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)

During repeat exercise testing in 10 patients with stable angina, individual optimal doses of nicardipine were determined. Hemodynamic values and cardiac metabolism were studied during 2 pacing periods carried out before and after this dose (mean 5.3 mg). Postpacing ST-segment depression diminished (1 mm) after nicardipine administration (p less than 0.05), whereas pacing time to onset of angina did not change. Nicardipine administration increased heart rate 16% (p less than 0.005) and reduced systolic (10%) and diastolic (8%) blood pressures (both p less than 0.005). Coronary blood flow increased 16% (p less than 0.05) and coronary vascular resistance decreased 24% (p less than 0.01). Myocardial oxygen consumption was unchanged despite an 11% decrease in rate-pressure product during pacing (p less than 0.02). In the control state before nicardipine administration, metabolic signs of ischemia included release of lactate across the heart in 7 patients, decreased mean free fatty acid and glutamate uptake and alanine release during pacing, together with increased glucose uptake and citrate release during recovery. After nicardipine lactate release decreased in 5 of the 7 patients, pacing no longer changed free fatty acid, glutamate and alanine uptake/release from the level at rest. During recovery glucose uptake was reduced and citrate release was unaffected. The hemodynamic data indicate that nicardipine is a systemic and coronary vasodilator, increasing oxygen supply to the ischemic myocardium. The metabolic results indicate a change in substrate utilization toward that of normal heart, suggesting improved aerobic energy supply.
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PMID:Metabolic and hemodynamic effects of nicardipine during pacing-induced angina pectoris. 381 68

Using a Langendorff rat heart preparation, we examined effects of nicardipine, a calcium channel blocker, on different stages of ischemic damage, characterized by a development of contracture and leakage of intracellular enzymes. Maximum recoveries of heart rate (HR) and peak left ventricular pressure-HR product after 20 min ischemia were attenuated by about 25% compared with those before ischemia. When nicardipine (0.1 mumol) was added to the perfusate 5 min prior to ischemia, this mechanical failure recovered completely to the pre-ischemic level. Although a significant increase in left ventricular end-diastolic pressure was observed in hearts exposed to 30 min ischemia, the amount of creatine kinase (CK) released during re-flow after 30 min ischemia was not enhanced by contracture but was proportional to the duration of ischemia (compared with that of 20 min ischemia). Nicardipine reduced CK leakage by 25% after 30 min ischemia but did not alter either ATP levels or coronary flow. The beneficial effects of nicardipine on ischemic damage are probably related to inhibition of calcium influx (Terai et al: Biochem Pharmacol 30: 375, 1981), which may accompany reperfusion of ischemic myocardium.
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PMID:Effects of nicardipine on ischemic mechanical failure and tissue injury in isolated perfused rat heart. 408 73

The effects of 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid 3-[2-(N-benzyl-N-methylamino)]ethyl ester 5-methyl ester hydrochloride (nicardipine, YC-93), a new potent calcium antagonistic coronary vasodilator, on coronary circulation and ischemia-induced conduction delay were examined in anesthetized open-chest dogs. Nicardipine increased both the coronary flow and regional myocardial blood flow in the pre-ischemic period in a dose-dependent manner. However, nicardipine in a dose of 30 micrograms/kg, which was sufficient to enhance the coronary circulation almost maximally, failed to reduce the conduction delay produced by coronary occlusion under a constant atrial pacing. A high dose of nicardipine (300 micrograms/kg) enough to exert a slow channel blocking action on the cardiac tissue was required to improve the conduction delay. These results suggest that the coronary vasodilating action of the calcium antagonists is unlikely to play an essential role in reducing the conduction delay in the ischemic myocardium.
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PMID:Effects of nicardipine, a new dihydropyridine vasodilator, on coronary circulation and ischemia-induced conduction delay in dogs. 720 68

