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 use of pharmacologic stress testing for detecting and assessing ischemic heart disease (IHD) is reviewed. Methods of diagnosing IHD are designed to emulate conditions that increase myocardial oxygen demand in order to identify areas of ischemia and atherosclerotic lesions and to evaluate their functional or anatomical importance. Diagnostic methods can be divided into functional assessment with stress testing and anatomical assessment with coronary angiography. Physical stressors, such as exercise or atrial pacing, or pharmacologic stressors, such as vasodilators or beta-adrenergic-receptor agonists, can be used in stress testing. Electrocardiography, thallium planar scintigraphy, echocardiography, and other techniques are used to evaluate the response to stress testing. Unlike exercise stress testing, pharmacologic testing does not require physical exertion. Adenosine, dipyridamole, and dobutamine are the principal agents used in pharmacologic stress testing. Adenosine and dipyridamole mediate coronary artery vasodilation. Adenosine, a direct agonist, has a rapid onset and short duration of action. Dipyridamole, the only agent with approved labeling for use in stress testing, inhibits adenosine indirectly. Dobutamine increases cardiac output and heart rate as well as promoting coronary artery vasodilation. Clinical trials show that all three drugs can be used safely and effectively in patients after acute myocardial infarction or before vascular surgery and in individuals with risk factors for or symptoms of IHD. The sensitivity and specificity of pharmacologic stress testing for detecting IHD are at least as high as those of exercise testing. Minor adverse effects, including chest pain, headache, and facial flushing, are common, but major adverse effects are rare. Pharmacologic stress testing can be used in patients who cannot undergo exercise testing and offers a noninvasive alternative to coronary angiography.
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PMID:Pharmacologic stress testing: experience with dipyridamole, adenosine, and dobutamine. 816 Jun 85

The aim of the present study was to elucidate the characteristics of patients in whom transient myocardial ischemia was evoked during adenosine infusion. Thallium-201 (Tl-201) myocardial imaging and two-dimensional echocardiography during adenosine infusion were performed simultaneously in 61 consecutive patients enrolled for the diagnosis of coronary artery disease. Transient reduction of systolic wall motion after adenosine infusion was considered evidence of myocardial ischemia. Tl-201 redistribution was noted in 38 patients, and 23 of them showed a wall motion abnormality during adenosine infusion. Stepwise discriminant analysis was applied to eight variables that showed significant differences by the univariate analysis between patients with the presence and the absence of adenosine-induced wall motion abnormality: myocardial infarction, anginal pain, ST depression, collateral vessels, Tl-201 redistribution, number of diseased vessels of > or = 75% or 90% stenosis and number of segments with Tl-201 redistribution. The number of diseased vessels with > or = 75% stenosis (F = 43.5, p < 0.0001), ST depression (F = 16.0, p < 0.0002), collateral vessels (F = 11.7, p < 0.001) and Tl-201 redistribution (F = 5.6, p < 0.02) were the statistically significant discriminators relating to adenosine-induced wall motion abnormality. Adenosine-induced myocardial ischemia was related to the number of coronary stenoses, reflecting the presence of severe coronary artery disease, and well-developed collaterals that might be integral factors in a coronary steal phenomenon.
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PMID:Adenosine-induced heterogeneous perfusion accompanies myocardial ischemia in the presence of advanced coronary artery disease. 817 54

Tissue injury associated with myocardial ischemia is assumed to largely result from the toxic effects of active oxygen species generated by accumulated polymorphonuclear leukocytes (PMNs). Recent reports have indicated that adenosine can interfere with the PMN function in vitro. The potential of adenosine to influence PMN-mediated myocardial tissue injury was assessed using a model of ischemia-reperfusion injury developed in the isolated working guinea-pig heart perfused with homologous PMNs. After an initial work phase, hearts were subjected to 30 min low-flow ischemia (1 ml/min) in the absence and presence of PMNs. Work was resumed after 15 min reperfusion in a non-working mode (Langendorff). Adenosine in the coronary effluent reached a maximum of 0.2 microM during low-flow ischemia. Recoveries of external heart work and cardiac output were reduced from about 80% to about 40% by PMNs. Infusion of adenosine deaminase (ADA, 5 U/ml), theophylline (50 microM) or the selective A1-antagonist dipropyl-8-cyclopentylxanthine (0.1 microM) prevented this effect. Furthermore, application of adenosine (0.1 microM) in combination with PMNs also resulted in a loss of pump function, even in the absence of a direct ischemic stimulus. The data indicate that adenosine contributes to post-ischemic, PMN-mediated damage in the isolated working guinea-pig heart model by a receptor-mediated action.
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PMID:Adenosine contributes to neutrophil-mediated loss of myocardial function in post-ischemic guinea-pig hearts. 826 62

