Katherine J Black1, Andrew T Lock1, Lindsay M Thomson1, Alexis R Cole1, Xiaoqi Tang1,2, Brian D Polizzotti3,4, John N Kheir5,6. 1. Department of Cardiology at Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA. 2. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA. 3. Department of Cardiology at Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA. brian.polizzotti@childrens.harvard.edu. 4. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA. brian.polizzotti@childrens.harvard.edu. 5. Department of Cardiology at Boston Children's Hospital, 300 Longwood Avenue, Boston, Massachusetts, 02115, USA. john.kheir@childrens.harvard.edu. 6. Department of Pediatrics, Harvard Medical School, Boston, Massachusetts, USA. john.kheir@childrens.harvard.edu.
Abstract
PURPOSE: Low oxygen levels, or hypoxemia, is a common cause of morbidity and mortality in critically ill patients. Hypoxemia is typically addressed by increasing the fraction of inspired oxygen, the use of mechanical ventilation, or more invasive measures. Recently, the injection of oxygen gas directly into the bloodstream by packaging it within lipid-based oxygen microbubbles (LOMs) has been explored. The purpose of this work is to examine the acute hemodynamic effects of intravenous injections of LOMs. METHODS: LOMs composed of 1,2-distearoyl-sn-glycero-3-phosphocoline and cholesterol were manufactured using a process of shear homogenization under an oxygen headspace. A 5 mL aliquot of either PlasmaLyte A, or low (37%) or high (55%) concentration LOMs (n = 10 per group) was injected over a 1 min period into Sprague Dawley rats instrumented for measurement of cardiac index and pulmonary (PVR) and systemic (SVR) vascular resistance during a 60 min observation period. Hemodynamics were compared between groups by linear mixed modeling. RESULTS: Approximately 1011 LOMs with mean diameter 3.77 ± 1.19 μm were injected over the 1 min period. Relative to controls, rodents treated with high concentration LOMs exhibited a higher pulmonary artery pressure (20 ± 0.4 mmHg vs 18 ± 0.4 mmHg, P < 0.001) and higher PVR (0.31 ± 0.01 vs 0.23 ± 0.01 mmHg/mL*min*kg, P < 0.001. Despite a stable cardiac index (62.2 ± 3.5 vs 62.3 ± 3.4 mL/min*kg, P < 0.001), mean arterial blood pressure decreased significantly in LOM-treated animals (46 ± 2 vs 60 ± 2 mmHg, P < 0.001) due to a decrease in SVR. Injections with aged LOM emulsions (>48 h since manufacture) resulted in a higher incidence of hemodynamic collapse during the observation period (P = 0.02). CONCLUSIONS: LOMs may be injected in quantities sufficient to deliver clinically meaningful volumes of oxygen but cause significant decrements in blood pressure and elevations in PVR.
PURPOSE: Low oxygen levels, or hypoxemia, is a common cause of morbidity and mortality in critically illpatients. Hypoxemia is typically addressed by increasing the fraction of inspired oxygen, the use of mechanical ventilation, or more invasive measures. Recently, the injection of oxygen gas directly into the bloodstream by packaging it within lipid-based oxygen microbubbles (LOMs) has been explored. The purpose of this work is to examine the acute hemodynamic effects of intravenous injections of LOMs. METHODS: LOMs composed of 1,2-distearoyl-sn-glycero-3-phosphocoline and cholesterol were manufactured using a process of shear homogenization under an oxygen headspace. A 5 mL aliquot of either PlasmaLyte A, or low (37%) or high (55%) concentration LOMs (n = 10 per group) was injected over a 1 min period into Sprague Dawley rats instrumented for measurement of cardiac index and pulmonary (PVR) and systemic (SVR) vascular resistance during a 60 min observation period. Hemodynamics were compared between groups by linear mixed modeling. RESULTS: Approximately 1011 LOMs with mean diameter 3.77 ± 1.19 μm were injected over the 1 min period. Relative to controls, rodents treated with high concentration LOMs exhibited a higher pulmonary artery pressure (20 ± 0.4 mmHg vs 18 ± 0.4 mmHg, P < 0.001) and higher PVR (0.31 ± 0.01 vs 0.23 ± 0.01 mmHg/mL*min*kg, P < 0.001. Despite a stable cardiac index (62.2 ± 3.5 vs 62.3 ± 3.4 mL/min*kg, P < 0.001), mean arterial blood pressure decreased significantly in LOM-treated animals (46 ± 2 vs 60 ± 2 mmHg, P < 0.001) due to a decrease in SVR. Injections with aged LOM emulsions (>48 h since manufacture) resulted in a higher incidence of hemodynamic collapse during the observation period (P = 0.02). CONCLUSIONS: LOMs may be injected in quantities sufficient to deliver clinically meaningful volumes of oxygen but cause significant decrements in blood pressure and elevations in PVR.
Authors: John N Kheir; Laurie A Scharp; Mark A Borden; Edward J Swanson; Andrew Loxley; James H Reese; Katherine J Black; Luis A Velazquez; Lindsay M Thomson; Brian K Walsh; Kathryn E Mullen; Dionne A Graham; Michael W Lawlor; Carlo Brugnara; David C Bell; Francis X McGowan Journal: Sci Transl Med Date: 2012-06-27 Impact factor: 17.956
Authors: Brian D Polizzotti; Lindsay M Thomson; Daniel W O'Connell; Francis X McGowan; John N Kheir Journal: J Biomed Mater Res B Appl Biomater Date: 2014-01-15 Impact factor: 3.368
Authors: Ashwin Kumar Vutha; Ryan Patenaude; Alexis Cole; Rajesh Kumar; John N Kheir; Brian D Polizzotti Journal: Proc Natl Acad Sci U S A Date: 2022-03-21 Impact factor: 12.779