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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several agents have been used to treat cocaine-related cardiovascular complications and toxicity occurring in sensitive individuals, yet the causes of hemodynamic responsiveness and differential sensitivity to cocaine are unknown. In this study, we sought to examine the role of different mediators in a model of variable cardiovascular responses to cocaine. As noted previously in conscious rats, cardiac output (CO) and systemic vascular resistance (SVR) responses to cocaine (5 mg/kg, i.v.) varied widely. Twenty of 34 rats exhibited cocaine-induced decreases in CO of > or =8% and large increases in SVR (designated vascular responders). The remaining rats with little change or an increase in CO and smaller increases in SVR were named mixed responders. Pretreatment with propranolol (1 mg/kg) or metoprolol (1 mg/kg) reduced heart rate. In mixed responders, propranolol or metoprolol reversed the cocaine-induced increase in CO and stroke volume and enhanced the increase in SVR, making these rats respond like vascular responders. Nicardipine (25 microg/kg) reduced the pressor response and selectively reversed the CO responses in vascular responders. N omega-nitro-L-arginine methyl ester (L-NAME; 2.7 mg/kg) increased arterial pressure by increasing SVR. Cocaine induced greater pressor and SVR responses apparently because of a shift in baseline values elicited by L-NAME alone. Therefore, differences in hemodynamic responses patterns may be the result of differences in beta-adrenergic activation or subsequent calcium channel activation or both. We predict that calcium channel antagonists may be useful to treat cocaine-induced cardiovascular complications, whereas beta-adrenergic antagonists are not likely to be beneficial.
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PMID:Mechanisms of hemodynamic responses to cocaine in conscious rats. 951 84

It has been reported that the production of oxygen radicals mediated by xanthine oxidase (XO) is stimulated in hypertensive cardiovascular endothelium, suggesting involvement of oxidative stress in pathogenesis of hypertension. In this study we estimated the effect of nicardipine, a calcium blocker, on the oxidative stress and antioxidant activities in left ventricles from spontaneously hypertensive rat (SHR) and stroke-prone SHR (SHRSP). The activity of XO increased 3.5-fold in SHR and 6.2-fold in SHRSP compared to that in normal controls (WKY). Interestingly, the levels of glutathione (GSH) and the activity of its synthesizing enzyme (gamma-glutamylcysteine synthetase, gamma-GCS) elevated concomitantly in SHR and SHRSP: the level of GSH increased 1.2-fold in SHR and 1.3-fold in SHRSP. The activity of gamma-GCS was elevated 1.5-fold in SHR and 2.4-fold in SHRSP, accompanying an increase in the expression of its mRNA. Treatment of these rats with nicardipine, for 4 weeks improved blood pressure, from 176 +/- 10 to 140 +/- 8 mmHg in SHR, and from 201 +/- 11 to 167 +/- 5 mmHg in SHRSP, respectively, and decreased wet weight of heart, levels of GSH, and the activities of XO and gamma-GCS. Nicardipine reduced the expression of gamma-GCS mRNA. Collectively, these results suggest that reactive oxygen species produced by XO in hypertensive rat heart cause induction of the expression of gamma-GCS and nicardipine plays a role in reducing the oxidative stress in hypertensive heart.
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PMID:Nicardipine normalizes elevated levels of antioxidant activity in response to xanthine oxidase-induced oxidative stress in hypertensive rat heart. 979 May 16

