John J. Marini, M.D.

Professor of Medicine

Summary of Academic Program
Physiology of Mechanical Ventilatory Support

Our research program utilizes mathematical modeling, laboratory simulation, and animal experimentation to better understand the pathophysiology of ventilatory support. Our current attention is focused in three specific areas:

1. Identification of the factors that contribute to ventilator-induced lung injury.
2. Exploration of patient/ventilator interactions.
3. Development of adjuncts to mechanical ventilation.

In prior work we have determined that the impact of a potentially stressful ventilatory pattern on the generation of ventilator-induced lung injury is conditioned by body position, vascular pressure, and temperature: three clinically-modifiable factors which had not previously been considered in this context. Moreover, we have determined that ventilatory frequency determines the rate at which lung injury develops when ventilatory stresses of sufficient magnitude are imposed. Such observations indicate that the signal for ventilator-induced lung inflammation is not simply tidal volume and/or end expiratory pressure but perhaps the cumulative number of stress cycles or intensity with which the tidal stimulus is applied. Key experimental data suggest that “materials fatigue” of the lungs' structural elements might be induced by repeated application of a sufficiently stressful tidal ventilatory pattern. We are actively engaged in a series of experiments which will use morphometric tools such as electron microscopy to determine whether physical disruption of structural elements occurs. Molecular biological techniques are also being applied to learn whether temperature mediation or drug modification of the inflammatory response can attenuate ventilator-induced lung injury. In clinical studies related to this theme, we are investigating the kinetics of gas exchange and thoracic mechanics that occur during repositioning and recruitment maneuvers. A second objective of our research program is to explore techniques which may be useful at the bedside to accomplish safe and effective mechanical ventilation. In recent work we have explored the impact of recruitment maneuvers performed in the supine and prone positions, the interaction of PEEP and tidal volume in opening the unstable lung units most at risk for ventilator-induced lung injury, and methods whereby recruitment can be accomplished in the spontaneously breathing subject. Such information will be confirmed in clinical studies already approved for implementation. A third major investigative theme relates to patient/ventilator interactions. We have recently determined that for certain combinations of ventilatory parameters in pressure-supported breathing, inherent dynamical instability may cause tidal volume and inspiratory time to vary unpredictably despite constant pressure support and unchanged patient mechanics. This instability may impact patient comfort and tolerance of ventilatory support. We are engaged in mathematical modeling and laboratory simulation as well as in vivo confirmation of these principles. By such techniques, we hope to identify the key variables that determine pattern instability and their critical ranges so as to guide clinical practice.

Investigators

John J. Marini, John R. Hotchkiss, David Dries, Alex Adams, Avi Nahum. International collaborators: Luciano Gattinoni (Italy), Marcelo Amato (Brazil), Lluis Blanch (Spain), Apostolos Armanaganidis (Greece), Sungchul Lim (Korea), Li Chen (China), Alain Broccard (Switzerland).

Recent Honors

• Jimmy Albert Young Medal, American Association For Respiratory Care (AARC), 1998. (Given annually to a single individual to recognize major and lasting contributions to the field of respiratory care: this is the highest honor conferred by this 36,000 member professional organization.)

Grant Support

• Project Director: “Optimization of ventilatory support in acute lung injury.” NIH specialized center of research (SCOR) project 5 1P50HL50152 (1993-2003)
• American Heart Association National Scientist Development Grant: "Vascular Barrier Fatigue Behavior in Ventilator Induced Lung Injury" JR Hotchkiss, D Olson, O Wangensteen, P Leo, P Crooke, J Marini 1999, $260,000
• HealthPartners Research Foundation Grant: "Inflammation and Ventilator Associated Lung Injury" D Dries, J Marini, J Hotchkiss 2000, $24,770

Selected Recent Publications

Marini JJ. Lung injury--settle for a sketch or design a blueprint? Crit Care Med, 2008; 36(10):2922-5. Review.

Marini JJ, Gattinoni L. Propagation prevention: a complementary mechanism for "lung protective" ventilation in acute respiratory distress syndrome. Crit Care Med, 2008; 36(12):3252-8. Review.

Navaravong L, Wudhikarn K, Marini JJ. Cigarette-induced acute eosinophilic pneumonia: a case report. Cases J. 2008; 1(1):414.