Epicardial placement of human placental membrane protects from heart injury in a swine model of myocardial infarction.

Cardiac ischemic reperfusion injury (IRI) is paradoxically instigated by reestablishing blood-flow to ischemic myocardium typically from a myocardial infarction (MI). Although revascularization following MI remains the standard of care, effective strategies remain limited to prevent or attenuate IRI. We hypothesized that epicardial placement of human placental amnion/chorion (HPAC) grafts will protect against IRI. Using a clinically relevant model of IRI, swine were subjected to 45 min percutaneous ischemia followed with (MI + HPAC, n = 3) or without (MI only, n = 3) HPAC. Cardiac function was assessed by echocardiography, and regional punch biopsies were collected 14 days post-operatively. A deep phenotyping approach was implemented by using histological interrogation and incorporating global proteomics and transcriptomics in nonischemic, ischemic, and border zone biopsies. Our results established HPAC limited the extent of cardiac injury by 50% (11.0 ± 2.0% vs. 22.0 ± 3.0%, p = 0.039) and preserved ejection fraction in HPAC-treated swine (46.8 ± 2.7% vs. 35.8 ± 4.5%, p = 0.014). We present comprehensive transcriptome and proteome profiles of infarct (IZ), border (BZ), and remote (RZ) zone punch biopsies from swine myocardium during the proliferative cardiac repair phase 14 days post-MI. Both HPAC-treated and untreated tissues showed regional dynamic responses, whereas only HPAC-treated IZ revealed active immune and extracellular matrix remodeling. Decreased endoplasmic reticulum (ER)-dependent protein secretion and increased antiapoptotic and anti-inflammatory responses were measured in HPAC-treated biopsies. We provide quantitative evidence HPAC reduced cardiac injury from MI in a preclinical swine model, establishing a potential new therapeutic strategy for IRI. Minimizing the impact of MI remains a central clinical challenge. We present a new strategy to attenuate post-MI cardiac injury using HPAC in a swine model of IRI. Placement of HPAC membrane on the heart following MI minimizes ischemic damage, preserves cardiac function, and promotes anti-inflammatory signaling pathways.

Study of the Expression Transition of Cardiac Myosin Using Polarization-Dependent SHG Microscopy.

Detection of the transition between the two myosin isoforms α- and ß-myosin in living cardiomyocytes is essential for understanding cardiac physiology and pathology. In this study, the differences in symmetry of polarization spectra obtained from α- and ß-myosin in various mammalian ventricles and propylthiouracil-treated rats are explored through polarization-dependent second harmonic generation microscopy. Here, we report for the, to our knowledge, first time that α- and ß-myosin, as protein crystals, possess different symmetries: the former has C6 symmetry, and the latter has C3v. A single-sarcomere line scan further demonstrated that the differences in polarization-spectrum symmetry between α- and ß-myosin came from their head regions: the head and neck domains of α- and ß-myosin account for the differences in symmetry. In addition, the dynamic transition of the polarization spectrum from C6 to C3v line profile was observed in a cell culture in which norepinephrine induced an α- to ß-myosin transition.

Fluid type influences acute hydration and muscle performance recovery in human subjects.

