High-risk lead removal by planned sequential transvenous laser extraction and minimally invasive right thoracotomy.

INTRODUCTION: Transvenous pacemaker or implantable cardioverter defibrillator (ICD) lead extraction via mechanical or excimer laser sheath is typically safe and effective. Longer duration from implant, presence of large vegetations or thrombi, fractured leads, and prior failed extraction are risk factors predicting higher complication rates or incomplete or failed lead removal. Techniques developed for minimally invasive valve surgery were used in conjunction with laser extraction to refine a "hybrid" technique for lead extraction. We assessed the outcomes of high-risk lead extraction using this hybrid lead extraction technique. METHODS AND RESULTS: Retrospective assessment of clinical parameters and procedural outcomes in patients undergoing planned hybrid lead extraction from February 2008 to September 2012 was performed. We report 8 cases of hybrid lead extraction performed at our institution. We extracted 21 leads with average lead age of 13.8 years since implant. All leads were removed with complete clinical and radiographic success. There were no intraprocedure complications. One patient died of continued sepsis and 1 other had symptoms consistent with pulmonary embolism. CONCLUSIONS: Hybrid lead extraction using this technique is a safe and effective approach for removal of high-risk chronic pacemaker or ICD leads. This method extends the range of approachable leads resulting in complete removal without median sternotomy. Hybrid lead extraction can be scheduled electively facilitating complete lead removal with a low complication rate and short postoperative recovery time, mitigating the risks inherent in midline sternotomy or emergent cardiac surgical rescue.

Angiotensin-converting enzyme inhibition or mineralocorticoid receptor blockade do not affect prevalence of atrial fibrillation in patients undergoing cardiac surgery.

OBJECTIVE: This study tested the hypothesis that interruption of the renin-angiotensin system with either an angiotensin-converting enzyme inhibitor or a mineralocorticoid receptor antagonist will decrease the prevalence of atrial fibrillation after cardiac surgery. DESIGN: Randomized double-blind placebo-controlled study. SETTING: University-affiliated hospitals. PATIENTS: Four hundred forty-five adult patients in normal sinus rhythm undergoing elective cardiac surgery. INTERVENTIONS: One week to 4 days prior to surgery, patients were randomized to treatment with placebo, ramipril (2.5 mg the first 3 days followed by 5 mg/day, with the dose reduced to 2.5 mg/day on the first postoperative day only), or spironolactone (25 mg/day). MEASUREMENTS: The primary endpoint was the occurrence of electrocardiographically confirmed postoperative atrial fibrillation. Secondary endpoints included acute renal failure, hyperkalemia, the prevalence of hypotension, length of hospital stay, stroke, and death. MAIN RESULTS: The prevalence of atrial fibrillation was 27.2% in the placebo group, 27.8% in the ramipril group, and 25.9% in the spironolactone group (p=.95). Patients in the ramipril (0.7%) or spironolactone (0.7%) group were less likely to develop acute renal failure than those randomized to placebo (5.4%, p=.006). Patients in the placebo group tended to be hospitalized longer than those in the ramipril or spironolactone group (6.8±8.2 days vs. 5.7±3.2 days and 5.8±3.4 days, respectively, p=.08 for the comparison of placebo vs. the active treatment groups using log-rank test). Compared with patients in the placebo group, patients in the spironolactone group were extubated sooner after surgery (576.4±761.5 mins vs. 1091.3±3067.3 mins, p=.04). CONCLUSIONS: Neither angiotensin-converting enzyme inhibition nor mineralocorticoid receptor blockade decreased the primary outcome of postoperative atrial fibrillation. Treatment with an angiotensin-converting enzyme inhibitor or mineralocorticoid receptor antagonist was associated with decreased acute renal failure. Spironolactone use was also associated with a shorter duration of mechanical ventilation after surgery.

Minimally invasive mitral valve surgery expands the surgical options for high-risks patients.

BACKGROUND: A simplified minimally invasive mitral valve surgery (MIMVS) approach avoiding cross-clamping and cardioplegic myocardial arrest using a small (5 cm) right antero-lateral incision was developed. We hypothesized that, in high-risk patients and in patients with prior sternotomy, this approach would yield superior results compared to those predicted by the Society of Thoracic Surgeons (STS) algorithm for standard median sternotomy mitral valve surgery. METHODS: Five hundred and four consecutive patients (249 males/255 females), median age 65 years (range 20-92 years) underwent MIMVS between 1/06 and 8/09. Median preoperative New York Heart Association function class was 3 (range 1-4). Eighty-two (16%) patients had an ejection fraction ≤35%. Forty-seven (9%) had a STS predicted mortality ≥10%. Under cold fibrillatory arrest (median temperature 28°C) without aortic cross-clamp, mitral valve repair (224/504, 44%) or replacement (280/504, 56%) was performed. RESULTS: Thirty-day mortality for the entire cohort was 2.2% (11/504). In patients with a STS predicted mortality ≥ 10% (range 10%-67%), the observed 30-day mortality was 4% (2/47), lower than the mean STS predicted mortality of 20%. Morbidity in this high-risk group was equally low: 1 of 47 (2%) patients underwent reexploration for bleeding, 1 of 47 (2%) patients suffered a permanent neurologic deficit, none had wound infection. The median length of stay was 8 days (range 1-68 days). CONCLUSIONS: This study demonstrates that MIMVS without aortic cross-clamp is reproducible with low mortality and morbidity rates. This approach expands the surgical options for high-risk patients and yields to superior results than the conventional median sternotomy approach.

