Cerebral blood flow and cerebrovascular autoregulation in a swine model of pediatric cardiac arrest and hypothermia

Abstract

Objective: Knowledge remains limited regarding cerebral blood flow autoregulation after cardiac arrest and during postresuscitation hypothermia. We determined the relationship of cerebral blood flow to cerebral perfusion pressure in a swine model of pediatric hypoxic-asphyxic cardiac arrest during normothermia and hypothermia and tested novel measures of autoregulation derived from near-infrared spectroscopy.

Design: Prospective, balanced animal study.

Setting: Basic physiology laboratory at an academic institution.

Subjects: Eighty-four neonatal swine.

Interventions: Piglets underwent hypoxic-asphyxic cardiac arrest or sham surgery and recovered for 2 hrs with normothermia followed by 4 hrs of either moderate hypothermia or normothermia. In half of the groups, blood pressure was slowly decreased through inflation of a balloon catheter in the inferior vena cava to identify the lower limit of cerebral autoregulation at 6 hrs postresuscitation. In the remaining groups, blood pressure was gradually increased by inflation of a balloon catheter in the aorta to determine the autoregulatory response to hypertension. Measures of autoregulation obtained from standard laser-Doppler flowmetry and indices derived from near-infrared spectroscopy were compared.

Measurements and main results: Laser-Doppler flux was lower in postarrest animals compared to sham-operated controls during the 2-hr normothermic period after resuscitation. During the subsequent 4-hr recovery, hypothermia decreased laser-Doppler flux in both the sham surgery and postarrest groups. Autoregulation was intact during hypertension in all groups. With arterial hypotension, postarrest, hypothermic piglets had a significant decrease in the perfusion pressure lower limit of autoregulation compared to postarrest, normothermic piglets. The near-infrared spectroscopy-derived measures of autoregulation accurately detected loss of autoregulation during hypotension.

Conclusions: In a pediatric model of cardiac arrest and resuscitation, delayed induction of hypothermia decreased cerebral perfusion and decreased the lower limit of autoregulation. Metrics derived from noninvasive near-infrared spectroscopy accurately identified the lower limit of autoregulation during normothermia and hypothermia in piglets resuscitated from arrest.

Figure 1

Both arrest (p = 0.006) and hypothermia (p < 0.001) significantly decreased laser-Doppler flux (LDF) without interaction effect. (A) Normothermic and hypothermic sham animals (n = 16 per group). (B) Normothermic and hypothermic post-arrest animals (n = 16 per group). Data are presented as means with 95% confidence intervals.

Figure 2

The cerebral perfusion pressure lower limit of autoregulation (LLA) was significantly lower in piglets after hypoxic-asphyxic cardiac arrest with post-resuscitation hypothermia compared to sham-operated piglets and piglets resuscitated from cardiac arrest with normothermia (p = 0.012). Data are presented as means with 95% confidence intervals.

Figure 3

Spline regression model fit lines of the hemoglobin volume (HVx) index during induced hypotension. Each piglet’s lower limit of autoregulation (LLA) is centered to zero on the x-axis, permitting comparison of each animal’s cerebral perfusion pressure (CPP) relative to LLA. HVx became more positive as CPP decreased below the LLA in (A) normothermic sham, (B) hypothermic sham, (C) normothermic post-arrest, and (D) hypothermic post-arrest piglets. (n = 8 per group). Spline regression analysis indicated that the slope of the relationship of HVx with CPP became significantly more negative below the LLA in normothermic sham (p = 0.022) and normothermic arrested groups (p = 0.006).

Figure 4

Spline regression model fit lines of the cerebral oximetry volume (COx) index during induced hypotension. Each piglet’s lower limit of autoregulation (LLA) is centered to zero on the x-axis, permitting comparison of each animal’s cerebral perfusion pressure (CPP) relative to LLA. COx became more positive as CPP decreased below the LLA in (A) normothermic sham, (B) hypothermic sham, (C) normothermic post-arrest, and (D) hypothermic post-arrest piglets. (n = 8 per group). Spline regression analysis indicated that the slope of the relationship of COx with CPP became significantly more negative below the LLA in the normothermic arrested group (p = 0.006).

Figure 5

All cohorts had preserved autoregulation during hypertension. (A) Sham piglets had relatively constant laser-Doppler flux (LDF, mean ± SD) during normothermia and hypothermia (n = 8 per group). (B) Piglets resuscitated from arrest also had relatively constant LDF during normothermia and hypothermia (n = 8 per group). (C) The static rate of autoregulation (sROR, mean, 95% confidence intervals) of all groups indicated intact autoregulation during hypertension (p = 0.466).

Figure 6

Linear regression lines show that the hemoglobin volume (HVx) and cerebral oximetry (COx) indices were consistent with preserved autoregulation during induced hypertension. (A) Post-arrest, normothermic piglets (n = 8), and (B) post-arrest, hypothermic piglets (n = 8) displayed negative HVx with rising cerebral perfusion pressure (CPP), indicating intact cerebrovascular reactivity. (C) Post-arrest, normothermic piglets (n = 8), and (D) post-arrest, hypothermic (n = 8) piglets also had overall low COx values, indicating functional autoregulation. Data are shown with 95% confidence intervals.