The Effect of Hypothermia and Osmotic Shock on the Electrocardiogram of Adult Zebrafish.

The use of zebrafish to explore cardiac physiology has been widely adopted within the scientific community. Whether this animal model can be used to determine drug cardiac toxicity via electrocardiogram (ECG) analysis is still an ongoing question. Several reports indicate that the recording configuration severely affects the ECG waveforms and its derived-parameters, emphasizing the need for improved characterization. To address this problem, we recorded ECGs from adult zebrafish hearts in three different configurations (unexposed heart, exposed heart, and extracted heart) to identify the most reliable method to explore ECG recordings at baseline and in response to commonly used clinical therapies. We found that the exposed heart configuration provided the most reliable and reproducible ECG recordings of waveforms and intervals. We were unable to determine T wave morphology in unexposed hearts. In extracted hearts, ECG intervals were lengthened and P waves were unstable. However, in the exposed heart configuration, we were able to reliably record ECGs and subsequently establish the QT-RR relationship (Holzgrefe correction) in response to changes in heart rate.

Early administration of cold water and adipose derived mesenchymal stem cell derived exosome effectively protects the heart from ischemia-reperfusion injury.

This study tested the hypothesis that early administration with cold water (CW)-assisted adipose-derived mesenchymal stem cell (ADMSC)-derived exosome (Exo) therapy was superior to either one on protecting the heart against ischemia-reperfusion (IR) (i.e., by ligation of 50 minutes and relieved by day 5 prior to euthanizing the animals) injury. Adult-male SD rats (n=30) were equally categorized into groups 1 (sham-operated control), 2 (IR), 3 (IR + CW), 4 (IR + Exo) and 5 (IR + CW-Exo). The left ventricular ejection fraction (LVEF) was highest in group 1, lowest in group 2, and significantly higher in group 5 than in groups 3 and 4, but no difference between groups 3 and 4 (all P<0.001). The protein expressions of oxidative-stress (NOX-1/NOX-2/NOX-4/oxidized protein), apoptotic/mitochondrial-damaged (mitochondrial-Bax/caspase 3/PARP/p53/cytosolic-cytochrome-C) and inflammatory (IL-1ß/TNF-α/NF-κB/MMP-9) biomarkers, and cellular-stress response signaling (PI3K/Akt/GSK3ß and p-m-TOR) showed an opposite pattern, whereas the anti-oxidants (SIRT1/SIRT3), anti-inflammation (IL-10) and IKB-α/p-AMKP/mitochondrial-cytochrome-C exhibited an identical pattern to the LVEF among the five groups (all P<0.0001). The cellular expressions of inflammation (CD68), total cellular ROS (i.e., stained by H2DCFDA) and the LV infarct/fibrotic/collagen-deposition areas displayed an opposite pattern, whereas the cell gap junction (coonexin 43) and sarcomere length exhibited an identical pattern of LVEF among the five groups (all P<0.0001). Conclusion: Combined CW-exosome therapy markedly protected the heart against IR injury.

Relationship between prolonged neural suppression and cerebral hemodynamic dysfunction during hypothermia in asphyxiated piglets.

OBJECTIVES: Hypothermia (HT) improves the outcome of neonatal hypoxic-ischemic encephalopathy. Here, we investigated changes during HT in cortical electrical activity using amplitude-integrated electroencephalography (aEEG) and in cerebral blood volume (CBV) and cerebral hemoglobin oxygen saturation using near-infrared time-resolved spectroscopy (TRS) and compared the results with those obtained during normothermia (NT) after a hypoxic-ischemic (HI) insult in a piglet model of asphyxia. We previously reported that a greater increase in CBV can indicate greater pressure-passive cerebral perfusion due to more severe brain injury and correlates with prolonged neural suppression during NT. We hypothesized that when energy metabolism is suppressed during HT, the cerebral hemodynamics of brains with severe injury would be suppressed to a greater extent, resulting in a greater decrease in CBV during HT that would correlate with prolonged neural suppression after insult. METHODS: Twenty-six piglets were divided into four groups: control with NT (C-NT, n = 3), control with HT (C-HT, n = 3), HI insult with NT (HI-NT, n = 10), and HI insult with HT (HI-HT, n = 10). TRS and aEEG were performed in all groups until 24 h after the insult. Piglets in the HI-HT group were maintained in a hypothermic state for 24 h after the insult. RESULTS: There was a positive linear correlation between changes in CBV at 1, 3, 6, and 12 h after the insult and low-amplitude aEEG (<5 µV) duration after insult in the HI-NT group, but a negative linear correlation between these two parameters at 6 and 12 h after the insult in the HI-HT group. The aEEG background score and low-amplitude EEG duration after the insult did not differ between these two groups. DISCUSSION AND CONCLUSION: A longer low-amplitude EEG duration after insult was associated with a greater CBV decrease during HT in the HI-HT group, suggesting that brains with more severe neural suppression could be more prone to HT-induced suppression of cerebral metabolism and circulation.

