Selective NOS inhibition restores myocardial contractility in endotoxemic rats; however, myocardial NO content does not correlate with myocardial dysfunction.
The role of nitric oxide (NO) in lipopolysaccharide (LPS)-induced myocardial dysfunction remains controversial as some investigators concluded that inhibition of NO synthesis improves left ventricular (LV) contractility, whereas others did not. We investigated the relationship between LPS-induced LV dysfunction and LV NO production. We postulated that high myocardial NO concentrations would correspond to decreased contractility and low NO concentrations would correspond to recovery. In a rat model of endotoxemia, we used the isolated papillary preparation to assess inotropic dysfunction. We measured LV NO content and hemodynamics at baseline, 4, 16, and 48 h after LPS administration. LPS caused a decrease in LV contractility at 16 h with recovery at 48 h. Myocardial NO levels were elevated at all time periods. However, at 48 h in spite of normalization of LV contractility, myocardial NO content remained elevated. Pretreatment of LPS animals with the nonselective nitric oxide synthase (NOS) inhibitor N (G)-nitro-L-arginine methyl ester (L-NAME) worsened LV contractility, decreased LV NO content, and increased mortality. However, pretreatment with the relatively selective inducible NOS (iNOS) inhibitor S-methylisothiourea sulfate (SMT) restored LV contractility. Myocardial NO content in the SMT was lower than that of the LPS only group, but higher than the L-NAME group. We conclude that SMT is beneficial to myocardial contractility in this model of endotoxemia, whereas pretreatment with L-NAME is associated with further deterioration of contractility and increased mortality. Moreover, our data indicate that high myocardial NO concentrations do not necessarily correlate with decreased contractility.
Afulukwe
I F
IF
Division of Pulmonary/Critical Care Medicine, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, New York, USA.
Cohen
R I
RI
Zeballos
G A
GA
Iqbal
M
M
Scharf
S M
SM
D000818:Animals; D019446:Endotoxemia / Q000503:physiopathology*; D006321:Heart / Q000503:physiopathology*; D006439:Hemodynamics; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000737:chemistry*; D009569:Nitric Oxide / Q000032:analysis* / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010210:Papillary Muscles / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase