Progress in pharmaceutical research for cerebral resuscitation after cardiac arrest / 中华危重病急救医学

With the popularization of cardiopulmonary resuscitation (CPR) technology, the success rate of restoration of spontaneous circulation (ROSC) is gradually improved, and the survival rate and neurological outcome of patients with cardiac arrest are improved. Currently, therapeutic methods for cerebral resuscitation after cardiac arrest are limited. In addition to mild hypothermia for clinical application, the majority of drugs remain in the animal experimental stage. Finding effective brain protection drugs has become a hot spot in the field of brain resuscitation research. This article will review the pharmaceutical progress of research for cerebral resuscitation after cardiac arrest, so that we can study the brain protection mechanism of these drugs better and more targeted.

Hemodynamic effects of mannitol infusion in patients with acute intracerebral hemorrhage

PURPOSE: To evaluate hemodynamic effects of mannitol infusion in patients with acute intracerebral hemorrhage. METHODS: Thirty patients with acute intracerebral hemorrhage were enrolled. Transcranial doppler was used to detect variables of bilateral middle cerebral arteria (MCA) including mean velocity (Vm) and pulsitility index (PI) before and after125ml and 250ml mannitol infusion (0, 30, 60, 90, 120, 180, 240 min). RESULTS: When 125ml or 250ml mannitol was infused in patients with acute intracerebral hemorrhage, Vm of bilateral MCA elevated, and reached the top at 30min, and then decreased. PI decreased in the affected MCA (250ml) and in the unaffected MCA (125ml and 250ml). CONCLUSION: Mannitol infusion in patients with acute intracerebral hemorrhage can improve cerebral blood flow in bilateral hemispheres and decrease intracranial pressure in the hemorrhagic hemisphere (250ml) and in the nonhemorrhagic hemisphere (125ml and 250ml).

Evaluation of the effect of donepezil on cerebral blood flow velocity in Alzheimer's disease

To evaluate the effect of Donepezil on cerebral blood flow velocity using non-invasive transcranial Doppler [TCD] sonography. This clinical trial was carried out in the Department of Neurology, Alzahra Hospital, Isfahan University of Medical Sciences, Isfahan, Iran from March 2008 to July 2009, on Alzheimer's disease [AD] patients in 2 groups of case and control, each consisting of 11 patients. The case group who received Donepezil medication was examined by TCD before [baseline], after 4 weeks of oral treatment with 5mg per day Donepezil, and a further 4 weeks of 10mg per day Donepezil, orally. The control group comprised AD patients who did not receive any medications, and were examined by TCD only once. Peak systolic [PSV], end-diastolic [EDV], and mean flow [MFV] velocities of the posterior cerebral artery [PCA] and the middle cerebral artery [MCA] was assessed by TCD. Also, mini-mental state examination [MMSE] was carried out. There were no significant differences between the case and control groups, in terms of age and gender. In the case group, the mean MMSE score reached 20.2 +/- 2.8 from a baseline value of 15.8 +/- 3.3 after 4 weeks of oral treatment with 5mg/d Donepezil, and reached 20.6 +/- 3.9 after 4 more weeks at 10mg/d Donepezil. In the MCA, the difference in PSV and MFV values after 4 weeks of treatment with 10mg/d Donepezil was statistically significant compared with the baseline values. In PCA, the values of MFV and EDV after 4 weeks of treatment with 10mg/d Donepezil were statistically significant in comparison with the baseline value. Donepezil [10mg/d] increased cerebral blood flow velocity and MMSE score in our AD patients, but more extensive trials are recommended

Hypocapnia Attenuates, and Nitrous Oxide Disturbs the Cerebral Oximetric Response to the Rapid Introduction of Desflurane

The aim of this study was to develop a nonlinear mixed-effects model for the increase in cerebral oximetry (rSO2) during the rapid introduction of desflurane, and to determine the effect of hypocapnia and N2O on the model. Twelve American Society of Anesthesiologist physical status class 1 and 2 subjects were allocated randomly into an Air and N2O group. After inducing anesthesia, desflurane was then increased abruptly from 4.0 to 12.0%. The PET(CO2), PET(DESF) and rSO2 were recorded at 12 predetermined periods for the following 10 min. The maximum increase in rSO2 reached +24-25% during normocapnia. The increase in rSO2 could be fitted to a four parameter logistic equation as a function of the logarithm of PET(DESF). Hypocapnia reduced the maximum response of rSO2, shifted the EC50 to the right, and increased the slope in the Air group. N2O shifted the EC50 to the right, and reduced the slope leaving the maximum rSO2 unchanged. The N2O-effects disappeared during hypocapnia. The cerebrovascular reactivity of rSO2 to CO2 is still preserved during the rapid introduction of desflurane. N2O slows the response of rSO2. Hypocapnia overwhelms all the effects of N2O.

