Hyperglycemia during Hypothermic Canine Cardiopulmonary Bypass Increases Cerebral Lactate

Background Hyperglycemia frequently occurs during cardiopulmonary bypass (CPB), although its direct effects on cerebral perfusion and metabolism are not known. Using a canine model of hypothermic CPB, we tested whether hyperglycemia alters cerebral blood flow and metabolism and cerebral energy charge. Methods Twenty anesthetized dogs were randomized into hyperglycemic (n = 10) and normoglycemic (n = 10) groups. The hyperglycemic group received an infusion of D50W, and the normoglycemic animals received an equal volume of 0.9% NaCl. Both groups underwent 120 min of hypothermic (28 degrees C) CPB using membrane oxygenators, followed by rewarming and termination of CPB. Cerebral blood flow (radioactive microspheres) and the cerebral metabolic rate for oxygen were measured intermittently during the experiment and brain tissue metabolites were obtained after bypass. Results Before CPB, the glucose-treated animals had higher serum glucose levels (534 +/- 12 mg/dL; mean +/- SE) than controls (103 +/- 4 mg/dL; P < 0.05), and this difference was maintained throughout the study. Cerebral blood flow and metabolism did not differ between groups at any time during the experiment. Sagittal sinus pressure was comparable between groups throughout CPB. Tissue high-energy phosphates and water contents were similar after CPB, although cerebral lactate levels were greater in hyperglycemic (37.2 +/- 5.7 mumol/g) than normoglycemic animals (19.7 +/- 3.7 mumol/g; P < 0.05). After CPB, pH values of cerebrospinal fluid for normoglycemic (7.33 +/- 0.01) and hyperglycemic (7.34 +/- 0.01) groups were similar. Conclusions Hyperglycemia during CPB significantly increases cerebral lactate levels without adversely affecting cerebral blood flow and metabolism, cerebrospinal fluid pH, or cerebral energy charge.

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Effects of MK-801 and NBQX on Acute Recovery of Piglet Cerebral Metabolism after Hypothermic Circulatory Arrest

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1994.21 ◽

1994 ◽

Vol 14 (1) ◽

pp. 156-165 ◽

Cited By ~ 19

Author(s):

Mitsuru Aoki ◽

Fumikazu Nomura ◽

Michael E. Stromski ◽

Miles K. Tsuji ◽

James C. Fackler ◽

...

Keyword(s):

Blood Flow ◽

Cerebral Blood Flow ◽

Oxygen Consumption ◽

Cardiopulmonary Bypass ◽

Circulatory Arrest ◽

High Energy ◽

Hypothermic Circulatory Arrest ◽

Cerebral Oxygen ◽

High Energy Phosphates ◽

Mk 801

Brain protection during open heart surgery in the neonate and infant remains inadequate. Effects of the excitatory neurotransmitter antagonists MK-801 and NBQX on recovery of brain cellular energy state and metabolic rates were evaluated in 34 4-week-old piglets (10 MK-801, 10 NBQX, 14 controls) undergoing cardiopulmonary bypass and hypothermic circulatory arrest at 15°C nasopharyngeal temperature for 1 h, as is used clinically for repair of congenital heart defects. MK-801 (dizocilpine) (0.75 mg/kg) or NBQX [2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo( F)quinoxaline] (25 mg/kg) was given intravenously before cardiopulmonary bypass. Equivalent doses were placed in the cardiopulmonary bypass prime plus continuous infusions after reperfusion (0.15 mg kg−1h−1 and 5 mg kg−1h−1). Changes in high-energy phosphate concentrations and pH were analyzed by magnetic resonance spectroscopy in 17 animals until 225 min after reperfusion. Cerebral blood flow determined by radioactive microspheres as well as cerebral oxygen and glucose consumption were studied in 17 other animals. Cerebral blood flow and oxygen consumption were depressed relative to control by both MK-801 and NBQX at baseline. Recovery of phosphocreatine (p = 0.010), ATP (p = 0.030), and intracellular pH (p = 0.004) was accelerated by MK-801 and retarded by NBQX over the 45 min of rewarming reperfusion and the first hour of normothermic reperfusion. The final recovery of ATP at 3 h and 45 min reperfusion was significantly reduced by NBQX (46 ± 26% baseline, mean ± SD) versus control (81 ± 19%) and MK-801 (75 ± 8%) (p = 0.030). Cerebral oxygen consumption recovered to 105 ± 30% baseline in group MK-801 and 94 ± 31% in control but only to 61 ± 22% in group NBQX (p = 0.070). Cerebral blood flow stayed significantly lower in group NBQX relative to control. Thus, MK-801 accelerates recovery of cerebral high-energy phosphates and metabolic rate after cardiopulmonary bypass and hypothermic circulatory arrest in the immature animal. At the dosage used NBQX exerts an adverse effect.

