Atrial fibrillation symptom reduction and improved quality of life following the hybrid convergent procedure: a CONVERGE trial subanalysis.

Background: CONVERGE was a prospective, multicenter, randomized controlled trial that evaluated the safety of Hybrid Atrial Fibrillation Convergent (HC) and compared its effectiveness to endocardial catheter ablation (CA) for the treatment of persistent atrial fibrillation (PersAF) and longstanding PersAF (LSPAF). In 2020, we reported that CONVERGE met its primary safety and effectiveness endpoints. The primary objective of the present study is to report CONVERGE trial results for quality of life (QOL) and Class I/III anti-arrhythmic drug (AAD) utilization following HC. Methods: Eligible patients had drug-refractory symptomatic PersAF or LSPAF and a left atrium diameter ≤6.0 cm. Enrolled patients were randomized 2:1 to receive HC or CA. Atrial Fibrillation Severity Scale (AFSS) and the 36-Item Short Form Health Survey (SF-36) were assessed at baseline and 12 months; statistical comparison was performed using paired t-tests. AAD utilization at baseline through 12 and 18 months post-procedure was evaluated; statistical comparison was performed using McNemar's tests. Results: A total of 153 patients were treated with either HC (n=102) or CA (n=51). Of the 102 HC patients, 38 had LSPAF. AFSS and SF-36 Mental and Physical Component scores were significantly improved at 12 months versus baseline with HC overall and for the subset of LSPAF patients treated with either HC or CA. The proportion of HC patients (n=102) who used Class I /III AADs at 12 and 18 months was significantly less (33.3% and 36.3%, respectively) than baseline (84.3%; P<0.001). In LSPAF patients who underwent HC (n=38), AADs use was 29.0% through 18 months follow-up versus 71.1% at baseline (P<0.001). Conclusions: HC reduced AF symptoms, significantly improved QOL, and reduced AAD use in patients with PersAF and LSPAF. ClinicalTrialsgov Identifier: NCT01984346.

Six-month preclinical results of novel vascular anastomosis device intended to facilitate open aortic and arch vessel reconstruction.

The surgical repair of type A aortic dissection often involves prosthetic proximal aortic and arch reconstruction. Hypothermic circulatory arrest is typically used in these complex surgeries given the required prolonged ischaemia and the associated morbidity and mortality. A novel vascular anastomoses device (Device) has been developed to rapidly connect a native vessel to a polyester graft. This study describes deployment of the Device in the ovine model (n = 3; 6 carotid arteries). Anastamoses were created rapidly, and brain ischaemia time was limited to 6 min in all but one vessel. All vessels remained fully patent with normal blood flow and thrombus-free transitions through 6 months. Results thus suggest that this Device has the potential to reduce anastomosis time versus conventional suturing techniques and thereby reduce hypothermic circulatory arrest time.

Total aortic arch replacement for the treatment of Kommerell's diverticulum in a Jehovah's Witness.

The treatment of Kommerell's diverticulum continues to evolve given advances in aortic surgery, cardiopulmonary bypass management, and endovascular techniques. This case report details the repair of a diverticulum of Kommerell in a Jehovah's witness with a right-sided aortic arch and reviews the surgical literature.

Sizing Strategy and Implant Considerations for the Avalus Valve.

Hemodynamic performance of the Avalus valve through 3 years after implant is comparable to that of contemporary surgical bioprostheses. Many variables affect hemodynamic outcomes, including surgical technique. This article describes our experience with the Avalus bioprosthesis and strategies to achieve optimal hemodynamic performance.

Subxiphoid Hybrid Epicardial-Endocardial Atrial Fibrillation Ablation and LAA Ligation: Initial Sub-X Hybrid MAZE Registry Results.

