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)

At the turn of this century, it was proposed that ischemic cardiac pain might be related to distension of the ventricular wall ("mechanical hypothesis"). Three decades later, it was hypothesized that ischemic pain might be elicited by the intramyocardial release of pain-producing substances induced by ischemia ("chemical hypothesis"). Studies carried out in the past 10 years have given strong support to the chemical hypothesis, because they have consistently shown that adenosine is a mediator of ischemic cardiac pain. Adenosine-induced ischemic cardiac pain is mediated primarily by stimulation of A1 receptors located in cardiac nerve endings and is potentiated by substance P. Conversely, the magnitude and rate of left ventricular dilation during ischemia do not predict the severity of angina. It is worth noting, however, that stretching of epicardial coronary arteries appears to potentiate the severity of angina caused by myocardial ischemia. The nervous activity generated by myocardial ischemia is modulated in intrinsic cardiac, mediastinal, and thoracic ganglia. Then it is further modulated in the central nervous system and projects bilaterally to the cortex, as demonstrated in humans by positron emission tomography, where it is decoded as a painful sensation. The causes responsible for the lack of angina during myocardial ischemia are probably different in patients who present both pain-free and painful myocardial ischemia, in patients with predominantly painless ischemia, and in diabetic patients.
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PMID:New look to an old symptom: angina pectoris. 939 81

The objective of this study was to evaluate the safety of myocardial perfusion scintigraphy with Tc-99 m sestamibi during adenosine stress in patients with recent thrombolytically treated myocardial infarction. Eighty-four patients with thrombolytically treated myocardial infarction, 59 males and 25 females, aged 62.9 +/- 8.4, were eligible for myocardial perfusion scintigraphy during adenosine provocation. Exclusion criteria for adenosine stress were hypotension, unstable angina pectoris, cardiac failure, pericarditis and atrioventricular block (AV block) II-III. Adenosine-stress and resting myocardial perfusion scintigraphy was performed 2-5 days after thrombolysis. Scintigraphy at rest was done 24 h after the stress study. Sixty patients (71%) experienced some kind of side-effects during adenosine infusion. The most frequent side-effects were dyspnoea in 43/84 patients (51%) and unspecific chest discomfort in 26/84 patients (31%). During infusion, ST depressions or elevations on ECG were seen in 9 patients (11%), 5 of whom experienced atypical chest discomfort. Five patients (6%) described typical angina but none of them showed electrographic signs of myocardial ischaemia during infusion. Six patients (7%) developed transient AV block I-II. Reversible scintigraphic perfusion defects were seen in 67 patients (79%). No serious complications, such as death, reinfarction or severe arrhythmias, occurred during adenosine infusion or during a 3-day clinical follow-up period. In conclusion, MIBI-SPECT during adenosine stress is a safe diagnostic method that can be performed in most patients early on after thrombolytically treated acute myocardial infarction. Side-effects are common but benign, and not different from those seen in patients with chronic coronary artery disease.
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PMID:Myocardial perfusion scintigraphy (SPECT) during adenosine stress can be performed safely early on after thrombolytic therapy in acute myocardial infarction. 956 47

Myocardial preconditioning describes the profound myocardial protection that follows a short episode of sublethal ischaemia. Adenosine is produced in ischaemic myocardium and is thought to be an important trigger of the protective mechanism. The exact pathway awaits full elucidation but activation of G proteins and subsequently protein kinase C appear to be important signals. End effectors responsible for delaying cell death include opening of K+ATP ion channels and the transcription of a family of cytoprotective proteins. Absolute proof that preconditioning occurs in man is still awaited, although cross clamping of the aorta during cardiac surgery, balloon inflation during coronary angioplasty, warm-up angina and preinfarction angina are surrogate models supporting its existence. A clearer understanding of the protective mechanisms involved could lead to the development of novel therapeutic agents that could save the infarcting myocardium.
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PMID:Myocardial preconditioning: mechanisms and man. 989 76

