Effect of riluzole on the neurological and neuropathological changes in an animal model of cardiac arrest-induced movement disorder.
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Posthypoxic myoclonus and seizures precipitate as secondary neurological consequences in ischemic/hypoxic insults of the central nervous system. Neuronal hyperexcitation may be due to excessive activation of glutamatergic neurotransmission, an effect that has been shown to follow ischemic/hypoxic events. Therefore, riluzole, an anticonvulsant that inhibits the release of glutamate by stabilizing the inactivated state of activated voltage-sensitive sodium channels, was tested for its antimyoclonic and neuroprotective properties in the cardiac arrest-induced animal model of posthypoxic myoclonus. Riluzole (4-12 mg/kg i.p.) dose-dependently attenuated the audiogenic seizures and action myoclonus seen in this animal model. Histological examination using Nissl staining and the novel Fluoro-Jade histochemistry in cardiac-arrested animals showed an extensive neuronal degeneration in the hippocampus and cerebellum. Riluzole treatment almost completely prevented the neuronal degeneration in these brain areas. The neuroprotective effect was more pronounced in hippocampal pyramidal neurons and cerebellar Purkinje cells. These effects were seen at therapeutically relevant doses of riluzole, and the animals tolerated the treatment well. These findings indicate that the pathogenesis of posthypoxic myoclonus and seizure may involve excessive activation of glutamate neurotransmission, and that riluzole may serve as an effective pharmacological agent with neuroprotective potential for the treatment of neurological conditions associated with cardiac arrest in humans. (+info)
Fibrinolytic activation markers predict myocardial infarction in the elderly. The Cardiovascular Health Study.
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Coagulation factor levels predict arterial thrombosis in epidemiological studies, but studies of older persons are needed. We studied 3 plasma antigenic markers of fibrinolysis, viz, plasminogen activator inhibitor-1 (PAI-1), fibrin fragment D-dimer, and plasmin-antiplasmin complex (PAP) for the prediction of arterial thrombosis in healthy elderly persons over age 65. The study was a nested case-control study in the Cardiovascular Health Study cohort of 5201 men and women >/=65 years of age who were enrolled from 1989 to 1990. Cases were 146 participants without baseline clinical vascular disease who developed myocardial infarction, angina, or coronary death during a follow-up of 2.4 years. Controls remained free of cardiovascular events and were matched 1:1 to cases with respect to sex, duration of follow-up, and baseline subclinical vascular disease status. With increasing quartile of D-dimer and PAP levels but not of PAI-1, there was an independent increased risk of myocardial infarction or coronary death, but not of angina. The relative risk for D-dimer above versus below the median value (>/=120 microg/L) was 2.5 (95% confidence interval, 1.1 to 5.9) and for PAP above the median (>/=5.25 nmol/L), 3.1 (1.3 to 7.7). Risks were independent of C-reactive protein and fibrinogen concentrations. There were no differences in risk by sex or presence of baseline subclinical disease. D-dimer and PAP, but not PAI-1, predicted future myocardial infarction in men and women over age 65. Relationships were independent of other risk factors, including inflammation markers. Results indicate a major role for these markers in identifying a high risk of arterial disease in this age group. (+info)
Repeated administration of vasopressin but not epinephrine maintains coronary perfusion pressure after early and late administration during prolonged cardiopulmonary resuscitation in pigs.
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BACKGROUND: It is unknown whether repeated dosages of vasopressin or epinephrine given early or late during basic life support cardiopulmonary resuscitation (CPR) may be able to increase coronary perfusion pressure above a threshold between 20 and 30 mm Hg that renders defibrillation successful. METHODS AND RESULTS: After 4 minutes of cardiac arrest, followed by 3 minutes of basic life support CPR, 12 animals were randomly assigned to receive, every 5 minutes, either vasopressin (early vasopressin: 0.4, 0.4, and 0.8 U/kg, respectively; n=6) or epinephrine (early epinephrine: 45, 45, and 200 microg/kg, respectively; n=6). Another 12 animals were randomly allocated after 4 minutes of cardiac arrest, followed by 8 minutes of basic life support CPR, to receive, every 5 minutes, either vasopressin (late vasopressin: 0.4 and 0.8 U/kg, respectively; n=6), or epinephrine (late epinephrine: 45 and 200 microg/kg, respectively; n=6). Defibrillation was attempted after 22 minutes of cardiac arrest. Mean+/-SEM coronary perfusion pressure was significantly higher 90 seconds after early vasopressin compared with early epinephrine (50+/-4 versus 34+/-3 mm Hg, P<0.02; 42+/-5 versus 15+/-3 mm Hg, P<0.0008; and 37+/-5 versus 11+/-3 mm Hg, P<0. 002, respectively). Mean+/-SEM coronary perfusion pressure was significantly higher 90 seconds after late vasopressin compared with late epinephrine (40+/-3 versus 22+/-4 mm Hg, P<0.004, and 32+/-4 versus 15+/-4 mm Hg, P<0.01, respectively). All vasopressin animals survived 60 minutes, whereas no epinephrine pig had return of spontaneous circulation (P<0.05). CONCLUSIONS: Repeated administration of vasopressin but only the first epinephrine dose given early and late during basic life support CPR maintained coronary perfusion pressure above the threshold that is needed for successful defibrillation. (+info)
Frequency of arrhythmias and other cardiac abnormalities in fulminant hepatic failure.
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In a series of 106 patients with fulminant hepatic failure and grade 4 encephalopathy, cardiac arrhythmias and other abnormalities occurred in 92 per cent. The most common was sinus tachycardia (75%) and this was the only abnormality in 22 per cent of the patients. Sudden cardiac arrest occurred in 25 per cent, various ectopic beats in 20 per cent, and heart block or bradycardia in 18 per cent. Other electrocardiographic abnormalities, mostly of the T wave and ST segment, were found in 31 per cent. Cardiac and respiratory arrests were usually unrelated to each other and both frequently occurred without warning. Only 7 out of 71 patients with arrhythmias other than sinus tachycardia survived, compared with 15 out of 31 patients without them (P less than 0-005). During the latter part of the series when an arrhythmia computer was used to monitor 38 patients, it was shown that significantly lower arterial oxygen levels occurred in those with arrhythmias, other than sinus tachycardia, than in those without. They were also found to be more acidotic and hyperkalaemic, and a higher number required dialysis and ventilation. Macroscopical cardiac abnormalities including scattered petechial haemorrhages, small pericardial effusions, and fatty, pale, and flabby ventricles, were found at necropsy in 64 per cent of the patients examined. Combinations of these macroscopical abnormalities occurred, particularly in the paracetamol overdose group. Another necropsy finding of possible significance in the pathogenesis of arrhythmias was cerebral oedema, present in 48 per cent of the patients examined, and often associated with coning of the brain stem. However, 7 of the 16 patients who suffered asystolic cardiac arrests had no macroscopical abnormality of either heart or brain. In the management of patients with fulminant hepatic failure continuous cardiac monitoring is essential. Correction of the biochemical and coagulation defects may decrease the frequency of arrhythmias but studies of the mechanism and control of cerebral oedema and its relation to cardiovascular function are urgently needed. (+info)
Bilateral vertebral artery occlusion following cervical spine trauma--case report.
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A 41-year-old female presented with a rare case of bilateral vertebral artery occlusion following C5-6 cervical spine subluxation after a fall of 30 feet. Digital subtraction angiography showed occlusion of the bilateral vertebral arteries. Unlocking of the facet joint, posterior wiring with iliac crest grafting, and anterior fusion were performed. The patient died on the 3rd day after the operation. This type of injury has a grim prognosis with less than a third of the patients achieving a good outcome. (+info)
Resuscitation from out-of-hospital cardiac arrest: is survival dependent on who is available at the scene?
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OBJECTIVE: To determine whether survival from out-of-hospital cardiac arrest is influenced by the on-scene availability of different grades of ambulance personnel and other health professionals. DESIGN: Population based, retrospective, observational study. SETTING: County of Nottinghamshire with a population of one million. SUBJECTS: All 2094 patients who had resuscitation attempted by Nottinghamshire Ambulance Service crew from 1991 to 1994; study of 1547 patients whose arrest were of cardiac aetiology. MAIN OUTCOME MEASURES: Survival to hospital admission and survival to hospital discharge. RESULTS: Overall survival from out-of-hospital cardiac arrest remains poor: 221 patients (14.3%) survived to reach hospital alive and only 94 (6.1%) survived to be discharged from hospital. Multivariate logistic regression analysis showed that the chances of those resuscitated by technician crew reaching hospital alive were poor but were greater when paramedic crew were either called to assist technicians or dealt with the arrest themselves (odds ratio 6.9 (95% confidence interval 3.92 to 26.61)). Compared to technician crew, survival to hospital discharge was only significantly improved with paramedic crew (3.55 (1.62 to 7.79)) and further improved when paramedics were assisted by either a health professional (9.91 (3.12 to 26.61)) or a medical practitioner (20.88 (6.72 to 64.94)). CONCLUSIONS: Survival from out-of-hospital cardiac arrest remains poor despite attendance at the scene of the arrest by ambulance crew and other health professionals. Patients resuscitated by a paramedic from out-of-hospital cardiac arrest caused by cardiac disease were more likely to survive to hospital discharge than when resuscitation was provided by an ambulance technician. Resuscitation by a paramedic assisted by a medical practitioner offers a patient the best chances of surviving the event. (+info)
Delayed ischemic hyperintensity on T1-weighted MRI in the caudoputamen and cerebral cortex of humans after spectacular shrinking deficit.
