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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

1. Late cerebral arterial spasm was induced by repeated injections of autologous blood in a total amount of 14-33 ml into the basal cisterns of baboons to mimick subarachnoid hemorrhage (SAH). Regional cerebral blood flow (CBF), sagittal sinus pressure, cerebral arterial caliber from angiograms, and cerebral metabolic rate of oxygen (CMRO2) were measured before and after the experimental SAH to determine responses to hypercapnia and induced hypertension. The effect of the calcium antagonist, Nimodipine, on CBF autoregulation pre- and post-SAH was tested. 2. One week after the blood injections were started there was about 10-20% reduction, depending on territory measured, in the arterial diameter of the carotid and vertebral systems. This was associated with an 18% reduction in CBF and 9% decrease in the brain metabolism. 3. During hypercapnia before and after experimental SAH the flow increased with a mean of 3.7 and 1.8 ml, respectively, for each mm Hg elevation of PaCO2. In control animals, graded angiotensin-induced hypertension did not overtly affect CBF. Following SAH, the CBF autoregulation was impaired in 5 of 6 animals tested. 4. I.v. infusion of Nimodipine markedly curtailed the CBF autoregulation in pre-SAH animals and, to a somewhat slighter extent, also in post-SAH animals.
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PMID:Late cerebral arterial spasm: the cerebrovascular response to hypercapnia, induced hypertension and the effect of nimodipine on blood flow autoregulation in experimental subarachnoid hemorrhage in primates. 682 30

Only 53%-58% of patients with a subarachnoid haemorrhage (SAB) following the rupture of a cerebral aneurysm survive without neurological damage. Morbidity and mortality are closely related to the delayed ischaemic neurological deficit due to cerebral vasospasm. The following review gives an account of pathophysiological mechanisms; the importance of treatment with calcium antagonists, hypervolaemic haemodilution, and induced arterial hypertension is discussed in light of the current literature. PATHOPHYSIOLOGY. In addition to other vasoactive substances in the blood, haemoglobin, which is released from lysed erythrocytes on the 2nd to 4th day after the haemorrhage, plays an important role in inducing vasospasm. An inflammatory angiopathy ensues, with complete resolution after 6-12 weeks. The cerebral blood flow (CBF) is reduced depending on the extent of vasospasm. Irreversible infarction may follow the decrease of CBF below a critical value. Severe vasospasm causes autoregulatory disturbances and reduced responsiveness of cerebral vessels to CO2. CALCIUM ANTAGONISTS. The calcium blocker nimodipine causes dilatation of small pial vessels with increased CBF. However, systemic vasodilation with the subsequent fall in blood pressure may limit the increase in CBF. Furthermore, it is known that nimodipine decreases intracellular calcium concentrations resulting in some protection against ischaemic cellular injury. Seven placebo-controlled clinical studies have shown that nimodipine improves the outcome of patients with severe neurological damage due to cerebral vasospasm. HYPERVOLAEMIC HAEMODILUTION. Volume expansion and haemodilution to a hematocrit of 30%-33% is suggested to improve cerebral perfusion during vasospasm. The central venous and pulmonary capillary wedge pressures should be 10-12 mm Hg and 15-18 mm Hg, respectively. But there is no evidence of improved outcome with this measure, and pulmonary edema is a frequent side effect. However, impairment of cerebral perfusion and increased neurological damage can be demonstrated with hypovolaemia and haemoconcentration. INDUCED ARTERIAL HYPERTENSION. In the presence of cerebral vasospasm and resulting autoregulatory disturbances, cerebral perfusion can be increased by raising systemic arterial pressure. This measure, too, fails to improve neurological outcome. CONCLUSION. Treatment of cerebral vasospasm following a SAB aims to avoid any impairment of cerebral perfusion. Hypovolaemia and haemoconcentration have to be corrected. Normoventilation should be established to avoid hypocapnic vasoconstriction. Nimodipine should be administered continuously after a SAB. In view of the autoregulatory disturbances, systemic hypotension with its danger of decreased CBF must be prevented. The importance of hypervolaemic haemodilution and/or induced arterial hypertension is not clear. Despite therapeutic efforts, the number of patients who have survived a SAB without a substantial neurological deficit has not increased.
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PMID:[Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Therapeutic value of treatment with calcium antagonists, hypervolemic hemodilution and induced arterial hypertension]. 778 50

