UMLS:C0022116 - FACTA Search

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)

Nicorandil is a potent coronary vasodilator. To assess its long-term antianginal effect, we designed a randomized, parallel double-blind trial of 6 weeks' duration comparing nicorandil (10 or 20 mg b.i.d.) with propranolol (40 or 80 mg t.i.d.). The study comprised 77 men with stable angina, no maintenance medication at entry, and an exercise test positive for angina and ST-segment depression. The therapy was started with 10 mg nicorandil b.i.d. or 40 mg propranolol t.i.d. After 3 weeks, the dosage could be doubled according to clinical criteria. Four men receiving nicorandil and one receiving propranolol were withdrawn with side effects; in three cases, the data were not complete. Thus, comparative data were obtained in 69 patients; in 51 of these (26 receiving nicorandil and 25 receiving propranolol), the dosage was increased to the higher level. Blood pressure and heart rate were unaltered by nicorandil and lowered by propranolol. The number of anginal attacks decreased relative to baseline on nicorandil and propranolol (p < 0.002), but total exercise duration was not influenced by either drug. The exercise test performed 2 h after either pill ingestion showed a decrease and a delay in occurrence of myocardial ischemia. The test performed 12 h after medication exhibited reduced ischemia, whereas only propranolol resulted in delayed ST-segment depression. The double product of heart rate and systolic blood pressure was affected only slightly by nicorandil and reduced significantly by propranolol (p < 0.001). Thus, nicorandil medication affords similar improvement as propranolol in patients with angina pectoris, but the mode of action appears to be different.
...
PMID:Efficacy of nicorandil versus propranolol in mild stable angina pectoris of effort: a long-term, double-blind, randomized study. 128 78

The potassium channel activator nicorandil, under evaluation for antianginal management, has been shown to decrease neutrophil respiratory burst. Since our laboratory has demonstrated that reactive oxygen species (ROS) increase tumor necrosis factor (TNF) production, we hypothesized that nicorandil might decrease TNF production from a lipopolysaccharide (LPS) challenge via reduction of respiratory burst. Macrophage viability and TNF production were determined after an 18-hr exposure to 5.0 micrograms/ml LPS and varying concentrations of nicorandil. Nicorandil was not toxic to macrophages below 12 mM (94 +/- 3% viability versus control) and decreased ROS and TNF production. Intracellular superoxide production decreased from 164 +/- 24 OD550 to 99 +/- 6 OD550 with 10 mM nicorandil and extracellular superoxide decreased from 3108 +/- 111 to 1760 +/- 210 nM. Hydrogen peroxide production was also decreased by 10 mM nicorandil. TNF production in response to 5 micrograms/ml LPS decreased from 6.8 +/- 0.6 to 2.7 +/- 0.4 ng/ml with 10 mM nicorandil. Northern and slot blot analyses demonstrate that nicorandil acts at a post-transcriptional site. These data imply that nicorandil decreases macrophage TNF production from an LPS challenge, possibly through a reduction in respiratory burst. Such compounds may prove useful in the treatment of conditions thought to be associated with free radical-lymphokine interactions such as ischemia-reperfusion injury, oxygen toxicity, adult respiratory distress syndrome, and septic shock.
...
PMID:Alterations in macrophage free radical and tumor necrosis factor production by a potassium channel activator. 153 87

We determined whether any of the antiischemic effects of nicorandil were due to direct cardioprotective effects such as potassium channel activation or to its peripheral hemodynamic effects. Nicorandil was administered either intravenously (i.v.) or directly into the ischemic coronary artery (i.c.) and compared with i.c. cromakalim (a potassium channel activator previously shown to improve reperfusion function directly in rat hearts) or vehicle for their ability to improve postischemic contractile function as measured by ultrasonic crystals in anesthetized dogs or in isolated perfused rat hearts. In a model of 25-min global ischemia and reperfusion in isolated perfused rat hearts, nicorandil (10-100 microM) did not improve reperfusion function or decrease LDH release, although 300 microM nicorandil did protect the hearts. Cromakalim (7 microM) significantly improved reperfusion function and reduced lactate dehydrogenase (LDH) release. In the dog studies, the left anterior descending coronary artery (LAD) was occluded for 15 min and was reperfused for 3 h. Nicorandil improved reperfusion function only when administered i.v., although i.c. cromakalim was efficacious in improving function. Neither nicorandil nor cromakalim improved collateral flow, although cromakalim significantly improved preischemic and reperfusion blood flows, particularly in the subepicardial region. Although i.c. treatment with cromakalim and nicorandil did not result in significant changes in peripheral hemodynamic status, i.v. nicorandil reduced both preload and afterload. Thus, at the dose used, nicorandil does not appear to have direct myocardial protective effects and the beneficial effects of nicorandil do not appear to be related to potassium channel activation in the myocardium. Potassium channel activation by cromakalim does result in direct cardioprotective effects whereas nicorandil appears to be dependent on peripheral actions for its efficacy.
...
PMID:Nicorandil improves postischemic contractile function independently of direct myocardial effects. 169 28

We examined influences of a blocker (glibenclamide) and an opener (nicorandil) of the ATP-sensitive potassium (KATP) channel on extracellular K concentration [( K+]e), as well as the myocardial function and metabolites during global ischemia and reperfusion in Langendorff-perfused rat heart preparation. In control hearts, [K+]e began to rise 20 s after the onset of ischemia up to an initial peak (8.3 +/- 0.3 mM) at 2.5 +/- 0.7 min, then fell to 6.0 +/- 0.8 mM after 8.2 +/- 0.7 min, and then rose progressively to 14.6 +/- 0.8 mM at the end of 30 min of ischemia. Glibenclamide (50 microM) reduced the initial peak of [K+]e to 7.2 +/- 0.3 mM (P less than 0.01), and nicorandil (200 microM) increased it to 9.4 +/- 0.6 mM (P less than 0.01). There were no significant differences in [K+]e values among all groups at the end of ischemia. During ischemia, nicorandil decreased the time to mechanical arrest from 1.9 +/- 0.1 min to 1.5 +/- 0.1 min, whereas it was increased by glibenclamide to 2.7 +/- 0.4 min. In control hearts, the time to onset of ischemic contracture was 14.7 +/- 1.8 min. Nicorandil delayed onset of contracture and glibenclamide accelerated it. Thus we have confirmed that some part of the early increase in [K+]e during ischemia is attributable to K+ efflux through the KATP channel in our model, and opening of the KATP channel may contribute to a rapid reduction of the contractility of the ischemic myocardium that subsequently protects the myocardium against further ischemic injury.
...
PMID:Effects of glibenclamide and nicorandil on cardiac function during ischemia and reperfusion in isolated perfused rat hearts. 183 11

In this study, we evaluated the postischemic myocardial tissue blood flow, specific enzymes, and functional recovery infused with a Nicorandil vasodilator-magnesium solution (Nico.: 8 mg/L, Mg: 20 mEq/L) given just prior to reperfusion (Terminal Cardioplegia, TCP). 27 patients undergoing valve replacement were divided into two groups; the hearts of group non-TCP (nTCP) (n = 15) were reperfused after ischemia without TCP, and in the other hearts of group TCP (n = 12), TCP was given for 2 min prior to reperfusion. During the reperfusion period, myocardial tissue blood flow (TBF) on the anterior wall of left ventricle were monitored by a laser blood flow-meter. Thereafter, serum CK-MB levels, MM3/MM1 values by CK-MM subbands (MM1, MM2, MM3) levels and LVSWI were measured until 24 hours after surgery. At 5 and 10 min of reperfusion, Group TCP had a significantly greater TBF than Group nTCP (5 min; G-TCP: 69.9 +/- 19.0 ml/100 g.min, G-nTCP: 47.5 +/- 20.9, p less than 0.05, 10 min; G-TCP: 74.9 +/- 22.8, G-nTCP: 56.1 +/- 23.4, p less than 0.05). At 3 hrs after surgery, an increase of MM3/MM1 values was significantly suppressed in Group TCP compared to Group nTCP (G-TCP: 2.6 +/- 0.6, G-nTCP: 3.4 +/- 1.0, p less than 0.05). Also, Group TCP had better recovery of LVSWI. These results indicate that the TCP might reduce the postischemic reperfusion injury by the improvement of myocardial TBF and metabolism.
...
PMID:[Preventive effect of post-ischemic reperfusion injury by terminal Nicorandil-Mg cardioplegia]. 183

Nicorandil and cromakalim relaxed rat aortic rings denuded of endothelium and precontracted with a low concentration of KCl (25 mM). Glibenclamide (1 microM) strongly antagonized only the effects of cromakalim while those of nicorandil were inhibited by methylene blue, an inhibitor of the soluble form of guanylate cyclase. High concentrations of nicorandil also produced vasorelaxation in aortic preparations contracted with 55 mM KCl, whereas cromakalim did not. In pentobarbital-anesthetized rats a 20-min i.v. infusion of cromakalim (5 micrograms/kg/min) or nicorandil (100 micrograms/kg/min) similarly decreased the mean carotid artery blood pressure. These effects, as well as the antihypertensive activity of nicorandil (5.0 mg/kg p.o.) and cromakalim (0.25 mg/kg p.o.) in spontaneously hypertensive rats were markedly inhibited by glibenclamide (20 mg/kg i.v.). Finally, glibenclamide (4 mg/kg i.v.) displaced to the right the control dose-coronary vasodilatory response curve to nicorandil injected into the left circumflex coronary artery of pentobarbital-anesthetized dogs. In conclusion, these results indicate that in a rat conductive vessel (aorta) nicorandil acts exclusively like nitrates, that is, it stimulates guanylate cyclase, and in resistance vessels (in the intact rat or dog coronary vascular bed) it opens K+ channels, as does cromakalim. Thus, nicorandil can be expected to have a broader spectrum of antianginal activity than drugs with a single mechanism of action. Additionally, as mentioned in the discussion section, substantial evidence exists that K+ channel opening can also afford marked cardioprotection against ischemia.
...
PMID:K+ channel opening mediates the vasorelaxant effects of nicorandil in the intact vascular system. 183 48

