Severe septic inflammation as a strong stimulus of myocardial NT-pro brain natriuretic peptide release.
BACKGROUND
Septic shock (SS) has recently been identified as stimulus of N-terminal pro-brain natriuretic peptide (NT-proBNP) release. We tested whether SS mediates NT-proBNP release through cardiomyocyte necrosis. Moreover, the discriminative value of NT-proBNP for the distinction between SS and non-septic shock (NSS) was assessed.


METHODS
The study included 50 ICU patients with SS (n=25) and NSS (n=25), 40 patients with acute coronary syndrome and elevated troponin-I (ACStrop+) and 16 patients with unstable angina and normal troponin-I (UAtrop-). Eleven subjects without inflammation or cardiac disease served as controls. NT-proBNP levels of coronary patients were measured on admission, those of ICU patients 48 h after onset of shock symptoms.


RESULTS
ACStrop+ (1525 [25th-75th percentile: 790-3820] pg/L) and NSS (687 [254-1552]) patients showed increased NT-proBNP levels above those of UAtrop- patients (107 [43-450], p<0.001) and controls (52 [42-99], p<0.001), but SS patients exhibited still higher levels (11,335 [4716-25,769], p<0.001 vs all others). Among ICU patients with shock symptoms, NT-proBNP discriminated SS and NSS with high sensitivity and specificity (area under ROC curve: 0.946 [95% confidence interval, 0.872-1.019]). NT-proBNP correlated with troponin-I, as marker of cardiomyocyte damage, among ACStrop+ (p<0.001) and SS patients (p=0.013). But, whereas SS patients showed the greatest NT-proBNP values, ACStrop+ patients had higher troponin-I levels (p<0.001), suggesting different mechanisms by which myocardial ischemia and SS mediate NT-proBNP release.


CONCLUSIONS
SS is a more potent stimulus of NT-proBNP release than myocardial ischemia. NT-proBNP reliably distinguishes SS from other forms of shock. SS-related NT-proBNP release appears to involve cardiomyocyte damage but not genuine cardiomyocyte necrosis.
Wolff
Birger
B
Department of Internal Medicine, Intensive Care Division, HELIOS Kliniken Schwerin, Wismarsche Strasse 393-397, 19049 Schwerin, Germany. birgerwolff@aol.com
Haase
Detlef
D
Lazarus
Peter
P
Machill
Klaus
K
Graf
Bernhard
B
Lestin
Heiko-Gundmar
HG
Werner
Dierk
D
D018806:APACHE; D000368:Aged; D000789:Angina, Unstable / Q000453:epidemiology / Q000378:metabolism*; D015897:Comorbidity; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000378:metabolism*; D009336:Necrosis; D010446:Peptide Fragments / Q000378:metabolism*; D011379:Prognosis; D012772:Shock, Septic / Q000453:epidemiology / Q000378:metabolism*; D013577:Syndrome
D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain