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)

201Tl myocardial perfusion imaging during adenosine infusion was performed in consecutive 55 patients with suspected coronary artery disease. Adenosine was infused intravenously at a rate of 0.14 mg/kg/min for 6 minutes and a dose of 111 MBq of 201Tl was administered in a separate vein at the end of third minute of infusion. Myocardial SPECT imaging was begun 5 minutes and 3 hours after the end of adenosine infusion. For evaluating the presence of perfusion defects, 2 short axis images at the basal and apical levels and a vertical long axis image at the mid left ventricle were used. The regions with decreased 201Tl uptake were assessed semi-quantitatively. Adenosine infusion caused a slight reduction in systolic blood pressure and an increase in heart rate. The rate pressure products increased slightly (9314 +/- 2377 vs. 10360 +/- 2148, p < 0.001). Chest pain (24%) and headache (13%) were the frequent side effects. The second-degree atrioventricular block was developed in 11 of 55 (20%) patients. All symptoms and hemodynamic changes were well tolerated and disappeared within 1 or 2 minutes after discontinuing adenosine infusion. The sensitivity and specificity for the detection of patients with coronary artery disease were 100% (31/31) and 88% (7/8), respectively. 201Tl myocardial imaging during adenosine infusion was considered to be safe and useful for evaluating the patients with ischemic heart disease.
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PMID:[Thallium-201 myocardial perfusion imaging during adenosine-induced coronary vasodilation in patients with ischemic heart disease]. 145 59

We hypothesized that either through local myocardial or systemic effects, adenosine could be used to control hypotension during ischemia. Therefore, we compared the effects of systemic with intracoronary infusion of adenosine on myocardial hemodynamics and metabolism during ischemia in 27 dogs. Left anterior descending artery (LADa) flow was measured and the LADa constricted by a micrometer to restrict resting flow by 50%, 75%, and 100%. Adenosine was infused either systemically (n = 9), to maintain mean aortic pressure at 50-60 mm Hg, or directly into the LADa (n = 9), to create maximal coronary hyperperfusion; no adenosine was infused in the control group (n = 9). With systemic adenosine, during each constriction aortic pressure, left ventricular first derivative (LV dP/dt), and heart rate (HR) decreased: aortic pressure by 56.1% +/- 2.9% (mean +/- SEM), LV dP/dt by 36.2% +/- 2.2%, systemic resistance by 42.7% +/- 5%, and HR by 38.7% +/- 3% during 50% constriction (P less than 0.05 for each variable). Intracoronary adenosine decreased only aortic pressure, LV dP/dt, and HR, all to a lesser extent: aortic pressure by 5% +/- 2.8%, LV dP/dt by 15% +/- 1.2%, and HR by 4.6% +/- 1.7% (P less than 0.05, compared with systemic adenosine for each variable). With systemic adenosine only in the nonischemic area, regional myocardial blood flow increased and remained high, from 224.6 +/- 65.2 to 342 +/- 46.2 mL.min-1.100 g-1 during 50% constriction (P less than 0.05); with intracoronary adenosine, ischemic zone regional myocardial blood flow increased, but not consistently. In the ischemic area, O2 consumption was less with than without systemic adenosine; also, lactate flux production was less positive (-60.2 +/- 37.6 compared with 80.3 +/- 20.2 mmol.min-1.100 g-1 x 10(-3) during 50% constriction; P less than 0.05). Systemic infusion of adenosine during coronary hypoperfusion improves regional metabolism during ischemia and, thus, may mitigate myocardial ischemia. The mechanism by which systemic infusion improves metabolic status may be by decreases in both systemic pressure and systemic vascular resistance.
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PMID:Adenosine for controlled hypotension: systemic compared with intracoronary infusion in dogs. 151 Feb 51

