Document Detail


Staphylococcal alpha-toxin provokes coronary vasoconstriction and loss in myocardial contractility in perfused rat hearts: role of thromboxane generation.
MedLine Citation:
PMID:  10618308     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Cardiac performance is severely depressed in septic shock. Endotoxin has been implicated as the causative agent in Gram-negative sepsis, but similar abnormalities are encountered in Gram-positive sepsis. We investigated the influence of the major exotoxin of Staphylococcus aureus, staphylococcal alpha-toxin, in isolated perfused rat hearts. METHODS AND RESULTS: Alpha-toxin 0.25 to 1 microg/mL caused a dose-dependent increase in coronary perfusion pressure that more than doubled. In parallel, we noted a decrease in left ventricular developed pressure and the maximum rate of left ventricular pressure rise (dP/dt(max)), dropping to a minimum of <60% of control. These changes were accompanied by a liberation of thromboxane A(2) and prostacyclin into the coronary effluent. The release of creatine kinase, lactate dehydrogenase, potassium, and lactate did not surpass control heart values, and leukotrienes were also not detected. Indomethacin, acetylsalicylic acid, and the thromboxane receptor antagonist daltroban fully blocked the alpha-toxin-induced coronary vasoconstrictor response and the decrease in left ventricular developed pressure and dP/dt(max), whereas the lipoxygenase inhibitor nordihydroguaiaretic acid, the platelet activating factor antagonist WEB 2086, and the alpha-adrenergic antagonist phentolamine were entirely ineffective. Inhibition of nitric oxide synthase even enhanced the alpha-toxin-induced increase in coronary perfusion pressure and the loss in myocardial performance. CONCLUSIONS: Purified staphylococcal alpha-toxin provokes coronary vasoconstriction and loss in myocardial contractility. The responses appear to be largely attributable to the generation of thromboxane and are even enhanced when the endogenous nitric oxide synthesis is blocked. Bacterial exotoxins, such as staphylococcal alpha-toxin, may thus be implicated in the loss of cardiac performance encountered in Gram-positive septic shock.
Authors:
U Sibelius; U Grandel; M Buerke; D Mueller; L Kiss; H J Kraemer; R Braun-Dullaeus; W Haberbosch; W Seeger; F Grimminger
Related Documents :
10027808 - One-year survival among patients with acute myocardial infarction complicated by cardio...
19713678 - Extracorporeal shock wave therapy as a new and non-invasive angiogenic strategy.
10688308 - Graded response and restitution hypotheses of ventricular vulnerability to fibrillation...
18608038 - Levosimendan as rescue therapy in severe cardiogenic shock after st-elevation myocardia...
2373098 - The significance of u wave polarity in patients with a prior anterior myocardial infarc...
3295138 - Fast washout of thallium-201 from area of myocardial infarction: possible artifact of b...
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Circulation     Volume:  101     ISSN:  0009-7322     ISO Abbreviation:  Circulation     Publication Date:    2000 Jan 4-11
Date Detail:
Created Date:  2000-02-24     Completed Date:  2000-02-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  78-85     Citation Subset:  AIM; IM    
Affiliation:
Department of Internal Medicine, Justus-Liebig-University, Giessen, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Aspirin / pharmacology
Azepines / pharmacology
Bacterial Toxins / pharmacology*
Edema
Epoprostenol / metabolism*
Exotoxins / pharmacology
Heart / drug effects,  physiology*
Hemolysin Proteins / pharmacology*
Indomethacin / pharmacology
L-Lactate Dehydrogenase / analysis
Lactates / metabolism
Male
Myocardial Contraction / drug effects*
Nordihydroguaiaretic Acid / pharmacology
Perfusion
Phenylacetates / pharmacology
Platelet Activating Factor / antagonists & inhibitors
Platelet Aggregation Inhibitors / pharmacology
Potassium / analysis
Rats
Rats, Wistar
Staphylococcus aureus
Sulfonamides / pharmacology
Thromboxane A2 / metabolism*
Triazoles / pharmacology
Vasoconstriction / drug effects
Ventricular Function, Left / drug effects,  physiology
Chemical
Reg. No./Substance:
0/Azepines; 0/Bacterial Toxins; 0/Exotoxins; 0/Hemolysin Proteins; 0/Lactates; 0/Phenylacetates; 0/Platelet Activating Factor; 0/Platelet Aggregation Inhibitors; 0/Sulfonamides; 0/Triazoles; 0/staphylococcal alpha-toxin; 105218-03-9/daltroban; 105219-56-5/WEB 2086; 35121-78-9/Epoprostenol; 50-78-2/Aspirin; 500-38-9/Nordihydroguaiaretic Acid; 53-86-1/Indomethacin; 57576-52-0/Thromboxane A2; 7440-09-7/Potassium; EC 1.1.1.27/L-Lactate Dehydrogenase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  beta(2)-adrenergic receptor overexpression exacerbates development of heart failure after aortic ste...
Next Document:  Electrophysiological effects of dofetilide in an in vitro model of &quot;border zone&quot; between n...