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)

There is no doubt that under normal conditions powerful local metabolic regulation adjusts coronary blood flow to myocardial oxygen consumption. 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, and recruitment of such a vasodilator results in improved regional myocardial blood flow and attenuated regional ischaemic 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, so that myocardial oxygen extraction increases to match the increased oxygen consumption. Alpha-adrenergic coronary constriction remains operative in ischaemic myocardium, thus precipitating or contributing to acute myocardial ischaemia 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 ischaemia has not been documented so far. Similarly, peptide hormones/transmitters such as NPY, vasopressin and angiotensin can induce myocardial ischaemia upon exogenous administration. Their pathophysiological role in myocardial ischaemia, however, remains to be established.
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PMID:Control of coronary vasomotor tone in ischaemic myocardium by local metabolism and neurohumoral mechanisms. 166 59

Intravenous (i.v.) bolus administration of adenosine causes increased ventilation and an angina pectoris-like chest pain. Whether adenosine per se or one of its metabolites such as inosine mediates these effects is not clear. Bolus doses of adenosine, inosine, or saline were administered i.v. blindly to six volunteers. Spirometry, ECG recordings, and pain ratings were taken. Adenosine induced both an increase in tidal volume and respiration rate, a dose-dependent chest pain and, at higher doses, various degrees of atrioventricular (AV) block. None of these effects were noted after equimolar injections of inosine or saline. The findings indicate that the angina pectoris-like pain and increased ventilation is induced by adenosine per se and is not produced by adenosine metabolites.
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PMID:Intravenous adenosine but not its first metabolite inosine provokes chest pain in healthy volunteers. 169 61

In this pilot study some cardiac effects of exogenous adenosine on the denervated heart were studied in a patient with transplanted heart since 3 years. He was instrumented with catheters into the left coronary artery, the coronary sinus and the right ventricle. Adenosine was given in increasing doses intracoronarily, into the aorta at the diaphragmal level and into a peripheral vein. When given into the aorta pain was provoked dose-dependently and not different from a reference group. When given intracoronarily no pain was provoked except at the highest dose when a slight discomfort of the chest was provoked. After intravenous injection no pain was provoked in the chest or in adjacent structures. Coronary sinus flow increased dose-dependently and not different from the reference group. No increased heart rate response occurred after intravenous or intracoronary injections. Extensive degrees of sinus and AV nodal blockade occurred. In conclusion, the results are in keeping with a role for adenosine as a messenger between myocardial ischaemia and angina pectoris and cardiac sympathetic pressure response. The importance of innervation for proper sinus and AV nodal function was also illustrated.
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PMID:Effects of exogenous adenosine in a patient with transplanted heart. Evidence for adenosine as a messenger in angina pectoris. 207 41

Adenosine is formed from adenosine triphosphate within the ischaemic cells from where it is released into the coronary circulation. Adenosine exhibits several cardiovascular effects which tend to protect the ischaemic myocardium. Based on the observation that in healthy volunteers the intravenous infusion of adenosine produces angina-like chest pain, it has been recently proposed that another cardioprotective action of this substance could be provocation of angina. If this is the case adenosine should not produce chest pain in patients with silent ischaemia. To test this hypothesis we infused this substance intravenously at increasing doses of 50, 100, 150, 200, 250 and 300 micrograms kg-1 min-1 in eight patients with silent ischaemia (group A). All of them developed ST depression (1.8 +/- 0.2 mm) during exercise testing and seven also during adenosine infusion (1.1 +/- 0.8 mm). However, none of the patients had chest pain during exercise while seven had chest pain during adenosine. We then infused adenosine in eight other patients (Group B) who had painful ischaemia and an exercise tolerance similar to that of Group A patients (time to 1 mm ST depression 8.6 +/- 2.7 min and 8.4 +/- 3 min, respectively, P = NS). Adenosine induced chest pain in all Group B patients. The time to pain onset during adenosine was similar in the two groups (9.3 +/- 2.3 min in Group B and 12.4 +/- 4.9 min in Group A).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine-induced chest pain in patients with silent and painful myocardial ischaemia: another clue to the importance of generalized defective perception of painful stimuli as a cause of silent ischaemia. 324 54

