C. Lenz

Local cerebral blood flow, Local cerebral glucose utilization, and flow-metabolism coupling during sevoflurane versus isoflurane anesthesia in rats

Background Compared to isoflurane, knowledge of local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) during sevoflurane anesthesia is limited. Methods LCGU, LCBF, and their overall means were measured in Sprague‐Dawley rats (8 groups, n = 6 each) during sevoflurane and isoflurane anesthesia, 1 and 2 MAC, and in conscious control animals (2 groups, n = 6 each) using the autoradiographic 2‐[(14) C]deoxy‐D‐glucose and 4‐iodo‐N‐methyl‐[(14) C]antipyrine methods. Results During anesthesia, mean cerebral glucose utilization was decreased: control, 56 +/− 5 [micro sign]mol [middle dot] 100 g‐1 [middle dot]‐1; 1 MAC isoflurane, 32 +/− 4 [micro sign]mol [middle dot] 100 g‐1 [middle dot] min‐1 (‐43%); 1 MAC sevoflurane, 37 +/− 5 [micro sign]mol [middle dot] 100 g‐1 [middle dot] min‐1 (‐34%); 2 MAC isoflurane, 23 +/− 3 [micro sign]mol [middle dot] 100 g‐1 [middle dot] min‐1 (‐58%); 2 MAC sevoflurane, 23 +/− 5 [micro sign]mol [middle dot] 100 g‐1 [middle dot] min‐1 (‐59%). Local analysis showed a reduction in LCGU in the majority of the 40 brain regions analyzed. Mean cerebral blood flow was increased as follows: control, 93 +/− 8 ml [middle dot] 100 g‐1 [middle dot] min‐1; 1 MAC isoflurane, 119 +/− 19 ml [middle dot] 100 g‐1 [middle dot] min‐1 (+28%); 1 MAC sevoflurane, 104 +/− 15 ml [middle dot] 100 g‐1 [middle dot] min‐1 (+12%); 2 MAC isoflurane, 149 +/− 17 ml [middle dot] 100 g‐1 [middle dot] min‐1 (+60%); 2 MAC sevoflurane, 118 +/− 21 ml [middle dot] 100 g‐1 [middle dot] min‐1 (+27%). LCBF was increased in most brain structures investigated. Correlation coefficients obtained for the relationship between LCGU and LCBF were as follows: control, 0.93; 1 MAC isoflurane, 0.89; 2 MAC isoflurane, 0.71; 1 MAC sevoflurane, 0.83; 2 MAC sevoflurane, 0.59). Conclusion Mean and local cerebral blood flows were lower during sevoflurane than during isoflurane anesthesia. This difference cannot be explained by differing changes in glucose utilization because glucose utilization was decreased to the same extent in both groups.

Evidence for apoptotic cell death in the choroid plexus following focal cerebral ischemia

Focal cerebral ischemia in rats subjected to middle cerebral artery (MCA) occlusion results in apoptotic DNA fragmentation and activation of putative cell death effector genes in neurons and functional impairment of the plexus choroideus. In the present study we investigated whether cerebral ischemia may induce apoptotic cell death in the choroid plexus. Using in situ end-labeling by terminal transferase and fluorescein-dUTP, nuclear DNA breaks were detected in the choroid plexus of the lateral ventricle of the ischemic hemisphere after 6 h but not after 1.5 h of MCA occlusion. Intense cytoplasmic immunostaining for pro-apoptotic Bax protein and moderate immunolabeling for Bcl-X was observed in the epithelium of the choroid plexus of the lateral and third ventricles. However, constitutive expression of Bax and Bcl-X proteins in the plexus choroideus did not change significantly following focal ischemia. Thus, cells of the choroid plexus may die by apoptosis after several hours of cerebral ischemia. Modulation of cell death effector genes of the bcl-2 family however, may not be required for apoptotic cell death to occur.