To examine the role of calcium influx in the early phase after brief forebrain ischemia and subsequent delayed neuronal cell death in the hippocampus, 45Ca autoradiography and electron microscopic cytochemistry, by a combined oxalate-pyroantimonate method, were carried out in gerbil brains after 5 min bilateral common carotid arterial occlusion. Further, neuronal damage during the ischemic and postischemic periods was determined by conventional or immunohistochemical staining for microtubule-associated protein 2 (MAP2) with and without calcium-entry blockers. 45Ca autoradiography showed a high peak of calcium in the hippocampus at 5 min of recirculation. Electron cytochemical microscopy also demonstrated accumulation of intracellular calcium pyroantimonate deposits in the neuronal cells in all regions. At 30 min of reperfusion, amounts of calcium in the hippocampus returned to the control levels, and intracellular dense calcium pyroantimonate deposits were reduced in these areas. Loss of the reaction for MAP2 was noted in the medial CA1 of the hippocampus immediately after 5 min ischemia and at 5 and 30 min after reperfusion. MK-801 (10 mg kg-1), an N-methyl-D-aspartate (NMDA) receptor antagonist, injected intraperitoneally 1 h before ischemia, suppressed the early increase of calcium in the forebrain and neuronal cell necrosis in the CA1. However, neither injection of MK-801 30 min after reperfusion nor preischemic treatment with 0.5 mg kg-1 Nimodipine or 1 mg kg-1 Nicardipine, voltage-sensitive calcium channel antagonists, prevented neuronal death. In immunohistochemical staining for MAP2, the ischemic lesion in the medial CA1 maintained after 5 min ischemia and the subsequent early reperfusion period in the untreated brains was protected by the preischemic injection of 10 mg kg-1 MK-801, but was not restored by the injection of 0.5 mg kg-1 Nimodipine or 1 mg kg-1 Nicardipine. In conclusion, it is suggested that an early excess of calcium influx could be caused mainly by excitatory amino acid overload through NMDA receptor-mediated calcium channels during the ischemic and early postischemic periods.
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PMID:The role of early Ca2+ influx in the pathogenesis of delayed neuronal death after brief forebrain ischemia in gerbils. 818 66

The effects of pretreatment with nicardipine (dihydropyridine Ca2+ channel antagonist), Bay K8644 (dihydropyridine Ca2+ channel agonist), and MK-801 (N-methyl-D-aspartate-receptor antagonist) on changes of platelet-activating factor (PAF) concentrations in transient ischemic brain are reported. The tissue concentration of PAF increases significantly in hippocampus, cortex and thalamus by 210%, 169% and 168% of controls without ischemia-reperfusion, respectively after 1 h of reperfusion. Nicardipine (5 mg/kg) reduces the accumulation of PAF, the remaining increases in hippocampus, cortex and thalamus being 151%, 138% and 145% of the controls, respectively. In contrast, Bay K8644 (2.5 mg/kg) enhances the accumulation of PAF, its concentrations in hippocampus, cortex and thalamus being 376%, 233% and 204% of the controls, respectively. The Bay K8644 enhancement in hippocampus is completely inhibited by pretreatment of nicardipine (5 mg/kg). MK-801 (10 mg/kg) reduces the accumulation of PAF, the remaining increases in hippocampus, cortex and thalamus being 152%, 147% and 144% of the controls, respectively. Moreover, brain tissue from animals subjected to the combined pretreatment with nicardipine (5 mg/kg) and MK-301 (10 mg/kg) indicates there is greater inhibition of ischemia-induced PAF increases than with either drug alone. These results indicate that PAF production in the ischemic brain may be regulated by Ca2+ influx through voltage-sensitive Ca2+ channels which are antagonized and agonized by nicardipine and Bay K8644, respectively and receptor-operated Ca2+ channels which are antagonized by MK-801. Because it is known that increases of intracellular Ca2+ in the brain accompany ischemia and early periods of reperfusion and that PAF exhibits neurotoxicity, the present findings support the role of PAF as a mediator in ischemia-induced brain damage at early stages of reperfusion.
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PMID:Nicardipine and MK-801 attenuate platelet-activating factor increases following cerebral ischemia-reperfusion in gerbils. 889 3