OBJECTIVES: The aim of this study was to assess the safety and efficacy of a new subxiphoid hybrid epicardial-endocardial atrial fibrillation (AF) ablation and left atrial appendage (LAA) ligation approach for the treatment of persistent AF. BACKGROUND: Surgical hybrid ablation procedures have shown promise for maintaining sinus rhythm versus catheter ablation but are associated with increased periprocedural adverse events. METHODS: Patients with symptomatic persistent AF (n = 33, mean age 64 ± 9 years, 25 men) who had antiarrhythmic drug therapy or prior catheter ablation was unsuccessful were referred for hybrid epicardial-endocardial AF ablation and LAA exclusion. LAA closure was confirmed by transesophageal echocardiographic Doppler flow and/or computed tomographic angiography 1 to 3 months post-ligation. The incidence of atrial tachycardia or AF recurrence, LAA closure, thromboembolic events, and post-operative complications were assessed. RESULTS: All 33 patients underwent successful LAA ligation with epicardial ablation of the posterior left atrial wall, as well as endocardial pulmonary vein isolation and cavotricuspid isthmus ablation. Freedom from atrial tachycardia or AF was 91% (20 of 22 patients) at 6 months, 90% (18 of 20 patients) at 12 months, 92% (11 of 12 patients) at 18 months, and 92% (11 of 12) at 24 months. There were no acute periprocedural complications (<7 days). Thirty-day adverse events included 2 patients with pericardial effusion requiring pericardiocentesis and 1 incisional hernia repair. There were no long-term complications, strokes, or deaths. LAA ligation was complete in 27 of 33 subjects (82%), with 6 subjects having leaks of <5 mm. CONCLUSIONS: Subxiphoid hybrid epicardial-endocardial ablation with LAA ligation is feasible, safe, and effective. Future prospective studies are needed to validate these initial findings.

Hybrid Convergent Procedure for the Treatment of Persistent and Long-Standing Persistent Atrial Fibrillation: Results of CONVERGE Clinical Trial.

BACKGROUND: The limited effectiveness of endocardial catheter ablation (CA) for persistent and long-standing persistent atrial fibrillation (AF) treatment led to the development of a minimally invasive epicardial/endocardial ablation approach (Hybrid Convergent) to achieve a more comprehensive lesion set with durable transmural lesions. The multicenter randomized controlled CONVERGE trial (Convergence of Epicardial and Endocardial Ablation for the Treatment of Symptomatic Persistent AF) evaluated the safety of Hybrid Convergent and compared its effectiveness to CA for persistent and long-standing persistent AF treatment. METHODS: One-hundred fifty-three patients were randomized 2:1 to Hybrid Convergent versus CA. Primary effectiveness was freedom from AF/atrial flutter/atrial tachycardia absent new/increased dosage of previously failed/intolerant class I/III antiarrhythmic drugs through 12 months. Primary safety was major adverse events through 30 days. CONVERGE permitted left atrium size up to 6 cm and imposed no limits on AF duration, making it the only ablation trial to substantially include long-standing persistent-AF, that is, 42% patients with long-standing persistent-AF. RESULTS: Of 149 evaluable patients at 12 months, primary effectiveness was achieved in 67.7% (67/99) patients with Hybrid Convergent and 50.0% (25/50) with CA (P=0.036) on/off previously failed antiarrhythmic drugs and in 53.5% (53/99) versus 32.0% (16/50; P=0.0128) respectively off antiarrhythmic drugs. At 18 months using 7-day Holter, 74.0% (53/72) Hybrid Convergent and 55% (23/42) CA patients experienced ≥90% AF burden reduction. A total of 2.9% (3/102) patients had primary safety events within 7 days, and 4.9% (5/102) between 8 and 30 days postprocedure. No deaths, cardiac perforations, or atrioesophageal fistulas occurred. All but one primary safety event resolved. CONCLUSIONS: The Hybrid Convergent procedure has superior effectiveness compared to the CA for the treatment of persistent and long-standing persistent atrial fibrillation. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01984346.

Characteristics of second primary lung malignancy in patients with known breast cancer.

BACKGROUND: As breast cancer survival improves, the incidence of additional malignancies will likely rise. Identification of a lung nodule in a patient with known breast cancer poses a challenging diagnostic problem. This study outlines the management of such patients and identifies factors that correlate with survival. METHODS: From 1977 through 2002, 35 patients with known breast cancer were identified with an additional primary lung cancer. Data were collected from a retrospective chart review. Median and 2- year survival were determined by the Kaplan-Meier method and Cox regression analysis identified independent predictors of survival. RESULTS: Nineteen patients (54%) were asymptomatic at the time of diagnosis and had their lung cancer discovered during workup and/or follow-up of their breast cancer. The diagnosis of lung cancer was made by preoperative biopsy in 23 patients (82%). Nineteen patients (54%) were successfully treated with surgery. Mean follow-up was 2.3 years. Median survival for all patients was 1.8 years. Factors associated with a statistically significant improvement in survival included asymptomatic presentation of lung cancer (P = 0.003), absence of tobacco use (P = 0.021), and stage I lung cancer (P = 0.009). Multivariate analysis revealed that tobacco use (RR = 3.6, P = 0.047) and advanced stage of lung cancer (II-IV) at the time of diagnosis (RR = 2.2, P < 0.001) were independent predictors of decreased survival. CONCLUSION: The presentation of a lung nodule in patients with breast cancer warrants a comprehensive evaluation to differentiate between primary lung and metastatic breast cancers, as diagnosis and resection of an early stage lung cancer is associated with improved survival.