Mild and Moderate Hypothermia (α-Stat) Do Not Impair the Coupling Between Local Cerebral Blood Flow and Metabolism in Rats

BACKGROUND AND PURPOSE The effects of hypothermia on global cerebral blood flow (CBF) and glucose utilization (CGU) have been extensively studied, but less information exists on a local cerebral level. We investigated the effects of normothermic and hypothermic anesthesia on local CBF (LCBF) and local CGU (LCGU). METHODS Thirty-six rats were anesthetized with isoflurane (1 MAC) and artificially ventilated to maintain normal PaCO(2) (alpha-stat). Pericranial temperature was maintained normothermic (37.5 degrees C, n=12) or was reduced to 35 degrees C (n=12) or 32 degrees C (n=12). Pericranial temperature was maintained constant for 60 min until LCBF and LCGU were measured with autoradiography. Twelve conscious rats served as normothermic control animals. RESULTS Normothermic anesthesia significantly increased mean CBF compared with conscious control animals (29%, P<0.05). Mean CBF was reduced to control values with mild hypothermia and to 30% below control animals with moderate hypothermia (P<0.05). Normothermic anesthesia reduced mean CGU by 44%. No additional effects were observed during mild hypothermia. Moderate hypothermia resulted in a further reduction in mean CGU (41%, P<0.05). Local analysis showed linear relationships between LCBF and LCGU in normothermic conscious (r=0.93), anesthetized (r=0.92), and both hypothermic groups (35 degrees C r=0. 96, 32 degrees C r=0.96, P<0.05). The LCBF-to-LCGU ratio increased from 1.5 to 2.5 mL/micromol during anesthesia (P<0.05), remained at 2.4 mL/micromol during mild hypothermia, and decreased during moderate hypothermia (2.1 mL/micromol, P<0.05). CONCLUSIONS Anesthesia and hypothermia induce divergent changes in mean CBF and CGU. However, local analysis demonstrates a well-maintained linear relationship between LCBF and LCGU during normothermic and hypothermic anesthesia.

Relationship between local cerebral blood flow and metabolism during mild and moderate hypothermia in rats.

Background: Hypothermia may interfere with the relationship between cerebral blood flow (CBF) and metabolism. Because this conclusion was based on the analysis of global values, the question remains whether hypothermic CBF/metabolism uncoupling exists on a local cerebral level. This study investigated the effects of hypothermic anesthesia on local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCGU). Methods: Thirty-six rats were anesthetized with isoflurane (1 minimum alveolar concentration) and artificially ventilated to maintain normal arterial carbon dioxide partial pressure (p H-stat). Pericranial temperature was maintained as normothermic (37.5°C, n = 12) or was reduced to 35°C (n = 12) or 32°C (n = 12). Pericranial temperature was maintained constant for 60 min until LCBF or LCGU were measured by autoradiography. Twelve conscious rats served as normothermic controls. Results: Compared with conscious animals, mean CBF remained unchanged during normothermic anesthesia. Mean CBF significantly increased during mild hypothermia but was unchanged during moderate hypothermia. During normothermic anesthesia, mean CGU was 45% lower than in conscious controls (P < 0.05). No further CGU reduction was found during mild hypothermia, whereas CGU further decreased during moderate hypothermia (48%;P < 0.05). Local analysis showed a linear LCBF/LCGU relationship in conscious (r = 0.94) and anesthetized (r = 0.94) normothermic animals, as well as in both hypothermic groups (35°C: r = 0.92; 32°C: r = 0.95;P < 0.05). The LCBF-to-LCGU ratio increased from 1.4 (conscious controls) to 2.4 (normothermic isoflurane) and 3.6 ml/&mgr;mol (mild and moderate hypothermia, P < 0.05). Conclusions: Decrease of mean CGU at unchanged or increased mean CBF during hypothermic anesthesia may not indicate uncoupling. Local analysis shows a maintained linear relationship that is reset to a higher CBF/CGU ratio.

Local coupling of cerebral blood flow to cerebral glucose metabolism during inhalational anesthesia in rats: desflurane versus isoflurane.

