Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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

Ischemic induces a nonexocytotic noradrenaline release in the heart, which leads to high and potentially harmful interstitial noradrenaline concentrations. The effect of beta-adrenoceptor antagonists on noradrenaline release in ischemia has been investigated in the present study. DL-Propranolol (1-100 mumol/l) concentration-dependently reduced noradrenaline release during 20 min of global and total ischemia in the perfused rat heart. Other beta-adrenoceptor blocking agents such as atenolol, metoprolol, and timolol (10 mumol/l each), however, did not share this effect. Moreover, both stereoisomers of propranolol were equipotent in suppression of ischemia-induced noradrenaline release, indicating a property of propranolol independent from interaction with beta-adrenoceptors. The well known local anesthetic action of propranolol was not likely to cause its inhibitory effect on ischemia-induced noradrenaline release, as lidocaine (10 mumol/l) did not affect noradrenaline overflow in ischemia. The effect of propranolol was further examined in cyanide intoxication, an experimental model of energy depletion. In this experimental setting the release of dihydroxyphenylethyleneglycol--the major neuronal metabolite of noradrenaline--served as indicator of increased axoplasmic noradrenaline levels which are present during nonexocytotic noradrenaline release. In cyanide intoxication DL-propranolol also reduced noradrenaline overflow but did not affect release of dihydroxyphenylethylene glycol. The latter finding suggests an interaction of propranolol with the neuronal membrane transport of noradrenaline. In ischemia and cyanide intoxication, transport of noradrenaline across the plasma membrane is known to be driven by the noradrenaline carrier (uptake1) working in reverse of its normal direction--from inside to outside. Consequently, inhibitors of the noradrenaline carrier like desipramine were shown to suppress nonexocytotic noradrenaline release in ischemia and cyanide intoxication.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Propranolol inhibits nonexocytotic noradrenaline release in myocardial ischemia. 231 83

To elucidate the role played by catecholamines in the early phase of ischemic derangement of the myocardial energy metabolism, effects of beta-blockers (propranolol, pindolol, and celiprolol) and isoproterenol, and of pretreatment with reserpine and 6-hydroxydopamine (6-OHDA), were studied using the isolated perfused rat heart. beta-Blockers and isoproterenol were infused for 12 min prior to induction of global ischemia. The myocardial energy consumption rate was assessed by calculating the product of left ventricular pressure and heart rate (LVP x HR). The myocardial cell creatine phosphate (CP), ATP and pH were determined with 31P nuclear magnetic resonance (31P-NMR). Global ischemia induced by cross-clamping of the aortic inflow line for 15 min resulted in falls in CP, ATP, and pH. Propranolol (6 x 10(-8) and 1.8 x 10(-7) mol/min) and pindolol (6 x 10(-7) mol/min) produced a decrease in LVP x HR and suppressed the pH fall during ischemia. Celiprolol was without significant effects on these two parameters. Isoproterenol (6 x 10(-12) mol/min) produced an increase in LVP x HR and tended to accelerate the pH fall. Catecholamine depletion with reserpine or 6-OHDA produced no beneficial effects on the pH fall. It was concluded that the beneficial effects of beta-blockers on the pH fall during early ischemia were not due to the specific beta-blocking action but to the nonspecific cardiodepressant effects of these compounds.
...
PMID:Effects of beta-blockers on the fall of pH in the early phase of ischemia in the isolated perfused rat heart: a nuclear magnetic resonance study. 245 26

Nicorandil was compared with placebo, propranolol and low and high doses of diltiazem therapy in 12 patients with chronic stable angina pectoris to elucidate its antianginal mechanism. A computer-assisted treadmill exercise test was performed after administration of either placebo, 30 mg of nicorandil, 40 mg of propranolol, or low-dose 60 and high-dose 120 mg of diltiazem. Exercise duration and time to the onset of ischemia were significantly increased after each drug administration and there was no significant difference in the percent increase in exercise duration between nicorandil (44 +/- 7%), propranolol (47 +/- 11%) and high-dose diltiazem (39 +/- 5%) compared with placebo. Nicorandil increased exercise duration in patients with 1-vessel disease more effectively (7.5 +/- 0.7 minutes, p less than 0.05) than either propranolol or low-dose diltiazem (6.7 +/- 0.7, 6.1 +/- 0.9 minutes, respectively). The decrease in blood pressure obtained with nicorandil was approximately the same as that with diltiazem. Nicorandil increased exercise duration associated with higher peak double product compared with low-dose diltiazem. In contrast, high-dose diltiazem increased exercise duration at the same double product as low-dose diltiazem. Propranolol increased exercise duration at a lower level of peak double product. Because our previous study demonstrated that low-dose diltiazem yielded a plasma concentration high enough to reduce coronary tone, it appears unlikely that nicorandil will reduce coronary tone further and subsequently increased coronary reserve. Therefore, left ventricular preload reduction may be the mechanism responsible for higher values of double product obtained with nicorandil.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Comparison of antianginal activity of nicorandil, propranolol and diltiazem with reference to the antianginal mechanism. 252 30