Adenosine is released during myocardial ischemia and can cause angina-like chest pain when given by intracoronary administration. We tested the hypothesis that intracoronary adenosine activates cardiac sympathetic afferent fibers and results in reflex sympathoexcitation. In dogs with sinoaortic denervation and vagotomy, we administered 2 mg of adenosine into the left anterior descending artery over 2 min. Before dipyridamole infusion, intracoronary adenosine resulted in no change in blood pressure or renal sympathetic nerve activity. After dipyridamole infusion, which blocks adenosine uptake, intracoronary adenosine resulted in a peak increase in sympathetic activity of 34 +/- 7%. We also investigated the adenosine-receptor subtype responsible for this sympathoexcitatory response. We found that the adenosine1 agonist N6-cyclopentyladenosine elicited a dose-dependent sympathoexcitatory response similar to adenosine but that the adenosine2 agonist 5'-(N-cyclopropyl)carboxamidoadenosine failed to elicit a sympathoexcitatory response. We conclude that adenosine activates cardiac sympathetic afferent fibers and leads to a sympathoexcitatory response due to activation of adenosine1 receptors.
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PMID:Activation of cardiac sympathetic afferents: effects of exogenous adenosine and adenosine analogues. 834 58

The powerful local metabolic regulation adjusting coronary blood flow to myocardial oxygen consumption under normal conditions is beyond doubt. However, despite substantial experimental efforts the responsible mediators are still largely unknown. Adenosine, a purported mediator of local metabolic control of coronary blood flow, is probably only involved in transient flow adaptations, but not in steady-state coronary autoregulation. Even below the autoregulatory range a substantial vasodilator reserve persists. Recruitment of such vasodilator reserve results in improved regional myocardial blood flow and attenuated regional ischemic dysfunction. beta-adrenergic coronary dilation is of minor functional importance. alpha-adrenergic coronary constriction acts to attenuate increases in coronary blood flow during sympathetic activation under normal conditions, such that myocardial oxygen extraction increases to match the increased oxygen consumption. alpha-adrenergic coronary constriction remains operative in ischemic myocardium, thus precipitating or contributing to acute myocardial ischemia during sympathetic activation and exercise in experimental animals as well as in patients with stable angina. The vagal transmitter acetylcholine--upon exogenous intracoronary infusion--induces critical constriction of epicardial coronary arteries with endothelial dysfunction and atherosclerosis. However, a vagal initiation of coronary spasm or myocardial ischemia has not been documented so far. Similarly, peptide hormones/transmitters such as NPY, vasopressin, and angiotensin can induce myocardial ischemia upon exogenous administration. Their pathophysiological role in myocardial ischemia and reperfusion, however, remains to be established.
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PMID:Local and neurohumoral control of coronary blood flow. 839 71

Percutaneous transluminal coronary angioplasty (PTCA) represents a suitable model to establish myocardial ischemia in man. Balloon inflation usually is accompanied by a significant deterioration in left ventricular systolic and diastolic properties. A brief episode of ischemia followed by reperfusion termed preconditioning has been identified as a mechanism rendering the myocardium more resistant to ischemia. Adenosine is considered as important mediator of preconditioning. Dipyridamole represents an important drug interfering with myocardial adenosine metabolism by inhibiting its cellular reuptake. The aim of this study was to investigate if an intracoronary infusion of dipyridamole represents a suitable tool in preventing the deterioration of left ventricular performance and hemodynamics during PTCA. In 20 patients undergoing elective coronary angioplasty of a major vessel assessment of angiographic left ventricular performance and left ventricular hemodynamics was performed before, during and after coronary angioplasty. Patients were randomly allocated to study group 1 receiving an intracoronary infusion of dipyridamole prior to PTCA and study group 2 where conventional pretreatment was performed. In study group 3 intracoronary dipyridamole infusion was performed in 10 patients with coronary artery disease during coronary angiography in order to evaluate its effect on baseline hemodynamics and left ventricular performance. Dipyridamole-pretreatment resulted in a significant preservation of systolic and diastolic left ventricular performance during PTCA, as documented by an uneffected global ejection fraction (in comparison to a deterioration of 29.2% in study group 2) and an increment in diastolic stiffness of only 12.7% (in comparison to an increment of 57.3% in study group 2). Furthermore, a significant prolongation of achievable balloon-inflation times of 48.4% could be obtained in study group 1. In addition, incidence of arrhythmias seemed to be reduced in study group 1. Apart from two cases of coronary steal phenomenon no significant side effects of dipyridamole infusion could be detected. Finally, in study group 3 dipyridamole-pretreatment per se induced a significant amelioration of angiographically assessed left ventricular systolic performance.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Pharmacologic myocardial protection during percutaneous transluminal coronary angioplasty (PTCA) by intracoronary dipyridamole: hemodynamic, contractile and dynamic ventricular consequences]. 857 41

