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

To what extent endothelial autacoids like endothelium-derived relaxant factor/nitric oxide (EDRF/NO), in addition to neural-humoral factors, are involved in the regulation of myocardial perfusion, is presently not known. Therefore, we investigated in conscious, chronically instrumented dogs the effect of stereospecific inhibitors (NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine (L-NNA), NG-monomethylester-L-arginine (L-NAME] of nitric oxide-synthesis and -release on epicardial coronary tone (and coronary diameter) and myocardial perfusion. A hydraulic coronary cuff was used, to produce reactive hyperemia and to keep the myocardial perfusion constant over short periods. 40 mg/kg L-NNA i.v. caused a long-lasting increase in mean arterial blood pressure from 94 +/- 8 to 129 +/- 11 mmHg and a simultaneous decrease in coronary diameter by 2.8 +/- 0.3%. Heart rate dropped from 87 to 58 min-1, but the double product of heart rate and blood pressure dropped by only 8 +/- 2% (p = 0.05). The maximal coronary conductance during peak reactive hyperemia (after 20 s ischemia) indicating complete coronary dilation was diminished by 48% after L-NNA. The severe drop in resting myocardial perfusion and O2-supply, and nearly unchanged rate pressure product and thus myocardial metabolic rate following the inhibition of nitric oxide formation demonstrate a substantial contribution of EDRF/NO to the regulation of myocardial perfusion.
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PMID:Endothelium-mediated regulation of coronary tone. 195 18

The antitumor agent flavone-8-acetic acid (FAA) is remarkable because it induces hemorrhagic necrosis, altered tumor blood flow, and cytokine synthesis. We show here that FAA and structurally related analogues increase plasma nitrite plus nitrate (NO2-/NO3-) levels in mice. Dose-dependent increases in plasma NO2-/NO3- concentrations, which reached maximum levels at 12 h, were found following administration of FAA. Furthermore, the presence of a palpable s.c. Colon 38 tumor significantly enhanced the response. Tumor-dependent increases were also observed with the active FAA analogues xanthenone-4-acetic acid, 5-methyl XAA, and 5,6-dimethyl XAA, while the inactive analogue 8-methyl XAA failed to increase plasma NO2-/NO3- concentrations substantially above basal levels. Increased plasma NO2-/NO3- levels were also observed in response to endotoxin (100 micrograms/mouse) and to recombinant human tumor necrosis factor alpha (4 to 16 micrograms/mouse). NO2-/NO3- levels may signify nitric oxide production as a result of stimulation of the L-arginine-dependent pathway in activated macrophages. The tumor dependence of the response may reflect the immunological stimulus imposed by tumor implantation. A clear relationship was found between increased plasma NO2-/NO3- levels and tumor growth delays induced by FAA and xanthenone-4-acetic acid analogues. It is suggested that nitric oxide may contribute to tumor cell death by two mechanisms, alteration of blood flow contributing to tumor ischemia and direct tumor cell killing. Plasma NO2-/NO3- concentrations may be a sensitive indication of the antitumor response to this class of compounds.
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PMID:Tumor-dependent increased plasma nitrate concentrations as an indication of the antitumor effect of flavone-8-acetic acid and analogues in mice. 198 9

Experiments were designed to determine whether endothelial injury contributes to augmented coronary vascular tone seen during myocardial reperfusion. Canine left anterior descending coronary arteries were exposed to ischemia followed by reperfusion (60 minutes each). Rings (3-4 mm) of the reperfused artery and of normal left circumflex (control) coronary artery segments were prepared. Rings were suspended for isometric force measurement in organ chambers containing modified Krebs' Ringer bicarbonate solution (37 degrees C, 95% O2-5% CO2). Endothelium-independent contractions to KCl and prostaglandin F2 alpha were unaltered after reperfusion. Endothelium-dependent relaxations to nitric oxide, sodium nitroprusside, and isoproterenol were comparable in control and reperfused arteries. However, reperfused coronary arteries contracted with prostaglandin F2 alpha lost the ability to express endothelium-dependent relaxations to aggregating platelets. Reperfused arterial rings also exhibited impaired endothelium-dependent relaxations to acetylcholine, the calcium ionophore A23187, and the platelet-derived compounds ADP and serotonin. Quiescent (noncontracted) reperfused arterial rings exhibited larger contractions than controls when exposed to aggregating platelets. In such quiescent rings, the endothelium-dependent increase in tension to hemoglobin was unaltered after reperfusion. Thus, coronary reperfusion impairs the normal endothelium-dependent relaxations to aggregating platelets and vasoactive drugs. This impairment of platelet-mediated coronary relaxation could help explain the increased vascular tone and tendency toward vasospasm commonly observed after reperfusion of the coronary arteries.
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PMID:Acute impairment of endothelium-dependent relaxations to aggregating platelets following reperfusion injury in canine coronary arteries. 211 21

