Importance of assessing biomarkers and physiological parameters of anemia-induced tissue hypoxia in the perioperative period

Abstract Anemia is associated with increased risk of Acute Kidney Injury (AKI), stroke and mortality in perioperative patients. We sought to understand the mechanism(s) by assessing the integrative physiological responses to anemia (kidney, brain), the degrees of anemia-induced tissue hypoxia, and associated biomarkers and physiological parameters. Experimental measurements demonstrate a linear relationship between blood Oxygen Content (CaO2) and renal microvascular PO2 (y = 0.30x + 6.9, r2= 0.75), demonstrating that renal hypoxia is proportional to the degree of anemia. This defines the kidney as a potential oxygen sensor during anemia. Further evidence of renal oxygen sensing is demonstrated by proportional increase in serum Erythropoietin (EPO) during anemia (y = 93.806*10−0.02, r2= 0.82). This data implicates systemic EPO levels as a biomarker of anemia-induced renal tissue hypoxia. By contrast, cerebral Oxygen Delivery (DO2) is defended by a profound proportional increase in Cerebral Blood Flow (CBF), minimizing tissue hypoxia in the brain, until more severe levels of anemia occur. We hypothesize that the kidney experiences profound early anemia-induced tissue hypoxia which contributes to adaptive mechanisms to preserve cerebral perfusion. At severe levels of anemia, renal hypoxia intensifies, and cerebral hypoxia occurs, possibly contributing to the mechanism(s) of AKI and stroke when adaptive mechanisms to preserve organ perfusion are overwhelmed. Clinical methods to detect renal tissue hypoxia (an early warning signal) and cerebral hypoxia (a later consequence of severe anemia) may inform clinical practice and support the assessment of clinical biomarkers (i.e., EPO) and physiological parameters (i.e., urinary PO2) of anemia-induced tissue hypoxia. This information may direct targeted treatment strategies to prevent adverse outcomes associated with anemia.

Chin tremor in full-term neonate after hypoxia / Tremor de mento em recém-nascido no termo após hipóxia neonatal

CONTEXT: Newborns may present a range of motor phenomena that are not epileptic in nature. Chin tremor is an unusual movement disorder that typically starts in early childhood and may be precipitated by stress and emotion. Its pathophysiology has not been fully elucidated. CASE REPORT: We describe a full-term newborn that, immediately after neonatal anoxia, presented body and chin tremors that were unresponsive to anti-epileptic drugs. Subsequent neurological evaluation revealed signs of pyramidal tract damage and chin tremor triggered by percussion and crying. We discuss the hypothesis that the anatomopathological abnormality may lie at the level of the higher cortical centers or midbrain. CONCLUSIONS: Further studies are needed in order to gain greater comprehension of neonatal tremors. Recognition of the various etiological possibilities and consequent management of treatable causes is essential for care optimization.

CONTEXTO: O recém-nascido está sujeito a uma gama de fenômenos motores de natureza não epiléptica. O tremor do mento é um distúrbio do movimento incomum que tem início habitual na infância e pode ser precipitado por estresse e emoção. Sua fisiopatologia não foi completamente elucidada. RELATO DE CASO: Descrevemos um recém-nascido no termo, que, após anóxia neonatal, apresentou tremor de corpo e mento não responsivo ao uso de drogas antiepilépticas. A avaliação neurológica posterior revelou sinais de lesão do trato piramidal e tremor de mento desencadeado por choro e percussão. Discutimos a hipótese de que as alterações anatomopatológicas estejam localizadas no mesencéfalo ou centros corticais superiores. CONCLUSÕES: São necessários novos estudos para maior compreensão dos tremores em recém-nascidos. O reconhecimento das diversas possibilidades etiológicas e o decorrente manejo das causas tratáveis são essenciais para a otimização do atendimento.

El juego de la asfixia en la adolescencia: entre la experimentación y el riesgo / The choking game in adolescence, between experimentation and risk

En el último año ha tenido lugar una serie de muertes de adolescentes en Salta que podrían estar relacionadas con un peligrosojuego llamado “juego de la asfixia”. Se lo practica desde hace muchos años en varios países del mundo y consiste en provocar hipoxia cerebral por algunos segundos, mediante diferentes técnicas, para obtener un instante de éxtasis y placer.Consideramos relevante que el equipo de salud conozca esta práctica y pueda identificar, a través de signos y íntomas, cuando un adolescente pueda estar jugando al juego de la asfixia.

