scholarly journals Additive Neuroprotection of a 20-HETE Inhibitor with Delayed Therapeutic Hypothermia after Hypoxia-Ischemia in Neonatal Piglets

2015 ◽  
Vol 37 (4-5) ◽  
pp. 376-389 ◽  
Author(s):  
Junchao Zhu ◽  
Bing Wang ◽  
Jeong-Hoo Lee ◽  
Jillian S. Armstrong ◽  
Ewa Kulikowicz ◽  
...  
Keyword(s):  
Therapeutic Hypothermia ◽  
Brain Regions ◽  
Therapeutic Benefit ◽  
Whole Body ◽  
Arachidonic Acid Metabolite ◽  
Synthesis Inhibitor ◽  
Neonatal Piglets ◽  
Hypoxia Ischemia ◽  
Ischemia Group ◽  
Whole Body Cooling

The severity of perinatal hypoxia-ischemia and the delay in initiating therapeutic hypothermia limit the efficacy of hypothermia. After hypoxia-ischemia in neonatal piglets, the arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) has been found to contribute to oxidative stress at 3 h of reoxygenation and to eventual neurodegeneration. We tested whether early administration of a 20-HETE synthesis inhibitor after reoxygenation augments neuroprotection with 3-hour delayed hypothermia. In two hypothermic groups, whole body cooling from 38.5 to 34°C was initiated 3 h after hypoxia-ischemia. Rewarming occurred from 20 to 24 h; then anesthesia was discontinued. One hypothermic group received a 20-HETE inhibitor at 5 min after reoxygenation. A sham-operated group and another hypoxia-ischemia group remained normothermic. At 10 days of recovery, resuscitated piglets with delayed hypothermia alone had significantly greater viable neuronal density in the putamen, caudate nucleus, sensorimotor cortex, CA3 hippocampus, and thalamus than did piglets with normothermic recovery, but the values remained less than those in the sham-operated group. In piglets administered the 20-HETE inhibitor before hypothermia, the density of viable neurons in the putamen, cortex and thalamus was significantly greater than in the group with hypothermia alone. Cytochrome P450 4A, which can synthesize 20-HETE, was expressed in piglet neurons in these regions. We conclude that early treatment with a 20-HETE inhibitor enhances the therapeutic benefit of delayed hypothermia in protecting neurons in brain regions known to be particularly vulnerable to hypoxia-ischemia in term newborns.

Subcutaneous fat necrosis, a rare but serious side effect of hypoxic-ischemic encephalopathy and whole-body hypothermia

2019 ◽  
Vol 47 (9) ◽  
pp. 986-990 ◽  
Author(s):  
Mahdi Alsaleem ◽  
Lina Saadeh ◽  
Valerie Elberson ◽  
Vasantha H.S. Kumar
Keyword(s):  
Therapeutic Hypothermia ◽  
Subcutaneous Fat ◽  
Whole Body ◽  
Subcutaneous Fat Necrosis ◽  
P Values ◽  
Life Threatening ◽  
The Mean ◽  
Body Cooling ◽  
Whole Body Cooling ◽  
Ischemic Encephalopathy

Abstract Objective To describe the clinical characteristics and risk factors in infants with subcutaneous fat necrosis (SFN) following therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE). Methods A case-control study was performed by a retrospective chart review of infants with moderate or severe HIE admitted to a level IV regional perinatal center and who underwent whole-body cooling. Results A total of 14 (8.1%) of 171 infants with moderate or severe HIE who underwent whole-body cooling developed SFN during hospitalization. There were more females [71% (10/14)] and large-for-gestational age (LGA) infants [28% (4/14)] in the SFN group vs. 36% females (57/157) and 8% LGA infants (13/157) in the group without SFN (P-values of 0.009 and 0.015, respectively). The mean lowest platelet count was lower 108 ± 55 109/L vs. 146 ± 62 109/L and the mean highest calcium level was higher 11.3 ± 2.5 vs. 10.6 ± 0.8 mg/dL in infants with SFN vs. infants without SFN, respectively (P-values of 0.0078 and 0.006, respectively). Distribution of skin lesions followed distinctive patterns representing the areas with direct contact with the cooling blanket. One infant developed severe, life-threatening hypercalcemia that required aggressive management, including diuretics, corticosteroids and bisphosphonates. Conclusion Although SFN is a rare complication of therapeutic hypothermia, it can be a life-threatening condition if complicated by severe hypercalcemia. Infants who undergo therapeutic hypothermia for HIE need regular skin examinations to evaluate for SFN. If SFN is identified, monitoring of serum calcium levels to prevent life-threatening hypercalcemia is recommended.

scholarly journals Therapeutic hypothermia in asphyxiated newborns: selective head cooling vs. whole body cooling — comparison of short term outcomes

2019 ◽  
Vol 90 (7) ◽  
pp. 403-410 ◽  
Author(s):  
Ewa Matylda Gulczynska ◽  
Janusz Gadzinowski ◽  
Marcin Kesiak ◽  
Barbara Sobolewska ◽  
Joanna Caputa ◽  
...  
Keyword(s):  
Therapeutic Hypothermia ◽  
Whole Body ◽  
Short Term ◽  
Head Cooling ◽  
Body Cooling ◽  
Whole Body Cooling

scholarly journals Systemic effects of whole-body cooling to 35 °C, 33.5 °C, and 30 °C in a piglet model of perinatal asphyxia: implications for therapeutic hypothermia

