Cardiopulmonary effects of low-dose arginine vasopressin in ovine acute lung injury.
OBJECTIVE
To elucidate the effects of low-dose arginine vasopressin on cardiopulmonary functions and nitrosative stress using an established model of acute lung injury.


METHODS
Prospective, randomized, controlled laboratory experiment.


METHODS
Investigational intensive care unit.


METHODS
Eighteen chronically instrumented sheep.


METHODS
Sheep were randomly assigned to a sham group without injury or treatment, an injury group without treatment (40% total body surface area third-degree burn and 48 breaths of cold cotton smoke), or an injured group treated with arginine vasopressin (0.02 IU·min⁻¹) from 1 hr after injury until the end of the 24-hr study period (each n = 6). All sheep were mechanically ventilated and fluid resuscitated using an established protocol.


RESULTS
There were no differences among groups at baseline. The injury was characterized by a severe deterioration of cardiopulmonary function (left ventricular stroke work indexes and Pao2/Fio2 ratio; p < .01 each vs. sham). Compared with controls, arginine vasopressin infusion improved myocardial function, as suggested by higher stroke volume indexes and left ventricular stroke work indexes (18-24 hrs and 6-24 hrs, respectively; p < .05 each). In addition to an improved gas exchange (higher Pao2/Fio2 ratios from 6 to 24 hrs, p < .01 each), pulmonary edema (bloodless wet-to-dry-weight ratio; p = .018), bronchial obstruction (p = .01), and pulmonary shunt fraction (12-24 hrs; p ≤ .001 each) were attenuated in arginine vasopressin-treated animals compared with controls. These changes occurred along with reduced nitrosative stress, as indicated by lower plasma levels of nitrate/nitrite (12-24 hrs, p < .01 each), as well as lower myocardial and pulmonary tissue concentrations of 3-nitrotyrosine (p = .041 and p = .042 vs. controls, respectively). At 24 hrs, pulmonary 3-nitrotyrosine concentrations were negatively correlated with Pao2/Fio2 ratio (r = -.882; p < .001) and myocardial 3-nitrotyrosine content with stroke volume indexes (r = -.701; p = .004).


CONCLUSIONS
Low-dose arginine vasopressin reduced nitrosative stress and improved cardiopulmonary functions in sheep with acute lung injury secondary to combined burn and smoke inhalation injury.
Department of Anesthesiology, The University of Texas Medical Branch, Galveston, TX, USA.
Martin
M
Westphal
Sebastian
S
Rehberg
Marc O
MO
Maybauer
Dirk M
DM
Maybauer
Perenlei
P
Enkhbaatar
Beena B
BB
Westphal-Varghese
Frank C
FC
Schmalstieg
Naoki
N
Morita
Robert A
RA
Cox
Lillian D
LD
Traber
Hal
H
Hawkins
Elbert
E
Whorton
Daniel L
DL
Traber
D055371:Acute Lung Injury / Q000188:drug therapy* / Q000209:etiology; D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage*; D002302:Cardiac Output / Q000187:drug effects; D002496:Central Venous Pressure / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D010101:Oxygen Consumption / Q000502:physiology; D011659:Pulmonary Gas Exchange; D011897:Random Allocation; D012016:Reference Values; D012756:Sheep; D034561:Sheep, Domestic; D015208:Smoke Inhalation Injury / Q000150:complications; D013318:Stroke Volume / Q000187:drug effects; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*
D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; C002744:3-nitrotyrosine; D014443:Tyrosine