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BACKGROUND AND PURPOSE: Transient internal carotid artery (ICA)-middle cerebral artery (MCA) occlusion caused by cardiogenic embolus can lead to spectacular shrinking deficit (SSD): sudden hemispheric stroke syndrome followed by rapid improvement. The aim of this study was to investigate sequential neuroradiological changes in the brains of patients after SSD compared with those after brief cardiac arrest and hypoglycemia, which we previously studied with the same methods. METHODS: We serially studied CT scans and MR images obtained at 1.5 T in 4 patients with SSD. All 4 patients suffered from transient neurological deficits due to cardiogenic embolus in ICA-MCA. The symptoms began to disappear from 25 to 50 minutes after onset. RESULTS: Repeated CT scans demonstrated no abnormal findings in the affected cerebral hemisphere in 3 of the 4 patients and a small cortical infarct in the remaining 1. In each patient, repeated MRI between day 7 and month 23 after stroke showed basal ganglionic and cortical lesions. These lesions were hyperintense on T1-weighted and relatively hypointense on T2-weighted imaging. These ischemic lesions of hyperintensity on T1-weighted MRI subsided with time. CONCLUSIONS: Transient ICA-MCA occlusion leading to SSD produces a specific ischemic change with delayed onset in the basal ganglia and cerebral cortex in humans on MRI but not CT scans. We speculate that the lesions represent incomplete ischemic injury, including selective neuronal death, proliferation of glial cells, paramagnetic substance deposition, and/or lipid accumulation. Unlike brief cardiac arrest or hypoglycemia, the localized lesions on MRI of patients after SSD seem to be incomplete and to differ from infarction or hemorrhage. (+info)
Dynamics of tissue oxygenation in isolated rabbit heart as measured with near-infrared spectroscopy.
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We investigated the role of myoglobin (Mb) in supplying O2 to mitochondria during transitions in cardiac workload. Isovolumic rabbit hearts (n = 7) were perfused retrogradely with hemoglobin-free Tyrode solution at 37 degrees C. Coronary venous O2 tension was measured polarographically, and tissue oxygenation was measured with two-wavelength near-infrared spectroscopy (NIRS), both at a time resolution of approximately 2 s. During transitions to anoxia, 68 +/- 2% (SE) of the NIRS signal was due to Mb and the rest to cytochrome oxidase. For heart rate steps from 120 to 190 or 220 beats/min, the NIRS signal decreased significantly by 6.9 +/- 1.3 or 11.1 +/- 2.1% of the full scale, respectively, with response times of 11.0 +/- 0.8 or 9.1 +/- 0.5 s, respectively. The response time of end-capillary O2 concentration ([O2]), estimated from the venous [O2], was 8.6 +/- 0.8 s for 190 beats/min (P < 0.05 vs. NIRS time) or 8.5 +/- 0.9 s for 220 beats/min (P > 0.05). The mean response times of mitochondrial O2 consumption (VO2) were 3.7 +/- 0.7 and 3.6 +/- 0.6 s, respectively. The deoxygenation of oxymyoglobin (MbO2) accounted for only 12-13% of the total decrease in tissue O2, with the rest being physically dissolved O2. During 11% reductions in perfusion flow at 220 beats/min, Mb was 1.5 +/- 0.4% deoxygenated (P < 0.05), despite the high venous PO2 of 377 +/- 17 mmHg, indicating metabolism-perfusion mismatch. We conclude that the contribution of MbO2 to the increase of VO2 during heart rate steps in saline-perfused hearts was small and slow compared with that of physically dissolved O2. (+info)