Inhibitory effect of Escherichia coli endotoxin on skeletal muscle contractility.
OBJECTIVE
Endotoxemia in rabbits is associated with decreases in oxygen transport, tissue hypoxia, metabolic acidosis, and impaired oxygen extraction. In this study, we tested the hypothesis that endotoxin also inhibits skeletal muscle contractility directly.


METHODS
Randomized animal study.


METHODS
Accredited animal research facility.


METHODS
New Zealand white rabbits of either sex, weighing 2.55 +/- 0.20 kg.


METHODS
We compared two groups of rabbits (n = 10 each) undergoing continuous electrical stimulation of the left hindlimb (maximal isometric twitch contraction at 0.25 Hz). One group (septic) was given an intravenous infusion of Escherichia coli endotoxin. The control group was subjected to decreases in cardiac output by inflating a balloon placed in the right ventricle.


RESULTS
Endotoxin or balloon inflation resulted in comparable decreases in cardiac output (49% and 53%, respectively). Hindlimb oxygen transport decreased to similar values for both groups (4.9 +/- 0.3 and 4.2 +/- 0.5 mL/min/kg, respectively). Systemic oxygen extraction ratio was greater in the control group (0.72 +/- 0.03) than in the septic group (0.55 +/- 0.04; p < .05). There were no differences in hindlimb oxygen extraction ratio. Decreases in hindlimb forces were greater in the septic group (42 +/- 4%) than in the control group (18 +/- 3%, p < .01). Force frequency curves obtained at the beginning and the end of the experiment showed greater fatigue in the septic group.


CONCLUSIONS
The intravenous infusion of Escherichia coli endotoxin produces a direct inhibitory effect on skeletal muscle contractility in rabbits. This phenomenon is independent of decreases in oxygen transport and blood pH. Our data support the notion of a direct cellular effect of endotoxin, or of an associated cytokine, on skeletal muscle contractility. The mechanism responsible for this phenomenon is unknown.
Gutierrez
G
G
Division of Pulmonary and Critical Care, University of Texas Health Science Center at Houston 77030.
Hurtado
F J
FJ
Fernandez
E
E
D000818:Animals; D002302:Cardiac Output / Q000502:physiology; D004558:Electric Stimulation; D004731:Endotoxins / Q000494:pharmacology*; D004926:Escherichia coli; D006614:Hindlimb; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D011817:Rabbits; D011897:Random Allocation
D004731:Endotoxins; D010100:Oxygen