John Ikonomidis - Academia.edu (original) (raw)

Papers by John Ikonomidis

Research paper thumbnail of Preconditioning human cardiomyocytes and endothelial cells

Background: The effects of simulated "ischemia" and "reperfusion" were evaluated in cell cultures... more Background: The effects of simulated "ischemia" and "reperfusion" were evaluated in cell cultures of human ventricular cardiomyocytes and human saphenous vein endothelial cells. Methods: Myocyte and endothelial cell cultures were exposed to a low volume (1.5 ml) of either hypoxic (oxygen tension ‫؍‬ 16 mm Hg) or anoxic (oxygen tension ‫؍‬ 0 mm Hg) phosphatebuffered saline solution for 90 minutes ("ischemia") followed by 30 minutes of simulated "reperfusion." Cell injury was evaluated by trypan blue exclusion. Next, the effects of a preconditioning stimulus were evaluated by a brief (10 minute) exposure to hypoxic or anoxic ischemia and 10 minutes of reperfusion before prolonged (90 minutes) anoxic ischemia. Finally, the effects of anoxic preconditioning on intracellular lactate accumulation and extracellular lactate and acid release were assessed. Results: "Ischemia" and "reperfusion" resulted in greater injury to endothelial cells than to cardiomyocytes. In both cell types, anoxic ischemia resulted in greater injury than hypoxic ischemia. Preconditioning reduced cell injury in myocytes but not in endothelial cells. Endothelial cells produced more lactate than cardiomyocytes under normoxic conditions. Ischemia increased lactate accumulation and release in cardiomyocytes but not endothelial cells. Preconditioning reduced lactate accumulation and release in cardiomyocytes but not endothelial cells. Conclusions: Endothelial cells were more susceptible to the same period of simulated ischemia than cardiomyocytes. Preconditioning protected cardiomyocytes but not endothelial cells from a subsequent prolonged period of ischemia and reperfusion. (J Thorac Cardiovasc Surg 1998;115:210-9)

Research paper thumbnail of Association Between Method of Cerebral Protection During Neonatal Aortic Arch Surgery and Attention Deficit/Hyperactivity Disorder

The Annals of thoracic surgery, Jan 30, 2015

Neonates undergoing repair of the aortic arch are at risk for adverse neurodevelopmental outcomes... more Neonates undergoing repair of the aortic arch are at risk for adverse neurodevelopmental outcomes, including attention deficit/hyperactivity disorder (ADHD). The purpose of this study was to compare the effect of deep hypothermic circulatory arrest versus regional cerebral perfusion on the long-term outcome of ADHD. This study is a cross-sectional observational study of ADHD in children who underwent neonatal aortic arch surgery. Attention Deficit/Hyperactivity Disorder-IV surveys were used to determine the prevalence of ADHD. Review of the medical records was performed to determine the primary method of cerebral protection and to extract related surgical variables. Surveys were sent to parents of 134 children, with 57 surveys completed (43%). The percentage of children classified as having ADHD was 44%. Children with a diagnosis of interrupted aortic arch had the highest prevalence of ADHD (85%). Multivariate analysis demonstrated that interrupted aortic arch was associated with an...

Research paper thumbnail of Relation of murine thoracic aortic structural and cellular changes with aging to passive and active mechanical properties

Journal of the American Heart Association, 2015

Maintenance of the structure and mechanical properties of the thoracic aorta contributes to aorti... more Maintenance of the structure and mechanical properties of the thoracic aorta contributes to aortic function and is dependent on the composition of the extracellular matrix and the cellular content within the aortic wall. Age-related alterations in the aorta include changes in cellular content and composition of the extracellular matrix; however, the precise roles of these age-related changes in altering aortic mechanical function are not well understood. Thoracic aortic rings from the descending segment were harvested from C57BL/6 mice aged 6 and 21 months. Thoracic aortic diameter and wall thickness were higher in the old mice. Cellular density was reduced in the medial layer of aortas from the old mice; concomitantly, collagen content was higher in old mice, but elastin content was similar between young and old mice. Stress relaxation, an index of compliance, was reduced in aortas from old mice and correlated with collagen fraction. Contractility of the aortic rings following pota...

Research paper thumbnail of Temporal patterns of matrix metalloproteinase-9 gene promoter induction and protein synthesis during thoracic aortic aneurysm progression

Journal of the American College of Surgeons, Volume 201, Issue 3, Pages S99, September 2005, Auth... more Journal of the American College of Surgeons, Volume 201, Issue 3, Pages S99, September 2005, Authors:John R. Barbour, MD; David McClister, BS; Rupak Mukherjee, PhD; Francis Spinale, MD, PhD; John Ikonomidis, MD, PhD. ...

