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1.
Surg Technol Int ; 36: 207-211, 2020 May 28.
Article in English | MEDLINE | ID: mdl-31821520

ABSTRACT

Minimally invasive cardiac surgery continues to evolve and expand as technology and surgeon experience develops. Among the barriers to the adoption of non-sternotomy minimally invasive valve surgery are the challenges associated with suture placement. Automated technology enables ergonomic remote suture placement that allows for reproducible results while shortening the learning curve. The objective of this review is to describe the latest advancements in automated suturing technology for minimally invasive valve surgery.


Subject(s)
Cardiac Surgical Procedures , Heart Valve Prosthesis Implantation , Aortic Valve/surgery , Minimally Invasive Surgical Procedures , Mitral Valve/surgery , Sutures , Treatment Outcome
2.
Anesth Analg ; 126(4): 1262-1267, 2018 04.
Article in English | MEDLINE | ID: mdl-28704244

ABSTRACT

BACKGROUND: Extracorporeal membrane oxygenation supplies oxygenated blood to the body supporting the heart and lungs. Survival rates of 20% to 50% are reported among patients receiving ECMO for cardiac arrest, severe cardiogenic shock, or failure to wean from cardiopulmonary bypass following cardiac surgery. Bleeding is one of the most common complications in ECMO patients due to coagulopathy, systemic anticoagulation, and the presence of large bore cannulas at systemic pressure. Absence of a standardized transfusion protocol in this population leads to inconsistent transfusion practices. Here, we assess a newly developed dedicated transfusion protocol in this clinical setting. METHODS: Data were retrospectively reviewed for the first 30 consecutive cardiac ECMO patients prior and post implementation of the ECMO transfusion protocol. Diagnoses, laboratory results, blood component utilization, and outcomes were collected and analyzed. RESULTS: Comorbidities were similar between the 2 eras, as well as the pre-ECMO ejection fraction (P = .568) and duration on ECMO (P = .278). Transfusion utilization data revealed statistically significant decreases in almost all blood components and a savings in blood component acquisition costs of 51% ($175, 970). In addition, an almost 2-fold increase in survival rate was observed in the post-ECMO transfusion protocol era (63% vs 33%; relative risk = 1.82; 95% confidence interval, 1.07-3.10; P = .028). CONCLUSIONS: Our data indicate that implementation of a standardized transfusion protocol, using more restrictive transfusion indications in cardiac ECMO patients, was associated with reduced blood product utilization, decreased complications, and improved survival. This multidepartmental approach facilitates better communication and adherence to consensus clinical decision making between intensive care unit, surgery, and transfusion service and optimizes care of complicated and acutely ill patients.


Subject(s)
Blood Transfusion/standards , Clinical Protocols/standards , Extracorporeal Membrane Oxygenation/standards , Heart Diseases/therapy , Adult , Aged , Aged, 80 and over , Blood Transfusion/economics , Blood Transfusion/mortality , Cost Savings , Cost-Benefit Analysis , Extracorporeal Membrane Oxygenation/adverse effects , Extracorporeal Membrane Oxygenation/economics , Extracorporeal Membrane Oxygenation/mortality , Female , Heart Diseases/economics , Heart Diseases/mortality , Heart Diseases/physiopathology , Hospital Costs , Humans , Male , Middle Aged , Recovery of Function , Retrospective Studies , Risk Factors , Time Factors , Treatment Outcome
3.
Circ Res ; 116(7): 1120-32, 2015 Mar 27.
Article in English | MEDLINE | ID: mdl-25608528

ABSTRACT

RATIONALE: Neointimal hyperplasia characterized by abnormal accumulation of vascular smooth muscle cells (SMCs) is a hallmark of occlusive disorders such as atherosclerosis, postangioplasty restenosis, vein graft stenosis, and allograft vasculopathy. Cyclic nucleotides are vital in SMC proliferation and migration, which are regulated by cyclic nucleotide phosphodiesterases (PDEs). OBJECTIVE: Our goal is to understand the regulation and function of PDEs in SMC pathogenesis of vascular diseases. METHODS AND RESULTS: We performed screening for genes differentially expressed in normal contractile versus proliferating synthetic SMCs. We observed that PDE1C expression was low in contractile SMCs but drastically elevated in synthetic SMCs in vitro and in various mouse vascular injury models in vivo. In addition, PDE1C was highly induced in neointimal SMCs of human coronary arteries. More importantly, injury-induced neointimal formation was significantly attenuated by PDE1C deficiency or PDE1 inhibition in vivo. PDE1 inhibition suppressed vascular remodeling of human saphenous vein explants ex vivo. In cultured SMCs, PDE1C deficiency or PDE1 inhibition attenuated SMC proliferation and migration. Mechanistic studies revealed that PDE1C plays a critical role in regulating the stability of growth factor receptors, such as PDGF receptor ß (PDGFRß) known to be important in pathological vascular remodeling. PDE1C interacts with low-density lipoprotein receptor-related protein-1 and PDGFRß, thus regulating PDGFRß endocytosis and lysosome-dependent degradation in an low-density lipoprotein receptor-related protein-1-dependent manner. A transmembrane adenylyl cyclase cAMP-dependent protein kinase cascade modulated by PDE1C is critical in regulating PDGFRß degradation. CONCLUSIONS: These findings demonstrated that PDE1C is an important regulator of SMC proliferation, migration, and neointimal hyperplasia, in part through modulating endosome/lysosome-dependent PDGFRß protein degradation via low-density lipoprotein receptor-related protein-1.


Subject(s)
Cyclic Nucleotide Phosphodiesterases, Type 1/physiology , Muscle, Smooth, Vascular/cytology , Myocytes, Smooth Muscle/enzymology , Neointima/enzymology , Animals , Carotid Artery Injuries/enzymology , Carotid Artery Injuries/pathology , Cell Division , Cell Movement , Cells, Cultured , Cyclic AMP/physiology , Cyclic Nucleotide Phosphodiesterases, Type 1/antagonists & inhibitors , Cyclic Nucleotide Phosphodiesterases, Type 1/deficiency , Endocytosis/physiology , Enzyme Induction , Humans , Low Density Lipoprotein Receptor-Related Protein-1/metabolism , Lysosomes/physiology , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Models, Animal , Myocytes, Smooth Muscle/cytology , Neointima/physiopathology , Protein Interaction Mapping , Protein Stability , Proteolysis , RNA Interference , Rats , Rats, Sprague-Dawley , Receptor, Platelet-Derived Growth Factor beta/metabolism , Signal Transduction/physiology
4.
Artif Organs ; 41(9): 827-834, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28589655

ABSTRACT

Cannulation-related complications are a known source of morbidity in patients supported on veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Despite its prevalence, little is known regarding the outcomes of patients who suffer such complications. This is a single institution review of cannulation-related complications and its effect on mortality in patients supported on VA-ECMO from January 2010-2015 using three cannulation strategies: axillary, femoral, and central. Complications were defined as advanced if they required major interventions (fasciotomy, amputation, site conversion). Patients were divided into two groups (complication present vs. not present) and Kaplan-Meier analysis was performed to determine any differences in their survival distributions. There were 103 patients supported on VA-ECMO: 41 (40%), 36 (35%), and 26 (25%) were cannulated via axillary, femoral, and central access, respectively. Cannulation-related complications occurred in 33 (32%) patients and this did not differ significantly between either axillary (34%), femoral (36%), or central (23%) strategies (P = 0.52). The most common complications encountered were hemorrhage and limb ischemia in 19 (18%) and 11 (11%) patients. Hemorrhagic complications did not differ between groups (P = 0.37), while limb ischemia and hyperperfusion were significantly associated with femoral and axillary cannulation, at a rate of 25% (P < 0.01) and 15% (P = 0.01), respectively. There was no difference in the incidence of advanced complications between cannulation groups: axillary (12%) vs. femoral (14%) vs. central (8%; P = 0.75). In addition, no increase in mortality was noted in patients who developed a cannulation-related complication by Kaplan-Meier estimates (P = 0.37). Cannulation-related complications affect a significant proportion of patients supported on VA-ECMO but do not differ in incidence between different cannulation strategies and do not affect patient mortality. Improved efforts at preventing these complications need to be developed to avoid the additional morbidity in an already critical patient population.


Subject(s)
Catheterization/adverse effects , Extracorporeal Membrane Oxygenation/adverse effects , Hospital Mortality , Postoperative Complications/epidemiology , Aorta , Axillary Artery , Female , Femoral Artery , Humans , Incidence , Ischemia , Kaplan-Meier Estimate , Male , Middle Aged , Postoperative Complications/etiology , Postoperative Complications/therapy , Prevalence , Retrospective Studies , Risk Factors
5.
J Card Surg ; 31(3): 177-82, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26809382

ABSTRACT

OBJECTIVE: Extracorporeal membrane oxygenation is an important therapeutic option for patients with refractory cardiogenic shock. Adequate decompression of the left ventricular in these patients is a key predictor of successful recovery. The currently available percutaneous decompression techniques are limited by their partial unloading capability. METHOD: We describe a series of four consecutive patients with refractory cardiogenic shock in whom adequate left ventricular decompression was achieved by integrating a transseptally placed left ventricular cannula into the existing extracorporeal membrane oxygenation circuit. RESULTS: From May to June 2015, four consecutive patients underwent transvenous transseptal left ventricular decompression with a 22 French cannula that was integrated into the extracorporeal membrane oxygenation circuit in a Y fashion. The mean age was 47.5 ± 20 years. All patients had refractory shock, and three patients failed prior decompression with an intra-aortic balloon pump. Fluoroscopy time was 12.15 ± 2.6 minutes. No procedural complications were noted. All patients had significant reduction in their pulmonary capillary wedge pressure and resolution of their pulmonary edema. Two patients died during the hospitalization due to sepsis and/or multiorgan failure. CONCLUSION: Antegrade transseptal left ventricular decompression is feasible in patients on extracorporeal membrane oxygenation and persistent pulmonary edema.