BACKGROUND: Exercise and heat trigger dehydration and an increase in extracellular fluid osmolality, leading to deficits in exercise performance and thermoregulation. Evidence from previous studies supports the potential for deep-ocean mineral water to improve recovery of exercise performance post-exercise. We therefore wished to determine whether acute rehydration and muscle strength recovery was enhanced by deep-ocean mineral water following a dehydrating exercise, compared to a sports drink or mountain spring water. We hypothesized that muscle strength would decrease as a result of dehydrating exercise, and that recovery of muscle strength and hydration would depend on the type of rehydrating fluid. METHODS: Using a counterbalanced, crossover study design, female (n = 8) and male (n = 9) participants performed a dehydrating exercise protocol under heat stress until achieving 3% body mass loss. Participants rehydrated with either deep-ocean mineral water (Deep), mountain spring water (Spring), or a carbohydrate-based sports drink (Sports) at a volume equal to the volume of fluid loss. We measured relative hydration using salivary osmolality (Sosm) and muscle strength using peak torque from a leg extension maneuver. RESULTS: Sosm significantly increased (p < 0.0001) with loss of body mass during the dehydrating exercise protocol. Males took less time (90.0 ± 18.3 min; P < 0.0034) to reach 3% body mass loss when compared to females (127.1 ± 20.0 min). We used a mono-exponential model to fit the return of Sosm to baseline values during the rehydrating phase. Whether fitting stimulated or unstimulated Sosm, male and female participants receiving Deep as the hydrating fluid exhibited the most rapid return to baseline Sosm (p < 0.0001) regardless of the fit parameter. Males compared to females generated more peak torque (p = 0.0005) at baseline (308.3 ± 56.7 Nm vs 172.8 ± 40.8 Nm, respectively) and immediately following 3% body mass loss (276.3 ± 39.5 Nm vs 153.5 ± 35.9 Nm). Participants experienced a loss. We also identified a significant effect of rehydrating fluid and sex on post-rehydration peak torque (p < 0.0117). CONCLUSION: We conclude that deep-ocean mineral water positively affected hydration recovery after dehydrating exercise, and that it may also be beneficial for muscle strength recovery, although this, as well as the influence of sex, needs to be further examined by future research. TRIAL REGISTRATION: clincialtrials.gov PRS, NCT02486224 . Registered 08 June 2015.

Evidence of Likely Autochthonous Transmission of Chagas Disease in Arizona.

A healthy 16-year-old girl born and raised in Tucson, AZ, had screening and confirmatory testing revealing Chagas disease; clinical evaluation established that she had the indeterminate form of chronic Chagas disease with evidence of likely autochthonous transmission. Trypanosoma cruzi DNA was detected by conventional polymerase chain reaction in Triatoma rubida captured at her home.

Complete antithrombin replacement for anticoagulation for cardiopulmonary bypass to repair severe infective mitral valve endocarditis.

: We present a case of a 26-year-old patient with severe infective endocarditis complicated with cerebral septic emboli that required essentially complete replacement of his circulating antithrombin activity to achieve an activated coagulation time near 480 s. The need for this degree of antithrombin administration may have been secondary to ongoing systemic inflammation and consequent thrombin generation despite blood culture results demonstrating no bacteremia. In sum, ongoing loss of endogenous antithrombin activity secondary to inflammation and the need for more than 80% normal activity to conduct safe cardiopulmonary bypass may require extraordinary administration of exogenous antithrombin in similar settings.

Remodeling Failing Human Myocardium With Hybrid Cell/Matrix and Transmyocardial Revascularization.

Given the limited treatment options for advanced heart failure, the intrinsic regenerative properties of stem cells have been evaluated for myocardial remodeling. Previous stem cells techniques for myocardiocyte remodeling have been limited by the low cellular retention. Presented is a hybrid approach for remodeling infarcted myocardium through implantation of allogeneic human amniotic fluid-derived mesenchymal stem cells within micronized human allograft-derived liquid matrix during the performance of transmyocardial revascularization (TMR). Given the induced increase in vascular density from TMR, we hypothesize that it may serve as a therapeutic delivery system for stem cell placement into damaged myocardium. We present a patient with ischemic cardiomyopathy and refractory angina, who clinically improved after this hybrid therapy of intraoperative TMR and placement of amniotic fluid-derived mesenchymal stem cells and liquid matrix within the TMR channels. Noninvasive testing of myocardial viability biomarkers utilizing both cardiac magnetic resonance imaging and thallium imaging supported the clinical improvement in cardiac symptom may be related to ventricular remodeling in a region of infarct with subsequent functional improvement.

3D printed mitral valve models: affordable simulation for robotic mitral valve repair.

