Assessment of the early cellular membrane response to live Escherichia coli bacteremia.
Alterations in skeletal muscle cellular function during septic shock have been previously demonstrated. However, whether these alterations represent a specific response to the septic state or are simply a consequence of low flow is uncertain. The present study was designed to evaluate the cellular membrane response to the early bacteremic state, prior to the onset of hemodynamic compromise. A clinically relevant model of sepsis was achieved in six mongrel dogs by intraarterial infusion of live Escherichia coli organisms and concurrent volume loading with lactated Ringer's solution. Four sham-treated dogs served as controls. Forty-eight hours after induction of sepsis, resting transmembrane potential (Em) was measured in a hindlimb adductor muscle. Contemporaneous muscle biopsy was performed for determination of transmembrane water and electrolyte distribution. The bacteremic state was associated with depolarization of Em to -79.7 +/- 1.2 mV from a basal value of -89.3 +/- 0.2 mV (P less than 0.01), while Em in the sham-treated group remained unchanged over the same time course. In addition, there was a significant increase in the calculated intracellular Na+ and Cl- concentrations in the septic group (P less than 0.02), while intracellular K+ was unchanged. These data are consistent with a selective increase in cell membrane permeability to Na+ and indicate that cellular alterations in skeletal muscle occur early in the septic course, in the absence of hemodynamic compromise. This alteration in membrane permeability appears to be common to cells of disparate organ systems in response to sepsis, and may represent a protean manifestation of cellular injury.
Shiono
S
S
Department of Surgery, New York Hospital-Cornell Medical Center, New York 10021.
Fantini
G A
GA
Roberts
J P
JP
Chiao
J
J
Shires
G T
GT
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D002462:Cell Membrane / Q000502:physiology*; D002463:Cell Membrane Permeability; D002712:Chlorides / Q000378:metabolism; D004285:Dogs; D004927:Escherichia coli Infections / Q000503:physiopathology*; D005260:Female; D006339:Heart Rate; D008297:Male; D008564:Membrane Potentials; D009132:Muscles / Q000503:physiopathology*; D010725:Phosphocreatine / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D011669:Pulmonary Wedge Pressure; D018805:Sepsis / Q000503:physiopathology*; D012964:Sodium / Q000378:metabolism; D014655:Vascular Resistance
D002712:Chlorides; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D012964:Sodium; D011188:Potassium