Although the incidence of acute death related to coronary artery disease has decreased with the a... more Although the incidence of acute death related to coronary artery disease has decreased with the advent of new interventional therapies, myocardial infarction remains one of the leading causes of death in the US. Current animal models developed to replicate this phenomenon have been associated with unacceptably high morbidity and mortality. A new model utilizing the first diagonal branch of the left anterior descending artery (D1-LAD) was developed to provide a clinically relevant lesion, while attempting to minimize the incidence of adverse complications associated with infarct creation. Eight Yucatan miniature pigs underwent percutaneous embolization of the D1-LAD via injection of 90 µm polystyrene micro-spheres. Cardiac structure and function were monitored at baseline, immediately post-operatively, and at 8-weeks post-infarct using transthoracic echocardiography. Post-mortem histopathology and biochemical analyses were performed to evaluate for changes in myocardial structure and...
Proceedings of the National Academy of Sciences of the United States of America, Mar 27, 2018
Heart failure (HF) following myocardial infarction (MI) is associated with high incidence of card... more Heart failure (HF) following myocardial infarction (MI) is associated with high incidence of cardiac arrhythmias. Development of therapeutic strategy requires detailed understanding of electrophysiological remodeling. However, changes of ionic currents in ischemic HF remain incompletely understood, especially in translational large-animal models. Here, we systematically measure the major ionic currents in ventricular myocytes from the infarct border and remote zones in a porcine model of post-MI HF. We recorded eight ionic currents during the cell's action potential (AP) under physiologically relevant conditions using AP-clamp sequential dissection. Compared with healthy controls, HF-remote zone myocytes exhibited increased late Na current, Ca-activated K current, Ca-activated Cl current, decreased rapid delayed rectifier K current, and altered Na/Ca exchange current profile. In HF-border zone myocytes, the above changes also occurred but with additional decrease of L-type Ca cu...
The in vivo therapeutic effect of mesenchymal stromal cells (MSCs) is currently believed to be ti... more The in vivo therapeutic effect of mesenchymal stromal cells (MSCs) is currently believed to be tightly linked to their paracrine secretion ability. However, insufficient or imprecise cell delivery, low cell survival and retention post-transplant, along with harsh donor site microenvironments, are major barriers to the clinical success of MSC therapies. Here we tested a small intestinal submucosa (SIS)-derived extracellular matrix (ECM) bioscaffold augmented with MSCs, with the hypothesis that they will facilitate the precise delivery of increased numbers of MSCs therefore improving cell viability and retention. In this study, we evaluated the secretion of angiogenic factors from three human MSC lines cultured on SIS ECM. We used human antibody array and enzyme-linked immunosorbent assay to measure the level of angiogenic factors released from MSCs when cultured on SIS ECM or regular tissue culture plastic. We tested MSCs cultured for three different time points. We found that the SI...
Background: Increased life expectancy and improved medical technology allow increasing numbers of... more Background: Increased life expectancy and improved medical technology allow increasing numbers of elderly patients to undergo cardiac surgery. Elderly patients may be at greater risk of postoperative morbidity and mortality. Complications can lead to worsened quality of life, shortened life expectancy and higher healthcare costs. Reducing perioperative complications, especially severe adverse events, is key to improving outcomes in patients undergoing cardiac surgery. The objective of this study is to determine whether perioperative lipid-lowering medication use is associated with a reduced risk of complications and mortality after coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). Methods: After IRB approval, we reviewed charts of 9,518 patients who underwent cardiac surgery with CPB at three medical centers between July 2001 and June 2015. The relationship between perioperative lipid-lowering treatment and postoperative outcome was investigated. 3,988 patien...
It remains disputable about perioperative use of renin-angiotensin system inhibitors (RASi) and t... more It remains disputable about perioperative use of renin-angiotensin system inhibitors (RASi) and their outcome effects. This multicenter retrospective cohort study examines association between use of perioperative RASi and outcomes in patients undergoing coronary artery bypass graft and/or valve surgery. After the exclusion, the patients are divided into 2 groups with or without preoperative RASi (PreRASi, n = 8581), or 2 groups with or without postoperative RASi (PostRASi, n = 8130). With using of propensity scores matching to reduce treatment selection bias, the study shows that PreRASi is associated with a significant reduction in postoperative 30-day mortality compared with without one (3.41% vs. 5.02%); PostRASi is associated with reduced long-term mortality rate compared with without one (6.62% vs. 7.70% at 2-year; 17.09% vs. 19.95% at 6-year). The results suggest that perioperative use of RASi has a significant benefit for the postoperative and long-term survival among patient...