Síndrome de Lance-Adams: presentación de dos casos / Lance-Adams syndrome: report of two cases

Lance-Adams syndrome was described in 1963 is a rare complication due to recovered hypoxic episodes or prolonged hypotension events. Is characterized by action myoclonus and cerebellar ataxia. We report two patients studied with this syndrome. A 51 year-old men and a 72 years-old men fully recovered after a brief cardiorespiratory arrest they developed intention myoclonus, triggered by voluntary movements, posture, also by sounds, touches and emotional stimuli. It also was accompanied by cerebellar syndrome, ataxia and posture control alterations. They had a Magnetic Resonance (MR), EEG and normal metabolic parameters. Myoclonus was treated with sodium valproate and clonazepam. The neurophysiologic interpretation of this motor imbalance is an abnormal functioning of the Central Pattern Generator Netwoks (CPGN) located in the mesencephalic region. Hypoxic lesions in vermian purkinje and paravermal cerebellum neurons have an inhibitory effect in this system, producing motor control attenuation, generating an imbalance in the motoneurons of the spinal cord contraction sequence, which starts shooting in an uncoordinated way. As in almost all cerebellar lesions with time they tend to compensate and to diminish myoclonus.

El Síndrome de Lance-Adams descrito en 1963, es una rara complicación que sigue tardíamente a episodios hipóxicos o de hipotensión prolongada, ya recuperados. Se caracteriza por mioclonías de acción y ataxia cerebelosa. Se describen dos pacientes estudiados con este síndrome. Son dos hombres de 51 y 72 años que después de un paro cardiorrespiratorio breve, de recuperación completa, iniciaron mioclonías de intención, activadas por movimientos voluntarios, posturas, estímulos sonoros, táctiles y afectivos. Acompañado además de un síndrome cerebeloso, ataxia de la marcha y alteraciones del control postural. Cursaron con RM (Resonancia Magnética), EEG (Electroencefalograma) y parámetros metabólicos sin relevancia patológica. Las mioclonías fueron controladas con ácido valproico y clonazepam. La interpretación neurofisiológica de este desajuste motor es la alteración en el funcionamiento del patrón central de circuitos generadores (PCCG) ubicado en la región mesencefálica. Las lesiones hipóxicas de las neuronas de Purkinje del vermis y paravermianas del cerebelo, que tienen un efecto inhibitorio para este sistema, producen una atenuación del control motor del PCCG, generando desajuste en la secuencia de la contracción de las motoneuronas de la médula espinal, que comienzan a dispararse de manera independientemente. Como ocurre con la mayoría de las lesiones cerebelosas, con el tiempo tienden a compensarse y por consiguiente a disminuir las mioclonías.

Effect of Scutellaria flavonoids on KCN-induced damages in rat pheochromocytoma PC12 cells.

BACKGROUND & OBJECTIVE: Cerebral hypoxia is known to be involved in many neurodegenerative diseases such as Alzheimer's and cerebrovascular dementia. The present study was designed to investigate the effects of flavonoids from aerial part of Scutellaria baicalensis Georgi (SSF) on potassium cyanide (KCN) -induced hypoxic cytotoxicity in rat pheochromocytoma cell line PC12, and to understand the probable mechanism. METHODS: The rat pheochromocytoma cell line PC12 was subjected to hypoxia by 200 microM KCN for 30 min. The cytotoxicity of KCN was assessed by cell viability assay, morphological observation, lactate dehydrogenase (LDH) release, malondialdehyde (MDA) production, and the activities of superoxide dismutase (SOD) and Na+-K+-ATPase measurements. The effects of SSF on the changes induced by KCN in PC12 cells were detected. RESULTS: Treatment of PC12 cells with 200 micriM KCN for 30 min increased cell death when compared with control, as assayed by MTT reduction, morphological observation and lactate dehydrogenase release measurement. These cell lesions were accompanied by disorders in SOD and Na+-K+-ATPase activities as well as MDA production. In contrast, the PC12 cells pre-treated with SSF for 24 h prior to 200 microM KCN exposure have shown protection against hypoxic toxicity. The KCN - induced decreased cell viability and activities of SOD and Na+-K+-ATPase, as well as increased MDA production were reversed by SSF pre-treatment. INTERPRETATION & CONCLUSION: SSF exerted neuroprotections against KCN - induced hypoxic cytotoxicity in PC12 cells and the probable mechanisms involved free radicals and energy metabolism. Our findings may have implications in future in the treatment of neurodegenerative diseases.

