Effects of endothelin-1 (ET-1) and thrombin antagonism on cardiovascular and respiratory dysfunctions during endotoxic shock in pig.
We evaluated the endothelin-1 (ET-1) and thrombin involvement in cardiovascular and respiratory dysfunction during endotoxic shock in 18 anaesthetized, mechanically ventilated pigs, divided into three groups. Group 1 was pre-treated only with lipopolysaccharide (LPS), group 2 was treated with lepirudin, a thrombin inhibitor, group 3 was pre-treated with bosentan, a dual inhibitor of ET-1 receptors. Results show that LPS caused systemic hypotension, pulmonary biphasic hypertension, increase in lung resistances (R(L)) and decrease in compliance (C(L)). Lepirudin partially reduced the LPS-dependent pulmonary hypertension, without affecting the changes in C(L) and R(L). On the contrary, bosentan completely abolished the pulmonary hypertension and the changes inC(L) and R(L), and worsened the LPS-dependent systemic hypotension. Our results show that ET-1 is largely responsible for pulmonary derangement due to endotoxic shock; at bronchial level, the ET-1 release seems due only to LPS, while, at pulmonary vascular level, it results also from LPS-dependent thrombin activation.
Albertini
M
M
Dipartimento di Patologia animale, Igiene e Sanità pubblica Veterinaria, Sez. di Biochimica e Fisiologia, Università degli Studi di Milano, Milano, Italy.
Borromeo
V
V
Mazzola
S
S
Ciminaghi
B
B
Clement
M G
MG
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000077300:Bosentan; D002319:Cardiovascular System / Q000187:drug effects* / Q000503:physiopathology*; D019332:Endothelin-1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006629:Hirudins / Q000031:analogs & derivatives* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology; D012137:Respiratory System / Q000187:drug effects* / Q000503:physiopathology*; D012772:Shock, Septic / Q000503:physiopathology*; D013449:Sulfonamides / Q000494:pharmacology; D013552:Swine; D013917:Thrombin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013997:Time Factors
D000959:Antihypertensive Agents; D019332:Endothelin-1; D005343:Fibrinolytic Agents; D006629:Hirudins; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D013449:Sulfonamides; D013917:Thrombin; D000077300:Bosentan; C083544:lepirudin