Inhibition of Cerebral Oxygen and Glucose Consumption in the Dog by Hypothermia, Pentobarbital, and Lidocaine

Astrup, Jens; Sørensen, P. Møller; Sørensen, H.

doi:10.1097/00000542-198109000-00013

Cited by 179 publications

(52 citation statements)

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“…Of the 22 studies listed in Table 2, approximately half provided measurements at more than 2 temperatures and therefore allowed construction, by either the original or present authors, of relevant plots of oxygen consumption rate versus temperature. Five studies (Astrup et al, 1981;Bering, 1961Bering, , 1974Conroy et al, 1998;Michenfelder and Theye, 1968) yielded an exponential relation with calculated Q 10 values of between 2.2 and 3.8. Greeley et al (1991) also found that their combined data after 5 minutes at 18°C All values are in units given by the original authors.…”

Section: Effect Of Temperature On Cerebral Atp Production and Cerebramentioning

confidence: 94%

“…(1) In several studies (Astrup et al, 1981;Bering, 1961Bering, , 1974Greeley et al, 1991;Hägerdal et al, 1975a;Tanaka et al, 1988) the plots of temperature versus CMRO 2 show no evidence of discontinuity even down to 13°C-18°C, which suggests a single Q 10 value. However, Milde (1991, 1992) reported that in dogs exposed to hypothermia between 27°C and 14°C, the Q 10 was much higher, 4.53 (which is twice the value they found between 27°C and 37°C), but it decreased again to 2.2 between 13°C and 7°C.…”

Section: Effect Of Temperature On Cerebral Atp Production and Cerebramentioning

confidence: 98%

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Effects of Hypothermia on Energy Metabolism in Mammalian Central Nervous System

Erecińska

Thoresen

Silver

2003

J Cereb Blood Flow Metab

387

238

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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.

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Section: Effect Of Temperature On Cerebral Atp Production and Cerebramentioning

confidence: 94%

Section: Effect Of Temperature On Cerebral Atp Production and Cerebramentioning

confidence: 98%

Effects of Hypothermia on Energy Metabolism in Mammalian Central Nervous System

Erecińska

Thoresen

Silver

2003

J Cereb Blood Flow Metab

387

238

View full text Add to dashboard Cite

show abstract

“…Studies in adult animals also have demonstrated that hypothermia has no adverse influence on the energy status of brain tissue, whereas selected glycolytic and tricarboxylic acid intermediates, including pyruvate and lactate, are reduced, suggesting that oxidative metabolic flux has been curtailed by the lower than normal brain temperature (2 1-23). That oxidative metabolism is reduced is supported by the well-established observation that hypothermia substantially lowers the cerebral metabolic rate for oxygen (24)(25)(26).…”

Section: Discussionmentioning

confidence: 96%

Cerebral Oxidative Metabolism during Hypothermia and Circulatory Arrest in Newborn Dogs

et al. 1992

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ABSTRACT. To ascertain the alterations in cerebral oxiHypothermic circulatory arrest has become an established dative and energy metabolism that occur during hypother-procedure for the operative correction of congenital heart anommic circulatory arrest, nitrous oxide-anesthetized, para-alies in infants and children (1). Despite the prevalence of its use lyzed, and artificially ventilated newborn dogs were surface in clinical practice, little basic research has been conducted to cooled to 18-20°C, after which their hearts were arrested investigate the protective influence of hypothermia superimposed with KCI. At 10, 30,60, and 105 min of circulatory arrest, upon systemic hypoxia, hypotension, or cardiac arrest in peritheir brains were prepared by in situ freezing for the natal animals (2-5). Accordingly, we have developed a model of regional analysis of glycolytic intermediates and high-hypothermic circulatory arrest in the newborn dog; the neuroenergy phosphate reserves. Hypothermia alone was asso-pathologic consequence thereof is now well documented (6, 7). ciated with optimal preservation of labile metabolites in Specifically, newborn dogs subjected to hypothermic circulatory brain, even in caudal brainstem and cerebellum, compared arrest of 1.0 h duration exhibit no brain damage at 4 or 24 h of with barbiturate-anesthetized littermates. After onset of recovery, whereas puppies arrested for 1.5 h or longer show hypothermic circulatory arrest, glucose decreased progres-progressively increasing ischemic injury to selectively vulnerable sively in cerebral cortex, caudate nucleus, hippocampus, structures. It is not known just how long a human infant can and subcortical white matter to negligible levels by 30 min. tolerate hypothermic circulatory arrest, although clinical studies Pyruvate increased transiently (+SO%) at 10 min, whereas suggest a "safe" interval (60-75 min) similar to that of the lactate increased and plateaued (10-11 mmol/kg) at 30 newborn dog (8-10). min. The disproportionate increases in pyruvate and lactateIn the present communication, we describe the results of an resulted in a progressive rise in the lactate/pyruvate ratio. investigation conducted in parallel with neuropathologic studies Phosphocreatine fell precipitously to ~0 . 5 mmol/kg in all to ascertain the nature and extent of alterations in cerebral structures, with a preservation of ATP for the first 10 min carbohydrate and energy metabolism during hypothermia alone of cerebral ischemia. Thereafter, ATP decreased to C0.1 and during hypothermic circulatory arrest. A major objective of mmol/kg in cerebral cortex and between 0.1 and 0.2 mmol/ the study was to correlate changes in regional metabolic activity kg in caudate nucleus, hippocampus, and white matter. during hypothermic cerebral ischemia with the known sensitivity Total adenine nucleotides (ATP + ADP + AMP) were (or resistance) of specific brain structures to ischemic damage. partially depleted by 30 min in the gray matter structures but were unchanged from control for 60 min in...

