Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This epidemiological study was undertaken to explore possible relationships among various haematological indices, prevalent ischaemic heart disease and platelet "function" as measured by two rather different methods. ADP-induced platelet impedance changes in whole blood were strongly associated with prevalent ischaemic heart disease in a general population of 49-66 year men at increased risk. Adenosine diphosphate (ADP) induced platelet aggregation in platelet rich plasma (PRP) at a constant platelet count and also the whole blood platelet count and red cell (RBC) count were strongly and independently related to ADP-induced platelet impedance changes. Both platelet count and platelet aggregation in PRP assessed by changes in optical density were directly related to increasing platelet "sensitivity" as measured by impedance changes in whole blood but RBC count was inversely related. Positive independent relationships between platelet impedance changes and plasma viscosity and fibrinogen were markedly attenuated when platelet count was taken into account, but this finding does not discount a role for these factors in platelet aggregation. No relationship was noted between white blood cell (WBC) count and platelet impedance changes; however, a significant inverse relationship was noted with platelet aggregation in PRP. These findings indicate that laboratory-based experimental findings can be observed in population based studies, and that these haematological factors may be important indicators of ischaemic disease in the population.
 ...
PMID:The association of platelet and red cell count with platelet impedance changes in whole blood and light-scattering changes in platelet rich plasma: evidence from the Caerphilly Collaborative Heart Disease Study. 227 May 30

The endogenous compound adenosine may play a role in limiting myocardial ischemia-reperfusion injury through its ability to cause vasodilation, modulate cardiac adrenergic responses, inhibit neutrophil function, or modulate energy supply and demand of the myocardium. The local anesthetic lidocaine has been shown to be protective against myocardial ischemia-reperfusion injury, although its mechanism of action remains unresolved. We hypothesized that administration of exogenous adenosine during reperfusion would limit the size of the infarct that results from a period of ischemia and reperfusion only when the animals are treated with lidocaine. Male, mongrel dogs (13.0-20.0 kg) were anesthetized (30 mg/kg i.v. sodium pentobarbital), and a left thoracotomy was performed. The left circumflex coronary artery (LCx) was isolated and instrumented with an electromagnetic flow probe, a 25-gauge nonobstructing intracoronary catheter, and a critical stenosis. The dogs were allocated randomly to one of four groups: 1) control, n = 13, (saline), 2) adenosine, n = 13, (0.15 mg/kg/ml/min i.c. for the first hour of reperfusion), 3) lidocaine, n = 9, (2.0 mg/kg i.v. given immediately before coronary artery occlusion and just before reperfusion), or 4) adenosine plus lidocaine, n = 11. The LCx was occluded for 90 minutes and reperfused for 6 hours. Regional myocardial blood flow (RMBF) was determined (n = 6 per group) at 80 minutes of occlusion and at 45 minutes of reperfusion with radiolabeled microspheres. RMBF determinations revealed an increase in blood flow to the inner two thirds of the myocardium at 45 minutes of reperfusion only in the presence of the combined treatment. Adenosine treatment alone or lidocaine treatment alone did not affect RMBF. Quantification of infarct size (triphenyltetrazolium method) expressed as a percent of the area at risk revealed a significant limitation of infarct size only in the group treated with both adenosine and lidocaine: control, 47.8 +/- 6.6%; adenosine, 45.0 +/- 3.2%; lidocaine, 46.9 +/- 6.0%; and adenosine and lidocaine, 20.8 +/- 5.6%. Statistical analyses were performed with two-way analysis of variance to account for the two individual drug treatments. The findings show that intracoronary administration of exogenous adenosine, at the dose used, is only effective at limiting myocardial infarct size when administered to lidocaine-treated animals.
 ...
PMID:Combined adenosine and lidocaine administration limits myocardial reperfusion injury. 237 6

