Rabya Saraf

Hemodynamic Testing of Patient-Specific Mitral Valves Using a Pulse Duplicator: A Clinical Application of Three-Dimensional Printing

OBJECTIVE To evaluate the feasibility of obtaining hemodynamic metrics of echocardiographically derived 3-dimensional printed mitral valve models deployed in a pulse-duplicator chamber. DESIGN Exploratory study. SETTING Tertiary-care university hospital. PARTICIPANTS Percutaneous MitraClip procedure patient. INTERVENTIONS Three-dimensional R-wave gated, full-volume transesophageal echocardiography images were obtained after deployment of the MitraClip device. A high-quality diastolic frame of the mitral valve was segmented using Mimics Innovation Suite and merged with a flange. The data were exported as a stereolithography (.stl) file, and a rigid 3-dimensional model was printed using a MakerBot Replicator 2 printer. A flexible silicone cast then was created and deployed in the pulse-duplicator chamber filled with a blood-mimicking fluid. MEASUREMENTS AND MAIN RESULTS The authors were able to obtain continuous-wave Doppler tracings of the valve inflow with a transesophageal echocardiography transducer. They also were able to generate diastolic ventricular and atrial pressure tracings. Pressure half-time and mitral valve area were computed from these measurements. CONCLUSION This pulse duplicator shows promising applications in hemodynamic testing of patient-specific anatomy. Future modifications to the system may allow for visualization and data collection of gradients across the aortic valve.

Neuropeptide Y is an angiogenic factor in cardiovascular regeneration

In diabetic cardiomyopathy, there is altered angiogenic signaling and increased oxidative stress. As a result, anti-angiogenic and pro-inflammatory pathways are activated. These disrupt cellular metabolism and cause fibrosis and apoptosis, leading to pathological remodeling. The autonomic nervous system and neurotransmitters play an important role in angiogenesis. Therapies that promote angiogenesis may be able to relieve the pathology in these disease states. Neuropeptide Y (NPY) is the most abundantly produced and expressed neuropeptide in the central and peripheral nervous systems in mammals and plays an important role in promoting angiogenesis and cardiomyocyte remodeling. It produces effects through G-protein-coupled Y receptors that are widely distributed and also present on the myocardium. Some of these receptors are also involved in diseased states of the heart. NPY has been implicated as a potent growth factor, causing cell proliferation in multiple systems while the NPY3-36 fragment is selective in stimulating angiogenesis and cardiomyocyte remodeling. Current research is focusing on developing a drug delivery mechanism for NPY to prolong therapy without having significant systemic consequences. This could be a promising innovation in the treatment of diabetic cardiomyopathy and ischemic heart disease.

Cardiopulmonary Bypass Decreases Activation of the Signal Transducer and Activator of Transcription 3 (STAT3) Pathway in Diabetic Human Myocardium

BACKGROUND Cardiopulmonary bypass (CPB) is associated with increased myocardial oxidative stress and apoptosis in diabetic patients. A mechanistic understanding of this relationship could have therapeutic value. To establish a possible mechanism, we compared the activation of the cardioprotective signal transducer and activator of transcription 3 (STAT3) pathway between patients with uncontrolled diabetes (UD) and nondiabetic (ND) patients. METHODS Right atrial tissue and serum were collected before and after CPB from 80 patients, 39 ND and 41 UD (HbA1c ≥ 6.5), undergoing cardiac operations. The samples were evaluated with Western blotting, immunohistochemistry, and microarray. RESULTS On Western blot, leptin levels were significantly increased in ND post-CPB (p < 0.05). Compared with ND, the expression of Janus kinase 2 and phosphorylation (p-) of STAT3 was significantly decreased in UD (p < 0.05). The apoptotic proteins p-Bc12/Bc12 and caspase 3 were significantly increased (p < 0.05), antiapoptotic proteins Mcl-1, Bcl-2, and p-Akt were significantly decreased (p < 0.05) in UD compared with ND. The microarray data suggested significantly increased expression of interleukin-6 R, proapoptotic p-STAT1, caspase 9, and decreased expression of Bc12 and protein inhibitor of activated STAT1 antiapoptotic genes (p = 0.05) in the UD patients. The oxidative stress marker nuclear factor-κB was significantly higher (p < 0.05) in UD patients post-CPB compared with the pre-CPB value, but was decreased, albeit insignificantly, in ND patients post-CPB. CONCLUSIONS Compared with ND, UD myocardium demonstrated attenuation of the cardioprotective STAT3 pathway. Identification of this mechanism offers a possible target for therapeutic modulation.