Efectos neurológicos de la ligadura de la carótida común izquierda e hipoxia inducida en ratas neonatas / Neurological effects by occlusion of the carotid artery and induced hypoxia in newborn rats

BACKGROUND: Hypoxic-ischemic encephalopathy is a cause of disability in the infant population. One of the most used animal models in the hypoxic-ischemic encephalopathy in immature brain is the preparation of Levine applied by Rice in newborn rats and consists of the bond of the left common carotid artery followed by induced hypoxia. The objective of this investigation was to study the neurological effects of the bond of the left common carotid and induced hypoxia in newborn rats. METHODS: Five control rats, five sham rats and five rats with hypoxic-ischemic lesion by means of the application of Levine's preparation at 7 days of age were used. On day 42, all rats were evaluated by time of grasping, posterior reflex test and analysis of the spontaneous locomotor activity (number of bipedal movements, number of stepped stalls, grooming time). RESULTS: The lesioned group presented less grasping time, lower number of positive responses to the posterior reflex and lower number of stepped stalls (p = 0.024, 0.002 and 0.0001, respectively). There were no statistically significant differences in grooming time or number of bipedal movements. CONCLUSIONS: Newborn rats in whom Levine preparation was applied presented clinical alterations that may resemble some of the signs that accompany infantile cerebral palsy (grasp problems, wrong response to postural reflexes and alteration in locomotion).

Nootropic effect of BR-16A (Mentat), a psychotropic herbal formulation, on cognitive deficits induced by prenatal undernutrition, postnatal environmental impoverishment and hypoxia in rats.

Subchronic administration of BR-16A (Mentat), a compound herbal formulation, and the nootropic agent, piracetam, augmented learning acquisition and retention of learning in normal rats, as well as in states of cognitive deficits induced by prenatal undernutrition, postnatal environmental impoverishment and sodium nitrite hypoxia. The test paradigms used were step-down latency in a passive avoidance test and transfer latency in elevated plus maze. The drugs were administered orally once daily for 7 days, behavioural testing being done 1 hr after the last administration on day 7. Post-trial performances of the rats at 24 hr and after another 7 days was assessed as indices of learning acquisition and retention of learning (memory), respectively. Mentat (100 mg/kg) and piracetam (100 mg/kg) induced statistically significant nootropic effect in all the test parameters. However, the lower dose (50 mg/kg) of Mentat did not significantly augment learning acquisition in normal rats and in induced states of cognitive deficits, but significantly improved retention of learning in normal rats and in animals with cognitive deficits. Acute single administration of either Mentat (100 mg/kg, orally) and piracetam (100 mg/kg, orally) did not exhibit any discernible nootropic effect in any of the paradigms or parameters investigated. The results indicate that Mentat, like piracetam, can facilitate learning and memory, and can be categorized as a nootropic agent. They also corroborate clinical reports on the memory-facilitative effect of Mentat and earlier experimental evidence of its nootropic activity in mice.

Delayed-onset focal dystonia after diffuse cerebral hypoxia: two case reports

The delayed-onset focal dystonia is a rare sequela of cerebrovascular disease or diffuse cerebral hypoxic damage. The responsible lesion sites for the dystonia are variable and the pathogenesis is uncertain. We describe two children with delayed-onset focal dystonia as a complication of perinatal anoxia. The intervals between hypoxic insult and onset of dystonia were 6 years in one and 3 in the other cases. Our patients did not have a focal lesion; one had scattered white matter lesion and the other had a diffuse frontoparietal atrophy. Delayed-onset dystonia after perinatal anoxia can be also caused by non-focal lesion such as diffuse frontoparietal atrophy or cerebral white matter lesion with long interval delay.

Seqüelas visuais após parada cardíaca: a propósito de um caso

Os AA. realatam o caso de uma jovem de 20 anos que sofreu parada cardíaca durante cirurgia maxilar, sob anestesia geral, realizada há cinco anos, num hospital de Porto Alegre. A padiente apresenta déficit campimétrico bilateral definitivo, central em OD e periférico em OE. A propósito, é feita uma revisäo dos aspectos envolvidos na síndrome da hipóxia cerebral aguda

Achados eletrencefalográficos na encefalopatia mioclônica pós anóxica / Electroencephalographic findings in post-anoxic myoclonic encephalopathy

Foram submetidos a exame eletrencefalográfico (EEG) 9 pacientes, 7 do sexo feminino e dois do masculino, os quais após terem sofrido períodos variáveis de hipoxia cerebral provocada ou por parada cárdio-respiratória (8 casos) ou por ferida da artéria carótida primitiva esquerda e choque séptico (um caso) desenvolveram abalos mioclônicos. As características do EEG de nossos enfermos, foram compatíveis às referidas por Gastaut e Rémond em 1952. Em dois pacientes (casos 6 e 9) o componente onda do complexo ponta onda foi mais rápido que os registrados nos traçados dos demais pacientes