Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The coronary microcirculation was examined for platelet and fibrin thrombi in hearts from 21 normal subjects and 244 cardiac patients, including 168 with ischemic heart disease (IHD) and 76 with other types of heart disease. Seventy-seven cases were sudden cardiac death (SCD). No microthrombi were present in any of the normal hearts, whereas platelet and fibrin thrombin were present in the coronary microcirculation in 32 of 244 cardiac cases (13.1%), including 19 with IHD and 13 with other types of heart disease and after cardiac surgery. The microthrombi were either embolic or represented in situ thrombosis, depending upon the underlying pathologic process. There was no significant difference in the incidence of microthrombi in SCD patients, with IHD (10 of 50, 20%) compared with patients who survived longer (nine of 93, 10%). In SCD patients, however, platelet microthrombin were more frequent in patients less than 45 years of age compared with those older than 45 years of age (p = 0.0002). We concluded that coronary microcirculatory thrombi are not uncommon in heart disease. A subgroup of SCD in young patients with IHD has been identified in whom microcirculatory platelet thrombosis is the main cardiac pathologic process. The significance of this process is emphasized by the associated myocardial damage.
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PMID:The relevance of platelet and fibrin thromboembolism of the coronary microcirculation, with special reference to sudden cardiac death. 741 78

Aspirin (ASA) is widely used in the treatment of cardiovascular diseases. Recently, we have found that aspirin decreases not only platelet aggregation but also thrombin generation. This effect, however, was seen only in certain subjects. Therefore we decided to examine influence of a single dose of aspirin (500 mg) on thrombin generation in healthy volunteers. Thrombin genesis was assessed by serial measurements of fibrinopeptide A concentration in blood emerging from standardised forearm skin incisions. Aspirin reduced thrombin generation in persons with normal serum level of lipids. This effect was lost, however, in subjects with high level of cholesterol and lipoprotein (a)--well known risk factors of ischaemic heart disease. While the mechanism by which aspirin affects thrombin generation remains to be elucidated, our data indicate that hypercholesterolemic subjects might benefit less than others from preventive aspirin treatment.
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PMID:[High levels of cholesterol and lipoprotein (A) in serum decreases the inhibitory effect of aspirin on generation of thrombin]. 749 48

Myocardial ischemia in vivo is associated with dramatic electrophysiologic alterations which occur within minutes of cessation of coronary flow and are rapidly reversible with reperfusion. This suggests that subtle and reversible biochemical and/or ionic alterations within or near the sarcolemma may contribute to the electrophysiologic derangements. Our studies have concentrated on 2 amphipathic metabolites, long-chain acylcarnitines and lysophosphatidylcholine (LPC) which have been shown to increase rapidly in ischemic tissue in vivo and to elicit electrophysiologic derangements in normoxic tissue in vitro. Incorporation of these amphiphiles into the sarcolemma at concentrations of 1 to 2 mol%, elicits profound electrophysiologic derangements analogous to those observed in ischemic myocardium in vivo. LPC is produced in endothelial cells and myocytes in response to thrombin. Thus, activation of the coagulation system during ischemia may result in extracellular production and accumulation of LPC. The pathophysiological effects of the accumulation of both amphiphiles are thought to be mediated by alterations in the biophysical properties of the sarcolemmal membrane, although there is a possibility of a direct effect on ion channels. Inhibition of carnitine acyltransferase I in the ischemic cat heart was found to prevent the increase in both long-chain acylcarnitines and LPC and to significantly reduce the incidence of malignant arrhythmias including ventricular tachycardia and fibrillation. This review focuses on the influence of these amphiphiles on cardiac ionic currents observed during early ischemia and presents data supporting the concept that accumulation of these amphiphiles within the sarcolemma contributes to changes in ionic conductances leading to electrophysiological derangements. The contribution and the accumulation of these amphiphiles to alterations in intracellular Ca2+ as related to changes in Na/K-ATPase activity and intracellular Na+ are examined. Other alterations occur during early myocardial ischemia in addition to the events reviewed here; however, the results of multiple studies over the past 2 decades indicate that accumulation of these amphiphiles contributes importantly to arrhythmogenesis and that development of specific inhibitors of carnitine acyltransferase I or phospholipase A2 may be a promising therapeutic strategy to attenuate the incidence of lethal arrhythmias associated with ischemic heart disease in man.
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PMID:Selected metabolic alterations in the ischemic heart and their contributions to arrhythmogenesis. 754 31