The effects of 2.5% and 5% of sevoflurane anesthesia on hemodynamics and myocardial metabolism were studied in pentobarbital-pancuronium anesthetized dogs. The interaction between nicardipine and 2.5% sevoflurane was also examined. Sevoflurane produced dose-dependent ( P << 0.05 to P << 0.01) decreases in systolic arterial pressure (SAP), heart rate (HR), cardiac index (CI), left ventricular minute work index (LVMWI), maximum rate of rise of left ventricular pressure (LV dP/dt), the time constant of fall in isovolumic left ventricular pressure (T) and systemic vascular resistance (SVR), whereas stroke volume index (SVI) and left ventricular end-diastolic pressure (LVEDP) remained unchanged. Central venous pressure (CVP) was significantly ( P << 0.05) increased at 5%. Myocardial oxygen consumption (MV(O)(2)), and myocardial lactate extraction ratio (ML ext) were decreased in a dose-dependent manner ( P << 0.05). Myocardial oxygen extraction ratio (M(O)(2) ext) was significantly ( P << 0.01) decreased at 5%. The ratio of the left ventricular minute work index to myocardial oxygen consumption (LVMWI/MV(O)(2)), i.e., left ventricular efficiency was significantly decreased only at 5% ( P << 0.05). Coronary sinus blood flow (CSBF) was significantly ( P << 0.05) decreased only at 2.5% sevoflurane and coronary vascular resistance (CVR) was significantly ( P << 0.01) decreased only at 5% sevoflurane. The ratio of CSBF to CO (CSBF/CO) showed a tendency to increase as sevoflurane concentrations were increased. Nicardipine (0.01 mg.kg(-1)) administered intravenously under 2.5% sevoflurane caused significant ( P << 0.05 to P << 0.01) decreases in SAP, HR, LV dP/dt, SVR, and CVR, and increases in CVP, SVI, CI, and CSBF ( P << 0.05 to P << 0.01). CSBF/CO remained unchanged. MV(O)(2), M(O)(2) ext, and ML ext were significantly ( P << 0.05 to P << 0.01) decreased. LVMWI/MV(O)(2) showed a tendency to increase. It is concluded that sevoflurane causes a rapidly and easily controlled cardiovascular depression and may not have unfavorable effects on coronary circulation and myocardial metabolism. Nicardipine exerts a synergistic myocardial depressant effect on sevoflurane, in terms of both cardiovascular dynamics and myocardial metabolism.
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PMID:Effects of sevoflurane on cardiovascular dynamics, coronary circulation and myocardial metabolism in dogs. 1523 85

We compared the haemodynamic effects of nicardipine and sodium nitroprusside after coronary artery bypass graft surgery. When post-surgery systolic blood pressure reached > 150 mmHg, patients were randomly given nicardipine (N group, n = 26) or sodium nitroprusside (S group, n = 21). The drugs were infused at a rate of 2 microg/kg per min for 10 min. If the target blood pressure (120-140 mmHg) was not achieved, the infusion rate was increased by 1 microg/kg per min every 10 min. Cardiac and stroke volume indices had increased significantly in the N group after 10 min and in both groups after 60 min. The infusion duration and total dose of drug were significantly lower in the N group compared with the S group. Nicardipine infusion controlled post-operative hypertension more rapidly and was superior to sodium nitroprusside in maintaining left ventricular performance immediately after drug infusion.
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PMID:Comparison of the effects of nicardipine and sodium nitroprusside for control of increased blood pressure after coronary artery bypass graft surgery. 1530 65

We investigated the combined effects of a moderate intensity static magnetic field (SMF) and an L-type voltage-gated Ca(2+) channel blocker, nicardipine in stroke-resistant spontaneously hypertensive rats during the development of hypertension. Five-week-old male rats were exposed to SMF intensity up to 180 mT (B(max)) with a peak spatial gradient of 133 mT/mm for 14 weeks. Four experimental groups of 14 animals each were examined: (1) sham exposure with intraperitoneal (ip) saline injection (control); (2) SMF exposure with ip saline injection (SMF); (3) sham exposure with ip nicardipine injection (NIC); (4) SMF exposure with ip nicardipine injection (SMF + NIC). A disc-shaped permanent magnet or a dummy magnet was implanted in the vicinity adjacent to the left carotid sinus baroreceptor region in the neck of each rat. Nicardipine (2 mg/kg ip) was administered three times a week for 14 weeks, and then 15 min after each injection, arterial blood pressure (BP), heart rate (HR), baroreflex sensitivity (BRS), skin blood flow (SBF), skin blood velocity (SBV), plasma nitric oxide (NO) metabolites (NO(x) = NO(2) (-) + NO(3) (-)), plasma catecholamine levels and behavioral parameters of a functional observational battery were monitored. The action of nicardipine significantly decreased BP, and increased HR, SBF, SBV, plasma epinephrine and norepinephrine in the NIC group compared with the control respective age-matched group without changing plasma NO(x) levels. Neck exposure to SMF alone for 5-8 weeks significantly suppressed or retarded the development of hypertension together with increased BRS in SMF group. Furthermore, the exposure to SMF for 1-8 weeks significantly promoted the nicardipine-induced BP decrease in the SMF + NIC group compared with the respective NIC group. Moreover, the SMF induced a significant increase in plasma NO(x) in the nicardipine-induced hypotension. There were no significant differences in any of the physiological or behavioral parameters measured between the SMF + NIC and the NIC groups, nor between the SMF and the control groups. These results suggest that the SMF may enhance nicardipine-induced hypotension by more effectively antagonizing the Ca(2+) influx through the Ca(2+) channels compared with the NIC treatment alone. Furthermore, the enhanced antihypertensive effects of the SMF on the nicardipine-treated group appear to be partially related to the increased NO(x). Theoretical considerations suggest that the applied SMF (B(max) 40 mT, 0 Hz) can be converted into a changing magnetic field (B(max) 30-40 mT, 5.7-6.5 Hz or 7.5-8.3 Hz) in the baroreceptor region by means of the carotid artery pulsation. Therefore, we propose that the moderate intensity changing magnetic field, i.e., the magnetic field modulated by the pulse rate, may influence the activity of baroreceptor and baroreflex function.
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PMID:Exposure to a moderate intensity static magnetic field enhances the hypotensive effect of a calcium channel blocker in spontaneously hypertensive rats. 1618 31

Nicardipine is a water soluble calcium channel antagonist, with predominantly vasodilatory actions. Intravenous (IV) nicardipine (Cardene IV), which demonstrates a relatively rapid onset/offset of action, is used in situations requiring the rapid control of blood pressure (BP). IV nicardipine was as effective as IV nitroprusside in the short-term reduction of BP in patients with severe or postoperative hypertension. A potential role for IV nicardipine in the intraoperative acute control of BP in patients undergoing various surgical procedures (including cardiovascular, neurovascular and abdominal surgery), and in the deliberate induction of reduced BP in surgical procedures in which haemostasis may be difficult (e.g. surgery involving the hip or spine) was demonstrated in preliminary studies. Preliminary studies also indicated the ability of a bolus dose of IV nicardipine to attenuate the hypertensive response, but not the increase in tachycardia, after laryngoscopy and tracheal intubation in anaesthetised patients. In large, well designed studies, IV nicardipine prevented cerebral vasospasm in patients with recent aneurysmal subarachnoid haemorrhage; however, overall clinical outcomes at 3 months were similar to those in patients who received standard management. Small preliminary studies have investigated the use of IV nicardipine in a variety of other settings, including acute intracerebral haemorrhage, acute ischaemic stroke, pre-eclampsia, acute aortic dissection, premature labour and electroconvulsive therapy.In conclusion, the efficacy of IV nicardipine in the short-term treatment of hypertension in settings for which oral therapy is not feasible or not desirable is well established. The ability to titrate IV nicardipine to the tolerance levels of individual patients makes this agent an attractive option, especially in critically ill patients or those undergoing surgery. Potential exists for further investigation of the use of this agent in clinical settings where a vasodilatory agent with minimal inotropic effects is appropriate.
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PMID:Intravenous nicardipine: its use in the short-term treatment of hypertension and various other indications. 1697 41

Control of blood pressure protects against the development of cerebrovascular lesions, stroke, and vascular dementia (VaD). Cerebrovascular disease is increasingly recognized as a cause of cognitive impairment and dementia primarily in the elderly. Nicardipine is a dihydropyridine-type calcium channel blocker (CCB) with a peculiar cerebrovascular profile developed approximately 30 years ago. This study has reviewed the main controlled clinical studies investigating the use of nicardipine in pathologies associated with cerebrovascular injury, such as subarachnoid haemorrhage (SAH), acute stroke, and VaD. SAH is a main cerebrovascular indication of CCBs. In this indication, CCBs prevent vasospasm and improve clinical outcomes. Nimodipine represents the CCB more investigated in this indication. Former studies did not demonstrate a clear advantage of nicardipine versus nimodipine in SAH. A more recent approach using implants of nicardipine prolonged-release showed a decreased incidence of vasospasm, delayed ischemic deficits, and improved clinical outcome after severe SAH. Controlled trials have shown the effectiveness of the drug in preventing stroke. Increasing evidence suggests some benefit of some CCBs in VaD or mixed degenerative and vascular dementia. In this setting, nicardipine has been investigated in approximately 6,000 patients, with an improvement of cognitive deterioration in more than 60% of patients treated. The pronounced anti-hypertensive activity of nicardipine and its safety and effectiveness in cognitive domain suggest its reconsideration in the treatment of cognitive impairment of vascular origin as well as for reducing the risk of recurrent stroke in patients at high risk of it.
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PMID:Nicardipine: a hypotensive dihydropyridine-type calcium antagonist with a peculiar cerebrovascular profile. 1902 Oct 30