Research paper thumbnail of inhibitors of metalloproteinases after thoracic aortic aneurysm formation Temporal disparity in the induction of matrix metalloproteinases and tissue

Research paper thumbnail of Pulmonary Aspiration of Milk and Cream: An Avoidable Complication

Research paper thumbnail of Acute Traumatic Aortic Injury: Imaging Evaluation and Management 1

Radiology, 2008

Despite recent advances in prehospital care, multidetector computed tomographic (CT) technology, ... more Despite recent advances in prehospital care, multidetector computed tomographic (CT) technology, and rapid definitive therapy, trauma to the aorta continues to be a substantial source of morbidity and mortality in patients with blunt trauma. The imaging evaluation of acute aortic injuries has undergone radical change over the past decade, mostly due to the advent of multidetector CT. Regardless of recent technologic advances, imaging of the aorta in the trauma setting remains a multimodality imaging practice, and thus broad knowledge by the radiologist is essential. Likewise, the therapy for acute aortic injuries has changed substantially. Though open surgical repair continues to be the mainstay of therapy, percutaneous endovascular repair is becoming commonplace in many trauma centers. Here, the historical and current status of imaging and therapy of acute traumatic aortic injuries will be reviewed.

Research paper thumbnail of Transforming Growth Factor-β Signaling in Thoracic Aortic Aneurysm Development: A Paradox in Pathogenesis

Journal of Vascular Research, 2009

Thoracic aortic aneurysms (TAAs) are potentially devastating, and due to their asymptomatic behav... more Thoracic aortic aneurysms (TAAs) are potentially devastating, and due to their asymptomatic behavior, pose a serious health risk characterized by the lack of medical treatment options and high rates of surgical morbidity and mortality. Independent of the inciting stimuli (biochemical/mechanical), TAA development proceeds by a multifactorial process influenced by both cellular and extracellular mechanisms, resulting in alterations of the structure and composition of the vascular extracellular matrix (ECM). While the role of enhanced ECM proteolysis in TAA formation remains undisputed, little attention has been focused on the upstream signaling events that drive the remodeling process. Recent evidence highlighting the dysregulation of transforming growth factor-beta (TGF-beta) signaling in ascending TAAs from Marfan syndrome patients has stimulated an interest in this intracellular signaling pathway. However, paradoxical discoveries have implicated both enhanced TGF-beta signaling and loss of function TGF-beta receptor mutations, in aneurysm formation; obfuscating a clear functional role for TGF-beta in aneurysm development. In an effort to elucidate this subject, TGF-beta signaling and its role in vascular remodeling and pathology will be reviewed, with the aim of identifying potential mechanisms of how TGF-beta signaling may contribute to the formation and progression of TAA.

Research paper thumbnail of Temporal disparity in the induction of matrix metalloproteinases and tissue inhibitors of metalloproteinases after thoracic aortic aneurysm formation

The Journal of Thoracic and Cardiovascular Surgery, 2006

Background: An important component of matrix remodeling during thoracic aortic aneurysm progressi... more Background: An important component of matrix remodeling during thoracic aortic aneurysm progression is the balance between matrix metalloproteinases and their endogenous inhibitors (tissue inhibitors of metalloproteinases). However, whether and to what degree matrix metalloproteinase/tissue inhibitor of metalloproteinases profiles change over time with an evolving thoracic aortic aneurysm remains unclear.

Research paper thumbnail of Preconditioning human cardiomyocytes and endothelial cells

The Journal of Thoracic and Cardiovascular Surgery, 1998

Background: The effects of simulated "ischemia" and "reperfusion" were evaluated in cell cultures... more Background: The effects of simulated "ischemia" and "reperfusion" were evaluated in cell cultures of human ventricular cardiomyocytes and human saphenous vein endothelial cells. Methods: Myocyte and endothelial cell cultures were exposed to a low volume (1.5 ml) of either hypoxic (oxygen tension ‫؍‬ 16 mm Hg) or anoxic (oxygen tension ‫؍‬ 0 mm Hg) phosphatebuffered saline solution for 90 minutes ("ischemia") followed by 30 minutes of simulated "reperfusion." Cell injury was evaluated by trypan blue exclusion. Next, the effects of a preconditioning stimulus were evaluated by a brief (10 minute) exposure to hypoxic or anoxic ischemia and 10 minutes of reperfusion before prolonged (90 minutes) anoxic ischemia. Finally, the effects of anoxic preconditioning on intracellular lactate accumulation and extracellular lactate and acid release were assessed. Results: "Ischemia" and "reperfusion" resulted in greater injury to endothelial cells than to cardiomyocytes. In both cell types, anoxic ischemia resulted in greater injury than hypoxic ischemia. Preconditioning reduced cell injury in myocytes but not in endothelial cells. Endothelial cells produced more lactate than cardiomyocytes under normoxic conditions. Ischemia increased lactate accumulation and release in cardiomyocytes but not endothelial cells. Preconditioning reduced lactate accumulation and release in cardiomyocytes but not endothelial cells. Conclusions: Endothelial cells were more susceptible to the same period of simulated ischemia than cardiomyocytes. Preconditioning protected cardiomyocytes but not endothelial cells from a subsequent prolonged period of ischemia and reperfusion. (J Thorac Cardiovasc Surg 1998;115:210-9)

Research paper thumbnail of Antegrade and retrograde cardioplegia: Alternate or simultaneous?

The Journal of Thoracic and Cardiovascular Surgery, 1996

Neither antegrade nor retrograde cardioplegic protection provides homogeneous distribution, and a... more Neither antegrade nor retrograde cardioplegic protection provides homogeneous distribution, and a combination may be required to avoid anaerobic metabolism and depressed postoperative ventricular function. Tepid cardioplegia (29 ° C) avoids the delayed recovery of cardiac function and metabolism associated with cold cardioplegia (15 ° C) and reduces the anaerobic metabolism seen with warm (37 ° C) cardioplegia. We compared two techniques that combine antegrade and retrograde tepid cardioplegia: alternate and simultaneous. Methods: Sixty patients undergoing elective isolated coronary artery bypass grafting were randomized to receive near continuous tepid retrograde and either intermittent antegrade cardioplegia (the alternate technique) or antegrade cardioplegia with the solution delivered concurrently through each completed vein graft (the simultaneous technique). Results: Myocardial lactate extraction was greater after crossclamp release following simultaneous than alternate cardioplegia. Postoperative ventricular function was better after alternate than simultaneous cardioplegia. Conclusion: Both techniques permitted rapid postoperative recovery of myocardial metabolism and ventricular function. However, simultaneous cardioplegia was simpler and did not require deairing the aortic root between antegrade infusions. (J Thorac Cardiovasc Surg 1996;112:787-96) mprovements in myocardial protection have contributed to the reduction in the morbidity and mortality of cardiac operations. 1 Continuous warm cardioplegia offered the promise of resuscitating the ischemic myocardium. 2 Unfortunately coronary obstructions and arterial grafts limit warm blood cardioplegic delivery by the antegrade r o u t e ) Retro-

Research paper thumbnail of Adequate distribution of warm cardioplegic solution

The Journal of Thoracic and Cardiovascular Surgery, 1995

Seventy-five patients undergoing coronary artery bypass grafting were randomized to receive warm ... more Seventy-five patients undergoing coronary artery bypass grafting were randomized to receive warm antegrade (N = 25), warm retrograde (N = 25), or a combination of warm antegrade and retrograde (N = 25) delivery of blood cardioplegic solution. Myocardial oxygen utilization, lactate and acid metabolism, and adenine nucleotides and their degradation products were measured during the operation and cardiac function was assessed postoperatively. Warm retrograde delivery of cardioplegic solution increased lactate and acid release during cardioplegia and reperfusion, decreased left ventricular adenosine triphosphate concentrations, and reduced the washout of adenine nucleotide degradation products from both left and right ventricles. Warm antegrade delivery of cardioplegic solution resulted in less lactate and acid release during cardioplegia but more lactate accumulated in the territory of the ler anterior descending artery during the crossclamp period. Intermittent antegrade delivery of the cardioplegic solution during combination cardioplegia washed out lactate and acid, which suggested inhomogeneous delivery of the cardiople. gic solution during continuous retrograde cardioplegia. Combination cardioplegia best preserved adenosine triphosphate in the lefl ventricle and resulted in the best postoperative left and right ventricular function. A combination of intermittent antegrade and continuous retrograde delivery of cardioplegic solution provided better myocardial protection than either antegrade or retrograde delivery of cardioplegic solution alone. (J THORAC CARDIOVASC SURG 1995;110:800-12)

Research paper thumbnail of Dynamic and differential changes in myocardial and plasma endothelin in patients undergoing cardiopulmonary bypass

The Journal of Thoracic and Cardiovascular Surgery, 2005

The bioactive peptide endothelin modulates left ventricular function by changing afterload, coron... more The bioactive peptide endothelin modulates left ventricular function by changing afterload, coronary vascular tone, and myocardial contractility. However, whether increased plasma endothelin levels observed in patients during and after coronary revascularization and cardiopulmonary bypass reflect actual myocardial interstitial levels are unknown.

Research paper thumbnail of Insulin stimulates pyruvate dehydrogenase and protects human ventricular cardiomyocytes from simulated ischemia

The Journal of Thoracic and Cardiovascular Surgery, 1998

Impaired myocardial metabolism after cardioplegic arrest results in persistent anaerobic lactate ... more Impaired myocardial metabolism after cardioplegic arrest results in persistent anaerobic lactate production. Insulin may protect the heart from ischemia and reperfusion by enhancing myocardial metabolic recovery. However, the stimulation of glycolysis during ischemia may be detrimental because of an accumulation of metabolic end-products. We examined the effect of insulin on quiescent human ventricular cardiomyocytes subjected to simulated cardioplegic ischemia and reperfusion. Primary cardiomyocyte cultures were established from patients undergoing corrective repair of tetralogy of Fallot. Cells were exposed to varying concentrations of glucose and insulin during 30 minutes of stabilization in 10 mL of phosphate-buffered saline solution. Ischemia was simulated by exposing the cells to a low volume (1.5 mL) of deoxygenated phosphate-buffered saline solution for 90 minutes followed by 30 minutes of simulated reperfusion in 10 mL of normoxic phosphate-buffered saline solution. Cell viability was assessed by trypan blue exclusion. The activity of mitochondrial pyruvate dehydrogenase was measured in 3 states: stabilization, ischemia, and reperfusion. In addition intracellular lactate, adenine nucleotides, extracellular lactate, pyruvate, and acid release were measured. Higher ambient glucose concentrations resulted in greater cellular injury although insulin-treated cells displayed less injury after ischemia and reperfusion. Insulin increased the pyruvate dehydrogenase activity by 31% in cardiomyocytes and reduced extracellular lactate production by 40%. Intracellular adenosine triphosphate was improved by 75% in cells exposed to high glucose concentrations in the presence of insulin. Insulin protected human ventricular cardiomyocytes from ischemia and reperfusion. This protection may be due to a stimulation of pyruvate dehydrogenase activity which resulted in improved aerobic metabolism.

Research paper thumbnail of Hemodynamics and myocardial blood flow patterns after placement of a cardiac passive restraint device in a model of dilated cardiomyopathy

The Journal of Thoracic and Cardiovascular Surgery, 2011

Background: The present study examined a cardiac passive restraint device which applies epicardia... more Background: The present study examined a cardiac passive restraint device which applies epicardial pressure (HeartNet Implant; Paracor Medical, Inc, Sunnyvale, Calif) in a clinically relevant model of dilated cardiomyopathy to determine effects on hemodynamic and myocardial blood flow patterns.

Research paper thumbnail of Expression of matrix metalloproteinases and endogenous inhibitors within ascending aortic aneurysms of patients with bicuspid or tricuspid aortic valves

The Journal of Thoracic and Cardiovascular Surgery, 2007

The mechanisms contributing to ascending thoracic aortic aneurysms associated with bicuspid aorti... more The mechanisms contributing to ascending thoracic aortic aneurysms associated with bicuspid aortic valves may differ from ascending thoracic aortic aneurysms with tricuspid aortic valves. Matrix metalloproteinases and their endogenous inhibitors have been causally linked to ascending thoracic aortic aneurysm formation. This study tested the hypothesis that specific and different matrix metalloproteinase and tissue inhibitors of metalloproteinase profiles would be observed in ascending thoracic aortic aneurysm samples from patients with bicuspid aortic valves versus tricuspid aortic valves. Ascending thoracic aortic aneurysm samples taken from patients with bicuspid aortic valve (n = 53) and patients with tricuspid aortic valve (n = 46) were assessed for representative subtypes of all matrix metalloproteinase classes and all 4 known tissue inhibitors of metalloproteinases. Levels were compared [optical density units, median (interquartile range)] both to reference control ascending aortic samples (n = 26) and within each valve group by aneurysm diameter (< or =3.9 cm, 4.0-5.9 cm and > or =6.0 cm). Different and specific matrix metalloproteinase and tissue inhibitors of metalloproteinase profiles were observed in the ascending thoracic aortic aneurysm groups. In bicuspid aortic valves, matrix metalloproteinase-2 increased by 34% when compared with either tricuspid aortic valves or control (P < .05), and matrix metalloproteinase-14 decreased by 59% compared with tricuspid aortic valves (P < .05). In tricuspid aortic valve samples, tissue inhibitors of metalloproteinase-2 decreased by 35% when compared with either tricuspid aortic valves or control (P < .05), and matrix metalloproteinase-13 increased by 140% in the 4.0- to 5.9-cm diameter range (P < .05). A unique matrix metalloproteinase and tissue inhibitor of metalloproteinase portfolio was observed in ascending thoracic aortic aneurysms from patients with bicuspid aortic valve compared with patients with tricuspid aortic valve. These differences, suggesting disparate mechanisms of extracellular matrix remodeling, may provide unique biochemical targets for ascending thoracic aortic aneurysm prognostication and treatment in these 2 groups of patients.

Research paper thumbnail of Optimizing myocardial perfusion during coronary bypass—A contrast echo study

Journal of the American Society of Echocardiography, 1995

Research paper thumbnail of Temporal patterns of matrix metalloproteinase-9 gene promoter induction and protein synthesis during thoracic aortic aneurysm progression

Journal of the American College of Surgeons, 2005

Journal of the American College of Surgeons, Volume 201, Issue 3, Pages S99, September 2005, Auth... more Journal of the American College of Surgeons, Volume 201, Issue 3, Pages S99, September 2005, Authors:John R. Barbour, MD; David McClister, BS; Rupak Mukherjee, PhD; Francis Spinale, MD, PhD; John Ikonomidis, MD, PhD. ...

Research paper thumbnail of 1014-225 Myocardial and plasma levels of matrix metalloproteinase-9 are increased with atrial fibrillation

Journal of the American College of Cardiology, 2004

Research paper thumbnail of Proteinase Systems and Thoracic Aortic Aneurysm Progression

Journal of Surgical Research, 2007

Thoracic aortic aneurysms (TAAs) are a rare but potentially devastating condition. Current surgic... more Thoracic aortic aneurysms (TAAs) are a rare but potentially devastating condition. Current surgical treatment of TAAs usually involves a major operation, which conveys many risks to the patient. Better knowledge of the cellular events that lead to aneurysm formation may elucidate less morbid treatment options for this condition. A number of recent studies have identified that the relative abundance and activity of extracellular matrix (ECM) proteolytic systems are increased with TAAs. Specifically, the matrix metalloproteinases (MMPs) have been linked through numerous studies to TAA formation.

