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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although the PGs operate mainly in the renal medulla the demonstration of PG biosynthesis in the renal cortex has provided a biochemical basis for a direct relationship between the PGs and the renin-angiotensin system. The formation of PGs is influenced by circulating levels of A I probably by indirect mechanisms. That the release of renin at least under certain experimental conditions is dependent on the PG system is suggested by the following findings: 1. C20:4 increases PRA in the rabbit and rat. 2. Indomethacin decreases PRA in the rabbit. 3. C20:4 stimulates renin release from slices of rabbit kidney cortex. 4. Reduced renal perfusion pressure and ischemia are accompanied by release of both PGs and renin. 5. The release of PG and renin following renal ischemia is blocked by treatment with indomethacin. The actions of the renin-angiotensin system and the renal PGs are, as far as we know them, antagonistic to each other. PGEs are vasodilator, increase renal blood flow, inhibit adrenergic neurotransmission, and cause excretion of electrolytes and water. Conversely, A II is vasoconstrictor, decreases renal blood flow, stimulates adrenergic neurotransmission, and conserves water and electrolytes. Thus, the interaction between the renal PGs and renin seems to be one in which the two hormonal systems stimulate each other's formation or release, but opposes each other's actions. Further studies are necessary to reconcile this apparent contradiction.
Adv Prostaglandin Thromboxane Res 1976
PMID:Interactions between the renal prostaglandins and the renin--angiotensin system. 79 Sep 16

Thromboxane is known to alter the endothelial cytoskeleton, thereby causing increased endothelial permeability and polymorphonuclear leukocyte (PMN) sequestration in the lungs. We investigated whether iloprost (a stable prostacyclin analog) can decrease thromboxane activity and consequently PMN sequestration because of its anti-platelet aggregation effect. This premise was investigated in a canine isolated gracilis muscle model using 18 animals. Six animals (group I) had the gracilis muscle subjected to 6 hours of complete ischemia followed by 48 hours of reperfusion. Group II (n = 6) received intravenous infusion of iloprost (0.45 micrograms/kg/hr) throughout the experiment (1 hour preischemia, 6 hours of ischemia and 1 hour of reperfusion) and boluses of 0.45 micrograms/kg 10 minutes before ischemia and reperfusion. Group III (n = 6) underwent a similar ischemic interval, but were given iloprost bolus of 0.45 micrograms/kg followed by intravenous infusion of 0.45 micrograms/kg/hr during 48 hours of reperfusion. Gracilis venous samples were obtained at preischemia (PI) and 1 hour of reperfusion (all 3 groups) and at 48 hours of reperfusion (groups I and III) to measure thromboxane (TXB2) levels. Muscle biopsies were taken at the same time to measure myeloperoxidase (MPO) activity, a marker of PMN infiltration. In group I, TXB2 level increased from a pre-ischemic value of 2983 +/- 1083 pg/ml to 9483 +/- 2218 pg/ml at 1 hour of reperfusion (p < 0.05) and then decreased to 2386 +/- 1533 pg/ml at 48 hours of reperfusion (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Does iloprost mediate thromboxane activity and polymorphonuclear leukocyte sequestration in ischemic skeletal muscle? 128 Feb 71

Prostacyclin (PGI2) improves regional contractility of postischemically dysfunctional ("stunned") myocardium. We determined whether defibrotide, a fraction of mammalian DNA known to stimulate endogenous formation of PGI2, also improves contractile recovery of stunned myocardium. Anesthetized, open-chest minipigs were subjected to coronary occlusion of 5 min (left anterior descending branch, LAD) followed by 120 min of reperfusion. The animals were treated with defibrotide (32 mg x kg-1 x h-1, intravenously, i.v.) or vehicle throughout the experimental period. Defibrotide improved regional contractility in the ischemic reperfused area from 30 (vehicle) to 78% of the preischemic control without altering the contractility of nonischemic myocardium. Transcardiac PGI2 formation, determined from the difference between coronary venous and arterial plasma concentrations, was elevated from 437 (preischemic control) to 869 pmol x l-1 in defibrotide-treated animals, but was unchanged in the vehicle-treated and a sham-operated group. Thromboxane A2 (TXA2) release was not modified. Defibrotide reduced ischemia-induced formation of platelet aggregates but did not affect the activity of polymorphonuclear neutrophil granulocytes. The data demonstrate an improvement of contractile recovery from stunning by defibrotide that may be related to an inhibition of ischemia-induced platelet activation and (or) membrane protection owing to enhanced transcardiac formation of PGI2.
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PMID:Stimulation of prostacyclin synthesis by defibrotide: improved contractile recovery from myocardial "stunning". 170 43