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“…The mechanism of the protective effect of hypothermia on brain tissue subjected to ischemic stress relates to a reduction in cerebral energy demands that are relatively proportionate to a reduction in cerebral blood flow (33)(34)(35)(36). Of necessity, a mismatch occurs between blood flow and metabolism during hypothermic circulatory arrest, because in the absence of cerebral perfusion, metabolism must continue at a basal rate to maintain ion gradients and structural integrity.…”

Section: Discussionmentioning

confidence: 99%

Physiologic and Neuropathologic Aspects of Hypothermic Circulatory Arrest in Newborn Dogs

1990

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ABSTRACT. A model of hypothermic circulatory arrest has been developed in the newborn dog. Ten puppies were anesthetized with halothane, paralyzed, and artificially ventilated with 70% nitrous oxide 30% oxygen to arterial oxygen pressure >8.0 kPa (60 mm Hg), arterial carbon dioxide pressure of 4.4-5.6 kPa (33-42 mm Hg), and arterial pH of 7. 35-7.42. Animals were surface cooled to 20°C, after which cardiac arrest was produced with i.v. KCI. Dogs remained asystolic without ventilation for 1.0 (n = 4), 1.5 (n = 3), or 2.0 (n = 3) h. Resuscitation was accomplished with closed-chest compression, mechanical ventilation, i.v. epinephrine and NaHC03, and rewarming to 37°C. Postarrest recovery was maintained for 3-4 h; thereafter, the puppies underwent perfusion-fixation of their brains for pathologic analysis. Plasma glucose (control = 8.3 mmol/L) increased slightly during hypothermic cardiac arrest (+36%) but was markedly elevated at 15 min postarrest (20 mmol/L). Blood lactate (control = 1.1 mmol/L) increased almost 200% during hypothermic circulatory arrest, with a further rise to 9.0 mmol/L at 15 min postarrest. Thereafter, lactate decreased in the 1-h arrested dogs but increased progressively in the other groups. Mean arterial blood pressure returned to baseline (73 mm Hg) by 15 min postarrest, remained stable in the 1-h dogs, but fell at 3 h to 62 and 34 mm Hg in the 1.5-and 2.0-h groups, respectively. No neuropathologic alterations were seen in puppies arrested for 1 h, whereas all puppies arrested for 1.5 or 2 h had varying degrees of cerebral cortical and hippocampal damage. Thus, newborn dogs tolerate 1 h of hypothermic circulatory arrest without brain damage, with graded neuronal injury thereafter. The experimental model has direct clinical relevance and can be used to study mechanisms of cellular injury in brain, heart, and other organs during prolonged ischemia. 3 5 in infants and children. The rationale for this surgical approach relates to the well-known observation that acute brain damage secondary to systemic hypoxia, hypotension, or cardiac arrest is prevented or at least substantially reduced by prior or concurrent hypothermia (1-5). It is the duration of cardiac arrest and its attendant total cerebral ischemia that is limiting for the prevention of brain damage. It is not known how long an infant can tolerate hypothermic circulatory arrest without sustaining ischemic brain injury, although clinical practice suggests a "safe" interval of 60-70 min (6-8). Unfortunately, infants occasionally sustain brain damage even when the duration of cardiac arrest is well within the "therapeutic window" (9, 10). It has not been established whether such brain damage arises as a silent complication of the surgical procedure itself (e.g. postoperative hypotension, air emboli, etc.) or as a result of cerebral ischemia beyond the safety margin for any specific individual infant. Given the fact that 0.5-1.0% of all infants are born with surgically correctable cardiac defects, it is surprising that little research has be...

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Inhibition of Cerebral Oxygen and Glucose Consumption in the Dog by Hypothermia, Pentobarbital, and Lidocaine

Cited by 179 publications

References 0 publications

Effects of Hypothermia on Energy Metabolism in Mammalian Central Nervous System

Effects of Hypothermia on Energy Metabolism in Mammalian Central Nervous System

Cerebral Oxidative Metabolism during Hypothermia and Circulatory Arrest in Newborn Dogs

Physiologic and Neuropathologic Aspects of Hypothermic Circulatory Arrest in Newborn Dogs

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