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)

It is widely known that other causes than recent coronary thrombosis may precipitate acute myocardial infarction in the presence of coronary atherosclerosis. A 48 year old male patient was admitted due to acute coronary insufficiency. The ECG showed anterolateral necrosis and lateral ischemia. Despite medication angina persisted and he died immediately after coronary angiography. At autopsy, established coagulation necrosis was observed in the internal half and the subendocardium of the lateral and posterior walls, of the left ventricle. Early coagulation necrosis occupied the inner half of the anterior, posterior and septal walls. Severe atherosclerotic coronary lesions were found in all major coronary trunks. An extensive panarteritis, involving extra and intramyocardial branches, consisting of mononuclear cells and prominent edema, was observed. A mixed mechanism may be invoked to explain the extensive myocardial necrosis: panarteritic infiltrates and extensive edema and humoral-induced coronary spasm.
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PMID:Panarteritis precipitating extensive circumferential acute myocardial infarction. A case report. 260 69

Fundamental observations and the conceptual framework underlying coronary thrombolysis have a history dating back to 1789. Recent enthusiasm for it is predicated on the recently established safety of cardiac catheterization in critically ill patients, the high incidence of coronary thrombosis underlying acute transmural myocardial infarction and demonstrable benefit conferred to the heart and the patient when thrombolysis is initiated early after the onset of ischemia. Clot-selective activators of the fibrinolytic system offer promise for safe induction of coronary thrombolysis without marked predisposition to bleeding. One such activator, tissue-type plasminogen activator (t-PA), has been synthesized by recombinant deoxyribonucleic acid (DNA) technology, amenable to large scale production of pharmaceutical agents and hence widespread availability. Initial clinical trials conducted with t-PA have demonstrated opening rates of completely occluded, infarct-related coronary arteries of approximately 75% without marked depletion of fibrinogen. The focus of research in progress includes: noninvasive delineation of recanalization and estimation of the extent of myocardium salvaged by initial recanalization, development of alternative routes of administration of thrombolytic agents potentially exploitable by paramedical personnel and, perhaps, high risk patients themselves, and definitive elucidation of the extent to which benefits conferred by thrombolysis can be enhanced with adjunctive pharmacologic interventions as well as early angioplasty or surgery.
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PMID:Coronary thrombolysis with tissue-type plasminogen activator (t-PA): emerging strategies. 309 55

Thromboxane A2 and cysteinyl leukotrienes are highly effective microvessel constrictors in normally perfused myocardium. Their release during acute coronary thrombosis might augment myocardial underperfusion. The constrictor action of these substances could be modified substantially, however, by concomitant myocardial ischemia. We compared the effects of the two eicosanoid constrictors in normally perfused and ischemic myocardium of 24 open-chest, pentobarbital-anesthetized pigs. Left anterior descending coronary flow was measured after intracoronary bolus injections of the stable thromboxane A2 analog U46619 (1-10 micrograms) or leukotriene D4 (LTD4, 1-10 micrograms). Each dose was given before and during myocardial ischemia induced by a snare adjusted to produce 63 +/- 2% decrease in coronary flow for 10 min. Marked dose-independent inhibition of eicosanoid-induced coronary flow decrease occurred during ischemia. With 10 micrograms U46619, coronary flow decrease in the unoccluded state (25 +/- 2 from 55 +/- 4 ml/min pretreatment baseline) was virtually eliminated during snare occlusion (1 +/- 1 from 21 +/- 3 ml/min pretreatment baseline, P less than 0.001). Similar results occurred with LTD4. Distal coronary pressure during ischemia indicated a lack of microvessel responsiveness to the eicosanoids rather than a buffering of resistance change by the snare. U46619 and LTD4 did induce transient, small reductions in regional shortening fraction during ischemia. Our data suggest that eicosanoid-induced constriction of myocardial resistance vessels is not a likely complication of acute coronary thrombosis. However, eicosanoids could depress residual contractility in moderately ischemic regions.
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PMID:Inhibition of eicosanoid-mediated coronary constriction during myocardial ischemia. 337 92

