Albumin resuscitation increases cardiomyocyte contractility and decreases nitric oxide synthase II expression in rat endotoxemia.
OBJECTIVE
Hypotension and hypoperfusion during septic shock may contribute to tissue hypoxia and the intramyocardial inflammatory response that results in myocardial dysfunction. Therefore, we hypothesized that crystalloid or colloid resuscitation may alter myocardial dysfunction.


METHODS
Randomized, controlled, prospective animal study.


METHODS
University animal laboratory.


METHODS
Sprague-Dawley rats (250-300 g, n = 6/group).


METHODS
Rats received an intraperitoneal injection of 10 mg/kg lipopolysaccharide or control. One hour later, rats were randomized to intravenous resuscitation and received either 30 mL/kg normal saline, 10 mL/kg 10% pentastarch, 10 mL/kg 5% rat albumin, or no volume.


RESULTS
We measured fractional shortening of cardiomyocytes isolated 5 hrs after lipopolysaccharide or control injection. In separate identical experiments, we measured myocardial interleukin-6, macrophage inhibitory protein-2, and nitric oxide synthase II protein and messenger RNA expression. Control fractional shortening of 24.1 +/- 2.2% was decreased by lipopolysaccharide to 18.8 +/- 1.2% (p <.001). Volume resuscitation after lipopolysaccharide significantly improved fractional shortening (p <.001). In particular, albumin resuscitation increased fractional shortening to 23.5 +/- 0.9%, which was more than either saline (fractional shortening 20.1 +/- 1.7%,p <.01) or pentastarch (fractional shortening 21.4 +/- 0.9%,p <.01). Myocardial macrophage inhibitory protein-2 protein and interleukin-6 and macrophage inhibitory protein-2 messenger RNA expression and neutrophil content were elevated following lipopolysaccharide (p <.05) but were not altered by volume resuscitation. Myocardial nitric oxide synthase II protein and messenger RNA expression increased following lipopolysaccharide (p <.01) and decreased with albumin resuscitation.


CONCLUSIONS
We conclude that following lipopolysaccharide injection, volume resuscitation improves cardiomyocyte fractional shortening. Albumin resuscitation is particularly beneficial in preventing reduced cardiomyocyte contractility, and this benefit may be related to an albumin-induced reduction in nitric oxide synthase II protein and messenger RNA expression following endotoxin injection.
Walley
Keith R
KR
University of British Columbia McDonald Research Laboratories/iCAPTURE Center, Vancouver, Canada. kwalley@mrl.ubc.ca
McDonald
Treena E
TE
Wang
Yingjin
Y
Dai
Shelley
S
Russell
James A
JA
D000418:Albumins / Q000494:pharmacology* / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D019446:Endotoxemia / Q000503:physiopathology / Q000628:therapy*; D005440:Fluid Therapy / Q000379:methods*; D008070:Lipopolysaccharides; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000187:drug effects* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000503:physiopathology / Q000628:therapy; D016276:Ventricular Function / Q000187:drug effects
D000418:Albumins; D008070:Lipopolysaccharides; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II