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)

In 21 control subjects with atypical chest pains and normal coronary arteries and in 64 patients with stable angina and coronary artery disease (CAD), myocardial exchanges of free fatty acids, glucose, lactate, citrate, glutamate, alanine and oxygen were determined before, during and after pacing. At rest, myocardial uptake of fatty acids was 50% lower in CAD patients than in the control subjects (p less than 0.001), whereas uptakes of glucose and lactate were twice as high (p less than 0.01). CAD patients showed increased myocardial glutamate uptake (p less than 0.001) and alanine release (p less than 0.001). In control subjects, myocardial fatty acid uptake was directly related (r = 0.54, p less than 0.01), whereas uptakes of glucose (r = -0.42, p less than 0.05) and lactate (r = -0.46, p less than 0.05) were inversely related to arterial fatty acid levels. Citrate release was inversely related to glucose uptake (R = 0.44, p less than 0.05). These relations were absent in CAD patients. Glutamate consumption correlated only with glucose uptake in CAD patients (p less than 0.001) but did so with lactate uptake and alanine release in all individuals (p less than 0.001). Pacing caused angina in the CAD patients but not in the control subjects. Pacing induced no metabolic changes among control subjects but provoked myocardial lactate release in 40 CAD patients, including an additional decrease of fatty acid uptake (p less than 0.05) and increase of glucose uptake (p less than 0.05) compared with resting levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Altered global myocardial substrate preference at rest and during pacing in coronary artery disease with stable angina pectoris. 342 Nov 65

Patients with typical effort angina have been considered to have normal myocardial metabolism at bodily rest (24). In contrast to this, the present study demonstrated, even in resting asymptomatic CAD patients, a decreased myocardial uptake of FFA, independent of arterial levels and probably reflecting a decreased capacity for FFA oxygenation. This was compensated for by increased aerobic, and in some cases anaerobic, carbohydrate utilization. Further more, there was increased alanine release and glutamate uptake, related to, and perhaps of importance for the maintenance of increased carbohydrate breakdown. The altered myocardial substrate preference related to the severity of ischemic disease, indicates a metabolic adaptation induced by chronic myocardial ischemia in CAD patients.
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PMID:Myocardial substrate utilization and amino acid metabolism in chronic coronary artery disease. 343 81

During repeat exercise testing in 10 patients with stable angina, individual optimal doses of nicardipine were determined. Hemodynamic values and cardiac metabolism were studied during 2 pacing periods carried out before and after this dose (mean 5.3 mg). Postpacing ST-segment depression diminished (1 mm) after nicardipine administration (p less than 0.05), whereas pacing time to onset of angina did not change. Nicardipine administration increased heart rate 16% (p less than 0.005) and reduced systolic (10%) and diastolic (8%) blood pressures (both p less than 0.005). Coronary blood flow increased 16% (p less than 0.05) and coronary vascular resistance decreased 24% (p less than 0.01). Myocardial oxygen consumption was unchanged despite an 11% decrease in rate-pressure product during pacing (p less than 0.02). In the control state before nicardipine administration, metabolic signs of ischemia included release of lactate across the heart in 7 patients, decreased mean free fatty acid and glutamate uptake and alanine release during pacing, together with increased glucose uptake and citrate release during recovery. After nicardipine lactate release decreased in 5 of the 7 patients, pacing no longer changed free fatty acid, glutamate and alanine uptake/release from the level at rest. During recovery glucose uptake was reduced and citrate release was unaffected. The hemodynamic data indicate that nicardipine is a systemic and coronary vasodilator, increasing oxygen supply to the ischemic myocardium. The metabolic results indicate a change in substrate utilization toward that of normal heart, suggesting improved aerobic energy supply.
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PMID:Metabolic and hemodynamic effects of nicardipine during pacing-induced angina pectoris. 381 68

The relation between the amount of exercise-induced ischemia and alterations in left ventricular (LV) function and metabolism at rest was studied in 18 coronary patients with stable angina pectoris. An ischemic defect area score was computed from quantitative exercise thallium-201 (Tl-201) scintigraphy; this estimation of the amount of ischemic myocardium was used to classify the patients in group I (n = 8; score less than 15%, mean 6.7 +/- 2.5%) and II (n = 10; score greater than 15%; mean 27.2 +/- 8.9%). Hemodynamics and metabolism were studied in basal state. No patient had anginal pain during the study, and the extent of angiographic coronary artery disease (CAD) was comparable in the two groups. Heart rate, aortic pressure, coronary blood flow, and myocardial oxygen uptake were also similar in both groups. However, ejection fraction was reduced in group II (51 +/- 13 vs 63 +/- 5%; p less than 0.01) and LV relaxation was impaired as shown by the increase in time-constant of isovolumic pressure fall (55 +/- 16 vs 44 +/- 6 ms in group I; p less than 0.05); the LV end-diastolic pressure was also increased in group II (19 +/- 8 vs 10 +/- 4 mmHg in group l; p less than 0.05). Furthermore, in group II, myocardial lactate uptake was reduced (4 +/- 19 vs 30 +/- 29 mumole/min in group I; p less than 0.01) and the productions of alanine and glutamine were augmented (-7.5 +/- 4.4 vs -4.6 +/- 1.6 mumole/min in group I; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alterations in myocardial metabolism and function at rest in stable angina pectoris: relations with the amount of exercise-induced thallium-201 perfusion defect. 381 6