Adenosine is released from the myocardium in response to a decrease in the oxygen supply/demand ratio, as is seen in myocardial ischemia; its protective role is manifested by coronary and collateral vessel vasodilation that increase oxygen supply and by multiple effects that act in concert to decrease myocardial oxygen demand (i.e., negative inotropism, chronotropism, and dromotropism). During periods of oxygen deprivation, adenosine enhances energy production via increased glycolytic flux and can act as a substrate for purine salvage to restore cellular energy charge during reperfusion. Adenosine limits the degree of vascular injury during ischemia and reperfusion by inhibition of oxygen radical release from activated neutrophils, thereby preventing endothelial cell damage, and by inhibition of platelet aggregation. These effects help to preserve endothelial cell function and microvascular perfusion. Long-term exposure to adenosine may also induce coronary angiogenesis.
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PMID:Protective effects of adenosine in myocardial ischemia. 153 25

Attempts to monitor coronary sinus adenosine as a clinical marker of myocardial ischemia in humans have been disappointing. Accordingly, procedures have been developed for detecting adenosine in blood collected from the human coronary sinus. Collection involves using a double-lumen metabolic catheter, which allows blood to be mixed with a stop solution at the catheter tip, thereby minimizing adenosine formation and degradation. A five-component stop solution almost completely arrests adenosine formation and degradation. Adenosine analysis is improved by using both boronate and C18 Sep-Pak columns to purify and concentrate adenosine in human plasma before HPLC. Plasma adenosine in the coronary sinus of patients with and without coronary artery disease, measured before and during peak atrial pacing, showed a twofold atrial pacing-induced increase in adenosine in the patients with coronary artery disease (n = 9, P less than 0.001) but no change in the patients with normal epicardial coronary arteries (n = 6). These preliminary results indicate that coronary sinus adenosine may provide an index of myocardial ischemia in patients with coronary artery disease.
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PMID:Improved detection of ischemia-induced increases in coronary sinus adenosine in patients with coronary artery disease. 154 Oct 9

Better understood in other tissues, the effects of adenosine on insulin-stimulated glucose uptake in the heart are poorly understood. Under pentobarbital anesthesia, we instrumented mongrel dogs to obtain general hemodynamics (blood pressure and heart rate), and arterial and coronary sinus blood samples for measuring oxygen and glucose concentrations. An electromagnetic blood flow probe around the circumflex coronary artery allowed determinations of blood flow, and calculation of substrate uptake by the heart (Fick principle). Somatostatin (SRIF) was infused intravenously (0.8 micrograms/kg/min) along with 0, 0.5, 1.0, 5.0, or 10 mU/kg/min regular insulin, and variable quantities of glucose to maintain euglycemia. Concomitant with the SRIF, insulin, and glucose infusions, adenosine was infused in logarithmically increasing rates (0, 0.01, 0.1, 1.0, 10 or 100 mumol/min) for 30 minutes each into the main left coronary arteries. Insulin infusions increased myocardial glucose uptake in a dose-dependent manner. The heart displayed exquisite sensitivity to insulin, with an ED50 of approximately 14 microU/mL (serum insulin). Adenosine infusions in the absence of insulin (SRIF infusion) increased coronary blood flow, but did not alter myocardial glucose uptake. In the presence of insulin, adenosine increased the maximal value for glucose uptake without changing sensitivity to insulin. These results indicate that adenosine enhances myocardial responsiveness to insulin, with respect to glucose uptake, independent of changes in blood flow. Since glucose can be used for anaerobic metabolism, and adenosine levels are known to increase under situations in which myocardial oxygenation is inadequate, these data have serious implications for conditions such as myocardial ischemia or hypoxia, when glycolytic substrate availability is vital.
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PMID:Adenosine enhances myocardial glucose uptake only in the presence of insulin. 168 Feb 14

