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Milrinone and esmolol decrease cardiac damage after resuscitation from prolonged cardiac arrest
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.ORCID iD: frank@zoerner.org
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 Science and Technology, Chemistry, Department of Chemistry - BMC.
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: Long-term survival after cardiac arrest (CA) due to shock-refractory ventricular fibrillation (VF) is low. Clearly, there is a need for new pharmacological interventions in the setting of cardiopulmonary resuscitation (CPR) to improve outcome. Here, hemodynamic parameters and cardiac damage are compared between the treatment group (milrinone, esmolol and vasopressin) and controls (vasopressin only) during resuscitation from prolonged CA in piglets.

Methods: Twenty-six immature male piglets were subjected to 12 min VF followed by 8 min CPR. The treatment group (n=13) received i.v. boluses vasopressin 0.4 U∙kg−1, esmolol 250 μg∙kg−1 and milrinone 25 μg∙kg−1 after 13 min, followed by i.v. boluses esmolol 375 μg∙kg−1 and milrinone 25 μg∙kg−1 after 18 min and continuous esmolol 15 μg∙kg−1∙h−1 infusion during 180 min reperfusion, while controls (n=13) received equal amounts of vasopressin and saline. A 200J monophasic counter-shock was delivered to achieve resumption of spontaneous circulation (ROSC) after 8 min CPR. If ROSC was not achieved, another 200J defibrillation and bolus vasopressin 0.4 U∙kg−1 were administered in both groups. DC shocks at 360J were applied as one shot min−1 over maximally 5 min. Hemodynamic variables and troponin I as a marker of cardiac injury were recorded.

Results: Troponin I levels after 180 min reperfusion were lower in the treatment group than in controls (p<0.05). The treatment group received less norepinephrine (p<0.01) and had greater diuresis (p<0.01). There was no difference in survival between groups.

Conclusions: The combination of milrinone, esmolol and vasopressin decreased cardiac injury compared with vasopressin alone. 

Keyword [en]
Cardiac arrest, resumption of spontaneous circulation, ROSC, milrinone, vasopressin, esmolol, I/R injury, reperfusion injury, cardioprotection, myocardial ischemia, epinephrine, resuscitation
National Category
Anesthesiology and Intensive Care Medical and Health Sciences
Research subject
Anaesthesiology and Intensive Care
Identifiers
URN: urn:nbn:se:uu:diva-237869OAI: oai:DiVA.org:uu-237869DiVA: diva2:769244
Available from: 2014-12-06 Created: 2014-12-06 Last updated: 2015-06-11
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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Zoerner, FrankLennmyr, FredrikWiklund, LarsSemenas, Egidijus

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