AGE-RELATED CARDIOVASCULAR CHANGES: Age-related changes in vascular structure and function may contribute to isolated systolic hypertension and target-organ damage. These include cardiac hypertrophy, systolic as well as diastolic dysfunction, congestive heart failure, coronary artery disease, cardiac arrhythmias, cerebrovascular diseases, peripheral vascular diseases and renal insufficiency. POTENTIAL ADVANTAGES OF CALCIUM ANTAGONISTS IN THE ELDERLY: Dihydropyridine calcium anatagonists have been advocated as first choice agents for the treatment of hypertension in the elderly on the grounds that (1) they may be more active in lowering blood pressure because of the predominantly low renin status in elderly hypertensives, (2) they may be better tolerated because side effects related to the activation of the sympathetic system may be less frequent because of attenuation of baroflexes during ageing and (3) they may have beneficial effects on a variety of concomitant cardiovascular diseases which are frequently present in the elderly. These assumptions, however are not always proven in clinical practice. ADVANTAGES OF NICARDIPINE: Additional to its potent vasodilatator action, nicardipine has anti-ischemic effects in both the coronary and the cerebral circulation, including antiplatelet and hemorrheological effects, and protection at ther cellular level against calcium overload and ischemia. The results of a large number of studies in cerebrovascular insufficiency suggest that nicardipine, may favourably affect the cerebral circulation and may improve the patient's cognitive function. Nicardipine may decrease left ventricular mass by about 4-12% and may reduce both the frequency and the severity of arrhythmias. The anti-anginal effects of nicardipine are well established. The drug is also able to decrease the progression of new atherosclerotic lesions in coronary arteries and is consequently potentially beneficial in elderly hypertensives with coronary artery disease. Nicardipine has no clinically significant negative inotropic effect. Nevertheless, in congestive heart failure, the use of calcium antagonists is usually not recommended because of the lack of clinical benefit and of possible harmful effects, including sympathetic and renin-angiotensin system stimulation. Although kidney protection may be provided by a strict and long-term control of blood pressure, the effects of nicardipine on long-term protection of renal function are not clear at present. RECENT CONTROVERSY CONCERNING SHORT-ACTING CALCIUM ANTAGONISTS: Much-debated recent case-control studies suggest that hypertensive patients treated with short-acting calcium antagonists may have an increased incidence of myocardial infarction and possibly of cardiovascular and total mortality. However, only well designed prospective comparative trials can answer this question.
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PMID:Concomitant diseases in elderly hypertensives: the position of nicardipine. 912 Jun 65

A reversible middle cerebral artery occlusion was performed in rats to determine whether nicardipine, a dihydropyridine voltage-sensitive Ca++ channel (VSCC) antagonist, exerts neuroprotective effects when administered 10 minutes following an ischemic insult, and if it does, whether this is due to its vasodilatory action and effect on cerebral blood flow (CBF) or to direct blockade of Ca++ entry into ischemic brain cells. An increase in the intracellular calcium, [Ca++]i, plays a major role in neuronal injury during cerebral ischemia. Although a large amount of Ca++ enters neurons through the VSCC during ischemia, inconsistent neuroprotective effects have been reported with the antagonists of the VSCC. An intraperitoneal injection of nicardipine (1.2 mg/kg) was administered to rats 10 minutes after the onset of ischemia, and 8, 16, and 24 hours after occlusion. Cortical CBF was determined by laser-Doppler flowmetry. Neurological and neuropathological examinations were performed after 72 hours. Neuron-specific enolase, a specific marker for the incidence of neuronal injury, was measured in plasma. The CBF and other physiological parameters were not affected by nicardipine during occlusion or reperfusion. However, nicardipine treatment significantly improved motor neurological outcome by 29%, and the infarction and edema volume in the pallium as well as the edema volume in the striatum were significantly reduced by 27%, 37%, and 52%, respectively. Nicardipine also reduced the neuron-specific enolase plasma levels by 50%, 42%, and 59% at 24, 48, and 72 hours after the occlusion, respectively. It is concluded that nicardipine may attenuate focal ischemic brain injury by exerting direct neuroprotective and antiedematous effects that do not depend on CBF.
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PMID:Attenuation of brain injury and reduction of neuron-specific enolase by nicardipine in systemic circulation following focal ischemia and reperfusion in a rat model. 934 82

