Protek Duo Rapid Deployment cannulation utilized to bridge to durable heartware left ventricular assist device.

A 43-year-old gentleman was transferred for management of acute on chronic cardiogenic shock (left ventricular ejection fraction < 10%). Upon arrival, we inserted a left axillary intra-aortic balloon pump for hemodynamic support. He underwent an emergent left and right-heart catheterization which showed patent stents and coronaries, in the setting of severely elevated pulmonary artery and pulmonary capillary wedge pressure. On hospital day 35, we escalated support to Centrimag in conjunction with a 31 French Protek Duo Rapid Deployment cannula. A centrimag cannula apical sewing cuff was sewn in continuous fashion along the left ventricular apex. Via modified seldinger technique, we tunneled the Protek Duo Rapid Deployment cannula through the silastic sewing cuff and the ventricular apex, traversing the aortic valve. On hospital day 50, he underwent left anterior thoracotomy and mini-sternotomy for implantation of durable Heartware left ventricular assist device. He was discharged home off inotropes and had resumed his normal activities. He is currently listed as status four for heart transplantation.

Successful use of extracorporeal membrane oxygenation support in severe septic shock with associated acute cardiomyopathy.

A 24-year-old female presented with sepsis and cardiogenic shock 4 days after vaginal delivery. Veno-arterial extracorporeal membrane oxygenation (VA ECMO) therapy was used for cardiovascular support as a bridge for recovery. The use of VA ECMO in patients with cardiogenic shock secondary to sepsis is reviewed.

Concomitant surgical cryoablation for refractory ventricular tachycardia and left ventricular assist device placement: a dual remedy but a recipe for thrombosis?

BACKGROUND: Ventricular tachycardia (VT) can persist following placement of a left ventricular assist device (LVAD). The optimal management strategy for VT during the peri-LVAD period is unknown. CASE PRESENTATIONS: Two case reports are presented that describe epicardial and endocardial VT ablation performed during LVAD placement. Subsequently, both patients developed LVAD thrombosis, a known and dreaded complication of LVADs, requiring re-operation. CONCLUSIONS: While LVAD thrombosis is likely multifactorial and remains an area of active research, these two cases should increase awareness of the possible risks of VT ablation-especially endocardial ablation-during LVAD placement. Further research is needed to understand the effects of VT ablation during the peri-LVAD period.

Continued Utility of Single-Lung Transplantation in Select Populations: Chronic Obstructive Pulmonary Disease.

BACKGROUND: The use of single lung transplantation (SLTx) for chronic obstructive pulmonary disease is often viewed as inferior therapy compared with bilateral lung transplantation (BLTx). We hypothesized from our experience that subpopulations of recipients with emphysema exist in which SLTx represents therapy that is equivalent to BLTx, therefore allowing more patients access to transplantation. METHODS: Consecutive patients undergoing LTx for emphysema between 1992 and 2012 at a single institution were identified and analyzed retrospectively. A similar cohort from the United Network of Organ Sharing (UNOS) national database was identified for comparison. Five-year survival in patients receiving SLTx and those receiving BLTx were compared using Kaplan-Meier survival curves and log-rank tests. RESULTS: Two hundred thirty-six patients meeting criteria were identified from our institution. Two hundred six underwent SLTx, and 30 underwent BLTx. Five-year survival for single-center SLTx (53.2% ± 3.6%) and BLTx (56.7% ± 10.2%) was not significantly different (p = 0.753). The national database included 7,256 patients meeting selection criteria, with 4,408 undergoing SLTx and 2,848 undergoing BLTx. Five-year survival among the national cohorts was lower for SLTx (46.4% ± 0.8%) compared with BLTx (55.9% ± 1.1%) (p < 0.0001). However, 5-year survival for our single-center SLTx experience (53.2% ± 3.6%) was comparable to the national BLTx cohort (55.9% ± 1.1%) (p = 0.539). CONCLUSIONS: Five-year survival after SLTx for emphysema was comparable to that for BLTx in cohorts from our institution and from the UNOS national database. Further study should focus on the mechanism behind these improved outcomes. Given the potential for a larger number of life-years saved, SLTx should continue to be considered a therapeutic option in appropriately selected patients with chronic obstructive pulmonary disease (COPD).

