Influence of Changes in Arterial P CO2 on Cerebral Blood Flow and Cerebral Energy State during Hypothermia in the Rat

An 15 O-labeled water (H 2 15 O) steady-state method for quantitative measurement of cerebral blood flow (CBF), which is less stressful to small animals with a few point blood sampling, was developed. After a simulation using a dose meter to achieve stable H 2 15 O radioactivity in the blood with a multiprogramming syringe pump programmed for slowly increasing injection volume, 10 rats were studied with the injection method. Arterial blood was sampled every minute during 6-minute positron emission tomography (PET) scans. After the PET scan, N-isopropyl-p-[ 125 I]-iodoamphetamine ( 125 I-IMP) was injected into the same rat to measure CBF using the autoradiography method based on a microsphere model. Regions of interest were placed on the whole brain in H 2 15 O-PET and 125 I-IMP-autoradiography images, and CBF values calculated from both methods were compared. Radioactivity in the dose meter achieved equilibrium B1 minute after starting the H 2 15 O injection. In rat studies, radioactivity in the blood and brain rapidly achieved equilibrium at 2 minutes after administration. The correlation of CBF values of H 2 15 O PET (49.2±5.4 mL per 100 g per minute) and those of 125 I-IMP autoradiography (49.1 ± 5.2 mL per 100 g per minute) was excellent (y = 1.01xÀ0.37, r 2 = 0.97). The H 2 15 O steady-state method with a continuously increasing injection is useful for CBF measurement in small animal studies, especially when multiple scans are required in the same animal.

Section: Discussioncontrasting

confidence: 60%

Development of an H₂¹⁵O Steady-State Method Combining a Bolus and Slow Increasing Injection with a Multiprogramming Syringe Pump

Kobayashi

Kiyono

Maruyama

et al. 2010

“…Even when brain perfusion declined to only 15% of its normothermic value, cerebral energy level remained undiminished (Hägerdal et al, 1975c). This indicates that at a global level the blood flow in hypothermia is adequate and there is no evidence of brain hypoxia.…”

Section: Temperature Dependence Of Cerebral Blood Flow In Relation Tomentioning

confidence: 70%

“…Despite obvious decreases in CBF at lowered temperatures, oxygen consumption at 20°C to 22°C remained stable when flow rate was reduced even further, either directly (Fox et al, 1984) or by hypocapnia (Hägerdal et al, 1975c). Even when brain perfusion declined to only 15% of its normothermic value, cerebral energy level remained undiminished (Hägerdal et al, 1975c).…”

Section: Temperature Dependence Of Cerebral Blood Flow In Relation Tomentioning

confidence: 99%

Effects of Hypothermia on Energy Metabolism in Mammalian Central Nervous System

Erecińska

Thoresen

Silver

2003

392

238

Summary:This review analyzes, in some depth, results of studies on the effect of lowered temperatures on cerebral energy metabolism in animals under normal conditions and in some selected pathologic situations. In sedated and paralyzed mammals, acute uncomplicated 0.5-to 3-h hypothermia decreases the global cerebral metabolic rate for glucose (CMR glc ) and oxygen (CMRO 2 ) but maintains a slightly better energy level, which indicates that ATP breakdown is reduced more than its synthesis. Intracellular alkalinization stimulates glycolysis and independently enhances energy generation. Lowering of temperature during hypoxia-ischemia slows the rate of glucose, phosphocreatine, and ATP breakdown and lactate and inorganic phosphate formation, and improves recovery of energetic parameters during reperfusion. Mild hypothermia of 12 to 24-h duration after normothermic hypoxic-ischemic insults seems to prevent or ameliorate secondary failures in energy parameters. The authors conclude that lowered head temperatures help to protect and maintain normal CNS function by preserving brain ATP supply and level. Hypothermia may thus prove a promising avenue in the treatment of stroke and trauma and, in particular, of perinatal brain injury.

“…The CBF was calculated to be 1.4 ± 0.4 ml g-I min -I (mean ± SD in four ROls from two experi- ments). In rats where CBF was measured under light anesthesia with a modified Kety-Schmidt technique, values between 1.0 and 1.3 have been reported (Borgstrom et al , 1974;Hagerdahl et al , 1975). The influence of the anesthetic procedure should be taken into account when comparing ki netic results from different studies.…”

Section: Resultsmentioning

confidence: 99%

Rapid Feasibility Studies of Tracers for Positron Emission Tomography: High-Resolution PET in Small Animals with Kinetic Analysis

Ingvar

Eriksson

Rogers

et al. 1991

The development of methods for production of a radiotracer for use in human studies with positron emission tomography (PET) is often a time-consuming process of optimizing radiolabelling yields and handling procedures. Sometimes the radiotracer is not the original drug, but rather a derivative with unknown in vivo pharmacological properties. We have developed a fast and simple method of testing putative new PET tracers in vivo in small animals. The procedure has been validated in rats with different PET tracers with known kinetic and pharmacological properties ([2-18F]2-fluoro-2-deoxy-D-glucose, [N-methyl-11C]Ro 15-1788, and [15O]butanol). The tracer concentration in arterial blood was continuously measured to obtain the brain input function. Following image reconstruction of the scans, time-activity curves of selected regions of interest were generated. Estimations of CMRglc (1.0 +/- 0.2 mumol g-1 min-1), CBF (1.4 +/- 0.4 ml g-1 min-1) and transport rate constants for [N-methyl-11C]Ro 15-1788 (K1 = 0.44 +/- 0.01 ml g-1 min-1 and k2 = 0.099 +/- 0.005 min-1) as well as calculated first pass extraction (0.32 +/- 0.1) are in reasonable agreement with literature values. Small animal studies require minimal amounts of radioactivity and can be performed without sterility and toxicology tests. They may serve as a preliminary basis for radiation safety calculations because whole body scans can be performed even with a head scanner.(ABSTRACT TRUNCATED AT 250 WORDS)