BACKGROUND It is not known whether the effects of desflurane on local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) are different from those of other volatile anesthetics. METHODS Using the autoradiographic iodoantipyrine and deoxyglucose methods, LCGU, LCBF, and their overall means were measured in 60 Sprague-Dawley rats (10 groups, n = 6 each) during desflurane and isoflurane anesthesia and in conscious controls. RESULTS During anesthesia, mean cerebral glucose utilization was decreased compared with conscious controls: 1 minimum alveolar concentration (MAC) desflurane: -52%; 1 MAC isoflurane: -44%; 2 MAC desflurane: -62%; and 2 MAC isoflurane: -60%. Local analysis showed a reduction of LCGU in the majority of the 40 brain regions analyzed. Mean cerebral blood flow was increased: 1 MAC desflurane: +40%; 1 MAC isoflurane: +43%; 2 MAC desflurane and 2 MAC isoflurane: +70%. LCBF was increased in all brain structures investigated except in the auditory cortex. No significant differences (P < 0.05) could be observed between both anesthetics for mean values of cerebral glucose use and blood flow. Correlation coefficients obtained for the relation between LCGU and LCBF were as follows: controls: 0.95; 1 MAC desflurane: 0.89; 2 MAC desflurane: 0.60; 1 MAC isoflurane: 0.87; and 2 MAC isoflurane: 0.68. CONCLUSION Differences in the physicochemical properties of desflurane compared with isoflurane are not associated with major differences in the effects of both volatile anesthetics on cerebral glucose utilization, blood flow, and the coupling between LCBF and LCGU.

Regional heterogeneity of cerebral blood flow response to graded pressure-controlled hemorrhage.

BACKGROUND Little is known about the regional distribution of cerebral blood flow (CBF) in nonanesthetized animals during periods of lowered blood pressure. The present investigation addresses the specific reaction patterns of local cerebral blood flow (LCBF) in comparison with mean CBF during graded pressure-controlled hemorrhagic shock in conscious rats. METHODS Conscious rats were subjected to graded pressure-controlled hemorrhage (to 85, 70, 55, or 40 mm Hg) by arterial blood withdrawal. After a period of 30 minutes, blood pressure was stabilized by withdrawal or reinfusion of blood. LCBF was determined autoradiographically by the iodo(14C)antipyrine method in 34 brain structures, and mean CBF was calculated and compared with the values of nonhemorrhaged control animals. RESULTS Mean CBF remained unchanged except for the group with the lowest blood pressure of 40 mm Hg (decrease in CBF of 28%). Otherwise, LCBF was increased in some brain structures at an unchanged mean CBF. Congruently, at 40 mm Hg, the decrease in mean CBF did not show up in all brain structures, the local pattern of CBF varying between an unchanged and a profoundly decreased CBF. The mean coefficient of variation of CBF was increased with the severity of hemorrhagic shock, which indicates an enhanced heterogeneity of CBF. CONCLUSION Because of the substantial heterogeneity in the responses of LCBF to pressure-controlled hemorrhage, autoregulation of CBF during pressure-controlled hemorrhagic shock has to be reconsidered on a regional basis.

Prophylaxis of intra- and postoperative nausea and vomiting in patients during cesarean section in spinal anesthesia

Background This paper describes a randomized prospective study conducted in 308 patients undergoing caesarean section in spinal anaesthesia at a single hospital between 2010 and 2012 to find a suitable anti-emetic strategy for these patients. Material/Methods Spinal anesthesia was performed in left prone position, at L3/L4 with hyperbaric 0.5% Bupivacaine according to a cc/cm body height ratio. There were no opioids given peri-operatively. The patients received either no prophylaxis (Group I) or tropisetron and metoclopramide (Group II) or dimenhydrinate and dexamethasone (Group III), or tropisetron as a single medication (Group IV). The primary outcome was nausea and/or vomiting (NV) in the intraoperative, early (0–2 h) or late (2–24 h) postoperative period. Multivariate statistical analysis was conducted with a regression analysis and a backward elimination of factors without significant correlation. Results All prophylactic agents significantly reduced NV incidence intraoperatively. Relative risk reduction for NV by prophylaxis was most effective (59.5%) in Group II (tropisetron and metoclopramide). In Group III (dimenhydrinate and dexamethasone), NV risk was reduced by 29.9% and by 28.7% in Group IV (tropisetron mono-therapy). The incidence of NV in the early (0–2 h) and the late (2–24 h) postoperative period was low all over (7.8%), but the relative risk reduction of NV in the early postoperative period was 54.1% (Group IV), 45.1% (Group III), and 34.8% (Group II), respectively. In the late postoperative period, there was no significant difference between the 4 groups. Conclusions We recommend a prophylactic medication with tropisetron 2 mg and metoclopramide 20 mg for patients during caesarean section. These agents are safe, reasonably priced, and highly efficient in preventing nausea and vomiting.