OBJECTIVES: 3D printed mitral valve (MV) models that capture the suture response of real tissue may be utilized as surgical training tools. Leveraging clinical imaging modalities, 3D computerized modelling and 3D printing technology to produce affordable models complements currently available virtual simulators and paves the way for patient- and pathology-specific preoperative rehearsal. METHODS: We used polyvinyl alcohol, a dissolvable thermoplastic, to 3D print moulds that were casted with liquid platinum-cure silicone yielding flexible, low-cost MV models capable of simulating valvular tissue. Silicone-moulded MV models were fabricated for 2 morphologies: the normal MV and the P2 flail. The moulded valves were plication and suture tested in a laparoscopic trainer box with a da Vinci Si robotic surgical system. One cardiothoracic surgery fellow and 1 attending surgeon qualitatively evaluated the ability of the valves to recapitulate tissue feel through surveys utilizing the 5-point Likert-type scale to grade impressions of the valves. RESULTS: Valves produced with the moulding and casting method maintained anatomical dimensions within 3% of directly 3D printed acrylonitrile butadiene styrene controls for both morphologies. Likert-type scale mean scores corresponded with a realistic material response to sutures (5.0/5), tensile strength that is similar to real MV tissue (5.0/5) and anatomical appearance resembling real MVs (5.0/5), indicating that evaluators 'agreed' that these aspects of the model were appropriate for training. Evaluators 'somewhat agreed' that the overall model durability was appropriate for training (4.0/5) due to the mounting design. Qualitative differences in repair quality were notable between fellow and attending surgeon. CONCLUSIONS: 3D computer-aided design, 3D printing and fabrication techniques can be applied to fabricate affordable, high-quality educational models for technical training that are capable of differentiating proficiency levels among users.

A dual therapy of off-pump temporary left ventricular extracorporeal device and amniotic stem cell for cardiogenic shock.

BACKGROUND: Temporary mechanical circulatory support device without sternotomy has been highly advocated for severe cardiogenic shock patient but little is known when coupled with amniotic stem cell therapy. CASE PRESENTATION: This case reports the first dual therapy of temporary left ventricular extracorporeal device CentriMag with distal banding technique and human amniotic stem cell injection for treating a severe refractory cardiogenic shock of an 68-year-old female patient. A minimally-invasive off-pump LVAD was established by draining from the left ventricle and returning to the right axillary artery with distal arterial banding to prevent right upper extremity hyperperfusion. Amniotic stem cells were injected intramyocardially at the left ventricular apex, lateral wall, inferior wall, and right subclavian vein. CONCLUSION: The concomitant use of the temporary minimally-invasive off-pump CentriMag placement and stem cell therapy not only provided an alternative to cardiopulmonary bypass and full-median sternotomy procedures but may have also synergistically enhanced myocardial reperfusion and regeneration.

A 24-year-old male with a painful and cold lower extremity.

CLINICAL INTRODUCTION: A 24-year-old male presented to the emergency department with intense pain in his right lower extremity. He has a medical history significant for systemic lupus erythematosus and antiphospholipid syndrome. He also had four prior episodes of deep venous thromboses on rivaroxaban. The patient stated that early in the morning, he started to feel intense pain that started from his knee and progressed to his calf, with associated numbness and paraesthesia. On physical examination, the limb felt cold with absent right popliteal and dorsalis pedis pulses. He was immediately taken for embolectomy after discovery of a distal common femoral artery occlusion. The patient's blood cultures remained negative. X-plane imaging on real-time three-dimensional transoesophageal echocardiography (RT-3DTEE) of the aortic valve (figure 1A) and colour Doppler (figure 1B) are shown. QUESTION: What is the diagnosis and management for this patient (assuming the patient will stay anticoagulated for life)? Infective endocarditis (IE); antibiotics and valve replacementLibman-Sacks endocarditis; corticosteroidsIE; antibiotics onlyLibman-Sacks endocarditis; valve replacementLibman-Sacks endocarditis; continuing anticoagulation only heartjnl;103/10/765/HEARTJNL2016310872F1F1HEARTJNL2016310872F1Figure 1Visualisation of the aortic valve on (A) X-plane imaging on real-time three-dimensional transoesophageal echocardiography (RT-3DTEE) and (B) colour Doppler.

A Physical Heart Failure Simulation System Utilizing the Total Artificial Heart and Modified Donovan Mock Circulation.

With the growth and diversity of mechanical circulatory support (MCS) systems entering clinical use, a need exists for a robust mock circulation system capable of reliably emulating and reproducing physiologic as well as pathophysiologic states for use in MCS training and inter-device comparison. We report on the development of such a platform utilizing the SynCardia Total Artificial Heart and a modified Donovan Mock Circulation System, capable of being driven at normal and reduced output. With this platform, clinically relevant heart failure hemodynamics could be reliably reproduced as evidenced by elevated left atrial pressure (+112%), reduced aortic flow (-12.6%), blunted Starling-like behavior, and increased afterload sensitivity when compared with normal function. Similarly, pressure-volume relationships demonstrated enhanced sensitivity to afterload and decreased Starling-like behavior in the heart failure model. Lastly, the platform was configured to allow the easy addition of a left ventricular assist device (HeartMate II at 9600 RPM), which upon insertion resulted in improvement of hemodynamics. The present configuration has the potential to serve as a viable system for training and research, aimed at fostering safe and effective MCS device use.

