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Improved neuroprotective effect of methylene blue with hypothermia after porcine cardiac arrest
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
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2013 (English)In: Acta Anaesthesiologica Scandinavica, ISSN 0001-5172, E-ISSN 1399-6576, Vol. 57, no 8, 1073-1082 p.Article in journal (Refereed) Published
Abstract [en]

Background

Induced mild hypothermia and administration of methylene blue (MB) have proved to have neuroprotective effects in cardiopulmonary resuscitation (CPR); however, induction of hypothermia takes time. We set out to determine if MB administered during CPR could add to the histologic neuroprotective effect of hypothermia.

Methods

A piglet model of extended cardiac arrest (12 min of untreated cardiac arrest and 8 min of CPR) was used to assess possible additional neuroprotective effects of MB when administered during CPR before mild therapeutic hypothermia induced 30 min after restoration of spontaneous circulation (ROSC). Three groups were compared: C group (n = 8) received standard CPR; PH group (n = 8) received standard CPR but 30 min after ROSC these piglets were cooled to 34°C; the PH+MB group (n = 8) received an MB infusion 1 min after commencement of CPR and the same cooling protocol as the PH group. Three hours later, the animals were killed. Immediately after death, the brains were harvested pending histological and immunohistological analysis.

Results

Circulatory variables were similar in the groups except that cardiac output was greater in the PH+MB group 2–3 h after ROSC. Cerebral cortical neuronal injury and blood–brain barrier disruption was greatest in the C group and least in the MB group. The neuroprotective effect of MB and hypothermia was significantly greater than that of delayed hypothermia alone.

Conclusion

Administration of MB during CPR added to the short term neuroprotective effects of induced mild hypothermia induced 30 min after ROSC.

Place, publisher, year, edition, pages
2013. Vol. 57, no 8, 1073-1082 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-199854DOI: 10.1111/aas.12106ISI: 000323075000017PubMedID: 23577658OAI: oai:DiVA.org:uu-199854DiVA: diva2:621762
Available from: 2013-05-17 Created: 2013-05-17 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Novel Interventions in Cardiac Arrest: Targeted Temperature Management, Methylene Blue, S-PBN, Amiodarone, Milrinone and Esmolol,  Endothelin and Nitric Oxide In Porcine Resuscitation Models
Open this publication in new window or tab >>Novel Interventions in Cardiac Arrest: Targeted Temperature Management, Methylene Blue, S-PBN, Amiodarone, Milrinone and Esmolol,  Endothelin and Nitric Oxide In Porcine Resuscitation Models
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

It is a major clinical problem that survival rates after out-of-hospital cardiac arrest have not markedly improved during the last decades, despite extensive research and the introduction of new interventions. However, recent studies have demonstrated promising treatments such as targeted temperature management (TTM) and methylene blue (MB).

In our first study, we investigated the effect of MB administered during experi-mental cardiopulmonary resuscitation (CPR) in the setting of postponed hypother-mia in piglets. We set out to study if MB could compensate for a delay to establish targeted TTM. The study demonstrated that MB more than compensated for 30 min delay in induction of TTM. The effect of MB added to that of TTM.

The second study examined the effects of TTM and S-PBN on the endothelin system and nitric oxide synthases (NOS) after prolonged CA in a porcine CPR mod-el. The study was designed to understand the cardioprotective mechanism of S-PBN and TTM by their influence on the endothelin system and NOS regulation. We veri-fied for the first time, that these two cardioprotective postresuscitative interventions activate endothelin-1 and its receptors concomitantly with eNOS and nNOS in the myocardium. We concluded that nitric oxide and endothelin pathways are implicated in the postresuscitative cardioprotective effects of TTM.

The third study compared survival and hemodynamic effects of low-dose amio-darone and vasopressin to vasopressin in a porcine hypovolemic CA model. The study was designed to evaluate whether resuscitation with amiodarone and vasopressin compared to vasopressin alone would have an impact on resuscitation success, survival, and hemodynamic parameters after hemorrhagic CA. We found that combined resuscitation with amiodarone and vasopressin after hemorrhagic circulatory arrest resulted in greater 3-hour survival, better preserved hemodynamic parameters and smaller myocardial injury compared to resuscitation with vasopressin only.

In our fourth study we planned to compare hemodynamic parameters between the treatment group (milrinone, esmolol and vasopressin; MEV) and control group (vasopressin only) during resuscitation from prolonged cardiac arrest in piglets. The study was designed to demonstrate if MEV treatment improved hemodynamics or cardiac damage compared to controls. We demonstrated that MEV treatment reduced cardiac injury compared with vasopressin alone.

Place, publisher, year, edition, pages
Uppsala: Uppsala universitet, 2015. 102 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1056
Keyword
restoration of spontaneous circulation, ROSC, cardiopulmonary resuscitation, CPR, cardiac arrest, methylene blue, MB, S-PBN, mild therapeutic hypothermia, MTH, targeted temperature management, TTM, endothelin, ET-1, ECE-1, ETAR, ETBR, nitric oxide, NO, nitric oxide synthase, NOS, eNOS, iNOS, nNOS, porcine, amiodarone, hypovolemia, milrinone, vasopressin, esmolol, epinephrine
National Category
Anesthesiology and Intensive Care Cell and Molecular Biology Physiology Cardiac and Cardiovascular Systems
Research subject
Anaesthesiology and Intensive Care; Medical Cell Biology; Cardiology
Identifiers
urn:nbn:se:uu:diva-236312 (URN)978-91-554-9116-1 (ISBN)
Public defence
2015-01-30, Hedstrandssalen, Akademiska sjukhuset, Ing. 70, Uppsala, 13:15 (Swedish)
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Supervisors
Available from: 2015-01-08 Created: 2014-11-17 Last updated: 2015-02-03

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Wiklund, LarsZoerner, FrankSemenas, EgidijusMiclescu, AdrianaBasu, SamarSharma, Hari Shanker

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