Minimally invasive right lateral thoracotomy without aortic cross-clamping: an attractive alternative to repeat sternotomy for reoperative mitral valve surgery.

BACKGROUND AND AIM OF THE STUDY: The study aim was to determine the safety and benefits of minimally invasive mitral valve surgery without aortic cross-clamping for mitral valve surgery after previous cardiac surgery. METHODS: Between January 2006 and August 2008, a total of 90 consecutive patients (38 females, 52 males; mean age 66 +/- 9 years) underwent minimally invasive mitral valve surgery after having undergone previous cardiac surgery. Of these patients, 80 (89%) underwent mitral valve replacement and 10 (11%) mitral valve repair utilizing a small (5 cm) right lateral thoracotomy along the 4th or 5th intercostal space under fibrillatory arrest (mean temperature 28 +/- 2 degrees C). The predicted mortality, calculated using the Society of Thoracic Surgeons (STS) algorithm, was compared to the observed mortality. RESULTS: The mean ejection fraction was 45 +/- 13%, mean NYHA class 3 +/- 1, while 66 patients (73%) had previous coronary artery bypass grafting and 37 (41%) had previous valve surgery. Twenty-six patients (29%) underwent non-elective surgery. Cardiopulmonary bypass was instituted through axillary (n = 19), femoral (n = 70) or direct use aortic (n = 1) cannulation. Operative mortality was 2% (2/90), lower than the STS-predicted mortality of 7%. Three patients (3%) developed acute renal failure postoperatively, one patient (1%) required new-onset hemodialysis, and one (1%) developed postoperative stroke. No patients developed postoperative myocardial infarction. The mean postoperative packed red blood cell transfusion requirement at 48 h was 2 +/- 3 units. CONCLUSION: Minimally invasive right thoracotomy without aortic cross-clamping is an excellent alternative to conventional redo-sternotomy for reoperative mitral valve surgery. The present study confirmed that this technique is safe and effective in reducing operative mortality in high-risk patients undergoing reoperative cardiac surgery.

Milrinone use is associated with postoperative atrial fibrillation after cardiac surgery.

BACKGROUND: Postoperative atrial fibrillation (AF), a frequent complication after cardiac surgery, causes morbidity and prolongs hospitalization. Inotropic drugs are commonly used perioperatively to support ventricular function. This study tested the hypothesis that the use of inotropic drugs is associated with postoperative AF. METHODS AND RESULTS: We evaluated perioperative risk factors in 232 patients who underwent elective cardiac surgery. All patients were in sinus rhythm at surgery. Sixty-seven patients (28.9%) developed AF a mean of 2.9+/-2.1 days after surgery. Patients who developed AF stayed in the hospital longer (P<0.001) and were more likely to die (P=0.02). Milrinone use was associated with an increased risk of postoperative AF (58.2% versus 26.1% in nonusers; P<0.001). Older age (63.4+/-10.7 versus 56.7+/-12.3 years; P<0.001), hypertension (P=0.04), lower preoperative ejection fraction (P=0.03), mitral valve surgery (P=0.02), right ventricular dysfunction (P=0.03), and higher mean pulmonary artery pressure (27.1+/-9.3 versus 21.8+/-7.5 mm Hg; P=0.001) also were associated with postoperative AF. In multivariable logistic regression, age (P<0.001), ejection fraction (P=0.02), and milrinone use (odds ratio, 4.86; 95% confidence interval, 2.31 to 10.25; P<0.001) independently predicted postoperative AF. When only data from patients with pulmonary artery catheters were analyzed and pulmonary artery pressure was included in the model, age, milrinone use (odds ratio, 4.45; 95% confidence interval, 2.01 to 9.84; P<0.001), and higher pulmonary artery pressure (P=0.02) were associated with an increased risk of postoperative AF. Adding other potential confounders or stratifying analysis by mitral valve surgery did not change the association of milrinone use with postoperative AF. CONCLUSIONS: Milrinone use is an independent risk factor for postoperative AF after elective cardiac surgery.