Minimally invasive approach for percutaneous CentriMag right ventricular assist device support using a single PROTEKDuo Cannula.

BACKGROUND: Right ventricular failure is a serious complication after left ventricular assist device placement. CASE PRESENTATION: A 70-year-old male in decompensated heart failure with right ventricular failure after the placement of a left ventricular assist device. A single dual-lumen PROTEKDuo cannula was inserted percutaneously via the internal jugular vein to draw blood from the right atrium and return into the pulmonary artery using the CentriMag system, by passing the failing ventricle. The patient was successfully weaned from right ventricular assist device. CONCLUSIONS: In comparison to two-cannula conventional procedures, this right ventrivular assist device system improves patient rehabilitation and minimizes blood loss and risk of infection, while shortening procedure time and improving clinical outcomes in right ventricular failure.

Total Artificial Heart, Augmented by Venovenous Extracorporeal Membrane Oxygenation.

Shortly after SynCardia total artificial heart (TAH) implant, venovenous extracorporeal membrane oxygenation (ECMO) via a 31 Fr Avalon cannula was used for profound hypoxic lung dysfunction. Immediately after starting ECMO, TAH flow increased by 1.5-2.0 L/min, presumably because of augmented TAH filling by the ECMO jet.

Hemolysate-mediated platelet aggregation: an additional risk mechanism contributing to thrombosis of continuous flow ventricular assist devices.

Despite the clinical success and growth in the utilization of continuous flow ventricular assist devices (cfVADs) for the treatment of advanced heart failure, hemolysis and thrombosis remain major limitations. Inadequate and/or ineffective anticoagulation regimens, combined with high pump speed and non-physiological flow patterns, can result in hemolysis which often is accompanied by pump thrombosis. An unexpected increase in cfVADs thrombosis was reported by multiple major VAD implanting centers in 2014, highlighting the association of hemolysis and a rise in lactate dehydrogenase (LDH) presaging thrombotic events. It is well established that thrombotic complications arise from the abnormal shear stresses generated by cfVADs. What remains unknown is the link between cfVAD-associated hemolysis and pump thrombosis. Can hemolysis of red blood cells (RBCs) contribute to platelet aggregation, thereby, facilitating prothrombotic complications in cfVADs? Herein, we examine the effect of RBC-hemolysate and selected major constituents, i.e., lactate dehydrogenase (LDH) and plasma free hemoglobin (pHb) on platelet aggregation, utilizing electrical resistance aggregometry. Our hypothesis is that elements of RBCs, released as a result of shear-mediated hemolysis, will contribute to platelet aggregation. We show that RBC hemolysate and pHb, but not LDH, are direct contributors to platelet aggregation, posing an additional risk mechanism for cfVAD thrombosis.

Physiological characterization of the SynCardia total artificial heart in a mock circulation system.

The SynCardia total artificial heart (TAH) has emerged as an effective, life-saving biventricular replacement system for a wide variety of patients with end-stage heart failure. Although the clinical performance of the TAH is established, modern physiological characterization, in terms of elastance behavior and pressure-volume (PV) characterization has not been defined. Herein, we examine the TAH in terms of elastance using a nonejecting left ventricle, and then characterize the PV relation of the TAH by varying preload and afterload parameters using a Donovan Mock Circulatory System. We demonstrate that the TAH does not operate with time-varying elastance, differing from the human heart. Furthermore, we show that the TAH has a PV relation behavior that also differs from that of the human heart. The TAH does exhibit Starling-like behavior, with output increasing via preload-dependent mechanisms, without reliance on an alteration of inotropic state within the operating window of the TAH. Within our testing range, the TAH is insensitive to variations in afterload; however, this insensitivity has a limit, the limit being the maximum driving pressure of the pneumatic driver. Understanding the physiology of the TAH affords insight into the functional parameters that govern artificial heart behavior providing perspective on differences compared with the human heart.

