Endotoxin-induced contractile dysfunction in guinea pig hearts is not mediated by nitric oxide

Abstract

The decreased contraction amplitude of isolated cardiac myocytes from guinea pigs exposed to lipopolysaccharide (LPS) was reported to be partially reversed by nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS) [Brady, et al., Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H1963-H1966, 1992]. We have tested the potential involvement of NO formation in LPS-induced cardiac depression in the intact heart. Isolated perfused hearts of LPS-treated guinea pigs (4 mg/kg 4 h before organ removal) displayed a greatly decreased left ventricular pressure (LVP) when compared with untreated controls (48 +/- 11 vs. 93 +/- 18 mmHg, n = 6 hearts each), whereas heart rate and coronary flow were similar. Perfusion of LPS-treated hearts with L-NMMA or L-NAME (100 microM each) at constant flow did not increase LVP (50 +/- 14 and 44 +/- 11, respectively, vs. 52 +/- 14 mmHg). However, coronary resistance increased significantly. There was no difference between LPS-treated and control hearts in venous adenosine release (104 +/- 58 vs. 133 +/- 86 pmol.min-1.g-1). Measurement of the activities of the induced (iNOS) and constitutive forms of NOS revealed that there was no difference in total NOS activity (237 +/- 82 vs. 181 +/- 97 fmol.min-1.mg protein-1. There was no measurable induction of iNOS in the LPS-treated hearts either. Finally, cardiac energy status was studied by 31P nuclear magnetic resonance spectroscopy. There was no difference between LPS-treated and control hearts in myocardial ATP, creatine phosphate, pH, and free ADP (59 +/- 20 vs. 50 +/- 27 microM).(ABSTRACT TRUNCATED AT 250 WORDS)

S-Methylisothiourea sulfate improves renal, but not hepatic dysfunction in canine endotoxic shock model

“…It has been suggested that myocardial depression during sepsis is largely mediated by cytokine-stimulated NO production [18,19]. In fact, it has been reported that administration of LPS failed to induce iNOS in the myocardium of guinea pig [20]. However, co-administration of SMT did not affect LPS-induced decrease in cardiac index in the present study.…”

Nitric oxide involvement in the hemodynamic response to fluid resuscitation in endotoxic shock in rats

“…The effects of NO on cardiac function alteration in sepsis is controversial between the isolated system studies (37)(38)(39) and the intact heart models (40,41). The similar alteration in Gmax induced by LNA in LPS and control animals in this study suggested that LPS itself did not modify the NO control of myocardial function, as shown elsewhere (42).…”

Cardiac Failure in Transgenic Mice With Myocardial Expression of Tumor Necrosis Factor-α

“…Parillo et al 35 and Reilly et al 36 first identified myocardial depressant substances in the serum of patients with septic shock. Cardiac dysfunction has since been documented in human volunteers given small doses of bacterial endotoxin 37 and in a variety of animal models, including administration of endotoxin to numerous species [38][39][40][41][42][43][44][45][46] ; intravenous administration of TNF to guinea pigs and dogs 20 -23 ; and implantation of intraperitoneal fibrin clots impregnated with Gram-positive or Gram-negative bacteria, endotoxin, or TNF in dogs. [47][48][49] Blockade of TNF activity prevents cardiac dysfunction after LPS challenge or cutane- …”