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)

An ATP-sparing effect has been demonstrated for a number of calcium antagonists. Nifedipine probably has a similar action, but data supporting this view are limited. Therefore we decided to study the effect of nifedipine on high-energy phosphate (and carbohydrate) metabolism in the ischemic rat heart. Langendorff preparations were made ischemic for less than 15 min. The reduction in coronary flow was 60 or 70%. Apex displacement during ischemia, a measure of contractility, was comparable for nifedipine-treated and untreated hearts. Ischemia caused a considerable release of the AMP catabolites adenosine, inosine and (hypo)xanthine, and of lactate. Nifedipine (10-100 micrograms/l) prevented this in a dose-dependent way. The highest dose reduced the release of purines and lactate by 90% (P less than 0.01) and 60% (P less than 0.001), respectively. The drug acted in a similar way during reperfusion. Due to ischemia, the adenylate energy charge (ATP + 0.5 ADP)/(ATP + ADP + AMP), decreased 15% (P less than 0.001); nifedipine at a concentration of 100 micrograms/l prevented this decrease (P less than 0.05). We conclude that nifedipine exerts a beneficial effect on myocardial adenine nucleotide metabolism during ischemia and reperfusion.
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PMID:Nifedipine reduces adenine nucleotide breakdown in ischemic rat heart. 711 72

Myocardial 45Ca sequestration was studied in dogs after an injection of 45CaCl2 during 60 minutes of global ischemia and 30 minutes of reperfusion using cardiopulmonary bypass (CPB) at 32 degrees C. Group I (n = 10) received a standard hyperkalemic cardioplegic solution and Group II (n = 10) received the same cardioplegia solution plus nifedipine (100 micrograms/300 cc). After aortic cross-clamping, 300 cc of cardioplegic solution was delivered at 0 and 30 minutes at 4 degrees C. Tissue specific activity (SA = cpm x 10(4)/gm) and plasma specific activity (SA = cpm x 10(4)/ml) were determined before release of the cross-clamp and serially by biopsy during reperfusion. The ratio of tissue SA to plasma SA, termed relative specific activity (RSA), indicates myocardial 45Ca sequestration. Nifedipine led to a marked decrease in sequestration. Group II RSAs were 31.5%, 82.1%, and 39.6% less than Group I RSAs at 0, 20, and 30 minutes of reperfusion. All differences were highly significant (p less than 0.01). During the first 20 minutes of reperfusion, the Group I RSA increased 498% while the Group II RSA increased only 23.8%. A correlation is shown between the decreased calcium sequestration and improved myocardial performance after CPB, demonstrated in previous experiments using nifedipine. Nifedipine in combination with a hypothermic hyperkalemic cardioplegic solution effectively controls myocardial calcium sequestration during 60 minutes of ischemia arrest and the immediate 30 minutes of reperfusion.
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PMID:The control of myocardial Ca++ sequestration with nifedipine cardioplegia. 713 7

Effects of two dihydropyridine calcium antagonists on regional myocardial blood flow produced by acute ligation of the left anterior descending coronary artery were examined in the pentobarbital-anesthetized open-chest dog. Equivalent hypotensive doses of nifedipine (1.25 and 2.5 microgram/kg/min) and FR 7534 (5 and 10 micrograms/kg/min) produced similar decreases in mean arterial pressure and myocardial oxygen consumption and increases in coronary blood flow, dp/dt and contractile force in the intact nonischemic dog heart. Heart rate was unaffected. Nifedipine was 4 times as potent as FR 7534. Effects on ischemic myocardial blood flow measured with radioactive microspheres were examined with the same doses and also at controlled mean arterial pressure by use of methoxamine. Despite significant hypotension, nifedipine maintained and FR 7534 increased ischemic blood flow. When perfusion pressure was controlled, both compounds produced significant increases in transmural blood flow to the ischemic region. The increase produced by FR 7534 was significantly greater. Both nifedipine and, to a lesser extent, FR 7534 decreased the subendocardial to subepicardial blood flow ratio in the nonischemic myocardium without altering that of the ischemic myocardium. Drug-induced increases in ischemic blood flow were positively correlated with initial flow rate. The results indicate that both dihydropyridine calcium antagonists are capable of improving the oxygen supply-demand relationship during ischemia by reducing overall myocardial oxygen demand by increasing collateral blood flow.
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PMID:Comparison of two dihydropyridine calcium antagonists on coronary collateral blood flow in acute myocardial ischemia. 720 54

