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

1994 ◽  
Vol 14 (1) ◽  
pp. 156-165 ◽  
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.

Hyperglycemia during Hypothermic Canine Cardiopulmonary Bypass Increases Cerebral Lactate 

1995 ◽  
Vol 82 (2) ◽  
pp. 512-520 ◽  
Author(s):  
Alan E. Feerick ◽  
William E. Johnston ◽  
Larry W. Jenkins ◽  
Cheng Y. Lin ◽  
Jonathan H. Mackay ◽  
...  
Keyword(s):  
Blood Flow ◽  
Cerebrospinal Fluid ◽  
Cerebral Blood Flow ◽  
Cardiopulmonary Bypass ◽  
Energy Charge ◽  
Canine Model ◽  
High Energy ◽  
Serum Glucose ◽  
High Energy Phosphates ◽  
Lactate Levels

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.

The effects of cardiopulmonary bypass and deep hypothermic circulatory arrest on blood viscoelasticity and cerebral blood flow in a neonatal piglet model

Perfusion ◽  
2000 ◽  
Vol 15 (2) ◽  
pp. 121-128 ◽  
Author(s):  
Akif Ündar ◽  
William K Vaughn ◽  
John H Calhoon
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Cardiopulmonary Bypass ◽  
Regional Cerebral Blood Flow ◽  
Circulatory Arrest ◽  
Deep Hypothermic Circulatory Arrest ◽  
Hypothermic Circulatory Arrest ◽  
Regional Cerebral Blood ◽  
Neonatal Piglet ◽  
Arterial Blood

The purpose of this study is to determine the effects of cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA) on the viscoelasticity (viscosity and elasticity) of blood and global and regional cerebral blood flow (CBF) in a neonatal piglet model. After initiation of CPB, all animals ( n = 3) were subjected to core cooling for 20 min to reduce the piglets’ nasopharyngeal temperatures to 18°C. This was followed by 60 min of DHCA, then 45 min of rewarming. During cooling and rewarming, the alpha-stat technique was used. Arterial blood samples were taken for viscoelasticity measurements and differently labeled microspheres were injected at pre-CPB, pre- and post-DHCA, 30 and 60 min after CPB for global and regional cerebral blood flow calculations. Viscosity and elasticity were measured at 2 Hz, 22°C and at a strain of 0.2, 1, and 5 using a Vilastic-3 Viscoelasticity Analyzer. Elasticity of blood at a strain = 1 decreased to 32%, 83%, 57%, and 61% ( p = 0.01, ANOVA) while the viscosity diminished 8.4%, 38%, 22%, 26% compared to the baseline values ( p = 0.01, ANOVA) at pre-DHCA, post-DHCA, 30 and 60 min after CPB, respectively. The viscoelasticity of blood at a strain of 0.2 and 5 also had similar statistically significant drops ( p < 0.05). Global and regional cerebral blood flow were also decreased 30%, 66%, 64% and 63% at the same experimental stages ( p < 0.05, ANOVA). CPB procedure with 60 min of DHCA significantly alters the blood viscoelasticity, global and regional cerebral blood flow. These large changes in viscoelasticity may have a significant impact on organ blood flow, particularly in the brain.

Comparison of pH-state and Alpha-stat Cardiopulmonary Bypass on Cerebral Oxygenation and Blood Flow in Relation to Hypothermic Circulatory Arrest in Piglets 

1998 ◽  
Vol 89 (1) ◽  
pp. 110-118 ◽  
Author(s):  
Dean C. Kurth ◽  
Maureen M. O'Rourke ◽  
Irene B. O'Hara
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Cardiopulmonary Bypass ◽  
Water Content ◽  
Adenosine Triphosphate ◽  
Half Life ◽  
Circulatory Arrest ◽  
Hypothermic Circulatory Arrest ◽  
Ph Stat ◽  
Hypothermic Arrest

