Corrigan Minehan Heart Center
Research efforts have led to significant historical contributions in the development of opioid anesthesia, as well as the study of blood conservation, protamine reactions, pulmonary vasoreactivity, right ventricular dysfunction and treatment and response to acute anemia by hemodilution.
Current research activities involve several topics in basic science, investigator-initiated clinical studies and industry-supported trials. These research initiatives include studying:
Research in the Ichinose Laboratory at the Massachusetts General Hospital Heart Center focuses on elucidating molecular mechanisms responsible for the depressed cardiomyocyte function in severe sepsis and other critical illness including cardiac arrest and cardiopulmonary resuscitation and ischemia and reperfusion injury.
Research interests in the Vidal Melo Laboratory at the Massachusetts General Hospital Heart Center are in the development and application of imaging and bioengineering techniques to investigate the cardiopulmonary system in different disease states and the study of functional changes during cardiac surgery. This laboratory conducts the investigations as translational studies in the Laboratory of Applied Biofluids (LAB)/DACC/MGH and clinical investigations in the cardiac operating rooms.
Research in the Ichinose Laboratory at the Massachusetts General Hospital Heart Center focuses on elucidating molecular mechanisms responsible for the depressed cardiomyocyte function in severe sepsis and other critical illness including cardiac arrest and cardiopulmonary resuscitation and ischemia and reperfusion injury.
Roles of Nitric Oxide or Hydrogen Sulfide-Dependent Signals on Cellular Functions
Of particular interests are the modulatory roles of nitric oxide (NO) or hydrogen sulfide (H2S)-dependent signals on cellular functions including mitochondrial respiration and calcium handling. Researchers have recently reported previously unrecognized protective impact of nitric oxide synthase 3 (NOS3) on sepsis-induced myocardial dysfunction.
These results led to further investigation of the role of cGMP-dependent and independent effects of NO in cardiomyocyte function in critical illness. Several studies are underway to elucidate the role of soluble guanylate cyclase and protein S-nitrosylation on cardiomyocyte function.
Effects of H2S on Cellular Metabolism and Organ Function
Another area of strong interest is in the effects of H2S on cellular metabolism and organ function. Recently, research groups have reported cardiovascular and metabolic effects of H2S inhalation in mice. A follow-up study is underway to examine the effects of H2S donor on systemic ischemia-reperfusion injury. This research is supported by Gas-Enabled Medical Innovation Fund.
Lung Function Through Non-Invasive Three-Dimensional High-Resolution Imaging
In collaboration with a multidisciplinary team of mechanical, systems and biomedical engineers, anesthesiologists and pulmonary/critical care physicians, researchers use mathematical modeling and tracer kinetics analysis of positron emission tomography (PET) images to study lung structure (density), function (ventilation and perfusion) and inflammation.
The area represents an innovative approach to the investigation of lung function through non-invasive three-dimensional high-resolution imaging. These techniques reveal in great detail at the regional level the mechanisms involved in the derangements of gas exchange and inflammation during lung disease and allow for the study of strategies to manage lung dysfunction.
Methods to Calculate Regional Ventilation-Perfusion (V/Q) Ratios Using Intravenous Injection of the Insoluble Tracer 13NN
Researchers have developed methods to calculate regional ventilation-perfusion (V/Q) ratios using intravenous injection of the insoluble tracer 13NN. The team has also enhanced the analysis and interpretation of the data by combining the PET derived V/Q distributions with compartmental models of gas exchange. Application of the methods to different models of lung diseases provided new insights into their pathophysiology. In studies during methacholine induced bronchoconstriction, researchers explored the ability to accurately estimate V/Q heterogeneities at the regional level to reveal that the topographic distribution of the V/Q heterogeneity involves a significant contribution from lung regions under 2.2 cm3.
Furthermore, the team showed that those regions are essential to explain the existence of the bimodal distribution of V/Q ratios observed in bronchoconstricted animals and asthmatic humans. Such results contributed to the development of a mathematical model to explain the development of large areas of air trapping in asthmatic humans.
Experimental Model of Acute Thrombotic Embolism in Sheep
Addressing pulmonary embolism, researchers developed an experimental model of acute thrombotic embolism in sheep and showed that a significant drop in regional ventilation occurs in embolized lung areas immediately following embolism. Investigating acute lung injury, researchers modeled arterial 13NN kinetics to show that the fraction of available alveolar gas volume effectively participating in gas exchange is reduced in the supine position in contrast to the prone position by an amount much larger than that expected from the sole reduction in lung volume.
Quantification of Regional Lung Metabolic Activity
More recently, laboratory researchers expanded their interest to the quantification of regional lung metabolic activity using the glucose analogue 18F-fluorodeoxyglucose (18F-FDG) to investigate regional lung inflammation. The combination of this method with the above mentioned 13NN methods provided a valuable set of tools to study non-invasively lung structure-function-inflammation relationships. With them, researchers have shown that in conditions such as ventilator induced lung injury (VILI) and smoke inhalation injury, inflammatory changes may precede and determine functional and structural changes.
Clinical Research Projects
In the clinical area, researchers have participated in several multicenter industry-initiated studies as well as conducted investigator-initiated research on lung function during cardiac surgery, echocardiography and ventricular assist devices, and perioperative neurocognitive dysfunction. Researchers are currently conducting a study on inflammatory mediators of respiratory dysfunction during cardiopulmonary bypass.
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