Ten patients with chronic effort angina and coronary artery disease (luminal diameter reduction greater than 75%) were stressed by atrial pacing (140 beats/minutes) before and 15 minutes after intravenous propranolol (mean dose 7.4 mg). Myocardial substrate exchange of oxygen, blood lactate, plasma free fatty acids, citrate, glucose, glutamate, and alanine as well as coronary sinus blood flow were measured. Coronary sinus blood flow, oxygen consumption, and systemic haemodynamics did not change after propranolol. Propranolol did not influence arterial lactate concentration, and it reduced the arterial concentration of free fatty acid by 37% and increased that of glutamate by 21%. During pacing myocardial lactate extraction increased in all 10 patients; in two lactate release was converted to lactate uptake. Propranolol reduced free fatty acid uptake and increased glutamate uptake during pacing. For both substances the changes in aortocoronary sinus differences or in uptake or both correlated positively with the changes in their delivery to the heart from extracardial sources (arterial concentrations/loads). In the unstressed state before pacing, aortocoronary sinus lactate differences correlated inversely with free fatty acid differences and positively with those of glutamate. During pacing the relation between lactate and glutamate differences remained positive while the inverse correlation between lactate and free fatty acid differences was lost. Myocardial citrate release was halved during pacing and recovery. Propranolol did not influence alanine or glucose exchanges. An improved myocardial lactate extraction after propranolol administration may be secondary to decreased free fatty acid uptake or increased glutamate uptake or both. In the unstressed state both mechanisms may be of importance. During pacing induced ischaemia, increased glutamate uptake is more likely than reduced free fatty acid uptake to be the mechanism responsible for the improvement in myocardial lactate extraction. The propranolol mediated alterations in myocardial substrate exchanges may reflect the extracardial effects of the drug.
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PMID:Improved myocardial lactate extraction after propranolol in coronary artery disease: effected by peripheral glutamate and free fatty acid metabolism. 394 48

The reproducibility of coronary sinus blood flow (CSBF) (thermodilution technique) and myocardial metabolism (exchange of oxygen, lactate, free fatty acids, glucose, citrate, glutamate and alanine) during two identical pacing periods separated by 45 min were studied in eight patients with chronic coronary artery disease. The mean of the individual difference (delta-values) between values during the first (T1) and second (T2) test, at corresponding times (rest, pacing and after 3-5 min of recovery), were calculated and expressed as a percentage of the resting level of each parameter in order to assess their reproducibility. All patients experienced angina pectoris during both pacing sessions, and pacetime to onset of symptoms did not differ between the tests. Group values for haemodynamics and exchange of metabolites were acceptably reproducible throughout the period under study. Mean delta-values of CSBF ranged from 10% to 16% and myocardial oxygen uptake from 14% to 22% in relation to the resting levels. In contrast, mean delta-values of metabolites ranged from 5% to 136% in relation to the respective A-V differences during the study. The greatest variation occurred during pacing and of all the metabolites lactate exchange varied most. A spontaneous variation in the degree of ischaemia during repeat stress tests might be the major reason for the metabolite variability. Changes in CSBF, however, tended to correlate inversely to the delta-aortocoronary sinus differences of substrates during pacing. Precision of chemical analysis and blood sampling technique were of minor importance for the variability. Since lactate exchange varied most, the study suggests that additional measurements should be made of more metabolites when assessing the efficacy of therapy by means of myocardial metabolism.
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PMID:Reproducibility of coronary haemodynamics and cardiac metabolism during pacing-induced angina pectoris. 404 75