The effects of acidified sodium nitrite (NaNO2) which releases nitric oxide, a substance which is thought to be indistinguishable from endothelium-derived relaxing factor, were investigated in a 6-h model of myocardial ischemia (MI) with reperfusion in open-chest, anesthetized cats. Acidified NaNO2 (12.5-50 mmol/kg/hr) was infused i.v., starting 30 min postocclusion followed by reperfusion 1 hr later, in cats subjected to MI by occlusion of the left anterior descending coronary artery. Acidified NaNO2 infusion (25 and 50 mmol/kg/hr) resulted in significantly lower plasma creatine kinase activities at every time beyond 1 hr for the MI + vehicle group, and was not significantly different when compared to sham MI + NaNO2 controls. The areas at risk expressed as percentage of the total left ventricular weights were not significantly different between the MI + vehicle and MI + acidified NaNO2 groups. However, the necrotic area expressed as a percentage of the myocardial area at risk was significantly lower in the 25 and 50 mmol/kg/hr NaNO2-treated cats. Cardiac myeloperoxidase activities indicated that significantly fewer neutrophils were attracted to the ischemic zone of the NaNO2-treated MI cats when compared to the vehicle-infused MI cats. Acidified NaNO2 significantly inhibited platelet aggregation in a dose-dependent manner in cat platelet-rich plasma. Thus, acidified NaNO2 exerts a significant protective action during ischemia and reperfusion injury, which suggests that endothelium-derived relaxing factor has a cardioprotective effect in MI.
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PMID:Cardioprotective effects of acidified sodium nitrite in myocardial ischemia with reperfusion. 215 7

The effects of acidified sodium nitrite (NaNO2), a releaser of nitric oxide (NO), combined with human superoxide dismutase (hSOD), were investigated in a 6-hour model of myocardial ischemia (MI) with reperfusion in open-chest, anesthetized cats. Acidified NaNO2 (12.5 mmol/kg/hr) was infused intravenously in cats starting 0.5 hour after occlusion of the left anterior descending (LAD) coronary artery, which was reperfused 1.5 hour following occlusion. Significantly lower plasma creatine phosphokinase activities were observed at all times beyond 3 hours for MI cats given NaNO2 + hSOD when compared with the other MI groups. The areas-at-risk expressed as percentages of the total left ventricular weights were not significantly different among any of the MI groups. However, the necrotic area expressed as a percentage of the myocardial area-at-risk was significantly lower in the MI + NaNO2 + hSOD-treated cats compared with all other MI groups. The NaNO2-treated group also produced a significant decrease in the necrotic area relative to the area-at-risk. Cardiac myeloperoxidase (MPO) activities indicated no significant difference in number of neutrophils attracted to the ischemic zone in the NaNO2 + hSOD-treated MI cats when compared with the other MI groups. Acidified NaNO2 + hSOD together exert significant protection on the myocardium subjected to ischemia and reperfusion injury. NaNO2 may act synergistically with hSOD to prolong the action of NO by scavenging free radicals that inactivate NO.
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PMID:Synergism between superoxide dismutase and sodium nitrite in cardioprotection following ischemia and reperfusion. 215 21

