Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of prostacyclin (PGI2) on ventricular arrhythmias following 20 min of coronary occlusion and release were studied in 34 conscious dogs. We administered PGI2 at 100 ng/kg/min and did not observe significant changes in heart rate, blood pressure, or systemic vascular resistance. During the control period, heart rate was 97 +/- 30 (mean +/- SEM) vs. 99 +/- 28 in the PGI2-treated group. Mean arterial pressure was 115 +/- 26 mm Hg and 109 +/- 10 mm Hg in the control and PGI2 groups, respectively. Systemic vascular resistance declined minimally from 2,985 +/- 221 dyn . s . cm-5 to 2,484 +/- 135 dyn . s . cm-5 during the PGI2 infusion (p = NS). Following coronary occlusion, the frequency of ventricular fibrillation was reduced from 53% (9/17) in the control group to 6% (1/17) in the PGI2 group (p less than 0.01). Overall 80-min postinfarction survival was 64% in the group receiving PGI2 infusion compared to 24% in the control group (p less than 0.05). The effects of PGI2 in preventing ventricular fibrillation following acute coronary occlusion can be ascribed to a direct action of this prostaglandin on the myocardium, rather than to an indirect effect due to a reduction in systemic vascular resistance.
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PMID:Administration of prostacyclin prevents ventricular fibrillation following coronary occlusion in conscious dogs. 618 7

The hemodynamic and antithrombotic action of ZK 36374, a stable carbacyclin derivative of prostacyclin, was studied during electrically-induced coronary artery thrombosis in the open chest anesthetized pig. Infusion of ZK 36374 (100 ng/kg/min, n = 6) had no effect on heart rate and cardiac output, but caused a 20% reduction in mean arterial blood pressure by peripheral vasodilation. In animals receiving solvent or no drug prior to thrombosis induction, the time to occlusive coronary artery thrombosis (TOT) was 30 +/- 2 minutes (mean +/- SEM, n = 17). Pretreatment with an i.v. infusion of ZK 36374 (100 ng/kg/min) prolonged TOT by 50% to 47 +/- 7 minutes (p less than 0.005, n = 6). This prolongation of TOT was not due to the lower blood pressure in the ZK 36374 group, as dihydralazine in a dose that lowered arterial blood pressure to the same extent had no effect on TOT (32 +/- 4 minutes, n = 4). The results indicate that ZK 36374 may be useful in delaying (or preventing) occlusive coronary artery thrombi.
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PMID:The effect of the stable prostacyclin analogue ZK 36374 on experimental coronary thrombosis in the pig. 620 20

This study was designed to examine the functional properties of myocardium subjected to acute coronary occlusion but surviving the ischemic insult. Ten conscious mongrel dogs underwent mild-circumflex coronary occlusion and were treated for 6 hours with prostacyclin, 540 ng/kg/min, and ibuprofen, 110 micrograms/kg/min, or dipyridamole (7-9.7 micrograms/kg/min). At 7 days, each dog was anesthetized, the chest was opened, and cross-sectional two-dimensional echocardiograms were obtained through the middle of the occluded vascular bed. A computer-aided contouring system was used to assess percent systolic thickening in 16 equally spaced segments around the left ventricle. Metal markers sewn to the epicardium permitted precise regional correlation of histology, percent systolic thickening, and flow, as measured by radioactive microspheres. Necrosis was minimal, averaging only 2.2 +/- 0.8% (+/- SEM) of the left ventricular ring corresponding to the echocardiographic cross section. Percent systolic thickening was 28.6 +/- 4.7 in the nonischemic anterior wall, but was reduced to -4.5 +/- 3.1 in the occluded bed (p less than 0.01). In individual echo segments, percent systolic thickening correlated with local flow (r = 0.69, p less than 0.001), but was still depressed even when flow was normal. In six segments within the occluded bed that had normal histology and flow, percent systolic thickening was 52% less than that in the nonischemic region (p less than 0.02). Thus, coronary artery occlusion combined with drug treatment results in myocardium that, although histologically normal and supplied by normal myocardial blood flow, remains functionally abnormal 7 days after occlusion.
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PMID:Impaired function of salvaged myocardium: two-dimensional echocardiographic quantification of regional wall thickening in the open-chest dog. 633 7

