There is a strong influence of gravity on the lung. The lung deforms under its own weight, stretching some regions and compressing others, affecting ventilation and blood flow. The deformation is strongly posture dependent because the thorax (the container shape) is not symmetrical. This asymmetry can be envisioned as a wedge, with the lung hanging from the shorter side in supine posture and the longer side in prone. The effects of asymmetry and gravity are additive in supine posture, but oppose one another in prone. Goal/Significance Early adoption of prone ventilation in severe Acute Respiratory Distress Syndrome (ARDS) markedly improves survival. This is especially true if arterial partial pressure of CO2 and dead space are decreased by prone posture, implying that this intervention recruits blood flow to match regions of well-ventilated lung. Our goal is to understand the mechanisms by which lung deformation and thoracic shape interact to affect pulmonary blood flow and gas exchange. Since prone ventilation greatly complicates patient care, understanding posture effects on blood flow distribution is critically important. This information will be to develop patient-specific metrics to identify which ARDS patients might benefit most from prone ventilation. This work may have other implications for patient management including fluid balance and inotropic therapy. Innovation Can the effects of prone posture on pulmonary blood flow and gas exchange be predicted from regional lung density distribution measured supine? To answer this question we have developed a suite of functional magnetic resonance imaging techniques that allow regional quantification of lung proton density, alveolar ventilation, and perfusion. This allows the evaluation of how container shape and lung deformation alter ventilation-perfusion (VA/Q) matching and regional dead space under clinically relevant conditions. We propose to combine our sophisticated imaging techniques with person-specific modeling of tissue deformation in collaboration with Dr. Merryn Tawhai (University of Auckland) to calculate regional tissue deformation and trans-pulmonary pressure gradients and evaluate the effect on local blood flow and VA/Qmatching. Approach we will test the hypothesis that regions of highly stretched (high local trans-pulmonary pressure) lung corresponding to regions of high V /Q ratio in supine posture will be reduced in prone posture. A resulting in more uniform V /Q matching. In normal subjects we will use data acquired in supine posture A combined with person-specific modeling to predict the effects on blood flow and VA/Q matching in prone posture, and test our predictions against measurements made in prone posture. This information will be used to develop biomarkers for optimal blood flow based on density distribution and thoracic shape (and thus measureable with routine clinical CT) that predict improvement with prone posture. This will be tested in collaboration with Dr. Harm Bogaard (VU Univ. Amsterdam) in a retrospective study of patients with ARDS who have undergone prone ventilation.
Our goal is to understand how lung deformation under the weight of gravity and chest shape, interact to affect pulmonary blood flow and gas exchange. We will combine our sophisticated magnetic resonance imaging techniques with patient-specific modeling of tissue deformation to develop biomarkers for the distribution of blood flow based on lung density distribution and thoracic shape measures in supine posture. We will this information to predict effects on pulmonary blood flow and gas exchange in prone posture and develop patient specific metrics to guide the decision for prone ventilation in patients, particularly thos suffering from Acute Respiratory Distress Syndrome
| Sands, Scott A; Edwards, Bradley A; Terrill, Philip I et al. (2018) Identifying obstructive sleep apnoea patients responsive to supplemental oxygen therapy. Eur Respir J 52: |
| Malhotra, Atul; Crocker, Maureen E; Willes, Leslee et al. (2018) Patient Engagement Using New Technology to Improve Adherence to Positive Airway Pressure Therapy: A Retrospective Analysis. Chest 153:843-850 |
| Orr, Jeremy E; Sands, Scott A; Edwards, Bradley A et al. (2018) Measuring Loop Gain via Home Sleep Testing in Patients with Obstructive Sleep Apnea. Am J Respir Crit Care Med 197:1353-1355 |
| Deacon-Diaz, Naomi; Malhotra, Atul (2018) Inherent vs. Induced Loop Gain Abnormalities in Obstructive Sleep Apnea. Front Neurol 9:896 |
| Light, Matthew; McCowen, Karen; Malhotra, Atul et al. (2018) Sleep apnea, metabolic disease, and the cutting edge of therapy. Metabolism 84:94-98 |
| Hepokoski, Mark L; Bellinghausen, Amy L; Bojanowski, Christine M et al. (2018) Can We DAMPen the Cross-Talk between the Lung and Kidney in the ICU? Am J Respir Crit Care Med 198:1220-1222 |
| Gupta, Ankit; Quan, Stuart F; Oldenburg, Olaf et al. (2018) Sleep-disordered breathing in hospitalized patients with congestive heart failure: a concise review and proposed algorithm. Heart Fail Rev 23:701-709 |
| Hepokoski, Mark L; Malhotra, Atul; Singh, Prabhleen et al. (2018) Ventilator-Induced Kidney Injury: Are Novel Biomarkers the Key to Prevention? Nephron 140:90-93 |
| Hepokoski, Mark L; Odish, Mazen; Malhotra, Atul (2018) Prone positioning in acute respiratory distress syndrome: why aren't we using it more? J Thorac Dis 10:S1020-S1024 |
| Malhotra, Atul; Morrell, Mary J; Eastwood, Peter R (2018) Update in respiratory sleep disorders: Epilogue to a modern review series. Respirology 23:16-17 |
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