Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Local chemical factors, such as H+, K+, Ca2+, adenosine, and osmolarity, affect cerebral resistance vessels. Their participation in the regulation of cerebral blood flow is suggested by changes in their concentration in the interstitial space during increased neuronal activity, strong hypoxia, and transient of incomplete ischemia. Such changes are not observed during autoregulation. Possible interactions between several factors must be considered when estimating their role. Autonomic nerves innervating cerebral vessels include: sympathetic nerves releasing the constrictor transmitter noradrenaline; parasympathetic nerves (liberating the dilator transmitter acetylcholine) and other dilator fibers (containing either serotonin, substance P, or vasoactive intestinal polypeptide). Participation of these systems in the adjustment of cerebral blood flow is still a matter of discussion, except for the protective effect of sympathetic nerves on the upper limit of autoregulation and on the blood--brain barrier. Humoral compounds, generated and released within the brain, which can affect cerebral blood flow include: histamine, bradykinin, and prostaglandins. Histamine, bradykinin, prostaglandin E2, and prostacyclin dilate cerebral arteries in situ, while prostaglandin F2 alpha reduces cerebral blood flow. Histamine and bradykinin alter the permeability of the blood--brain barrier and might be involved in pathological events, such as edema.
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PMID:Local chemical, neural, and humoral regulation of cerebrovascular resistance vessels. 240 98

The effects of a stable prostacyclin mimetic, iloprost (30 nmol/l), and of indomethacin (3 mumol/l) on ischemia-plus-reperfusion-induced changes in myocardial hemodynamics and sympathetic nerve function were examined in Langendorff-perfused rabbit heart isolated except for the postganglionic sympathetic cardiac nerves. Noradrenaline overflow was measured during an initial 1-min period of nerve stimulation (S1), compared with an identical stimulation (S2) made after 2 h of low-flow ischemia followed by a 30-min reperfusion period. Myocardial catecholamine content of left ventricular tissue was also measured. Pretreatment with iloprost, indomethacin, or vehicle began 10 min before ischemia. Global ischemia plus reperfusion reduced myocardial catecholamine content by 19% (vehicle), and the reduction was greater in indomethacin-pretreated hearts (37%, p less than 0.05), whereas iloprost increased tissue noradrenaline 18% above vehicle control (p less than 0.05). Initially, nerve stimulation-induced noradrenaline overflow ranged from 213 to 247 pmoles, and was significantly reduced after ischemia and reperfusion, the difference (S1-S2) being 198 pmoles (vehicle) and 117 pmoles (indomethacin), but only 44 pmoles after iloprost pretreatment (all groups p less than 0.01). In addition, iloprost improved the recovery of active systolic pressure development, coronary perfusion and left ventricular compliance on reperfusion, whereas a tendency toward further deterioration was observed in indomethacin-pretreated hearts. The results suggest that iloprost may protect both myocardial muscle and nerve cells from ischemia-plus-reperfusion injury. Preservation of myocardial catecholamine levels and sympathetic nerve responsiveness may contribute to improved recovery of reperfused ischemic myocardium.
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PMID:Prostaglandins and myocardial noradrenaline overflow after sympathetic nerve stimulation during ischemia and reperfusion. 241 Jul 36

The effects of iloprost (ZK 36 374) on myocardial ischemia and infarction were studied in three groups of four anesthetized and heparinized pigs. Coronary microembolization was evoked by the injection of microspheres (50 microM) into the left coronary artery. A dose of 12 million beads/kg was followed by ventricular fibrillation and death after 11 +/- 5 min (group A). In group B, ischemia was evident at 15 min after the injection of 6 million beads/kg from an ST segment elevation in the precordial electrocardiogram (2.9 +/- 1.1 mV; p less than 0.05) and from an arterial-coronary venous difference in inosine concentration of -8.5 +/- 0.3 microM (p less than 0.05). However, in the presence of iloprost--an infusion of 0.18 micrograms/kg/min started 30 min before embolization--no ST segment elevation (0.45 +/- 0.23 mV; NS) or inosine release (-1.5 +/- 1.0 microM) was detected after the injection of 12 million beads/kg (group C). After 7 days, the animals from group B had more frequent spontaneous ventricular arrhythmias than those from group C. Programmed electrical stimulation induced intraventricular reentry in some animals of both groups (3 of 4 in B and 2 of 4 in C). Ventricular tachycardia was induced in two animals from group B. Postmortem examination revealed small myocardial infarcts in all group B animals; however, in group C no infarcts were detected. These data corroborate the view that prostacyclin-mimetic compounds are beneficial in the acute and in the chronic phases of myocardial infarction.
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PMID:Sustained protection by iloprost of the porcine heart in the acute and chronic phases of myocardial infarction. 241 2