Celiprolol, propranolol or saline were administered to separate groups (n = 5-6) of anesthetized dogs in which a critical stenosis was applied to the circumflex coronary artery for 90 min and then reperfused for 30 min. Test drugs were administered at 30 min poststenosis and the effects on pH, regional function and endocardiogram were monitored. A reduction in coronary flow of 54 +/- 2% (n = 27) yielded marked increases in hydrogen ion concentration (H+) of 17 +/- 2 X 10(-8) and ischemic endocardial ST segment of 6 +/- 1 mV while ischemic segmental shortening decreased 75 +/- 9%. Heart rate, arterial pressure and normal regional function were not altered. Celiprolol 0.1 and 1 mg/kg, i.v., reversed the alterations in H+ and ischemic ST segment to prestenosis values while improving ischemic segmental shortening 20 and 38%, respectively, and not affecting heart rate. Propranolol 0.1 and 1 mg/kg, i.v., reversed the alterations in H+ and ischemic ST segment to prestenosis values while further decreasing ischemic segmental shortening 66 and 30%, respectively. Upon reperfusion, ischemic segmental shortening returned to prestenosis values in the group treated with celiprolol 1 mg/kg, i.v., while the propranolol- and saline-treated groups further decreased. It is concluded that celiprolol is efficacious in normalizing myocardial function and ischemia-induced electrophysiological changes following coronary artery stenosis.
...
PMID:Celiprolol, a compound which attenuates myocardial acidosis and improves regional segmental function following ischemia in dogs: a comparison with propranolol. 257 7

In 24 patients with stable spontaneous and effort-related angina, ischemic episodes at rest were not preceded by changes in circulatory variables (heart rate, systemic and pulmonary arterial pressures) that may raise myocardial oxygen consumption. We interpreted these episodes as caused by critical and reversible coronary flow reduction at the site of a stenotic lesion, and evaluated the clinical efficacy of nifedipine and propranolol in the treatment of this condition. Propranolol fully abolished or reduced the number of spontaneous ischemic episodes in a significantly larger number of patients than did nifedipine; it was also effective in several cases in whom nifedipine had failed or had even caused a paradoxic effect. Quantitative angiographic evaluation of the influence of nifedipine (Group 1, 12 patients, 10 mg sublingually) and propranolol (Group 2, 12 patients, 0.1 mg/kg intravenously) on the residual lumen diameter of 1 significant coronary stenosis in each patient showed that after nifedipine, the lumen was unchanged in 1, augmented in 7, and reduced in 4 cases; variations ranged between +1.59 and -1.2 mm, and their direction correlated closely with the influence of oral nifedipine on the episodes of spontaneous ischemia; and in no case did treatment with propranolol vary the stenosis lumen by more than 0.3mm. In this form of angina, a number of lesions seem to offer a compliant substrate for vasomotion and, possibly, for critical changes in flow. The vasomotor influences of nifedipine on these lesions are variable as well as the efficacy of the drug on the manifestations of ischemia at rest.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:[Greater efficacy of propranolol versus nifedipine in angina with 2 components, that results in varying influence on coronary vasomotility]. 260 73

In myocardial necrosis produced by isoproterenol (beta-adrenergic agonist) marked increase in creatine phosphokinase, phospholipase and significant decrease in cardiac glycogen and phospholipid levels were observed. The enhanced levels of lipid peroxides, xanthine oxidase activity and lowering of superoxide dismutase may lead to excessive formation of free radicals resulting in cardiac cell damage. Nifedipine--a calcium antagonist, Propranolol--a beta-blocker and guggulsterone a lipid lowering agent showed marked reversal of these metabolic changes related to ischemia induced by isoproterenol.
...
PMID:Reversal of changes of lipid peroxide, xanthine oxidase and superoxide dismutase by cardio-protective drugs in isoproterenol induced myocardial necrosis in rats. 263 88

A placebo-controlled, double-blind, crossover study was conducted to determine the effects of nifedipine (60 to 90 mg per day) monotherapy and propranolol (240 mg per day) monotherapy on symptoms, angina threshold, and cardiac function in patients with chronic stable angina. Following a two-week placebo period, patients were randomly assigned to receive either nifedipine or propranolol for a five-week treatment period, after which they crossed over to the alternative regimen. All 21 patients were men with chronic stable angina pectoris, 13 of whom had symptoms both at rest and on exertion. New York Heart Association functional class improved in patients taking either nifedipine or propranolol, and nitroglycerin consumption decreased with both treatments compared with placebo. Nifedipine significantly delayed the onset of chest pain and 1 mm of ST-segment depression during bicycle exercise; increases with propranolol were smaller and not statistically significant. Nine patients had a preferential clinical response to nifedipine compared with six patients to propranolol; this was unrelated to the presence or absence of pain at rest or to any baseline hemodynamic finding. Nifedipine and propranolol were equally effective in relieving exertional ischemia as shown by improvement in radionuclide ejection fraction at identical work loads. Exercise wall motion, assessed by a semiquantitative wall motion score, also improved with both drugs. Propranolol treatment decreased exercise cardiac output by 14 percent (p = 0.01) through its effect on heart rate. In contrast, nifedipine treatment had no effect on cardiac output. Thus, nifedipine is more effective on several measurements than propranolol when administered as single drug therapy in stable angina and has the advantage of preserving cardiac output during exercise.
...
PMID:Chronic stable angina monotherapy. Nifedipine versus propranolol. 264 28

The influence of cold on the threshold for myocardial ischemia and the efficacy of antianginal drugs in a cold environment were assessed in 24 patients with stable angina and exercise-induced ST depression. Treadmill exercise tests were done according to a randomized double-blind protocol 90 minutes after administration of placebo, 80 mg propranolol, or 120 mg diltiazem, each at both -8 degrees and 20 degrees C. Eight of the patients were classified by history as cold-sensitive before the study. For the entire group, none of the exercise end points differed significantly between cold and normal temperatures with placebo. However, cold-sensitive patients developed 1 mm ST depression 30% sooner (169 +/- 41 versus 244 +/- 38 seconds, p less than 0.01) at -8 degrees C compared with 20 degrees C. At the onset of ischemia, rate-pressure product was lower in the cold (19.8 +/- 1.0 versus 22.0 +/- 1.6 x 10(-3), p less than 0.05). Both propranolol and diltiazem prolonged time to onset of 1 mm ST depression at both temperatures. The magnitude of improvement at -8 degrees C was equal to that at 20 degrees C, and differences between the two drugs were not statistically significant. Only diltiazem prolonged total exercise duration. Thus, as assessed by exercise testing, cold does not worsen ischemic threshold in most stable angina patients. However, in a subgroup identifiable by history, ischemic threshold is lower in the cold. Propranolol and diltiazem are as effective for exercise-induced ischemia in a cold environment as at normal temperatures.
...
PMID:Exercise-induced myocardial ischemia in a cold environment. Effect of antianginal medications. 271 70

The effect of propranolol on the accumulation of non-esterified fatty acids (NEFA) in the isolated, perfused working rat heart was investigated. Ischemia was induced by lowering the afterload pressure to 0 mm Hg for 20 min and for reperfusion, the pressure was raised to the pre-ischemic pressure (60 mm Hg) for 20 min. The heart was frozen for biochemical studies immediately after ischemia or reperfusion. Ischemia decreased mechanical function, increased the levels of palmitoleic, arachidonic and linoleic acids, left oleic, lauric, myristic, palmitic and stearic acids unchanged, decreased the levels of adenosine triphosphate (ATP), creatine phosphate (CrP) and the energy charge potential (ECP), and increased the level of lactate. Propranolol (10(-5) or 3 x 10(-5) M) restored mechanical function and inhibited the changes in NEFA, ATP and ECP caused by ischemia. It is suggested that propranolol inhibits the decrease in mechanical function and high energy phosphates caused by ischemia, and thereby inhibits the accumulation of NEFA, especially of the unsaturated fatty acids such as arachidonic acid, during ischemia.
...
PMID:Effect of propranolol on accumulation of NEFA in the ischemic perfused rat heart. 271 64

To determine specificity of rodent models of arrhythmia for different Vaughan Williams classes of antiarrhythmic drugs, we tested 17 drugs from the four classes in one in vitro and four in vivo models. In the mouse chloroform-induced ventricular fibrillation model and in the guinea pig ouabain-induced arrhythmia model, drugs of classes I (amefalone, aprindine, lidocaine, mexiletine, phenytoin, procainamide, or quinidine), II (metoprolol or propranolol), and IV (bepridil) were active. Class III drugs (bretylium, clofilium, or melperone did not suppress ouabain arrhythmias, but were active in the mouse chloroform model. In the rat coronary artery ligation model, disopyramide (class I), amefalone and melperone significantly (P less than 0.05) reduced the number of extrasystoles. Propranolol, sotalol, and verapamil (class IV) were less effective. In the rat coronary artery ligation/reperfusion model, all four classes of antiarrhythmic agents were active in vitro (isolated heart) and in vivo (anesthetized rat). Thus, one model of automaticity, the guinea pig ouabain model, detected class I, II, and IV drugs, whereas another automaticity model, the mouse chloroform model, also detected class III agents. The model of reentry induced by ischemia plus reperfusion (rat coronary artery ligation reperfusion) can be recommended as a screen for new antiarrhythmic agents based on its sensitivity to all four classes of antiarrhythmic drugs. The Vaughan Williams class of an antiarrhythmic agent must be determined, however, by additional mechanism studies.
...
PMID:Broad sensitivity of rodent arrhythmia models to class I, II, III, and IV antiarrhythmic agents. 272 85


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

---