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Resuscitation with amiodarone increases survival after hemorrhage and ventricular fibrillation in pigs
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Anaesthesiology and Intensive Care.
2014 (English)In: Journal of Trauma and Acute Care Surgery, ISSN 2163-0755, Vol. 76, no 6, 1402-1408 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: The aim of this experimental study was to compare survival and hemodynamic effects of a low-dose amiodarone and vasopressin compared with vasopressin in hypovolemic cardiac arrest model in piglets. METHODS: Eighteen anesthetized male piglets (with a weight of 25.3 [1.8] kg) were bled approximately 30% of the total blood volume via the femoral artery to a mean arterial blood pressure of 35 mm Hg in a 15-minute period. Afterward, the piglets were subjected to 4 minutes of untreated ventricular fibrillation followed by 11 minutes of open-chest cardiopulmonary resuscitation. At 5 minutes, circulatory arrest amiodarone 1 mg/kg was intravenously administered in the amiodarone group (n = 9), while the control group received the same amount of saline (n = 9). At the same time, all piglets received vasopressin 0.4 U/kg intravenously administered and hypertonic-hyperoncotic solution 3-mL/kg infusion for 20 minutes. Internal defibrillation was attempted from 7 minutes of cardiac arrest to achieve restoration of spontaneous circulation. The experiment was terminated 3 hours after resuscitation. RESULTS: Three-hour survival was greater in the amiodarone group (p = 0.02). After the successful resuscitation, the amiodarone group piglets had significantly lower heart rate as well as greater systolic, diastolic, and mean arterial pressure. Troponin I plasma concentrations were lower and urine output was greater in the amiodarone group. CONCLUSION: 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 with resuscitation with vasopressin only.

Place, publisher, year, edition, pages
2014. Vol. 76, no 6, 1402-1408 p.
Keyword [en]
Amiodarone, cardiac arrest, ventricular fibrillation, hemorrhage, pigs
National Category
Surgery
Identifiers
URN: urn:nbn:se:uu:diva-228547DOI: 10.1097/TA.0000000000000243ISI: 000337145500011OAI: oai:DiVA.org:uu-228547DiVA: diva2:734459
Available from: 2014-07-17 Created: 2014-07-16 Last updated: 2015-02-03Bibliographically 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)
Opponent
Supervisors
Available from: 2015-01-08 Created: 2014-11-17 Last updated: 2015-02-03

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