The possible antifibrillatory effect of cicletanide, a new diuretic antihypertensive drug, was investigated at random in 50 anesthetized dogs subjected to left circumflex coronary artery ligation for 60 min and later reperfused. In this model, standard electrocardiographic leads 2 and 3 were continuously registered to measure delta R wave percent changes, to count the number of ventricular premature beats, and to document the onset of ventricular fibrillation; aortic pressure was recorded; 6-keto PGF1 alpha and TXB2 plasma levels were determined. Cicletanide significantly reduced early (Phase 1a) postischemic ventricular fibrillation (5 of 25 vs. 12 of 25, p = 0.036) but failed to reduce the incidence of global ischemia-induced ventricular fibrillation. On the other hand, the incidence of postreperfusion ventricular fibrillation was lower in the cicletanide group (1 of 14 vs. 5 of 9, p = 0.04). In addition, the total survival rate was improved in cicletanide treated dogs (p = 0.0257). While the rate-pressure product was lowered by the drug independent of the presence of ischemia, delta R% changes after occlusion were less in treated dogs than in controls. Moreover, the drug reduced significantly the number of ventricular premature beats in the early (Phase 1a) postischemic period. Finally, the drug increased (mean two-fold) the plasma levels of 6-keto PGF1 alpha as compared with controls; however, this increase was less than that achieved (mean 20-fold) after 100 ng/kg/min epoprostenol (prostacyclin) given in a further series of animals. Thus, improved outcome follows 10 mg/kg i.v. cicletanide administration in this model.
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PMID:Cicletanide improves outcome after left circumflex coronary artery occlusion-reperfusion in the dog. 241 86

Protective effects of prostacyclin (PGI2) and Iloprost in experimental cardiac ischemia are reported by several authors. However, the effects of continuous administration on the final outcome of myocardial infarction are not yet known. We investigated the effects of Iloprost on cardiac unperfused area (UA) and necrotic zone (NZ) as assessed by Evans blue perfusion and extraction and nitrobluetetrazolium staining, respectively, using osmotic minipumps for continuous intravenous drug administration. Starting 3-4 hours after left descending coronary artery-ligation (LAD-L) Iloprost was infused at doses of 0.1 microgram and 0.5 microgram X kg-1 X min-1. While the lower dose is below pharmacological effect level, the higher dose in rats slightly lowered blood pressure and effectively inhibited platelet aggregation. LAD-L in control rats resulted in UA and NZ extending to 34.2 and 16.9%, respectively, of total ventricular mass (VM) after 24 hours and 28.3 and 21.3% of VM, respectively, after 7 days. At the dose of 0.1 micrograms X kg-1 X min-1 Iloprost was ineffective in reducing UA 24 hours after LAD-L. However, at 0.5 microgram X kg-1 X min-1 Iloprost with UA and NZ of 16.3 and 8.4% of VM, respectively, after 24 hours and 8.5 and 5.2% of VM, respectively, after 7 days reduced the extension of myocardial infarction by approximately 50% after 24 hours and 70% after 7 days, as compared to controls. As assessed in unperfused ventricular tissue after LAD-L and normal myocardium of sham-operated rats following 24 hours of Iloprost infusion, myocardial tissue concentrations of Iloprost amount to approximately half of the plasma levels irrespective of LAD-L.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Limitation of myocardial unperfused area and necrotic zone 24 hours and 7 days after coronary artery ligation in rats by the stable prostacyclin analogue iloprost. 242 67

