Skip to main content

Selective V1a agonism reduces vascular leakage and cardiopulmonary dysfunction in methicillin-resistant Staphylococcus aureus sepsis


This randomized, controlled experimental trial was performed to compare the effects of the selective V1a-receptor agonist (Phe2Orn8) vasotocin (POV) and the mixed V1a/V2-receptor agonist (Arg8) vasopressin (AVP) on vascular leakage and cardiopulmonary dysfunction associated with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia-induced septic shock using an established ovine model.


After instrumentation for chronic hemodynamic monitoring and tracheostomy, sheep were subjected to 48 breaths of cotton smoke (<40°C) and MRSA was placed into both lungs under deep anesthesia. Following a 10 mmHg drop in mean arterial pressure (MAP) from baseline, sheep were randomly assigned to receive intravenous infusions of either POV, AVP or the vehicle (0.9% NaCl; n = 6 each). POV and AVP were titrated to keep MAP above baseline - 10 mmHg. All sheep were awake, mechanically ventilated and fluid resuscitated to maintain hematocrit at baseline ± 3%. Data are expressed as mean ± SEM at 24 hours. Fluids are represented as the average over time to account for individual survival times.


Both treatment strategies significantly reduced fluid input (AVP: 7.7 ± 0.6 ml/kg/hour; POV: 5.8 ± 0.8 ml/kg/hour), positive net fluid balance (AVP: 4.9 ± 0.5 ml/kg/hour; POV: 0.4 ± 0.6 ml/kg/hour), thoracic (AVP: 0.8 ± 0.2 ml/kg/hour; POV: 0.3 ± 0.1 ml/kg/hour) and abdominal fluid (AVP: 0.10 ± 0.04 ml/kg/hour; POV: 0.01 ± 0.01 ml/kg/hour) as well as extravascular lung water (AVP: 22.6 ± 1.4 ml/kg; POV: 15.8 ± 1.9 ml/kg) and increased plasma oncotic pressures (AVP: 12.5 ± 0.9 mmHg; POV: 15.9 ± 1.1 mmHg) vs control animals (9.6 ± 0.4 ml/kg/hour; 7.7 ± 0.4 ml/kg/hour; 2.2 ± 0.4 ml/kg/hour; 0.29 ± 0.13 ml/kg/hour; 22.9 ± 2.8 ml/kg; 8.9 ± 0.1 mmHg, respectively). Notably, POV was superior to AVP in all these variables (P < 0.05 each). Myocardial contractility was higher in the POV group vs AVP and control animals as suggested by higher left ventricular stroke work indexes (66 ± 3 vs 48 ± 7 and 43 ± 3 g/m/m2, respectively; P < 0.05 each) at lower or similar global end-diastolic volumes. Pulmonary dysfunction (decrease in PaO2/FiO2 ratio) was attenuated in POV (364 ± 47 mmHg) as compared with AVP (195 ± 66 mmHg; P < 0.05) and control animals (213 ± 76 mmHg; P < 0.05). Whereas one AVP and three control animals had to be sacrificed prematurely, all POV-treated animals survived the 24-hour study period.


In MRSA pneumonia-induced ovine septic shock, the selective V1a-receptor agonist POV is superior to the mixed V1a/V2-receptor agonist AVP in reducing vascular leakage and cardiopulmonary dysfunction when administered as a first-line vasopressor.

Author information



Corresponding author

Correspondence to S Rehberg.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Rehberg, S., Enkhbaatar, P., Yamamoto, Y. et al. Selective V1a agonism reduces vascular leakage and cardiopulmonary dysfunction in methicillin-resistant Staphylococcus aureus sepsis. Crit Care 14, P397 (2010).

Download citation


  • Septic Shock
  • Mean Arterial Pressure
  • Vascular Leakage
  • Stroke Work Index
  • Ventricular Stroke Work Index