Hypothermia and postconditioning after cardiopulmonary resuscitation reduce cardiac dysfunction by modulating inflammation, apoptosis and remodeling.
BACKGROUND
Mild therapeutic hypothermia following cardiac arrest is neuroprotective, but its effect on myocardial dysfunction that is a critical issue following resuscitation is not clear. This study sought to examine whether hypothermia and the combination of hypothermia and pharmacological postconditioning are cardioprotective in a model of cardiopulmonary resuscitation following acute myocardial ischemia.


RESULTS
Thirty pigs (28-34 kg) were subjected to cardiac arrest following left anterior descending coronary artery ischemia. After 7 minutes of ventricular fibrillation and 2 minutes of basic life support, advanced cardiac life support was started according to the current AHA guidelines. After successful return of spontaneous circulation (n = 21), coronary perfusion was reestablished after 60 minutes of occlusion, and animals were randomized to either normothermia at 38 degrees C, hypothermia at 33 degrees C or hypothermia at 33 degrees C combined with sevoflurane (each group n = 7) for 24 hours. The effects on cardiac damage especially on inflammation, apoptosis, and remodeling were studied using cellular and molecular approaches. Five animals were sham operated. Animals treated with hypothermia had lower troponin T levels (p<0.01), reduced infarct size (34+/-7 versus 57+/-12%; p<0.05) and improved left ventricular function compared to normothermia (p<0.05). Hypothermia was associated with a reduction in: (i) immune cell infiltration, (ii) apoptosis, (iii) IL-1beta and IL-6 mRNA up-regulation, and (iv) IL-1beta protein expression (p<0.05). Moreover, decreased matrix metalloproteinase-9 activity was detected in the ischemic myocardium after treatment with mild hypothermia. Sevoflurane conferred additional protective effects although statistic significance was not reached.


CONCLUSIONS
Hypothermia reduced myocardial damage and dysfunction after cardiopulmonary resuscitation possible via a reduced rate of apoptosis and pro-inflammatory cytokine expression.
Department of Anaesthesiology and Intensive Care Medicine, University Hospital Schleswig-Holstein, Kiel, Germany. meybohm@anaesthesie.uni-kiel.de
Patrick
P
Meybohm
Matthias
M
Gruenewald
Martin
M
Albrecht
Kai D
KD
Zacharowski
Ralph
R
Lucius
Karina
K
Zitta
Alexander
A
Koch
Nguyen
N
Tran
Jens
J
Scholz
Berthold
B
Bein
D000818:Animals; D017209:Apoptosis; D016887:Cardiopulmonary Resuscitation / Q000379:methods*; D005260:Female; D006323:Heart Arrest / Q000534:rehabilitation / Q000628:therapy; D007035:Hypothermia; D007249:Inflammation; D008297:Male; D008954:Models, Biological; D010477:Perfusion; D011897:Random Allocation; D013552:Swine; D016896:Treatment Outcome; D020107:Troponin T / Q000378:metabolism; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
D020107:Troponin T