Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085383 (hypocapnia)
 1,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The chemistry, pharmacology, pharmacokinetics, adverse effects, dosage, and availability of nimodipine are discussed, and the clinical use of nimodipine in preventing and treating cerebral arterial spasm in patients with subarachnoid hemorrhage is reviewed. Nimodipine is a highly lipid-soluble dihydropyridine derivative that readily crosses the blood-brain barrier. In animal studies, nimodipine has been shown to be effective in increasing cerebral blood flow; preventing vasoconstriction attributable to sympathetic stimulation, hypocapnia, and hypertension; and improving neurological outcome after cerebral ischemia. Nimodipine is reported to be 90% protein bound; its half-life is approximately 13 hours, with substantial interpatient variability. Nimodipine has been studied in the prevention and treatment of cerebral arterial spasm in patients with subarachnoid hemorrhage. In four open trials, in which nimodipine was administered orally, intravenously, topically during surgery, or by intracarotid injection, and in two double-blind, placebo-controlled trials, neurological outcomes were improved in patients receiving the drug. However, in both sets of trials nimodipine had limited effects on cerebral arterial spasm. Although nimodipine can cause hypotension, no serious adverse reactions to the drug were reported in clinical trials in patients with subarachnoid hemorrhage. Based on limited data currently available, nimodipine appears to improve neurological outcome in patients with subarachnoid hemorrhage. However, its efficacy in preventing or treating cerebral arterial spasm in these patients seems to be limited.
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PMID:Use of nimodipine for prevention and treatment of cerebral arterial spasm in patients with subarachnoid hemorrhage. 332 39

The purpose of this study was to examine effects of nimodipine (Bay e 9736), a calcium blocker, on constrictor responses of cerebral vessels in vivo. Pial artery diameter was measured in anesthetized cats. In the control state, sympathetic nerve stimulation, acute hypertension, and hypocapnia produced maximal decreases in pial artery diameter of 13.7 +/- 1.4, 12.1 +/- 2.7, and 13.3 +/- 2.7% (SE), respectively. Low doses of nimodipine (0.1-0.25 microgram X kg-1 X min-1) decreased the vasoconstrictor response to all three stimuli, and higher doses (0.5-1.0) virtually abolished the response (P less than 0.05 vs. control). In other experiments in cats and monkeys, cerebral blood flow (CBF) was measured with microspheres during acute increases in arterial pressure. Elevation of arterial pressure by approximately 40 mmHg in cats produced only a modest increase in CBF from 48 +/- 3 to 57 +/- 3 ml X min-1 X 100 g-1 in the control state and a larger increase in CBF from 53 +/- 6 to 87 +/- 9 ml X min-1 X 100 g-1 during nimodipine (P less than 0.05, control vs. nimodipine). Nimodipine also inhibited autoregulatory vasoconstriction in monkeys. Nimodipine, in the doses used, had only modest effects on resting vessel diameter, CBF, or arterial pressure. We conclude that nimodipine inhibits cerebral vasoconstrictor responses to several physiological stimuli in vivo.
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PMID:Effects of nimodipine on cerebral vasoconstrictor responses. 643 30

The two major neurological complications of subarachnoid haemorrhage (SAH) due to an intracranial aneurysm are rebleeding and delayed cerebral ischaemia related to cerebral vasospasm. The best way to prevent rebleeding is early surgery. Even when surgery is performed within the first 72 hours posthaemorrhage, the risk of cerebral ischaemia due to vasospasm is high. Conventional medical treatment of cerebral vasospasm includes haemodilution, hypervolaemia and increase of arterial blood pressure. Haemodilution is of limited value as the patients suffering from SAH have usually a low haematocrit. The effectiveness of hypervolaemia is controversial and it may worsen cerebral and pulmonary oedema. Systemic hypertension is an effective therapy of vasospasm, but which can only be used once the aneurysm is controlled. Nimodipine and nicardipine, two calcium antagonists, have a beneficial effect on neurologic outcome following SAH. Today, it is still debated whether the beneficial effect of nimodipine results from the vascular effect of the drug or from a direct cerebral cytoprotective mechanism. Early surgery implies that surgeons operate on brains in acute inflammatory state. Thus, it is mandatory to use peroperative techniques improving cerebral exposure. These techniques include infusion of mannitol, lumbar cerebrospinal fluid (CSF) drainage, administration of anaesthetic agents known to decrease cerebral blood flow (CBF) and hypocapnia. Usually, the effect of CSF drainage is very effective and sufficient by itself. The second objective in the peroperative period is to avoid ischaemia. In areas with decreased flow distal to vasospasm, autoregulation is impaired and CBF is directly dependent on cerebral perfusion pressure. Furthermore, the safe practice of transient clipping of vessels supplying the aneurysm has dramatically reduced the indications of controlled hypotension. During temporary clipping, some authors recommend a pharmacological brain protection using barbiturates, etomidate or propofol, but this practice has not been validated by randomized studies. However, it is generally agreed that the arterial pressure should be increased during temporary clipping to improve collateral blood flow and to maintain it after the aneurysm has been secured. To conclude, together with lumbar CSF drainage and transient clipping, the anaesthetic management of the patients should include: maintenance of the arterial blood pressure close to its preoperative level, maintenance of PaCO2 between 30 and 35 mmHg and of normovolaemia through replacement of fluid and blood losses. After completion of surgery, recovery from anaesthesia should be rapid to allow fast diagnosis of neurological complications. The monitoring of the status of consciousness is the key of the diagnosis of early postoperative complications.
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PMID:[Anesthesia in surgery for intracranial aneurysms]. 781 6

Nimodipine is a calcium entry blocker that shows promise in the therapy for cerebral ischemia. This study was undertaken to examine the interaction of nimodipine with the use of hypocapnia to control cerebral blood volume by reduction in cerebral blood flow (CBF), as might be applicable to patients undergoing anesthesia for neurosurgical procedures. Male adult Sprague-Dawley rats were anesthetized with pentobarbital 50 mg/kg i.p. and were mechanically ventilated at either normocapnia (Paco2 35-40 mm Hg) or hypocapnia (Paco2 23-25 mm Hg). Animals were randomized into four experimental groups in a 2 x 2 factorial design, employing Paco2 level and drug group as between-group factors: vehicle plus normocapnia (group 1, n = 6), nimodipine plus normocapnia (group 2, n = 7), vehicle plus hypocapnia (group 3, n = 6), and nimodipine plus hypocapnia (group 4, n = 6). Nimodipine (1 mug/kg/min) or vehicle was administered i.v. for a period of 45 min. CBF was then measured using [C]iodoantipyrine autoradiography. Hypocapnia decreased global CBF (p <0.0001) and nimodipine increased CBF (p <0.05). Although nimodipine increased global CBF (p <0.05) during normocapnia (89 +/- 8 versus 61 +/- 4 ml/100 g/min), during hypocapnia there was no significant difference between nimodipine and vehicle (45 +/- 3 versus 40 +/- 2 ml/100 g/min). Hypocapnia decreased local CBF in all structures examined, whereas nimodipine increased local CBF in some, but not all structures. In this model, prior institution of hypocapnia prevented nimodipine-induced global CBF increases.
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PMID:Nimodipine does not increase cerebral blood flow during hypocapnia in the rat. 1581 65