Intravenous infusion of mesenchymal stem cells enhances regional perfusion and improves ventricular function in a porcine model of myocardial infarction.

Transplantation of stem cells may improve regional perfusion and post-infarct ventricular function, but the optimal dose and efficacy of cell delivery via the intravenous route has not been determined. This study tested the hypothesis that intravenous infusion of bone marrow-derived mesenchymal stem cells (MSCs) enhances regional perfusion and improves ventricular function after myocardial infarction. In a closed-chest pig model, the LAD coronary artery was occluded for 75 min by angioplasty balloon inflation followed by 12 weeks of reperfusion. After 15 min of reperfusion, pigs randomly received 1 of 4 treatments: (1) Vehicle (Control, n = 10); (2) 1 x 10(6) MSCs/kg (1 mill, n = 7); (3) 3 x 10(6) MSCs/kg (3 mill, n = 8) and (4) 10 x 10(6) MSCs/kg (10 mill, n = 8). Angiogenesis was demonstrated by immunohistochemical staining, myocardial blood flow (steady state and vasodilator reserve) was measured using 15 microm neutron-activated microspheres, and cardiac function was determined by contrast left ventriculography (ejection fraction) and pressure-volume relationships. After 12 week of reperfusion, von Willebrand Factor-positive vessels and tissue vascular endothelial growth factor (VEGF) expression in the scar zone was significantly greater in all MSCs-treated animals relative to Control. Steady state myocardial blood flow in the scar tissue was comparable among groups. However, adenosine recruited vasodilator reserve in the scar zone induced by intracoronary adenosine was significantly higher in the MSC-treated animals compared to Control. Furthermore, preload-recruitable stroke work and systolic performance were significantly greater compared to Control. In conclusion, these data demonstrate that intravenous delivery of MSCs during early reperfusion augments vasculogenesis, enhances regional perfusion, and improves post-infarct ventricular function. The results suggest that intravenous infusion of MSCs is an effective modality for the treatment of ischemia/reperfusion induced myocardial injury.

Off-pump coronary bypass surgery for high-risk patients: only in expert centers?

PURPOSE OF REVIEW: Off-pump coronary artery bypass (OPCAB) grafting has been increasingly adopted in an effort to prevent deleterious effects of cardiopulmonary bypass, including the associated inflammatory response, global myocardial ischemia and the risks of aortic manipulation. In many studies, the greatest benefit of OPCAB has been in high-risk patients. This review will summarize the recent literature examining outcomes of OPCAB versus on-pump coronary artery bypass in high-risk subgroups, and will examine the safety of routine application of OPCAB in these patients. RECENT FINDINGS: Prospective randomized trials have shown that in comparison to on-pump coronary artery bypass, OPCAB reduces perioperative morbidity, but have failed to show a mortality benefit, owing to small sample sizes. However, numerous large retrospective series and meta-analyses have demonstrated a reduction in risk-adjusted mortality and morbidity with respect to the following outcomes: stroke, pulmonary function, renal function, atrial fibrillation, need for early reoperation, blood transfusion requirements, length of ICU and hospital stay, and hospital costs. An even greater benefit has been seen in the following high-risk patients: those with acute myocardial infarction, left ventricular dysfunction, previous history of stroke, renal insufficiency, women, elderly patients, and those undergoing reoperations. SUMMARY: Risk-adjusted outcomes are superior after OPCAB versus on-pump coronary artery bypass for mortality and numerous morbidity endpoints. This benefit is most easily demonstrated in high-risk patient populations.

1-Year Outcomes of Transcatheter Mitral Valve Replacement in Patients With Severe Mitral Annular Calcification.

