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)

Indomethacin, meclofenamic acid and acetylsalicylic acid are prostaglandin synthetase-inhibiting, nonsteroidal anti-inflammatory drugs. Their effects on hemodynamic and enzymatic responses to coronary artery occlusion were evaluated in the cat. The direct effects of these drugs on isolated tissue preparations (i.e., cat papillary muscle, aortic strip and liver lysosomes) were also studied. None of the drugs tested exhibited any significant hemodynamic or biochemical effects which would indicate protection against damage due to myocardial ischemia during the 5-hour experimental period. Furthermore, only indomethacin produced significant effects on the isolated tissues studied. Indomethacin increased the tension of aortic strips confirming a pressor effect seen in the intact animal and exerted a modest stabilization of isolated liver lysosomes. All three anti-inflammatory drugs inhibited prostaglandin F2alpha, release in heart homogenates by 82 to 87%. It is concluded that nonsteroidal anti-inflammatory drugs do not significantly influence the early course of myocardial ischemia in the cat, in contrast to the previously reported preservation of myocardial integrity afforded by dexamethasone and methylprednisolone.
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PMID:Influence of nonsteroidal anti-inflammatory agents on myocardial ischemia in the cat. 93 91

Nitric oxide (NO) and prostacyclin (PGI2) were determined in effluents of Langendorff-perfused rabbit hearts subjected to 2 h of global low-flow ischemia and subsequent reperfusion. PGI2 release [6-oxo-prostaglandin (PG) F1 alpha] was significantly enhanced during early reperfusion and remained elevated. NO formation was reduced during ischemia but did increase substantially during reperfusion. Indomethacin (3 microM) significantly suppressed ischemia-related 6-oxo-PGF1 alpha and NO release. This was accompanied by severely diminished myocardial recovery. NG-nitro-L-arginine (L-NNA) (100 microM) suppressed NO generation without major effects on 6-oxo-PGF1 alpha generation and cardiac dysfunction but with a remarkable increase in coronary perfusion pressure. These effects of L-NNA were antagonized by L-arginine, whereas the effects of indomethacin were not. There was a substantial loss of creatine kinase specific activity from reperfused ischemic hearts, which was further aggravated by indomethacin but not by L-NNA. These data demonstrate a cardioprotective and endothelium-protective role of PGI2 in myocardial ischemia, which also involves preservation of NO generation. Endogenous NO appears to be important for local regulation of coronary flow.
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PMID:Prostacyclin rather than endogenous nitric oxide is a tissue protective factor in myocardial ischemia. 144 94

This study showed that the 1-O-hexadecyl form of platelet-activating factor (PAF) is released along with 6-keto-prostacyclin1 alpha (6-keto-PGF1 alpha) in the perfusates of ischemic-isolated rabbit heart. During the early phase of the reperfusion, the release of PAF and 6-keto-PGF1 alpha was particularly increased (PAF, from 5.4 +/- 1.2 to 19.7 +/- 2.0 ng/min; 6-keto-PGF1 alpha, from 2.3 +/- 0.1 to 27.4 +/- 1.8 ng/min) and this event was coupled with the characteristic mechanical alterations of myocardial performance and perfusion pressure (PP). These changes were effectively antagonized by pretreatment of the hearts with both prostacyclin (PGI2, 20 ng/ml) and the PGI2-releaser defibrotide (400 micrograms/ml). The protecting activity observed with PGI2 was paralleled by a reduction in the rate of PAF release during reperfusion (from 19.7 +/- 2.0 to 6.8 +/- 0.2 ng/min). In defibrotide-treated preparations, inhibition of PAF formation was associated with a pronounced stimulation of 6-keto-PGF1 alpha generation, which was particularly marked on reperfusion (from 27.4 +/- 1.8 to 197.5 +/- 8.2 ng/min). Indomethacin (1 microgram/ml) ablated the antiischemic effect of defibrotide but did not potentiate the rate of formation of PAF despite inhibition of 6-keto-PGF1 alpha biosynthesis. From these results, we conclude that in a model of severe myocardial ischemia, in which the major determinants of cardiac performance are under control, generation of PAF and PGI2 appears to play an important biologic role in determination of the severity of myocardial ischemic damage.
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PMID:Production and biologic interactions of prostacyclin and platelet-activating factor in acute myocardial ischemia in the perfused rabbit heart. 170 93