The antifibrillatory, antithrombotic and hemodynamic properties of intraventricular prostacyclin (PGI2) application were studied in conscious canine model of sudden cardiac death. In anesthetized dogs, a wire electrode was implanted into the left circumflex coronary artery (LCX) and acute myocardial ischemia was produced by 90 min occlusion of the left anterior descending coronary artery (LAD) followed by reperfusion. An intracardiac pressure transducer measured ventricular pressure, heart rate, filling pressure and dP/dt. The ECG was obtained from subcutaneous chest needles. Six days later while in ambulatory state, a 180 microA DC current was applied for 4 h to the LCX intimal lining in Tris-HCl (n = 10) and PGI2-treated dogs (50 and 100 ng/kg/min, 11 and 12 dogs, respectively). Myocardial injury and coronary thrombosis induced by electrical stimulation produced ventricular fibrillation in all vehicle-treated dogs at 145 +/- 33 min (mean +/- S.D.). In PGI2-treated hearts only 2 animals fibrillated at 150 +/- 29 min and 180 +/- 52 min following 50 and 100 ng/kg/min of the prostanoid, respectively. Thus, 18/23 PGI2-treated dogs survived 4 h electrical stimulation of the artery. Within the LAD perfusion zone infarction was observed of equal volumes in vehicle and PGI2-treated animals. No ischemia occurred distal to the LCX coronary thrombosis. Ventricular pressure fell in all groups. Heart rate increased in the controls and those animals treated with 50 ng/kg/min PGI2 while 100 ng/kg/min PGI2 increased heart rate by 22 +/- 5% (p less than 0.05). Filling pressure increased in controls but fell in the PGI2-treated hearts. The results indicate that PGI2 can prevent ventricular fibrillation resulting from acute ischemia at a site distant to previous myocardial ischemia with superimposed intimal injury and coronary thrombosis. The PGI2 properties are due to prevention of coronary thrombosis and the occlusion of the artery. Antifibrillatory effects of the prostanoids are suggested.
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PMID:Prostacyclin prevents ventricular fibrillation in a canine model of sudden cardiac death. 352 79

In order to investigate the role of coronary thrombosis as a precipitating factor of acute myocardial infarction (AMI), we examined coronary angiographic findings in 89 patients with AMI taken within 24 hours of the onset and in 42 patients with prolonged angina attack of impending myocardial infarction (impending MI) taken within 50 hours of the last angina attack. Furthermore, in the patients with impending MI, the effects of intracoronary and intravenous thrombolytic therapy and anticoagulant therapy used to prevent impending MI from developing into AMI, were also studied. (1) In 72 of 89 patients (81%) with AMI, coronary thrombi were detected angiographically. The thrombi were detected most frequently (88%) in angiographs taken within 3 hours of onset. (2) In 23 of 42 patients with impending MI, coronary thrombi were detected angiographically. In 6 patients with coronary thrombi who underwent intracoronary thrombolysis during angina attack, occlusive coronary thrombi in ischemia-related vessels were the observed, and recanalization by thrombolysis with intracoronary urokinase infusion relieved chest pain and improved ECG changes. (3) The incidence of AMI in 42 patients with impending MI who were treated with intracoronary and intravenous thrombolytic therapy and anticoagulant therapy was significantly less than in the conventional therapy group (80 patients) (11.9% vs. 27.5%; p less than 0.05). In 4 of 5 patients with developing AMI, coronary thrombi were detected angiographically in the acute phase of impending MI. These results indicate that coronary thrombosis plays an important role not only in the precipitation of impending MI but also in the development of impending MI to AMI.
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PMID:Pathogenesis of impending myocardial infarction and acute myocardial infarction: clinical and angiographic evaluation of coronary thrombosis as a precipitating factor. 372 81

