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

Mechanisms responsible for atrioventricular (AV) block during acute inferior myocardial infarction are only partially understood. Increased parasympathetic tone is the factor usually postulated; however, persistence of AV block after atropine administration is frequently observed. Adenosine, an endogenous ischemic metabolite, has well established depressant effects on AV node conduction. In this report, an episode of atropine-resistant AV block was reversed by aminophylline, a competitive adenosine antagonist, in a patient with an acute inferior myocardial infarction. This observation suggests a role for adenosine in the mediation of ischemia-induced AV node block.
 ...
PMID:Mechanism of atropine-resistant atrioventricular block during inferior myocardial infarction: possible role of adenosine. 376 Mar 93

An activation of cardiac sympathetic nerves increases coronary vascular resistance distal to severe stenoses and induces ischemia of the dependent myocardium. The selective alpha 2-adrenoceptor antagonist rauwolscine and the calcium antagonist nifedipine prevent both poststenotic vasoconstriction and ischemia. To exclude the possibility that the beneficial action of nifedipine is based on unspecific coronary dilation rather than a functional antagonism against alpha 2-adrenoceptor mediated poststenotic vasoconstriction we now tested coronary dilatory drugs with a different underlying mechanism. The left ventrolateral cervical cardiac sympathetic nerve was stimulated in 12 anesthetized, vagotomized dogs. A severe stenosis of left circumflex coronary artery was defined by the absence of a postocclusive reactive hyperemia. Sympathetic stimulation increased end-diastolic poststenotic resistance from 0.45 +/- 0.10 to 0.83 +/- 0.18 mmHg X min X 100 g/ml and induced a net lactate production of the poststenotic myocardium. Adenosine (50 micrograms/kg X min i.c., n = 5), dipyridamole (0.2 mg/kg i.v., n = 3) and isosorbide-dinitrate (1 mg i.c., n = 4) did not prevent the increase in resistance and the net lactate production. Thus the effectiveness to prevent alpha 2-adrenergic poststenotic coronary constriction appears to be specific for alpha 2-antagonists and calcium antagonists.
 ...
PMID:Adenosine, dipyridamole and isosorbide dinitrate are ineffective to prevent the sympathetic initiation of poststenotic myocardial ischemia. 376 70

Adenosine as well as hypoxia and ischemia are known to cause atrioventricular conduction block. To test the hypothesis that adenosine is the primary mediator of hypoxia-induced atrioventricular conduction delay in isolated perfused guinea pig hearts, we characterized a) the time courses of hypoxia-induced adenosine release and delay in atrioventricular conduction, b) the relationships between oxygen tension, adenosine concentration in the effluent, and atria-to-His-bundle interval, and c) the adenosine receptor mediating the negative dromotropic effect of hypoxia. Oxygen tension and effluent adenosine levels were linearly related with a correlation coefficient (r) of -0.85 and a slope of -6.3 +/- 0.37 pmol/min/g/torr. Likewise, oxygen tension and atria-to-His-bundle interval prolongation were linearly related with r = -0.85 and a slope of -0.180 +/- 0.013 msec/torr. The EC50 of effluent adenosine in causing atria-to-His-bundle prolongation was 0.26 +/- 0.02 microM. Adenosine deaminase, an enzyme that deaminates adenosine to inosine and is limited to the extracellular space, significantly attenuated (61%) the atria-to-His-bundle interval prolongation caused by hypoxia. This prolongation was further reduced (81%) by a combination of adenosine deaminase and theophylline, an adenosine receptor blocker. Adenosine deaminase also reduced (by 95%) the atria-to-His-bundle interval prolongation in normoxic recipient hearts caused by the effluent of hypoxic donor hearts. Several adenosine antagonists, i.e., theophylline, 8-phenyltheophylline, and 8-(p-sulfophenyl)theophylline antagonized in a dose-dependent manner the negative dromotropic effect of exogenous adenosine and hypoxia. Schild analysis of the antagonism of hypoxia-induced atria-to-His-bundle interval prolongation by 8-(p-sulfophenyl)theophylline yielded the following pA2 values: 5.30 +/- 0.25 and 5.28 +/- 0.31 using oxygen tension and effluent adenosine vs. AH interval prolongation, respectively. 8-(p-Sulfophenyl)theophylline also antagonized to an equal extent atria-to-His-bundle interval prolongations of similar magnitude caused either by adenosine or hypoxia. We conclude that 1) adenosine is the primary mediator of hypoxia-induced atrioventricular conduction delay, and 2) the adenosine receptor that mediates the negative dromotropic effect of hypoxia is similar to that of exogenous adenosine.
 ...
PMID:Effect of adenosine on atrioventricular conduction. II: Modulation of atrioventricular node transmission by adenosine in hypoxic isolated guinea pig hearts. 379 84