Subject(s)
Decompression, Surgical/methods , Extracorporeal Membrane Oxygenation/methods , Shock, Cardiogenic/therapy , Adult , Aged , Catheterization/methods , Feasibility Studies , Female , Heart Ventricles/surgery , Humans , Intra-Aortic Balloon Pumping , Male , Middle Aged , Pulmonary Edema/therapy , Pulmonary Wedge Pressure , Treatment Outcome , Young Adult
6.
J Vasc Surg ; 62(2): 464-70, 2015 Aug.
Article in English | MEDLINE | ID: mdl-24768363

ABSTRACT

OBJECTIVE: The molecular mechanisms leading to the development of abdominal aortic aneurysms (AAAs) remain poorly understood. The aim of this study was to determine the expression of Sonic Hedgehog (SHh), transforming growth factor ß (TGF-ß), and Notch signaling components in human aneurysmal and nonaneurysmal aorta in vivo. METHODS: Paired tissue samples were obtained from aneurysmal and nonaneurysmal (control) segments of the aortic wall of eight patients with suitable anatomy undergoing open repair of infrarenal AAAs. Protein and messenger RNA (mRNA) expression levels were determined by Western blot and quantitative real-time polymerase chain reaction analysis. RESULTS: Aneurysm development resulted in a significant reduction in vascular smooth muscle (vSMC) differentiation genes α-actin and SMC22α at both mRNA and protein levels. In parallel experiments, an 80.0% ± 15% reduction in SHh protein expression was observed in aneurysmal tissue compared with control. SHh and Ptc-1 mRNA levels were also significantly decreased, by 82.0% ± 10% and 75.0% ± 5%, respectively, in aneurysmal tissue compared with nonaneurysmal control tissue. Similarly, there was a 50.0% ± 9% and 60.0% ± 4% reduction in Notch receptor 1 intracellular domain and Hrt-2 protein expression, respectively, in addition to significant reductions in Notch 1, Notch ligand Delta like 4, and Hrt-2 mRNA expression in aneurysmal tissue compared with nonaneurysmal tissue. There was no change in Hrt-1 expression observed in aneurysmal tissue compared with control. In parallel experiments, we found a 2.2 ± 0.2-fold and a 5.6 ± 2.2-fold increase in TGF-ß mRNA and protein expression, respectively, in aneurysmal tissue compared with nonaneurysmal tissue. In vitro, Hedgehog signaling inhibition with cyclopamine in human aortic SMCs resulted in decreased Hedgehog/Notch signaling component and vSMC differentiation gene expression. Moreover, cyclopamine significantly increased TGF-ß1 mRNA expression by 2.6 ± 0.9-fold. CONCLUSIONS: These results suggest that SHh/Notch and TGF-ß signaling are differentially regulated in aneurysmal tissue compared with nonaneurysmal tissue. Changes in these signaling pathways and the resulting changes in vSMC content may play a causative role in the development of AAAs.


Subject(s)
Aortic Aneurysm, Abdominal/metabolism , Hedgehog Proteins/biosynthesis , Muscle, Smooth, Vascular/metabolism , Receptors, Notch/biosynthesis , Transforming Growth Factor beta/biosynthesis , Actins/biosynthesis , Actins/genetics , Aortic Aneurysm, Abdominal/genetics , Aortic Aneurysm, Abdominal/physiopathology , Female , Gene Expression , Hedgehog Proteins/genetics , Humans , Male , Muscle, Smooth, Vascular/physiopathology , Myocytes, Smooth Muscle/metabolism , Receptors, Notch/genetics , Transforming Growth Factor beta/genetics
7.
Catheter Cardiovasc Interv ; 83(5): E174-7, 2014 Apr 01.
Article in English | MEDLINE | ID: mdl-23703782

ABSTRACT

Internal mammary artery (IMA) arteriovenous fistulae (AVF) are exceedingly rare. There have been a few case reports documenting incidences of IMA AVFs arising from traumatic, iatrogenic, and congenital causes. Recommendations for management of IMA AVFs vary from open surgical ligation-excision to transcatheter embolization to observation. We present an unusual case of a patient who presented with ventricular arrhythmias and heart failure symptoms due to a left IMA AVF that formed after open heart surgery. The patient ultimately underwent percutaneous embolization of the fistulous connection.


Subject(s)
Arteriovenous Fistula/therapy , Coronary Artery Bypass/adverse effects , Embolization, Therapeutic , Iatrogenic Disease , Mammary Arteries/injuries , Saphenous Vein/transplantation , Sternotomy/adverse effects , Vascular System Injuries/therapy , Aged , Aneurysm, False/etiology , Aneurysm, False/therapy , Arrhythmias, Cardiac/etiology , Arteriovenous Fistula/diagnosis , Arteriovenous Fistula/etiology , Female , Heart Failure/etiology , Humans , Mammary Arteries/diagnostic imaging , Radiography , Treatment Outcome , Vascular System Injuries/diagnosis , Vascular System Injuries/etiology
8.
Sleep Adv ; 5(1): zpae034, 2024.
Article in English | MEDLINE | ID: mdl-38947231