Complete fusion of a percutaneous aortic valve placed after ventricular assist device.

Severe aortic insufficiency following continuous flow left ventricular assist device (LVAD) placement requires intervention. Conventional corrective approaches are varied and morbid. Increasingly, percutaneous solutions, such as transcatheter aortic valve replacement (TAVR), have been used to rescue these patients. The unique flow characteristics in the aortic root following LVAD implantation may have unintended consequences to the TAVR leaflets. We describe the premature fusion of TAVR leaflets following 159 days of LVAD support. TAVR should be used with some caution in patients with continuous flow LVADs.

Angiographic Efficacy of the Atriclip Left Atrial Appendage Exclusion Device Placed by Minimally Invasive Thoracoscopic Approach.

OBJECTIVES: This study sought to assess long-term left atrial appendage (LAA) closure efficacy of the Atriclip applied via totally thoracoscopic (TT) approach with computed tomographic angiography. BACKGROUND: LAA closure is associated with a low risk for atrial fibrillation-related embolic stroke. The Atriclip exclusion device allows epicardial LAA closure, avoiding the need for post-operative oral anticoagulation. Previous data with Atriclip during open chest procedures show a high efficacy rate of closure >95%. METHODS: Three-dimensional volumetric 2-phase computed tomographic angiography ≥90 days post-implantation was independently assessed by chest radiology for complete LAA closure on all consented subjects identified retrospectively as having had a TT-placed Atriclip at Vanderbilt University Medical Center from June 13, 2011, to October 6, 2015. RESULTS: Complete LAA closure (defined by complete exclusion of the LAA with no exposed trabeculations, and clip within 1 cm from the left circumflex artery) was found in 61 of 65 subjects (93.9%). Four cases had incomplete closure (6.2%). Two clips were placed too distally, leaving a large stump with exposed trabeculae. Two clips failed to address a secondary LAA lobe. No major complications were associated with TT placement of the Atriclip. Follow-up over 183 patient-years revealed 1 stroke in a patient with complete LAA closure and no thrombus (hypertensive cerebrovascular accident). CONCLUSIONS: Angiographic LAA closure efficacy with a TT-placed Atriclip is high (93.9%). The clinical significance of a remnant stump is unknown. Confirmation of complete LAA occlusion should be made before cessation of systemic anticoagulation.

Coronary artery bypass in patients 80 years and over: is off-pump the operation of choice?

BACKGROUND: Octogenarians are at increased risk for perioperative morbidity and mortality after coronary artery bypass. In this study we compared our experience with patients undergoing on-pump coronary artery bypass (CAB) and those undergoing off-pump coronary artery bypass (OPCAB) to assess outcomes. METHODS: We used hospital database analysis in patients 80 years and older who underwent nonemergent coronary artery bypass with (N = 169) and without (N = 60) cardiopulmonary bypass from January 1999 through June 2001. RESULTS: Both groups were at increased perioperative risk based on the Society of Thoracic Surgeons risk model (7.7% OPCAB vs 5.8% CAB, p = 0.03). There were no operative deaths in the OPCAB group but there were eight (4.7%) in the CAB group (p = NS). Perioperative stroke (0% OPCAB vs 7.1% CAB, p = 0.04), prolonged ventilation (1.7% OPCAB vs 11.8% CAB, p = 0.02), and transfusion rate (33% OPCAB vs 70.4% CAB, p < 0.001) were all lower in the OPCAB group. A shorter hospital stay (6.3 days OPCAB vs 11.5 days CAB, p < 0.001) resulted in lower hospital cost in the OPCAB group ($9,363 OPCAB vs $12,312 CAB, p < 0.001). CONCLUSIONS: In this study, off-pump coronary artery bypass grafting in elderly patients was associated with fewer complications, a shorter hospital stay, and lower hospital cost. Off-pump coronary artery bypass grafting may be the operation of choice for octogenarians requiring surgical myocardial revascularization.

Quantitative Imaging of Preamyloid Oligomers, a Novel Structural Abnormality, in Human Atrial Samples.

Abnormalities in atrial myocardium increase the likelihood of arrhythmias, including atrial fibrillation (AF). The deposition of misfolded protein, or amyloidosis, plays an important role in the pathophysiology of many diseases, including human cardiomyopathies. We have shown that genes implicated in amyloidosis are activated in a cellular model of AF, with the development of preamyloid oligomers (PAOs). PAOs are intermediates in the formation of amyloid fibrils, and they are now recognized to be the cytotoxic species during amyloidosis. To investigate the presence of PAOs in human atrium, we developed a microscopic imaging-based protocol to enable robust and reproducible quantitative analysis of PAO burden in atrial samples harvested at the time of elective cardiac surgery. Using PAO- and myocardial-specific antibodies, we found that PAO distribution was typically heterogeneous within a myocardial sample. Rigorous imaging and analysis protocols were developed to quantify the relative area of myocardium containing PAOs, termed the Green/Red ratio (G/R), for a given sample. Using these methods, reproducible G/R values were obtained when different sections of a sample were independently processed, imaged, and analyzed by different investigators. This robust technique will enable studies to investigate the role of this novel structural abnormality in the pathophysiology of and arrhythmia generation in human atrial tissue.