The anti-ischemic effects of nafazatrom (10 mg/kg intraduodenally) have been studied in a canine model of myocardial infarction. Nafazatrom was given 30 min before and 2 h after occlusion of the left anterior descending coronary artery (LAD). Effects were compared with those after intravenous indomethacin (10 mg/kg) treatment. Infarct size was measured at 6 h of coronary occlusion by postmortem tetrazolium staining. Myocardial ischemia was reduced after nafazatrom administration, whether related to total left ventricle (18 +/- 3.3 vs. 30.7 +/- 4.8%; p less than 0.05) or to the LAD vessel area at risk for infarction (51.4 +/- 4.0 vs. 82.5 +/- 4.5%; p less than 0.01). Salvage with nafazatrom occurred in the subepicardial and endomural tissues without lateral protection. Indomethacin had no effects on infarction. The LAD occlusion-induced hemodynamic consequences were reduced at 15 min by nafazatrom and remained unchanged by indomethacin. During the following experimental course, no differences were noted between the groups. At 6 h, blood flow in the nonoccluded circumflex artery increased by 12.6 +/- 3.2 ml/min (p less than 0.05) following nafazatrom treatment. Thus, nafazatrom reduced ischemia by a mechanism unrelated to changes in hemodynamics. Most likely, this was due to 5-lipoxygenase inhibition. This may shift arachidonic acid metabolism to cyclooxygenase products and prevent release of deleterious lipoxygenase products by neutrophils during ischemic injury.
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PMID:Effects of nafazatrom and indomethacin on experimental myocardial ischemia in the anesthetized dog. 241 12

The possibility of a coexistence of coronary arteriolar constriction mediated by the renin-angiotensin system and myocardial ischemia was evaluated. Left anterior descending coronary artery was cannulated and perfused at normal (mean aortic), intermediate (50 mm Hg), and low (30-40 mm Hg) pressure in analogy to a progressive coronary stenosis. Lactate production was present at low coronary pressure indicating myocardial ischemia. In control animals (n = 18), mean coronary conductance was higher (p less than 0.005) at intermediate than at high coronary pressure consistent with autoregulation at coronary flow. Coronary conductance was lower (p less than 0.05) at low than at intermediate coronary pressure, indicating coronary constriction during myocardial ischemia. Adenosine (20 micrograms/kg per min i.c., n = 6) resulted in higher coronary conductance, suggesting coronary vasodilator reserve even at low coronary pressure. Indomethacin (5 mg/kg i.v., n = 12) resulted in low coronary conductance; however, the increase at intermediate (autoregulation) and the decrease (constriction) at low pressure was maintained. Plasma renin activity increased, and saralasin (0.1 microgram/kg per min i.c.) and captopril (0.25 mg/kg i.v.) acted as coronary vasodilators in various models of myocardial ischemia. Captopril limited myocardial infarct size at 6 hours of coronary occlusion, diminished flow repayment and prevented lactate production after 30 s of coronary occlusion, and abolished the deterioration of myocardial function during myocardial ischemia induced by coronary hypoperfusion and atrial pacing. Thus, myocardial ischemia does not generally represent a state of maximal coronary dilatation. The renin-angiotensin system is activated by myocardial ischemia and may exert a coronary constrictive tone. Captopril was beneficial in experimental myocardial ischemia.
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PMID:Coronary vasoconstriction in experimental myocardial ischemia. 244 Dec 6

