title: Endothelin receptor blockade does not improve hypoxemia following acute pulmonary thromboembolism.
abstract: We studied the roles of endothelins in determining ventilation (Va) and perfusion (Q) mismatch in a porcine model of acute pulmonary thromboembolism (APTE), using a nonspecific endothelin antagonist, tezosentan. Nine anesthetized piglets (approximately 23 kg) received autologous clots (approximately 20 g) via a central venous catheter at time = 0 min. The distribution of Va and Q at five different time points (-30, -5, 30, 60, 120 min) was mapped by fluorescent microspheres of 10 different colors. Five piglets (group 1) received tezosentan (courtesy of Actelion) starting at time = 40 min for 2 h, and four piglets (group 2) received only saline and served as control. Our results showed that, in all of the animals at 30 min following APTE but before tezosentan, the mean Va/Q was increased, as was Va/Q heterogeneity (log SD Va/Q), which represented a widening of its main peak. Afterwards, tezosentan attenuated the pulmonary hypertension in group 1 but also produced moderate systemic hypotension. However, it did not improve arterial PO2 or Va/Q mismatch. We concluded that endothelin antagonism had minimal impact on gas exchange following APTE and confirmed our earlier observation that the main mechanism for hypoxemia in APTE was due to the mechanical redistribution of pulmonary regional blood flow away from the embolized vessels, resulting in the creation of many divergent low and high Va/Q regions.
authors.affiliation: James Hogg iCAPTURE Research Lab., University of British Columbia, Vancouver, British Columbia, Canada. jtsang@interchange.ubc.ca
authors.forename: John Y C
authors.initials: JY
authors.lastname: Tsang
authors.forename: Wayne J E
authors.initials: WJ
authors.lastname: Lamm
authors.forename: Blazej
authors.initials: B
authors.lastname: Neradilek
authors.forename: Nayak L
authors.initials: NL
authors.lastname: Polissar
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hlastala
mesh_terms: D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D065128:Endothelin Receptor Antagonists; D000860:Hypoxia / Q000209:etiology* / Q000503:physiopathology*; D021621:Imaging, Three-Dimensional; D008168:Lung / Q000098:blood supply / Q000503:physiopathology; D008863:Microspheres; D011655:Pulmonary Embolism / Q000150:complications* / Q000503:physiopathology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects / Q000502:physiology; D012123:Pulmonary Ventilation / Q000187:drug effects / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013552:Swine; D013777:Tetrazoles / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D014692:Ventilation-Perfusion Ratio / Q000187:drug effects / Q000502:physiology
chemical_list: D065128:Endothelin Receptor Antagonists; D011725:Pyridines; D017466:Receptors, Endothelin; D013777:Tetrazoles; D014665:Vasodilator Agents; C120582:tezosentan