Research paper thumbnail of Preconditioning human cardiomyocytes and endothelial cells

Background: The effects of simulated "ischemia" and "reperfusion" were evaluated in cell cultures... more Background: The effects of simulated "ischemia" and "reperfusion" were evaluated in cell cultures of human ventricular cardiomyocytes and human saphenous vein endothelial cells. Methods: Myocyte and endothelial cell cultures were exposed to a low volume (1.5 ml) of either hypoxic (oxygen tension ‫؍‬ 16 mm Hg) or anoxic (oxygen tension ‫؍‬ 0 mm Hg) phosphatebuffered saline solution for 90 minutes ("ischemia") followed by 30 minutes of simulated "reperfusion." Cell injury was evaluated by trypan blue exclusion. Next, the effects of a preconditioning stimulus were evaluated by a brief (10 minute) exposure to hypoxic or anoxic ischemia and 10 minutes of reperfusion before prolonged (90 minutes) anoxic ischemia. Finally, the effects of anoxic preconditioning on intracellular lactate accumulation and extracellular lactate and acid release were assessed. Results: "Ischemia" and "reperfusion" resulted in greater injury to endothelial cells than to cardiomyocytes. In both cell types, anoxic ischemia resulted in greater injury than hypoxic ischemia. Preconditioning reduced cell injury in myocytes but not in endothelial cells. Endothelial cells produced more lactate than cardiomyocytes under normoxic conditions. Ischemia increased lactate accumulation and release in cardiomyocytes but not endothelial cells. Preconditioning reduced lactate accumulation and release in cardiomyocytes but not endothelial cells. Conclusions: Endothelial cells were more susceptible to the same period of simulated ischemia than cardiomyocytes. Preconditioning protected cardiomyocytes but not endothelial cells from a subsequent prolonged period of ischemia and reperfusion. (J Thorac Cardiovasc Surg 1998;115:210-9)

Research paper thumbnail of Association Between Method of Cerebral Protection During Neonatal Aortic Arch Surgery and Attention Deficit/Hyperactivity Disorder

The Annals of thoracic surgery, Jan 30, 2015

Neonates undergoing repair of the aortic arch are at risk for adverse neurodevelopmental outcomes... more Neonates undergoing repair of the aortic arch are at risk for adverse neurodevelopmental outcomes, including attention deficit/hyperactivity disorder (ADHD). The purpose of this study was to compare the effect of deep hypothermic circulatory arrest versus regional cerebral perfusion on the long-term outcome of ADHD. This study is a cross-sectional observational study of ADHD in children who underwent neonatal aortic arch surgery. Attention Deficit/Hyperactivity Disorder-IV surveys were used to determine the prevalence of ADHD. Review of the medical records was performed to determine the primary method of cerebral protection and to extract related surgical variables. Surveys were sent to parents of 134 children, with 57 surveys completed (43%). The percentage of children classified as having ADHD was 44%. Children with a diagnosis of interrupted aortic arch had the highest prevalence of ADHD (85%). Multivariate analysis demonstrated that interrupted aortic arch was associated with an...

Research paper thumbnail of Relation of murine thoracic aortic structural and cellular changes with aging to passive and active mechanical properties

Journal of the American Heart Association, 2015

Maintenance of the structure and mechanical properties of the thoracic aorta contributes to aorti... more Maintenance of the structure and mechanical properties of the thoracic aorta contributes to aortic function and is dependent on the composition of the extracellular matrix and the cellular content within the aortic wall. Age-related alterations in the aorta include changes in cellular content and composition of the extracellular matrix; however, the precise roles of these age-related changes in altering aortic mechanical function are not well understood. Thoracic aortic rings from the descending segment were harvested from C57BL/6 mice aged 6 and 21 months. Thoracic aortic diameter and wall thickness were higher in the old mice. Cellular density was reduced in the medial layer of aortas from the old mice; concomitantly, collagen content was higher in old mice, but elastin content was similar between young and old mice. Stress relaxation, an index of compliance, was reduced in aortas from old mice and correlated with collagen fraction. Contractility of the aortic rings following pota...

Research paper thumbnail of Temporal patterns of matrix metalloproteinase-9 gene promoter induction and protein synthesis during thoracic aortic aneurysm progression

Journal of the American College of Surgeons, Volume 201, Issue 3, Pages S99, September 2005, Auth... more Journal of the American College of Surgeons, Volume 201, Issue 3, Pages S99, September 2005, Authors:John R. Barbour, MD; David McClister, BS; Rupak Mukherjee, PhD; Francis Spinale, MD, PhD; John Ikonomidis, MD, PhD. ...

