Left ventricular dysfunction in early E. coli endotoxemia: effects of naloxone.
Although the opiate receptor antagonist naloxone (NAL) has been reported to improve in vivo systolic performance of the heart in different circulatory shock syndromes, the influence of this drug on intrinsic cardiac mechanical function during hypodynamic circulatory states is unknown. The present study was designed to determine the effects of in vivo NAL on contraction-relaxation properties of isovolumic left ventricular (LV) preparations isolated from guinea pigs 4 h after induction of gram-negative endotoxemia. Animals were given a 1 mg/kg ip injection of Escherichia coli endotoxin and immediately treated intravenously with either NAL (4 mg/kg iv bolus plus 4 mg.kg-1.h-1 infusion) or an equivalent volume of saline. Endotoxin produced significant reduction of LV contractile function in coronary-perfused hearts, a response unaffected by NAL therapy. For example, LV systolic pressure at approximately 10 mmHg end-diastolic pressure averaged 78 +/- 3 and 82 +/- 6 mmHg in hearts from saline and NAL control animals, respectively, but only 41 +/- 2 and 40 +/- 2 mmHg in endotoxin and endotoxin plus NAL groups, respectively. LV end-diastolic pressure-volume relationships in endotoxin hearts were shifted upward and to the left of controls in the direction of decreased diastolic compliance (P less than 0.05). Importantly, in vivo NAL prevented the endotoxin-induced decrease in LV compliance of the isolated heart preparations (P less than 0.05). Thus intrinsic cardiac complications of early (4 h) nonhypotensive endotoxemia included decreased diastolic compliance as well as diminished contractility of the left ventricle. Only the diastolic compliance changes were NAL responsive and therefore may involve endogenous opioid systems in their pathophysiological expression.
Dalton Research Center, University of Missouri, Columbia 65211.
J L
JL
Parker
R S
RS
Keller
L L
LL
Behm
H R
HR
Adams
D000818:Animals; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D006168:Guinea Pigs; D006321:Heart; D006352:Heart Ventricles; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D009270:Naloxone / Q000494:pharmacology*; D011312:Pressure; D013318:Stroke Volume
D004731:Endotoxins; D009270:Naloxone