Nifedipine has been suggested to have more potent slow channel blocking action than other agents of this type. However, its use in the treatment of cardiac arrhythmias has been limited. Electrophysiologic studies on AV conduction have shown that nifedipine lacks any significant effect. However, the action of the drug on intraventricular conduction has not been investigated with regard to its potential in the treatment of ventricular arrhythmias especially during ischemia. Therefore, the effects of nifedipine on conduction delay during ischemia and reperfusion were assessed in the present study. Sixteen dogs (eight control and eight nifedipine-treated dogs) were used. Transmural electrodes were positioned in normal, ischemic, and reperfused tissue, and at the border of these segments. The left anterior descending artery was initially ligated below the second diagonal branch (first ligation) and 30 minutes later below the first diagonal branch (second ligation); the second ligation was released 30 minutes later. Conduction of electrically induced premature impulses from the midwall of the left ventricle was recorded at epicardial and endocardial sites. Conduction delay was measured from the stimulus artifact to the first high-frequency deflection in each zone in the anterograde (base to apex) and retrograde (apex to base) directions. Intravenous nifedipine 0.1 mg/kg was given over 10 minutes immediately after the first ligation. Nifedipine slightly decreased the magnitude of conduction delay in the ischemic myocardium at 15 minutes of ischemia, which corresponded with the peak plasma nifedipine level. However, conduction delay throughout the remainder of the study was essentially unaltered by nifedipine. In conclusion, though nifedipine may improve ischemic myocardial metabolism, infarct size, and hemodynamics, the effect on the electrophysiologic parameters affecting conduction was insignificant. This lack of any further deterioration in conduction in the ischemic and reperfused tissue by the drug further attests to its safety during acute myocardial ischemia.
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PMID:Effects of nifedipine on conduction delay during ventricular myocardial ischemia and reperfusion. 724 12

The effectiveness of nifedipine in treating angina pectoris at rest was evaluated in 14 patients with frequent ischemic episodes associated with S-T segment elevation or depression. The trial consisted of (1) a 48 hour control period; (2) a placebo period and a period of treatment with nifedipine of 48 hours each; and (3) a second placebo period and a second period of treatment with nifedipine of 24 hours each. The efficacy of treatment was evaluated by continuous electrocardiographic recording to detect painless ischemic episodes. During coronary angiography coronary spasm was demonstrated in five patients. The ergonovine maleate test was positive in seven of eight patients. No statistically significant difference was found in the mean daily number of ischemic episodes between the control period and the first placebo period, or between the control and the second placebo periods. Nifedipine produced a highly significant reduction in the mean daily number of episodes compared with the response to placebo during the first as well as the second period. Nifedipine is effective in angina at rest caused by coronary arterial spasm. The prevention of ischemia may be related to the ability of nifedipine to decrease calcium-dependent coronary muscle tone and to prevent coronary spasm.
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PMID:Treatment of angina at rest with nifedipine: a short-term controlled study. 736 74