Calcium channel antagonists inhibit platelet function in vitro and ex vivo, but the mechanism responsible has not been clearly defined. The concentrations of these agents required to inhibit platelet aggregation in vitro are several fold higher than those attained in vivo. Adenosine, a known inhibitor of platelet function, is produced in large quantities in ischemic myocardium. In order to test the hypothesis that adenosine may potentiate the platelet-inhibitory effects of calcium channel antagonists, we studied the effect of adenosine plus nifedipine, verapamil or diltiazem on human platelet aggregation induced by thromboxane A2 or the stable endoperoxide/thromboxane A2 mimic, U46619 +/- epinephrine. Adenosine, in concentrations achieved in the plasma during myocardial ischemia (0.01-0.1 microM), enhanced the inhibitory effects of nifedipine, verapamil and diltiazem on platelet aggregation 5-100 fold. The same concentrations of adenosine alone did not inhibit platelet aggregation. In the presence of non-inhibitory concentrations of adenosine, nifedipine, in concentrations approaching those attained in vivo following standard therapeutic doses (as low as 0.29 microM), significantly inhibited thromboxane A2-induced platelet aggregation. Therefore, adenosine potentiates the in vitro inhibitory effects of calcium channel antagonists on platelet aggregation induced by thromboxane A2 or thromboxane A2 plus epinephrine. These results suggest that adenosine production by ischemic myocardium may augment the inhibitory effect of calcium channel antagonists on platelets.
 ...
PMID:Adenosine potentiates the inhibitory effects of calcium channel antagonists on human platelet aggregation induced by thromboxane A2 or U46619. 239 26

The interaction between leukotriene D4 and adenosine or the prostacyclin analogue iloprost was studied in isolated guinea-pig hearts. Adenosine (1 X 10(-6) M) or iloprost (5 X 10(-8) M) abolished or greatly attenuated the vasoconstrictive effect of leukotriene D4 over a wide dose range of leukotriene D4 (0.01-1000 ng), and myocardial ischemia as a consequence of coronary insufficiency completely disappeared. Comparison of myocardial levels of reduced pyridine nucleotide fluorescence in hearts treated with leukotriene D4 and in hearts subjected to varying degrees of high-flow hypoxia, or the calcium agonist BAY-K 8644, revealed low levels of reduced pyridine nucleotides in the leukotriene D4-treated hearts, suggesting that leukotriene D4 directly suppressed myocardial contractility. These findings were supported by full restoration of cardiac work by the receptor antagonist FPL 55712 following leukotriene D4 treatment. It is concluded that adenosine and iloprost are potent inhibitors of leukotriene D4-induced reduction in coronary flow in guinea-pig hearts, and that myocardial ischaemia and suppressed cardiac work are prevented during leukotriene D4 study in adenosine or iloprost perfused hearts. Low levels of myocardial-reduced pyridine nucleotides during leukotriene D4 treatment and restoration of cardiac work by FPL 55712 indicate that leukotriene D4 may also have a direct suppressive effect on myocardial contractility.
 ...
PMID:Interaction between leukotriene D4 and adenosine or iloprost in the isolated working guinea-pig heart: prevention of the leukotriene D4 effect. 243 41

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)
 ...
PMID:Inducers of adenylate cyclase reverse the effect of leukotriene D4 in isolated working guinea pig heart. 243 50

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.
 ...
PMID:Coronary vasoconstriction in experimental myocardial ischemia. 244 Dec 6

Morbidity and mortality from acute coronary artery occlusion may be reduced if local myocardial adenosine concentration is augmented because 1) coronary collateral blood flow during ischemia increases with adenosine infusion, and 2) granulocytes that accumulate in the microcirculation during ischemia are, to a large extent, inhibited by adenosine from generating superoxide anion free radicals, from adhering to vascular endothelium, and from damaging endothelial cells in culture. Using a cultured lymphoblast model system, we found that 5-amino-4-imidazole carboxamide (AICA) riboside enhanced adenosine accumulation during ATP catabolism. Therefore, AICA riboside pretreatment was used in canine myocardium to selectively increase adenosine concentration in the ischemic area during 1 hour of ischemia. At 5 minutes of ischemia, endocardial flow to ischemic myocardium in saline-treated and AICA riboside-treated dogs was 0.06 +/- 0.03 and 0.34 +/- 0.11 ml/min/g, respectively (p less than 0.01); flow to nonischemic myocardium was not affected. Ventricular tachycardia and premature ventricular depolarizations were significantly attenuated in the AICA riboside-treated dogs. Blood pressure and heart rate were not affected by AICA riboside. In venous blood from ischemic tissue, adenosine increased from undetectable levels (less than 0.01 microM) to 0.22 +/- 0.08 microM in saline and 1.79 +/- 0.06 microM in AICA riboside-treated dogs, respectively (p less than 0.001). Coronary vein inosine concentrations were greater in saline than in AICA riboside-treated dogs. In separate in vitro studies, AICA riboside did not alter the removal rate of adenosine from canine blood. Indium-labeled granulocyte accumulation was significantly less in ischemic myocardium in AICA riboside-treated compared with saline-treated dogs. In addition, adenosine, but not AICA riboside, inhibited in vitro canine granulocyte superoxide production. We conclude that AICA riboside given before myocardial ischemia augments adenosine concentration, decreases arrhythmias, decreases granulocyte accumulation, and improves collateral flow to ischemic myocardium. One of the beneficial mechanisms could be an increased production of adenosine rather than inosine from ATP catabolism that causes vasodilation and inhibition of granulocytes. We propose a new hypothesis regarding regulation of the inflammatory reaction to ischemia in the microcirculation. Adenosine, in addition to its vasodilator action, is an anti-injury autacoid that links ATP catabolism to inhibition of granulocyte adherence, microvascular obstruction, and superoxide anion formation.
 ...
PMID:Increased adenosine concentration in blood from ischemic myocardium by AICA riboside. Effects on flow, granulocytes, and injury. 255 98

