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Antithrombin administration during experimental cardiopulmonary resuscitation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. (Anaesthesiology and Intensive Care)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care. (Anaesthesiology and Intensive Care)
2004 (English)In: Resuscitation, ISSN 0300-9572, E-ISSN 1873-1570, Vol. 62, no 1, 71-78 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE: To determine whether antithrombin (AT) administration during cardiopulmonary resuscitation (CPR) increased cerebral circulation and reduced reperfusion injury.

METHODS: Ventricular fibrillation was induced in 24 anaesthetised pigs. After a 5-min non-intervention interval, CPR was started. The animals were randomised into two groups. The treatment group received AT (250 U/kg) and the control group received placebo, after 7 min of CPR. Defibrillation was attempted after 9 min of CPR. If restoration of spontaneous circulation (ROSC) was achieved, the animals were observed for 4 h. Cortical cerebral blood flow was measured using laser-Doppler flowmetry. Cerebral oxygen extraction was calculated to reflect the relation between global cerebral circulation and oxygen demand. Measurements of eicosanoids (8-iso-PGF(2alpha) and 15-keto-dihydro-PGF(2alpha)), AT, thrombin-antithrombin complex (TAT) and soluble fibrin in jugular bulb plasma were performed to detect any signs of cerebral oxidative injury, inflammation and coagulation.

RESULTS: There was no difference between the groups in cortical cerebral blood flow, cerebral oxygen extraction, or levels of eicosanoids, TAT or soluble fibrin in jugular bulb plasma after ROSC. In the control group reduction of AT began 15 min after ROSC and continued throughout the entire observation period (P < 0.05). Eicosanoids and TAT were increased compared to baseline in all animals (P < 0.01).

CONCLUSIONS: In this experimental model of CPR, AT administration did not increase cerebral circulation or reduce reperfusion injury after ROSC.

Place, publisher, year, edition, pages
2004. Vol. 62, no 1, 71-78 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-91831DOI: 10.1016/j.resuscitation.2004.02.010PubMedID: 15246586OAI: oai:DiVA.org:uu-91831DiVA: diva2:164688
Available from: 2004-05-07 Created: 2004-05-07 Last updated: 2010-10-18Bibliographically approved
In thesis
1. Cardiopulmonary Resuscitation: Pharmacological Interventions for Augmentation of Cerebral Blood Flow
Open this publication in new window or tab >>Cardiopulmonary Resuscitation: Pharmacological Interventions for Augmentation of Cerebral Blood Flow
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cardiac arrest results in immediate interruption of blood flow. The primary goal of cardiopulmonary resuscitation (CPR) is to re-establish blood flow and hence oxygen delivery to the vital organs. This thesis describes different pharmacological interventions aimed at increasing cerebral blood flow during CPR and after restoration of spontaneous circulation (ROSC).

In a porcine model of cardiac arrest, continuous infusion of adrenaline generated higher cortical cerebral blood flow during CPR as compared to bolus administration of adrenaline. While bolus doses resulted in temporary peaks in cerebral blood flow, continuous infusion led to a sustained increase in this flow.

Administration of vasopressin resulted in higher cortical cerebral blood flow and a lower cerebral oxygen extraction ratio as compared to continuous infusion of adrenaline during CPR. In addition, vasopressin generated higher coronary perfusion pressure during CPR and increased the likelihood of achieving ROSC.

Parameters of coagulation and inflammation were measured after successful resuscitation from cardiac arrest. Immediately after ROSC, thrombin-antithrombin complex, a marker of thrombin generation, was elevated and eicosanoid levels were increased, indicating activation of coagulation and inflammation after ROSC. The thrombin generation was accompanied by a reduction in antithrombin. In addition, there was substantial haemoconcentration in the initial period after ROSC.

By administration of antithrombin during CPR, supraphysiological levels of antithrombin were achieved. However, antithrombin administration did not increase cerebral circulation or reduce reperfusion injury, as measured by cortical cerebral blood flow, cerebral oxygen extraction and levels of eicosanoids, after ROSC.

In a clinical study, the adrenaline dose interval was found to be longer than recommended in the majority of cases of cardiac arrest. Thus, the adherence to recommended guidelines regarding the adrenaline dose interval seems to be poor.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 59 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1355
Keyword
Anaesthesiology and intensive care, Adrenaline (epinephrine), Cardiac arrest, Cardiopulmonary resuscitation, Cerebral blood flow, Guidelines, Post-resuscitation period, Vasopressin, Anestesiologi och intensivvård
National Category
Anesthesiology and Intensive Care
Identifiers
urn:nbn:se:uu:diva-4281 (URN)91-554-5981-1 (ISBN)
Public defence
2004-06-02, Hedstrandsalen, Akademiska Sjukhuset ing. 70, Uppsala, 09:15
Opponent
Supervisors
Available from: 2004-05-07 Created: 2004-05-07Bibliographically approved

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Johansson, JakobRidefelt, PeterBasu, SamarRubertsson, Sten

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