ABSTRACT

Study Objectives: A high prevalence of sleep apnea has been reported among transcatheter aortic valve replacement (AVR) patients; however, the prevalence of sleep apnea in the younger and relatively healthier population of surgical AVR (SAVR) patients is unknown. Methods: We assessed the prevalence of sleep apnea and overall sleep quality in patients having SAVR. Participants aged 50-89 were eligible for recruitment. All participants completed type II HST before SAVR. Sleep apnea was defined as an apnea-hypopnea index (AHI) ≥ 5 events/hour. The current use of positive airway pressure was exclusionary. Results: The 46 participants (32 males/14 females) had a mean age of 66.6 years, body mass index of 30, AHI of 23.5, and obstructive AHI of 22.0. Only four participants had a prior sleep apnea diagnosis, yet all but one had sleep apnea on type II sleep testing. Two-thirds of sleep apnea was moderate or severe (AHI ≥ 15). A quarter of respiratory events were defined by arousals without desaturations. Whereas most sleep parameters resembled those of similarly aged community cohorts, mean percentage of N3 was reduced, accounting for only 3.8% of total sleep time. Conclusions: Type II home sleep testing (HST) revealed a 97.8% prevalence of sleep apnea in this sample, most of which was undiagnosed obstructive sleep apnea. Roughly two-thirds of sleep apnea was moderate or severe. Such a high impact of obstructive sleep apnea among patients with severe aortic valve disease deserves further investigation on potential underlying mechanisms and clinical implications.

9.
Catheter Cardiovasc Interv ; 81(7): 1249-52, 2013 Jun 01.
Article in English | MEDLINE | ID: mdl-23225750

ABSTRACT

Symptomatic paravalvular leaks (PVL) are a relatively uncommon, but potentially significant postoperative complication of valve replacement surgery. Percutaneous repair of PVLs has become an increasingly utilized approach in patients whose comorbidities obviate surgical repair. We present an interesting case of a gentleman who underwent successful repair of a mitral PVL with Amplatzer devices following initial aortic and mitral valve replacements for bacterial endocarditis. He later developed fungal endocarditis that ultimately required re-operation to remove the devices and replace his mitral and aortic valves. This complication of closure devices, although reportedly rare, should be considered when contemplating a percutaneous approach. © 2012 Wiley Periodicals, Inc.


Subject(s)
Candidiasis/microbiology , Cardiac Catheterization/adverse effects , Endocarditis, Bacterial/surgery , Heart Valve Prosthesis Implantation/adverse effects , Mitral Valve/surgery , Pneumococcal Infections/surgery , Postoperative Complications/therapy , Prosthesis-Related Infections/microbiology , Septal Occluder Device/adverse effects , Adult , Antifungal Agents/therapeutic use , Aortic Valve/microbiology , Aortic Valve/surgery , Candidiasis/diagnosis , Candidiasis/surgery , Cardiac Catheterization/instrumentation , Device Removal , Echocardiography, Doppler, Color , Echocardiography, Three-Dimensional , Echocardiography, Transesophageal , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/microbiology , Humans , Male , Mitral Valve/microbiology , Pneumococcal Infections/diagnosis , Pneumococcal Infections/microbiology , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Prosthesis-Related Infections/diagnosis , Prosthesis-Related Infections/surgery , Radiography, Interventional , Reoperation , Streptococcus pneumoniae/isolation & purification , Treatment Outcome
10.
J Pharmacol Exp Ther ; 343(2): 479-88, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22915768

ABSTRACT

Abnormal vascular smooth muscle cell (SMC) activation is associated with various vascular disorders such as atherosclerosis, in-stent restenosis, vein graft disease, and transplantation-associated vasculopathy. Vinpocetine, a derivative of the alkaloid vincamine, has long been used as a cerebral blood flow enhancer for treating cognitive impairment. However, its role in pathological vascular remodeling remains unexplored. Herein, we show that systemic administration of vinpocetine significantly reduced neointimal formation in carotid arteries after ligation injury. Vinpocetine also markedly decreased spontaneous remodeling of human saphenous vein explants in ex vivo culture. In cultured SMCs, vinpocetine dose-dependently suppressed cell proliferation and caused G1-phase cell cycle arrest, which is associated with a decrease in cyclin D1 and an increase in p27Kip1 levels. In addition, vinpocetine dose-dependently inhibited platelet-derived growth factor (PDGF)-stimulated SMC migration as determined by the two-dimensional migration assays and three-dimensional aortic medial explant invasive assay. Moreover, vinpocetine significantly reduced PDGF-induced type I collagen and fibronectin expression. It is noteworthy that PDGF-stimulated phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2), but not protein kinase B, was specifically inhibited by vinpocetine. Vinpocetine powerfully attenuated intracellular reactive oxidative species (ROS) production, which largely mediates the inhibitory effects of vinpocetine on ERK1/2 activation and SMC growth. Taken together, our results reveal a novel function of vinpocetine in attenuating neointimal hyperplasia and pathological vascular remodeling, at least partially through suppressing ROS production and ERK1/2 activation in SMCs. Given the safety profile of vinpocetine, this study provides insight into the therapeutic potential of vinpocetine in proliferative vascular disorders.