In this study, we evaluated the preventive effect of post-ischemic reperfusion injury by Nicorandil-Mg cardioplegia (Nic: 8 mg/l, Mg: 20 mEq/l) given just prior to reperfusion as "terminal cardioplegia". Nineteen dogs were placed on cardiopulmonary bypass and the aorta was cross-clamped for 90 min under hypothermic (17-19 degrees C) cardioplegic arrest. The hearts of ten dogs were reperfused without terminal cardioplegia (Group A). In the other nine dogs, terminal cardioplegia was given for 2 min prior to reperfusion (Group B). During and after a period of ischemia, myocardial tissue calcium ion (t-Ca) and PCO2 (t-PCO2) were continuously monitored by ISFET (ion sensitive filed effective transistor) sensor. Myocardial tissue blood flow, oxygen consumption and lactate flux were calculated at 5, 10, 20, 40 min of reperfusion. And myocardial function was evaluated at 45 min of reperfusion. In the initial reperfusion period, Group B showed an improved myocardial tissue blood flow compared to group A (at 5 min of reperfusion in group A: 29.4% of control, in group B: 42.7% of control, p less than 0.025). T-Ca and T-PCO2 in Group B were rapidly and significantly decreased at 5 min of reperfusion (t-Ca in group A: 2.8 +/- 0.5 mM----1.7 +/- 0.5 mM, in group B: 3.1 +/- 0.6----1.2 +/- 0.4, p less than 0.05; t-PCO2 in group A: 117.5 +/- 23.0 mmHg----82.5 +/- 17.4 mmHg, in group B: 127.5 +/- 22.5----42.5 +/- 9.7, p less than 0.001), and group B had better metablic recovery evaluated by myocardial oxygen consumption and lactate flux.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:[Preventive effect of post-ischemic reperfusion injury by terminal Nicorandil-Mg cardioplegia]. 214 Aug 50

We examined the effect of nicorandil and nipradilol on the ischemic myocardium in the isolated perfused rat heart. The heart was perfused by the working heart technique with an afterload pressure of 60 mm Hg and with a left atrial filling pressure of 9 mm Hg. Ischemia was induced for 20 min by lowering the afterload pressure. The afterload pressure was raised to 60 mm Hg again during reperfusion. Ischemia decreased the pressure-rate product, coronary flow, adenosine triphosphate level and creatine phosphate level, and increased the lactate level. Reperfusion could not restore the pressure-rate product nor the adenosine triphosphate level completely. Nicorandil (5 x 10(-5) and 1.5 x 10(-4) M) or nipradilol (10(-5), 5 x 10(-5) and 1.5 x 10(-4) M) was introduced 5 min before ischemia. Nipradilol preserved the levels of adenosine triphosphate and creatine phosphate after 20 min of ischemia and increased the extent of recovery of the pressure-rate product during reperfusion, whereas nicorandil did not. Nipradilol, but not nicorandil, can protect the myocardium against ischemic damage.
...
PMID:Effects of nicorandil and nipradilol on ischemic myocardium in perfused rat heart. 252 96

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

The potential pro- and antiarrhythmic effects of nicorandil (1-100 microM) were assessed in isolated rat hearts subjected to coronary artery ligation and reperfusion under conditions of normal (5.9 mM) and lowered (3.2 mM) perfusate K+. Nicorandil dose dependently increased coronary flow, induced a moderate negative inotropic effect but had no chronotropic effects. During ligation (15 min), only high concentrations of nicorandil (50 and 100 microM) significantly reduced the incidence of ventricular premature beats and ventricular tachycardia in normal perfusate, but ventricular fibrillation was observed in 2/9 hearts. No antiarrhythmic effects were observed with hypokalemic conditions. During reperfusion, nicorandil was associated with a more rapid degeneration into ventricular fibrillation in normal perfusate while the incidence of ventricular fibrillation was only reduced by 100 microM nicorandil. No antiarrhythmic effects were observed during reperfusion with lowered K+ and all drug-treated hearts demonstrated irreversible ventricular fibrillation. Nicorandil perfusion (50 microM; 5.9 mM K+) did not affect the depression of ATP or elevation of lactate within the ischemic tissue during coronary artery ligation. These data do not support an effect of nicorandil against ischemia- or reperfusion-induced arrhythmias in the intact heart in vitro and may suggest a proarrhythmic effect particularly at lowered K+ concentrations.
...
PMID:Assessment of the antiarrhythmic activity of nicorandil during myocardial ischemia and reperfusion. 252 21

1 2 3 4 5 6 7 Next >>