Effect of deep hypothermic circulatory arrest followed by low-flow cardiopulmonary bypass on brain metabolism in newborn piglets: Comparison of pH-stat and α-stat management

Abstract

Objective-To compare the effects of pH-stat and alpha-stat management prior to deep hypothermic circulatory arrest (DHCA) followed by a period of low flow (two rates) cardiopulmonary bypass (CPB) on cortical oxygenation and selected regulatory proteins: Bax, Bcl-2, Caspase-3 and phospho-Akt.Design-Piglets were placed on CPB, cooled with pH-stat or alpha-stat management to 18°C over 30 min, subjected to 30 min DHCA and 1h low flow at 20 (LF-20) or 50 ml/kg/min (LF-50), rewarmed to 37°C, separated from CPB, and recovered for 6 h.Subjects-Newborn piglets, 2-5 days old, randomly assigned to experimental groups.Measurements and main results-Cortical oxygen was measured by oxygen-dependent quenching of phosphorescence; proteins were measured by western blots. The means from 6 experiments ± standard error (SEM) are presented as % of alpha-stat. Significance was by t-test. For LF-20, cortical oxygenation was similar for alpha-stat and pH-stat, whereas for LF-50 it was significantly better using pH-stat. For LF-20, the measured proteins were not different except for Bax in the cortex (214±24%, p=0.006) and hippocampus (118% ± 6%, p=0.024) and Caspase 3 in striatum (126% ± 7%, p=0.019). For LF-50, in pH-stat group: In cortex, Bax and Caspase-3 were lower (72±8%, p=0.001 and 72±10%, p=0.004, respectively) and pAkt was higher (138±12%, p=0.049). In hippocampus, Bcl-2 and Bax were not different but pAkt was higher 212±37% (p=0.005) and Caspase 3 lower (84 ± 4%, p=0.018). In striatum, Bax and pAkt did not differ but Bcl-2 increased (146±11%, p=0.001) and Caspase-3 decreased (81±11%, p=0.042).Conclusions-In this DHCA-LF model, when flow was 20ml/kg/min there was little difference between alpha-stat and pH-stat management. However for LF-50, pH-stat management resulted in better cortical oxygenation during recovery and Bax, Bcl-2, pAkt and Caspase-3 changes consistent with lesser activation of pro-apoptotic signaling with pH-stat than with alpha-stat.

Ulinastatin as a neuroprotective and anti‐inflammatory agent in infant piglets model undergoing surgery on hypothermic low‐flow cardiopulmonary bypass

“…In this study, results of histological examination of hippocampus in group C showed that the timeframe of 120-min hypothermic low-flow CPB surgery resulted in brain injury in infant piglets, mainly represented by neuronal and glial cell damage accompanied by inflammatory cell infiltration. This is consistent with the majority of similar studies in the literature (5,14).…”

“…*P < 0.05, compared to Group S, # P < 0.05, compared to Group C. Histopathologic slides were scored as follows: 0 = normal neuronal structure; 1 = rare clusters (<5) of damaged neurons; 2 = occasional clusters(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) of damaged neurons; 3 = frequent clusters (>15) of damaged neurons; and 4 = diffusely distributed damaged neurons. Typical histologic examination results in the three groups, photomicrographs of a cluster of damaged neurons in the superficial hippocampus.…”

Near‐infrared spectroscopy: exposing the dark (venous) side of the circulation

“…Continuous rSO 2 C monitoring during ACP aids the detection of cerebral perfusion abnormalities and is critical to ensuring optimal cerebral flow and adequate antegrade flow. Animal and human data demonstrate improved cerebral outcomes only if ACP flow is adequate to normalize cerebral blood flow, detectable by TCD or NIRS .…”

Clinical Practice Variability in Temperature Correction of Arterial Blood Gas Measurements and Outcomes in Hypothermia-Treated Patients After Cardiac Arrest

“…Total body PaCO 2 and cerebral blood flow (CBF) might, therefore, be higher in a patient ventilated with the pH-stat method (Kofstad, 1996;Kollmar et al, 2002;Pynnonen et al, 2011) by avoiding hyperventilation, which would have exerted a vasoconstrictive effect (Diringer et al, 2002;Imberti et al, 2002;Coles et al, 2007). Borrowing from literature performed in other than populations, there are possibly improved outcomes with pH-stat in hypothermic cardiopulmonary bypass patients (du Plessis et al, 1997;Laussen et al, 2002) and increased tissue oxygenation with pH-stat in animal studies (Duebener et al, 2002;Markowitz et al, 2007;Pirzadeh et al, 2011). Animal (Kollmar et al, 2002) and human (Kollmar et al, 2009) studies in ischemic stroke have demonstrated this phenomenon of reduced cerebral infarct volume and higher CBF when ventilated using pH-versus a-stat methods.…”