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)

Plasma bradykinin and prostaglandin metabolism are related to the anginal pain modulating system in patients with ischemic heart disease. We carried out a placebo controlled single blind test of diltiazem (30 mg three times a day) in 15 patients with chronic stable angina. The effect of diltiazem was evaluated by exercise treadmill testing and 48-h ambulatory electrocardiographic monitoring. Plasma bradykinin, thromboxane B2, and 6-keto-prostaglandin F1 alpha levels were determined by radioimmunoassay prior to and during diltiazem therapy. Diltiazem significantly increased the exercise time and reduced episodes of angina. Diltiazem, however, did not appreciably improve either the frequency of silent myocardial ischemic episodes or the total duration of the silent myocardial ischemic episodes. Diltiazem also tended to decrease plasma bradykinin, thromboxane B2, and 6-keto-prostaglandin F1 alpha levels. When ischemic episodes on ambulatory electrocardiographic monitoring are categorized according to heart rate change at the onset of episode (type A, preceded by heart rate increase > or = 5 beats/min; type B, no preceding heart rate increase), diltiazem was only effective on type A ischemic episodes as well as on symptomatic ischemia. Further, bradykinin was significantly decreased by diltiazem only in patients with exercise-induced silent ischemia or no exercise-induced ischemia, while the thromboxane B2/6-keto-prostaglandin F1 alpha ratio was unaffected by the administration of diltiazem. Thus, silent and symptomatic ischemia may be associated with different bradykinin and prostaglandin responses.
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PMID:Effect of diltiazem on silent ischemic episodes, plasma bradykinin and prostaglandin metabolism. 145 74

This study investigated the effects of a low dose of nisoldipine (5 mg, p.o.) in 10 patients with ischemic heart disease. The patients were subjected to a 90-min exercise regimen before and after a 5 mg dose of nisoldipine, using a supine bicycle ergometer adjusted to each patient's limitations. The mean blood plasma level of nisoldipine was 3.8 +/- 3.1 (SD) ng/ml. The drug significantly decreased the systolic arterial pressure in patients throughout the experimental session, whereas a change in the diastolic arterial pressure appeared only at the submaximal stage of the exercise. Additionally, at maximal exercise, nisoldipine caused a decrease in the mean coronary sinus pressure from 11.4 +/- 7 mmHg to 6.5 +/- 5 mmHg (p less than 0.01). By contrast, while at rest, nisoldipine decreased the coronary vascular resistance from 1.5 +/- 0.7 mmHg/ml/min to 1.0 +/- 0.7 mmHg/ml/min (p less than 0.05). After exercise, the drug decreased thromboxane B2 levels from 1133 +/- 907 pg/ml to 720 +/- 379 pg/ml (p less than 0.05) in the coronary sinus blood, and increased the 6 keto-prostaglandin F1 alpha levels from 465 +/- 135 pg/ml to 559 +/- 167 pg/ml (p less than 0.05) in brachial artery blood. This suggests that a low, oral dose of nisoldipine can moderately improve the systemic and coronary hemodynamics and afterloads, and may assist in improving the prostaglandin metabolism in ischemic heart disease patients.
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PMID:Effects of a low, oral dose of nisoldipine on the systemic and coronary hemodynamics and the prostaglandin metabolism of ischemic heart disease patients. 221 32