Granulocyte (PMN)-endothelial interactions have been implicated in the primary events of vascular injury and atherogenesis. We now present data which show that endogenous opioid peptides, e.g. enkephalins (ENK), dampen immune-triggered, granulocyte-induced endothelial damage by enhancing prostacyclin production. Concurrent exposure of human umbilical vein endothelial cells (HUEC) to Met5-enkephalin increased arachidonic acid (AA, 20 muM) and thrombin (T, 10 U/ml) induced 6-keto-PGF1 alpha-release to respectively 197.2 +/- 28.1% and 204.1 +/- 17.8% (mean +/- SEM) of base line stimulation (p less than 0.025). The increases noted were significant at ENK-concentrations as low as 10(-12)M. Simultaneous addition of naloxone with ENK completely abolished the enhanced 6-keto-PGF1 alpha-release. Addition of a protease resistant enkephalin analogue significantly (p less than 0.01 over several different concentrations) reduced PMN adherence to HUEC; concomitantly 51Cr-leakage from HUEC that had been exposed to PMN plus activated serum complement was decreased. The even further enhanced 51Cr-leakage that occurs when platelet release products (e.g. serotonin) are included is also decreased by added enkephalin. These data suggest that endogenous neurotransmitters may affect endothelial prostaglandin metabolism, and by so doing provide a protective effect during in vitro, and perhaps in vivo, PMN mediated endothelial injury. This link between neurohumoral and inflammatory systems might enhance our understanding of stress-related phenomena in inflammation and vascular diseases.
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PMID:Enkephalins modify granulocyte-endothelial interactions by stimulating prostacyclin production. 635 55

NZW rabbits with acute serum sickness given Cyclosporin A (CyA) 25 mg/kg/day develop glomerular capillary thrombosis similar to that seem in the haemolytic uraemic syndrome (HUS). Bone marrow recipients treated with CyA may also develop a similar renal lesion associated with a haemolytic uraemic-like syndrome. In the HUS, impaired production of prostacyclin by vascular tissue may be found and has been associated with a lack of a plasma factor which stimulates prostacyclin synthesis. We therefore examined, in six normal rabbits, treated with CyA 25 mg/kg for five days, the ability of plasma from treated and untreated rabbits to stimulate prostacyclin synthesis from normal rabbit aortic rings. Plasma from untreated rabbits produced 21.5 +/- 6.9 ng 6-keto PGF1 alpha/ml/mg wet weight aorta (mean +/- SEM). However, the ability of plasma from CyA-treated rabbits to stimulate prostacyclin production was profoundly reduced. This was apparent within 24 hours of starting and persisted for seven days after therapy was stopped: mean of values from all rabbits bled from start of therapy until seven days after therapy stopped was 3.7 +/- 0.5 ng/ml/mg. We suggest that the renal complications of CyA therapy are related to a failure of normal vascular prostacyclin synthesis due to lack of a prostacyclin-stimulating plasma factor.
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PMID:Effect of Cyclosporin A on prostacyclin synthesis by vascular tissue. 636 59

Prostacyclin has been implicated as a mediator of renin release, whereas angiotensin II evokes prostaglandin I2 (PGI2) release from both vascular and nonvascular tissues in vitro. The physiological significance of these observations was assessed by measurement of an index of endogenous prostacyclin biosynthesis in human volunteers during varied activation of the renin-angiotensin system secondary to manipulation of dietary sodium. Excretion of the major urinary metabolite of prostacyclin in man, 2,3-dinor-6-keto-PGF1 alpha (PGI-M), fell from 295 +/- 51 to 176 +/- 35 (+/- SEM) ng g creatinine-1 (P less than 0.01) in 10 normal subjects when sodium intake was decreased from 150 to 10 meq/day. In five patients with primary hyperaldosteronism, PGI-M fell from 199 +/- 34 ng g creatinine-1 preoperatively to 120 +/- 26 pg/mg creatinine-1 after removal of the adenoma. In such patients, the reduction in PGI-M was associated with a significant increase in PRA. Thus, in both normal subjects and patients with hyperaldosteronism, PGI-M excretion fell rather than increased with activation of the renin-angiotensin system. This suggests that systemic biosynthesis of PGI2 is unrelated to renin release and that angiotensin II is unlikely to stimulate endogenous prostacyclin biosynthesis under these conditions in man.
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PMID:Endogenous prostacyclin synthesis is decreased during activation of the renin-angiotensin system in man. 636 36

