| Background: Perioperative hypoxic-ischemia (HI) myocardial andneurologic damage caused by cardiac arrest (CA) is the leading cause of acutedeath and chronic disability in children. There is no comprehensive preventionand treatment to CA-induced pediatric HI damage. Hypothemia is an importantmanagement for myocardial protection during cardiopulmonary bypass (CPB)cardiac surgery, it is also the only effective way for post-resuscitation treatmentthrough reduces the metabolism and attenuates tissue edema in children. But thetime window and clinical efficacy of hypothermia in pediatric CA is limited.Therefore, a clinical need remains for finding agents or intervention that can beadministered easily and that can provide an added benefit with delayedhypothermia in protecting the heart and brain from HI.Oxidant stress is considered a major contributing factor to CA–induced HIdamage in immature heart and brain. In our previous studies demonstrated thathypothermia-mediated myocardial/neurologic protection is related to increased formation of protein carbonyl groups, nitration of proteins and nucleic acids, andhydroxylation of nucleic acids. And early antioxidant therapy can provide partialneuroprotection after resuscitation. Therefore, we presume that interventions or agentswith an antioxidant capacity would provide additive cardio/neuroprotection fordelayed hypothermia. Acupuncture mimics pretreatment that exertsneuroprotective and cardioprotective effects through increasing activity ofantioxidant enzyme and enhancing ability of free radical scavenging in animalmodels and in adult patients underwent cardiac surgery; however, data in effect oftranscutaneous electrical acupoint stimulation on pediatric ischemiccardio/cerebral damage from cardiac arrest are unavailable.In this study part I, we tested the hypothesis that treatment with thesuperoxide dismutase-catalase mimetic EUK-134at30minutes of recoveryprovides additive neuronal protection when combined with one day of wholebody hypothermia implemented4hours after resuscitation. In Part II, through aclinical controlled trial, we investigated that the effects of transcutaneouselectrical acupoint stimulation on the hypoxic ischemia heart and brain damagecaused by CA with hypothermia in the pediatric open heart surgery，to determinewhether these measures can be used as an alternative prevention to reduce heartand brain damage from perioperative CA in children.Part I Effect of Combined Early Antioxidant Treatmentand Delayed Hypothermia on Neuroprotection afterHypoxic-Ischemia in PigletObjective: To test the hypothesis that treatment with the superoxidedismutase-catalase mimetic EUK-134at30minutes of recovery provides additive neuronal protection when combined with one day of whole body hypothermiaimplemented4hours after resuscitation in a piglet model of hypoxic-ischmia(HI).Methods: Anesthetized piglets were subjected to40minutes of hypoxia(10%inspired oxygen) followed by7minutes of airway occlusion andresuscitation. EUK-134was administrated with a bolus dose2.5mg/kg at30minutes of recovery, plus1.25mg/kg/h intravenous infusion until4hours ofrecovery. Body temperature was maintained at38.5°C in normothermic groupsand at34°C in hypothermic groups. All groups were mechanically ventilated,sedated, and received muscle relaxants during the first day of recovery.Results: At10days of recovery, neuronal viability in putamen of anormothermic group treated with saline vehicle was reduced to17±9%(±SD) ofthe value in a sham-operated control group (100±18%). Intravenous infusion ofEUK-134with normothermic recovery resulted in40±17%viable neurons inputamen. Treatment with saline vehicle followed by delayed hypothermiaresulted in partial protection (46±21%). Combining early EUK-134treatmentwith delayed hypothermia did not produce additional protection in putamen(47±25%). Furthermore, no additive neuroprotection was detected in caudatenucleus or parasagittal neocortex, where neuronal loss was less severe.Conclusions: We conclude that early treatment with this antioxidant doesnot extend the therapeutic benefit of hypothermia in protecting highly vulnerableneurons in ischemic-ischemia (HI)-insulted pediatrics, possibly because basalganglia neurons are already undergoing irreversible cell death signaling by thetime EUK-134is administered or because this compound and hypothermiaattenuate similar mechanisms of injury. Part II Myocardial/Neurologic Protection of TEAS in thePediatric Cardiac Patients: A Randomized Controlled TrialObjective: To investigate the effects of transcutaneous electric acupointstimulation (TEAS) on acute myocardial/neurologic injury from pediatricopen-heart surgery.Methods: Children, aged2–12years, with congenital heart defectsscheduled for surgical repair were enrolled. They were randomized to TEAS(administrated at bilateral P6acupoint for30min after basal anesthesia) andcontrol (an electrode was placed on the arm without stimulus) groups. Theduration of cardiopulmonary bypass and aortic cross-clamp time was recorded.The primary end point was serum cardiac troponin I (cTnI) and S100βlevelover24h after aortic unclamping. Furthermore, clinical outcome, and serummyohemoglobin (Myo), interleukin (IL-8, IL-10), tumor necrosis factor (TNF-α),C-reactive protein (CRP) and8-isoprostane (8-iso PGF2α) concentrations wereevaluated pre-and postoperatively.Results: Seventy eligible children were analyzed,36in controls and34inTEAS group. Compared with controls, the mean serum Myo concentration wassignificantly lower in TEAS group at2h (P=0.037); the mean cTnI levels weresignificantly lower in TEAS group at8h (P=0.043) and24h (P=0.046) afteraortic unclamping. After aortic unclamping, S100βlevel significantly increasedand rearched a peak at30min (control group1.44±0.67ug/L vs. TEAS group1.35±0.58ug/L), thereafter, declined rapidly; the serum concentration of S100βdecreased to a half of peak values by2h (0.67±0.46ug/L vs.0.77±0.4ug/L),then recovered to preoperative level at24h; there is no significant differences of serum S100β elevated level in each time point between groups. The duration ofventilation (P=0.004) and length of ICU stay (P=0.032) was significantly longerin controls than in TEAS group. There was a significant difference in the releaseof C-reactive protein at8h (P=0.039) between two groups, whereas the valuesfor8-iso PGF2α and cytokines were not significant.Conclusion: Transcutaneous electric acupoint stimulation on the bilateral P6acupoint is effective for attenuation myocardial injury in children undergoingcardiac surgery. The beneficial effects may be partially associated with reductionin cTnI and C-reactive protein level in the early postoperative period. |
PDF Full Text Request