The responses of eicosanoids to acute myocardial ischemia induced by either exercise stress testing (EX) or percutaneous transluminal coronary angioplasty (PTCA) were investigated in 23 patients with effort angina pectoris (EAP). EX was useful procedure to determine the therapeutic plan in each cases, and PTCA is the novel therapeutic operation for EAP. The relations between these metabolites and either hemodynamics or coronary circulation were then evaluated. The effect of the calcium entry blocker nisoldipine (oral administration of 5 mg) was also studied in 10 patients with EAP. The plasma levels of thromboxane B2 (TXB2), 6-keto-prostaglandin F1 alpha (6KPGF1 alpha) and leukotriene C4 (LTC4) were determined by radioimmunoassay. in arterial and coronary sinus blood samples before and immediately after acute myocardial ischemia. The changes in hemodynamics and coronary circulation during exercise stress testing were assessed by measuring direct brachial artery pressure, cardiac output by the dye dilution method and coronary sinus flow by the thermodilution method. The TXB2/6KPGF1 alpha ratio in coronary sinus blood significantly increased after ischemia in both EX and PTCA, but there was no significant change in LTC4 levels of coronary sinus blood immediately after acute ischemia. The 6KPGF1 alpha levels in both arterial and coronary venous blood were significantly correlated to coronary perfusion pressure and mean brachial artery pressure. Arterial LTC4 levels tended to correlate to mean brachial artery pressure and coronary sinus flow. Nisoldipine improved the ischemic electrocardiography response to EX. Nisoldipine also significantly increased arterial 6KPGF1 alpha at peak exercise. It significantly decreased brachial artery pressure, pressure rate product (PRP), mean coronary sinus pressure and coronary vascular resistance both at rest and peak exercise. The response of PRP significantly correlated with the response of arterial 6KPGF1 alpha. These results suggest: 1 The imbalance of the TXB2/6KPGF1 alpha ratio may be induced more rapidly than LTC4. 2 PGI2 and LTC4 may have some role in the regulation of hemodynamics and coronary circulation during acute myocardial ischemia. 3 Nisoldipine may ameliorate myocardial ischemia through improvement of systemic hemodynamics and prostaglandin metabolism apart from through direct action on the heart.
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PMID:[Responses of plasma eicosanoids and hemodynamics to myocardial ischemia and the salutary effect of calcium entry blocker]. 232 80

Coronary artery inflammation in Kawasaki disease is accompanied by thrombocytosis and platelet activation. It was hypothesized that abnormal metabolism of bioactive eicosanoids could result from or contribute to these events. Circulating plasma thromboxane B2, 6-keto-prostaglandin F1 alpha and prostaglandin E were measured by double antibody radioimmunoassay in patients with Kawasaki disease before and after aspirin alone or aspirin and intravenous gamma globulin therapy. Plasma prostaglandin E concentrations were normal in all patient groups. Pretreatment thromboxane B2 was elevated compared with age-matched controls, fell moderately with high-dose aspirin (60 to 100 mg/kg/day) and marginally increased with low-dose aspirin (3 to 5 mg/kg/day) 6 to 8 weeks after treatment. Plasma 6-keto-prostaglandin F1 alpha was not detected in 12 of 16 patients before therapy and remained low in all but 1 patients by 6 to 8 weeks. Thromboxane B2 correlated weakly with serum salicylate concentration but had no relation to platelet mass. The results in these patients with Kawasaki disease indicate only partial thromboxane suppression and depressed prostacyclin generation regardless of therapy. This balance favors coronary vasoconstriction and platelet aggregation capable of potentiating myocardial ischemia or infarction. The results justify consideration of higher or more frequent aspirin doses for longer duration and thromboxane receptor blockade in this disease.
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PMID:Effects of current therapy of Kawasaki disease on eicosanoid metabolism. 245 25

Cessation of ovarian function is associated with a marked increased in morbidity and mortality secondary to ischemic heart disease. Estrogen replacement has been shown to impart protection against ischemic heart disease. We hypothesized that estrogen may influence vascular production of vasodilators such as prostacyclin. To investigate this relationship we have measured the production of 6-keto-prostaglandin F1 alpha, and thromboxane B2 by superfused uterine arteries from pre- and postmenopausal women. Arterial specimens from healthy normotensive premenopausal (n = 5) and postmenopausal women (n = 5) were superfused for 5 hours. Production of 6-keto-prostaglandin F1 alpha reached steady state levels by 120 minutes and remained linear for the length of the experiment. Indomethacin (4 x 10(-5) mol/L) added at 120 minutes significantly decreased prostanoid production. In subsequent experiments, 17 beta-estradiol in concentrations of 10, 100, 1000 ng/ml was added to the superfusion media at 120 minutes. Total production of 6-keto-prostaglandin F1 alpha by premenopausal arteries superfused with neat media during the steady state interval (3 hours) was significantly greater than that of postmenopausal specimens (1.25 versus 0.27 ng/mg dry tissue, p less than 0.05). Thromboxane B2 levels were undetectable in spent media. However, the addition of 17 beta-estradiol did not alter production of 6-keto-prostaglandin F1 alpha. These data suggest that arterial production of prostacyclin is significantly decreased in uterine arteries from postmenopausal women, but in this in vitro model system estrogens did not affect vascular prostanoid production.
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PMID:Decreased in vitro production of 6-keto-prostaglandin F1 alpha by uterine arteries from postmenopausal women. 260 25