Oxygen-Carrying Blood Substitutes

Transfusion of human blood components still has major drawbacks, such as transfusion-transmitted diseases, requirements for blood type analysis and cross-match testing, availability and supply, storag

Effects of chronic isovolaemic haemodilution on regional cerebral blood flow in conscious rats

Background and objective: Acute isovolaemic haemodilution increases local and mean cerebral blood flow. It is not known whether a single haemodilution has a short-term effect only or whether it affects cerebral perfusion over a longer time period. In the present study, local and mean cerebral blood flow were determined in conscious rats after a 4, 24 and 48 h period following one-time haemodilution. Methods: Thirty-six rats were randomized to three untreated sham groups and three groups of haemodilution (4, 24 or 48 h, n = 6 for each group). Isovolaemic haemodilution with albumin 5% aimed to a target haematocrit of 0.2. Local cerebral blood flow was measured in 38 brain regions by the iodo-[14C]antipyrine method in conscious normothermic rats. Results: Isovolaemic haemodilution reduced haematocrit from 0.44 to 0.20. During the following 24 and 48 h periods, haematocrit remained low (0.22 and 0.21). Mean cerebral blood flow was similar in untreated sham groups (88 ± 12 after 4 h, 92 ± 11 after 24 h, 96 ± 10 mL 100 g−1 min−1 after 48 h). Haemodilution increased mean cerebral blood flow after 4 h (184 ± 11 mL 100 g−1 min−1), after 24 h (153 ± 13 mL 100 g−1 min−1) and 48 h (149 ± 15 mL 100 g−1 min−1) (P ⩽ 0.05). Local cerebral blood flow increased in all 38 structures after 4 h haemodilution but decreased with time in six of 38 brain structures after 24 h and in 15 regions after 48 h (P ⩽ 0.05). Conclusions: A single one-time haemodilution increased mean cerebral blood flow for 2 days. However, local adaptation of cerebral blood flow to a chronic low haematocrit occurred but was heterogeneous within the brain.

Influence of blood viscosity on blood flow in the forebrain but not hindbrain after carotid occlusion in rats.

That cerebral blood flow remains unchanged at an increased blood viscosity, as long as the vascular supply is not compromised, was tested. To induce a reduced blood supply of some parts of the brain and to keep the supply unchanged in others both carotid arteries were occluded in anesthetized, ventilated rats. By this procedure, blood supply to the rostral brain, but not to the brainstem and cerebellum, was compromised. Blood viscosity was increased by intravenous infusion of 20% polyvinylpyrrolidone (high viscosity group) or decreased by infusion of 5% albumin (low viscosity group). Cerebral blood flow was measured by the [14C]iodoantipyrine method in 50 complete coronal sections of the rostral brain and 22 complete coronal sections of the brainstem and cerebellum in each rat. In the high viscosity group, mean cerebral blood flow of the rostral brain was significantly lower (46 ± 7 mL/100 g−1 · min−1) than in the low viscosity group (82 ± 18 mL/100 g−1 · min−1). No differences could be observed in brainstem and cerebellum between both groups (162 ± 29 mL/100 g−1 · min−1 vs. 156 ± 18 mL/100 g−1 · min−1). Local analysis of cerebral blood flow in different brain structures of the coronal sections showed the same identical results; i.e., in 29 of the 31 brain structures analyzed in rostral brain, local cerebral blood flow was lower in the high viscosity group, whereas no differences could be observed in the 11 brain structures analyzed in the brainstem and cerebellum. It is concluded that under normal conditions cerebral blood flow can be maintained at an increased blood viscosity by a compensatory vasodilation. When the capacity for vasodilation is exhausted by occlusion of supplying arteries, an increased blood viscosity results in a decrease of cerebral blood flow.