Research paper thumbnail of inhibitors of metalloproteinases after thoracic aortic aneurysm formation Temporal disparity in the induction of matrix metalloproteinases and tissue

Research paper thumbnail of Pulmonary Aspiration of Milk and Cream: An Avoidable Complication

Research paper thumbnail of Acute Traumatic Aortic Injury: Imaging Evaluation and Management 1

Radiology, 2008

Despite recent advances in prehospital care, multidetector computed tomographic (CT) technology, ... more Despite recent advances in prehospital care, multidetector computed tomographic (CT) technology, and rapid definitive therapy, trauma to the aorta continues to be a substantial source of morbidity and mortality in patients with blunt trauma. The imaging evaluation of acute aortic injuries has undergone radical change over the past decade, mostly due to the advent of multidetector CT. Regardless of recent technologic advances, imaging of the aorta in the trauma setting remains a multimodality imaging practice, and thus broad knowledge by the radiologist is essential. Likewise, the therapy for acute aortic injuries has changed substantially. Though open surgical repair continues to be the mainstay of therapy, percutaneous endovascular repair is becoming commonplace in many trauma centers. Here, the historical and current status of imaging and therapy of acute traumatic aortic injuries will be reviewed.

Research paper thumbnail of Transforming Growth Factor-β Signaling in Thoracic Aortic Aneurysm Development: A Paradox in Pathogenesis

Journal of Vascular Research, 2009

Thoracic aortic aneurysms (TAAs) are potentially devastating, and due to their asymptomatic behav... more Thoracic aortic aneurysms (TAAs) are potentially devastating, and due to their asymptomatic behavior, pose a serious health risk characterized by the lack of medical treatment options and high rates of surgical morbidity and mortality. Independent of the inciting stimuli (biochemical/mechanical), TAA development proceeds by a multifactorial process influenced by both cellular and extracellular mechanisms, resulting in alterations of the structure and composition of the vascular extracellular matrix (ECM). While the role of enhanced ECM proteolysis in TAA formation remains undisputed, little attention has been focused on the upstream signaling events that drive the remodeling process. Recent evidence highlighting the dysregulation of transforming growth factor-beta (TGF-beta) signaling in ascending TAAs from Marfan syndrome patients has stimulated an interest in this intracellular signaling pathway. However, paradoxical discoveries have implicated both enhanced TGF-beta signaling and loss of function TGF-beta receptor mutations, in aneurysm formation; obfuscating a clear functional role for TGF-beta in aneurysm development. In an effort to elucidate this subject, TGF-beta signaling and its role in vascular remodeling and pathology will be reviewed, with the aim of identifying potential mechanisms of how TGF-beta signaling may contribute to the formation and progression of TAA.

Research paper thumbnail of Temporal disparity in the induction of matrix metalloproteinases and tissue inhibitors of metalloproteinases after thoracic aortic aneurysm formation

The Journal of Thoracic and Cardiovascular Surgery, 2006

Background: An important component of matrix remodeling during thoracic aortic aneurysm progressi... more Background: An important component of matrix remodeling during thoracic aortic aneurysm progression is the balance between matrix metalloproteinases and their endogenous inhibitors (tissue inhibitors of metalloproteinases). However, whether and to what degree matrix metalloproteinase/tissue inhibitor of metalloproteinases profiles change over time with an evolving thoracic aortic aneurysm remains unclear.

Research paper thumbnail of Preconditioning human cardiomyocytes and endothelial cells

The Journal of Thoracic and Cardiovascular Surgery, 1998

Background: The effects of simulated "ischemia" and "reperfusion" were evaluated in cell cultures... more Background: The effects of simulated "ischemia" and "reperfusion" were evaluated in cell cultures of human ventricular cardiomyocytes and human saphenous vein endothelial cells. Methods: Myocyte and endothelial cell cultures were exposed to a low volume (1.5 ml) of either hypoxic (oxygen tension ‫؍‬ 16 mm Hg) or anoxic (oxygen tension ‫؍‬ 0 mm Hg) phosphatebuffered saline solution for 90 minutes ("ischemia") followed by 30 minutes of simulated "reperfusion." Cell injury was evaluated by trypan blue exclusion. Next, the effects of a preconditioning stimulus were evaluated by a brief (10 minute) exposure to hypoxic or anoxic ischemia and 10 minutes of reperfusion before prolonged (90 minutes) anoxic ischemia. Finally, the effects of anoxic preconditioning on intracellular lactate accumulation and extracellular lactate and acid release were assessed. Results: "Ischemia" and "reperfusion" resulted in greater injury to endothelial cells than to cardiomyocytes. In both cell types, anoxic ischemia resulted in greater injury than hypoxic ischemia. Preconditioning reduced cell injury in myocytes but not in endothelial cells. Endothelial cells produced more lactate than cardiomyocytes under normoxic conditions. Ischemia increased lactate accumulation and release in cardiomyocytes but not endothelial cells. Preconditioning reduced lactate accumulation and release in cardiomyocytes but not endothelial cells. Conclusions: Endothelial cells were more susceptible to the same period of simulated ischemia than cardiomyocytes. Preconditioning protected cardiomyocytes but not endothelial cells from a subsequent prolonged period of ischemia and reperfusion. (J Thorac Cardiovasc Surg 1998;115:210-9)

Research paper thumbnail of Antegrade and retrograde cardioplegia: Alternate or simultaneous?