The present investigation was undertaken to study cardiac release of adenosine and prostacyclin (prostaglandin [PG] I2) in patients with ischemic heart disease (IHD), and to assess coronary vascular resistance before and after inhibition of synthesis in such patients. In 48 patients with IHD, arterial and coronary sinus blood samples were taken at rest, during atrial pacing to angina, and after pacing. Levels of purines were determined by high-performance liquid chromatography and the PGI2 metabolite 6-keto-PGF1 alpha was measured with radioimmunoassay. Coronary sinus blood flow was determined with retrograde continuous thermodilution before and after oral administration of indomethacin, aspirin, naproxen, or ibuprofen. Atrial pacing induced myocardial ischemia, as evidenced by typical chest pain and arrested lactate extraction. Adenosine was extracted at rest, but during ischemia there was a significant release of its metabolite hypoxanthine, indicating increased myocardial breakdown of high-energy adenine nucleotides. Arterial and coronary sinus concentrations of 6-keto-PGF1 alpha were low and no significant differences between them were found. After administration of the PG-synthesis inhibitor indomethacin, coronary vascular resistance was elevated, as was the cardiac oxygen extraction. The three other PG-synthesis inhibitors (aspirin, naproxen, and ibuprofen) did not, however, induce any change in coronary vascular resistance or in the cardiac extraction of oxygen. On the basis of these data we suggest that in patients with IHD cardiac ischemia results in increased myocardial production and release of purines, cardiac ischemia does not elicit any detectable increase in coronary production of prostacyclin, and the increased coronary resistance induced by indomethacin does not reflect the involvement of locally formed PG in the maintenance of coronary flow, but is rather a direct effect of the drug.
 ...
PMID:Coronary flow regulation in patients with ischemic heart disease: release of purines and prostacyclin and the effect of inhibitors of prostaglandin formation. 388 37

To investigate transmural variations in coronary flow reserve, we studied 20 anesthetized dogs with a Gregg cannula in the left main coronary artery. In 11 dogs, radionuclide-labeled microspheres were injected over a range of perfusion pressures in the control state and during maximal coronary vasodilation produced with chromonar or adenosine. In another nine dogs, control, reactive hyperemic, and adenosine-vasodilated flows were compared at the same perfusion pressures. Adenosine dilated vessels more than did reactive hyperemia, which in turn vasodilated more than did hypoperfusion. Adenosine or chromonar vasodilated more than did hypoperfusion alone in all layers of the heart at perfusion pressures as low as 30 mmHg (P less than 0.05). This effect was greatest in the subepicardium and least in the subendocardium and varied with perfusion pressure (P less than 0.05). Subendocardial-to-subepicardial flow ratios declined with diminishing perfusion pressure despite the fact that flow reserve was present in all layers. We conclude that exhaustion of flow reserve is not the mechanism by which subendocardial ischemia occurs.
 ...
PMID:Transmural coronary flow reserve patterns in dogs. 394 28

Adenosine is a prime candidate for the role of mediator between myocardial metabolic state and coronary blood flow. However, there are few reports concerning the direct effects of exogenously added adenosine on coronary autoregulation. The present investigation in the open-chest dog studied the effects of a threshold dose of intracoronary adenosine infusion on reactive hyperemia following brief coronary occlusions. The infused dose did not increase nonocclusive flow by greater than 10%. Adenosine enhanced total hyperemic flow at all occlusions tested (5, 10, 15, 20, and 30 s). Aminophylline pretreatment reduced reactive hyperemia below the control level even in the presence of an intracoronary infusion of adenosine. Adenosine injected into the left atrium and intracoronarily infused papaverine did not affect hyperemic response to 5- and 15-s coronary occlusions. The results suggest that a minimum dose of exogenously added adenosine enhances myocardial reactive hyperemia, possibly by potentiating the effects of endogenous adenosine released during ischemia.
 ...
PMID:Intracoronary adenosine enhances myocardial reactive hyperemia after brief coronary occlusion. 400 61