This study was undertaken to determine whether atherosclerosis impairs relaxations mediated by endothelium-derived relaxing factor (EDRF) in human coronary arteries. Epicardial coronary arteries were obtained from the hearts of cardiac transplantation patients with or without histologically documented coronary atherosclerosis (atherosclerotic arteries were from patients aged 42-55 years, nonatherosclerotic arteries were from patients aged 14-24 years). Transverse strip preparations were mounted in organ baths for isometric tension recording. Tension was induced with prostaglandins F2 alpha. Indomethacin (10(-5) M) was present to prevent possible interference from endogenously formed prostaglandins. The EDRF-mediated relaxations in response to substance P (10(-10) to 10(-8) M), bradykinin (10(-9) to 10(-7) M), and Ca2+-ionophore A23187 (10(-9) to 10(-7) M) were significantly attenuated in atherosclerotic arteries. In deendothelialized tissues these compounds had no effect. In contrast, endothelium-independent relaxations induced by isoprenaline (10(-7) to 10(-5) M) were not affected by atherosclerosis. Atherosclerotic arteries showed also normal relaxations with high concentrations of glyceryl trinitrate (10(-8) to 10(-7) M), but reduced relaxations with a lower concentration of the compound (10(-9) M). Acetylcholine (10(-7) to 10(-6) M) only produced endothelium-dependent relaxations in 8 of 60 arterial preparations (with or without atherosclerosis). In most of the arteries, it was a direct vasoconstrictor (which may have masked EDRF release in many cases). Omission of indomethacin from the bath solution increased the incidence of moderate acetylcholine-induced relaxations (9 of 16 preparations). It is concluded that atherosclerosis attenuates EDRF-mediated vasospasm and myocardial ischemia.
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PMID:Selective attenuation of endothelium-mediated vasodilation in atherosclerotic human coronary arteries. 244 55

Myocardial ischemia was induced in perfused paced isovolumic left heart preparation of the rabbit by reducing, for a period of 40 min, the flow rate from 20 ml/min to 0.2 ml/min (severe model) and to 1 ml/min (moderate model). The relationship between prostaglandin biosynthesis and cardiac ischemic damage was evaluated in the two experimental models. The results obtained indicate that the total amount of 6-keto-PGF1 alpha generated increases with the severity of the ischemia, particularly during the 20 min of reperfusion (moderate model 81.8 +/- 13.7 ng: severe model 375 +/- 102 ng). The inhibition of the prostaglandin synthesis, prostaglandin-E2, and 6-keto-prostaglandin-F1 alpha (PGE2 and 6-keto-PGF1 alpha levels below the detection limits) by Aspirin (20 micrograms/ml) and Indomethacin (1 microgram/ml) in moderate myocardial ischemia was correlated with greater increments in resting diastolic tension (nearly 100% and 40%, respectively). This phenomenon was also associated to a further decrease on cardiac contractility and increase on coronary perfusion pressure upon reperfusion. On the contrary drugs which stimulated prostaglandin generation in myocardial tissue, such as Defibrotide (400 micrograms/ml), completely protected the organ from ischemia. U-60257 (3 micrograms/ml) and FPL-55712 (2 micrograms/ml), compounds, which respectively inhibits biosynthesis and the effects of leukotrienes, displayed a beneficial activity on this moderate model of ischemia. The present data suggests that the deleterious effect of nonsteroidal antiinflammatory drugs in low flow myocardial ischemia and reperfusion damage may be associated with removal of PGI2 and PGE2 from ischemic myocardium.
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PMID:Nonsteroidal antiinflammatory drugs aggravate acute myocardial ischemia in the perfused rabbit heart: a role for prostacyclin. 246 44

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

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

Bradykinin applied to the epicardium stimulates cardiac sympathetic afferents and evokes a reflex increase in arterial blood pressure. In anesthetized cats we examined the potentiation of these effects by prostaglandin E1 (PGE1) applied to the ventricular epicardium. We recorded cardiac afferent impulses from the second to the fifth left thoracic sympathetic rami. PGE1 (0.1 microgram/ml) alone had little effect on blood pressure, but it significantly increased the pressor response to bradykinin, and it reduced or abolished tachyphylaxis to repeated applications of bradykinin. Both mechanosensitive and chemosensitive sympathetic cardiac afferents were stimulated by bradykinin. Indomethacin (intravenous) caused a small reduction in the afferent response to bradykinin. Epicardial application of PGE1 significantly increased the response (magnitude and duration) of chemosensitive endings to bradykinin but not that of mechanosensitive endings; however, PGE1 abolished the tachyphylaxis of both chemosensitive and mechanosensitive endings to repeated applications of bradykinin. Because both bradykinin and prostaglandins are released in the ischemic myocardium, their interactive effect on cardiac sympathetic afferents could play a part in the sensory and reflex responses to myocardial ischemia.
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PMID:Interaction of bradykinin and prostaglandin E1 on cardiac pressor reflex and sympathetic afferents. 370 68


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