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)

Isolated canine hearts were preserved at 4 degrees C with multi-dose cardioplegic solution every hour for 6 hours. Reperfusion was observed for 2 hours under cross-circulation without cardiotonic drugs. The aprotinin group (n = 8), which received cardioplegic solution with added aprotinin (150 KIU/mL), was compared with the control group (n = 6). The increase in tissue adenosine triphosphate and total adenine nucleotide content during reperfusion was significant in the aprotinin group; there was no change in the control group, and the levels at the end of reperfusion tended to be higher in the aprotinin group than in the control group. Tissue adenosine diphosphate levels remained unchanged in both groups. Tissue adenosine monophosphate levels declined during reperfusion in both groups and were slightly lower in the control group. Tissue levels of cyclic adenosine monophosphate remained unchanged in the aprotinin group whereas they increased during ischemia and declined significantly during reperfusion in the control group. Tissue levels of cyclic guanosine monophosphate declined during reperfusion in both groups without difference. Creatine phosphate levels recovered in both groups without difference. Serum cyclic guanosine monophosphate concentration tended to be lower in the aprotinin group than in the control group. Serum creatine kinase-MB level increased slightly during reperfusion in both groups without difference. N-acetyl-beta-D-glucosaminidase levels were significantly suppressed during reperfusion in the aprotinin group as compared with the control group. These results suggest that aprotinin is effective in preserving adenine nucleotide and adenosine triphosphate levels and in stabilizing tissue cyclic adenosine monophosphate levels in prolonged hypothermic cardioplegic preservation followed by reperfusion.
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PMID:Effect of aprotinin to improve myocardial viability in myocardial preservation followed by reperfusion. 171 31

Amiloride has previously been shown to facilitate receptor binding of atrial natriuretic factor (ANF) to membranes of adrenal cortex and to enhance ANF induced inhibition of steroid secretion in vitro. This interaction of amiloride and ANF also holds true for the cardiovascular system. In precontracted rabbit aortic strips the relaxing effect induced by the combination of ANF (10(-10) mol/l) and amiloride (10(-5) mol/l) was overadditional. The production of cyclic guanosine monophosphate (cGMP), which parallels ANF induced relaxations of vascular strips, was not affected by amiloride alone up to 10(-3) mol/l, but was concentration-dependently increased in the presence of ANF (10(-8) mol/l). In spontaneously hypertensive rats ANF-induced decreases in blood pressure were potentiated by amiloride. Post ischemia reperfusion arrhythmias in isolated rat hearts were reduced by ANF. Amiloride increased this effect. The binding experiments revealed an interaction of amiloride and ANF on the receptor level. Binding of labeled ANF to aortic tissue was concentration-dependently increased by amiloride. Addition of ATP had the opposite effect. Therefore it can be suggested that amiloride and ATP interfere with a mechanism regulating the sensitivity of the vascular ANF-receptor for its ligand regarding binding and signal transforming presumably by a kinase mediated phosphorylation/dephosphorylation process.
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PMID:Potentiation of the effects of atrial natriuretic factor on the cardiovascular system by amiloride. 255 51

The effects of the synthetic 28-amino-acid alpha-human atrial natriuretic peptide (ANP) on the proximal coronary arteries and coronary blood flow were evaluated in 17 patients. Proximal coronary dimension was quantitated by digital angiography, and coronary flow was quantitated with 3F Doppler flow catheters. ANP, when given as a 2.5-micrograms/kg bolus in the left ventricle, caused sustained significant proximal coronary dilations from 3.49 +/- 0.57 to 4.09 +/- 0.76 mm, lasting more than 30 minutes. The proximal coronary diameter did not increase further after intracoronary injection of 0.3 mg nitroglycerin (4.08 +/- 0.79 mm). Coronary flow (resistance coronary dilation) was not significantly increased at 5 minutes after ANP (87 +/- 55 to 102 +/- 54 vol flow units), indicating that the proximal coronary dilations were not flow dependent. The persistent proximal coronary dilations were associated with minor and transient decreases in aortic pressure and left ventricular end-diastolic pressure and with minor and transient increases in heart rate, cardiac output, and left ventricular contractility. Plasma ANP level increased significantly by more than sixfold from 39.8 +/- 8.8 to 245.8 +/- 168.5 pg/ml. The time course of proximal coronary dilations was related more closely to the time course of increase in plasma cyclic guanosine monophosphate than that of plasma ANP. This study demonstrates that bolus injection of ANP (2.5 micrograms/kg), an endogenous vasodilator, caused marked sustained preferential proximal coronary dilations and brief minor changes in cardiac and systemic hemodynamics. Although additional studies are needed to assess its clinical efficacy as a coronary dilator in the treatment of coronary artery disease, these data suggest a potential of ANP in the therapy of ischemia.
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PMID:Effects of atrial natriuretic peptide on the coronary arterial vasculature in humans. 255 73