The present investigation was undertaken to study cardiac release of adenosine and prostacyclin (prostaglandin [PG] I2) in patients with ischemic heart disease (IHD), and to assess coronary vascular resistance before and after inhibition of synthesis in such patients. In 48 patients with IHD, arterial and coronary sinus blood samples were taken at rest, during atrial pacing to angina, and after pacing. Levels of purines were determined by high-performance liquid chromatography and the PGI2 metabolite 6-keto-PGF1 alpha was measured with radioimmunoassay. Coronary sinus blood flow was determined with retrograde continuous thermodilution before and after oral administration of indomethacin, aspirin, naproxen, or ibuprofen. Atrial pacing induced myocardial ischemia, as evidenced by typical chest pain and arrested lactate extraction. Adenosine was extracted at rest, but during ischemia there was a significant release of its metabolite hypoxanthine, indicating increased myocardial breakdown of high-energy adenine nucleotides. Arterial and coronary sinus concentrations of 6-keto-PGF1 alpha were low and no significant differences between them were found. After administration of the PG-synthesis inhibitor indomethacin, coronary vascular resistance was elevated, as was the cardiac oxygen extraction. The three other PG-synthesis inhibitors (aspirin, naproxen, and ibuprofen) did not, however, induce any change in coronary vascular resistance or in the cardiac extraction of oxygen. On the basis of these data we suggest that in patients with IHD cardiac ischemia results in increased myocardial production and release of purines, cardiac ischemia does not elicit any detectable increase in coronary production of prostacyclin, and the increased coronary resistance induced by indomethacin does not reflect the involvement of locally formed PG in the maintenance of coronary flow, but is rather a direct effect of the drug.
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PMID:Coronary flow regulation in patients with ischemic heart disease: release of purines and prostacyclin and the effect of inhibitors of prostaglandin formation. 388 37

This study was designed to determine whether human hearts release adenosine, a possible regulator of coronary flow, during temporary myocardial ischemia and, if so, to examine the mechanisms involved. Release of adenosine from canine hearts had been reported during reactive hyperemia following brief coronary occlusion, and we initially confirmed this observation in six dogs hearts. Angina was then produced in 15 patients with anginal syndrome and severe coronary atherosclerosis by rapid atrial pacing during diagnostic studies. In 13 of these patients, adenosine appeared in coronary sinus blood, at a mean level of 40 nmol/100 ml blood (SE = +/-9). In 11 of these 13, adenosine was not detectable in control or recovery samples; when measured, there was concomitant production of lactate and minimal leakage of K(+), but no significant release of creatine phosphokinase, lactic acid dehydrogenase, creatine, or Na(+). THERE WAS NO DETECTABLE RELEASE OF ADENOSINE BY HEARTS DURING PACING OR EXERCISE IN THREE CONTROL GROUPS OF PATIENTS: nine with anginal syndrome and severe coronary atherosclerosis who did not develop angina or produce lactate during rapid pacing, five with normal coronaries and no myocardial disease, and three with normal coronaries but with left ventricular failure. The results indicate that human hearts release significant amounts of adenosine during severe regional myocardial ischemia and anaerobic metabolism. Adenosine release might provide a useful supplementary index of the early effects of ischemia on myocardial metabolism, and might influence regional coronary flow during or after angina pectoris.
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PMID:Release of adenosine from human hearts during angina induced by rapid atrial pacing. 482 35

The function of blood platelets sampled from the coronary sinus and the superior vena cava was studied in 50 men with coronary artery disease at rest and during pacing-induced angina. At rest, a lower platelet aggregation and retention response was found in coronary sinus compared with vena caval blood. This may be due to refractoriness after previous platelet stimulation or to release of platelet inhibitors in the coronary circulation. During pacing-induced angina, lactate levels indicated that blood was sampled from ischemic myocardium in only 27 of the patients. Pacing-induced angina influenced platelet function differently in blood from ischemic and nonischemic regions. Adenosine diphosphate- and collagen-induced aggregation, platelet retention and plasma beta-thromboglobulin levels remained unchanged in blood from ischemic myocardium during pacing, but increased in blood from nonischemic regions. Thus, factors other than ischemia activated platelets in the coronary circulation during tachycardia-induced stress.
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PMID:Effects induced on blood platelets in ischemic and nonischemic myocardium. 622 28