Subject(s)
Angiogenesis Inhibitors , Muscle, Smooth, Vascular/drug effects , Myocytes, Smooth Muscle/drug effects , Neovascularization, Pathologic/drug therapy , Vinca Alkaloids/pharmacology , Actins/metabolism , Animals , Antimetabolites , Aorta/cytology , Aorta/drug effects , Blotting, Western , Bromodeoxyuridine , Carotid Arteries/physiology , Cell Movement/drug effects , Cell Proliferation/drug effects , Cell Transplantation , Extracellular Matrix/drug effects , Humans , Immunohistochemistry , Male , Mice , RNA/biosynthesis , RNA/isolation & purification , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolism , Saphenous Vein/drug effects , Wound Healing/drug effects
11.
Arterioscler Thromb Vasc Biol ; 31(3): 616-23, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21148428

ABSTRACT

OBJECTIVE: The phenotypic modulation of vascular smooth muscle cells (VSMCs) to a synthetic phenotype is vital during pathological vascular remodeling and the development of various vascular diseases. An increase in type I collagen (collagen I) has been implicated in synthetic VSMCs, and cyclic nucleotide signaling is critical in collagen I regulation. Herein, we investigate the role and underlying mechanism of cyclic nucleotide phosphodiesterase 1 (PDE1) in regulating collagen I in synthetic VSMCs. METHODS AND RESULTS: The PDE1 inhibitor IC86340 significantly reduced collagen I in human saphenous vein explants undergoing spontaneous remodeling via ex vivo culture. In synthetic VSMCs, high basal levels of intracellular and extracellular collagen I protein were markedly decreased by IC86340. This attenuation was due to diminished protein but not mRNA. Inhibition of lysosome function abolished the effect of IC86340 on collagen I protein expression. PDE1C but not PDE1A is the major isoform responsible for mediating the effects of IC86340. Bicarbonate-sensitive soluble adenylyl cyclase/cAMP signaling was modulated by PDE1C, which is critical in collagen I degradation in VSMCs. CONCLUSIONS: These data demonstrate that PDE1C regulates soluble adenylyl cyclase/cAMP signaling and lysosome-mediated collagen I protein degradation, and they suggest that PDE1C plays a critical role in regulating collagen homeostasis during pathological vascular remodeling.


Subject(s)
Collagen Type I/metabolism , Cyclic Nucleotide Phosphodiesterases, Type 1/metabolism , Lysosomes/enzymology , Muscle, Smooth, Vascular/enzymology , Myocytes, Smooth Muscle/enzymology , Adenylyl Cyclases/genetics , Adenylyl Cyclases/metabolism , Animals , Bicarbonates/metabolism , Cells, Cultured , Cyclic AMP/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Cyclic GMP-Dependent Protein Kinases/metabolism , Cyclic Nucleotide Phosphodiesterases, Type 1/antagonists & inhibitors , Cyclic Nucleotide-Gated Cation Channels/metabolism , Guanine Nucleotide Exchange Factors/metabolism , Humans , Lysosomes/drug effects , Muscle, Smooth, Vascular/drug effects , Myocytes, Smooth Muscle/drug effects , Phenotype , Phosphodiesterase Inhibitors/pharmacology , RNA Interference , Rats , Signal Transduction , Tissue Culture Techniques
12.
Cardiovasc Res ; 118(12): 2703-2717, 2022 09 20.
Article in English | MEDLINE | ID: mdl-34550322

ABSTRACT

AIMS: Intimal hyperplasia is a common feature of vascular remodelling disorders. Accumulation of synthetic smooth muscle cell (SMC)-like cells is the main underlying cause. Current therapeutic approaches including drug-eluting stents are not perfect due to the toxicity on endothelial cells and novel therapeutic strategies are needed. Our preliminary screening for dysregulated cyclic nucleotide phosphodiesterases (PDEs) in growing SMCs revealed the alteration of PDE10A expression. Herein, we investigated the function of PDE10A in SMC proliferation and intimal hyperplasia both in vitro and in vivo. METHODS AND RESULTS: RT-qPCR, immunoblot, and in situ proximity ligation assay were performed to determine PDE10A expression in synthetic SMCs and injured vessels. We found that PDE10A mRNA and/or protein levels are up-regulated in cultured SMCs upon growth stimulation, as well as in intimal cells in injured mouse femoral arteries. To determine the cellular functions of PDE10A, we focused on its role in SMC proliferation. The anti-mitogenic effects of PDE10A on SMCs were evaluated via cell counting, BrdU incorporation, and flow cytometry. We found that PDE10A deficiency or inhibition arrested the SMC cell cycle at G1-phase with a reduction of cyclin D1. The anti-mitotic effect of PDE10A inhibition was dependent on cGMP-dependent protein kinase Iα (PKGIα), involving C-natriuretic peptide (CNP) and particulate guanylate cyclase natriuretic peptide receptor 2 (NPR2). In addition, the effects of genetic depletion and pharmacological inhibition of PDE10A on neointimal formation were examined in a mouse model of femoral artery wire injury. Both PDE10A knockout and inhibition decreased injury-induced intimal thickening in femoral arteries by at least 50%. Moreover, PDE10A inhibition decreased ex vivo remodelling of cultured human saphenous vein segments. CONCLUSIONS: Our findings indicate that PDE10A contributes to SMC proliferation and intimal hyperplasia at least partially via antagonizing CNP/NPR2/cGMP/PKG1α signalling and suggest that PDE10A may be a novel drug target for treating vascular occlusive disease.


