An improved in vivo rat model for the study of mechanical ventilatory support effects on organs distal to the lung

Franco Valenza, Silvio Sibilla, Giuliana Anna Porro, Anna Brambilla, Stefano Tredici, Gabriella Nicolini, Mariarosaria Miloso, Giovanni Tredici, Luciano Gattinoni

Research output: Contribution to journalArticlepeer-review


Objective: To study the influence of different mechanical ventilatory support strategies on organs distal to the lung, we developed an in vivo rat model, in which the effects of different tidal volume values can be studied while maintaining other indexes. Design: Prospective, randomized animal laboratory investigation. Setting: University laboratory of Ospedale Maggiore di Milano-Instituto di Ricovero e Cura a Carattere Scientifico. Subjects: Anesthetized, paralyzed, and mechanically ventilated male Sprague-Dawley rats. Interventions: Two groups of seven rats each were randomized to receive tidal volumes of either 25% or 75% of inspiratory capacity (IC), calculated from a preliminary estimation of total lung capacity. Ventilation strategies for the two groups were as follows: a) 25% IC, 9.9 ± 0.8 mL/kg; frequency, 59 ± 4 beats/min; positive end-expiratory pressure, 3.6 ± 0.8 cm H2O; and peak inspiratory airway pressure (P̄āw), 13.2 ± 2 cm H2O; and b) 75% IC, 29.8 ± 2.9; frequency, 23 ± 13; positive end-expiratory pressure, 0; peak inspiratory P̄āw 29.0 ± 3. Measurements and Main Results: Mean arterial pressure (invasively monitored) remained well above adequate perfusion pressure values throughout, and no significant difference was seen between the two groups. Pa(O2), pHa, and Pa(CO2) values were compared after 60 mins of ventilation and again, no significant difference was seen between the two groups (Pa(O2), 269 ± 25 and 260 ± 55 torr; pHa, 7.432 ± 0.09 and 7.415 ± 0.03; Pa(CO2), 35.4 ± 8 and 32.5 ± 2 torr, for the 25% IC and 75% IC groups, respectively). Mean Paws were not different (6.4 ± 0.8 cm H2O in the 25% IC groups, and 6.1 ± 1.2 in the 75% IC groups, respectively). At the end of the experiment, animals were killed and the liver and kidney isolated, fixed in 4% formalin, cut, and stained for optic microscopy. Kidneys from rats ventilated with 75% IC showed increased Bowman's space with collapse of the glomerular capillaries. This occurred in a greater percentage of rats ventilated with 75% IC (0.67 ± 0.2 vs. 0.29 ± 0.2, 75% IC vs. 25% IC, respectively; p <.05). Perivascular edema was also present in rats ventilated with 75% IC (p <.05). Morphometric determinations of the empty zones (index of edema) demonstrated a trend toward differences between 75% IC livers and 25% IC (0.14 ± 0.05 vs. 0.11 ± 0.02, respectively). Conclusion: We conclude that it is possible to study the effects of mechanical ventilatory support on organs distal to the lung by means of an in vivo rat model.

Original languageEnglish
Pages (from-to)3697-3704
Number of pages8
JournalCritical Care Medicine
Issue number11
Publication statusPublished - 2000


  • Animal
  • Gas exchange
  • Hemodynamics
  • Mechanical ventilatory support
  • Multiple organ failure
  • Pathology
  • Rat
  • Respiratory mechanics

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine


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