This study was designed to determine whether human hearts release adenosine, a possible regulator of coronary flow, during temporary myocardial ischemia and, if so, to examine the mechanisms involved. Release of adenosine from canine hearts had been reported during reactive hyperemia following brief coronary occlusion, and we initially confirmed this observation in six dogs hearts. Angina was then produced in 15 patients with anginal syndrome and severe coronary atherosclerosis by rapid atrial pacing during diagnostic studies. In 13 of these patients, adenosine appeared in coronary sinus blood, at a mean level of 40 nmol/100 ml blood (SE = +/-9). In 11 of these 13, adenosine was not detectable in control or recovery samples; when measured, there was concomitant production of lactate and minimal leakage of K(+), but no significant release of creatine phosphokinase, lactic acid dehydrogenase, creatine, or Na(+). THERE WAS NO DETECTABLE RELEASE OF ADENOSINE BY HEARTS DURING PACING OR EXERCISE IN THREE CONTROL GROUPS OF PATIENTS: nine with anginal syndrome and severe coronary atherosclerosis who did not develop angina or produce lactate during rapid pacing, five with normal coronaries and no myocardial disease, and three with normal coronaries but with left ventricular failure. The results indicate that human hearts release significant amounts of adenosine during severe regional myocardial ischemia and anaerobic metabolism. Adenosine release might provide a useful supplementary index of the early effects of ischemia on myocardial metabolism, and might influence regional coronary flow during or after angina pectoris.
 ...
PMID:Release of adenosine from human hearts during angina induced by rapid atrial pacing. 482 35

Adenosine diphosphate (ADP) injection into a unilateral vertebral artery in rabbits decreased per-rotational nystagmus; the nystagmus beating toward the injected side was predominantly suppressed. This influence became obvious when the animal's blood pressure was low. Field potentials were recorded in the vestibular nuclei upon electric stimulation of the vestibular labyrinth. ADP administration into the vertebral artery also suppressed the amplitude of vestibular evoked potentials (VEPs). Effects of ADP upon the vestibulo-ocular reflex and VEP were considered to be due to regional ischemia induced by the microemboli, which consisted of platelet aggregation.
 ...
PMID:Effects of adenosine diphosphate administration on the vestibulo-oculomotor reflex of rabbits. 612 15

The function of blood platelets sampled from the coronary sinus and the superior vena cava was studied in 50 men with coronary artery disease at rest and during pacing-induced angina. At rest, a lower platelet aggregation and retention response was found in coronary sinus compared with vena caval blood. This may be due to refractoriness after previous platelet stimulation or to release of platelet inhibitors in the coronary circulation. During pacing-induced angina, lactate levels indicated that blood was sampled from ischemic myocardium in only 27 of the patients. Pacing-induced angina influenced platelet function differently in blood from ischemic and nonischemic regions. Adenosine diphosphate- and collagen-induced aggregation, platelet retention and plasma beta-thromboglobulin levels remained unchanged in blood from ischemic myocardium during pacing, but increased in blood from nonischemic regions. Thus, factors other than ischemia activated platelets in the coronary circulation during tachycardia-induced stress.
 ...
PMID:Effects induced on blood platelets in ischemic and nonischemic myocardium. 622 28

The decreased filtration fraction and glomerular filtration rate characteristic of renal failure could be produced, at least in part, by increased concentration of an endogenous substance which constricts afferent and dilates efferent arterioles. Adenosine satisfies several criteria: (a) exogenous adenosine and its precursors decrease filtration fraction and glomerular filtration rate; (b) the kidneys produce and release adenosine, and production and release are augmented during conditions associated with the induction of renal failure--hypoxia, ischemia, and renal vasoconstriction; (c) several substances known to antagonize adenosine-uptake processes in some cells, which could thereby increase extracellular adenosine concentration, not only have "adenosine-like" effects on the kidney but also induce and/or potentiate existing renal failure. A corollary of this hypothesis is that adenosine-receptor antagonists, such as the methylxanthines, should counteract the hemodynamic changes characteristic of renal failure. It has been known for several years that aminophylline (1,3-dimethylxanthine ethylenediamine) increases the filtration fraction and the glomerular filtration rate.
 ...
PMID:Hypothesis: adenosine mediates hemodynamic changes in renal failure. 628 27


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>