Here, we report advanced materials and devices that enable highefficiency mechanical-to-electrical energy conversion from the natural contractile and relaxation motions of the heart, lung, and diaphragm, demonstrated in several different animal models, each of which has organs with sizes that approach human scales. A cointegrated collection of such energy-harvesting elements with rectifiers and microbatteries provides an entire flexible system, capable of viable integration with the beating heart via medical sutures and operation with efficiencies of ∼2%. Additional experiments, computational models, and results in multilayer configurations capture the key behaviors, illuminate essential design aspects, and offer sufficient power outputs for operation of pacemakers, with or without battery assist.biomedical implants | flexible electronics | transfer printing | wearable electronics | heterogeneous integration N early all classes of active wearable and implantable biomedical devices rely on some form of battery power for operation. Heart rate monitors, pacemakers, implantable cardioverterdefibrillators, and neural stimulators together represent a broad subset of bioelectronic devices that provide continuous diagnostics and therapy in this mode. Although advances in battery technology have led to substantial reductions in overall sizes and increases in storage capacities, operational lifetimes remain limited, rarely exceeding a few days for wearable devices and a few years for implants. Surgical procedures to replace the depleted batteries of implantable devices are thus essential, exposing patients to health risks, heightened morbidity, and even potential mortality. The health burden and costs are substantial, and thus motivate efforts to eliminate batteries altogether, or to extend their lifetimes in a significant way.Investigations into energy-harvesting strategies to replace batteries demonstrate several unusual ways to extract power from chemical, mechanical, electrical, and thermal processes in the human body (1, 2). Examples include use of glucose oxidation (3), electric potentials of the inner ear (4), mechanical movements of limbs, and natural vibrations of internal organs (5-7). Such phenomena provide promising opportunities for power supply to wearable and implantable devices (6-8). A recent example involves a hybrid kinetic device integrated with the heart for applications with pacemakers (7). More speculative approaches, based on analytical models of harvesting from pressure-driven deformations of an artery by magneto-hydrodynamics, also exist (9).Cardiac and lung motions, in particular, serve as inexhaustible sources of energy during the lifespan of a patient. Mechanicalto-electrical transduction mechanisms in piezoelectric materials offer viable routes to energy harvesting in such cases, as demonstrated and analyzed by several groups recently (10-17). For example, proposals exist for devices that convert heartbeat vibrations into electrical energy using resonantly coupled motions of thick (1-2 mm) pi...

Our analysis demonstrated that more than 2 million life-years were saved to date by solid-organ transplants during a 25-year study period. Transplants should be supported and organ donation encouraged.

The increased risk of POI and length of hospitalization posed by postoperative hyperglycemia is independent of diabetic status and needs further evaluation to assess for possible benefits of postoperative glycemic control in patients who have undergone general surgery.

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 (∼1–3cm3) 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.

Pulmonary vascular remodeling characterized by concentric wall thickening and intraluminal obliteration is a major contributor to the elevated pulmonary vascular resistance in patients with idiopathic pulmonary arterial hypertension (IPAH). Here we report that increased hypoxia-inducible factor 2α (HIF-2α) in lung vascular endothelial cells (LVECs) under normoxic conditions is involved in the development of pulmonary hypertension (PH) by inducing endothelial-to-mesenchymal transition (EndMT), which subsequently results in vascular remodeling and occlusive lesions. We observed significant EndMT and markedly increased expression of SNAI, an inducer of EndMT, in LVECs from patients with IPAH and animals with experimental PH compared with normal controls. LVECs isolated from IPAH patients had a higher level of HIF-2α than that from normal subjects, whereas HIF-1α was upregulated in pulmonary arterial smooth muscle cells (PASMCs) from IPAH patients. The increased HIF-2α level, due to downregulated prolyl hydroxylase domain protein 2 (PHD2), a prolyl hydroxylase that promotes HIF-2α degradation, was involved in enhanced EndMT and upregulated SNAI1/2 in LVECs from patients with IPAH. Moreover, knockdown of HIF-2α (but not HIF-1α) with siRNA decreases both SNAI1 and SNAI2 expression in IPAH-LVECs. Mice with endothelial cell (EC)-specific knockout (KO) of the PHD2 gene, egln1 (egln1), developed severe PH under normoxic conditions, whereas Snai1/2 and EndMT were increased in LVECs of egln1 mice. EC-specific KO of the HIF-2α gene, hif2a, prevented mice from developing hypoxia-induced PH, whereas EC-specific deletion of the HIF-1α gene, hif1a, or smooth muscle cell (SMC)-specific deletion of hif2a, negligibly affected the development of PH. Also, exposure to hypoxia for 48-72 h increased protein level of HIF-1α in normal human PASMCs and HIF-2α in normal human LVECs. These data indicate that increased HIF-2α in LVECs plays a pathogenic role in the development of severe PH by upregulating SNAI1/2, inducing EndMT, and causing obliterative pulmonary vascular lesions and vascular remodeling.

Background-We investigated the potential of conversion to sirolimus (SRL) as a primary immunosuppressant in attenuating cardiac allograft vasculopathy progression. Methods and Results-Twenty-nine cardiac transplant recipients were converted to SRL 3.8Ϯ3.4 years after transplantation with complete calcineurin inhibitor (CNI) withdrawal. Secondary immunosuppressants (azathioprine or mycophenolate) and steroids remained unchanged. Forty patients (controls) 4.8Ϯ4.0 years from transplantation were maintained on CNIs. Three-dimensional intravascular ultrasound studies were performed at baseline and 12.1Ϯ2.6 months later.

Background-Use of an internal mammary artery (IMA) is a well-recognized, nationally endorsed quality indicator for evaluating the process of operative care for coronary artery bypass graft surgery.

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.