Chest pain can arise from cardiovascular or noncardiovascular causes. Among the latter are the skin, the chest wall, intrathoracic structures, or subdiaphragmatic organs. The problem to attribute the chest discomfort to either the heart or extracardiac organs arises because the heart, pleura, aorta, and esophagus are all supplied by sensory fibers from the same spinal segments. In contrast to the diseases mentioned above, angina pectoris in sensu strictu is defined as chest pain or discomfort of cardiac origin that arises because of temporary imbalance between myocardial oxygen supply and demand. The metabolic oxygen requirements of the myocardium are essentially dictated by myocardial contraction since only a fraction of the consumed oxygen is needed by the quiescent heart. Therefore, the factors that primarily influence myocardial oxygen consumption include heart rate, the force of cardiac contraction, and myocardial wall tension, as determined by pressure (afterload), volume (preload), and wall thickness. Extracoronary diseases, e.g. hypertensive heart disease, aortic stenosis or cardiomyopathies, can influence these factors and induce angina pectoris (Figure 1). On the other hand, different diseases influencing the oxygen supply, e.g. anemia, can cause angina pectoris, too. In addition, the modulation of the coronary tone by mediators and cytokines can cause angina, coronary spasm being one example. The neurophysiological substrate of angina pectoris are ganglia which are present within the heart, particularly in epicardial fat. The sympathetic nervous system is the main conveyer of afferent pain fibers from the heart and pericardium, but many fibers may travel by the vagus and the phrenic nerves. Therefore, multiple thoracic structures may cause similar pain syndromes in the distressed patient. The blood supply of intrinsic cardiac ganglia arises primarily from branches of the proximal coronary arteries. Adenosine, among a number of substances, can modulate the activity generated by cardiac afferent nerve endings and intrinsic cardiac neurones. During myocardial ischemia adenosine is released in large quantities into the interstitial space. Given as an intravenous bolus to healthy volunteers or to patients with ischemic heart disease and angina pectoris, adenosine provokes angina pectoris-like pain, which is similar to habitual angina pectoris with regard to quality and location. But other mediators (e.g. bradykinin, histamine, prostaglandins, potassium, lactate) can be involved in the development of angina pectoris, too. As most emphasis should be given to the most serious causes first, the cardiologist has to consider ischemic cardiac disease in the differential diagnosis of nearly every case of acute chest pain. The differential diagnosis contains several causes of nonischemic cardiac chest pain. Dissecting aortic aneurysm may cause severe anterior chest pain that can be mistaken for myocardial infarction. Patients frequently will note the sudden onset of the pain rather than the relatively slower onset of ischemic pain. Furthermore, they feel as a tear and describe it as the most severe pain they have ever had. Pericarditis can be characterized as a sharp precordial knife-like pain that is often increased by lying down, breathing, swallowing, or any other thoracic motion. Radiation of pericardial pain is often relieved by sitting up or leaning forward. It may involve the shoulders, upper back, and neck because of the irritation of the diaphragmatic pleura. Acute pulmonary embolism is associated with severe chest pain. It may mimic acute myocardial infarction. Pulmonary embolism should be suspected when dyspnea or tachypnea seems to be disproportionate to the severity of the chest pain. Diffuse esophageal spasm is the extracardiac condition that is confused most often with ischemic cardiac chest pain. This pain presents as a deep thoracic pain that may be present over most of the thorax. It may extend down the anterome
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PMID:[Angina pectoris in extracoronary diseases]. 1037 99