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Effects of Cerebroprotective Agents on Cerebral Blood Flow and on Postischemic Energy Metabolism in the Rat Brain

Journal of Cerebral Blood Flow & Metabolism ◽

10.1038/jcbfm.1987.91 ◽

1987 ◽

Vol 7 (4) ◽

pp. 480-488 ◽

Cited By ~ 43

Author(s):

Gerhard Wilhelm Bielenberg ◽

Thomas Beck ◽

Dirk Sauer ◽

Marta Burniol ◽

Josef Krieglstein

Keyword(s):

Blood Pressure ◽

Blood Flow ◽

Cerebral Blood Flow ◽

Energy Metabolism ◽

Glucose Level ◽

Recovery Period ◽

High Energy ◽

High Energy Phosphates ◽

Early Recovery ◽

Conscious Rat

Male Wistar rats were subjected to forebrain ischemia of 10 min duration by clamping both common carotid arteries and simultaneously lowering systemic blood pressure to 40 mm Hg by exsanguination. Recovery was achieved by removing the arterial clamps and reinfusing the blood. Cortical levels of high-energy phosphates and glycolytic substrates were determined enzymatically. Naftidrofuryl (10 or 20 mg/kg i.p.) or ketamine (5 mg/kg i.v.) were applied 30 min prior to the induction of ischemia. S(-)-Emopamil (4 mg/kg) or nimodipine (50 μg/kg) were administered by intravenous infusion over 30 min. Nimodipine and emopamil increased the blood glucose level and lowered preischemic blood pressure. Under control conditions, a tendency toward a higher cortical glucose level was observed in treated brains. Brain energy stores were exhausted after ischemia in control and treated animals to the same degree. Lactate levels, however, were higher in emopamil-treated animals. This effect was attributed to the elevated pre-ischemic glucose levels. During the early recovery period, the restoration of high-energy phosphates was accelerated by both calcium entry blockers. Nimodipine and emopamil increased the levels of glucose and glucoses-phosphate in the early postischemic period. Naftidrofuryl (10 mg/kg) increased the level of creatine-phosphate and ATP after 2 min of recovery. Naftidrofuryl (20 mg/kg) exerted no effect on cerebral energy metabolism, but considerably reduced postischemic blood pressure (possibly thereby masking its ameliorative action). Ketamine accelerated the postischemic restoration of high-energy phosphates. In the conscious rat, local cerebral blood flow (LCBF) was determined with the 14C-iodoantipyrine technique following emopamil (20 mg/kg s.c.) or naftidrofuryl (10 mg/kg i.v.) application. Both compounds increased LCBF values in the majority of grey matter structures. It was concluded that the cerebroprotective agents investigated share an accelerating effect on the postischemic restoration of high-energy phosphates in cerebral cortex.

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Blood flow and high-energy phosphates in microregions of left ventricular subendocardium

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1981.240.5.h804 ◽

1981 ◽

Vol 240 (5) ◽

pp. H804-H810 ◽

Cited By ~ 1

Author(s):

H. D. Kleinert ◽

H. R. Weiss

Keyword(s):

Blood Flow ◽

Linear Relationship ◽

Tissue Perfusion ◽

High Energy ◽

Left Ventricular ◽

Significant Loss ◽

Tissue Blood Flow ◽

High Energy Phosphates ◽

Tissue Samples ◽

Heterogeneous Distribution

Blood flow and high-energy phosphate (HEP) content were determined simultaneously in multiple microregions of left ventricular subendocardium in 29 normal anesthetized open-chest rabbits by use of a new micromethod to determine whether a direct linear relationship existed between these parameters. Tissue samples weighed 1-2 mg. ATP and creatine phosphate (CP) content were quantitated in quick-frozen hearts by fluorometry at sites where tissue perfusion was measured by H2 clearance by use of bare-tipped platinum electrodes. A series of validation studies were conducted to ensure that 1) no significant damage to the tissue surrounding the electrode occurred during the period of experimentation and 2) no significant loss of biochemical constituents had occurred due to labile processes during freezing or storage of the tissue. Blood flow, ATP, and CP values averaged 79.1 +/- 24.1 (SD) ml.min-1.100 g-1, 4.9 +/- 1.3 mumol/g tissue, and 8.0 +/- 3.0 mumol/g tissue, respectively, and are similar to those reported in studies using larger tissue samples. Correlation between the heterogeneous distribution of tissue perfusion and HEP revealed no direct linear relationship between these parameters in the normal unstressed rabbit subendocardium.

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