, is a state of chronic contractile dysfunction which is fully reversible upon reperfusion. Clinical syndromes consistent with the existence of myocardial hibernation include unstable and stable angina, acute myocardial infarction and left ventricular dysfunction and/or congestive heart failure. In long-term hibernating myocardium morphological alterations occur; the myofibrils are reduced in number and disorganized and myocardial glycogen content as well as the extracellular collagen network are increased. Thus, despite the fact that the myocardium remains viable during persistent ischemia and contractile dysfunction is reversible upon reperfusion, there are severe morphological alterations. Understandably, full functional recovery following reperfusion might therefore require weeks or even months.
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PMID:Hibernating myocardium: a review. 900 53

The purpose of the present study was to examine the effects of a long-acting calcium antagonist, amlodipine, on the development of cardiac remodeling. Dihydropyridine calcium antagonists have been used widely for many years in the treatment of hypertension and angina pectoris. It has been reported, however, that a prototype of dihydropyridines, nifedipine, does not reduce mortality of patients with ischemic heart disease, possibly because of reflex stimulation of the sympathetic nervous system. A calcium antagonist, amlodipine, has been reported to have potential benefits by virtue of a gradual onset of action and a long duration of effects. Amlodipine (8 mg/kg per day, once a day) or nifedipine (24 mg/kg per day, three times a day) was administered to spontaneously hypertensive 12-week-old rats for 12 weeks. Left ventricular wall thickness was measured by echocardiography, and relative amounts of myosin heavy chain isoforms were assessed by pyrophosphate gels. Expressions of "fetal type" genes and type 1 collagen gene were examined by Northern blot analysis. Amlodipine and nifedipine both markedly reduced systolic blood pressure. However, the decrease in systolic blood pressure caused by nifedipine continued for no more than 8 hours, whereas the blood pressure-lowering effect of amlodipine continued for more than 16 hours post dose. Amlodipine markedly reduced left ventricular wall thickness, whereas nifedipine only weakly attenuated an increase in the wall thickness. Amlodipine, but not nifedipine, prevented an increase in the relative amount of V3 myosin heavy chain isoform and suppressed an increase in mRNA levels of beta-myosin heavy chain, skeletal alpha-actin, and type 1 collagen. Unlike nifedipine, amlodipine effectively prevented cardiac remodeling secondary to high blood pressure at biochemical levels and morphological levels. These results suggest that a long-acting calcium antagonist is more effective than a short-acting one in preventing organ injury in hypertensive subjects.
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PMID:Efficient inhibition of the development of cardiac remodeling by a long-acting calcium antagonist amlodipine. 944 87

Therapeutic ultrasound was shown to ablate thrombi and to disrupt atherosclerotic plaques in vitro and recently to recanalize occluded coronary arteries in acute myocardial infarction (AMI). The goal of this article is to update collective experience and to weigh the promising and unresolved aspects of this newly developed technology and its clinical results. As therapeutic ultrasound was for long known a synonym for lithotripsy of calculi diseases, it lastly received high attention as a catheter-based ultrasound method to ablate thrombi and disrupt atherosclerotic plaques in interventional cardiology (Figure 1). The effect of therapeutic ultrasound to ablate selectively pathological tissue depends on its bioselectivity for elastic fibers: After ultrasound sonication, healthy tissue-rich in elastin and collagen-including arterial wall remains intact whereas thrombus and plaque with their minimal elastic support are found to be highly susceptible to ablation. Our catheter for coronary ultrasound thrombolysis (Figure 2) consists of a solid metal probe and is connected to a piezo-electric transducer at its proximal end. The distal part ends in a three-wire flexible segment with a 1.6 mm tip ball to guarantee maximal wire flexibility and optimal transmission of ultrasound energy. The initial in vitro studies resulted in a fundamental understanding of the destructive effect of ultrasound on tissue based on 4 factors: mechanical vibration, thermal effects, microcurrents, and cavitation. The first studies on human peripheral vessels were published in 1991 being performed during femoral bypass surgery on occluded and partially obstructed arteries. The procedure was performed without perforation, no adverse side effects emerged, restenosis rate was 20%. The clinical application of coronary ultrasound angioplasty was initiated in 1991; Siegel published his data on 44 patients. In his study, 30 patients with chronic atherosclerotic occlusive lesions and 14 with unstable or stable angina or AMI were treated by ultrasound angioplasty. Residual stenosis after ultrasound treatment was 71%, after balloon dilation reduced to 34%. In the 6-month follow-up angiograms showed no major adverse effect or restenosis. Our experience with coronary ultrasound thrombolysis (CUT) is based on the analysis of 33 patients' data in the feasibility (Table 1) plus multicenter phase of the ACUTE trial (Analysis of Coronary Ultrasound Thrombolysis Endpoints) (Figure 3). Our patients were exclusively treated for AMI by ultrasound angioplasty and afterwards by PTCA if required (Figure 4). The average final percent stenosis was 20% (Figure 5). The main efficacy parameters, device success and angiographic success rates were 100%, clinical success rate was 91.7% (Figure 6 and Table 2). The adverse clinical events of CUT are limited--at least in our studies--to reocclusion of infarct-related artery and ischemia and could be reversed by additional PTCA. No adverse clinical side effects were observed during sonication of the coronary tree. Final angiography revealed residual stenosis of 20% without morphological signs. These excellent results suggest that bioselectivity of ultrasound together with the developed skills of the catheter system induces rapid and selective thrombolysis with no need to cross the target lesion before sonication. But what is the better solution for thrombosis and which for plaque disruption? The development of transluminal balloon catheter really modified therapeutic approach to obstructive coronary and peripheral arterial disease but it is still accompanied by a high rate of abrupt closure, AMI and death. Although the use of intravenous thrombolytic agents is well established in the treatment of AMI and these agents are widely used, a large patient collective remains (up to 33% and more) in whom their use is inadvisable due to recent stroke, surgery, trauma or other contraindications. (ABSTRACT TRUNCATED)
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PMID:[Ultrasound coronary angioplasty: state of the art and new clinical aspects]. 948 36