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

In this prospective study we report the outcome for all patients with a verified aneurysmal SAH managed at the Department of Neurosurgery at the University Hospital in Lund, Sweden during the four-year span from June 1, 1989 to May 31, 1993. A total of 275 patients were admitted during the study period. The vast majority of patients (196 individuals, i.e. 71%) was admitted within 24 h after the bleed. Mean age was 54.3 years and the female/male ratio 1.8/1. Nimodipine was administered in 231 (84%) of the 275 patients. We clipped the ruptured aneurysm in 199 patients. At follow-up 3 months after the bleed 161 patients were classified as having made a good neurological recovery (59%). The morbidity was 20% and 59 patients (21%) had died. The overwhelming cause for morbidity and mortality was damage from the initial bleed (62 patients, 23%). Notably, considering morbidity and mortality, delayed ischemia was less frequent than both surgical complications and rebleeding, respectively. Of the 275 patients, 13 (5%) patients made an unfavorable outcome due to delayed ischemic deterioration. There was a strict correlation between the initial clinical condition and final outcome. Of 51 grade V patients, only 2 made a good recovery. There was also a strict correlation between the amount of extravasated blood and outcome. There was no difference in clinical outcome between patients with arterial hypertension versus normotensive individuals. The mortality rate was worse for posterior circulation aneurysms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Which are the major determinants for outcome in aneurysmal subarachnoid hemorrhage? A prospective total management study from a strictly unselected series. 783 9

Today calcium antagonists (Ca-antagonists) are widely used agents in the management of various diseases of the circulatory system. More than 20 years ago the Ca-antagonists of the so-called 1st generation (Verapamil, Diltiazem, Nifedipine) were introduced for treatment of angina pectoris and later of essential hypertension. In the last decade an increasing number of agents structurally related to dihydropyridines were developed for the treatment of hypertension and/or coronary heart disease or cerebral disorders; the main target was to reduce side effects and to guarantee once or at least twice daily administration. Therefore the Ca-antagonists of the so-called 2nd generation (e.g. Amlodipine, Felodipine, Isradipine, Nitrendipine, Nicardipine, Nimodipine, Nisoldipine) tend to longer elimination-half-lives; Amlodipin is an exception with an elimination-half-life of 30 hours on the average. Apart from elimination rates, however, the biopharmaceutical and pharmacokinetic characteristics of all Ca-antagonists are similar: they are highly cleared drugs and are relatively highly protein bound. As they are subject to significant hepatic first-pass-metabolism old age and hepatic disease will increase their plasma-concentrations. Renal impairment affects little their pharmacokinetics since the fraction eliminated unchanged by the kidneys is small. For most agents, plasma-concentration-response relationships have been described. With exception of nicardipine a linear pharmacokinetic in all Ca-antagonists was demonstrated. Drugs and food affecting hepatic blood flow and drug metabolising capacity have predictable interaction potential. With regard to the acute pharmacodynamic effects the Ca-antagonists show similar qualitative effects, though there are quantitative differences. Orally administered dihydropyridine-derivatives induce acute hypotensive effects, whereas the other compounds show clinically relevant hypotensive effects only when administered chronically per os or less pronounced when given as intravenous infusion.
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PMID:[Principles of the pharmacokinetics and pharmacodynamics of calcium antagonists]. 813 31

Over a seven-year period, 130 patients with delayed ischaemia after cerebral aneurysm haemorrhage were treated with intravenous nimodipine. The delay from the last haemorrhage to the appearance of ischaemic symptoms was one to 18 days, and vasospasm was confirmed in most cases. Nimodipine treatment was started within three days of delayed ischaemic deficit (DID) onset, at a low dose increased quickly to 30-45 ug/kg/hr, and reduced gradually over the last day or two of the course. The duration of treatment was one to 27 days. Side effects were minor, and serious complications few. Hypotension occurred in 35 cases. During treatment, there were highly significant improvements in both clinical grade and Glasgow Coma Score. The final outcome was 98 good (Glasgow Outcome Score 1), 18 permanent deficits (eight GOS 2, ten GOS 3), and 14 dead. Ischaemia was directly involved in only half the deaths. These results are much better than the natural history (about 1/3 dead and 1/3 disabled), and a considerable improvement over fluid and hypertensive treatment (17% dead, 29% deficits), calculated from a literature review. Nimodipine is also safer than induced hypertension, especially pre-operatively.
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PMID:Treatment of symptomatic vasospasm with nimodipine. 821 89