Myocardial ischemia results in a breakdown of adenosine triphosphate (ATP), which is associated with an accumulation of its catabolites adenosine and inosine. Adenosine is a potent but ineffective cardioprotective agent because it is rapidly transported to the endothelium and irreversibly catabolized. With the use of specific nucleoside transport inhibition (NTI), however, endogenous adenosine may accumulate at its site of production, and its further breakdown and washout on reperfusion is prevented. In this study we tested this concept and assessed the effect of NTI drug administration on 24 hours' preservation of donor hearts for transplantation. Twelve dogs were randomly allocated to two groups. In the first group (group 1, n = 6) the hearts were arrested with a cold hyperkalemic cardioplegic solution, excised and stored for 24 hours at 0.5 degrees C. After 24 hours the hearts were transplanted orthotopically. In group 2 (n = 6) the same procedure was followed, but a specific NTI agent was added to the cardioplegic solution (1 mg/L) and administered intravenously to the recipient dog before reperfusion of the transplanted heart (0.1 mg/kg). Despite maximal positive inotropic support, none of the control animals (group 1) could be weaned from cardiopulmonary bypass: within 1 hour irreversible cardiogenic shock occurred in all animals. In group 2 all hearts could be weaned from cardiopulmonary bypass and were hemodynamically stable without positive inotropic support. Serial transmural left ventricular biopsies revealed in group 1 moderate catabolism of ATP during cold storage. On reperfusion a further decline of the ATP content was seen, and the accumulated nucleosides were washed out.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A new concept of long-term donor heart preservation: nucleoside transport inhibition. 175 66

Adenosine is known to regulate myocardial and coronary circulatory functions. Adenosine not only dilates coronary vessels, but attenuates beta-adrenergic receptor-mediated increases in myocardial contractility and depresses both sinoatrial and atrioventricular node activities. The effects of adenosine are mediated by two distinct receptors (i.e., A1 and A2 receptors). A1 adenosine receptors, located in atrial and ventricular myocardium and sinoatrial/atrioventricular nodes, are responsible for inhibition of adenylyl cyclase activity. A2 adenosine receptors, located in coronary endothelial and smooth muscle cells, are responsible for stimulation of this enzyme activity. During increased myocardial oxygen demand due to rapid pacing and exercise, although both coronary blood flow and adenosine concentrations in the myocardium and coronary efflux increased, there is no clear consensus explaining its cause and effect relation at present. However, ischemia/reperfusion-induced coronary hyperemia is believed to be mostly attributed to released adenosine, and it has been proven that adenosine attenuates the severity of ischemia due to its coronary vasodilatory action. The beneficial effects of adenosine during ischemia/reperfusion processes do not seem simple. This is because myocardial ischemia and reperfusion injury is caused by 1) activated leukocytes and platelets, 2) ATP depletion and calcium overload of myocardium, and 3) catecholamine release from the presynaptic nerves as well as 4) the impaired coronary circulation. Intriguingly adenosine attenuates all of these deleterious actions and thereby attenuates ischemia/reperfusion injury. Indeed, adenosine attenuates the severity of contractile dysfunction (myocardial stunning) and limits the infarct size. Thus, administration of adenosine or potentiators of adenosine production in the ischemic myocardium may be beneficial for the attenuation of ischemic and reperfusion injuries, although further clinical investigations are necessary.
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PMID:Adenosine, the heart, and coronary circulation. 193 58

Adenosine is a ubiquitous purine base that has many physiological actions in the body, including arterial vasodilation in all vascular beds, with the exception of the kidneys. Myocardial ischemia causes an immediate breakdown of adenosine triphosphate and generates adenosine, thereby producing coronary vasodilation and restoring flow. Adenosine produces vasodilation by interacting with the adenosine receptors in the cell wall. Exogenously administered adenosine has a very short half-life (less than 10 seconds) and produces maximal or near-maximal coronary vasodilation in a dose-dependent fashion. The underlying mechanism for production of myocardial perfusion defects by adenosine thallium 201 scintigraphy is a greater coronary flow increase in the normal arteries and a lesser increase in the stenotic arteries. The ultra-short half-life of adenosine requires a continuous intravenous infusion for its use. Adenosine is often administered as a continuous intravenous infusion at a dose of 140 micrograms/kg per minute for 6 minutes, with the thallium injection given midway through the infusion. The safety of this regimen has been demonstrated in several thousand patients around the country. Side effects, due in great part to the potent vasodilatory effect of the drug, occur in most patients during adenosine infusion. Chest pain also occurs often and in some cases may be due to a true coronary steal phenomenon. First-degree atrioventricular (AV) block occurs in approximately 10% and second- or third-degree AV block in approximately 4% of patients due to the inhibitory effect of adenosine on the AV node conduction. The side effects are very short-lived and typically disappear within 1 or 2 minutes after discontinuing the adenosine infusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pharmacological stress with adenosine for myocardial perfusion imaging. 183 35