BACKGROUND: The risk of surgical mitral valve replacement in patients with severe mitral annular calcification (MAC) is high. Several patients worldwide with severe MAC have been treated successfully with transcatheter mitral valve replacement (TMVR) using balloon-expandable aortic transcatheter valves. The TMVR in MAC Global Registry is a multicenter registry that collects data on outcomes of these procedures. OBJECTIVES: The goal of this study was to evaluate 1-year outcomes in this registry. METHODS: This study was a multicenter retrospective review of clinical outcomes. RESULTS: A total of 116 extreme surgical risk patients with severe MAC underwent TMVR; 106 had a procedure date >1 year before data-lock and were included in the analysis. Their mean age was 73 ± 12 years, and 68% were female. The mean Society of Thoracic Surgeons score was 15.3 ± 11.6%, and 90% were in New York Heart Association functional class III or IV. Thirty-day and 1-year all-cause mortality was 25% and 53.7%, respectively. Most patients who survived 30 days were alive at 1 year (49 of 77 [63.6%]), and the majority (71.8%) were in New York Heart Association functional class I or II. Echocardiography data at 1 year were available in 34 patients. Mean left ventricular ejection fraction was 58.6 ± 11.2%, mean mitral valve area was 1.9 ± 0.5 cm2, mean mitral gradient was 5.8 ± 2.2 mm Hg, and 75% had zero or trace mitral regurgitation. CONCLUSIONS: TMVR with balloon-expandable aortic valves in extreme surgical risk patients with severe MAC is feasible but associated with high 30-day and 1-year mortality. Most patients who survive the 30-day post-procedural period are alive at 1 year and have sustained improvement of symptoms and transcatheter valve performance. The role of TMVR in patients with MAC requires further evaluation in clinical trials.

Postconditioning reduces infarct size via adenosine receptor activation by endogenous adenosine.

OBJECTIVE: This study tested the hypothesis that brief cycles of iterative ischemia-reperfusion at onset of reperfusion (termed "postconditioning", post-con) delays washout of intravascular adenosine and thereby increases endogenous adenosine receptor (AR) activation during the early moments of reperfusion (R). METHODS: Isolated mouse hearts were subjected to 20 min global ischemia (I) and 30 min R with or without post-con (3 or 6 cycles of 10 s R&I). Intravascular purines in coronary effluent were analyzed by HPLC. To assess the functional role of endogenous AR activation in post-con, an open-chest rat model of myocardial infarction was employed. Rats were randomly divided into 11 groups: control, no intervention at R; post-con, three cycles of 10 s R followed by 10 s LCA re-occlusion immediately upon R. In the following interventions, drugs (or vehicle) were administered 5 min before R in the absence or presence (+/-) of post-con. Vehicle (DMSO < 300 microl/kg); 8-SPT (non-selective AR antagonist, 10 mg/kg) +/- post-con; DPCPX (A(1A)R antagonist, 0.1 mg/kg) +/- post-con; ZM241385 (A(2A)AR antagonist, 0.2 mg/kg) +/- post-con; MRS1523 (A(3)AR antagonist, 2 mg/kg) +/- post-con. RESULTS: In isolated mouse hearts, post-con reduced diastolic pressure during both early (26+/-3* vs. 37+/-3 mmHg at 5 min) and late (22+/-3* vs. 34+/-3 mmHg at 30 min) R. Post-con also hastened the early recovery of contractile function (developed pressure 39+/-6* vs. 16+/-2 mmHg at 5 min R), although differences did not persist at 30 min R. Importantly, post-con was associated with reduced adenosine washout (58+/-5* vs. 155+/-16 nM/min/g) at 2 min R suggesting greater retention time of intravascular adenosine. In rats, post-con significantly attenuated infarct size compared to control (40+/-3% vs. 53 +/- 2%* in control), an effect that was unaltered by DPCPX (42 +/- 2%) but was abrogated by 8-SPT (50 +/- 2%), ZM241385 (49 +/- 3%) or MRS1523 (52 +/- 1%) (P < 0.02). CONCLUSION: These data suggest that post-con involves endogenous activation of A(2A) and A3 but not A1AR subtypes. This activation may be linked to the delay in the washout of intravascular adenosine during the early minutes of R during which post-con is applied.

Premeasured Chordal Loops for Mitral Valve Repair.