Extreme arterial vasoconstriction (vasospasm) is a common problem encountered in microvascular surgery. An ideal pharmacologic tool able to counteract ischemia during microsurgery should be easy to apply and exert its action both locally and distally in the microcirculation of the flap. We have compared in vitro and in vivo vascular properties of nicardipine, papaverine, and lidocaine in the rabbit carotid artery. In vitro, rings from the rabbit carotid artery (n = 7) were bathed in Krebs-Ringers solution and stretched progressively to an optimal tension of 3.7 to 4.2 g. The specimens were contracted with norepinephrine (1 microM), and a cumulative dose response curve was established. In vivo, microvascular anastomoses were performed bilaterally in the rabbit carotid artery in 35 animals using 9-0 nylon suture and standard microsurgical techniques. During and after the anastomoses, nicardipine (0.1, 0.01 mg topical, or 0.1 mg/hour IV), papaverine (30 mg/cc topical), and lidocaine (2% with and without epinephrine) were applied (blinded) at the anastomotic site in five rabbits each. Heparinized sodium chloride was used as topical irrigation for control and to clean the anastomosis. Blood flow changes were monitored continuously with the transonic Doppler for 30 minutes after the procedure. The systemic blood pressure was also monitored in a group of pilot experiments. A documented decrease in blood flow was noted in all animals after the microvascular anastomosis. Nicardipine and papaverine evoked a concentration-dependent relaxation to precontracted rings to norepinephrine. Nicardipine was greater than papaverine in inducing relaxation. Lidocaine demonstrated a biphasic response with low concentrations potentiating contraction. Systemic nicardipine and papaverine significantly increased the blood flow in the rabbit carotid artery. Topical application of nicardipine and lidocaine did not significantly alter the blood flow; however, the application of nicardipine demonstrates a trend toward increased flow. Lidocaine with epinephrine significantly decreased the blood flow. No drug was found to alter the blood pressure of the animals. Our results demonstrate that nicardipine and papaverine seem to be pharmacologic tools able to increase the blood flow in anastomotic arteries. In contrast, the use of 2% lidocaine as a spasmolytic agent should be re-evaluated, since this substance may act as a partial agonist.
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PMID:Drug-induced vasodilation in an in vitro and in vivo study: the effects of nicardipine, papaverine, and lidocaine on the rabbit carotid artery. 938 59

The purpose of this study was to determine if nicardipine, a calcium ion channel blocker, affects pyruvate dehydrogenase (PDH) activity and improves energy metabolism during cerebral ischemia and reperfusion. Cerebral ischemia was induced, using the bilateral carotid artery occlusion method, for 60 min followed by reperfusion up to 120 min in gerbils. Nicardipine (1 mg/kg) or saline (vehicle-treated) was given to gerbils 30 min prior to the occlusion of the common carotid arteries. PDH activity and metabolites (ATP, PCr, and lactate) were measured in cortex prior to ischemia, immediately following ischemia, and after each reperfusion period. After 60 min ischemia, PDH activity increased in both groups, and was significantly higher in the nicardipine-treated group. After 20 min reperfusion, PDH activity in the nicardipine-treated group recovered to control levels, whereas, the PDH activity in the vehicle-treated group remained elevated, and was higher than the nicardipine-treated animals. At 60 and 120 min reperfusion, the activities in the vehicle-treated group were significantly below control levels, there were no differences, however, between the two groups. ATP and PCr concentrations were markedly depleted immediately after ischemia in both groups. ATP levels at 20 min reperfusion and PCr levels at 60 min reperfusion were significantly higher in the nicardipine-treated group. Lactate concentrations in both groups increased 7-8 fold, similarly, immediately after ischemia. During reperfusion, the lactate remained elevated in both groups, though the levels in the nicardipine-treated group were lower than those in the vehicle-treated group, but not significantly. Nicardipine treatment normalized PDH activity quickly and improved energy metabolism after reperfusion.
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PMID:Effect of nicardipine, a Ca2+ channel blocker, on pyruvate dehydrogenase activity and energy metabolites during cerebral ischemia and reperfusion in gerbil brain. 950 35

When both common carotid arteries of Mongolian gerbils were occluded for 5 min to produce ischemic insult, locomotor activity was increased the following day. The effect of calcium channel blockers on this ischemia-induced hyperactivity was investigated. Nimodipine, at doses of 5, 10, and 20 mg/kg, dose dependently and significantly decreased ischemia-induced hyperactivity. Nicardipine significantly decreased ischemia-induced hyperactivity and doses of 10 and 20 mg/kg. Nifedipine and flunaridine also significantly decreased ischemia-induced hyperactivity at doses of 20 mg/kg. Verapamil had no effect on ischemia-induced hyperactivity at a dose of 20 mg/kg. These findings suggest that ischemia-induced hyperactivity is related to calcium channels. These relationship between calcium channels and dopaminergic function is discussed.
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PMID:Effect of calcium channel blockers on cerebral ischemia-induced hyperactivity in Mongolian gerbils. 1054 96


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