Diet and sex modify exercise and cardiac adaptation in the mouse.

The heart adapts to exercise stimuli in a sex-dimorphic manner when mice are fed the traditional soy-based chow. Females undergo more voluntary exercise (4 wk) than males and exhibit more cardiac hypertrophy per kilometer run (18, 32). We have found that diet plays a critical role in cage wheel exercise and cardiac adaptation to the exercise stimulus in this sex dimorphism. Specifically, feeding male mice a casein-based, soy-free diet increases daily running distance over soy-fed counterparts to equal that of females. Moreover, casein-fed males have a greater capacity to increase their cardiac mass in response to exercise compared with soy-fed males. To further explore the biochemical mechanisms for these differences, we performed a candidate-based RT-PCR screen on genes previously implicated in diet- or exercise-based cardiac hypertrophy. Of the genes screened, many exhibit significant exercise, diet, or sex effects but only transforming growth factor-ß1 shows a significant three-way interaction with no genes showing a two-way interaction. Finally, we show that the expression and activity of adenosine monophosphate-activated kinase-α2 and acetyl-CoA carboxylase is dependent on exercise, diet, and sex.

Three-dimensional scaffolds of acellular human and porcine lungs for high throughput studies of lung disease and regeneration.

Acellular scaffolds from complex whole organs such as lung are being increasingly studied for ex vivo organ generation and for in vitro studies of cell-extracellular matrix interactions. We have established effective methods for efficient de and recellularization of large animal and human lungs including techniques which allow multiple small segments (∼ 1-3 cm(3)) to be excised that retain 3-dimensional lung structure. Coupled with the use of a synthetic pleural coating, cells can be selectively physiologically inoculated via preserved vascular and airway conduits. Inoculated segments can be further sliced for high throughput studies. Further, we demonstrate thermography as a powerful noninvasive technique for monitoring perfusion decellularization and for evaluating preservation of vascular and airway networks following human and porcine lung decellularization. Collectively, these techniques are a significant step forward as they allow high throughput in vitro studies from a single lung or lobe in a more biologically relevant, three-dimensional acellular scaffold.

Extensive endarterectomy and reconstruction of the left anterior descending artery: early and late outcomes.

OBJECTIVES: Coronary endarterectomy has been shown to be an effective adjunctive technique of revascularization for diffuse coronary artery disease. A long arteriotomy and reconstruction of the left anterior descending artery (LAD) are occasionally required for complete extraction of the atherosclerotic plaque. The aim of this study was to examine early and late results of this technique and compare 2 different reconstruction methods. METHODS: We retrospectively reviewed 224 consecutive patients who underwent extensive LAD endarterectomy and reconstruction between January 1992 and March 2010. For reconstruction, 101 patients underwent saphenous vein patch and LAD grafting (group A) and 123 patients had left internal thoracic artery onlay patch grafting (group B). We compared early and late outcomes and assessed the association of the reconstruction method and long-term survival. RESULTS: The mean age was 66 and 67 years in groups A and B, respectively. Operative mortality was 3.0% and 4.1%, and the incidence of perioperative myocardial infarction in the LAD territory was 4.0% and 4.1% in groups A and B, respectively. There was no significant difference in early operative outcomes (P > .05). Actuarial 5-year survival was 78.6% and 87.1% and 10-year survival was 45.4% and 49.4% in groups A and B, respectively. Cox hazard proportional analysis showed that the reconstruction method did not have a significant impact on long-term survival. CONCLUSIONS: Extensive LAD endarterectomy and reconstruction is a safe and feasible technique of revascularization for diffuse coronary artery disease. The reconstruction method should be based on the availability of conduits and length of the arteriotomy.

Accommodation: preventing injury in transplantation and disease.

Humoral immunity, as a cause of damage to blood vessels, poses a major barrier to successful transplantation of organs. Under some conditions, humoral immunity causes little or no damage to an organ graft. We have referred to this condition, in which a vascularized graft functions in the face of humoral immunity directed against it, as "accommodation." In this paper, we review changes in the graft and in the host that may account for accommodation, and we consider that what we call accommodation of organ grafts may occur widely in the context of immune responses, enabling immune responses to target infectious organisms without harming self-tissues.