Background The development of a ventricular septal defect(VSD) after myocardial infarction(MI) is an uncommon but highly lethal complication. We examined the Society of Thoracic Surgeons(STS) database to characterize patients undergoing surgical repair of post-MI VSD and to identify risk factors for poor outcomes. Methods This was a retrospective review of the STS database to identify adult(≥18 years) patients who underwent post-MI VSD repair between 1999–2010. Patients with congenital heart disease were excluded. The primary outcome was operative mortality. The covariates in the current STS model for predicted coronary artery bypass(CABG) operative mortality were incorporated in a logistic regression model in this cohort. Results There were 2,876 patients included. Mean age was 68±11 years, and 1,624(56.5%) were men. 215(7.5%) patients had prior CABG surgery, 950(33%) had prior percutaneous intervention, and 1,869(65.0%) were supported preoperatively with an intra-aortic balloon pump. Surgical status was urgent in 1,007(35.0%) and emergent in 1,430(49.7%). Concomitant CABG was performed in 1,837(63.9%). Operative mortality was 54.1%(1,077/1,990) if repair was ≤7 days from MI, and 18.4%(158/856) if >7 days from MI. Multivariable analysis identified several factors associated with increased odds of operative mortality. Conclusions In the largest study to date to examine post-MI VSD repair, ventricular septal rupture remains a devastating complication. As alternative therapies emerge to treat this condition, these results will serve as a benchmark for future comparisons.

Preparation of hippocampal slices and perfusionAll experiments were performed in the CA1 or CA3 regions of hippocampal brain slices prepared from Sprague-Dawley rats (175-250 g). Rats were anaesthetized with ethyl ether and decapitated. The experimental protocol was reviewed and approved by the Institution Animal Care and Use Committee. The brain was rapidly removed and one hemisphere glued to the stage of a Vibroslicer (Vibroslice, Campden Instruments Ltd, London, UK) Slicing was carried out in cold (3-4°C), oxygenated sucrose-based artificial cerebrospinal fluid (ACSF) consisting of (mM): sucrose 220, KCl 3, NaH 2 PO 4 1.25, MgSO 4 2, NaHCO 3 26, CaCl 2 2, dextrose 10. The resulting 350 mm thick slices were immediately transferred to a holding chamber with 'normal' ACSF consisting of (mM): NaCl 124, KCl 3.75, KH 2 PO 4 1.25, CaCl 2 2, MgSO 4 2, NaHCO 3 26, dextrose 10, held at room temperature and bubbled with 95 % O 2 -5 % CO 2 .

Sinusoidal high frequency (20‐50 Hz) electric fields induced across rat hippocampal slices were found to suppress zero‐Ca2+, low‐Ca2+, picrotoxin, and high‐K+ epileptiform activity for the duration of the stimulus and for up to several minutes following the stimulus. Suppression of spontaneous activity by high frequency stimulation was found to be frequency (< 500 Hz) but not orientation or waveform dependent. Potassium‐sensitive microelectrodes showed that block of epileptiform activity was always coincident with a stimulus‐induced rise in extracellular potassium concentration during stimulation. Post‐stimulus inhibition was always associated with a decrease in extracellular potassium activity below baseline levels. Intracellular recordings and optical imaging with voltage‐sensitive dyes showed that during suppression neurons were depolarized yet did not fire action potentials. Direct injection of sinusoidal current into individual pyramidal cells did not result in a tonic depolarization. Injection of large direct current (DC) depolarized neurons and suppressed action potential generation. These findings suggest that high frequency stimulation suppresses epileptiform activity by inducing potassium efflux and depolarization block.

