Coupling of Cerebral Blood Flow and Oxygen Metabolism in Infant Pigs during Selective Brain Hypothermia

Abstract

Summary:Studies documenting the cerebral hemodynamic consequences of selective brain hypothermia (SBH) have yielded conflicting data. Therefore, the authors have studied the effect of SBH on the relation of cerebral blood flow (CBF) and CMRO 2 in the forebrain of pigs. Selective brain hypothermia was induced in seven juvenile pigs by bicarotid perfusion of the head with extracorporally cooled blood. Cooling and stepwise rewarming of the brain to a T brain of 38°C, 25°C, 30°C, and 38°C at normothermic T trunk (38°C) decreased CBF from 71 ± 12 mL 100 g −1 min −1 at normothermia to 26 ± 3 mL 100 g −1 min −1 and 40 ± 12 mL 100 g −1 min −1 at a T brain of 25°C and 30°C, respectively. The decrease of CMRO 2 during cooling of the brain to a T brain of 25°C resulted in a mean Q 10 of 2.8. The ratio between CBF and CMRO 2 was increased at a T brain of 25°C indicating a change in coupling of flow and metabolism. Despite this change, regional perfusion remained coupled to regional temperatures during deep cerebral hypothermia. The data demonstrate that SBH decreases CBF and oxygen metabolism to a degree comparable with the cerebrovascular and metabolic effects of systemic hypothermia. The authors conclude that, irrespective of a change in coupling of blood flow and metabolism during deep cerebral hypothermia, cerebral metabolism is a main determinant of CBF during SBH. Key Words: Selective brain hypothermia-Cerebral flowmetabolism coupling-Microspheres-Pig.There is considerable evidence that hypothermia is a useful intrainsult and postinsult treatment modality for brain injury caused by hypoxia-ischemia, trauma, or neonatal asphyxia (Dietrich, 1992, Gunn et al., 1998bWass et al., 1996). Moreover, systemic hypothermia is routinely used during cardiopulmonary bypass in cardiovascular surgery (McCullough et al., 1999;Jonas, 1998). Because systemic hypothermia causes potentially hazardous side effects (for review see Schubert, 1995), selective brain hypothermia (SBH) is being looked at more intensively with respect to feasibility and cerebroprotective effects (Gunn et al., 1997;Kuluz et al., 1992;Schwartz et al., 1996b).Hypothermic cerebral protection is mediated in part by a reduction of cerebral metabolism (Lanier, 1995). Numerous animal and human studies have shown that systemic hypothermia decreases cerebral blood flow (CBF) and CMRO 2 (Greeley et al., 1993;Michenfelder et al., 1991). However, very few studies have addressed the cerebrovascular and cerebral metabolic responses to SBH. Currently there is no study documenting the physiologic effects of SBH on CMRO 2 and, consequently, on the coupling of CBF and CMRO 2 . Furthermore, investigations documenting the hemodynamic consequences of SBH have reported seemingly conflicting data on the cerebrovascular effects of SBH. A single study in rats has shown that external head cooling results in an increase of CBF (Kuluz et al., 1993). Based on this study it has been concluded that the method of cooling (systemic vs. selective) may be a key factor in determining the cerebral he...

A theoretical model of selective cooling using intracarotid cold saline infusion in the human brain

“…Animal studies suggest that, during circulatory arrest, the reduction of metabolic rate nearly parallels the decrease in CBF (22). Moreover, there is direct evidence of coupling of CBF to cerebral oxygen metabolism from swine (12,62) and dog (39) studies. However, there is also evidence of uncoupling between CBF and cerebral oxygen metabolism during deep (20 -26°C) and profound (Ͻ20°C) cooling (12,39).…”

Effect of Mild Hypothermia and Hypoxia on Blood Flow and Oxygen Consumption of the Fetal Sheep Brain

“…However, the oxygen consumption of most individual organs falls in response to hypothermia because of the biophysical effect of temperature on metabolic activity. The brain is no exception, as its oxygen consumption decreases 50 to 75% for every 10°C decrease in brain temperature (1,4,13). In the present study, the effect of hypothermia on fetal cerebral oxygen consumption was similar to that of previous reports in the newborn and adult, with a 1.6°C decrease in brain temperature resulting in a 25% decrease in cerebral oxygen consumption.…”

“…In the newborn and adult, lowering cerebral oxygen consumption with either hypothermia (1,4,6) or barbiturates (2,3,5) results in commensurate decreases in cerebral oxygen delivery, with little or no change in cerebral oxygen extraction. In the present study, we observed in the fetus a similar relationship between cerebral oxygen consumption and cerebral oxygen delivery (Fig.…”

“…Under normal physiologic conditions, the rate at which the brain is consuming oxygen is the primary determinant of cerebral oxygen delivery. In the newborn and adult, this relationship has been demonstrated by observing that hypothermia or barbiturate-induced decreases in cerebral oxygen consumption result in comparable decreases in cerebral oxygen delivery (1)(2)(3)(4)(5)(6). Although the relationship between cerebral oxygen delivery and consumption has been studied extensively in the fetus by inducing changes in arterial oxygen content (7), the approach of altering cerebral oxygen consumption and observing changes in oxygen delivery has not been fully explored.…”

“…Under normoxic conditions, cerebral hypothermia results in decreases in cerebral oxygen consumption and parallel reductions of cerebral blood flow and oxygen delivery (4). These responses are associated with increased cerebrovascular resistance, but little or no change in cerebral oxygen extraction.…”