Seven healthy male volunteers were studied at the end of 7 days placebo period and after 7 days treatment with verapamil (120 mg twice daily). Verapamil increased significantly plasma renin activity and urinary excretion of 6-keto prostaglandin F1 alpha without significant modification of plasma aldosterone. Metoclopramide (10 mg i. v.) induced a significant increase of plasma aldosterone with the peak values 15 min after the injection of the drug. The results indicate that verapamil does not lead to secondary hyperaldosteronism which is characteristic of most other vasodilators. The increase of prostacyclin, measured as 6-keto prostaglandin F1 alpha can contribute to the efficacy of verapamil in patients with ischemic heart disease and hypertension. The present study suggests that the aldosterone response to metoclopramide is not directly dependent on calcium, but an indirect effect of calcium through renin-angiotensin system cannot be excluded.
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PMID:Effect of verapamil on renin-angiotensin-aldosterone system, urinary 6-keto prostaglandin F1 alpha and aldosterone response to metoclopramide in normal man. 263 2

There is increasing evidence that platelets play an important role in the pathogenesis of acute ischemic heart disease. Therefore, an understanding of factors which impact on platelet performance is important. The present study was undertaken 1. to characterize during evolving myocardial infarction (MI) platelet activity in the peripheral circulation and across the ischemic/infarcting myocardial compartment, the locus of presumed platelet hyperactivity, and 2. to evaluate the effects of prostacyclin (PGI2), a most potent antiplatelet agent and vasodilator. A total of 59 patients with evolving MI were studied. 22 patients were instrumented with arterial and coronary sinus catheters and received intravenous infusion of PGI2, 13 +/- 4.5 ng/kg/min (mean +/- SD), for 90 minutes. In 15 of these patients, who had an anterior MI, transcardiac platelet function and response to PGI2 were studied. The results are as follows: Plasma levels of beta-thromboglobulin (beta-TG) and of thromboxane B2 (TxB2), in vivo measures of platelet activity, are elevated three and ten fold. 6-keto-prostaglandin F1 alpha, the stable end product of PGI2, is less than 10 pg/ml, reflecting a leftward shift of the TxB2/PGI2 ratio. Platelets, circulating during evolving MI ("ischemic platelets") are hyperaggregable in response to adenosine diphosphate and relatively resistent to PGI2, both in vivo and in vitro. Concentrations of platelet cyclic adenosine monophosphate and the cAMP response to PGI2 are diminished. The platelet hyper-reactivity is most intense early during infarct evolution and decreases with time. Transcardiac measurements indicate that thromboxane is produced across the ischemic/infarcting compartment in ten of 15 patients with anterior MI. The antiplatelet effect of PGI2 is greatly diminished. In summary, the data define an abnormal pattern of platelet behavior during evolving MI characterized by a pro-aggregatory environment, heightened platelet re-activity, both in the peripheral and coronary circulation, and relative resistance to PGI2. The clinical consequence of the data are that the infarct patient in the acute phase may benefit from platelet function suppression and requires significantly greater doses of prostacyclin than normal subjects. The data also suggest future directions for therapeutic manipulation of platelet hyper-reactivity in the setting of acute myocardial ischemia.
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PMID:Platelet hyperactivity in acute myocardial infarction in man--effects of prostacyclin. 293 12