Fifty patients of either sex with acute and chronic cerebrovascular disorders were submitted to an observation protocol and treated with oral nimodipine (tablets or drops) at a daily dosage of 90 mg for 1 to 3 months. Nimodipine proved useful both from the therapeutic point of view and for its easy handling in acute pathology (TIA, RIND, minor stroke, complete stroke) as well as chronic cerebral ischemia. The drug was well tolerated both locally and systemically; in patients with concomitant arterial hypertension, nimodipine reduced blood pressure with a tendency towards stabilization at near-normal levels.
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PMID:[Nimodipine in ischemic cerebropathy]. 847 25

Sixteen patients (6 women, 10 men; mean age: 52.5 years) suffering from spontaneous subarachnoid haemorrhage (SAH) of unknown origin underwent a protocol of initial and then weekly computed tomography (CT), initial four-vessel digital subtraction angiography (DSA) and at least one control pancerebral DSA. Fourteen patients had magnetic resonance imaging before undergoing first control DSA. All patients had calcium-antagonists (Nimodipine) via a central venous catheter, were kept on the neurosurgical intensive care unit and followed daily with transcranial Doppler ultrasonography (TCD). One patient (6.3%) developed moderate and 5 (31.1%) developed severe cerebral vasospasm as documented with TCD and exhibited deterioration of their level of consciousness. These 6 patients were treated with induced hypertension, hypervolaemia and haemodilution. Their blood flow velocities were elevated for a mean of 8 (5-17) days with a peak after 12.5 (9-17) days following SAH. No complications due to treatment were noted. One patient of the non-vasospastic group died of pulmonary embolism, another patient had an ischaemic incident during angiography, which has led to permanent disability. On follow-up 2-24 months after SAH 14 patients had returned to their premorbid state. It is concluded that patients suffering from SAH of unknown origin should undergo repeated angiographic investigation and subsequent daily monitoring of their neurologic status including daily TCD recordings so that haemodynamic treatment can be established in the event of cerebral vasospasm, which may occur in up to one third of these patients.
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PMID:Cerebral vasospasm after subarachnoid haemorrhage of unknown aetiology: a clinical and transcranial Doppler study. 880 Mar 32

The idea of using induced hypertension to treat the symptomatic ischaemia resulting from vasospasm after subarachnoidal hemorrhage, and the effect of this therapy on the blood-brain barrier, is checked in animal experiments. This therapy is combined with the application of nimodipine, which is recognised as the standard medication for prophylaxis of vasospasm. The effects of the induced hypertension combination with Nimodipine and in combination with another calcium antagonist, Flunarizine are compared. Seventy-four narcotised rats, one group with 22 animals treated with Nimodipine and 22 with placebo, and a second group 20 animals treated with Flunarizine and 10 with placebo, are evaluated. The blood pressure is raised to 150-180 mmHg by i.v. application of norfenephrine and measured continuously. The standard tracer, horseradish peroxidase, is applied as indicator for the blood-brain barrier function. 15 minutes later the experimental animals are exsanguinated by perfusion with saline, then perfused with Karnovsky's solution. After removal, the brains are stained for peroxidase to visualise extravasation of the horseradish peroxidase, and after evaluation of the results each brain is assigned to its experimental group. In the Nimodipine group, a significant accumulation (p < 0.001) of perivascular deposits of peroxidase reaction product were found, these were not found in the placebo group. The Flunarizine group does not differ from its placebo group in the number of extravasates, and thus, with respect to protein extravasation, appears better than the Nimodipine group. In electron micrographs of the extravasates one sees intact tight junctions and a neuroendothelial transport, and also vesicles, filled with horseradish peroxidase in the endothelium, the muscle cells, and the brain parenchyma, which arise from pinocytosis. The vesicles, which transport the high-molecular-weight protein, horseradish peroxidase, also transport other proteins and can, therefore, cause a brain edema. It follows from these morphological results that Nimodipine can disrupt the blood brain barrier function and can, therefore, also interfere with cerebral autoregulation, which depends on the resistance of vessels.
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PMID:Ultrastructural changes in the blood-brain barrier in rats after treatment with nimodipine and flunarizine. A comparison. 900 89


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