Premeasured expanded polytetrafluoroethylene chordal loops with integrated sutures for attachment to the papillary muscle and leaflet edges facilitate correction of mitral valve prolapse. Configured as a group of 3 loops (length range 12 to 24 mm), the loops are attached to a pledget that is passed through the papillary muscle and tied. Each of the loops has 2 sutures with attached needles; these needles are passed through the free edge of the leaflet and then the sutures are tied to each other, securing the chordal loop to the leaflet.

Transcatheter Mitral Valve Replacement in Native Mitral Valve Disease With Severe Mitral Annular Calcification: Results From the First Multicenter Global Registry.

OBJECTIVES: This study sought to evaluate the outcomes of the early experience of transcatheter mitral valve replacement (TMVR) with balloon-expandable valves in patients with severe mitral annular calcification (MAC) and reports the first large series from a multicenter global registry. BACKGROUND: The risk of surgical mitral valve replacement in patients with severe MAC is high. There are isolated reports of successful TMVR with balloon-expandable valves in this patient population. METHODS: We performed a multicenter retrospective review of clinical outcomes of patients with severe MAC undergoing TMVR. RESULTS: From September 2012 to July of 2015, 64 patients in 32 centers underwent TMVR with compassionate use of balloon-expandable valves. Mean age was 73 ± 13 years, 66% were female, and mean Society of Thoracic Surgeons score was 14.4 ± 9.5%. The mean mitral gradient was 11.45 ± 4.4 mm Hg and the mean mitral area was 1.18 ± 0.5 cm(2). SAPIEN valves (Edwards Lifesciences, Irvine, California) were used in 7.8%, SAPIEN XT in 59.4%, SAPIEN 3 in 28.1%, and Inovare (Braile Biomedica, Brazil) in 4.7%. Access was transatrial in 15.6%, transapical in 43.8%, and transseptal in 40.6%. Technical success according to Mitral Valve Academic Research Consortium criteria was achieved in 46 (72%) patients, primarily limited by the need for a second valve in 11 (17.2%). Six (9.3%) had left ventricular tract obstruction with hemodynamic compromise. Mean mitral gradient post-procedure was 4 ± 2.2 mm Hg, paravalvular regurgitation was mild or absent in all. Thirty-day all-cause mortality was 29.7% (cardiovascular = 12.5% and noncardiac = 17.2%); 84% of the survivors with follow-up data available were in New York Heart Association functional class I or II at 30 days (n = 25). CONCLUSIONS: TMVR with balloon-expandable valves in patients with severe MAC is feasible but may be associated with significant adverse events. This strategy might be an alternative for selected high-risk patients with limited treatment options.

Polarized arrest with warm or cold adenosine/lidocaine blood cardioplegia is equivalent to hypothermic potassium blood cardioplegia.

BACKGROUND: Hypothermic depolarizing hyperkalemic (K + 20 mEq/L) blood cardioplegia is the "gold standard" in cardiac surgery. K + has been associated with deleterious consequences, eg, intracellular calcium overload. This study tested the hypothesis that elective arrest in a polarized state with adenosine (400 micromol/L via adenosine triphosphate-sensitive potassium channel opening) and the Na + channel blocker lidocaine (750 micromol/L) as the arresting agents in blood cardioplegia provides cardioprotection comparable to standard hypothermic K + -blood cardioplegia. METHODS: Anesthetized dogs were placed on cardiopulmonary bypass and assigned to 1 of 3 groups receiving antegrade cardioplegia delivered every 20 minutes for 1 hour of arrest: cold (10 degrees C) K + -blood cardioplegia (n = 6), cold (10 degrees C) adenosine/lidocaine blood cardioplegia (n = 6), or warm (37 degrees C) adenosine/lidocaine blood cardioplegia (n = 6). After an hour of arrest, cardiopulmonary bypass was discontinued, and reperfusion was continued for 120 minutes. RESULTS: Time to arrest was longer with cold and warm adenosine/lidocaine blood cardioplegia (175 +/- 19 seconds and 143 +/- 19 seconds, respectively) compared with K + -blood cardioplegia (27 +/- 2 seconds; P < .001). Postcardioplegia left ventricular systolic function (slope of the end-systolic pressure/dimension relationship) was comparable among the 3 groups (K + -blood cardioplegia, 15.2 +/- 2.1 mm Hg/mm; cold adenosine/lidocaine blood cardioplegia, 15.9 +/- 3.4 mm Hg/mm; warm adenosine/lidocaine blood cardioplegia, 14.1 +/- 2.8 mm Hg/mm; P = .90). Plasma creatine kinase activity in cold and warm adenosine/lidocaine blood cardioplegia was similar to that in K + -blood cardioplegia at 120 minutes of reperfusion (cold adenosine/lidocaine blood cardioplegia, 11.5 +/- 2.1 IU/g protein; warm adenosine/lidocaine blood cardioplegia, 10.1 +/- 0.9 IU/g protein; K + -blood cardioplegia, 7.6 +/- 0.8 IU/g protein; P = .17). Postcardioplegia coronary artery endothelial function was preserved in all groups. CONCLUSIONS: Intermittent polarized arrest with warm or cold adenosine/lidocaine blood cardioplegia provided the same degree of myocardial protection as intermittent hypothermic K + -blood cardioplegia in normal hearts.

Replacement of mechanical mitral valve prosthesis due to patient intolerance of clicking noise: case report.

A 55-year-old male underwent combined coronary artery bypass grafting and mitral valve replacement with a No. 31 St. Jude Medical mechanical prosthetic valve. Over the next few months, the patient experienced severe difficulty with the 'clicking' noise of the mechanical valve, to the extent that it affected his daily activities. At approximately four months after the first operation, and at the patient's insistence, he underwent redo sternotomy and replacement of the mechanical mitral valve with a Mosaic porcine bio-prosthesis, with an uneventful recovery. While this case represents an unusual indication for valve replacement, it illustrates the importance of considering non-traditional factors when choosing the optimal prosthetic valve.

Postconditioning attenuates myocardial ischemia-reperfusion injury by inhibiting events in the early minutes of reperfusion.

OBJECTIVE: We previously showed that brief intermittent ischemia applied during the onset of reperfusion (i.e., postconditioning) is cardioprotective in a canine model of ischemia-reperfusion. This study tested the hypothesis that the early minutes of reperfusion (R) during which postconditioning (Post-con) is applied are critical to its cardioprotection. METHODS: In anesthetized open-chest rats, the left coronary artery (LCA) was occluded for 30 min and reperfused for 3 h. All rats were randomly divided into six groups: Control (n=8): no intervention at R; Ischemic preconditioning (IPC) (n=8): the LCA was occluded for 5 min followed by 10 min of R before the index occlusion; Post-con 1 (n=8): after LCA occlusion, three cycles of 10 s R followed by 10 s LCA re-occlusion were applied during the first minute of R; Post-con 2 (n=8): Six cycles of 10 s R and 10 s re-occlusion were applied during the first 2 min of R; Delayed Post-con (n=8): the ligature was loosened for full reflow for the first minute of R, after which the three-cycle Post-con algorithm was applied; Sham (n=6): the surgical procedure was identical to other groups, but the LCA ligature was not ligated. RESULTS: Infarct size (TTC staining) was 23% smaller in Post-con 1 (40+/-2%*) than in Control (52+/-3%), confirmed by plasma creatine kinase activity (18+/-2* vs. 46+/-6 IU/g protein). There was no further reduction in infarct size with 6 cycles of Post-con (40+/-2.9%, p>0.05 vs. Post-con 1). Meanwhile, infarct size reduction was significantly greater in the IPC group (17+/-3%) than in Post-con1 (p<0.01). The plasma lipid peroxidation product malondialdehyde (MDA, microM/ml) was less after R in IPC and Post-con 1 (0.8+/-0.07* and 0.8+/-0.06*) vs. Control (1.21+/-0.08), consistent with a visual decrease in superoxide anion generation (dihydroethidium staining) in the AAR myocardium after 3 h of reperfusion. Neutrophil accumulation (myeloperoxidase activity, MPO, U/100 g tissue) in the AAR was less in IPC (1.4+/-0.3*) and Post-con 1 (2.5+/-0.3*) vs. Control (5.5+/-0.6). The reductions in infarct size, creatine kinase, MDA and DHE staining were lost with delayed Post-con, while MPO activity remained lower than in Control (3.2+/-0.4*). CONCLUSIONS: (1) Post-con at onset of R reduces myocardial injury; (2) cardioprotection may be mediated, in part, by inhibiting oxidant generation and oxidant mediated injury; (3) the first minute of R in the rat model is critical to cardioprotection by Post-con; and (4) cardioprotection by Post-con may be independent of neutrophil accumulation in AAR. *p<0.05 Post-con vs. Control.