Over the past few years the focus of patient management has begun to extend from the mere detection and treatment of chronic coronary atherosclerotic obstructions to the attempt to understand, diagnose and treat the varied mechanisms responsible for acute myocardial ischemia. Management of patients with ischemic episodes is directed to: control of symptoms and/or signs of ischemia; improve prognosis. Several types of effective drugs are available but because of the incomplete knowledge of pathogenesis their use is still largely empirical. When medical therapy fails, surgery and angioplasty can improve coronary flow reserve considerably and even bring it back to normal. In contrast the goal of improving prognosis is more difficult to assess on an individual basis due to the heterogeneity of groups sufficiently large to ensure statistical analysis in long term follow-up and randomised studies. This makes it impossible to apply the average risk of a group to individual patients. For the future, major challenges remain: it will be necessary to learn more not only about the pathogenesis of coronary atherosclerosis but also about the vasomotor control of large and small coronary arteries, the local and systemic factors leading to coronary thrombosis, the myocardial and coronary response to ischemia, and the genesis of ischemic arrhythmias. Finally, since for the majority of coronary patients management is more often concerned with prognosis than with symptoms, we ought to know in more detail the natural history of the various forms of ischemic heart disease: if any given patient is to be allocated with reasonable precision to a prognostic group, the criteria used to categorize patients must be accurate and multiple.
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PMID:Myocardial ischemia in man: current concepts, changing views and future investigation. 375 94

The second Pisa Conference nine years ago established the frequency of transient reduction of coronary flow, as a cause of angina. Understanding of mechanisms remains very incomplete and there is great overlap between different clinical syndromes. The following facts appear established: Episodes of spontaneous ischemia are frequently asymptomatic and may occur even in patients with classic stable angina of effort: Large coronary arteries exhibit tone; they do not take part in autoregulation: In the presence of advanced organic obstruction, large coronary artery tone may be sufficiently increased by physiological alpha-adrenergic stimulation to provoke ischemia. The following deductions seem justifiable: Clinically, increased large coronary tone can be suspected as a cause of ischemia when there is a background of severe organic coronary narrowing with effort angina, when rest attacks occur in association with stimuli such as cold or isometric stress and when their frequency can be reduced by alpha blockade: Spasm, as distinct from physiological increase in tone, can be suspected when there is minimal organic disease, an absence of effort angina and when attacks are unrelated to stress: The mechanism of spasm is unknown; it may be associated with intimal trauma and probably is more frequent in the presence of early atherosclerotic change: Spasm may be simulated by pseudo-spasm where a physiological increase in tone may cause marked luminal narrowing at a site of still pliable quite mild intimal proliferation; it may be suspected when apparent localised spasm is associated with diffuse acute narrowing of all coronary arteries. Apart from the smooth muscle, acute luminal narrowing with rest angina can result from coronary thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of transient myocardial ischemia. 375 98

The effects of intraventricular infusion of prostacyclin (PGI2; 50, 100 ng/kg/min) on hemodynamics, the ECG, coronary thrombosis and myocardial ischemia were studied in chronically equipped, resting conscious dogs and compared to those of intracardiac administration of Tris-HCl as vehicle. Coronary thrombosis was induced by electrical stimulation of an artery over an implanted wire for 6 hr. PGI2 infusion at 100 ng/kg/min decreased blood pressure by 24 +/- 3% (p less than 0.01) for 5 hr, increased heart rate at 1 hr by 28 +/- 4% (p less than 0.05) followed by a decrement, and elevated cardiac output by 41 +/- 3% (p less than 0.05). Filling pressure and dP/dtmax did not change. Treatment with PGI2 prevented ischemic S-T segment alterations in the ECG and arrhythmias observed in controls. The prostanoid infusion reduced coronary thrombus weight from 64 +/- 7.8 mg (mean +/- S.D.) in controls to 10.7 +/- 6.3 mg and 5.2 +/- 7.1 mg (both p less than 0.001) after 50 and 100 ng/kg/min, respectively. It also reduced myocardial ischemia following occlusive coronary thrombosis from 48 +/- 12% of the left ventricle in controls to 8.8 +/- 8.7% (p less than 0.01) and 2.4 +/- 5.2% (p less than 0.001) in the hearts treated with 50 or 100 ng/kg/min PGI2. The results suggest that PGI2 infusion exerts beneficial effects on heart performance by long-lasting blood pressure reduction and elevation of cardiac output caused by dilation of arterial vessels. PGI2 infusion prevents occlusive coronary artery thrombosis in response to intimal damage by anti-thrombotic properties and vasodilation of coronary arteries. This protects the heart from ischemia observed in controls.
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PMID:Influence of prostacyclin on coronary thrombosis and myocardial ischemia in conscious canine experiments. 391 92