N,N,N-trimethylsphingosine (TMS), a stable synthetic sphingosine derivative, was investigated in a feline model of myocardial ischemia (90 min) and reperfusion (270 min) injury. TMS (60 micrograms/kg), administered intravenously 10 min before reperfusion, significantly attenuated myocardial necrosis (15 +/- 3 vs. 31 +/- 4% necrosis of area at risk, P < 0.01) and cardiac myeloperoxidase activities, a marker of neutrophil accumulation, compared with vehicle-treated cats. Endothelium-dependent relaxation to acetylcholine in ischemic-reperfused coronary artery rings treated with TMS was also significantly preserved compared with vehicle (73 +/- 4 vs. 34 +/- 4% vasorelaxation, P < 0.01). Polymorphonuclear neutrophil (PMN) adherence to coronary endothelium 270 min after reperfusion was markedly attenuated in the TMS group compared with vehicle-treated cats (37 +/- 5 vs. 76 +/- 5 PMN/mm2, P < 0.01). TMS also attenuated upregulation of P-selectin on coronary venular endothelium by immunohistochemistry. This was consistent with in vitro findings that TMS attenuates PMN adherence to thrombin-stimulated coronary endothelium and P-selectin upregulation on thrombin-stimulated cat platelets. A sphingolipid derivative, TMS at physiological concentrations exerts cardioprotective actions and preserves coronary endothelial function following myocardial ischemia and reperfusion in vivo. The effects appear to be mediated by the inhibition of PMN-endothelial interaction and subsequent accumulation into the ischemic myocardium. Thus TMS may be a useful agent in attenuating myocardial reperfusion injury.
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PMID:Myocardial and endothelial protection by TMS in ischemia-reperfusion injury. 754 41

The cardioprotective effects of an mAb to P-selectin designated mAb PB1.3 was examined in a feline model of myocardial ischemia (MI) and reperfusion. PB1.3 (1 mg/kg), administered after 80 min of ischemia (i.e., 10 min before reperfusion), significantly attenuated myocardial necrosis compared to a non-blocking mAb (NBP1.6) for P-selectin (15 +/- 3 vs 35 +/- 3% of area at risk, P < 0.01). Moreover, endothelial release of endothelium derived relaxing factor, as assessed by relaxation to acetylcholine, was also significantly preserved in ischemic-reperfused coronary arteries isolated from cats treated with mAb PB1.3 compared to mAb NBP1.6 (67 +/- 6 vs 11 +/- 3, P < 0.01). This endothelial preservation was directly related to reduced endothelial adherence of PMNs in ischemic-reperfused coronary arteries. Immunohistochemical localization of P-selectin was significantly upregulated in the cytoplasm of endothelial cells that lined coronary arteries and veins after 90 min of ischemia and 20 min of reperfusion. The principal site of intracytoplasmic expression was in venous vessels. mAb PB1.3 significantly decreased (P < 0.01) adherence of unstimulated PMNs to thrombin and histamine stimulated endothelial cells in a concentration-dependent manner in vitro. These results demonstrate that PMN adherence to endothelium by P-selectin is an important early consequence of reperfusion injury, and a specific monoclonal antibody to P-selectin exerts significant endothelial preservation and cardioprotection in myocardial ischemia and reperfusion.
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PMID:In vivo neutralization of P-selectin protects feline heart and endothelium in myocardial ischemia and reperfusion injury. 851 48

Warfarin has been widely used for an oral anticoagulant therapy against thrombotic diseases. For the monitoring of its anticoagulant intensities, prothrombin time (PT) ratio and percentage of thrombotest (TT) are commonly used in Japan. Recently, International Normalized Ratio (INR) was recommended by ICSH/ICTH. Practicality and usefulness of INR and its combined use of thrombin-antithrombin III complex (TAT) for the monitoring of oral anticoagulation therapy were evaluated among patients of ischemic heart disease with or without interventions, and of cardiomyopathies and valvular diseases. Difference in thromboplastin sensitivities have been shown to cause errors in PT elongation and in the evaluation of anticoagulant activity, so that the monitoring only by PT ratio is considered to be irrelevant, and that INR is recommended to be used. INR was comparable to the levels of TT. Majority of the patients, whose TAT levels were kept normal, were controlled below the proposed therapeutic ranges of INR. With the combination of INR and TAT monitoring, anticoagulant effect of warfarin could be achieved safer in lower dose than the levels that might cause bleeding accidents.
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PMID:[Monitoring for oral anticoagulant therapy]. 778 35