Involvement of Na+/H+ exchanger in hypoxia/re-oxygenation-induced neonatal rat cardiomyocyte apoptosis.

Although increased Na(+)/H(+) exchanger type-1 (NHE-1) activity has been implicated in the pathogenesis of myocardial infarction, the role of NHE-1 in induction of apoptosis, and the potential mechanisms involved have not been fully characterized. This study tested the hypothesis that NHE-1 activity is involved in hypoxia (H)/re-oxygenation (Re)-induced cardiomyocyte apoptosis by increasing mitochondrial Ca(2+) ([Ca(2+)]m). Primary cultured neonatal rat cardiomyocytes were subjected to 4.5 h of H followed by 12 h of Re. Relative to H alone, the level of X-rhod-1 acetoxymethyl (AM)-labeled [Ca(2+)]m was increased, and the frequency of cell death (propidium iodide (PI) staining) and apoptotic cells (terminal deoxynucleotidyl transferase (TdT)-mediated-UTP nick end labeling [TUNEL]), confirmed by Annexin-V, were augmented at the end of Re, along with appearance of cytosolic cytochrome c, activation of caspase-3, and increased ratio of Bax and Bcl-2. Addition of cariporide (20 micromol/l), a well-known NHE-1 inhibitor, to cultured cells before H significantly reduced [Ca(2+)]m, the number of PI and TUNEL positive cells relative to the levels at end of Re, but did not completely eliminate these changes compared to Sham control. There was a strong trend for attenuation in increased levels of [Ca(2+)]m, and the number of PI and TUNEL positive cells when same dose of cariporide was added only at Re, but the difference in these variables did not reach significance. In contrast, the levels of [Ca(2+)]m and the number of PI and TUNEL positive cells were significantly reduced to a level comparable to Sham control when cariporide (20 micromol/l) was administered before H and during Re, respectively, associated with a reduction in cytosolic cytochrome c, caspase-3 activity and ratio of Bax and Bcl-2. In conclusion, these data suggest that NHE-1 is involved in induction of cardiomyocyte apoptosis during both H and Re through a [Ca(2+)]m-dependent manner, thereby resulting in activation of cytochrome c-caspase-3 signaling pathways.

Inhibition of myosin light chain kinase provides prolonged attenuation of radial artery vasospasm.

OBJECTIVE: Current treatments for conduit vessel vasospasm are short-acting and do not inhibit all vasospastic stimuli. This study tests the hypothesis that irreversible inactivation of myosin light chain kinase provides sustained inhibition of arterial vasoconstriction stimulated by a spectrum of vasopressors. METHODS: Canine radial artery segments were soaked for 60 min in control buffer or buffer with wortmannin, an irreversible inhibitor of myosin light chain kinase. The vessels were then thoroughly washed and contractile responses were quantified in response to a spectrum of vasopressors at 2 and 48 h after treatment. After 48 h, selected vessels were examined for morphologic changes and development of apoptosis. RESULTS: Two hours after treatment, wortmannin-soaked vessels contracted significantly less than controls in response to norepinephrine (0.19+/-0.07 g vs. 7.22+/-0.37 g, P<0.001), serotonin (0.92+/-0.35 g vs. 9.64+/-0.67 g, P<0.001), thromboxane-mimetic U46619 (1.25+/-0.17 g vs. 10.99+/-0.50 g, P<0.001), and KCl (1.98+/-0.27 g vs.15.00+/-0.48 g, P<0.001). At 48 h, vasoconstriction remained significantly inhibited in wortmannin-treated vessels compared to control vessels in response to norepinephrine (2.36+/-0.17 vs. 6.95+/-0.47 g, P<0.001), serotonin (4.67+/-0.39 vs. 12.42+/-0.70 g, P<0.001), U46619 (5.42+/-0.34 vs. 9.29+/-0.74 g, P=0.008), and KCl (7.49+/-0.48 vs. 13.32+/-0.60 g, P<0.001). Histology of wortmannin-treated vessels revealed no overt smooth muscle or endothelial cell damage. TUNEL staining revealed a significantly greater proportion of apoptotic smooth muscle and endothelial cells in wortmannin-treated vessels as compared to controls. CONCLUSIONS: Disengaging the smooth muscle contractile apparatus by irreversibly binding myosin light chain kinase with wortmannin significantly attenuates radial artery vasoconstriction up to 48 h after brief treatment. This novel strategy may prevent vasospasm of arterial grafts from all causes for several postoperative days.