Changes in Aortic Wall Structure, Composition, and Stiffness With Continuous-Flow Left Ventricular Assist Devices: A Pilot Study.

BACKGROUND: The effects of nonpulsatile flow on the aorta are unknown. Our aim was to examine the structure of the aorta from patients with continuous-flow left ventricular assist devices (LVADs) and directly measure aortic wall composition and stiffness. METHODS AND RESULTS: Age-matched aortic wall samples were collected from consecutive patients with heart failure (HF) at the time of transplantation and compared with nonfailing donor hearts. An unbiased stereological approach was used to quantify aortic morphometry and composition, and biomechanical testing was performed to determine the stress-strain relationship of the vessel. Data were obtained from 4 patients without a left ventricular assist device (HF group: mean age, 58.3±8.0 years), 7 patients with a continuous-flow LVAD (HF+LVAD group: mean, 57.7±5.6 years), and 3 nonfailing donors (mean, 53.3±12.9 years). Compared with HF, the aortic walls from HF+LVAD had an increase in wall thickness, collagen, and smooth muscle content accompanied by a reduction in elastin and mucinous ground-substance content. Stress-strain curves from the aortas revealed increased vessel stiffness in HF+LVAD compared with HF and nonfailing. The physiological modulus of the aorta progressively stiffened from 74.3±5.5 kPa in the nonfailing to 134.4±35.0 kPa in the HF to 201.7±36.4kPa in the HF+LVAD groups (P<0.001). CONCLUSIONS: Among continuous-flow LVAD patients without aortic valve opening, there are changes in the structure and composition of the aorta as well as an increase in aortic wall stiffness compared with age-matched HF patients and nonfailing donors. Further studies examining the role of nonpulsatile blood flow on aortic function and the potential resultant systemic sequelae are needed.

Hemoglobin-based oxygen carrier induces heme oxygenase-1 in the heart and lung but not brain.

BACKGROUND: The clinical sequel of ischemia and reperfusion remains a challenge in several clinical areas. Overexpression of heme oxygenase-1 (HO-1), using viral vectors, endotoxemia, and hypoxia, provides protection against ischemia and reperfusion injury. To date, however, no clinically viable therapy exists to safely induce HO-1. We have recently observed that administration of a hemoglobin-based oxygen carrier (HBOC) attenuates postinjury systemic inflammation. We have further demonstrated that an HBOC can induce HO-1 in vitro. We now explore the tissue-specific induction of heme oxygenase-1 after administration of an HBOC. STUDY DESIGN: Rats were infused with doses of HBOC or saline through femoral vein injection (n=5 per group). Animals were sacrificed and organs were flushed. Heart, lung, and brain samples were taken for evaluation of total organ levels of HO-1 induction and for histologic localization of the cellular expression of the HO-1. Heat shock protein 72 levels were also analyzed to determine whether HO-1 induction was a generalized stress response. RESULTS: Both the heart and lung demonstrated a dose-dependent induction of total organ HO-1. Interestingly, brain tissue did not have any significant amount of HO-1, either at baseline or after HBOC therapy. The cellular localization of HO-1 between organs was also specific, predominantly occurring in the cardiac myocyte and alveolar macrophages. Heat shock protein 72 levels were not significantly changed in any group examined, suggesting the induction of HO-1 is specific. CONCLUSIONS: This study demonstrates that a clinically accessible product, HBOC, can specifically and selectively induce the expression of the protective enzyme HO-1 in vivo. These findings begin to characterize which organ systems may benefit by preischemic treatments with HBOC and further expand potential clinical applications of HBOCs.

Lipopolysaccharide stimulation of human aortic valve interstitial cells activates inflammation and osteogenesis.

