The effect of two different glycemic management protocols on postoperative cognitive dysfunction in coronary artery bypass surgery / Efeito de dois protocolos de controle glicêmico diferentes sobre a disfunção cognitiva após cirurgia de revascularização do miocárdio

Abstract Introduction: Postoperative cognitive dysfunction (POCD) is an adverse outcome of surgery that is more common after open heart procedures. The aim of this study is to investigate the role of tightly controlled blood glucose levels during coronary artery surgery on early and late cognitive decline. Methods: 40 patients older than 50 years undergoing elective coronary surgery were randomized into two groups. In the "Tight Control" group (GI), the glycemia was maintained between 80 and 120 mg dL-1 while in the "Liberal" group (GII), it ranged between 80-180 mg dL-1. A neuropsychological test battery was performed three times: baseline before surgery and follow-up first and 12th weeks, postoperatively. POCD was defined as a drop of one standard deviation from baseline on two or more tests. Results: At the postoperative first week, neurocognitive tests showed that 10 patients in the GI and 11 patients in GII had POCD. The incidence of early POCD was similar between groups. However the late assessment revealed that cognitive dysfunction persisted in five patients in the GII whereas none was rated as cognitively impaired in GI (p = 0.047). Conclusion: We suggest that tight perioperative glycemic control in coronary surgery may play a role in preventing persistent cognitive impairment.

Resumo Introdução: A disfunção cognitiva pós-operatória (DCPO) é um resultado adverso cirúrgico que é mais comum após cirurgias cardíacas abertas. O objetivo deste estudo foi investigar o papel dos níveis de glicose no sangue rigorosamente controlados durante a cirurgia coronariana no declínio cognitivo precoce e tardio. Métodos: Foram randomizados em dois grupos 40 pacientes acima de 50 anos e submetidos à cirurgia coronariana eletiva. No grupo "controle rigoroso" (GI), a glicemia foi mantida entre 80-120 mg.dL-1; enquanto no grupo "liberal" (GII), variou entre 80-180 mg.dL-1. A bateria de testes neuropsicológicos foi feita três vezes: fase basal, antes da cirurgia e na primeira e 12ª semana de acompanhamento no pós-operatório. DCPO foi definida como uma queda de um desvio padrão da fase basal em dois ou mais testes. Resultados: Na primeira semana de pós-operatório, os testes neurocognitivos mostraram que 10 pacientes no GI e 11 pacientes no GII apresentaram DCPO. A incidência de DCPO precoce foi semelhante entre os grupos. No entanto, a avaliação tardia revelou que a disfunção cognitiva persistiu em cinco pacientes no GII, enquanto nenhum paciente foi classificado como cognitivamente prejudicado no GI (p = 0,047). Conclusão: Sugerimos que o controle glicêmico rigoroso no perioperatório de cirurgia coronariana pode desempenhar um papel na prevenção da deterioração cognitiva persistente.

[The effect of two different glycemic management protocols on postoperative cognitive dysfunction in coronary artery bypass surgery]. / Efeito de dois protocolos de controle glicêmico diferentes sobre a disfunção cognitiva após cirurgia de revascularização do miocárdio.

INTRODUCTION: Postoperative cognitive dysfunction (POCD) is an adverse outcome of surgery that is more common after open heart procedures. The aim of this study is to investigate the role of tightly controlled blood glucose levels during coronary artery surgery on early and late cognitive decline. METHODS: 40 patients older than 50 years undergoing elective coronary surgery were randomized into two groups. In the "Tight Control" group (GI), the glycemia was maintained between 80 and 120mg·dL-1 while in the "Liberal" group (GII), it ranged between 80-180mg·dL-1. A neuropsychological test battery was performed three times: baseline before surgery and follow-up first and 12th weeks, postoperatively. POCD was defined as a drop of one standard deviation from baseline on two or more tests. RESULTS: At the postoperative first week, neurocognitive tests showed that 10 patients in the GI and 11 patients in GII had POCD. The incidence of early POCD was similar between groups. However the late assessment revealed that cognitive dysfunction persisted in five patients in the GII whereas none was rated as cognitively impaired in GI (p=0.047). CONCLUSION: We suggest that tight perioperative glycemic control in coronary surgery may play a role in preventing persistent cognitive impairment.

Effects of estradiol, estrogen receptor subtype-selective agonists and genistein on glucose metabolism in leptin resistant female Zucker diabetic fatty (ZDF) rats.