Patients undergoing abdominal aortic aneurysmectomy (AAA) develop depressed cardiac function during aortic clamping. The importance of volume status and thromboxane (Tx) mediated declines in cardiac contractility in determining this event was studied. In a blinded fashion, patients received the cyclo-oxygenase inhibitor ibuprofen 12 mg/kg by mouth (n = 11) or a placebo (n = 15), 1.5 hours prior to surgery. In the placebo group levels of 6-keto-PGF1 alpha, the hydrolysis product of prostacyclin (PGI2) rose from 20 +/- 10 to 1170 +/- 80 pg/ml (p less than 0.05) soon after incision. Concentrations of TxB2, the stable hydrolysis product of TxA2, were unchanged until 30 minutes after the aorta was clamped when arterial TxB2 concentrations rose from 90 +/- 20 to 230 +/- 30 pg/ml (mean +/- SEM) (p less than 0.05). A pulmonary source for PGI2 and TxA2 was indicated by the observation that arterial 6-keto-PGF1 alpha and TxB2 levels exceeded those in pulmonary arterial blood by 180 +/- 50 and 110 +/- 30 pg/ml, respectively (p less than 0.05). Levels of TxB2 in circulating platelets remained unchanged from baseline in the placebo group. During aortic clamping, cardiac index (CI) fell 0.7 +/- 0.2 1/min X m2 (p less than 0.05) in placebo treated patients, and there was a 6% decline in plasma contractility as bioassayed with a rat papillary muscle (p less than 0.05). Placebo patients entered surgery with a PAWP greater than or equal to 10 mmHg (mean 13 mm). Ibuprofen suppressed production of TxB2, such that 30 minutes after aortic clamping TxB2 was 70 +/- 30 pg/ml, a value lower than control patients (p less than 0.05). Further, plasma no longer depressed contractility of the papillary muscle. Five patients given ibuprofen had an initial pulmonary arterial wedge pressure (PAWP) of 10 mmHg or greater (mean 12 mmHg). During aortic clamping there was an insignificant decrease in CI of 0.2 +/- 0.1 1/min X m2. This was in contrast to the CI decrease in six other ibuprofen treated patients of 0.9 +/- 0.2 1/min X m2 whose PAWP at the start of surgery was less than 10 mmHg (mean 6 mmHg) (p less than 0.05), and to placebo patients whose initial PAWP was greater than or equal to 10 (p less than 0.05). Platelet counts fell from 185,000 to 121,000/mm3 in placebo patients (p less than 0.05), but did not fall when ibuprofen was given. Creatinine concentrations were unaffected by ibuprofen. Blood replacement in placebo and ibuprofen patients was similar, 1.90 +/- 0.20 and 0.65 +/- 0.15 1, respectively. Results indicate that CI will not decrease during AAA if sufficient volume is given before surgery to increase PAWP above 10 mmHg, and secondly, if TxB2 synthesis is inhibited.
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PMID:Determinants of cardiovascular stability during abdominal aortic aneurysmectomy (AAA). 636 2