2012 ◽  
Vol 71 (5) ◽  
pp. 573-582 ◽  
Author(s):  
Aron Kerenyi ◽  
Dorottya Kelen ◽  
Stuart D. Faulkner ◽  
Alan Bainbridge ◽  
Manigandan Chandrasekaran ◽  
...  
Keyword(s):  
Therapeutic Hypothermia ◽  
Perinatal Asphyxia ◽  
Whole Body ◽  
Systemic Effects ◽  
Body Cooling ◽  
Whole Body Cooling

scholarly journals Therapeutic Hypothermia Achieves Neuroprotection via a Decrease in Acetylcholine with a Concurrent Increase in Carnitine in the Neonatal Hypoxia-Ischemia

2015 ◽  
Vol 35 (5) ◽  
pp. 794-805 ◽  
Author(s):  
Toshiki Takenouchi ◽  
Yuki Sugiura ◽  
Takayuki Morikawa ◽  
Tsuyoshi Nakanishi ◽  
Yoshiko Nagahata ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Therapeutic Hypothermia ◽  
Quantitative Imaging ◽  
Imaging Mass Spectrometry ◽  
Brain Regions ◽  
Acetyl Coa ◽  
Neuroprotective Effects ◽  
Neurologic Outcomes ◽  
Hypoxia Ischemia ◽  
The Brain

Although therapeutic hypothermia is known to improve neurologic outcomes after perinatal cerebral hypoxia-ischemia, etiology remains unknown. To decipher the mechanisms whereby hypothermia regulates metabolic dynamics in different brain regions, we used a two-step approach: a metabolomics to target metabolic pathways responding to cooling, and a quantitative imaging mass spectrometry to reveal spatial alterations in targeted metabolites in the brain. Seven-day postnatal rats underwent the permanent ligation of the left common carotid artery followed by exposure to 8% O2 for 2.5 hours. The pups were returned to normoxic conditions at either 38°C or 30°C for 3 hours. The brain metabolic states were rapidly fixed using in situ freezing. The profiling of 107 metabolites showed that hypothermia diminishes the carbon biomass related to acetyl moieties, such as pyruvate and acetyl-CoA; conversely, it increases deacetylated metabolites, such as carnitine and choline. Quantitative imaging mass spectrometry demarcated that hypothermia diminishes the acetylcholine contents specifically in hippocampus and amygdala. Such decreases were associated with an inverse increase in carnitine in the same anatomic regions. These findings imply that hypothermia achieves its neuroprotective effects by mediating the cellular acetylation status through a coordinated suppression of acetyl-CoA, which resides in metabolic junctions of glycolysis, amino-acid catabolism, and ketolysis.

Control of translation in the cold: implications for therapeutic hypothermia

2015 ◽  
Vol 43 (3) ◽  
pp. 333-337 ◽  
Author(s):  
John R.P. Knight ◽  
Anne E. Willis
Keyword(s):  
Blood Flow ◽  
Therapeutic Hypothermia ◽  
Heart Surgery ◽  
Whole Body ◽  
Potential Importance ◽  
Therapeutic Gain ◽  
Body Cooling ◽  
Whole Body Cooling ◽  
The Brain ◽  
Reduced Temperature

Controlled whole-body cooling has been used since the 1950s to protect the brain from injury where cerebral blood flow is reduced. Therapeutic hypothermia has been used successfully during heart surgery, following cardiac arrest and with varied success in other instances of reduced blood flow to the brain. However, why reduced temperature is beneficial is largely unknown. Here we review the use of therapeutic hypothermia with a view to understanding the underlying biology contributing to the phenomenon. Interestingly, the benefits of cooling have recently been extended to treatment of chronic neurodegenerative diseases in two mouse models. Concurrently studies have demonstrated the importance of the regulation of protein synthesis, translation, to the cooling response, which is also emerging as a targetable process in neurodegeneration. Through these studies the potential importance of the rewarming process following cooling is also beginning to emerge. Altogether, these lines of research present new opportunities to manipulate cooling pathways for therapeutic gain.

scholarly journals Delayed Hypothermia as Selective Head Cooling or Whole Body Cooling Does Not Protect Brain or Body in Newborn Pig Subjected to Hypoxia-Ischemia

2008 ◽  
Vol 64 (1) ◽  
pp. 74-80 ◽  
Author(s):  
Mathias Karlsson ◽  
James R Tooley ◽  
Saulius Satas ◽  
Catherine E Hobbs ◽  
Ela Chakkarapani ◽  
...  
Keyword(s):  
Whole Body ◽  
Head Cooling ◽  
Hypoxia Ischemia ◽  
Body Cooling ◽  
Whole Body Cooling

scholarly journals Distribution and Severity of Hypoxic-Ischemic Lesions on Brain MRI Following Therapeutic Cooling: Selective Head Versus Whole Body Cooling

2011 ◽  
Vol 70 ◽  
pp. 722-722
Author(s):  
S Sarkar ◽  
J R Bapuraj ◽  
S M Donn ◽  
I Bhagat ◽  
J D Barks
Keyword(s):  
Brain Mri ◽  
Whole Body ◽  
Body Cooling ◽  
Whole Body Cooling
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