The leptin resistant Zucker diabetic fatty (ZDF) rats are hyperphagic and become obese, but whereas the males develop type 2 diabetes mellitus (T2DM), the females remain euglycaemic. As estrogen deficiency is known to increase the risk of developing T2DM, we evaluated the role of ER subtypes alpha and beta in the development of glucose tolerance in leptin resistant ovariectomized (OVX) ZDF rats. At least six rats per group were treated with either vehicle (OVX), 17ß-estradiol (E2), ER subtype-selective agonists (Alpha and Beta), or genistein (Gen) for 17 weeks. At the end of the treatment period a glucose tolerance assay was performed and the metabolic flux of (13)C-glucose for the E2 group was investigated. OVX ZDF rats treated with E2, Alpha, Beta, and Gen tolerated the glucose significantly better than untreated controls. E2 treatment increased absorbance/flux of (13)C-glucose to metabolic relevant tissues such liver, adipose tissue, gastrocnemius, and soleus muscle. Moreover, whereas Alpha treatment markedly increased mRNA expression of GLUT4 in gastrocnemius muscle, Beta treatment resulted in the largest fiber sizes of the soleus muscle. Treatment with Gen increased both the mRNA expression of GLUT 4 and the fiber sizes in the skeletal muscle. In addition, E2 and Alpha treatment decreased food intake and body weight gain. In summary, estrogen-improved glucose absorption is mediated via different molecular mechanisms: while activation of ER alpha seems to stimulate muscular GLUT4 functionality, activation of ER beta results in a hypertrophy of muscle fibers. In addition, selective activation of ER alpha decreased food intake and body weight gain. Our data further indicate that ER subtype-selective agonists and genistein improve systemic glucose tolerance also in the absence of a functional leptin signaling pathway.

Delayed argon administration provides robust protection against cardiac arrest-induced neurological damage.

INTRODUCTION: Argon at a dosage of 70 % is neuroprotective, when given 1 h after cardiac arrest (CA) in rats. We investigated if a neuroprotective effect of argon would also be observed, when administration was delayed. METHODS: Twenty-four male Sprague-Dawley rats, weighing between 400 and 500 g were subjected to 7 min of CA and 3 min of cardiopulmonary resuscitation. Animals were randomized to receive either 1 h of 70 % argon ventilation 1 h (n = 8) or 3 h (n = 8) after return of spontaneous circulation or no argon treatment (n = 8). For all animals, a neurological deficit score (NDS) was calculated daily for 7 days following the experiment. On day 8, rats were re-anesthetized and transcardially perfused before brains were harvested for histopathological analyses. RESULTS: All animals survived. Control animals exhibited severe neurologic dysfunction at all time points as measured with the NDS. Argon-treated animals showed significant improvements in the NDS through all postoperative days, even when argon administration was delayed for 3 h. This was paralleled by a significant reduction in the neuronal damage index in the neocortex and the hippocampal CA 3/4 region in argon-treated animals, regardless of the timing of argon administration. However, animals of the delayed argon administration group additionally showed significant reductions in the basal ganglia in comparison with control animals. CONCLUSION: Our study demonstrates that a 1-h application of argon provided a significant reduction in histopathological damage, associated with a marked improvement in functional neurologic recovery even when treatment was delayed for 3 h. This is highly significant with regard to clinical situations, where argon treatment cannot be provided timely.

Dose dependent neuroprotection of the noble gas argon after cardiac arrest in rats is not mediated by K(ATP)-channel opening.

PURPOSE: Argon at a dosage of 70% is neuroprotective when given 1 h after cardiac arrest (CA) in rats. In a rodent model, we investigated if the neuroprotective effects of argon are dose dependent and mediated by adenosine triphosphate dependent potassium (K(ATP)) channels. METHODS: Forty-seven male Sprague-Dawley rats were subjected to 7 min of CA and 3 min of cardiopulmonary resuscitation (CPR). In protocol I animals were randomized to receive either 70% or 40% argon ventilation 1 h after successful CPR or no argon-treatment. Animals of the second protocol also received 1 h of 70% argon ventilation or no argon treatment but were randomized to a group receiving the K(ATP) channel blocker 5-hydroxydecanoate (5-HD). For all animals a neurological deficit score (NDS) was calculated daily for seven days following the experiment before the animals were killed and the brains harvested for histopathological analyses. RESULTS: All animals survived. Control animals exhibited severe neurologic dysfunction at all points in time as measured with the NDS. Argon treated animals showed significant improvements in the NDS through all postoperative days in a dose dependent fashion. This was paralleled by a significant reduction in the neuronal damage index in the neocortex and the hippocampal CA 3/4 region. Administration of 5-HD neither abolished the positive effects on functional recovery nor on histopathologic changes observed in the argon group. CONCLUSION: Our study demonstrates a dose dependent neuroprotective effect of argon administration in this rodent model, which is not mediated via ATP dependent potassium channels.