Myocardial cytokine IL-8 and nitric oxide synthase activity during and after resuscitation: preliminary observations in regards to post-resuscitation myocardial dysfunction.
OBJECTIVE
Increases in serum cytokines have been reported after successful resuscitation from prolonged ventricular fibrillation (VF). Pro-inflammatory cytokines can stimulate inducible nitric oxide synthase (iNOS) to produce excessive levels of nitric oxide (NO). High levels of both myocardial inflammatory cytokines and nitric oxide levels can depress myocardial contractile function. We hypothesized that myocardial pro-inflammatory cytokines and iNOS activity would increase following successful resuscitation from prolonged ventricular fibrillation cardiac arrest, and that such increases would parallel the development of post-resuscitation myocardial dysfunction.


METHODS
Ventricular fibrillation cardiac arrest was induced in seven domestic swine (25+/-5 kg). After 10 min of untreated VF, the animals were defibrillated and resuscitated. Left ventricular (LV) systolic and diastolic function measurements, serum samples (arterial and coronary sinus) for IL-8 cytokine quantification, and LV myocardial biopsies were collected before, during, and after resuscitation. Quantification of myocardial endothelial (eNOS) and inducible (iNOS) nitric oxide synthase protein levels were determined using immunoblot analyses and protein localization was examined using immunohistochemistry.


RESULTS
Post-resuscitation LV systolic and diastolic functions were depressed while increases in both coronary sinus IL-8 levels and myocardial iNOS activity were found. Compared to pre-arrest baseline, levels of iNOS protein increased during VF (p < or = 0.05) and continued to increase throughout the post-resuscitation study period of 6 h (p < or = 0.05).


CONCLUSIONS
Myocardial inflammatory cytokines and iNOS activity increase during and after prolonged cardiac arrest and successful resuscitation. These increases correspond to the well described decrease in LV function post-resuscitation.
Kern
Karl B
KB
Sarver Heart Center, University of Arizona College of Medicine, 1501 N. Campbell, Tucson, AZ 85724, USA. kernk@email.arizona.edu
Berg
Robert A
RA
Hilwig
Ronald W
RW
Larson
Douglas F
DF
Gaballa
Mohamed A
MA
D000818:Animals; D005260:Female; D006321:Heart / Q000503:physiopathology*; D016209:Interleukin-8 / Q000032:analysis / Q000096:biosynthesis*; D008297:Male; D009206:Myocardium / Q000737:chemistry; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000096:biosynthesis* / Q000378:metabolism; D012151:Resuscitation; D013552:Swine; D014693:Ventricular Fibrillation / Q000378:metabolism* / Q000628:therapy*
D016209:Interleukin-8; D019001:Nitric Oxide Synthase