Cardiopulmonary effects of low-dose arginine vasopressin in ovine acute lung injury

Martin Westphal, Sebastian Rehberg, Marc O. Maybauer, Dirk M. Maybauer, Perenlei Enkhbaatar, Beena B. Westphal-Varghese, Frank C. Schmalstieg, Naoki Morita, Robert A. Cox, Lillian D. Traber, Hal Hawkins, Elbert Whorton, Daniel L. Traber

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Objective: To elucidate the effects of low-dose arginine vasopressin on cardiopulmonary functions and nitrosative stress using an established model of acute lung injury. Design: Prospective, randomized, controlled laboratory experiment. Setting: Investigational intensive care unit. Subjects: Eighteen chronically instrumented sheep. Interventions: 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) 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. Measurements and Main 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.

Original languageEnglish (US)
Pages (from-to)357-363
Number of pages7
JournalCritical Care Medicine
Volume39
Issue number2
DOIs
StatePublished - Feb 2011

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Arginine Vasopressin
Acute Lung Injury
Sheep
Wounds and Injuries
Stroke Volume
Lung
Smoke Inhalation Injury
Stroke
Body Surface Area
Pulmonary Edema
Nitrites
Left Ventricular Function
Smoke
Nitrates
Intensive Care Units
Gases
Weights and Measures
3-nitrotyrosine

Keywords

  • acute respiratory distress syndrome
  • arginine vasopressin
  • burn
  • nitrosative stress
  • smoke inhalation injury

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Westphal, M., Rehberg, S., Maybauer, M. O., Maybauer, D. M., Enkhbaatar, P., Westphal-Varghese, B. B., ... Traber, D. L. (2011). Cardiopulmonary effects of low-dose arginine vasopressin in ovine acute lung injury. Critical Care Medicine, 39(2), 357-363. https://doi.org/10.1097/CCM.0b013e3181feb802

Cardiopulmonary effects of low-dose arginine vasopressin in ovine acute lung injury. / Westphal, Martin; Rehberg, Sebastian; Maybauer, Marc O.; Maybauer, Dirk M.; Enkhbaatar, Perenlei; Westphal-Varghese, Beena B.; Schmalstieg, Frank C.; Morita, Naoki; Cox, Robert A.; Traber, Lillian D.; Hawkins, Hal; Whorton, Elbert; Traber, Daniel L.

In: Critical Care Medicine, Vol. 39, No. 2, 02.2011, p. 357-363.

Research output: Contribution to journalArticle

Westphal, M, Rehberg, S, Maybauer, MO, Maybauer, DM, Enkhbaatar, P, Westphal-Varghese, BB, Schmalstieg, FC, Morita, N, Cox, RA, Traber, LD, Hawkins, H, Whorton, E & Traber, DL 2011, 'Cardiopulmonary effects of low-dose arginine vasopressin in ovine acute lung injury', Critical Care Medicine, vol. 39, no. 2, pp. 357-363. https://doi.org/10.1097/CCM.0b013e3181feb802
Westphal, Martin ; Rehberg, Sebastian ; Maybauer, Marc O. ; Maybauer, Dirk M. ; Enkhbaatar, Perenlei ; Westphal-Varghese, Beena B. ; Schmalstieg, Frank C. ; Morita, Naoki ; Cox, Robert A. ; Traber, Lillian D. ; Hawkins, Hal ; Whorton, Elbert ; Traber, Daniel L. / Cardiopulmonary effects of low-dose arginine vasopressin in ovine acute lung injury. In: Critical Care Medicine. 2011 ; Vol. 39, No. 2. pp. 357-363.
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AU - Westphal-Varghese, Beena B.

AU - Schmalstieg, Frank C.

AU - Morita, Naoki

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N2 - Objective: To elucidate the effects of low-dose arginine vasopressin on cardiopulmonary functions and nitrosative stress using an established model of acute lung injury. Design: Prospective, randomized, controlled laboratory experiment. Setting: Investigational intensive care unit. Subjects: Eighteen chronically instrumented sheep. Interventions: 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) 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. Measurements and Main 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.

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KW - acute respiratory distress syndrome

KW - arginine vasopressin

KW - burn

KW - nitrosative stress

KW - smoke inhalation injury

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