The Journal of Thoracic and Cardiovascular Surgery, 1996

Neither antegrade nor retrograde cardioplegic protection provides homogeneous distribution, and a... more Neither antegrade nor retrograde cardioplegic protection provides homogeneous distribution, and a combination may be required to avoid anaerobic metabolism and depressed postoperative ventricular function. Tepid cardioplegia (29 ° C) avoids the delayed recovery of cardiac function and metabolism associated with cold cardioplegia (15 ° C) and reduces the anaerobic metabolism seen with warm (37 ° C) cardioplegia. We compared two techniques that combine antegrade and retrograde tepid cardioplegia: alternate and simultaneous. Methods: Sixty patients undergoing elective isolated coronary artery bypass grafting were randomized to receive near continuous tepid retrograde and either intermittent antegrade cardioplegia (the alternate technique) or antegrade cardioplegia with the solution delivered concurrently through each completed vein graft (the simultaneous technique). Results: Myocardial lactate extraction was greater after crossclamp release following simultaneous than alternate cardioplegia. Postoperative ventricular function was better after alternate than simultaneous cardioplegia. Conclusion: Both techniques permitted rapid postoperative recovery of myocardial metabolism and ventricular function. However, simultaneous cardioplegia was simpler and did not require deairing the aortic root between antegrade infusions. (J Thorac Cardiovasc Surg 1996;112:787-96) mprovements in myocardial protection have contributed to the reduction in the morbidity and mortality of cardiac operations. 1 Continuous warm cardioplegia offered the promise of resuscitating the ischemic myocardium. 2 Unfortunately coronary obstructions and arterial grafts limit warm blood cardioplegic delivery by the antegrade r o u t e ) Retro-

Research paper thumbnail of Adequate distribution of warm cardioplegic solution

The Journal of Thoracic and Cardiovascular Surgery, 1995

Seventy-five patients undergoing coronary artery bypass grafting were randomized to receive warm ... more Seventy-five patients undergoing coronary artery bypass grafting were randomized to receive warm antegrade (N = 25), warm retrograde (N = 25), or a combination of warm antegrade and retrograde (N = 25) delivery of blood cardioplegic solution. Myocardial oxygen utilization, lactate and acid metabolism, and adenine nucleotides and their degradation products were measured during the operation and cardiac function was assessed postoperatively. Warm retrograde delivery of cardioplegic solution increased lactate and acid release during cardioplegia and reperfusion, decreased left ventricular adenosine triphosphate concentrations, and reduced the washout of adenine nucleotide degradation products from both left and right ventricles. Warm antegrade delivery of cardioplegic solution resulted in less lactate and acid release during cardioplegia but more lactate accumulated in the territory of the ler anterior descending artery during the crossclamp period. Intermittent antegrade delivery of the cardioplegic solution during combination cardioplegia washed out lactate and acid, which suggested inhomogeneous delivery of the cardiople. gic solution during continuous retrograde cardioplegia. Combination cardioplegia best preserved adenosine triphosphate in the lefl ventricle and resulted in the best postoperative left and right ventricular function. A combination of intermittent antegrade and continuous retrograde delivery of cardioplegic solution provided better myocardial protection than either antegrade or retrograde delivery of cardioplegic solution alone. (J THORAC CARDIOVASC SURG 1995;110:800-12)

Research paper thumbnail of Dynamic and differential changes in myocardial and plasma endothelin in patients undergoing cardiopulmonary bypass

The Journal of Thoracic and Cardiovascular Surgery, 2005

The bioactive peptide endothelin modulates left ventricular function by changing afterload, coron... more The bioactive peptide endothelin modulates left ventricular function by changing afterload, coronary vascular tone, and myocardial contractility. However, whether increased plasma endothelin levels observed in patients during and after coronary revascularization and cardiopulmonary bypass reflect actual myocardial interstitial levels are unknown.

Research paper thumbnail of Insulin stimulates pyruvate dehydrogenase and protects human ventricular cardiomyocytes from simulated ischemia

The Journal of Thoracic and Cardiovascular Surgery, 1998

Impaired myocardial metabolism after cardioplegic arrest results in persistent anaerobic lactate ... more Impaired myocardial metabolism after cardioplegic arrest results in persistent anaerobic lactate production. Insulin may protect the heart from ischemia and reperfusion by enhancing myocardial metabolic recovery. However, the stimulation of glycolysis during ischemia may be detrimental because of an accumulation of metabolic end-products. We examined the effect of insulin on quiescent human ventricular cardiomyocytes subjected to simulated cardioplegic ischemia and reperfusion. Primary cardiomyocyte cultures were established from patients undergoing corrective repair of tetralogy of Fallot. Cells were exposed to varying concentrations of glucose and insulin during 30 minutes of stabilization in 10 mL of phosphate-buffered saline solution. Ischemia was simulated by exposing the cells to a low volume (1.5 mL) of deoxygenated phosphate-buffered saline solution for 90 minutes followed by 30 minutes of simulated reperfusion in 10 mL of normoxic phosphate-buffered saline solution. Cell viability was assessed by trypan blue exclusion. The activity of mitochondrial pyruvate dehydrogenase was measured in 3 states: stabilization, ischemia, and reperfusion. In addition intracellular lactate, adenine nucleotides, extracellular lactate, pyruvate, and acid release were measured. Higher ambient glucose concentrations resulted in greater cellular injury although insulin-treated cells displayed less injury after ischemia and reperfusion. Insulin increased the pyruvate dehydrogenase activity by 31% in cardiomyocytes and reduced extracellular lactate production by 40%. Intracellular adenosine triphosphate was improved by 75% in cells exposed to high glucose concentrations in the presence of insulin. Insulin protected human ventricular cardiomyocytes from ischemia and reperfusion. This protection may be due to a stimulation of pyruvate dehydrogenase activity which resulted in improved aerobic metabolism.