The potential therapeutic value of the chemically stable carbacyclin analogue iloprost on the course of postischemic acute renal failure was studied in six conscious chronically instrumented dogs and compared with five controls. Immediately after temporary ischemia (180-min cessation of blood flow by inflation of a pneumatic cuff), the investigational group PC received a continuous intraaortal infusion of iloprost (50 ng X min-1 X kg-1) over a period of seven days, whereas the control group C received 0.9% saline. The glomerular filtration rate [( 51Cr]EDTA clearance, endogenous creatinine clearance) was less decreased in the prostacyclin analogue group than in the control group [3rd day, 18 +/- 2.5 vs. 12 +/- 1 ml X min-1 (p less than 0.05); 7th day, 23 +/- 3 vs. 12 +/- 2 ml X min-1 (p less than 0.05)]. On day 1, renal blood flow (electromagnetic flow probe) was markedly lower in the control group (129 +/- 29 ml X min-1) than in the PC group (212 +/- 29 ml X min-1; p less than 0.05), even exceeding baseline levels in the latter group. Accordingly, the excessive rise in renal vascular resistance in the control group (+136%) was abolished in the PC group (-32%; p less than 0.01). Nitrogen retention was also markedly improved. Osmolar clearance was markedly lower in the control group (0.58 +/- 0.2 ml X min-1) than in the PC group (1.41 +/- 0.17 ml X min-1; p less than 0.05). It is suggested that the beneficial effect of iloprost is mediated by preservation of renal perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Amelioration of postischemic acute renal failure by prostacyclin analogue (iloprost): long-term studies with chronically instrumented conscious dogs. 242 19

This study reports coronary and systemic hemodynamics, and metabolic responses to atrial pacing, prostacyclin (PGI2), and iloprost, its stable analogue, in 16 patients with severe coronary obstruction as well as predominant narrowing in the left anterior descending artery. PGI2 caused ischemia in six patients with low anginal threshold during pacing. In three of them ischemia was also precipitated by iloprost. Drugs were infused at therapeutic doses and were discontinued when pain occurred. Angina disappeared promptly (less than or equal to 3 minutes) and spontaneously after the infusion of PGI2, whereas after the analogue it was long lasting (greater than or equal to 5 minutes) and was relieved by 125 mg intravenous aminophylline, an antagonist of dipyridamole-induced coronary dilation. Ischemia was associated with a drug-induced decrease in arterial blood pressure and reflex tachycardia, and occurred despite increased great cardiac vein (GCV) blood flow and decreased resistance, which is consistent with either a failure of regional flow to increase proportionally to the metabolic demand or a subendocardial-subepicardial steal. However, the following findings favor the latter hypothesis: heart rate and rate-pressure product at the onset of pain were lower with drugs than with pacing, and GCV blood flow, measured at a comparable heart rate, was less with pacing than with drugs. In conclusion, PGI2 and analogues may induce ischemia in patients with advanced coronary artery disease. The mechanism appears to be related to a dipyridamole-like maldistribution of flow. Counteraction of ischemia can be achieved by aminophylline.
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PMID:Myocardial ischemia during intravenous prostacyclin administration: hemodynamic findings and precautionary measures. 243 21

Reperfusion of ischemic myocardium is recognized as potentially beneficial because mortality is directly related to infarct size, and the latter is related to the severity and duration of ischemia. However, reperfusion is associated with extension of the injury that is additive to that produced by ischemia alone. The phenomenon of reperfusion injury is caused in large part by oxygen-derived free radicals from both extracellular and intracellular sources. The loci of oxygen-free radical formation include: myocardial sources (mitochondria), vascular endothelial sources (xanthine oxidase and other oxidases), or the inflammatory cellular infiltrate (neutrophils). Experimental studies have shown that free radical scavengers and agents that prevent free radical production can reduce myocardial infarct size in dogs subjected to temporary regional ischemia followed by reperfusion. Superoxide dismutase and catalase, which catalyze the breakdown of superoxide anion and hydrogen peroxide, respectively, limit experimental myocardial infarct size. The free radical scavenging agent N-(2-mercaptopropionyl)glycine (MPG) is reported to be effective in limiting infarct size. The ischemic-reperfused myocardium derives significant protection when experimental animals are pretreated with the xanthine oxidase inhibitor allopurinol. Neutrophils also serve as a significant source of oxygen-derived free radicals at the site of tissue injury. A number of agents have been shown to directly inhibit neutrophil-derived oxygen free radical formation and neutrophil accumulation within the reperfused myocardium. These agents include ibuprofen, nafazatrom, BW755C, prostacyclin, and iloprost. Thus, free radical scavengers and agents that prevent free radical formation can provide significant protection to the ischemic-reperfused myocardium.
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PMID:Free radical scavengers in myocardial ischemia. 243 51