Subject(s)
Muscle, Smooth, Vascular , Vascular System Injuries , Animals , Bromodeoxyuridine/metabolism , Bromodeoxyuridine/pharmacology , Cell Proliferation , Cells, Cultured , Cyclic GMP/metabolism , Cyclic GMP-Dependent Protein Kinase Type I/metabolism , Cyclin D1/metabolism , Endothelial Cells/metabolism , Guanylate Cyclase/metabolism , Guanylate Cyclase/pharmacology , Humans , Hyperplasia/metabolism , Hyperplasia/pathology , Mice , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Phosphoric Diester Hydrolases/metabolism , RNA, Messenger/metabolism , Vascular Remodeling , Vascular System Injuries/drug therapy , Vascular System Injuries/genetics , Vascular System Injuries/metabolism
13.
Innovations (Phila) ; 16(1): 52-57, 2021.
Article in English | MEDLINE | ID: mdl-33337279

ABSTRACT

OBJECTIVE: The aim of this study is to evaluate early and intermediate outcomes and hemodynamics of the latest-generation Trifecta valve implanted using right anterior minithoracotomy. METHODS: We performed a single-center, retrospective, observational study including 175 individuals who underwent isolated minimally invasive aortic valve replacement with the latest-generation Trifecta valves through a right anterior minithoracotomy between January 2016 and January 2019. Exclusion criteria for follow-up echocardiographic study included concomitant procedures, conversion to median sternotomy, and nonsurvival during the index admission. Analyses addressed implantation safety, 30-day and intermediate-term survival and hemodynamic performance of the valves. RESULTS: Overall, patients were followed with duration ranging from 0.5 to 3 years. Early (<30 days) mortality occurred in 2 patients (1.1%), and there were 9 (5.1%) late (>30 days) deaths. Early thromboembolic events and postoperative bleeding requiring reoperation occurred at a rate of 4.0% (n = 7) and 6.2% (n = 11), respectively. Overall in 175 patients who met inclusion criteria for the follow-up echocardiography study, mean gradients across all valve sizes were 41.3 ± 14.9 (standard deviation) mm Hg preoperatively and remained low at 7.2 ± 3.9 mm Hg with mean effective orifice area of 1.8 ± 0.5 cm2 on the last follow-up echo. There was 1 case of infective prosthetic endocarditis, which did not require valve explant. There were no reoperations due to valve-related problems during the study period. CONCLUSIONS: This is the largest series reporting on outcomes of the latest-generation Trifecta valve implanted using right anterior minithoracotomy. Our results demonstrate that this valve can be safely implanted via a minimally invasive approach with excellent early and intermediate outcomes and hemodynamic performance.


Subject(s)
Aortic Valve Stenosis , Bioprosthesis , Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve Stenosis/surgery , Heart Valve Prosthesis/adverse effects , Hemodynamics , Humans , Prosthesis Design , Retrospective Studies , Treatment Outcome
14.
Innovations (Phila) ; 16(2): 175-180, 2021.
Article in English | MEDLINE | ID: mdl-33470874

ABSTRACT

OBJECTIVE: Bilateral internal thoracic artery (BITA) bypass can enable more complete arterial revascularization procedures. Minimally invasive cardiac surgery (MICS) can offer significant patient benefits. New minimally invasive technology for sternal retraction and tissue manipulation is needed to enable ergonomic and reliable minimally invasive ITA harvesting. The goal of this research was to develop technology and techniques, along with experimental testing and training models, for a sternal-sparing approach to in situ BITA harvesting through a small subxiphoid access site. METHODS: This study focused on optimizing custom equipment and methods for subxiphoid BITA harvesting initially in a porcine model (19 pig carcasses, 36 ITAs) and subsequently in 7 cadavers (14 ITAs). RESULTS: Fifty consecutive ITAs were successfully harvested using this remote access approach. The last 20 ITA specimens harvested from the porcine model were explanted and measured; the average length of the free ITA grafts was 12.8 ± 0.9 cm (range 10.8 to 14.2 cm) with a mean time of 23.3 ± 5.2 minutes (range 13 to 25 minutes) for each harvest. CONCLUSIONS: Early results demonstrate that both ITAs can be reliably harvested in a skeletonized fashion in situ through sternal-sparing, small subxiphoid access in 2 experimental models. This innovative approach warrants further exploration toward facilitating complete arterial revascularization and the further adoption of minimally invasive coronary artery bypass graft surgery.