Reperfusion of the globally ischemic myocardium with mannitol has been shown to preserve myocardial function. However, it remains unclear whether the mechanism of mannitol protection relates to its hyperosmolar or free radical scavenging properties. Three groups of isolated, perfused rabbit hearts underwent 45 min of normothermic ischemia without cardioplegia in an experimental paradigm analogous to the clinical situation of coronary artery thrombosis with subsequent reperfusion. Six hearts were reperfused with an isosmolar solution, eight hearts were reperfused with a mannitol-containing solution (20 mOsm/liter), and five hearts were reperfused with a solution containing additional sodium chloride (10 meq/liter, 20 mOsm/liter) to control for the hyperosmotic effects of mannitol. Left ventricular developed pressure, its derivative dP/dt, and diastolic compliance were all significantly improved in the mannitol-reperfused hearts when compared with the hypertonic saline and control groups (p less than .05). There were no intergroup differences in myocardial edema formation, oxygen consumption, or lactate production. These data indicate that mannitol reperfusion offers significant myocardial protection independent of hyperosmolar properties. Free radical scavenging activity appears to be the most credible explanation for these observations, although confirmation of this mechanism awaits further biochemical and cellular investigation.
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PMID:Preservation of myocardial function with mannitol reperfusate. 392 90

The effects of aspirin on coronary hemodynamics and transcardiac concentrations of thromboxane B2 (the stable metabolite of thromboxane A2) were determined at rest and during pacing-induced myocardial ischemia in 11 patients with coronary disease. Control coronary sinus pacing increased both arterial thromboxane B2 (331 +/- 70 to 623 +/- 132 pg/ml, p less than 0.02) and coronary sinus thromboxane B2 (184 +/- 3 to 403 +/- 156 pg/ml, p less than 0.05), but positive transmyocardial gradients developed in only three patients. After 650 mg of oral aspirin, more than 90% inhibition of in vitro thromboxane B2 production was demonstrated and circulating thromboxane B2 was undetectable at rest and during pacing in all patients. Despite these changes in thromboxane B2 concentrations, coronary blood flow was unchanged by aspirin at rest (107 +/- 14 versus 112 +/- 13 ml/min, p = NS) and during pacing (189 +/- 29 versus 181 +/- 25 ml/min, p = NS). Myocardial lactate extraction was also unchanged at rest (24 +/- 7 versus 19 +/- 5%, p = NS) and during pacing (5 +/- 6 versus 9 +/- 5%, p = NS). No change occurred in the anginal threshold. Thus, aspirin does not have the vasoconstrictive properties that have been reported with another cyclo-oxygenase inhibitor, indomethacin. These findings also suggest that thromboxane A2 production does not play a major role in the pathogenesis of stress-induced ischemia. Nonetheless, intracoronary thromboxane A2 production in some patients may potentiate platelet activation and coronary thrombosis. Such patients may benefit from long-term aspirin therapy and can be treated with aspirin without risk of adverse coronary hemodynamic effects.
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PMID:Effect of high dose aspirin on coronary hemodynamics during pacing-induced myocardial ischemia. 396 5


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