Drug-related hepatotoxicity is now the leading cause of acute liver failure in the United States, especially among patients who have no prior liver disease. Nicardipine is the only IV calcium channel blocker available for the short-term treatment of hypertension with a considerably good safety profile. We report a case of nicardipine-induced hepatitis. A patient with history of hypertension was admitted because of right middle cerebral artery infarction. Computed tomography of the brain showed evolving stroke. The patient went for cerebral angiography and stent placement, and during the procedure he had cerebral hemorrhage. He was transferred to neurosurgery. After surgery, he was started on hypertonic saline, mannitol for cerebral edema, and nicardipine drip for blood pressure control. On the fourth day after operation, he started to have fever with progressive elevation of liver enzymes [Aspartate amino transferase (AST) 450, Alanine amino transferase (ALT) 356, and alkaline phosphatase 299]. Serum bilirubin was 0.6. He did not receive blood transfusion. No medical history of hepatitis or liver disease was reported. Other medications included metoprolol and heparin. White blood cell count was 13,000. Chest x-ray did not show evidence of consolidation. Urine analysis was unremarkable. Cultures were negative. Acute hepatitis panel was negative. Cerebrospinal fluid examination was normal. Liver enzymes were trending up gradually with normal protein and bilirubin. Computed tomography of the abdomen was unremarkable. The patient's medications were reviewed. It was noticed that the patient started to have fever and elevated liver enzymes after administration of nicardipine drip. It was postulated that nicardipine may be the culprit of acute hepatitis. Nicardipine drip was stopped, and the patient was started on labetalol. Fever started to resolve, and liver enzymes started trending down toward normal. The patient remained afebrile after that.
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PMID:Nicardipine-induced acute hepatitis in an intensive care unit patient. 1909 42

Nicardipine is a dihydropyridine-type Ca(2+) channel blocker (CCB) with strong antihypertensive activity and with a peculiar cerebrovascular profile. This paper has reviewed the main controlled clinical studies on nicardipine in pathologies associated with cerebrovascular impairment. Subarachnoid haemorrhage (SAH) is managed with CCBs to prevent vasospasm and improve clinical outcomes. Nimodipine is the CCB licensed for this indication. Former studies did not demonstrate an advantage of nicardipine versus nimodipine in SAH. A more recent approach administering the drug intra-arterially or using implants of nicardipine prolonged-release showed a decreased incidence of vasospasm, delayed ischemic deficits and improved clinical outcome after severe SAH. Nicardipine is recommended for elevated blood pressure after acute ischemic stroke or intracerebral haemorrhage and is effective in prevention of stroke. More recent investigations were focused on the treatment of cognitive deterioration of vascular origin. In this setting nicardipine has been investigated in more than 6000 patients, with improvement of cognitive deterioration in more than 60% of patients treated. The anti-hypertensive activity of nicardipine, its safety and effectiveness in cognitive domain, suggests re-considering this drug in the treatment of cognitive impairment of vascular origin and for reducing the risk of recurrent stroke in patients at high risk of it.
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PMID:Nicardipine use in cerebrovascular disease: a review of controlled clinical studies. 1930 80

Injectable nicardipine is increasingly being used to manage neurovascular conditions. To better understand its place in therapy, we conducted an evidenced-based literature review. Two-hundred twenty-three article abstracts were identified; after independent review by two individuals and a supplemental manual search, 29 were deemed relevant and were included in this review. Nicardipine has been studied or recommended for management of hypertension in many neurovascular settings (ischemic stroke, intracerebral hemorrhage, craniotomy, and spinal surgery), for vasospasm in aneurysmal subarachnoid hemorrhage, and in acute traumatic brain injury. In the management of hypertension in acute stroke, nicardipine is one of several recommended options available; expert opinion forms the basis of these recommendations in clinical guidelines, with limited randomized controlled trial evidence to support its use. Among the various antihypertensive agents, nicardipine has the highest drug acquisition cost. In two meta-analyses, intravenous nicardipine had no impact on patient outcomes (death, disability) in patients with acute traumatic brain injury (relative risk [RR] 0.25, 95% confidence interval [CI] 0.05-1.27) or in patients with aneursymal subarachnoid hemorrhage (RR 0.97, 95% CI 0.78-1.20). Intraarterial nicardipine reduced angiographic diameter (p value not reported) and peak systolic velocities on transcranial Doppler images (p<0.001) in published case series. Given nicardipine's high cost relative to that of other agents and the limited evidence to support its use in patients with neurovascular conditions, this drug should be considered only in patients who have failed or have contraindications to alternative agents in the management of hypertension. Although intraarterial nicardipine appears to be promising in aneurysmal subarachnoid hemorrhage, well-designed studies are needed in this setting before its use can be routinely recommended.
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PMID:Use of injectable nicardipine for neurovascular indications. 1932 19


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