Background Deep hypothermic circulatory arrest is used in neonatal cardiac surgery. Recent work has suggested improved neurologic recovery after deep hypothermic arrest with pH-stat cardiopulmonary bypass (CPB) compared with alpha-stat CPB. This study examined cortical oxygen saturation (ScO2), cortical blood flow (CBF), and cortical physiologic recovery in relation to deep hypothermic arrest with alpha-stat or pH-stat CPB. Methods Sixteen piglets were cooled with pH-stat or alpha-stat CPB to 19 degrees C (cortex) and subjected to 60 min of circulatory arrest, followed by CPB reperfusion and rewarming and separation from CPB. Near infrared spectroscopy and laser Doppler flowmetry were used to monitor ScO2 and CBF. Cortical physiologic recovery was assessed 2 h after the piglets were separated from CPB by cortical adenosine triphosphate concentrations, cortical water content, CBF, and ScO2. Results During CPB cooling, ScO2 increased more with pH-stat than with alpha-stat bypass (123 +/- 33% vs. 80 +/- 25%); superficial and deep CBF were also greater with pH-stat than with alpha-stat bypass (22 +/- 25% vs. -56 +/- 22%, 3 +/- 19% vs. -29 +/- 28%). During arrest, ScO2 half-life was greater with pH-stat than with alpha-stat bypass (10 +/- 2 min vs. 7 +/- 2 min), and cortical oxygen consumption lasted longer with pH-stat than with alpha-stat bypass (36 +/- 8 min vs. 25 +/- 8 min). During CPB reperfusion, superficial and deep CBF were less with alpha-stat than with pH-stat bypass (-40 +/- 22% vs. 10 +/- 39%, -38 +/- 28% vs. 5 +/- 28%). After CPB, deep cortical adenosine triphosphate and CBF were less with alpha-stat than with pH-stat bypass (11 +/- 6 pmole/mg vs. 17 +/- 8 pmole/mg, -24 +/- 16% vs. 16 +/- 32%); cortical water content was greater with alpha-stat than with pH-stat bypass (superficial: 82.4 +/- 0.3% vs. 81.8 +/- 1%, deep: 79.1 +/- 2% vs. 78 +/- 1.6%). Conclusions Cortical deoxygenation during hypothermic arrest was slower after pH-stat CPB. pH-stat bypass increased the prearrest ScO2 and arrest ScO2 half-life, to increase the cortical oxygen supply and slow cortical oxygen consumption. Improved cortical physiologic recovery after hypothermic arrest was suggested with pH-stat management.

Influence of endogenous norepinephrine on cerebral blood flow and metabolism

1976 ◽  
Vol 231 (2) ◽  
pp. 489-494 ◽  
Author(s):  
ET MacKenzie ◽  
J McCulloch ◽  
AM Harper
Keyword(s):  
Blood Flow ◽  
Cerebral Blood Flow ◽  
Oxygen Consumption ◽  
Glucose Uptake ◽  
Cerebral Circulation ◽  
Brain Metabolism ◽  
Cerebral Metabolism ◽  
Cerebral Oxygen ◽  
Brain Norepinephrine ◽  
Cerebral Oxygen Consumption

The influence of brain norepinephrine on cerebral metabolism and blood flow was examined because exogenous norepinephrine, administered in a way that the blood-brain barrier is bypassed, has been shown to effect pronounced changes in the cerebral circulation. Reserpine (40 mug/kg, by intracarotid infusion) was administered in order to release brain norepinephrine in five anesthetized baboons. Reserpine significantly increased cerebral oxygen consumption (23%) and cerebral blood flow (50%). This response lasted for approximately 60 min. In a further five animals, effects of central beta-adrenoreceptor blockade were studied. Pro pranolol (12 mug/kg-min) produced an immediate, significant reduction in both cerebral oxygen consumption (40%) and cerebral glucose uptake (39%). Cerebral blood flow was reduced minimally. However, the responsiveness of the cerebral circulation to induced hypercapnia was severely attenuated from a gradient of 3.22 before, to 1,11 after, administration. These experiments suggest that central norepinephrine can influence the cerebral circulation primarily through noradrenergic effects on brain metabolism.

Sign in / Sign up

Export Citation Format

Share Document