Subject(s)
Mammary Arteries , Animals , Coronary Artery Bypass , Humans , Mammary Arteries/surgery , Minimally Invasive Surgical Procedures , Sternum , Swine , Tissue and Organ Harvesting
15.
Gen Hosp Psychiatry ; 71: 43-46, 2021.
Article in English | MEDLINE | ID: mdl-33932735

ABSTRACT

OBJECTIVE: The goal is to assess the feasibility of conducting unattended (type II) sleep studies before surgical aortic valve replacement (SAVR) to examine the relationship between baseline sleep measures and postoperative delirium. METHODS: This single-site study recruited 18 of 20 study referrals with aortic stenosis undergoing first lifetime SAVR. Subjects completed a home-based type II sleep study. Delirium was assessed postoperative days 1-5. Exact logistic regression was used to determine whether sleep efficiency or apnea/hypopnea index predicts delirium. RESULTS: Of 18 study participants, 15 successfully completed a home sleep study (mean age: 71.7 +/- 8.1 years old; 10 male subjects). Five subjects (33.3%) developed delirium. Preliminary analyses found that greater sleep efficiency was associated with a large reduction in delirium odds but was not statistically significant (OR = 0.31, 95% CI: 0.06, 1.03, p = 0.057). The point estimate of the relationship between apnea/hypopnea index and delirium was not similarly sizeable (OR 1.10, 95% CI: 0.35, 3.37, p = 0.85). CONCLUSIONS: Our findings suggest that home type II sleep studies before SAVR are feasible, and they support adequately powered studies investigating type II home sleep studies as a predictor of postoperative delirium and other important postsurgical outcomes.


Subject(s)
Delirium , Heart Valve Prosthesis Implantation , Aged , Aortic Valve/surgery , Delirium/diagnosis , Delirium/epidemiology , Delirium/etiology , Feasibility Studies , Heart Valve Prosthesis Implantation/adverse effects , Humans , Male , Middle Aged , Prospective Studies , Risk Factors , Sleep , Treatment Outcome
16.
Innovations (Phila) ; 15(4): 355-360, 2020.
Article in English | MEDLINE | ID: mdl-32703047

ABSTRACT

OBJECTIVE: Our objective is to identify the incidence of urgent transvenous (TV) pacing wire placement following minimally invasive aortic valve replacement (mini-AVR). METHODS: This is a single-center, retrospective, observational study including 359 individuals who underwent isolated mini-AVR through right anterior mini-thoracotomy between January 2015 and September 2019. Patients were grouped according to avoidance or insertion of epicardial pacing wires, and further subdivided based on the requirement for postoperative emergent temporary TV pacing or permanent pacemaker (PPM) placement during the index admission. RESULTS: Two hundred forty-two (67.4%) had acceptable rate and no high-degree atrioventricular (AV) block prior to chest closure and did not have insertion of epicardial pacing wires. Of those patients, only 3 (1.2%) required emergent TV pacing and 6 (2.5%) required nonemergent TV pacing with or without PPM placement during the index admission. Sixty-two (17.3%) patients received only atrial epicardial pacing leads secondary to sinus bradycardia or junctional rhythm and 3 (4.8%) of those patients required PPM placement due to sick sinus syndrome and 1 (1.6%) patient required nonemergent TV pacing and PPM due to high-grade AV heart block. Fifty-five (15.3%) patients received ventricular leads due to high-grade AV heart block and 7 (12.7%) of those patients required PPM placement during the index admission. CONCLUSIONS: Temporary epicardial lead insertion is not routinely required in mini-AVR in patients with normal rate and acceptable AV conduction prior to chest closure. In the absence of epicardial ventricular lead insertion, the chance of requiring urgent TV pacing wire placement during the index admission is 0.99%.


Subject(s)
Aortic Valve/surgery , Heart Valve Prosthesis Implantation/methods , Pacemaker, Artificial , Aged , Cardiac Pacing, Artificial , Female , Heart Valve Prosthesis , Humans , Male , Middle Aged , Minimally Invasive Surgical Procedures , Postoperative Care , Retrospective Studies
17.
Anat Sci Educ ; 13(3): 413-425, 2020 May.
Article in English | MEDLINE | ID: mdl-31232510

ABSTRACT

Simulation training has become increasingly relevant in the educational curriculum of surgical trainees. The types of simulation models used, goals of simulation training, and an objective assessment of its utility and effectiveness are highly variable. The role and effectiveness of cadaveric simulation in cardiothoracic surgical training has not been well established. The objective of this study was to evaluate the current medical literature available on the utility and the effectiveness of cadaveric simulation in cardiothoracic surgical residency training. A literature search was performed using PubMed, Cochrane Library, Embase, Scopus, and CINAHL from inception to February 2019. Of the 362 citations obtained, 23 articles were identified and retrieved for full review, yielding ten eligible articles that were included for analysis. One additional study was identified and included in the analysis. Extraction of data from the selected articles was performed using predetermined data fields, including study design, study participants, simulation task, performance metrics, and costs. Most of these studies were only descriptive of a cadaveric or perfused cadaveric simulation model that could be used to augment clinical operative training in cardiothoracic surgery. There is a paucity of evidence in the literature that specifically evaluates the utility and the efficacy of cadavers in cardiothoracic surgery training. Of the few studies that have been published in the literature, cadaveric simulation does seem to have a role in cardiothoracic surgery training beyond simply learning basic skills. Additional research in this area is needed.