Much evidence has implied a deficient production of the antiaggregatory and vasodilator agent prostacyclin (PGI2) in preeclampsia and some other chronic fetoplacental insufficiency syndromes. So that we could study whether this might be due to the possible effects of the mode of delivery and maternal epidural or general anesthesia, specimens of the umbilical arteries of infants born after normal (n = 46) or complicated (n = 25) pregnancies were superfused in vitro and their production of PGI2 was determined by measuring 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha, the hydrolysis product of PGI2) by radioimmunoassay. The amounts of umbilical 6-keto-PGF1 alpha released in normal pregnancies after induced vaginal delivery (20.9 +/- 2.4 ng/gm/min dry weight of tissue, mean +/- SEM) and elective cesarean section (21.8 +/- 2.2 ng/gm/min) were smaller (p less than 0.025) than the amounts released after spontaneous onset of labor (35.0 +/- 6.2 ng/gm/min). Epidural or general anesthesia had no effect on this production. When the types of deliveries were matched, the production of 6-keto-PGF1 alpha was even less (p less than 0.05) in cases of preeclampsia (14.2 +/- 3.7 ng/gm/min; n = 9) than in the control subjects (21.3 +/- 1.6 ng/gm/min) and in cases of essential hypertension (21.6 +/- 5.2 ng/gm/min). Our data suggest that umbilical PGI2 deficiency is a specific feature of preeclampsia.
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PMID:Evidence that prostacyclin deficiency is a specific feature in preeclampsia. 636 77

Prostacyclin (PGI2) has been used clinically in the treatment of ischemic peripheral vascular disease. While intravenous infusions have been reported to be beneficial, the preferred route of administration (intravenous or intraarterial) and the influence of PGI2 on distribution of femoral blood flow have yet to be established. Bilateral femoral arterial blood flow was measured electromagnetically in 10 anesthetized adult mongrel dogs. The distribution of femoral arterial blood flow (FAQ) to skin, muscle, bone, and arteriovenous anastomoses (AVA) was determined by using femoral intraarterial injections of radioactively labeled microspheres before, during, and 30 min after 20-min intravenous (n = 5) and intraarterial (n = 5) infusions of PGI2 at 0.1 microgram kg-1 min-1. Control FAQ was 76 +/- 15 (mean +/- SEM) ml/min and its distribution to skin, muscle, bone, and AVA was 13 +/- 3%, 43 +/- 8%, 17 +/- 4%, and 26 +/- 7%, respectively. Arterial pressure was 127 +/- 7 mm Hg. Intraarterial infusions of PGI2 significantly (P less than 0.05) increased FAQ to 240 +/- 43 ml/min which was sustained throughout the infusion. Distribution of FAQ to skin increased significantly (P less than 0.05) to 47 +/- 8%, while that to the muscle of the thigh decreased to 17 +/- 4% (P less than 0.05). During intravenous infusion of PGI2 at the same concentration, FAQ did not change significantly and its distribution remained unchanged; however, there was a significant (P less than 0.05) reduction in arterial pressure to 78 +/- 6 mm Hg. No significant changes occurred in cardiac output, pulmonary arterial pressure, arterial blood gases, paw or core body temperatures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Influence of prostacyclin on distribution of canine femoral blood flow. 636 81

The production of vasodilatory, antiaggregatory prostacyclin (PGI2) and vasoconstrictory, proaggregatory thromboxane A2 (TxA2) by the placenta was studied in the cases of hypertensive pregnancy complications by superfusing pieces from maternal and fetal sides of placentae of 9 pre-eclamptic, 6 hypertensive and 11 healthy women in vitro and measuring the release of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and thromboxane B2 (TxB2), the breakdown products of PGI2 and TxA2 respectively, from the superfusate. Both sides of the placentae from the controls produced 6-keto-PGF1 alpha (maternal side 0.5 +/- 0.1 ng/g/min dry weight of tissue, mean +/- SEM; fetal side 0.7 +/- 0.2 ng/g/min) and TxB2 (maternal side 2.5 +/- 0.4 ng/g/min; fetal side 2.7 +/- 0.5 ng/g/min) with no correlation between the two. The 6-keto-PGF1 alpha production was normal in hypertensive complications whereas the TxB2 production was increased on the fetal side of the placentae obtained from the pre-eclamptic (3.7 +/- 0.3 ng/g/min: p less than 0.05) and hypertensive women (4.1 +/- 0.4 ng/g/min; p less than 0.025). This may explain the occurrence of microthrombi and infarctions in placentae of hypertensive women.
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PMID:Increased thromboxane A2 production but normal prostacyclin by the placenta in hypertensive pregnancies. 636 1


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