Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151814 (coronary occlusion)
 3,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In anaesthetized open-chest casts with occlusion of the left anterior descending coronary artery (LAD), adenine nucleotides and degradation products were studied in small myocardial tissue samples (10-20 mg) with high-pressure liquid chromatography, and tissue blood flow was measured with radioactive microspheres 5, 10, 20, 40, and 60 min after LAD occlusion. There was a rapid and parallel decrease of myocardial ATP and accumulation of adenosine, inosine, hypoxanthine, and xanthine both in epicardial and endocardial half-layers of the ischaemic myocardium within the first 20 min of coronary occlusion. After 40 and 60 min, myocardial ATP content decreased and degradation products accumulated further in the endocardium but stabilized epicardially. Analysis of covariance showed that the slightly higher blood flow in ischaemic epicardial layers, did not explain the transmural difference in ATP content after 40 and 60 min. Adenosine decreased after 40 min of ischaemia in both wall layers reaching negligible amounts after 60 min. It is concluded that breakdown of energy stores is less severe in epicardial than in endocardial wall layers during the first hour after acute coronary occlusion in the cat heart. This transmural difference cannot be explained entirely by less severe epicardial ischaemia. Therefore, transmural heterogeneity in metabolic function during severe ischaemia may also be important.
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PMID:Myocardial adenine nucleotide depletion within 1 h of acute coronary artery occlusion. 145 54

Effects of ventricular compression on maximally dilated left circumflex coronary blood flow were investigated in seven mongrel dogs under pentobarbital anesthesia. The left circumflex artery was perfused with the animals' own blood at a constant pressure (63 mmHg) while left ventricular pressure was experimentally altered. Adenosine was infused to produce maximal vasodilation, verified by the hyperemic response to coronary occlusion. Alterations of peak left ventricular pressure from 50 to 250 mmHg resulted in a linear decrease in total circumflex flow of 1.10 ml.min-1 x 100 g heart wt-1 for each 10 mmHg of peak ventricular to coronary perfusion pressure gradient; a 2.6% decrease from control levels. Similar slopes were obtained for systolic and diastolic flows as for total mean flow, implying equal compressive forces in systole as in diastole. Increases in left ventricular end-diastolic pressure accounted for 29% of the flow changes associated with an increase in peak ventricular pressure. Doubling circumferential wall tension had a minimal effect on total circumflex flow. When the slopes were extrapolated to zero, assuming linearity, a peak left ventricular pressure of 385 mmHg greater than coronary perfusion pressure would be required to reduce coronary flow to zero. The experiments were repeated in five additional animals but at different perfusion pressures from 40 to 160 mmHg. Higher perfusion pressures gave similar results but with even less effect of ventricular pressure on coronary flow or coronary conductance. These results argue for an active storage site for systolic arterial flow in the dilated coronary system.
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PMID:Contribution of extravascular compression to reduction of maximal coronary blood flow. 173 24

In isolated perfused rat hearts with occlusion of the left coronary artery the release of adenosine and its degradation products inosine, hypoxanthine, xanthine and uric acid was investigated with and without exogenous addition of adenosine deaminase. In the control experiments large amounts of the adenine nucleotide catabolites appeared in the perfusate during coronary reperfusion. The greater part was represented by adenosine and inosine. During the coronary occlusion itself only a minor increase in the release of adenine nucleotide catabolites was observed, compared with the basal release before the coronary occlusion. Depending on the duration of the coronary occlusion more or less severe tachyarrhythmias occurred during the reperfusion of the previously ischaemic myocardium. Reperfusion-induced ventricular fibrillation was associated with a significant increase in the release of adenine nucleotide catabolites, compared with non-fibrillating hearts. In the presence of exogenously-added adenosine deaminase the release of adenine nucleotide catabolites from reperfused hearts was further increased. Adenosine itself, however, almost completely disappeared from the perfusate. In adenosine-deaminase treated hearts the incidence of reperfusion-induced fibrillation increased, thereby contributing to the enhanced release of adenine nucleotide catabolites. However, the release was also increased by the enzyme when only the fibrillating hearts were considered, suggesting that rapid elimination of adenosine from the interstitial space also directly increases the release of adenine nucleotide catabolites from the heart.
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PMID:Effect of exogenous adenosine deaminase on arrhythmias and the release of adenine nucleotide catabolites in isolated rat hearts with coronary occlusion and reperfusion. 181 Nov 71