In contrast to in vitro studies, experiments in intact animals could not detect a positive inotropic effect of endothelin-1 (ET-1). We presumed that the ET-induced direct positive inotropy is antagonized in vivo by an indirect cardiodepressant effect due to a mainly ETA-mediated and ET-induced coronary constriction, with consequent myocardial ischemia. To confirm this hypothesis we examined in thoracotomized rats the effects of a nonselective activation of ETA and ETB receptors by 1 nmol/kg ET-1 with and without the vasodilator adenosine (2.0 mg/kg/min), and the effects of a selective activation of ETB receptors by the ETB agonist IRL 1620 (2 nmol/kg) on myocardial contractility and energy metabolism (ATP, ADP, AMP). In addition to recordings in the intact circulation, isovolumic measurements (peak LVSP, peak dP/dtmax) were performed for quantification of myocardial contractility. ET-1 had no positive inotropic effect (peak dP/dtmax -2% vs. control, n.s.) due to a marked vasoconstriction with a consequent fall in the myocardial ATP content (-17%; p < 0.01). Adenosine antagonized the ET-induced vasoconstriction in part, normalized myocardial energy metabolism (ATP -7%), and thus unmasked the positive inotropic effect of ET-1 (peak dP/dtmax +20%; p < 0.01). Selective activation of ETB receptors by IRL 1620 had only a small vasoconstrictor effect, which did not produce myocardial ischemia (ATP + 10%; n.s.) and thus caused a positive inotropic effect in vivo (peak dP/dtmax +22%; p < 0.01). The positive inotropic effect of ET-1 is not detectable in vivo as its marked, mainly ETA-mediated, vaso- and coronary constriction causes myocardial ischemia that thus produces an indirect negative inotropic effect.
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PMID:Effects of endothelin-1 and IRL 1620 on myocardial contractility and myocardial energy metabolism. 858 48

As the mechanism of ischemic preconditioning unfolds, various strategies for inducing pharmacologic preconditioning become apparent. Adenosine receptor agonists, KATP channel activators, and endothelial-neutrophil adhesion antagonists have enjoyed cardioprotective activity against ischemia/reperfusion injury in at least some preclinical models. Monophosphoryl lipid A (MLA), a structural derivative of the pharmacophore of endotoxin, enjoys an improved therapeutic index in relation to the parent biological product. MLA has found clinical application as a vaccine adjuvant and protects from sepsis and septic shock in the preclinical setting. In animal models of myocardial ischemia/reperfusion injury, pretreatment 12-24 hours prior to ischemia with a single IV bolus injection of MLA limits infarct size 50 to 75 percent in standard canine and rabbit models at doses of 10-35 micrograms/kg. Regional myocardial stunning following multiple 5-minute ischemic episodes as assessed by segment shortening is reduced in dogs pretreated 24 but not 1 hour prior to ischemia. Global cardiac function, as evaluated by pressure-volume constructs generated in dogs being weaned from cardiopulmonary bypass, recovers more quickly in animals pretreated with MLA. Cardiac protection in various models is associated with preservation of ATP during ischemia, induction of 5' nucleotidase and enhancement of calcium reuptake by SR during reperfusion. Limitation of infarct size by MLA in dogs and rabbits can be reversed by the administration of glibenclamide just prior to ischemia, suggesting a role for KATP channel opening during the first minutes of sustained ischemia. A clinical formulation of MLA (MPL-C) is currently undergoing clinical investigation in the Phase II setting in coronary artery bypass surgical patients. MLA may represent a novel means of inducing pharmacologic preconditioning, with potential for clinical application as a pretreatment before planned myocardial ischemia.
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PMID:Pharmacologic myocardial preconditioning with monophosphoryl lipid A (MLA) reduces infarct size and stunning in dogs and rabbits. 890 81