Subject(s)
Cadaver , High Fidelity Simulation Training/methods , Internship and Residency/methods , Thoracic Surgery/education , Clinical Competence/statistics & numerical data , Curriculum , Humans , Internship and Residency/statistics & numerical data , Learning
18.
Innovations (Phila) ; 14(2): 159-167, 2019 Apr.
Article in English | MEDLINE | ID: mdl-31039682

ABSTRACT

OBJECTIVE: Aortic root enlargement may be necessary to implant adequately sized valves to avoid patient-prosthetic mismatch. Our objective was to assess the feasibility of annular enlargement during aortic valve replacement via a right anterior minithoracotomy. METHODS: Twelve consecutive patients undergoing elective minimally invasive aortic valve replacement requiring annular enlargement over a 2-year period were retrospectively reviewed. A right anterior minithoracotomy was performed in all patients. Cardiopulmonary bypass and aortic crossclamp times, hospital length of stay, postoperative complications, rate of reoperation, echocardiographic data, and mortality were analyzed. RESULTS: Mean age was 66 years ± 14. Mean body mass index was 34 ± 7.8 kg/m2. All patients had normal preoperative ejection fractions. Indications for aortic valve replacement were severe (3/12, 25%) or critical (9/12, 75%) aortic stenosis due to degenerative aortic valve disease (10/12, 83%) and congenitally bicuspid aortic valve (2/12, 17%). Cardiopulmonary bypass and aortic crossclamp times were 144.7 ± 14.7 minutes and 111.7 ± 10.6 minutes, respectively. The median postoperative length of stay was 4 days. Peak and mean aortic valve gradients on postreplacement intraoperative transesophageal echocardiography were 14.5 ± 9.4 mmHg and 7.2 ± 4.2 mmHg, respectively, with no perivalvular leak on intraoperative or follow-up transthoracic echocardiogram. Postoperative transthoracic echocardiography had peak and mean aortic valve gradients of 12.1 ± 6.9 mmHg and 6.3 ± 3.7 mmHg, respectively. There were no postoperative mortalities. Freedom from reoperation was 100%. CONCLUSIONS: Annular enlargement performed during minimally invasive aortic valve replacement is feasible. Basic minimally invasive skills are recommended prior to instituting these more advanced techniques.


Subject(s)
Aortic Valve Stenosis/surgery , Aortic Valve/surgery , Cardiac Valve Annuloplasty/methods , Heart Valve Prosthesis Implantation/methods , Minimally Invasive Surgical Procedures/methods , Aged , Aged, 80 and over , Aortic Valve/abnormalities , Aortic Valve/diagnostic imaging , Aortic Valve/pathology , Aortic Valve Stenosis/ethnology , Cardiac Valve Annuloplasty/mortality , Cardiopulmonary Bypass/standards , Echocardiography/methods , Feasibility Studies , Female , Heart Valve Prosthesis Implantation/mortality , Humans , Length of Stay , Middle Aged , Postoperative Complications , Retrospective Studies , Thoracotomy/methods , Thoracotomy/trends
19.
Ann Thorac Surg ; 107(1): 128-134, 2019 01.
Article in English | MEDLINE | ID: mdl-30170012

ABSTRACT

BACKGROUND: Optimal pain control continues to be a concern in cardiac surgery. Current strategies for postoperative pain management often yield suboptimal results. The superiority of Exparel (Pacira Pharmaceuticals, Inc, Parsippany, NJ) in providing postoperative pain control and opioid sparing is equivocal. This prospective, randomized, double-blind study examines the efficacy of Exparel as a novel single-dose application parasternal nerve block in postoperative pain control and opioid sparing. METHODS: This single-surgeon study included 79 patients undergoing median sternotomy for coronary revascularization. Study participants were randomized to either the drug or a control arm. Each participant received Exparel or normal saline placebo administered as a parasternal nerve block. Postoperative pain was rated according to the nonverbal pain scale or numeric rating scale. Total amount of narcotic pain medication used and patients' pain scores within the first 72 hours postoperatively were compared. Secondary outcomes compared the intensive care unit length of stay, hospital length of stay, time to extubation, time to return of bowel function, and time to return to work or daily activities. RESULTS: The primary endpoint of pain levels between the two groups demonstrated no significant difference when analyzing the individual time points postoperatively. However, overall pain levels were significantly lower in the study drug group (p = 0.04). There was no significant difference in the amount of analgesics required postoperatively or in secondary endpoints between the groups. CONCLUSIONS: Exparel does not provide an opioid-sparing benefit or any secondary outcome benefit compared with placebo. Exparel may be associated with a marginal decrease in postoperative pain levels. (Parasternal Nerve Bock in Cardiac Patients; NCT01826851.).


Subject(s)
Bupivacaine/administration & dosage , Nerve Block/methods , Pain, Postoperative/drug therapy , Sternotomy/methods , Aged , Anesthetics, Local/administration & dosage , Cardiac Surgical Procedures/methods , Double-Blind Method , Female , Follow-Up Studies , Humans , Intercostal Nerves , Male , Middle Aged , Pain Measurement , Pain, Postoperative/diagnosis , Prospective Studies , Treatment Outcome
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