Trabecular cutting: a novel surgical therapy to increase diastolic compliance.

Heart failure with preserved ejection fraction (HFpEF) is a common cause of hospital admission in patients over 65 yr old and has high mortality. HFpEF is characterized by left ventricular (LV) hypertrophy that reduces compliance. Current HFpEF therapies control symptoms, but no existing medications or therapies can sustainably increase LV compliance. LV trabeculae develop hypertrophy and fibrosis that contribute to reduced LV compliance. This study expands our previous results in ex vivo human hearts to show that severing LV trabeculae increases diastolic compliance in an ex vivo working rabbit heart model. Trabecular cutting was performed in ex vivo rabbit hearts set up in a working heart perfusion system perfused with oxygenated Krebs-Henseleit buffer. A hook was inserted in the LV to cut trabeculae. End-systolic and end-diastolic pressure-volume relationships during transient preload reduction were recorded using an admittance catheter in the following three groups: control (no cutting; n = 9), mild cutting (15 cuts; n = 5), and aggressive cutting (30 cuts; n = 5). In a second experiment, each heart served as its own control. Hemodynamic data were recorded before and after trabecular cutting (n = 10) or sham cutting (n = 5) within the same heart. In the first experiments, trabecular cutting did not affect systolic function (P > 0.05) but significantly increased overall diastolic compliance (P = 0.009). Greater compliance was seen as trabecular cutting increased (P = 0.002, r2 = 0.435). In the second experiment, significant increases in systolic function (P = 0.048) and diastolic compliance (P = 0.002) were seen after trabecular cutting compared with baseline. In conclusion, trabecular cutting significantly increases diastolic compliance without reducing systolic function.NEW & NOTEWORTHY We postulate that, in mammalian hearts, free-running trabeculae carneae exist to provide tensile support to the left ventricle and minimize diastolic wall stress. Because of hypertrophy and fibrosis of trabeculae in patients with left ventricular hypertrophy, this supportive role can become pathologic, worsening diastolic compliance. We demonstrate a novel operation involving cutting trabeculae as a method to acutely increase diastolic compliance in patients presenting with heart failure and diastolic dysfunction to improve their left ventricle compliance.

Tunable Buckled Beams with Mesoporous PVDF-TrFE/SWCNT Composite Film for Energy Harvesting.

By incorporating mesoporous piezoelectric materials and tuning mechanical boundary conditions a simple beam structure can significantly take advantage of limited mechanical displacements for energy harvesting. Specifically, we employed a mesoporous PVDF-TrFE composite thin film mixed with single-wall carbon nanotubes to improve the formation of the crystalline phase in this piezoelectric polymer. The film was then patterned on a thin buckled beam to form a compact energy harvester, which was used to study the effects of two boundary conditions, including the end rotation angle and the location of a mechanical stop along the beam. We carefully designed controlled experiments using mesoporous PVDF-TrFE film and PVDF-TrFE/SWCNT composite films, both of which were tested under two cases of boundary conditions, namely, the rotation of the end angle and the addition of a mechanical stop. The voltage and current of the energy harvester under these two boundary conditions were, respectively, increased by approximately 160.1% and 200.5% compared to the results of its counterpart without imposing any boundary conditions. Thereby, our study offers a promising platform for efficiently powering implantable and wearable devices for harnessing energy from the human body which would otherwise have been wasted.

Nox4-derived reactive oxygen species mediate cardiomyocyte injury in early type 1 diabetes.

Oxidative stress contributes to diabetic cardiomyopathy. This study explored the role of the NADPH oxidase Nox4 as a source of reactive oxygen species (ROS) involved in the development of diabetic cardiomyopathy. Phosphorothioated antisense (AS) or sense (S) oligonucleotides for Nox4 were administered for 2 wk to rats made diabetic by streptozotocin. NADPH oxidase activity, ROS generation, and the expression of Nox4, but Nox1 or Nox2, were increased in left ventricular tissue of the diabetic rats. Expression of molecular markers of hypertrophy and myofibrosis including fibronectin, collagen, α-smooth muscle actin, and ß-myosin heavy chain were also increased. These parameters were attenuated by the administration of AS but not S Nox4. Moreover, the impairment of contractility observed in diabetic rats was prevented in AS- but not S-treated animals. Exposure of cultured cardiac myocytes to 25 mM glucose [high glucose (HG)] increased NADPH oxidase activity, the expression of Nox4, and molecular markers of cardiac injury. These effects of HG were prevented in cells infected with adenoviral vector containing a dominant negative form of Nox4. This study provides strong evidence that Nox4 is an important source of ROS in the left ventricle and that Nox4-derived ROS contribute to cardiomyopathy at early stages of type 1 diabetes.