We compared two newer dihydropyridine-calcium antagonists (lacidipine and nisoldipine) with the classic prototype of this group, nifedipine, in the rat working heart preparation. The hearts were paced at a frequency of 5 Hz and perfused with Tyrode's solution of 37 degrees C. The following five parameters were determined: left ventricular pressure (LVP), maximal rate of pressure increase (+dP/dtmax), aortic output (AO), coronary blood flow (CBF), and cardiac output (CO). First, dose-response curves were constructed; from these data the EC50 concentration for the three calcium antagonists was calculated. Subsequently, washout from the cardiac tissue for these three compounds was determined. The effects of lacidipine did not diminish during < or = 90-min washout, whereas the effects of nifedipine disappeared completely in 10 min. The effects of nisoldipine, however, disappeared partly in 10 min. In separate experiments, the antiischemic activity of the three calcium antagonists was analyzed, using low-flow ischemia. The calcium antagonists were used in a concentration that produced a 60% reduction in contractile force (EC60). Nifedipine and nisoldipine caused significant improvement in functional recovery. The antiischemic properties of lacidipine could not be shown because of its slow kinetic properties with accumulation in the membrane phase and slow kinetics with the channel. Nisoldipine and lacidipine appear to be more potent calcium antagonists as compared with nifedipine, whereas lacidipine displays a clearly different kinetic pattern in comparison to nifedipine and nisoldipine. In particular, the extremely slow onset and very long duration of action of lacidipine are of interest.
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PMID:Hemodynamic and antiischemic effects of nifedipine, lacidipine, and nisoldipine in rat isolated working heart. 750 27

Cardiac ischemia can be provoked by different methods in animal models and in isolated organs. Accordingly, three different procedures were followed to find the most sensitive model for the analysis of the anti-ischemic activity of calcium antagonists. The experiments were performed in the isolated working heart preparation of the rat, paced at the frequency of 5 Hz and perfused with Tyrode solution at 37 degrees C. Global ischemia was achieved by closing off the supply of the perfusion medium and surrounding the heart with Tyrode solution of 37 degrees C gassed with N2; low-flow ischemia was achieved by reducing the cardiac afterload from 51.5 to 11.0 mm Hg; ligation of the left descending coronary artery was performed in order to provoke regional ischemia. Nifedipine was applied in a concentration (EC50) known to reduce the contractile force by one-half of its basal value. The following parameters were determined after 15 min of nifedipine pretreatment and at the end of the experiment: LVP (left ventricular pressure),+dP/dtmax (LVP's first derivative), AO (aortic output), CF (coronary flow), and CO (cardiac output). From the data obtained, the percentages of recovery were calculated. Nifedipine caused a significant improvement in the functional recovery of most of the parameters studied. This improvement, however, was much more pronounced in the model of the low-flow ischemia, which is obviously more sensitive to the anti-ischemic activity of calcium antagonists than the other experimental procedures studied. Low-flow ischemia appears to be preferable to other procedures for the screening of the potential anti-ischemic activity of calcium antagonists and other drugs.
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PMID:Cardioprotection by nifedipine in isolated working hearts: a comparative study on three different types of experimental ischemia. 767 82