The endothelial-derived relaxing factor is a vasodilator agent that is formed in the vascular endothelium in response to various stimuli. It has been identified as nitric oxide (NO). Due to its short half-life the endothelial-derived relaxing factor offers certain analytical problems. We present here a method for quantitative analysis of nitrite, the oxidation product of NO, in human plasma. NO binds strongly to hemoglobin. If the resulting NO-hemoglobin (Hb) complex is subjected to a magnetic field and microwave radiation, a characteristic electron paramagnetic resonance spectrum is obtained. This spectrum is highly specific and its amplitude can be used for quantitative determination of NO in the nanomolar range. Columns of bovine Hb covalently bound to agarose were prepared, and an excess amount of dithionite was used to ensure that the Hb was reduced to a ferrous, nonoxygenated state. Samples of human plasma were treated with dithionite to convert nitrite to nitric oxide. They were then passed over the columns, which were subsequently analyzed at 77 degrees K in an electron paramagnetic resonance spectrometer. As an external standard nitrite was used. The amplitude of the spectrum was linear in the range 1-100 nmol. In healthy subjects the venous plasma level of nitrite ranged from 0 to 0.6 microM. Following forearm or leg ischemia the plasma level of nitrite increased substantially. These data are the first to demonstrate circulating levels of an index of the endothelial-derived relaxing factor in human plasma.
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PMID:Detection of endothelial-derived relaxing factor in human plasma in the basal state and following ischemia using electron paramagnetic resonance spectrometry. 216 51

Many of the circulating algesic agents released in response to ischemia produce a profound vasodilatation possibly through the release of an endothelium-derived relaxing factor (EDRF) as well as pain. We report here that intravenously administered S-nitrosocysteine, a putative EDRF, and not the nitric oxide liberating compound sodium nitroprusside produces significant alterations in nociceptive behavior that are abolished by bilateral vagotomy. These results are consistent with a role for EDRF in peripheral nociceptive mechanisms.
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PMID:Is there a role for an endothelium-derived relaxing factor in nociception? 228 34

Experiments were designed and performed to determine whether endothelial function remained chronically impaired after coronary artery reperfusion. Canine left anterior descending coronary arteries were exposed to ischemia (60 minutes) followed by reperfusion (12 weeks). Rings (3-4 mm wide) of the reperfused artery and of normal left circumflex (control) coronary artery segments were suspended in organ chambers containing physiological saline solution (37 degrees C, gassed with 95% O2-5% CO2) for isometric force measurement. Endothelium-independent contractions to KCl or prostaglandin F2 alpha and endothelium-independent relaxations to nitric oxide or isoproterenol were comparable in control and chronically reperfused arteries. However, chronically reperfused coronary arteries exhibited impaired endothelium-dependent relaxations to aggregating platelets. In addition, the reperfused coronary arteries exhibited impaired endothelium-dependent relaxations to the platelet-derived compounds adenosine diphosphate, serotonin, and thrombin. However, the endothelium-dependent relaxations to acetylcholine were comparable between control and reperfused arteries. Thus, after 12 weeks of reperfusion, previously occluded coronary arteries exhibited a selective impairment of endothelium-dependent relaxation evoked by aggregating platelets. In vivo, this phenomenon could favor platelet adhesion, aggregation, and platelet-induced contraction of coronary smooth muscle and thus facilitate ischemic events such as vasospasm and coronary thrombosis.
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PMID:Long-term impairment of endothelium-dependent relaxations to aggregating platelets after reperfusion injury in canine coronary arteries. 234 84

Circulatory disturbances of the tongue are extremely rare because of its rich blood supply. Based on five case reports and a review of the literature we show that lingual circulatory disturbances may be due to impairment of venous drainage resulting in a large acute swelling of the tongue, or to ischemia carrying a painful tongue swelling, and possibly ulceration or partial tongue necrosis. The impairment of venous drainage appears to develop only as a consequence of an extensive posttraumatic or inflammatory edema of the floor of the mouth and tongue base. Ischemic lingual necrosis is most often due to giant cell arteritis and mostly occurs in elderly women. The correct diagnosis should be established as soon as possible because high-dose cortisone therapy both relieves the patient's complaints and prevents life-threatening complications such as myocardial infarction and apoplexy.
HNO 1988 Feb
PMID:[Acute circulatory disorders of the tongue]. 336 Jun 28

In cats the mean arterial blood pressure (MABP) was reduced to 40 or 30 mm Hg by controlled hemorrhage. In 3 animals the cochlea action potentials (CAP) are not changed between 30 and 380 Min by 40 mm Hg MABP. In 4 animals we saw a latent or permanent decrease of CAP between 4 and 115 Min by 30 mm Hg MABP. A singular experiment shows, that a CAP-decrease is caused by injection of an acetylcholin blockade substance. We did not find a correlation to the length of time of the ischemia and a CAP decrease. We found an exact correlation to the hypovolemic sympathetic palsy and a CAP decrease. In reduced blood perfusion the cochlea of cats is more resistant than the brain.
HNO 1984 Apr
PMID:[Cochlear potentials and reduced blood supply]. 672 23


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