The recovery of coronary flow and cardiac work was studied in isolated guinea pig hearts (working-heart preparation) after successive bolus injections of leukotriene D4 (LTD4) at increasing doses (0.01-1,000 ng). LTD4 caused an immediate (within 1 min) reduction in coronary flow and cardiac work and an increase in myocardial NADH fluorescence. There was limited spontaneous recovery at any dose and at the end of the cumulative LTD4 study, coronary flow recovered only from 41.4 +/- (SE) 3.5 (n = 10) to 53.5 +/- 4.7% of initial values, and cardiac work recovered from 21.2 +/- 4.1 to 33.1 +/- 5.6% (P less than 0.05). Adenosine (1 X 10(-6) M) or iloprost (1 X 10(-7) M) restored coronary flow but not cardiac work after LTD4 injections, in contrast to full recovery of cardiac work observed in hearts subjected to a similar degree of ischemia induced by reducing the coronary flow by a peristaltic pump, or hypoxia caused by reducing PO2 of the perfusion fluid. Adenosine (1 X 10(-6) M) and forskolin (1 X 10(-6) M) in combination, or iloprost (1 X 10(-7) M) and isoproterenol (1 X 10(-8) M) in combination, restored both coronary flow and cardiac work to control levels. Myocardial NADH levels, which increased immediately after LTD4 injections, returned to normal after perfusion with adenosine or iloprost. The data suggest that LTD4 has a prolonged vasoconstrictive effect on the heart. Reversal of this effect by compounds that stimulate adenylate cyclase of the vascular tissue (adenosine, prostacyclin) revealed a direct suppressive effect on the myocardium independent of the vascular effect and myocardial ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inducers of adenylate cyclase reverse the effect of leukotriene D4 in isolated working guinea pig heart. 243 50

The prostacyclin analogue iloprost (ZK 36374) inhibits neutrophil activation in vitro, reduces neutrophil accumulation in inflammatory skin lesions, and reduces ultimate infarct size in an anesthetized open-chest canine model of regional ischemia and reperfusion. Iloprost (0.1-100 microM) inhibited the in vitro production of superoxide anion by canine neutrophils in a concentration-dependent manner. Iloprost (100 ng/kg/min i.v.) inhibited C5a-induced neutrophil migration into inflammatory skin lesions as assessed by the neutrophil-specific enzyme marker, myeloperoxidase. The myeloperoxidase activity determined 2 hours after the intradermal administration of C5a in each of the groups was control 13.3 +/- 1.8 units/g tissue (n = 12) and iloprost 6.5 +/- 0.9 units/g (n = 12), p less than 0.01. Iloprost was administered to anesthetized open-chest dogs (100 ng/kg/min) 10 minutes after left circumflex coronary artery (LCCA) occlusion and continued during the 90-minute occlusion period and the first 2 hours of reperfusion. Regional myocardial blood flow was similar between treatment groups at baseline, 5 minutes and 80 minutes after LCCA occlusion, and after 1 hour of reperfusion. Infarct size, assessed 6 hours after reperfusion, was reduced by iloprost treatment: 22.4 +/- 3.1% of the area at risk (n = 15) compared with 42.4 +/- 3.3% of control (n = 13), p less than 0.01. Iloprost treatment reduced the accumulation of neutrophils (measured by myeloperoxidase activity) in the ischemic myocardium at the interface between infarcted and noninfarcted tissue: control (n = 9) 9.0 +/- 1.8 units/g tissue, iloprost (n = 6) 2.0 +/- 0.4 units/g, p less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Iloprost inhibits neutrophil function in vitro and in vivo and limits experimental infarct size in canine heart. 243 29


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