The possibility of a coexistence of coronary arteriolar constriction mediated by the renin-angiotensin system and myocardial ischemia was evaluated. Left anterior descending coronary artery was cannulated and perfused at normal (mean aortic), intermediate (50 mm Hg), and low (30-40 mm Hg) pressure in analogy to a progressive coronary stenosis. Lactate production was present at low coronary pressure indicating myocardial ischemia. In control animals (n = 18), mean coronary conductance was higher (p less than 0.005) at intermediate than at high coronary pressure consistent with autoregulation at coronary flow. Coronary conductance was lower (p less than 0.05) at low than at intermediate coronary pressure, indicating coronary constriction during myocardial ischemia. Adenosine (20 micrograms/kg per min i.c., n = 6) resulted in higher coronary conductance, suggesting coronary vasodilator reserve even at low coronary pressure. Indomethacin (5 mg/kg i.v., n = 12) resulted in low coronary conductance; however, the increase at intermediate (autoregulation) and the decrease (constriction) at low pressure was maintained. Plasma renin activity increased, and saralasin (0.1 microgram/kg per min i.c.) and captopril (0.25 mg/kg i.v.) acted as coronary vasodilators in various models of myocardial ischemia. Captopril limited myocardial infarct size at 6 hours of coronary occlusion, diminished flow repayment and prevented lactate production after 30 s of coronary occlusion, and abolished the deterioration of myocardial function during myocardial ischemia induced by coronary hypoperfusion and atrial pacing. Thus, myocardial ischemia does not generally represent a state of maximal coronary dilatation. The renin-angiotensin system is activated by myocardial ischemia and may exert a coronary constrictive tone. Captopril was beneficial in experimental myocardial ischemia.
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PMID:Coronary vasoconstriction in experimental myocardial ischemia. 244 Dec 6

The effects of acute subtotal embolisation of small coronary arteries on regional coronary flow and vasodilator reserve were investigated in seven open chest dogs. Unlabelled plastic microspheres (26(2) micron in diameter) were injected as boluses of 200,000-400,000 microspheres into the circumflex artery. Embolisation was repeated until reactive hyperaemia was totally abolished, which occurred after the injection of 62,000(4000) microspheres per gram. Intracoronary adenosine was then infused for 20 min at 1.2 mg.min-1. Regional myocardial blood flow was measured by radioactive microspheres under control conditions, after coronary embolisation, and during adenosine infusion. Coronary blood flow (0.98(0.07) ml.min-1.g-1) was reduced to 0.66(0.08) ml.min-1.g-1 after embolisation (p less than 0.005) when reactive hyperaemia was practically abolished. Embolisation reduced epicardial flow from 0.93(0.08) to 0.40(0.09) ml.min-1.g-1 (p less than 0.001), whereas endocardial flow was unchanged (1.03(0.11) vs 0.92(0.14) ml.min-1.g-1; NS); as a consequence, the endocardial to epicardial flow ratio increased from the control value of 1.11(0.06) to 2.31(0.35) (p less than 0.005). Adenosine infusion increased coronary blood flow from 0.66(0.08) to 1.66(0.41) ml.min-1.g-1 (p less than 0.05). Endocardial blood flow increased more than epicardial blood flow, leading to a further increase in the endocardial to epicardial flow ratio (3.79(0.13); p less than 0.05). Thus it is concluded that (a) embolisation of small arteries abolishes the reactive hyperaemic response to transient coronary occlusion; (b) microembolisation predominantly reduces subepicardial perfusion; and (c) adenosine administration may increase total and regional flow after subtotal occlusion of coronary small arteries.
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PMID:Persistence of subendocardial perfusion after subtotal coronary embolisation. 316 33

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.
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PMID:Release of adenosine from human hearts during angina induced by rapid atrial pacing. 482 35

The accumulation of adenosine during a brief coronary occlusion has been proposed to mediate the infarct size-limiting effect of ischemic preconditioning. The purpose of this study was to compare the effects of ischemic preconditioning and a transient adenosine infusion on myocardial interstitial fluid (ISF) adenosine levels and infarct size. Microdialysis fibers (10.0 mm length) were placed in the left ventricular myocardium of pentobarbital sodium-anesthetized rabbits to estimate ISF adenosine. Ischemic preconditioning was induced by 5 min of coronary artery occlusion and 10 min of reperfusion before 45 min of occlusion. Adenosine preconditioning was induced with 5 min of intravenous adenosine infusion (140 micrograms.kg-1.min-1) followed by a 10-min washout before the prolonged occlusion. Myocardial infarct size was determined by triphenyltetrazolium chloride staining after 3 h of reperfusion. Five minutes of ischemia and 5 min of adenosine infusion produced comparable increases in dialysate adenosine levels (from 0.19 +/- 0.02 to 0.69 +/0- 0.11 and 0.28 +/- 0.10 to 0.71 +/- 0.18 microM, respectively) that decreased to baseline before the prolonged ischemia; however, ischemic-preconditioned hearts exhibited elevated dialysate adenosine levels for the first 5 min of reperfusion. Ischemic-preconditioned hearts exhibited significantly reduced dialysate adenosine concentrations for the first 20 min of the prolonged occlusion (P < 0.05 vs. control), and infarct size was reduced from 41 +/- 6 to 10 +/- 4% of risk area. Adenosine preconditioning had no effect on dialysate adenosine levels during prolonged ischemia but did reduce infarct size to 25 +/- 5% of risk area. These results indicate that a transient increase in ISF adenosine can reduce myocardial infarct size, but adenosine alone does not fully replicate the protective effects of ischemic preconditioning.
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PMID:Effects of ischemic and adenosine preconditioning on interstitial fluid adenosine and myocardial infarct size. 748 81