Available data indicate that platelet function and arachidonic acid metabolism are important factors in hemostasis and regulation of vascular tone. Plasma membrane and intracellular mobilization of calcium ions are intimately related to platelet activation and release of platelet contents. Release of arachidonic acid from membrane phospholipids as well as subsequent synthesis and release of vasoconstrictor thromboxane A2 are also regulated by movement of calcium ions. Adenosine 3':5'-cyclic phosphate in turn controls levels of free calcium ions in platelets and regulates calcium-dependent reactions. Slow-channel calcium blockers, such as verapamil, diltiazem and nifedipine, inhibit platelet activation in vitro, and decrease platelet adhesion intravascularly. These agents have also been shown to decrease platelet nucleotide release and thromboxane A2 generation. Some preliminary data suggest that calcium blockers also increase generation of vasodilator and platelet antiaggregant prostacyclin, which could contribute to decrease in platelet function. These effects of calcium blockers on platelet function and arachidonic acid metabolism could contribute in part to their efficacy in patients with ischemic heart disease.
 ...
PMID:Influence of calcium-channel blockers on platelet function and arachidonic acid metabolism. 298 52

Adenosine effects on the transmembrane potential characteristics and the sarcolemmal Na+-K+ ATPase activity of human atrial myocardium were studied in tissue from 20 patients who were divided into 2 groups based on the maximum diastolic potentials (MDP) greater than or less than -60 mV. Group A consisted of 10 patients with MDP of 70.84 +/- 4.20 mV and Na+-K+ ATPase activity of 15.37 +/- 0.46 mumole Pi/mg/hr. Ten patients with MDP of 44.54 +/- 6.24 mV and Na+-K+ ATPase activity of 12.55 +/- 0.42 mumole Pi/mg/hr were included in group B. Adenosine had no effects on the electrophysiological properties and the sarcolemmal Na+-K+ ATPase activity of atrial myocardium at concentrations below 1 X 10(-5) M in either group. Adenosine resulted in mildly altered atrial transmembranes potentials without significant effect on Na+-K+ ATPase activity at concentrations between 1 X 10(-5) M and 5 X 10(-4) M. However, a significant reduction of transmembrane potentials and an apparent inhibition of Na+-K+ ATPase activity were observed only in tissue from group B. These results suggest that: 1) adenosine has no effect on the electrophysiological properties and the sarcolemmal Na+-K+ ATPase activity of human atrial myocardium at physiological concentrations; 2) adenosine induced inhibition of the sarcolemmal Na+-K+ ATPase activity in slow channel-dependent atrial tissues may be a mechanism responsible for the alterations of transmembrane potentials under unphysiological conditions; and 3) adenosine contributes to the genesis of cardiac arrhythmias during acute myocardial ischemia, which can reduce transmembrane potentials of the myocardial cells and may increase the myocardial adenosine level above its effective concentration.
 ...
PMID:Effects of adenosine on transmembrane potential and sarcolemmal Na+-K+ ATPase activity of human atrial myocardium. 298 73

Adenosine and ATP exert pronounced electrophysiologic actions on the mammalian heart including a negative chronotropic action on cardiac pacemakers and a negative dromotropic action on atrioventricular conduction. These actions are modulated by complex interactions of the two compounds with the autonomic nervous system. Since both adenosine and ATP are released from myocardial cells under physiologic and pathophysiologic conditions, they could play an important modulating role in cardiac electrophysiology. Indeed, studies during the last decade have yielded strong evidence for the role of adenosine in the genesis of specific arrhythmias associated with myocardial ischemia. Further studies are required to fully elucidate the mechanisms of actions of adenosine and ATP in vivo. These will undoubtedly enhance the understanding of the potential arrhythmogenic, as well as the antiarrhythmic actions of endogenous and exogenous adenosine and ATP.
 ...
PMID:On the mechanisms of cardiac electrophysiologic actions of adenosine and adenosine 5'-triphosphate. 305 Oct 10


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