Adenosine (ADO) is an important endogenous protective metabolite of the heart which also exerts beneficial effects when exogenously supplied before or after ischemia. Previous studies established that after initial massive release of ADO, its endogenous production could be significantly reduced following myocardial ischemia. However, the mechanism and consequences of this phenomenon are not clear. We investigated whether this suppressed endogenous ADO production could be reversed by a transient supply of exogenous ADO during reperfusion. Furthermore, we studied the recovery of mechanical function, coronary flow and myocardial nucleotide levels after this intervention. Three concentrations of ADO were applied: 1 microM, which exerts maximal vasodilatation: 30 microM, optimal for adenylate resynthesis: and 1 mM which exerts a cardioplegic effect. Rat hearts perfused in the Langendorff mode were divided into five groups (n = 6-9 per group): all hearts had transient (30-s) ischemia at 20 min (TI-1) and 70 min (TI-3) of perfusion. Group 1 (control) had an additional transient (30-s) ischemia at 45 min (TI-2). Group 2 (ischemic control) had 10-min ischemia at 30 min: groups 3, 4 and 5 also had 10-min ischemia at 30 min but were reperfused for the initial 15 min with 1 microM, 30 microM or 1 mM ADO. Developed tension, coronary flow and coronary effluent purines and pyrimidines were measured throughout the 75-min experimental period. Nucleotide content was evaluated in freeze-clamped hearts at the end of the experiment. Endogenous ADO release to the coronary effluent increased immediately after TI-1 in all groups. This increase was similar after TI-1 and after TI-3 in control, while it was reduced to 30% in ischemic control group. In the 30 microM ADO group the increase in endogenous ADO release after TI-3 was restored and was similar to that after TI-1. A similar trend was observed with 1 mM ADO, while in 1 microM group recovery of endogenous ADO release after TI-3 was not observed. The highest recovery of developed tension (+ S.E.) occurred with 1 microM and 30 microM ADO (72 +/- 3% and 72 +/- 5% of pre-ischemic value, respectively) compared to 53 +/- 5% and 63 +/- 5% in ischemic control and 1 mM ADO groups, respectively (P <0.05). Coronary flow was restored 30 s after 10 min ischemia in hearts treated with 1 microM and 30 microM ADO, whereas more than 2 min were necessary in ischemic control or 1 mM ADO groups. Furthermore, hyperemic response after TI-3 was significantly enhanced in the 1 microM or 30 microM ADO groups. ATP content at the end of reperfusion was highest in the 30 microM ADO group (18.9 +/- 0.5 micromol/g dry wt.) as compared to ischemic control. 1 microM or 1 mM ADO groups (15.2 +/- O.6, 16.4 +/- 0.4, and 17.2 +/- 0.4 micromol/g dry wt. respectively). Concentrations of other nucleotide triphosphates (GTP, UTP and CTP) were similar in all hearts subjected to 10-min ischemia. In summary, depressed endogenous ADO production in the post-ischemic heart could be ameliorated by transient supply of exogenous ADO during reperfusion at 30 microM concentration. This effect was found to be related to the elevation of the adenine nucleotide pool. However, restoration of endogenous ADO production was not necessary for improvement in the recovery of mechanical function by exogenous ADO.
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PMID:Exogenous adenosine, supplied transiently during reperfusion, ameliorates depressed endogenous adenosine production in the post-ischemic rat heart. 904 48

Epidemiologic studies indicate that long-term alcohol consumption decreases the incidence of coronary disease and may improve outcome after myocardial infarction. Attenuation of ischemia-reperfusion injury after myocardial infarction improves survival. This study investigates the possibility that alcohol consumption can improve survival after myocardial infarction by reducing ischemia-reperfusion injury. Hearts were isolated from guinea pigs after drinking ethanol for 3-12 weeks and subjected to global ischemia and reperfusion. Hearts from animals drinking ethanol showed improved functional recovery and decreased myocyte damage when compared with controls. Adenosine A1 receptor blockade abolished the protection provided by ethanol consumption. These findings indicate that long-term alcohol consumption reduces myocardial ischemia-reperfusion injury and that adenosine A1 receptors are required for this protective effect of ethanol. This cardioprotective effect of long-term alcohol consumption mimics preconditioning and may, in part, account for the beneficial effect of moderate drinking on cardiac health.
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PMID:Regular alcohol consumption mimics cardiac preconditioning by protecting against ischemia-reperfusion injury. 909 76


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