Self-perceived video-assisted thoracic surgery lobectomy proficiency by recent graduates of North American thoracic residencies.

Minimally invasive surgical techniques offer several advantages over traditional open procedures, yet the pathway to minimally invasive proficiency can be difficult to navigate. As a part of an effort of the Joint Council of Thoracic Surgical Education to increase access to this skill set in the general thoracic community, recent graduates of thoracic residencies were surveyed to determine the self-reported achievement of video-assisted thoracic surgery (VATS) lobectomy proficiency and the merits of various educational opportunities. The objective of this study was to estimate the comfort level of recent graduates with the minimally invasive approach, as this demographic not only reflects the current status of training, but represents the future of the specialty. Surgeons graduating North American thoracic residencies between 2006 and 2008 identifying themselves as practitioners of general thoracic surgery were surveyed. A total of 271 surgeons completed training between 2006 and 2008 and indicated general thoracic to be a part of their practice (84 dedicated thoracic and 187 mixed). One hundred and forty-six surgeons completed the survey (54%) including 74 of 84 (88%) dedicated thoracic surgeons. Overall, 58% of recent graduates who perform general thoracic procedures consider themselves proficient in VATS lobectomies (86% of dedicated thoracic surgeons and 28% of surgeons with a mixed practice, P < 0.0001). Of surgeons considering themselves to be proficient at VATS lobectomies, 66% felt thoracic residency was critical or very important to achieving proficiency. Fellowships after completing board residency, animal labs, and follow-up VATS courses put on by experts were much less consistently beneficial. The vast majority of the 25 dedicated general thoracic surgeons who graduate each year consider themselves proficient in VATS lobectomies, largely due to training in their thoracic residencies. On the other hand, the minority of surgeons performing general thoracic procedures as a part of a mixed practice consider themselves proficient in VATS lobectomies. Further study is warranted to enhance the VATS lobectomy experience of mixed practice surgeons particularly during their thoracic residencies.

Impact of off-pump coronary artery bypass graft surgery on postoperative pulmonary complications in patients with chronic lung disease.

BACKGROUND: Off-pump coronary artery bypass graft surgery (OPCAB) has proven to be beneficial in many high-risk subgroups. This study aims to determine whether OPCAB lowers the incidence of pulmonary complications among patients with chronic lung disease (CLD) when compared with on-pump coronary artery bypass graft surgery (ONCAB). METHODS: From 2002 to 2007, 7,060 patients underwent isolated coronary artery bypass graft surgery in an academic center. Patients were classified according to surgery type (ONCAB or OPCAB) and presence or absence of CLD. A propensity score was produced to estimate each patient's likelihood of being assigned to OPCAB on the basis of 39 preoperative risk factors. Multiple logistic regression models and adjusted odds ratios with 95% confidence intervals were used to evaluate the effect of surgery type, CLD, and their interaction on pulmonary-related complications and mortality. RESULTS: Among OPCAB patients, 15.3% (720 of 4,693) had CLD compared with 11.2% (264 of 2,367) for ONCAB. Off-pump coronary artery bypass graft surgery was performed in 73.2% of CLD patients compared with 66.5% in those without CLD (p<0.0001). Chronic lung disease was associated with a greater incidence of prolonged ventilation, reintubation, pneumonia, intensive care unit hours, and non-home discharge. After propensity score adjustment, OPCAB was associated with a significantly reduced incidence of prolonged ventilation, pneumonia, intensive care unit stay, and mortality. No significant interactions existed between surgery type and CLD status, suggesting that OPCAB was equally beneficial to patients with and without CLD. CONCLUSIONS: In this series, patients with CLD were more likely to undergo OPCAB. Patients with CLD are at significantly greater risk of pulmonary-related complications than patients without CLD. Off-pump coronary artery bypass graft surgery reduced the incidence of pulmonary complications and mortality in all patients. Importantly, this benefit was seen similarly for patients with and without CLD.