Effects of nimodipine on cerebral hemodynamics, and prognosis of diffuse axonal injury patients

To evaluate the effects of nimodipine on hemodynamic state, vasospasm, and short time prognosis of diffuse axonal injury [DAI] patients. In a prospective, clinical trial double blind study, 40 DAI patients with Glasgow coma scale of 5-8 were selected and randomly divided into 2 equal groups. The first group was treated with 60 mg of nimodipine every 4 hours immediately after admission, and the control group did not receive this treatment. Mean blood flow velocity [MFV] and pulsatility index of both middle cerebral arteries were measured using transcranial Doppler on the 1st, 3rd, and 10th days of admission. Glasgow outcome scale was evaluated one month after admission. This study was performed from June 2003 to June 2004 at Imam Medical Center, Tabriz, Iran. There were significant differences in MFV among the 3 transcranial Doppler, which demonstrated hemodynamic changes in these patients. Nimodipine did not have any significant difference on MFV between the treatment and control groups. In the nimodipine group, 45% had good prognosis [30% in the control group] and nobody had vasospasm on the 10th day Doppler study [15% in the control group], although it did not show any statistical significant difference between them. Nimodipine improved the prognosis and decreased vasospasm, however, there was no statistical difference. Therefore, we suggest further studies in a larger number of DAI patients

Pharmacotherapy and Regional Cerebral Blood Flow in Children with Obsessive Compulsive Disorder

While regional cerebral blood flow (rCBF) studies on adults involving the caudate, prefrontal, orbitofrontal, and cingulated areas have been reported, no such published data on children exist. In this study, we aimed to determine the significance of pre- and post-treatment regional cerebral blood flow (rCBF) differences in children with obsessive compulsive disorder (OCD) and compared them with healthy controls. Eighteen drug-free obsessive compulsive children, aged 11 to 15, without comorbid states except for anxiety disorders - participated in this study. The control group consisted of 12 children, aged 11 to 15, with no medical or psychiatric illnesses. Using SPECT (Single Photon Emission Computerized Tomography) scans with Technetium-99m-HMPAO-hexamethly propyleneamine oxime (Tc99mHMPAO), the rCBF was calculated in 15 regions of the control group according to a standard protocol, while in the study group, it was measured at baseline and after 12 weeks of treatment with a fixed dose of paroxetine (20 mg qd). We compared the resulting pre- and post-treatment CBF values for the control group and study group. The right and left caudates, right and left dorsolateral prefrontals, and cingulate had significantly higher rCBF in children with obsessive compulsive disorder than in the control group. These areas, in addition to the right anteromedial temporal, showed significant rCBF reduction after treatment with paroxetine. The mean percentage of change in obsession scores during the treatment correlated significantly with the baseline and post- treatment rCBF level of the right caudate, post-treatment left caudate, and baseline left caudate. Our findings on children are consistent with adult studies and support the theory of a cortical-striatal-thalamic-cortical loop disturbance in OCD.

Effects of Dopamine Infusion on Cerebral Blood Flow, Brain Cell Membrane Function and Energy Metabolism in Experimental Escherichia coli Meningitis in the Newborn Piglet

In the present study, we tested whether maintenance of adequate cerebral perfusion pressure (CPP) by pharmacologically preventing systemic hypotension with dopamine infusion would prevent cerebral ischemia and attenuate energy depletion and neuronal injury even though intracranial pressure remains elevated in a newborn piglet meningitis model. Cerebral blood flow, measured at the end of the experiment using fluorescent microspheres, was significantly increased by dopamine infusion. The decreased cerebral cortical cell membrane Na+, K+-ATPase activity and increased lipid peroxidation products, indicative of meningitis-induced brain damage, were significantly attenuated by dopamine infusion. Dopamine also significantly attenuated the meningitis-induced reduction in both brain ATP and phosphocreatine levels and the increase in brain lactate level. In summary, maintenance of adequate CPP with dopamine prevented cerebral ischemia, reduced cerebral energy depletion, and attenuated brain injury in neonatal bacterial meningitis.