Nitrate tolerance is defined as an attenuation or even loss of hemodynamic and anti-ischemic effects during continuous nitrate medication. The blunted response may be due to the development of pseudotolerance and true pharmacologic tolerance. Pseudotolerance is the result of volume and salt retention, as well as the stimulation of counter-regulatory mechanisms which may alter the baseline hemodynamics of a patient during nitrate therapy. Far less important are changes in nitrate pharmacokinetics. True pharmacological tolerance may also be of practical importance. Diminished uptake of nitrates into the vascular smooth muscle cell, a decrease in intracellular SH groups, inhibition of the guanylate-cyclase, and stimulation of a specific phosphodiesterase may result in a decrease of cyclic GMP formation and hence to a decrease in nitrate induced vasodilatation. Tolerance development may be prevented by intermittent nitrate administration providing intervals with low plasma and tissue nitrate levels. In consequence, nitrates should be used predominantly for treatment of ischemic episodes, but 24-hour anti-ischemic action for the prevention of ischemia can be better achieved by treatment with a beta-blocker and/or a calcium antagonist. Nitrates should be added in times of maximum susceptibility to ischemia, while allowing nitrate levels to fall at other times.
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PMID:[Nitrate tolerance]. 290 73

Supplementation with phosphoenolpyruvate (PEP) and ATP was previously found to enhance the protective effect of potassium cardioplegia on rat hearts subjected to extensive ischemic trauma (30 min at 37 degrees C) in the paracorporeal rat heart model. In the present experiments, the ischemia time was reduced to 20 min (37 degrees C). Ventricular work after ischemia was best in control rats with potassium cardioplegia only. Supplementing the cardioplegic solution with PEP and ATP (group I) resulted in significantly reduced postischemic ventricular work and increased efflux of the creatine kinase isoenzyme MB (CK-MB). The same result was obtained when adenosine monophosphate (AMP) was added to the supplementation (group II). When guanosine monophosphate (GMP) was added instead of AMP (group III), the negative effects of PEP and ATP in the cardioplegic solution were partly abolished. Plain potassium cardioplegia, without additives, nevertheless gave the best results. There were no significant intergroup differences in the myocardial content of adenine nucleotides. The results contrasted with those in the previous study of more protracted ischemic trauma (30 min at 37 degrees C) and possible explanations are discussed.
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PMID:Interrelated effects of nucleoside mono- and triphosphates and phosphoenolpyruvate on rat hearts subjected to cardioplegic arrest at normothermia. 303 9

Purine nucleotides, nucleosides, nucleobases, dinucleotides and nucleosides derivatives from acid-extracted rat liver and diaphragm were separated and quantitated by reversed-phase ion-pair high-performance liquid chromatography with a mobile phase composed of 90 mM potassium phosphate, 15 mM tetrabutylammonium hydroxide and a 1-30% methanol gradient. During 5 min of ischemia, adenine and guanine nucleotides decreased along with significant declines in NAD and increases in adenosine, inosine, hypoxanthine, xanthine, NADP and adenylosuccinate. Nitrobenzylthioinosine by gavage (5 mg/kg per day for five days) increased adenosine levels but without any alteration in nucleobase levels. Adenosine was shuttled to every available intracellular reservoir which included in declining order of magnitude GDP greater than adenosylhomocysteine greater than adenosine greater than ADP greater than AMP greater than IMP = XMP = GMP.
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PMID:Demonstration of the adenosine reservoirs with nitrobenzylthioinosine in liver and diaphragm by high-performance liquid chromatography. 339 39