Non-competitive N-methyl-D-aspartate receptor antagonists, including phencyclidine, ketamine, and MK801, produce vacuoles and induce the hsp 70 stress gene in layer III pyramidal neurons of the rat cingulate cortex. This study shows that phencyclidine (50 mg/kg) induces hsp 70 messenger RNA and HSP70 stress protein primarily in pyramidal neurons in posterior cingulate and retrosplenial cortex, neocortex, insular cortex, piriform cortex, hippocampus, and in the basal nuclei of the amygdala. Several neurotransmitter receptor antagonists inhibited induction of HSP70 produced by phencyclidine (50 mg/kg): haloperidol (ED50 = 0.8 mg/kg), clozapine (ED50 = 1 mg/kg), valium (ED50 = 1 mg/kg), SCH 23390 (ED50 = 7 mg/kg) and muscimol (ED50 = 3 mg/kg). Baclofen had no effect. Nifedipine blocked the induction of HSP70 produced by phencyclidine in some regions (cingulate, neocortex, insular cortex) but only partially blocked HSP70 induction in other regions (piriform cortex, amygdala). These results suggest that phencyclidine injuries pyramidal neurons via dopamine D1, D2, D4, sigma and other receptors. Several factors appear to contribute to this unusual multi-receptor mediated injury. (1) Phencyclidine blocks N-methyl-D-aspartate receptors on GABAergic interneurons resulting in decreased inhibition of pyramidal neurons. This may help to explain why multiple excitatory receptors mediate the injury and why GABAA agonists decrease the injury produced by phencyclidine. (2) Phencyclidine blockade of an amine transporter helps explain why dopamine receptor antagonists ameliorate injury. (3) Phencyclidine depolarizes neurons and produces high, potentially damaging intracellular calcium levels probably by blocking K+ channels that may be linked to sigma receptors. Since nifedipine prevents injury in cingulate, insula, and neocortex, it appears that calcium entry through L-type voltage gated calcium channels plays a role in the pyramidal neuronal injury produced by phencyclidine in these regions. There are similarities between the cingulate neurons injured by phencyclidine and circuits recently hypothesized to explain receptor changes in cingulate gyrus of schizophrenic patients. The present and previous studies also provide approaches for decreasing the clinical side effects of N-methyl-D-aspartate receptor antagonists to facilitate their possible use in the treatment of ischemia and other disorders.
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PMID:Phencyclidine induction of the hsp 70 stress gene in injured pyramidal neurons is mediated via multiple receptors and voltage gated calcium channels. 784 88

The effect of the blockers of calcium channels on the development of myocardial ischaemia in rats with an occlusion of the coronary artery was examined. An occlusion of the coronary artery was carried out in rats anaesthetized with pentobarbital by tightening the ends of the ligature freely placed under the left coronary artery - ramus interventricularis seven days prior to ligation. The ischaemia-induced changes in the R-wave and ST-segment were recorded using ECG. The occlusion of the coronary artery produced arrhythmias, a significant elevation of the ST-segment and a slight increase in the heart rate. The blockers of calcium channels with different pharmacological properties - verapamil, nifedipine and diltiazem influenced the ischaemia-induced changes with different intensity. Nifedipine (0.02 mg.kg-1, i.v., 30 min prior to occlusion), verapamil (0.2 mg.kg-1, i.v., 10 mins prior to ischaemia), and diltiazem (0.3 mg.kg-1, i.v., 10 mins prior to ischemia) significantly reduced the increased elevation of the ST-segment. The highest effect on the above-mentioned model was shown by verapamil.
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PMID:[The effect of calcium channel blockers in experimental myocardial infarct in rats]. 840 64

There are conflicting results concerning the anti-ischemic effect of nifedipine in patients with chronic stable angina. Therefore, the purpose of this study was to assess whether the anti-ischemic effect of nifedipine may be related to coronary collateral circulation. Forty-one patients with stable angina and coronary artery disease were randomized to a parallel double-blind study with nifedipine and metoprolol, and compared for effects on transient ischemic episodes during ambulatory electrocardiographic monitoring and exercise-induced ischemia. The effects were correlated to the presence of collateral circulation. In 17 patients, angiographically poor or no collateral flow was observed (group 1), and 24 had good collateral flow (group 2). Nifedipine was administered to 20 patients (8 in group 1, and 12 in group 2). In group 1, nifedipine reduced the frequency of total and asymptomatic ischemic episodes (p < 0.05), whereas significant increases in both total (p < 0.05) and silent (p < 0.01) ischemia were observed in group 2. Exercise variables were slightly improved (p = NS) during nifedipine therapy in group 1, and slightly worsened (p = NS) in group 2. Reflex tachycardia was not observed at either the onset of transient ischemia out of the hospital or exercise-induced ischemia. This was in contrast with the effect in 21 patients treated with metoprolol (9 in group 1, and 12 in group 2) where significant reductions were observed in the frequency of both total (p < 0.01) and silent (p < 0.01) ischemia in both groups. Furthermore, a beneficial effect was observed on all exercise variables.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transient myocardial ischemia during nifedipine therapy in stable angina pectoris, and its relation to coronary collateral flow and comparison with metoprolol. 842 80


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