Influence of Isoflurane Anesthesia on Pulsatility Index and Peak Systolic Velocity of Basilar Artery in Dogs by Doppler Ultrasonography

This study was performed to examine the influence of isoflurane anesthesia on the pulsatility index (PI) and the peak systolic velocity (PSV) of the blood flow in the basilar artery of dogs by duplex Doppler ultrasonography. Twelve healthy dogs were used to measure the PI and the PSV under the conscious state and isoflurane anesthesia. The pulsatility index (PI) and the peak systolic velocity (PSV) in the basilar artery were measured five times with random intervals. The blood pressure was measured. The PI and PSV values in dogs under isoflurane anesthesia were 1.37 +/- 0.32 and 72 +/- 19 cm/sec, whereas those in the conscious dogs were 1.37 +/- 0.13 and 81 +/- 16 cm/sec, respectively. The indirect mean arterial systolic and diastolic pressures under isoflurane anesthesia were 107 and 51 mmHg, whereas those in the conscious dogs were 133 and 74 mmHg. Though the isoflurane is generally known to induce hypotension, there were no significant differences in the PI and PSV between the isoflurane-anesthetized and the conscious dogs. In conclusion, the isoflurane anesthesia did not influence the PI and PSV in the basilar artery of dogs.

Methylphenidate increased regional cerebral blood flow in subjects with attention deficit/hyperactivity disorder

The regional cerebral blood flow (rCBF) responses to methylphenidate (MPH) treatment were examined in children with attention deficit/hyperactivity disorder (ADHD). Thirty-two male children, diagnosed with ADHD by the DSM-IV diagnostic criteria, other behavioral assessment scales and neuropsychological battery, were studied using 99mTc-HMPAO-single photon emission computed tomography (SPECT). Subjects were studied before and after MPH treatment. First, using an image subtraction method, we obtained a NDR parametric image of each patient and found increased cerebral blood flow in the frontal lobes, caudate nuclei and thalamic areas after treatment. When the changes in SPECT and clinical response were compared, the matching rate, sensitivity and specificity between them were found to be 77.1, 80.0 and 79.2%, respectively. Second, three transaxial brain slices delineating anatomically defined regions of interest (ROI) at 20, 40, and 60mm above the orbitomeatal line (OML) were used, with the average number of counts for each region of interest normalized to the area of the cerebellar maximal uptake. The left and right prefrontal areas, and caudate and thalamic areas showed significant increases in rCBF after MPH treatment. These findings suggested MPH could affect the function of the fronto-striato-thalamic circuit, which is known as the pathophysiologic site of ADHD and could be used to correct the underlying brain dysfunction of ADHD.

Control of hypertension during labour and obstetric operation by using nifedipine and its effect on maternal cerebral circulation

Nifedipine is an effective drug in the management and the control of primary and secondary hypertension and hypertensive crisis during the gynecological and obstetric operation and it also reduces the mean blood flow velocity of the middle cerebral artery

The role of the endothelial dependent relaxing factor in the regulation of cerebral circulation

Recentemente foi descoberto que o endotélio vascular deve estar intacto para que vasos sanguíneos dilatem quando estimulados por agentes fisiológicos. Acredita-se que uma substância química ainda desconhecida, genericamente chamada Fator Relaxante Endotelial (FRE), produzida pelo endotélio, é indispensavel para o relaxamento vascular. Neste trabalho é revista a fisisologia circulatória cerebral e possíveis açöes do FRE. Discute-se também a importância de lesöes endoteliais em relaçäo ao controle circulatório cerebral

Cerebral vasospasm

Vasoespasmo cerebral ocorre em patologias como enxaqueca, hemorragia subaracnóidea, trauma de crânio, após isquemia e/ou hipoxia. A fisiopatologia do vasoespasmo cerebral nestas patologias näo está completamente desvendada. Neste artigo säo analisados os fatores neuroquímicos e morfológicos responsáveis pelo controle circulatório cerebral. As alteraçöes circulatórios que seguem a hemorragia subaracnóidea säo utilizadas como exemplo. Conclui-se que fatores bioquímicos, fisiológicos e morfológicos säo responsáveis pelas manifestaçöes vasculares que ocorrem após a hemorragia subaracnóidea. Alternativas de tratamento do vasoespasmo cerebral säo discutidas

Ensayo multicéntrico con vincamina en las manifestaciones clínicas por deterioso cerebral en insuficiencia circulatoria / Multicenter trial with vincamine in clinical manifestations of cerebral circulatory insufficiency

Trescientos cincuenta y tres pacientes, divididos en tres grupos, con manifestaciones de insuficiencia circulatoria cerebral, pérdida de la autonomía y sintomatología neurosensorial, fueron tratados con 60 mg de vinvamina* al día, durante 30,45 y 60 días. Se observó mejoría de la sintomatología objetiva y subjetiva que acompaña a la insuficiencia circulatoria cerebral y se comprobó mediante análisis estadístico con la prueba t de Student. Todos los parámetros mostraron resultados altamente significativos con p <0.001. La tolerancia fue excelente, sólo 5% de los 353 pacientes tratados presentaron efectos secundarios leves y pasajeros que no impidieron la contaminación del estudio