The long-acting antianginal drug molsidomine has been shown experimentally to reduce myocardial infarct size when administered prior to or after cardiac insult. This is due to several drug actions. Dilation of postcapillary capacitance vessels diminishes venous return, preload, heart dimensions, and myocardial oxygen consumption. Relaxation of stenosed conductive coronary arteries increases the perfusion of myocardial areas at risk of infarction due to enhanced collateral circulation. Increased regional blood supply nourishes predominantly subendocardial cardiac muscles as a result of reduction of extravascular coronary pressure, and resistance. The stable heart rate and cardiac contractility favor improved heart performance. The inhibition of platelet aggregation in vivo by molsidomine or its active metabolites, SIN-1 and SIN-1A, is linked to the stimulation of prostacyclin synthesis, inhibition of thromboxane release with induction of thrombosis and vasoconstriction, and enhanced concentrations of cyclic guanosine monophosphate. Dilation of coronary arteries after intracoronary administration of SIN-1, with inhibition of platelet aggregation by restrained release of adenosine diphosphate and stabilization of platelet membranes, facilitates the recanalization of stenosed arteries and reduces coronary muscle tone at the site of thrombosis. Activation of the human fibrinolytic system and drug-induced release of a plasminogen activator favor dysaggregatory effects. The drug's inhibiting actions on lipoxygenase products of arachidonate (e.g., 12-hydroperoxy-eicosatetraenoic acid and leukotrienes) may shift prostaglandin catabolism to cyclooxygenase products (e.g., prostacyclin) that protect against the expansion of ischemia and the induction of coronary spasm. Experimentally, the hemodynamic effectiveness of molsidomine can be antagonized by catecholamines (afterload effects) and dihydroergotamine (preload and afterload effects) respectively. Further clinical investigations will clarify the application of these mechanisms for the therapeutic success of the drug in human myocardial infarction.
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PMID:Molsidomine: alternative approaches to treat myocardial ischemia. 355 58

The protective effect of prostaglandin I2 (PGI2) on ischemia-induced liver cell injury was investigated during 60-min, 75-min, and 90-min liver ischemia. Vehicle-treated rats tolerated the 75-min hepatic ischemia poorly. Only 25% of the rats in this group survived more than 7 days. However, the survival rate of PGI2-treated rats (350 ng/kg/min) significantly improved to 67%. Liver cell organelles were well-preserved by the PGI2 treatment. Adenosine triphosphate levels in the liver of the PGI2-treated rats were significantly higher than those of vehicle-treated rats at 60 min of reoxygenation following 75-min ischemia. Cyclic 3'-5' adenosine monophosphate levels markedly increased during 60-min PGI2 infusion. Cyclic 3'-5' guanosine monophosphate levels also significantly increased during the PGI2 infusion and were still higher than those of vehicle-treated rats at the end of the 75-min ischemia. Although the exact cytoprotective mechanism of PGI2 at the cellular level is still unclear, our results demonstrate that elevated ATP and cyclic nucleotides levels play an important role in liver cell preservation during ischemia.
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PMID:Cytoprotective effect of prostaglandin I2 on ischemia-induced hepatic cell injury. 631 Aug 31