Adenosine is a possible mediator of cardiac pain during myocardial ischemia; however, little is known about the influence of adenosine on cardiac sympathetic afferent activity and thereby on its algogenic mechanism. In 20 anaesthetized, decerebrated, curarized and artificially ventilated cats, we studied the impulse activity of 20 single afferent sympathetic fibers with a left ventricular receptive field in relation to epicardial applications of adenosine, coronary artery occlusions and arterial pressure rises. All fibers increased their impulse activity (from 1.2 +/- 0.2 to 2.6 +/- 0.5 imp/s; P < 0.001) during slight (20 +/- 8%) rises in aortic pressure, thus exhibiting low-threshold receptor characteristics. In 10 cats, epicardial applications of three different doses of adenosine (0.1, 1 and 10 mg/ml) caused a brief increase in neural activity with dose-related responses. This response was abolished by aminophylline, a P1 purinergic inhibitor. In the other group of 10 cats, four subsequent 30-s occlusions of the coronary arterial vessel supplying the receptive fields of the fibers were performed, in control conditions and 30 s, 3 and 7 min, respectively, after the end of excitation induced by adenosine (1 mg/ml) application. During the control coronary occlusion the impulse activity increased from 1.1 +/- 0.1 to 5.5 +/- 0.7 imp/s (P < 0.0001). A similar activation was present during the second occlusion initiated 30 s after the end of adenosine-induced activation. In contrast, a significant potentiation of the response was observed (8.8 +/- 1.2 vs. 5.3 +/- 0.9 imp/s; P < 0.001) during the occlusion initiated 3 min after the end of excitation by adenosine. This effect was no longer present during the last occlusion performed after 7 min. When the protocol was repeated substituting adenosine with saline (n = 5) or after i.v. administration of aminophylline (n = 5), no potentiation was observed, even though the excitatory response to coronary occlusion was preserved. These data show that adenosine can activate cardiac sympathetic afferent fibers in a dose-related manner, and potentiate their responses to coronary occlusion, while leaving unaffected the responsiveness to a hemodynamic stimulus. The excitatory effects are likely to involve the P1 purinergic receptors. The potentiation phenomenon might play a role in the genesis of an algogenic code.
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PMID:Adenosine activates cardiac sympathetic afferent fibers and potentiates the excitation induced by coronary occlusion. 756 Jul 54

To investigate the rate of metabolism of nitrogen-13 labelled ammonia (13NH3) in different conditions, we have determined the relative amount of unchanged 13NH3 in the blood of dogs, volunteers and transplant patients at different times following injection. In dogs, the determinations were made under basal conditions, during adenosine administration and after coronary occlusion. The results show that adenosine administration increases the metabolic rate whereas coronary occlusion does not affect 13NH3 metabolism. For both human volunteers and transplant patients the metabolic rate of 13NH3 was assessed under basal conditions and during adenosine administration. 13NH3 metabolism proceeds faster in transplant patients than in volunteers under both conditions. Adenosine administration causes a faster 13NH3 turnover in volunteers but not in transplant patients. Application of individual metabolite correction resulted in a 16% decrease in the calculated blood flow compared to uncorrected values. A smaller difference (5%) was observed between correction with mean metabolite values and individually acquired metabolite values.
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PMID:Metabolism of nitrogen-13 labelled ammonia in different conditions in dogs, human volunteers and transplant patients. 775 97

Adenosine receptor activation has been assumed to play a role in the cardioprotective effect of ischemic preconditioning. The actions of adenosine are terminated by the naturally occurring substance adenosine deaminase. We determined whether 2'-deoxycoformycin (DCF), a potent inhibitor of adenosine deaminase, could mimic the effect of preconditioning in nonpreconditioned rats and potentiate the salutary effect of preconditioning in preconditioned rats. We assessed the effect of DCF on myocardial infarct size and the incidence of ventricular arrhythmias in four groups of anesthetized rats: control (nonpreconditioned) + vehicle, control + DCF, preconditioned + vehicle, and preconditioned + DCF. All rats underwent 90 minutes of coronary artery occlusion followed by 4 hours of reperfusion, while preconditioned rats received three cycles of 3-minute episodes of ischemia and 5 minutes of reperfusion before the 90-minute occlusion. Following 4 hours of reperfusion, area at risk was determined by intravenous injection of blue dye during a brief coronary occlusion, and area of necrosis was determined by incubation of heart slices in triphenyltetrazolium chloride. In the nonpreconditioned control rats receiving vehicle, myocardial infarct size expressed as a percentage of the area at risk averaged 44.8 +/- 7.6%. Pretreatment with DCF had no effect on infarct size (49.4 +/- 4.9%) in the nonpreconditioned control rats. Both the preconditioned+vehicle (19.2 +/- 7.8%) and the preconditioned + DCF (17.9 +/- 5.1%) groups had a significant reduction in infarct size (p < 0.05 versus control + vehicle and control + DCF), with no significant difference in infarct size between the two preconditioned groups. The incidence of ventricular tachycardia (VT) during the 90 minutes of ischemia was significantly attenuated in both preconditioned groups (p < 0.05 versus controls).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine deaminase inhibition is not cardioprotective in the rat. 824 84


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