Left ventricular assist device (LVAD) support is an accepted treatment of patients with end-stage heart failure. The increased applicability and excellent results with LVADs have revolutionized the treatment options available for such patients. Success with LVADs as bridge-to-transplant therapy has led to their successful use as an alternate to a transplant (ie, as destination therapy [DT]). The use of these devices as DT represents a relatively newer but growing indication. Until recently, most patients who have undergone LVAD implantation have been supported by pulsatile devices. Newer continuous-flow (CF) pumps have resulted in superior outcomes, including significantly reduced complication rates with improved durability over first-generation pulsatile design pumps. However, as with all new technology, the newer LVADs have introduced management challenges that were either unimportant or absent with pulsatile LVADs. This article reviews the current state of left ventricular devices, focusing on the CF pumps that currently dominate the field, including clinical outcomes, the physiologic and pathologic effects that are associated with CF pumps, and their unique management issues and complications.
During growth on one-carbon (C 1 ) compounds, the aerobic ␣-proteobacterium Methylobacterium extorquens AM1 synthesizes the tetrahydromethanopterin (H 4 MPT) derivative dephospho-H 4 MPT as a C 1 carrier in addition to tetrahydrofolate. The enzymes involved in dephospho-H 4 MPT biosynthesis have not been identified in bacteria. In archaea, the final step in the proposed pathway of H 4 MPT biosynthesis is the reduction of dihydromethanopterin (H 2 MPT) to H 4 MPT, a reaction analogous to the reaction of the bacterial dihydrofolate reductase. A gene encoding a dihydrofolate reductase homolog has previously been reported for M. extorquens and assigned as the putative H 2 MPT reductase gene (dmrA). In the present work, we describe the biochemical characterization of H 2 MPT reductase (DmrA), which is encoded by dmrA. The gene was expressed with a six-histidine tag in Escherichia coli, and the recombinant protein was purified by nickel affinity chromatography and gel filtration. Purified DmrA catalyzed the NAD(P)H-dependent reduction of H 2 MPT with a specific activity of 2.8 mol of NADPH oxidized per min per mg of protein at 30°C and pH 5.3. Dihydrofolate was not a substrate for DmrA at the physiological pH of 6.8. While the existence of an H 2 MPT reductase has been proposed previously, this is the first biochemical evidence for such an enzyme in any organism, including archaea. Curiously, no DmrA homologs have been identified in the genomes of known methanogenic archaea, suggesting that bacteria and archaea produce two evolutionarily distinct forms of dihydromethanopterin reductase. This may be a consequence of different electron donors, NAD(P)H versus reduced F 420 , used, respectively, in bacteria and methanogenic archaea.
Currently, blood pressure (BP) measurement is obtained noninvasively in patients with continuous flow left ventricular assist device (LVAD) by placing a Doppler probe over the brachial or radial artery with inflation and deflation of a manual BP cuff. We hypothesized that replacing the Doppler probe with a finger-based pulse oximeter can yield BP measurements similar to the Doppler derived mean arterial pressure (MAP). We conducted a prospective study consisting of patients with contemporary continuous flow LVADs. In a small pilot phase I inpatient study, we compared direct arterial line measurements with an automated blood pressure (ABP) cuff, Doppler and pulse oximeter derived MAP. Our main phase II study included LVAD outpatients with a comparison between Doppler, ABP, and pulse oximeter derived MAP. A total of five phase I and 36 phase II patients were recruited during February-June 2014. In phase I, the average MAP measured by pulse oximeter was closer to arterial line MAP rather than Doppler (P = 0.06) or ABP (P < 0.01). In phase II, pulse oximeter MAP (96.6 mm Hg) was significantly closer to Doppler MAP (96.5 mm Hg) when compared to ABP (82.1 mm Hg) (P = 0.0001). Pulse oximeter derived blood pressure measurement may be as reliable as Doppler in patients with continuous flow LVADs.
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