This paper is a synopsis on recent reports dealing with the pharmacological basis of molsidomine-induced circulatory effects. The therapy of coronary insufficiency by molsidomine is based on different pathophysiological and pharmacological mechanisms. The inactive compound molsidomine is metabolized--mainly in the liver--to form the vasoactive and antiaggregatory compound SIN-1 and SIN-1A. Due to the gradual conversion into the active compound, the peak effects are observed only after 15 min (intravenously) or 30 to 60 min (orally). The effects are long-lasting and can be observed up to four to six hours. The c-GMP mediated dilation of various vascular sites comprise mainly the venous system (both small and large veins), resulting in a significant preload reduction, a decrease in cardiac output, a decrease in heart size and circumferential wall stress, a decrease in myocardial oxygen consumption and a therapeutically important improvement of O2-delivery versus myocardial O2-consumption. This effect results in a significant improvement of myocardial ischemia (reducing frequency of anginal attacks, improvement of exercise tolerance and of exercise induced ST-depressions). In animal experiments molsidomine diminishes infarct size and suppresses reperfusion-induced ventricular fibrillation following ischemia. Molsidomine dilates, like nitroglycerin, the large coronary arteries. Therefore, in coronary heart disease, it may improve collateral flow in addition to beneficial effects on subendocardial perfusion resulting from the reduction of ventricular wall stress. In addition to direct dilating effects on collateral vessels an improvement in perfusion of asynergistically contracting ventricular sections has been observed. In contrast to nitroglycerin, effects on peripheral resistance appear only under extremely high dosages and reflex increases in heart rate are rarely observed. In general molsidomine-induced changes (increases) in heart rate, in stroke volume (decreases), and in cardiac output (decreases) are of small magnitude. Recently interesting findings on molsidomine-induced suppression of thrombocyte aggregation, of thromboxan-synthesis inhibition and of increased prostacyclin formation have been presented, which may be important in the improvement of myocardial (micro-) circulation under ischemic conditions.
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PMID:[Pharmacological basis of therapy with molsidomine]. 689 44

The effects of aspirin and L-arginine (biological precursor of nitric oxide) on the production of hydroxyl radicals, cyclic guanosine monophosphate levels, vascular tone, and the recovery of the ischemic myocardium were investigated in isolated rat hearts subjected to ischemia and reperfusion. After 30 minutes of perfusion, hearts were arrested with St. Thomas' Hospital cardioplegic solution, global ischemia was induced at 37 degrees C for 45 minutes, and the hearts were then reperfused at 37 degrees C for 30 minutes. The percent change in recovery of pulse pressure and maximal change of this pressure with time were better in the group perfused with Krebs-Henseleit solution containing aspirin plus L-arginine (17% +/- 23%, p = 0.001, and 10% +/- 25%, p = 0.002, respectively) compared with these values in the control group perfused with Krebs-Henseleit solution alone (-7% +/- 14% and -11% +/- 16%, respectively). Coronary vascular resistance before and after ischemia were lower in the aspirin plus L-arginine group (0.19 +/- 0.03 dynes.sec/cm5, p = 0.001, and 0.23 +/- 0.04 dynes.sec/cm5, p = 0.01, respectively) compared with those of the control group (0.24 +/- 0.02 and 0.28 +/- 0.07 dynes.sec/cm5, respectively). Cyclic guanosine monophosphate levels increased from 22.5 +/- 6 pmol/100 mg of tissue in the control group to 37.1 +/- 8.9 pmol/100 mg (p = 0.002) in the aspirin plus L-arginine group. Adding N omega-nitro-L-arginine methyl ester to the perfusion medium caused a deterioration in pulse pressure and maximal change of this pressure with time, a decrease in cyclic guanosine monophosphate, and a rise in coronary vascular resistance. The addition of L-arginine to the solution in the Krebs-Henseleit solution plus aspirin group increased the production of hydroxyl radicals from 0.32 +/- 0.18 nmol/gm per 3 minutes to 0.75 +/- 0.33 nmol/gm per 3 minutes (p = 0.03). Despite the association of nitric oxide with increased hydroxyl radical production, it appears that nitric oxide has an overall beneficial effect on the recovery of the ischemic myocardium. The synergism between aspirin and arginine may be caused in part by the scavenging of hydroxyl radicals. Alternatively, by inhibiting the prostaglandin pathway, aspirin may reduce the generation of superoxide anion, a free radical that inactivates nitric oxide. The prolonged half-life of nitric oxide may explain the increased levels of cyclic guanosine monophosphate seen in the group perfused with Krebs-Henseleit solution plus aspirin plus L-arginine. Aspirin and L-arginine, both readily available, may be useful adjuncts to clinical cardioplegia strategy.
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PMID:Simultaneous manipulation of the nitric oxide and prostanoid pathways reduces myocardial reperfusion injury. 747 34


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