Recently, we reported the cloning and expression of the rat renal electrogenic Na(+)-HCO(-)(3) cotransporter (rkNBC) in Xenopus oocytes [M. F. Romero, P. Fong, U. V. Berger, M. A. Hediger, and W. F. Boron. Am. J. Physiol. 274 (Renal Physiol. 43): F425-F432, 1998]. Thus far, all NBC cDNAs are at least 95% homologous. Additionally, when expressed in oocytes the NBCs are 1) electrogenic, 2) Na(+) dependent, 3) HCO(-)(3) dependent, and 4) inhibited by stilbenes such as DIDS. The apparent HCO(-)(3):Na(+) coupling ratio ranges from 3:1 in kidney to 2:1 in pancreas and brain to 1:1 in the heart. This study investigates the cation and voltage dependence of rkNBC expressed in Xenopus oocytes to better understand NBC's apparent tissue-specific physiology. Using two-electrode voltage clamp, we studied the cation specificity, Na(+) dependence, and the current-voltage (I-V) profile of rkNBC. These experiments indicate that K(+) and choline do not stimulate HCO(-)(3)-sensitive currents via rkNBC, and Li(+) elicits only 3 +/- 2% of the total Na(+) current. The Na(+) dose response studies show that the apparent affinity of rkNBC for extracellular Na(+) ( approximately 30 mM [Na(+)](o)) is voltage and HCO(-)(3) independent, whereas the rkNBC I-V relationship is Na(+) dependent. At [Na(+)](o) v(max) (96 mM), the I-V response is approximately linear; both inward and outward Na(+)-HCO(-)(3) cotransport are observed. In contrast, only outward cotransport occurs at low [Na(+)](o) (<1 mM [Na(+)](o)). All rkNBC currents are inhibited by extracellular application of DIDS, independent of voltage and [Na(+)](o). Using ion-selective microelectrodes, we monitored intracellular pH and Na(+) activity. We then calculated intracellular [HCO(-)(3)] and, with the observed reversal potentials, calculated the stoichiometry of rkNBC over a range of [Na(+)](o) values from 10 to 96 mM at 10 and 33 mM [HCO(-)(3)](o). rkNBC stoichiometry is 2 HCO(-)(3):1 Na(+) over this entire Na(+) range at both HCO(-)(3) concentrations. Our results indicate that rkNBC is highly selective for Na(+), with transport direction and magnitude sensitive to [Na(+)](o) as well as membrane potential. Since the rkNBC protein alone in oocytes exhibits a stoichiometry of less than the 3 HCO(-)(3):1 Na(+) thought necessary for HCO(-)(3) reabsorption by the renal proximal tubule, a control mechanism or signal that alters its in vivo function is hypothesized.

OBJECTIVES: Extracorporeal membrane oxygenation is a life-sustaining therapy for severe respiratory failure. Extracorporeal membrane oxygenation circuits require systemic anticoagulation that creates a delicate balance between circuit-related thrombosis and bleeding-related complications. Although unfractionated heparin is most widely used anticoagulant, alternative agents such as bivalirudin have been used. We sought to compare extracorporeal membrane oxygenation circuit thrombosis and bleeding-related outcomes in respiratory failure patients receiving either unfractionated heparin or bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation support. DESIGN: Retrospective cohort study. SETTING: Single-center, cardiothoracic ICU. PATIENTS: Consecutive patients requiring venovenous extracorporeal membrane oxygenation who were maintained on anticoagulation between 2013 and 2020. INTERNVENTIONS: IV bivalirudin or IV unfractionated heparin. MEASUREMENTS AND MAIN RESULTS: Primary outcomes were the presence of extracorporeal membrane oxygenation in-circuit–related thrombotic complications and volume of blood products administered during extracorporeal membrane oxygenation duration. One hundred sixty-two patients receiving unfractionated heparin were compared with 133 patients receiving bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation. In patients receiving bivalirudin, there was an overall decrease in the number of extracorporeal membrane oxygenation circuit thrombotic complications (p < 0.005) and a significant increase in time to circuit thrombosis (p = 0.007). Multivariable Cox regression found that heparin was associated with a significant increase in risk of clots (Exp[B] = 2.31, p = 0.001). Patients who received bivalirudin received significantly less volume of packed RBCs, fresh frozen plasma, and platelet transfusion (p < 0.001 for each). There was a significant decrease in the number major bleeding events in patients receiving bivalirudin, 40.7% versus 11.7%, p < 0.001. CONCLUSIONS: Patients receiving bivalirudin for systemic anticoagulation on venovenous extracorporeal membrane oxygenation experienced a decrease in the number of extracorporeal membrane oxygenation circuit-related thrombotic events as well as a significant decrease in volume of blood products administered.