To evaluate the interaction of coronary vasomotor tone and stenosis, we studied the effects of ergonovine and adenosine on partially obstructed coronary arteries in 6 closed chest dogs. Coronary stenosis was created by partially inflating a balloon catheter with a distal lumen in the left anterior descending or circumflex coronary artery. Stenotic resistance was calculated as the mean pressure gradient across the stenosis divided by the mean blood flow measured with 15 micron radioactive microspheres. Coronary artery vasoconstriction, induced by ergonovine (0.6 mg i.v.), caused a small, but nonsignificant, increase in stenotic resistance (1.42 +/- 0.25 to 2.68 +/- 0.64 mm Hg/ml per min) and had no effect on myocardial blood flow. Coronary arteriolar dilation induced by adenosine increased stenotic resistance (1.52 +/- 0.25 to 9.01 +/- 2.49 mm Hg/ml per min, P less than 0.05) and the pressure gradient across the stenosis (18.8 +/- 3.0 to 41.3 +/- 7.5 mm Hg, P less than 0.05). Adenosine increased myocardial blood flow from 0.52 +/- 0.05 ml/min per g to 1.43 +/- 0.20 ml/min per g (P less than 0.05) in the regions supplied by unstenosed arteries, while in the region perfused by the stenosed artery blood flow fell from 0.51 +/- 0.06 to 0.29 +/- 0.13 ml/min per g (P less than 0.05), with the endocardium most severely affected (0.55 +/- 0.04 ml/min per g to 0.26 +/- 0.09 ml/min per g, P less than 0.05). Thus changes in severity of stenosis produced by altered coronary pressure and flow can influence blood flow to the myocardium. Such dynamic changes in coronary artery stenosis may be important in the pathogenesis of angina and myocardial infarction.
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PMID:Reduced myocardial blood flow resulting from dynamic changes in coronary artery stenosis. 664 64

The action on left ventricular function of Astragalus Membranaceus (AM), a Qi-tonic, in 20 patients with angina pectoris was studied by means of Doppler Echocardiogram (DEC). It showed that cardiac output increased from 5.09 +/- 0.21 to 5.95 +/- 0.18 L/min 2 weeks after AM was administered (P < 0.01), and no improvement of left ventricular diastolic function appeared. Adenosine triphosphatase activity was not inhibited by using AM, which was different from that of digitalis.
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PMID:[Action of Astragalus membranaceus on left ventricular function of angina pectoris]. 795 Jan 92

Abnormal constriction of coronary resistive vessels can induce angina and myocardial ischemia. The possibility that a microvascular vasomotor dysfunction could cause ischemia is in contrast with the well-known traditional notion that a metabolically induced vasodilation could compensate for the effect of an epicardial coronary stenosis. Vasoconstrictor stimuli can plausibly act on vessels situated immediately proximal (prearterioles) to those that can be dilated by ischemia metabolites (arterioles). This functional 2-compartment model of resistive vessels is based on the ability of different substances to cause opposite actions on resistive vessels with different sizes. The possible mechanisms of prearteriolar dysfunction, observed in patients with syndrome X, single vessel disease after a successful PTCA and in a subset of chronic stable patients include: an organic reduction of total vascular section; vascular smooth muscle hyperreactivity to heterogeneous constrictor stimuli; an impaired flow-mediated endothelium-dependent vasodilation (possibly due to a reduced NO and/or EDHF synthesis). The first and third hypothesis can only account for anginal episodes at effort while the second model could explain episodes occurring at rest and without an increase in heart rate. Those mechanisms causing an imbalance between myocardial oxygen supply and demand, induce an increased release of adenosine in order to promote a compensating vasodilation. Adenosine can possibly avoid the occurrence of ischemia but, being a powerful algogenic stimulus, causes pain. It is worth noting that the presence of patchy prearteriolar dysfunction induces areas with excessive release of adenosine. Since total vascular section is extremely large a massive adenosine spill-over can occur with a consequential boosting of algogenic and vasodilatory effect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Mechanisms of coronary microvascular dysfunction]. 802 13


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