General recognition of the thrombotic component in ischaemic heart disease (IHD) is comparatively recent. Despite the obvious role of platelets, it has in many ways--and certainly epidemiologically--been work on the coagulation system that has been more rewarding in characterising those at high risk of IHD on account of haemostatic abnormalities. Raised plasma fibrinogen levels are clearly and independently associated with the onset of both clinically manifest IHD and stroke and probably with lower extremity arterial disease as well. High fibrinogen levels also increase recurrence rates and the progression of these conditions. High factor VII activity levels are associated with increased mortality from IHD but not with non-fatal episodes. Low fibrinolytic activity and raised factor VIII levels are also associated with increased IHD incidence. High fibrinogen levels predispose to thrombosis by effects on viscosity, platelet aggregability, fibrin deposition and the atherogenic process. There is increasing evidence that raised factor VII activity levels lead to increased thrombin production. Associations of several personal characteristics--notably smoking in the case of fibrinogen and dietary fat intake in the case of factor VII activity--influence the coagulation system in ways that are likely to predispose to thrombosis. Besides well known agents such as aspirin and anticoagulants, increasing attention ought now to be given to the antithrombotic potential of fibrinogen-lowering agents.
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PMID:Haemostatic function and arterial disease. 780 29

The Northwick Park Heart Study suggested that factor VII activity might be more strongly related to fatal than non-fatal events of ischaemic heart disease. We used polychotomous logistic regression to model simultaneously the probabilities of fatal events, non-fatal myocardial infarction, dying of causes other than ischaemic heart disease and of events, non-fatal myocardial infarction, dying of causes other than ischaemic heart disease and of event-free survival. We followed 1459 white men aged 40-64 at recruitment for a mean period of 16.1 years. Of these, 92 died of ischaemic heart disease, 100 experienced non-fatal myocardial infarction, 173 died of other causes, and 1094 men were alive. Factor VII activity was strongly related to fatal events of ischaemic heart disease but not to non-fatal events (p = 0.008). A difference of 1 SD in factor VII activity was associated with a difference of nearly 50% in the probability of dying of ischaemic heart disease, but with no difference for non-fatal myocardial infarction. This contrast was not seen for smoking, cholesterol, blood pressure, fibrinogen or factor VIII activity. High levels of VII activity may influence outcome at the time of plaque rupture and tissue factor release by enhancing thrombin production and thus fibrin deposition and platelet aggregability. The apparently differential effect of factor VII activity on fatal and non-fatal ischaemic heart disease may have important screening and prophylactic implications.
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PMID:Factor-VII activity and ischaemic heart disease: fatal and non-fatal events. 792 91

The relationship of ischaemic heart disease (IHD) to seasonal and latitude variation has prompted speculation that exposure to the ultraviolet component of solar radiation may reduce IHD risk. This hypothesis was partially tested by exposing 14 post-myocardial infarction patients to a 6 week course of artificial whole-body ultraviolet radiation (UVR). Serum lipoprotein and plasma coagulation factor concentrations were measured before and after the course of UVR. Results were compared with similar measurements from a placebo-controlled group of 13 post-myocardial patients. Despite a more than two-fold rise in mean serum 25-OHD, serum lipoprotein and plasma fibrinogen, antithrombin III and plasminogen concentrations did not change significantly in the UVR group. Significant but minor change in prothrombin time and thrombin time in the placebo group appear unlikely to be of biological significance. Seasonal and latitude variation in these IHD risk factors appear unrelated to corresponding variation in solar UVR exposure.
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PMID:Artificial ultraviolet whole-body radiation does not modify serum lipoprotein, plasma fibrinogen, plasminogen or antithrombin III concentrations in post-myocardial infarction patients. 794 60

The relationship between thrombosis and atherosclerosis has been already suggested in the middle of the last century. More recently, in 1976 a hypothesis has been put forward which emphasize the leading role of chronic injury to endothelial cells followed by platelet attachment and the release of platelet derived growth factors in pathogenesis of atherosclerosis. There is also a growing body of evidence that cytokines, thrombin and the fibrinolytic system are involved in the initiation and progression of atherosclerotic lesions. Lipoprotein (a) is emerging as a link between atherogenic role of lipids and the haemostatic system. At the same time epidemiological data are pointing at the possible role of fibrinogen, factor VII and plasminogen activator inhibitor-1 as risk factors for ischemic heart disease. Thrombus formation is also responsible for the majority of acute coronary syndromes. On the other hand aspirin and other antiplatelet drugs seem to protect from vascular complications of atherosclerosis. Than the question which rather arises is: what is the best antithrombotic strategy in patients with cardiovascular diseases?
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PMID:[Should hemostatic factors be considered in the prevention of cardiovascular disease?]. 797 94


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