Neuroprotective effect of selective antegrade cerebral perfusion during prolonged deep hypothermic circulatory arrest: Cerebral metabolism evidence in a pig model

Abstract

Objective: The aim of this study was to elucidate the mechanism of cerebral injury and to evaluate selective antegrade cerebral perfusion (SACP) as a superior neuroprotective strategy for prolonged deep hypothermic circulatory arrest (DHCA).

Methods: Twelve pigs (6-8-week old) were randomly assigned to DHCA alone (n=6) and DHCA with SACP (n=6) at 18°C for 80 min groups. Serum S100 was determined using an immunoassay analyzer. The concentrations of cerebral dialysate glucose, lactate, pyruvate, glycerol, and glutamate were measured using a microdialysis analyzer.

Results: Compared with a peak at T4 (after 60 min of rewarming) in the DHCA group, the serum S100 in the SACP group was significantly lower throughout the study. The DHCA group was susceptible to significant increases in the levels of lactate, glycerol, and glutamate and the ratio of lactate/pyruvate as well as decreases in the level of glucose. These microdialysis variables showed only minor changes in the SACP group. There was a positive correlation between cerebral lactate and intracranial pressure during reperfusion in the DHCA group. However, the apoptosis index and C-FOS protein levels were lower in the SACP group.

Conclusion: Metabolic dysfunction is involved in the mechanism of cerebral injury. SACP is a superior neuroprotective strategy for both mild and prolonged DHCA.

Figure 1

(a) Experimental protocol schematic diagram for this study: T1. Baseline, at a cerebral temperature of 36°C, just before cooling; T2. After 45 min of cooling, at a nasopharynx/esophagus temperature of 18°C, before DHCA/SACP; T3. After an 80-min DHCA/SACP, before initiation of cardiopulmonary bypass (CPB); T4. after 60 min of rewarming; T5. After 120 min of reperfusion; T6. endpoint, after a 180-min reperfusion. (b) The skull sketch map for placing probes (A for coronal suture; B for sagittal suture; C for ICP; D for temperature; E for microdalysis; F for bregma)

Figure 2

(a) The serum S100 concentration detected by electrochemiluminescence immunoassay (PostCA, after circulatory arrest; RW, rewarm; RP, reperfusion *, P<0.05; #, P<0.01), and the electron micrograph (b) of the cerebral cortex (original magnification, ×13500) of the DHCA and SACP groups. Ultrastructure was rarefaction and disorganization (red arrow), mitochondria distension significant in DHCA group. The ultrastructure was nearly normal despite the moderately distant mitochondria (red arrow) and swollen cytoplasm in the SACP group

Figure 3

Fluorescence TUNEL staining of the frontal cortex (original magnification, x400). A more positive TUNEL reaction staining was seen in the nuclei of the neurons in the DHCA Group. There was lesser positive TUNEL staining in the SACP group. B is the apoptosis index calculated in the DHCA and SACP groups (17.89±5.35 vs. 9.66±1.97, t=3.319, P=0.02)

Figure 4

The dynamic change of intracranial pressure (ICP) (a) in both groups, and correlation analysis (b) between cerebral lactate and ICP during reperfusion in the DHCA group (r=0.64, P=0.046) are shown in the experiment, CA-circulatory arrest; RP-reperfusion, RW-rewarm; *, P<0.05; #, P<0.01

Figure 5

Cerebral cortex microdialysis results for the DHCA and SACP groups. (a) glucose; (b) lactate, (c) pyruvate; (d) lactate/pyruvate ratio; (e)glycerol; (f) glutamate. *, P<0.05, #, P<0.01.CA CA - circulatory arrest; RP - reperfusion; RW - rewarm

Figure 6

Western blotting for relative C-FOS protein levels. C-FOS of the SACP group was significantly lower than that of the DHCA group (t=3.304, P=0.012)