Because of its unique ability to demonstrate the metabolic consequences of myocardial ischemia, positron emission tomography (PET) is extremely valuable in assessing myocardial viability. PET imaging can identify the myocardial segments that are likely to improve after revascularization and may be more sensitive and specific for the detection of coronary artery disease compared with thallium perfusion imaging. Adenosine has several advantages over dipyridamole as a pharmacologic stress agent for use with PET. It produces maximal vasodilation in a significantly greater percentage of patients, is a more potent coronary vasodilator, and its very short half-life may be ideal for use with the very short half-life radioactive tracers used in PET. When combined with metabolic studies, adenosine may be useful for the assessment of patients who received thrombolytic therapy for an acute myocardial infarction.
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PMID:Adenosine in myocardial perfusion imaging using positron emission tomography. 206 60

During myocardial ischemia, malignant arrhythmias and acceleration of cell damage may be induced by sympathetic overstimulation of the heart. This stimulation is due to excessive concentrations of catecholamines within the underperfused myocardium, in combination with enhanced myocyte sensitivity to adrenergic stimuli. Various mechanisms may account for local accumulation of catecholamines in the extracellular space of the ischemic but still viable myocardium. In early myocardial infarction, plasma noradrenaline and adrenaline concentrations are enhanced, reflecting increased activity of the whole sympathetic nervous system, rather than local activity in the heart. In uncomplicated infarction, these concentrations are only five times the normal levels at rest, and there are no convincing data that these mildly increased levels of plasma catecholamines directly induce a major deterioration of myocardial function during the ischemic process. Of more importance is the reflex increase in cardiac sympathetic nerve activity that is induced by pain, anxiety, and a fall in cardiac output or arterial blood pressure and that is accompanied by local exocytotic release of noradrenaline from sympathetic nerve endings of the heart. Excessive accumulation of the neurotransmitter, however, is prevented by at least three mechanisms: 1) Released noradrenaline is rapidly removed so long as neuronal catecholamine reuptake is functional. 2) Adenosine accumulating in the ischemic myocardium effectively suppresses exocytotic noradrenaline release by stimulating presynaptic A1-adenosine receptors. 3) Exocytotic catecholamine release ceases when the sympathetic neurons become depleted of adenosine triphosphate since this release mechanism requires high-energy phosphates. However, with progression of ischemia (i.e., greater than 10 minutes), the myocardium is no longer protected against excess adrenergic stimulation since local metabolic release mechanisms become increasingly important. This release, which is independent of both central sympathetic activation and extracellular calcium, occurs in two steps. First, catecholamines escape from their storage vesicles and accumulate in the cytoplasm of the neuron. In the second, rate-limiting step, noradrenaline is transported across the axolemma from the cytoplasm to the interstitial space via the neuronal uptake carrier in reverse of its normal transport direction. As a consequence of this nonexocytotic local metabolic release, extracellular noradrenaline reaches 100-1,000 times its normal plasma concentrations within 30 minutes of ischemia. Concentrations of this magnitude are capable of producing myocardial necrosis, even in the nonischemic heart, and may play an important role in the pathogenesis of ventricular fibrillation in early ischemia.
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PMID:Catecholamines in myocardial ischemia. Systemic and cardiac release. 220 58


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