Pharmacological postconditioning with sevoflurane after cardiopulmonary resuscitation reduces myocardial dysfunction.
BACKGROUND
In this study, we sought to examine whether pharmacological postconditioning with sevoflurane (SEVO) is neuro- and cardioprotective in a pig model of cardiopulmonary resuscitation.


METHODS
Twenty-two pigs were subjected to cardiac arrest. After 8 minutes of ventricular fibrillation and 2 minutes of basic life support, advanced cardiac life support was started. After successful return of spontaneous circulation (N = 16), animals were randomized to either (1) propofol (CONTROL) anesthesia or (2) SEVO anesthesia for 4 hours. Neurological function was assessed 24 hours after return of spontaneous circulation. The effects on myocardial and cerebral damage, especially on inflammation, apoptosis and tissue remodeling, were studied using cellular and molecular approaches.


RESULTS
Animals treated with SEVO had lower peak troponin T levels (median [IQR]) (CONTROL vs SEVO = 0.31 pg/mL [0.2 to 0.65] vs 0.14 pg/mL [0.09 to 0.25]; P < 0.05) and improved left ventricular systolic and diastolic function compared to the CONTROL group (P < 0.05). SEVO was associated with a reduction in myocardial IL-1β protein concentrations (0.16 pg/μg total protein [0.14 to 0.17] vs 0.12 pg/μg total protein [0.11 to 0.14]; P < 0.01), a reduction in apoptosis (increased procaspase-3 protein levels (0.94 arbitrary units [0.86 to 1.04] vs 1.18 arbitrary units [1.03 to 1.28]; P < 0.05), increased hypoxia-inducible factor (HIF)-1α protein expression (P < 0.05) and increased activity of matrix metalloproteinase 9 (P < 0.05). SEVO did not, however, affect neurological deficit score or cerebral cellular and molecular pathways.


CONCLUSIONS
SEVO reduced myocardial damage and dysfunction after cardiopulmonary resuscitation in the early postresuscitation period. The reduction was associated with a reduced rate of myocardial proinflammatory cytokine expression, apoptosis, increased HIF-1α expression and increased activity of matrix metalloproteinase 9. Early administration of SEVO may not, however, improve neurological recovery.
Department of Anaesthesiology and Intensive Care Medicine, Schleswig-Holstein University Hospital, Campus Kiel, Schwanenweg 21, D-24105 Kiel, Germany. meybohm@anaesthesie.uni-kiel.de
Patrick
P
Meybohm
Matthias
M
Gruenewald
Martin
M
Albrecht
Christina
C
Müller
Karina
K
Zitta
Nikola
N
Foesel
Moritz
M
Maracke
Sabine
S
Tacke
Jürgen
J
Schrezenmeir
Jens
J
Scholz
Berthold
B
Bein
D000818:Animals; D016887:Cardiopulmonary Resuscitation; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000628:therapy; D008738:Methyl Ethers / Q000627:therapeutic use*; D017682:Myocardial Stunning / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011897:Random Allocation; D000077149:Sevoflurane; D013552:Swine; D016896:Treatment Outcome
D002316:Cardiotonic Agents; D008738:Methyl Ethers; D018696:Neuroprotective Agents; D000077149:Sevoflurane