Thromboxane (Tx)B2 and 6-keto-prostaglandin (6-keto-PG) F1 alpha formation in the hippocampus and caudate nucleus were evaluated by microdialysis during and following forebrain ischemia. Spontaneously hypertensive rats were subjected to bilateral carotid artery occlusion with simultaneous hypotension for 8, 14, or 20 min. Dialysate was collected during the ischemic interval and during the reperfusion period. TxB2 and 6-keto-PGF1 alpha levels were measured by radioimmunoassay. In both structures, TxB2 production increased significantly during the reperfusion period in all three ischemic groups. By contrast, increased 6-keto-PGF1 alpha elaboration was observed after only the longest ischemic duration. While TxB2 levels gradually decreased during the 3-h reperfusion period in all groups, the levels in the group subjected to 8 min of ischemia returned to control values most rapidly. A relationship between the duration of ischemia and TxB2 production was therefore evident. 6-Keto-PGF1 alpha levels increased in only the group subjected to 20 min of ischemia and, by contrast to the pattern of TxB2 change, 6-keto-PGF1 alpha levels remained elevated throughout the reperfusion period. During reperfusion, the ratio of TxB2 to 6-keto-PGF1 alpha increased substantially versus the preischemic period in both structures. The data demonstrate that eicosanoid elaboration following cerebral ischemia can be evaluated by the microdialysis technique. In addition, they indicate that the thresholds (duration of ischemia) for the postischemic production and the temporal profiles of TxB2 and 6-keto-PGF1 alpha in the caudate and hippocampus differ. They also demonstrate that there is regional heterogeneity in the patterns of eicosanoid elaboration after forebrain ischemia.
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PMID:Eicosanoid production in the caudate nucleus and dorsal hippocampus after forebrain ischemia: a microdialysis study. 172 45

The origin of pre-eclampsia lies in uteroplacental ischemia due to an anomaly of the "vascular insertion" of the placenta. Although the cause of this anomaly remains unknown, it would appear to include both a genetic and an immunological origin possibly favourised by special underlying conditions and certain obstetric circumstances. Prostaglandin imbalance (in particular prostacyclins and Thromboxane A2) appears to be one of the chief factors governing these anomalies. One of the consequences of these mechanisms is the onset of hypertension but other disturbances are essential features. In particular, disseminated intravascular coagulation may occur leading to the release of numerous microthrombi which cause placental (leading to chronic fetal distress), renal, hepatic and cerebral lesions.
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PMID:[Physiopathological elements of pre-eclampsia and the role of the main complementary tests]. 176 67

Ischemia of the lower extremity has been shown to cause pulmonary leukostasis and increased pulmonary artery pressure. Thromboxane (TX) has been implicated as a mediator in this process. The effect of OKY-046, a TX synthetase inhibitor, on polymorphonuclear leukocyte (PMN) production of superoxide anion (O2-) as determined by ferricytochrome reduction was examined. Fourteen dogs were subjected to 6 hours of bilateral gracilis muscle ischemia followed by 1 hour of reperfusion. O2- production from resting PMNs and PMNs stimulated with opsonized zymosan (OZ, 0.1 mg/ml) was measured prior to ischemia or drug treatment (baseline), and following reperfusion in both treated (n = 7) and control groups (n = 7). Serum TX levels were measured using a radioimmunoassay. Following reperfusion, TX levels in the treated group were decreased as compared with the control group (18 +/- 2 pg/ml vs. 72 +/- 26 pg/ml, P less than 0.05). Superoxide production by both resting and stimulated PMNs was also decreased in the treated group; from 0.98 +/- 0.16 nmol to 0.43 +/- 0.12 nmol O2- in the resting state (P less than 0.05) and from 13.3 +/- 1.5 nmol to 9.0 +/- 1.1 nmol O2- after stimulation (P less than 0.005). O2- production was increased in the control group following reperfusion as compared with baseline samples, and this increase was attenuated by treatment with OKY-046. TX synthetase inhibition decreases activation of PMNs following hindlimb ischemia.
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PMID:Thromboxane synthetase inhibition decreases polymorphonuclear leukocyte activation following hindlimb ischemia. 184 27

