Local Cerebral Blood Flow is Preserved in Sepsis

Abstract

Sepsis is often complicated by encephalopathy, neuroendocrine dysfunction and cardiovascular autonomic failure. The cause of septic brain dysfunction is not fully understood. The aim of the present study is to explore whether septic brain dysfunction in a common septic model in the rat correlates with abnormalities either of local cerebral blood flow (LCBF) of defined brain areas or of whole brain blood flow (CBF). 45 male Wistar rats (320+/-13 g) were randomly assigned to a sepsis group (31 rats, cecal ligature and puncture, CLP) or a control group (14 rats, sham operation). Of these 45 rats, 16 rats were used for blood analysis; the remaining 29 rats were used for CBF/LCBF measurements. LCBF measurements were performed 24h after initial surgery using quantitative autoradiography with 4-iodo[N-methyl-(14)C]antipyrine, which allows to analyze CBF on a regional/local and global basis. In 42 different brain regions bilateral optical density measurements were performed. Septic rats (vs. control) presented tachycardia (507+/-37 vs. 452+/-44 min(-1), P<0.05), leukocytopenia (2.96+/-2.37 vs. 8.83+/-2.9710(9) x L(-1), P<0.05), hypocapnia (29.3+/-4.6 vs. 36.4+/-3.9 mmHg, P<0.05), and higher serum lactate concentrations (5.7+/-3.9 vs. 2.2+/-2.0 mmol x L(-1), P<0.05). LCBF of all 42 areas, as well as, CBF (116+/-59 vs. 115+/-52 m x 100 g(-1)min(-1), n.s.) did not differ. The results showed that severe sepsis (mortality rate of 43 %) did not induce alterations in mean CBF and LCBF. It is concluded that brain dysfunction is not reflected in changes of CBF during severe sepsis.

Autoregulative function in the brain in an endotoxic rat shock model

“…Unfortunately the authors did not perform serial measurements to exclude a transient cerebral hyperemia and also did not investigate autoregulative function. However, since blood pressure levels remained above 100 mmHg [27] a direct comparability to the present study of septic shock might also not be given.…”

“…However, in more severe cases in which higher toxin doses are assumable (septic patients) [26] or actually have been given (animal models) [22] significant hyperemia and autoregulative failure was present. A recent study in a CLP rat model did not find changes in resting cerebral blood flow 24 h after sepsis induction using quantitative autoradiography [27]. Unfortunately the authors did not perform serial measurements to exclude a transient cerebral hyperemia and also did not investigate autoregulative function.…”

“…Controversies in literature concerning autoregulative function can be explained by the different stimulation techniques, varying time points of investigation and different types and severity of sepsis syndromes [11,[24][25][26][27]. Some groups using classical autoregulative tests did not find relevant changes in cerebral blood flow regulation and concluded unaffected cerebral autoregulation [11] whereas others found significant affection of autoregulative function [12].…”

Endotoxin-induced gene expression differences in the brain and effects of iNOS inhibition and norepinephrine

“…Interestingly, microcirculatory dysfunction and inappropriate blood supply of organ cells on a microscopic level occur when overall blood flow and blood pressure (BP) are still in the normal range. This might explain, why studies on the overall cerebral blood flow did not find a relation to early sepsis-associated delirium [7,8]. However, by preventing excessive NO-production selective iNOS inhibitors attenuate the vascular dysfunction in a sepsis syndrome such as hypotension, endothelial dysfunction and microvascular shunting [9,10].…”

Frühzeitige Veränderungen der Proteinexpression im Gehirn der Ratte bei Sepsis

“…B. Abfall des arteriellen Mitteldrucks bzw. Perfusionsdrucks) wurden als direkte Auslöser in Betracht gezogen [26], konnten aber bisher nicht verifiziert werden [17]. Die Rolle von funktionellen intrazerebralen Veränderungen wie beispielsweise der Blut-Hirn-Schranke ("blood brain barrier", BBB; [8,15,20,25]), des lokalen Glucosemetabolismus im Gehirn [34] oder des Gehalts von Aminosäuren, Neurotransmittern oder Metaboliten [8,12,15] ist ebenfalls nach wie vor unklar.…”