Tumor necrosis factor depresses myocardial contractility in endotoxemic swine.
BACKGROUND
Depression of myocardial contractility occurs in septic shock.


METHODS
Fourteen pigs were instrumented to measure cardiopulmonary dynamics after a challenge of Escherichia coli endotoxin (lipopolysaccharide endotoxin, LPS). A volumetric Swan-Ganz catheter was placed via the jugular vein, and a carotid arterial line was placed into the aortic root. Eight pigs received LPS alone and six pigs received tumor necrosis factor monoclonal antibody (TNF MAb) 15 minutes before the administration of LPS. Pulmonary artery and aortic root blood were sampled for amounts of TNF. Ninety minutes after LPS administration, thoracotomy was performed to biopsy the right and left ventricles for TNF levels. Contractility was determined from the end systolic pressure-volume relationships of pressure-volume diagrams.


RESULTS
Right ventricular end diastolic volume index nearly doubled and myocardial contractility decreased by 40% from baseline in the pigs receiving only LPS. Pigs that received TNF MAb had no change in myocardial contractility or right ventricular end diastolic volume index from baseline. There was a higher level of TNF in the aortic sample than in the pulmonary samples at 60 minutes. Right ventricular tissue TNF levels were significantly higher in the LPS-alone group. There was no such difference in left ventricular tissue.


CONCLUSIONS
The left and right ventricles have different susceptibilities to TNF MAb. TNF may decrease myocardial contractility in sepsis. Blockade of TNF with TNF MAb reverses the depression of myocardial contractility and the right ventricular dilatation associated with septic shock.
Kraut
E J
EJ
Department of Surgery, University of California, Davis, Medical Center, Sacramento 95817, USA.
Chen
S
S
Hubbard
N E
NE
Erickson
K L
KL
Wisner
D H
DH
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001794:Blood Pressure; D002302:Cardiac Output; D019446:Endotoxemia / Q000503:physiopathology*; D004731:Endotoxins / Q000008:administration & dosage; D004926:Escherichia coli; D008070:Lipopolysaccharides / Q000008:administration & dosage; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000737:chemistry; D011651:Pulmonary Artery; D013318:Stroke Volume; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology / Q000502:physiology*; D016276:Ventricular Function
D000911:Antibodies, Monoclonal; D004731:Endotoxins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C044101:endotoxin, Escherichia coli