The CD36 molecule is a multifunctional membrane type receptor glycoprotein that reacts with thrombospondin, collagen, oxidized LDL and long-chain fatty acids (LCFA). LCFA are one of the major cardiac energy substrates, hence LCFA metabolism may have an important role in cardiac diseases. In this study, we analyzed CD36 expression in 200 patients with heart diseases [44 patients with hypertrophic cardiomyopathy (HCM), 16 with dilated cardiomyopathy (DCM), 26 with old myocardial infarction (OMI), 55 with angina pectoris (AP) and 59 with other miscellaneous heart diseases] using a flow cytometer. 123I-beta-methyl-p-iodophenylpentadecanoic acid (BMIPP) myocardial accumulation was also examined in some patients. Eight patients (2 with HCM, 1 with DCM, 2 with OMI, and 3 with AP) were diagnosed as having type I CD36 deficiency (neither platelets nor monocytes expressed CD36). Sixteen patients (3 with HCM, 1 with DCM, 1 with OMI, 8 with AP, and 3 with other heart diseases) showed type II CD36 deficiency (monocytes expressed CD36 but platelets did not). In all 8 patients with type I CD36 deficiency, there was no BMIPP accumulation in the heart. However, in 13 patients with type II CD36 deficiency, focally reduced BMIPP accumulation was observed, but there were no patients without BMIPP accumulation. CD36 deficiency was observed in a higher proportion (12%) of patients with heart disease in this study than in a reported control study. Type I CD36 deficiency is associated with absence of BMIPP accumulation in the heart, hence it may have an important role in LCFA metabolic disorders and some types of cardiac hypertrophy as well as other heart diseases.
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PMID:[Different patterns of 123I-BMIPP myocardial accumulation in patients with type I and II CD36 deficiency]. 949 34

The fact that certain ethnic groups and specific populations residing in certain geographic areas carry an increased risk for thrombosis and that thrombosis occurs in young patients without established risk factors indicates the presence of new, previously unrecognized inherited conditions predisposing to thrombosis. We are now aware that interindividual variations within the loci coding for proteins relevant to lipid and vascular metabolisms as well as blood coagulation are universally found. Platelets play central roles in cerebrovascular diseases and acute coronary syndromes, as demonstrated by histopathological findings and clinical observations showing the efficacy of antiplatelet therapies for these disorders. In this article, we show our recent findings on the association between coronary artery disease (CAD) and polymorphisms in platelet membrane glycoproteins. The glycoprotein (GP) Ib/IX complex is a receptor for von Willebrand factor, which mediates shear stress-dependent platelet activation. It has recently been implicated in the pathogenesis of acute coronary syndromes. We have determined genotypes of the "size-polymorphism" of GPIb alpha--i.e., the variable number (1-4) of a 13 amino acid sequence (399-411)--in angiographically proven Japanese CAD patients with myocardial infarction or angina pectoris as well as in individuals from the general population with no history of angina or other heart diseases and normal resting electrocardiograms (ECG). We have found that the genotypes having at least one 4-repeat allele (4R) are more frequently found in patients than in controls. Logistic regression analyses for the adjustment of age, sex, and other acquired coronary risk factors provided an odds ratio of 7.94 (p=0.0043) for those with 4R vs. those without 4R, suggesting that the presence of 4R is an independent risk factor for CAD. The molecular mechanisms underlying this association are currently under investigation. Relationships between arterial thrombosis and polymorphisms in other platelet GPs (collagen receptor and fibrinogen receptor), blood coagulation factors, fibrinolytic factors, vasoactive substances, and factors relevant for lipid metabolisms are also discussed.
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PMID:Genetic polymorphisms and risk of coronary artery disease. 970 55

By presenting this series of 127 cases of coronary atherectomy the authors join the workers who study morphological differences between the atherosclerotic plaques in stable and unstable angina. Routine staining of formalin-fixed, paraffin-embedded material was completed by the detection of T lymphocytes, macrophages, mast cells, smooth myocytes and grown-in capillaries using monoclonal antibodies (DAKO), as well as by the immunofluorescent demonstration of fibrinogen in the plaques. The plaques derived from patients with unstable angina showed a higher incidence of mast cells (significant) and macrophages (insignificant). These cells render the plaque more susceptible to rupture or fissuring. There was also significantly more frequent and quantitatively more abundant permeation of the plaque by fibrinogen that raises the chance of thrombosis. These findings support the view that unstable angina correlates with the phenomena that favour the rupture of the plaque and thrombosis. Electron microscopy has not been used so far to study coronary atherosclerotic plaques. This material includes 15 plaques from stable and 18 plaques from unstable angina. A cover of fibrin and blood platelets is a regular formation on the surface and in the superficial layer of the plaque from unstable angina. It contributes to the "thrombotic proneness" of the coronary artery. These plaques also show abundant elastic fibres. This pattern corresponds to myo-elastic intimal hyperplasia ("intimal thickening") where the production of intimal elastin constitutes an essential phenomenon. Intimal thickening is interpreted as a preatherosclerotic event. The presence of elastin reflects an early stage of the development of the plaque. The plaque from stable angina shows abundant collagen fibres, which aggravate the lesion.
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PMID:Light and electron microscopic picture of atherosclerotic plaque in stable and unstable angina. 1048 32


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