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Evidence for Time-dependent Maximum Increase ofFree Radical Damage and Eicosanoid Formation in theBrain as Related to Duration of Cardiac Arrest andCardio-pulmonary Resuscitation
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för folkhälso- och vårdvetenskap, Klinisk nutrition och metabolism.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för kirurgiska vetenskaper, Anestesiologi och intensivvård. (cardiopulmonary resuscitation)
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2003 (Engelska)Ingår i: Free radical research, ISSN 1071-5762, E-ISSN 1029-2470, Vol. 37, nr 3, s. 251-256Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Recovery of neurological function in patients following cardiac arrest and cardiopulmonary resuscitation (CPR) is a complex event. Free radical induced oxidative stress is supposed to be involved in this process. We studied levels of 8-iso-PGF2alpha (indicating oxidative injury) and 15-keto-dihydro-PGF2alpha (indicating inflammatory response) in venous plasma obtained from the jugular bulb in a porcine model of experimental cardiopulmonary resuscitation (CPR) where 2, 5, 8, 10 or 12 min of ventricular fibrillation (VF) was followed by 5 or 8 min of closed-chest CPR. A significant increase of 8-iso-PGF2alpha was observed immediately following restoration of spontaneous circulation in all experiments of various duration of VF and CPR. No such increase was seen in a control group. When compared between the groups there was a duration-dependent maximum increase of 8-iso-PGF2alpha which was greatest in animals subjected to the longest period (VF12 min + CPR8 min) of no or low blood flow. In contrast, the greatest increase of 15-keto-dihydro-PGF2alpha was observed in the 13 min group (VF8 min + CPR5 min). Thus, a time-dependent cerebral oxidative injury occurs in conjunction which cardiac arrest and CPR.

Ort, förlag, år, upplaga, sidor
2003. Vol. 37, nr 3, s. 251-256
Nyckelord [en]
Ischemia reperfusion, Prostaglandins, Isoprostanes
Nationell ämneskategori
Anestesi och intensivvård
Identifikatorer
URN: urn:nbn:se:uu:diva-106804DOI: 10.1080/1071576021000043058PubMedID: 12688420OAI: oai:DiVA.org:uu-106804DiVA, id: diva2:226762
Tillgänglig från: 2009-07-06 Skapad: 2009-07-04 Senast uppdaterad: 2017-12-13Bibliografiskt granskad
Ingår i avhandling
1. Cerebral Protection in Experimental Cardiopulmonary Resuscitation: With Special Reference to the Effects of Methylene Blue
Öppna denna publikation i ny flik eller fönster >>Cerebral Protection in Experimental Cardiopulmonary Resuscitation: With Special Reference to the Effects of Methylene Blue
2009 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Although survival rates are increasing, brain injury continues to be a leading cause of death after cardiac arrest (CA). Permanent brain damage after CA is determined by limited tolerance to ischemia from CA and cardiopulmonary resuscitation (CPR), as well as the unique cerebral response to reperfusion after return of spontaneous circulation (ROSC). A major pathway leading to neurotoxic cascade and neuronal injury after CA involves the increased presence of reactive oxygen and nitrogen species generated during ischemia and reperfusion. The magnitude of cerebral oxidative injury induced by free radicals increased with the duration of CA (Paper I). Nitric oxide (NO), a free radical responsible for the formation of reactive nitrogen species, is increased during global ischemia from CA and reperfusion (Paper IV). Hypothetically, the administration of a drug that counteracts the overproduction of NO and also acts as a scavenger of oxygen free radicals might be warranted in order to reduce the damage caused by nitrosative and oxidative stress. For these purposes we used methylene blue (MB), an old dye that has been used in medicine for almost half a century, and an experimental pig model of 20 min of ventricular fibrillation (VF) to reflect a clinical scenario of ischemia/reperfusion injury. Administration of MB added to a hypertonic-hyperoncotic solution (MBHSD) that was started during CPR and continued for 50 min after ROSC increased short-term survival by decreasing myocardial damage, as well as cerebral peroxidation and inflammatory injury (Paper II). Immunostaining of cerebral tissue collected at different time points after CA and ROSC (Paper IV) provided experimental evidence that cortical blood-brain barrier (BBB) disruption begins as early as  during the initial phase of untreated as well as treated CA. The results indicated that MB administration reduced the neurologic injury and BBB disruption considerably, but did not reverse the ongoing detrimental processes. The demonstrated positive effects of MB were related to a decrease of nitrite/nitrate tissue content, and thus to a decrease of excess NO due to the MB inhibitory effects on NOS isoforms. A mixture of MB in hypertonic sodium lactate (MBL) was investigated to facilitate administration of MB in “the field.” Based on findings that MBL cardio- and neuroprotective properties were similar to those of MBHSD, there is reason to believe that the use of MBL might be extended during ongoing CPR and after ROSC (Paper III). It would therefore make sense to try using MB as a pharmacological neuroprotectant during or after clinical CPR in order to expand the temporal therapeutic window before other measures for neuroprotection such as hypothermia are available.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2009. s. 79
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 466
Nyckelord
Cardiac arrest, cardiopulmonary resuscitation, reperfusion injury, methylene blue, nitric oxide, nitric oxide synthases, blood-brain barrier
Nationell ämneskategori
Anestesi och intensivvård
Forskningsämne
Anestesiologi
Identifikatorer
urn:nbn:se:uu:diva-106831 (URN)978-91-554-7566-6 (ISBN)
Disputation
2009-09-11, Hedstrandsalen, Akademiska Sjukhuset, entrance no. 70, Uppsala, 09:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2009-08-20 Skapad: 2009-07-06 Senast uppdaterad: 2010-05-28Bibliografiskt granskad

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