Hibernation is a chronic condition that can be due to either chronic low perfusion or repetitive stunning. When oxygen demands increase, prolonged periods of ischemia occur, resulting in multiple episodes of stunning. Because hibernation may play a significant role in refractory failure, the diagnosis of hibernation followed by reperfusion can be life saving. Myocardium that has sustained a transient sublethal injury but has the potential for recovery with time is referred to as stunned myocardium. Myocardial stunning is commonly seen after coronary artery bypass surgery: variable periods of myocardial ischemia are sustained during coronary artery bypass graft surgery, and when these patients return to the intensive care unit, their ventricular function is severely impaired because of the prolonged anoxia during bypass. With the support of artificial assist devices, counterpulsation or temporary use of catecholamines, these patients improve and have a favorable prognosis. Similarly, recovery occurs with time in stunning that follows AMI or cardiac transplantation because in either case the heart had been temporarily anoxic. Clinical observations of ischemic preconditioning include the following: (1) first-effort angina or "warm-up phenomenon," i.e., angina with exercise early, but similar or greater effort the rest of the day does not cause any angina and (2) mortality of AMI is lower in patients with a history of angina preceding AMI. Angina 1 to 2 hours before AMI is the most effective time window for ischemic preconditioning. A less potent "second window" is observed when angina occurs during the second to fourth day before AMI. Adenosine possesses marked cardioprotective properties and has been used to pharmacologically induce ischemic preconditioning with some success. Work is still in progress.
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PMID:Hibernating myocardium, stunning, ischemic preconditioning: clinical relevance. 1107 59

Adenosine stress echocardiography was performed in nine patients (58 (+/-3) years, eight women) with documented microvascular angina. Global ventricular function was assessed by Tc(99m) blood pool imaging and Doppler, whereas longitudinal ventricular function was assessed by simultaneous tissue Doppler echocardiography of the lateral mitral annulus. Adenosine was infused incrementally to onset of chest pain in all patients. There was no significant change in global or longitudinal systolic function. Adenosine induced global diastolic dysfunction, demonstrated by blood pool imaging and by Doppler of the transmitral flow. All patients had long axis diastolic dysfunction at peak adenosine, revealed by a ratio of early to late diastolic velocity of lateral mitral annulus <1, which was absent at rest. Adenosine, as a stress agent, provokes regional and global diastolic dysfunction in microvascular angina, which may be a consequence of subendocardial ischaemia. Long axis diastolic dysfunction can be easily revealed by tissue Doppler of the lateral annular motion.
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PMID:Adenosine provokes diastolic dysfunction in microvascular angina. 1179 72

Intravenous dipyridamole increases the concentration of circulating adenosine and produces coronary vasodilation. However, it decreases global cerebral blood flow (CBF) due to hyperventilation side effect of adenosine. In the present study, changes in regional CBF during dipyridamole stress were identified in detail. In 11 healthy men (51-71 years of age), CBF was measured by positron emission tomography with oxygen-15-labeled water at rest (baseline) and during dipyridamole stress. All images were normalized to global CBF and transformed to standard brain anatomy. A t map between baseline and dipyridamole stress conditions was then created on a pixel-by-pixel basis. CBF was globally decreased during dipyridamole stress. However, a significant relative increase in CBF was observed bilaterally in the thalamus and prefrontal cortex, indicating neural activation in these regions. Adenosine plays an important role in the production of anginal pain by stimulation of A(1) adenosine receptors. Neural activation in the thalamus and prefrontal cortex during angina pectoris has been reported. Although no subject felt chest pain during dipyridamole stress, neural activation in the thalamus and prefrontal cortex indicates that stimulation of A(1) adenosine receptors during dipyridamole stress may produce input from the heart to the thalamus through the vagal fiber.
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PMID:Regional changes in human cerebral blood flow during dipyridamole stress: neural activation in the thalamus and prefrontal cortex. 1216 62