We studied the effect of intracoronary leukotriene B4, C4, D4 and E4 (0.1-3 micrograms) on coronary artery blood flow and resistance in anesthetized pigs. Conventional hemodynamics were measured, and the peripheral electrocardiogram was obtained in lead II. Thromboxane B2 and 6-keto-prostaglandin F1 alpha (as breakdown products of thromboxane and prostacyclin, respectively) were measured during the influence of leukotrienes on the heart. All leukotrienes except B4 reduced coronary flow. Peak reduction was produced by 3 micrograms of each eicosanoid: C4 = 96 +/- 4%+; D4 = 98 +/- 2%+; E4 = 82 +/- 8%+. Coronary resistance increased after the same dose B4 = 65 +/- 18%; C4 = 225 +/- 94% (P less than 0.01); D4 = 442 +/- 118%+; E4 = 110 +/- 43% (+ = P less than 0.001). Increase in filling pressure and heart rate but blood pressure reduction and diminution in left ventricular d P/dtmax were observed with leukotriene C4, D4 and E4. The S-T segments of the electrocardiogram were elevated, thus indicating myocardial ischemia during the blood flow reduction. Indomethacin (5 mg/kg i.v.) had no effects on the leukotriene-induced hemodynamic sequelae. Thromboxane B2 concentration in coronary sinus blood plasma increased by 132-176% (P less than 0.05) at peak leukotriene effects on blood flow. Thus, leukotriene C4, D4, and E4 are vasoconstrictors in the situ porcine heart. Leukotriene B4, however, exerts no hemodynamic effects. The electrocardiographic ischemia and changes in hemodynamics indicate actions on coronary resistance and myocardial depression. These eicosanoids may contribute to cardiac dysfunction and vasospasm in coronary artery disease.
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PMID:Leukotrienes on porcine hemodynamics and prostanoid release. 299 76

To determine changes in platelet activity, prostaglandin metabolism and catecholamine release along with changes in hemodynamics during exercise, we measured these parameters before and immediately after treadmill exercise. Measurements were made on peripheral arterial blood simultaneously with a direct aortic pressure recording in 30 patients with coronary artery disease (Group 1), in 20 patients without significant coronary disease (Group 2), and in 11 young healthy volunteers as controls. At the peak of the exercise regimen, the ST segment depression was found to be significantly lower in Group 1 than in Group 2, whereas the changes in the DPTI/TTI ratio in Group 2 and the controls decreased with the increase in the duration of exercise. The increased serum lactate level at the intermediate level of exercise (420 +/- 20 sec) was significantly lower in the controls than in the other 2 groups. Changes in beta thromboglobulin, platelet factor 4, and plasma norepinephrine were similarly increased in all 3 groups by exercise. At the termination of exercise, however, 6 keto-prostaglandin F1 alpha in Group 1 was insignificantly elevated, whereas it increased from 42.9 +/- 7 pg/ml to 55.7 +/- 7.1 (p less than 0.05) in Group 2 and from 38.2 +/- 5.7 pg/ml to 45.1 +/- 6.8 (p less than 0.01) in the controls. These results suggest that decreased prostacyclin production in the vessel wall might be an indicator of myocardial ischemia, and that the administration of prostacyclin may modulate the coronary vascular tone exaggerated by exercise.
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PMID:The role of prostacyclin during exercise in patients with chronic angina pectoris. 305 98

The effects of the inhibition of phospholipid degradation and superoxide radical generation on prostaglandin synthesis associated with myocardial ischemia and reperfusion were studied in the isolated, in-situ pig heart model subjected to 60 mins of regional ischemia and a further 60 mins of hypothermic potassium cardioplegic arrest, followed by 60 mins of reperfusion. Myocardial biopsies were taken from the ischemic and non-ischemic regions of the myocardium for measurement of phospholipids, and samples of the perfusate were drawn for estimation of the end-products of arachidonic acid metabolism, 6-keto-prostaglandin-F1 alpha and thromboxane B2. A significant amount of 6-keto-prostaglandin F1 alpha and thromboxane B2 appeared during reperfusion, corresponding with the loss of membrane phospholipids in control animals. Mepacrine, a phospholipase inhibitor, protected the depletion of membrane phospholipids and inhibited the products of arachidonate metabolism. Superoxide dismutase (SOD) and catalase, on the other hand, enhanced the formation of 6-keto-prostaglandin F1 alpha and thromboxane B2. The effects of both mepacrine and the free radical scavengers were pronounced during the reperfusion phase when the most significant depletion in membrane phospholipids occurred. These results suggest that the arachidonate cascade is activated during reperfusion of ischemic myocardium as a consequence of phospholipid breakdown, and this activation can be attenuated by inhibiting phospholipases or enhanced by scavenging oxygen-free radicals generated during reperfusion.
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PMID:Enhanced prostaglandin synthesis due to phospholipid breakdown in ischemic-reperfused myocardium. Control of its production by a phospholipase inhibitor or free radical scavengers. 309 30


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