An examination of the cellular and molecular mechanisms of neuronal cell damage may lead to the design of pharmacologic interventions during presumed or actual fetal asphyxia. Hypoxia-ischemia in its severest form results in insufficient adenosine 5'-triphosphate production. The most important effect of this is failure of adenosine 5'-triphosphate-dependent membrane functions, which maintain ionic homeostasis, that is, ionic pumping. There is K+ efflux and Na+ influx across the cell membrane, depolarization of the cell membrane, opening of the voltage-dependent calcium channels, and entrance of Ca++ into the cell. Cytosolic Ca++ is also increased by Ca++ efflux from the mitochondria and the sarcoplasmic reticulum. Ca++ is a toxin in high cytosolic concentrations; it activates phospholipases A and C, which cause membrane breakdown and release of free fatty acids, including arachidonic acid. The membrane is damaged, lysis occurs, and the neuron dies. High cytosolic Ca++ also causes release of excitatory amino acids (especially glutamate), which overwhelm the suppressant neurotransmitters, causing seizures, increased metabolism, and aggravation of the insufficient adenosine 5'-triphosphate availability. Thromboxane A2 is generated from arachidonic acid, increasing smooth muscle tone and thereby worsening the ischemia. Cyclooxygenase activity also results in formation of oxygen-free radicals that contribute to cell membrane damage, lysis, and death. Possibilities for pharmacologic interventions include (1) calcium channel blockers and antagonists, (2) excitatory neurotransmitter blockers, (3) oxygen-free radical scavengers (e.g., superoxide dismutase), (4) cyclooxygenase or prostaglandin synthesis inhibitors, and (5) seizure suppressants (e.g., phenobarbital). Some of these treatments have been shown experimentally to limit neuronal death in the adult and fetus, and after more investigative work they may be applicable to clinical practice.
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PMID:Mechanisms of asphyxial brain damage, and possible pharmacologic interventions, in the fetus. 190 82

Adenosine diphosphate-induced platelet aggregation and associated thromboxane B2 release were studied in 52 patients with subarachnoid hemorrhage (SAH) in order to detect a possible association between altered platelet function and development of cerebral ischemic complications after SAH. Compared to the values on admission, the patients showed significantly increased platelet aggregability (p less than 0.05) and thromboxane release (p less than 0.001) 1 to 2 weeks after SAH. The highest values of thromboxane release were seen in patients who deteriorated due to delayed cerebral ischemia with a permanent neurological deficit. Thromboxane release was significantly higher (p less than 0.05) before the onset of severe delayed ischemia in six patients with preoperative ischemia compared to the patients without delayed ischemia. In five others, both ischemic deterioration and elevated thromboxane release occurred after operation. These patients had preoperative values similar to the values in those without ischemic symptoms. The observations suggest that increased platelet aggregability and thromboxane release are associated with delayed cerebral ischemia both before and after surgery.
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PMID:Platelet thromboxane release and delayed cerebral ischemia in patients with subarachnoid hemorrhage. 199 3

Thromboxane A2 (TxA2) has been implicated as a potential mediator of myocardial damage during acute ischemia. A potent and specific TxA2 receptor antagonist, SQ-29,548 (2 mg/kg bolus + 2 mg/kg/h) was tested in a cat acute coronary ligation model of myocardial ischemia over a 5-h observation period. Those cats given the TxA2 receptor antagonist had a significant reduction in elevated S-T segment from 0.32 to 0.17 mV (p less than 0.01) in contrast to cats given only vehicle which showed a progressive increase in S-T segment elevation over the 5-h course of the experiment. Furthermore, the rise in plasma creatine kinase (CK) activity during myocardial ischemia was significantly attenuated after SQ-29,548 administration (p less than 0.05). This was confirmed by direct myocardial biopsies which demonstrated a reduction in the loss of myocardial CK and nitrogenous compounds from the ischemic region. Because heart rate (HR), mean arterial blood pressure (MABP), and the pressure rate index (PRI) were unaffected by SQ-29,548 administration, its mechanism of protection probably does not occur through reduction of myocardial oxygen demand. Furthermore, specificity of SQ-29,548 for thromboxane/endoperoxide receptors was demonstrated in the isolated cat coronary arteries. These data suggest that SQ-29,548 reduces the damage associated with myocardial ischemia through direct TxA2 receptor antagonism. The data are also consistent with an important role of TxA2 in the pathophysiology of myocardial ischemia.
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PMID:Cardioprotective actions of specific thromboxane receptor antagonist in acute myocardial ischemia. 243 97

In the hamster cheek pouch, microvascular effects of iloprost at a nonhypotensive dose include vasodilatation at the level of arterioles and venules without changes in microvascular permeability, increased number of perfused capillaries/cm2, prevention of microvascular spasm and capillary ischemia as caused by LTD4, and inhibition of histamine- and 5-HT-induced venular leakage of FITC-dextrane. As regards the effects on basal vessel tone, capillary density, and prevention of LTD4 effects, PGE1 had similar effects as also shown by others in the human cutaneous microcirculation. However, PGE1 did not prevent the microvascular leakage caused by histamine. The Ca2+-antagonist nifedipine, apart from arteriolar vasodilatation, neither increased venular diameter and capillary perfusion nor prevented the effects of LTD4 and histamine. The microvascular actions of iloprost by improvement of tissue perfusion and prevention of mediator-induced tissue edema and vasospasm could contribute to the beneficial effects observed in ischemic diseases.
Adv Prostaglandin Thromboxane Leukot Res 1987
PMID:Microvascular effects of iloprost in the hamster cheek pouch. 244 80


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