BACKGROUND: Adenosine plays a major role in protecting ischaemic myocardium and may potentiate ischaemic preconditioning. Nucleosine transport inhibition may enhance these favourable effects. DESIGN: Randomized, double blind, placebo controlled study, to investigate the haemodynamic and cardioprotective effects of nucleoside transport inhibition during ischaemia in patients with coronary artery disease. PATIENTS AND METHODS: Elective left anterior descending (LAD) coronary angioplasty was used to produce reversible ischaemia in 24 patients with stable angina and a single LAD lesion. They were randomized to receive either the nucleoside transport inhibitor draflazine or placebo. The study medication was infused between the 2nd and 3rd balloon inflation. The primary endpoint was ischaemia-induced wall motion abnormalities as measured by left septal echo amplitude, which was plotted against time to produce an area under the curve. RESULTS: No differences were observed in the systemic haemodynamics or the myocardial collateral circulation of the two groups. The ischaemia-induced regional wall motion abnormalities improved significantly after draflazine, while no difference was observed in the placebo group. This improvement was even more pronounced in patients with low caffeine levels compared with those with high caffeine levels. CONCLUSIONS: Draflazine, in the dose and route used, is associated with a significant improvement in regional myocardial function of the ischaemic area, without affecting systemic or collateral circulation, when compared with placebo. This implies that draflazine has a cardio-protective effect in ischaemic myocardium. High caffeine blood levels reduce these effects.
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PMID:Cardioprotective effects of adenosine transport inhibition during reversible ischaemia in patients with coronary artery disease. 1262 87

Forty-four patients with effort angina pectoris were evaluated with SUNY4001 (adenosine) thallium-201 (201Tl) myocardial scintigraphy to detect coronary artery disease. These patients had single-vessel disease (> or = AHA 90% stenosis) in either RCA or LAD. Adenosine was infused at the rate of 120 or 140 microg/kg/min for six minutes. 111 MBq of 201Tl was injected after three minutes of the start of the infusion. The early and delayed images were obtained by SPECT imaging. The sensitivity was 94.7% at 120 microg/kg/min and 84.2% at 140 microg/kg/min. Adenosine 201Tl myocardial scintigraphy showed high accuracy for detecting significant coronary artery disease. Adverse reactions occurred in 77.3% of the patients. Regarding the rates of the adverse reactions, there was no significant difference between 120 and 140 microg/kg/min. Major adverse reactions were Chest pain/discomfort (52.3%) and Flushing/Feeling of warmth (27.3%). No serious complication was observed at any infusion rate. Most of adverse reactions disappeared sortly. Only two patients required treatment for moderate chest pain, which, however, disappeared in several minutes. One of the treatments was merely the termination of adenosine infusion, and the other was sublingual spray of nitroglycerin. Adenosine infusion caused slight decrease in blood pressure and increase in heart rate. The hemodynamic changes resolved within several minutes after the adenosine infusion. Decrease in systolic blood pressure of more than 20 mmHg from the base level occurred in 26.1% and 52.4% at 120 and 140 microg/kg/min infusion rate respectively. Therefore, the adenosine infusion at 120 microg/kg/min should be considered safe and useful for the diagnosis of coronary artery disease by pharmacologic stress imaging.
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PMID:[Diagnosis of coronary artery disease by thallium-201 myocardial scintigraphy with intravenous infusion of SUNY4001 (adenosine) in effort angina pectoris--the clinical trial report at multi-center: phase II]. 1535 25

Dipyridamole, developed almost half a century ago, acts by inhibiting nucleoside transport, which increases adenosine levels leading to inhibition of platelet aggregation and vasodilatation mainly in the coronary tree. It is a vaso-protective drug with proven efficacy in the prevention of strokes. Adenosine receptor 2 inhibitory purines, ubiquitously available in food and drink, inhibit the vasomotor effects of dipyridamole but not its action on platelet aggregation. This and the slow build-up of blood levels of dipyridamole after oral application may explain why incidents of drug-induced angina ("coronary steal") were never reported in the prevention trials. The prevention of arterial thrombosis and the positive remodeling of the arterial system (arteriogenesis) by elevated blood flows suggest that dipyridamole may be able to halt the progression of organ manifestations of atherosclerosis. Clinical trials for the secondary prevention of vascular occlusions in other vascular beds should be encouraged.
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PMID:Dipyridamole, an underestimated vascular protective drug. 1638 98


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