BACKGROUND: Calcific aortic stenosis may be an inflammatory disease with active bone formation in the valve leaflets rather than a disease of passive calcium deposition. Epidemiologic data demonstrating correlation of poor dental hygiene to atherosclerotic pathologies suggests that circulating bacterial products could be involved in the pathogenesis of aortic valve stenosis. We hypothesized that lipopolysaccharide (LPS) stimulation of human aortic valve interstitial cells (HAVICs) would induce inflammatory and osteogenic gene expression. METHODS: The HAVICs were isolated from normal aortic valves obtained from explanted hearts during transplantation (n = 5) and grown in culture. Cells underwent 4 and 24 hours of LPS stimulation (LPS, 200 ng/mL) or beta-glycerol phosphate treatment (BGP) (osteogenic media as positive control). Media was removed for interleukin (IL)-6 and IL-8 immunoassay. Ribonucleic acid was extracted for microarray analysis. Statistics were by analysis of variance with post-hoc analysis (p < 0.05). RESULTS: The LPS stimulation induced the gene expression of proinflammatory cytokines, chemokines, and adhesion molecules. Protein level confirmation by immunoassay demonstrated 3.4-fold (+/- 0.35, p < 0.01) and 9.5-fold (+/- 1.5 p < 0.01) increase over control of IL-6 and IL-8, respectively. The LPS and BGP both induced critical mediators of osteogenesis including bone morphogenetic protein 2 and platelet-derived growth factor alpha. CONCLUSIONS: The LPS stimulation of HAVICs not only induces inflammatory mediators but also induces gene expression of osteogenic factors, similar to that induced by osteogenic media. Bacterial products stimulation, likely by toll-like receptor 4 and the innate immune system, may contribute to the pathogenesis of aortic valve stenosis.

Microvascular destruction identifies murine allografts that cannot be rescued from airway fibrosis.

Small airway fibrosis (bronchiolitis obliterans syndrome) is the primary obstacle to long-term survival following lung transplantation. Here, we show the importance of functional microvasculature in the prevention of epithelial loss and fibrosis due to rejection and for the first time, relate allograft microvascular injury and loss of tissue perfusion to immunotherapy-resistant rejection. To explore the role of alloimmune rejection and airway ischemia in the development of fibroproliferation, we used a murine orthotopic tracheal transplant model. We determined that transplants were reperfused by connection of recipient vessels to donor vessels at the surgical anastomosis site. Microcirculation through the newly formed vascular anastomoses appeared partially dependent on VEGFR2 and CXCR2 pathways. In the absence of immunosuppression, the microvasculature in rejecting allografts exhibited vascular complement deposition, diminished endothelial CD31 expression, and absent perfusion prior to the onset of fibroproliferation. Rejecting grafts with extensive endothelial cell injury were refractory to immunotherapy. After early microvascular loss, neovascularization was eventually observed in the membranous trachea, indicating a reestablishment of graft perfusion in established fibrosis. One implication of this study is that bronchial artery revascularization at the time of lung transplantation may decrease the risk of subsequent airway fibrosis.

Hemoglobin-based oxygen carrier induces hepatic heme oxygenase 1 expression in Kupffer cells.

BACKGROUND: Kupffer cells (liver macrophages) are a key initiator of inflammation following hepatic insults such as infection, ischemia/reperfusion, and rejection. Heme oxygenase 1 (HO-1) is protective against inflammatory injury. A hemoglobin-based oxygen carrier (HBOC) has been shown to prevent organ inflammation from hemorrhagic shock as well as induce HO-1 at the cellular level. Therefore, we hypothesize that HBOC can induce Kupffer cell HO-1 production. METHODS: Mice administered 20% blood volume HBOC or saline intravenously were sacrificed at 0, 12, 24, 48 hours (n = 4-6/group). Hepatic protein underwent Western blotting for HO-1 and heat shock protein 72. Hepatic frozen sections underwent immunofluorescent staining for HO-1/CD68. RESULTS: Following HBOC injection, hepatic HO-1 fold change peaked at 12 hours (7.3 +/- 0.8) (p < .01), remained increased at 24 hours (4.7 +/- 0.4) (p < .01), and returned to baseline by 48 hours. HSP72 expression was unaffected in all groups. Twleve-hour liver section immunostaining confirmed significant induction of HO-1 by HBOC. Double staining for HO-1 and CD68 identified Kupffer cells as the majority of cells expressing HO-1. CONCLUSION: HBOC induces hepatic HO-1 expression in Kupffer cells without heat shock protein response. These data provide the basis for further investigation into a clinical therapy to induce Kupffer cell HO-1 expression with the goal of attenuating the hepatic immunoresponse to various insults.

The matrix comes to lung transplantation.

Lung transplantation is complicated by fibroproliferation, which is likely mediated in part by matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs. This commentary briefly discusses what is known about these mediators in fibrotic pulmonary diseases and how an important new study by Yoshida and colleagues sheds light on the diverse functions of these proteins in alloimmune inflammation.