Although the incidence of acute death related to coronary artery disease has decreased with the a... more Although the incidence of acute death related to coronary artery disease has decreased with the advent of new interventional therapies, myocardial infarction remains one of the leading causes of death in the US. Current animal models developed to replicate this phenomenon have been associated with unacceptably high morbidity and mortality. A new model utilizing the first diagonal branch of the left anterior descending artery (D1-LAD) was developed to provide a clinically relevant lesion, while attempting to minimize the incidence of adverse complications associated with infarct creation. Eight Yucatan miniature pigs underwent percutaneous embolization of the D1-LAD via injection of 90 µm polystyrene micro-spheres. Cardiac structure and function were monitored at baseline, immediately post-operatively, and at 8-weeks post-infarct using transthoracic echocardiography. Post-mortem histopathology and biochemical analyses were performed to evaluate for changes in myocardial structure and...
Proceedings of the National Academy of Sciences of the United States of America, Mar 27, 2018
Heart failure (HF) following myocardial infarction (MI) is associated with high incidence of card... more Heart failure (HF) following myocardial infarction (MI) is associated with high incidence of cardiac arrhythmias. Development of therapeutic strategy requires detailed understanding of electrophysiological remodeling. However, changes of ionic currents in ischemic HF remain incompletely understood, especially in translational large-animal models. Here, we systematically measure the major ionic currents in ventricular myocytes from the infarct border and remote zones in a porcine model of post-MI HF. We recorded eight ionic currents during the cell's action potential (AP) under physiologically relevant conditions using AP-clamp sequential dissection. Compared with healthy controls, HF-remote zone myocytes exhibited increased late Na current, Ca-activated K current, Ca-activated Cl current, decreased rapid delayed rectifier K current, and altered Na/Ca exchange current profile. In HF-border zone myocytes, the above changes also occurred but with additional decrease of L-type Ca cu...
The in vivo therapeutic effect of mesenchymal stromal cells (MSCs) is currently believed to be ti... more The in vivo therapeutic effect of mesenchymal stromal cells (MSCs) is currently believed to be tightly linked to their paracrine secretion ability. However, insufficient or imprecise cell delivery, low cell survival and retention post-transplant, along with harsh donor site microenvironments, are major barriers to the clinical success of MSC therapies. Here we tested a small intestinal submucosa (SIS)-derived extracellular matrix (ECM) bioscaffold augmented with MSCs, with the hypothesis that they will facilitate the precise delivery of increased numbers of MSCs therefore improving cell viability and retention. In this study, we evaluated the secretion of angiogenic factors from three human MSC lines cultured on SIS ECM. We used human antibody array and enzyme-linked immunosorbent assay to measure the level of angiogenic factors released from MSCs when cultured on SIS ECM or regular tissue culture plastic. We tested MSCs cultured for three different time points. We found that the SI...
Background: Increased life expectancy and improved medical technology allow increasing numbers of... more Background: Increased life expectancy and improved medical technology allow increasing numbers of elderly patients to undergo cardiac surgery. Elderly patients may be at greater risk of postoperative morbidity and mortality. Complications can lead to worsened quality of life, shortened life expectancy and higher healthcare costs. Reducing perioperative complications, especially severe adverse events, is key to improving outcomes in patients undergoing cardiac surgery. The objective of this study is to determine whether perioperative lipid-lowering medication use is associated with a reduced risk of complications and mortality after coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). Methods: After IRB approval, we reviewed charts of 9,518 patients who underwent cardiac surgery with CPB at three medical centers between July 2001 and June 2015. The relationship between perioperative lipid-lowering treatment and postoperative outcome was investigated. 3,988 patien...
It remains disputable about perioperative use of renin-angiotensin system inhibitors (RASi) and t... more It remains disputable about perioperative use of renin-angiotensin system inhibitors (RASi) and their outcome effects. This multicenter retrospective cohort study examines association between use of perioperative RASi and outcomes in patients undergoing coronary artery bypass graft and/or valve surgery. After the exclusion, the patients are divided into 2 groups with or without preoperative RASi (PreRASi, n = 8581), or 2 groups with or without postoperative RASi (PostRASi, n = 8130). With using of propensity scores matching to reduce treatment selection bias, the study shows that PreRASi is associated with a significant reduction in postoperative 30-day mortality compared with without one (3.41% vs. 5.02%); PostRASi is associated with reduced long-term mortality rate compared with without one (6.62% vs. 7.70% at 2-year; 17.09% vs. 19.95% at 6-year). The results suggest that perioperative use of RASi has a significant benefit for the postoperative and long-term survival among patient...
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Papers by Douglas Boyd