8 patients with exertional angina pectoris were treated for 3 months with a low-fat, low-calorie diet. Serum cholesterol was reduced by 28% and body-weight by 7.9 kg on average. The effect of the dietary intervention was assessed by a heart metabolic study during pacing-induced tachycardia. After dietary treatment coronary sinus blood-flow and myocardial oxygen consumption were considerably reduced, but pacing time before angina developed increased. Other improvements were a reduction in lactate release during pacing, a reduction in citrate release during recovery, a reduction in alanine output during rest and recovery, and a lower uptake of glutamate. The results suggest a beneficial effect of low-fat, low-calorie dietary treatment on myocardial energy metabolism in patients with exertional angina pectoris.
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PMID:Beneficial effect of a low-fat low-calorie diet on myocardial energy metabolism in patients with angina pectoris. 614 7

The effects of aorto-coronary bypass surgery on myocardial lactate, free fatty acid and certain amino acid metabolism were studied in 30 coronary patients presenting with unstable, invalidating angina resistant to medical therapy. These patients had electrical signs of anterior wall ischemia without necrosis, significant proximal stenosis of the left anterior descending artery with good distal run-off, and underwent bypass surgery on this artery without signs of postoperative myocardial infarction. This study involved pre- and postoperative hemodynamic investigation with a Swan-Ganz catheter and a metabolic study of the coronary arteriovenous lactate (n = 30), free fatty acid, alanine and glutamate (n = 12) levels under basal conditions and after atrial pacing. These results were compared with those in 10 non-coronary control patients, operated for monovascular replacements. The increase of the pulmonary capillary pressure associated with a fall in systolic index at the 6th postoperative hour showed a reduction in left ventricular performance which tended to correct itself at the 24th hour. In the coronary patients, myocardial lactate production increased, alanine production increased and the uptake of free fatty acids fell during atrial pacing after surgery. These metabolic changes reflect the stimulation of anaerobic glycolysis secondary to myocardial ischemia which disappeared after surgery to compare with the control subjects. Therefore, effective myocardial revascularisation in patients with coronary artery disease is accompanied by the regression of the metabolic stigmata of myocardial ischemia.
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PMID:[Metabolic myocardial modifications following surgical revascularization]. 641 7

Cytoprotection or metabolic modulation is a new principle in the treatment of angina pectoris. The effect of ranolazine (a cytoprotective drug) on ischemic threshold, coronary sinus blood flow, and myocardial metabolism was evaluated by means of two pacing sequences in nine male patients with coronary artery disease (CAD) and in eight male controls. Ranolazine was given as an intravenous bolus followed by continuous infusion; the mean total dose was 32.7 mg and 31.7 mg in patients and controls, respectively. Angina pectoris was relieved in two patients after ranolazine but pacing time to pain was unchanged in the remaining patients. Maximal ST depression was lower (p = 0.02), but pacing time to maximal and to 1-mm ST depression remained unchanged after the drug. Ranolazine had no overall influence on coronary sinus blood flow, cardiac oxygen consumption, blood pressure, and heart rate. Cardiac uptake of free fatty acids (FFA) was reduced (p = 0.01), and net uptakes of glucose (p = 0.07) and lactate (p = 0.06) tended to be lower after ranolazine in CAD patients and controls. Ranolazine had no direct influence on cardiac exchange of glutamate, alanine, and citrate or on the arterial concentration of any metabolite. In the present study ranolazine had minimal clinical effects. A decrease in myocardial FFA utilization, however, allows greater myocardial glucose oxidation, which may increase the energy production in relation to oxygen availability.
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PMID:Effects of ranolazine on ischemic threshold, coronary sinus blood flow, and myocardial metabolism in coronary artery disease. 931 Feb 77

ET-1 is the most potent vasoconstrictor known to date, causing vasoconstriction when bound to the ET(A) receptor. Inhibitors of the binding of ET-1 to the ET(A) receptor would be of immense value as potential therapeutic agents in the treatment of cardiovascular disorders such as angina and hypertension. We present here the rational design of such an inhibitor, which is arrived at on the basis of a model of the ET-1/ET(A) receptor complex proposed by us. The model is found to be consistent with binding and mutagenesis studies of ET-1 as well as of BQ123, a known, potent ET(A)-selective antagonist which competes with ET-1 for receptor binding. BQ123 is a peptidic antagonist which is constrained to adopt a definite conformation on account of its cyclic nature. The noncyclic peptide antagonist designed by us also has a unique conformation because it contains two dehydro-Alanine (deltaAla) residues which, on account of their planarity, cause the peptide backbone to bend in a specific and predictable manner. The folding rules for peptides containing deltaAla were derived in our earlier studies. Energy minimization and modelling of the complex of the designed peptide with the ET(A) receptor indicate that the antagonist is ET(A)-selective and the binding is more stable and more specific as compared to that of BQ123.
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PMID:Molecular modeling of the complex of endothelin-1 (ET-1) with the endothelin type A (ET(A)) receptor and the rational design of a peptide antagonist. 1094 63


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