Localized intestinal perforations as a potential complication of brain hypothermic therapy for perinatal asphyxia.

Brain hypothermic therapy (BHT) is becoming a frequently used standard of care for perinatal asphyxia. Although cardiovascular side effects, coagulation disorders, renal impairment, electrolyte abnormalities, impaired liver function, opportunistic infections, and skin lesions are well-known adverse effects of BHT in newborns, little information is available on the clinical features of intestinal perforation-related BHT. We herein report a case of therapeutic brain cooling for perinatal asphyxia complicated by localized intestinal perforation. In practice, the neonatologist should be aware that intestinal perforation in an infant with perinatal asphyxia is possible, particularly following BHT.

Brain hypothermia therapy for childhood acute encephalopathy based on clinical evidence.

Although previous studies have reported on the effectiveness of brain hypothermia therapy in childhood acute encephalopathy, additional studies in this field are necessary. In this review, we discussed brain hypothermia therapy methods for two clinical conditions for which sufficient evidences are currently available in the literature. The first condition is known as hypoxic-ischemic encephalopathy and occurs in newborns and the second condition is acute encephalopathy which occurs in adults following cardiopulmonary resuscitation associated with out-of-hospital cardiac arrest state resulting from ventricular arrhythmia. Furthermore, we assessed the prospects of applying these therapies to acute encephalopathy in children.

Simultaneous measurement of cerebral hemoglobin oxygen saturation and blood volume in asphyxiated neonates by near-infrared time-resolved spectroscopy.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) usually results in a poor clinical outcome even when treated with hypothermic therapy (HT). Early postnatal changes in cerebral blood oxygenation and hemodynamics may be critical determinants of brain injury and the efficacy of HT. OBJECTIVES: We measured cerebral hemoglobin oxygen saturation (ScO2) and cerebral blood volume (CBV) by near-infrared time-resolved spectroscopy (TRS) in HT-treated and non-HT-treated neonatal HIE patients to assess the influence of these parameters on clinical outcome. METHODS: We retrospectively compared ScO2, CBV, and clinical outcomes of 11 neonates with HIE: 5 were treated by HT (HT-treated; 33.5°C±0.5°C for 72h starting approximately 6h after delivery) and 6 were not (non-HT-treated). Both CBV and ScO2 were measured by TRS at 6, 24, 48, and 72h after birth. Magnetic resonance imaging (MRI) was performed 1-2weeks after birth to assess brain injury. RESULTS: Five neonates had adverse outcomes (3 HT-treated, 2 non-HT-treated). Of these, 1 died within 3days of birth and 4 had abnormal MRI findings, including basal ganglia, white matter, and/or thalamic lesions. The other 6 neonates had normal MRI findings (favorable outcome). At 6h after birth, CBV was significantly higher in neonates with adverse outcomes compared with those with a favorable outcome. At 24h after birth, ScO2 was significantly higher in neonates with adverse outcomes. Furthermore, we found that combined CBV at 24h after birth plus ScO2 had the best predictive ability for neurological outcome: sensitivity, specificity, positive predictive value, and negative predictive value were all 100%. CONCLUSION: Early postnatal CBV and ScO2 elevations were predictive of a poor outcome in HIE. Therefore, measuring combined CBV plus ScO2 at 24h after birth can allow more precise prediction of neurological outcome. Control of postnatal CBV and ScO2 is critical for effective HIE treatment.

Hypoxic cardiopulmonary arrest with full recovery after induced hypothermic therapy.

CASE: The patient's chart was reviewed, summarized, and presented. OUTCOME: A 41-year-old male collapsed after complaining of dyspnea just before the end of a hemodialysis session. He was just being introduced to hemodialysis. The patient's percutaneous oxygen saturation dropped to 50% even under inhalation of 10 L/minute of oxygen and he developed pulseless electrical activity. After tracheal intubation, a return of spontaneous circulation was noted. His truncal CT disclosed a bilateral diffuse ground glass appearance and pleural effusion were noted. Induced mild hypothermic therapy and mechanical ventilation resulted in the improvement of his respiratory function and consciousness. A coronary angiogram and left ventriculography showed no significant lesion, and his pulmonary edema was considered to have been induced by over-hydration due to renal failure, diastolic heart failure or dialysis disequilibrium syndrome. He was discharged without any neurological deficit. CONCLUSION: Tracheal intubation with ventilation for hypoxic cardiopulmonary arrest and induced hypothermic therapy after obtaining spontaneous circulation may be factors of favorable outcome of this case.