Research paper thumbnail of Hemodynamics and myocardial blood flow patterns after placement of a cardiac passive restraint device in a model of dilated cardiomyopathy

The Journal of Thoracic and Cardiovascular Surgery, 2011

Background: The present study examined a cardiac passive restraint device which applies epicardia... more Background: The present study examined a cardiac passive restraint device which applies epicardial pressure (HeartNet Implant; Paracor Medical, Inc, Sunnyvale, Calif) in a clinically relevant model of dilated cardiomyopathy to determine effects on hemodynamic and myocardial blood flow patterns.

Research paper thumbnail of Expression of matrix metalloproteinases and endogenous inhibitors within ascending aortic aneurysms of patients with bicuspid or tricuspid aortic valves

The Journal of Thoracic and Cardiovascular Surgery, 2007

The mechanisms contributing to ascending thoracic aortic aneurysms associated with bicuspid aorti... more The mechanisms contributing to ascending thoracic aortic aneurysms associated with bicuspid aortic valves may differ from ascending thoracic aortic aneurysms with tricuspid aortic valves. Matrix metalloproteinases and their endogenous inhibitors have been causally linked to ascending thoracic aortic aneurysm formation. This study tested the hypothesis that specific and different matrix metalloproteinase and tissue inhibitors of metalloproteinase profiles would be observed in ascending thoracic aortic aneurysm samples from patients with bicuspid aortic valves versus tricuspid aortic valves. Ascending thoracic aortic aneurysm samples taken from patients with bicuspid aortic valve (n = 53) and patients with tricuspid aortic valve (n = 46) were assessed for representative subtypes of all matrix metalloproteinase classes and all 4 known tissue inhibitors of metalloproteinases. Levels were compared [optical density units, median (interquartile range)] both to reference control ascending aortic samples (n = 26) and within each valve group by aneurysm diameter (< or =3.9 cm, 4.0-5.9 cm and > or =6.0 cm). Different and specific matrix metalloproteinase and tissue inhibitors of metalloproteinase profiles were observed in the ascending thoracic aortic aneurysm groups. In bicuspid aortic valves, matrix metalloproteinase-2 increased by 34% when compared with either tricuspid aortic valves or control (P < .05), and matrix metalloproteinase-14 decreased by 59% compared with tricuspid aortic valves (P < .05). In tricuspid aortic valve samples, tissue inhibitors of metalloproteinase-2 decreased by 35% when compared with either tricuspid aortic valves or control (P < .05), and matrix metalloproteinase-13 increased by 140% in the 4.0- to 5.9-cm diameter range (P < .05). A unique matrix metalloproteinase and tissue inhibitor of metalloproteinase portfolio was observed in ascending thoracic aortic aneurysms from patients with bicuspid aortic valve compared with patients with tricuspid aortic valve. These differences, suggesting disparate mechanisms of extracellular matrix remodeling, may provide unique biochemical targets for ascending thoracic aortic aneurysm prognostication and treatment in these 2 groups of patients.

Research paper thumbnail of Optimizing myocardial perfusion during coronary bypass—A contrast echo study

Journal of the American Society of Echocardiography, 1995

Research paper thumbnail of Temporal patterns of matrix metalloproteinase-9 gene promoter induction and protein synthesis during thoracic aortic aneurysm progression

Journal of the American College of Surgeons, 2005

Journal of the American College of Surgeons, Volume 201, Issue 3, Pages S99, September 2005, Auth... more Journal of the American College of Surgeons, Volume 201, Issue 3, Pages S99, September 2005, Authors:John R. Barbour, MD; David McClister, BS; Rupak Mukherjee, PhD; Francis Spinale, MD, PhD; John Ikonomidis, MD, PhD. ...

Research paper thumbnail of 1014-225 Myocardial and plasma levels of matrix metalloproteinase-9 are increased with atrial fibrillation

Journal of the American College of Cardiology, 2004

Research paper thumbnail of Proteinase Systems and Thoracic Aortic Aneurysm Progression

Journal of Surgical Research, 2007

Thoracic aortic aneurysms (TAAs) are a rare but potentially devastating condition. Current surgic... more Thoracic aortic aneurysms (TAAs) are a rare but potentially devastating condition. Current surgical treatment of TAAs usually involves a major operation, which conveys many risks to the patient. Better knowledge of the cellular events that lead to aneurysm formation may elucidate less morbid treatment options for this condition. A number of recent studies have identified that the relative abundance and activity of extracellular matrix (ECM) proteolytic systems are increased with TAAs. Specifically, the matrix metalloproteinases (MMPs) have been linked through numerous studies to TAA formation.