Neuropeptide Y3-36 incorporated into PVAX nanoparticle improves functional blood flow in a murine model of hind limb ischemia

We generated a novel nanoparticle called PVAX, which has intrinsic antiapoptotic and anti-inflammatory properties. This nanoparticle was loaded with neuropeptide Y3-36 (NPY3-36), an angiogenic neurohormone that plays a central role in angiogenesis. Subsequently, we investigated whether PVAX-NPY3-36 could act as a therapeutic agent and induce angiogenesis and vascular remodeling in a murine model of hind limb ischemia. Adult C57BL/J6 mice (n = 40) were assigned to treatment groups: control, ischemia PBS, ischemia PVAX, ischemia NPY3-36, and Ischemia PVAX-NPY3-36 Ischemia was induced by ligation of the femoral artery in all groups except control and given relevant treatments (PBS, PVAX, NPY3-36, and PVAX-NPY3-36). Blood flow was quantified using laser Doppler imaging. On days 3 and 14 posttreatment, mice were euthanized to harvest gastrocnemius muscle for immunohistochemistry and immunoblotting. Blood flow was significantly improved in the PVAX-NPY3-36 group after 14 days. Western blot showed an increase in angiogenic factors VEGF-R2 and PDGF-β (P = 0.0035 and P = 0.031, respectively) and antiapoptotic marker Bcl-2 in the PVAX-NPY3-36 group compared with ischemia PBS group (P = 0.023). Proapoptotic marker Smad5 was significantly decreased in the PVAX-NPY3-36 group as compared with the ischemia PBS group (P = 0.028). Furthermore, Y2 receptors were visualized in endothelial cells of newly formed arteries in the PVAX-NPY3-36 group. In conclusion, we were able to show that PVAX-NPY3-36 can induce angiogenesis and arteriogenesis as well as improve functional blood flow in a murine model of hind limb ischemia.NEW & NOTEWORTHY Our research project proposes a novel method for drug delivery. Our patented PVAX nanoparticle can detect areas of ischemia and oxidative stress. Although there have been studies about delivering angiogenic molecules to areas of ischemic injury, there are drawbacks of nonspecific delivery as well as short half-lives. Our study is unique because it can specifically deliver NPY3-36 to ischemic tissue and appears to extend the amount of time therapy is available, despite NPY3-36s short half-life.

Early Cellular Changes in the Ascending Aorta and Myocardium in a Swine Model of Metabolic Syndrome

Background Metabolic syndrome is associated with pathological remodeling of the heart and adjacent vessels. The early biochemical and cellular changes underlying the vascular damage are not fully understood. In this study, we sought to establish the nature, extent, and initial timeline of cytochemical derangements underlying reduced ventriculo-arterial compliance in a swine model of metabolic syndrome. Methods Yorkshire swine (n = 8 per group) were fed a normal diet (ND) or a high-cholesterol (HCD) for 12 weeks. Myocardial function and blood flow was assessed before harvesting the heart. Immuno-blotting and immuno-histochemical staining were used to assess the cellular changes in the myocardium, ascending aorta and left anterior descending artery (LAD). Results There was significant increase in body mass index, blood glucose and mean arterial pressures (p = 0.002, p = 0.001 and p = 0.024 respectively) in HCD group. At the cellular level there was significant increase in anti-apoptotic factors p-Akt (p = 0.007 and p = 0.002) and Bcl-xL (p = 0.05 and p = 0.01) in the HCD aorta and myocardium, respectively. Pro-fibrotic markers TGF-β (p = 0.01), pSmad1/5 (p = 0.03) and MMP-9 (p = 0.005) were significantly increased in the HCD aorta. The levels of pro-apoptotic p38MAPK, Apaf-1 and cleaved Caspase3 were significantly increased in aorta of HCD (p = 0.03, p = 0.04 and p = 0.007 respectively). Similar changes in coronary arteries were not observed in either group. Functionally, the high cholesterol diet resulted in significant increase in ventricular end systolic pressure and–dp/dt (p = 0.05 and p = 0.007 respectively) in the HCD group. Conclusion Preclinical metabolic syndrome initiates pro-apoptosis and pro-fibrosis pathways in the heart and ascending aorta, while sparing coronary arteries at this early stage of dietary modification.

A Complex Atrial Septal Defect and Three-Dimensional Echocardiography: A Question and an Answer

From the Departments of *Anesthesia; and †Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. Address reprint requests to Feroze Mahmood, MD, Harvard Medical School, Beth Israel Deaconess Medical Center, 1 Deaconess Road, CC-454, Boston, MA, 02215. E-mail: fmahmood@bidmc.harvard.edu

The Coanda Effect.

582 www.anesthesia-analgesia.org September 2016 • Volume 123 • Number 3 A 57-year-old man presented for an urgent coronary artery bypass grafting surgery. On routine intraoperative 2-dimensional transesophageal echocardiography (2D TEE), an eccentric mitral regurgitant (MR) jet hugging the left atrial (LA) wall was appreciated in the 2D midesophageal long-axis view. (Figure 1A; Supplemental Digital Content 1, Video 1, left panel, http://links.lww.com/AA/B459) and 3dimensional (3D) TEE (Figure 1B; Supplemental Digital Content 1, Video 1, right panel, http://links.lww.com/AA/B459). The MR was graded as moderate to severe, and mitral valve repair was performed using an annuloplasty ring.

A Tight Spot After Pulmonary Vein Catheter Ablation

A 52-YEAR-OLD woman with a history of embolic stroke due to paroxysmal atrial fibrillation was referred to the authors’ institution for epicardial surgical pulmonary vein isolation with left atrial appendage resection. The patient had 2 previous failed pulmonary vein catheter ablations. Dense fibrous tissue surrounding the left upper pulmonary vein was seen during surgery. Transesophageal echocardiography revealed the following image (Fig 1). What is the diagnosis?

Cardiac Imaging-3-Dimensional Echocardiography.

Perioperative transesophageal echocardiography (TEE) has established itself as a vital intraoperative imaging modality. Its role has evolved from being a hemodynamic monitor to a procedural adjunct. With advances in cardiac surgery increasing the popularity of minimally invasive approaches to structural heart diseases, TEE imaging has become an integral component of intraoperative decision-making. The traditional 2-dimensional (2D) TEE examination is limited in that it interrogates a complex anatomic structure that does not share any structural axes with the rest of the body (Fig. 1). It is difficult to image the heart through narrow echo windows with thin 2D scan planes (Fig. 2). There is also significant interpolation to mentally reconstruct a 3-dimensional (3D) model of the heart. Therefore, despite a dynamic display of cardiac anatomy, traditional 2D imaging is spatially limited. Although the limitation of 2D interrogation of a complex anatomic structure has always been recognized, technological impediments have precluded introduction of 3D imaging until recently. Traditional 2D TEE probes generally have 300 piezoelectric crystals arranged in an array at the tip of the TEE probe. The active element of most acoustic transducers used today is a piezoelectric ceramic, which can be cut in various ways to produce different wave modes. The prefix piezois Greek for “press” or “squeeze” and the word piezoelectric literally means electricity caused by pressure. A piezoelectric sensor then is a device that measures change in temperature, pressure, acceleration, or force by converting it into electrical charge. These elements are sequentially fired electrically to generate a razor-thin scan plane. The