Hypertension is associated with preamyloid oligomers in human atrium: a missing link in atrial pathophysiology?

BACKGROUND: Increasing evidence indicates that proteotoxicity plays a pathophysiologic role in experimental and human cardiomyopathy. In organ-specific amyloidoses, soluble protein oligomers are the primary cytotoxic species in the process of protein aggregation. While isolated atrial amyloidosis can develop with aging, the presence of preamyloid oligomers (PAOs) in atrial tissue has not been previously investigated. METHODS AND RESULTS: Atrial samples were collected during elective cardiac surgery in patients without a history of atrial arrhythmias, congestive heart failure, cardiomyopathy, or amyloidosis. Immunohistochemistry was performed for PAOs using a conformation-specific antibody, as well as for candidate proteins identified previously in isolated atrial amyloidosis. Using a myocardium-specific marker, the fraction of myocardium colocalizing with PAOs (PAO burden) was quantified (green/red ratio). Atrial samples were obtained from 92 patients, with a mean age of 61.7±13.8 years. Most patients (62%) were male, 23% had diabetes, 72% had hypertension, and 42% had coronary artery disease. A majority (n=62) underwent aortic valve replacement, with fewer undergoing coronary artery bypass grafting (n=34) or mitral valve replacement/repair (n=24). Immunostaining detected intracellular PAOs in a majority of atrial samples, with a heterogeneous distribution throughout the myocardium. Mean green/red ratio value for the samples was 0.11±0.1 (range 0.03 to 0.77), with a value ≥0.05 in 74 patients. Atrial natriuretic peptide colocalized with PAOs in myocardium, whereas transthyretin was located in the interstitium. Adjusting for multiple covariates, PAO burden was independently associated with the presence of hypertension. CONCLUSION: PAOs are frequently detected in human atrium, where their presence is associated with clinical hypertension.

Postoperative acute kidney injury is associated with hemoglobinemia and an enhanced oxidative stress response.

Acute kidney injury (AKI) frequently afflicts patients undergoing cardiopulmonary bypass and independently predicts death. Both hemoglobinemia and myoglobinemia are independent predictors of postoperative AKI. Release of free hemeproteins into the circulation is known to cause oxidative injury to the kidneys. This study tested the hypothesis that postoperative AKI is associated with both enhanced intraoperative hemeprotein release and increased lipid peroxidation assessed by measuring F2-isoprostanes and isofurans. In a case-control study nested within an ongoing randomized trial of perioperative statin treatment and AKI, we compared levels of F2-isoprostanes and isofurans with plasma levels of free hemoglobin and myoglobin in 10 cardiac surgery AKI patients to those of 10 risk-matched controls. Peak plasma free hemoglobin concentrations were significantly higher in AKI subjects (289.0 ± 37.8 versus 104.4 ± 36.5mg/dl, P = 0.01), whereas plasma myoglobin concentrations were similar between groups. The change in plasma F2-isoprostane and isofuran levels (repeated-measures ANOVA, P = 0.02 and P = 0.001, respectively) as well as the change in urine isofuran levels (P = 0.04) was significantly greater in AKI subjects. In addition, change in peak plasma isofuran levels correlated not only with peak free plasma hemoglobin concentrations (r² = 0.39, P = 0.001) but also with peak change in serum creatinine (r² = 0.20, P = 0.01). Postoperative AKI is associated with both enhanced intraoperative hemeprotein release and enhanced lipid peroxidation. The correlations among hemoglobinemia, lipid peroxidation, and AKI indicate a potential role for hemeprotein-induced oxidative damage in the pathogenesis of postoperative AKI.

Current status of hybrid coronary revascularization.

Hybrid coronary revascularization combines coronary artery bypass surgery with percutaneous coronary intervention techniques to treat coronary artery disease. The potential benefits of such a technique are to offer the patients the best available treatments for coronary artery disease while minimizing the risks of the surgery. Hybrid coronary revascularization has resulted in the establishment of new 'hybrid operating suites', which incorporate and integrate the capabilities of a cardiac surgery operating room with that of an interventional cardiology laboratory. Hybrid coronary revascularization has greatly augmented teamwork and cooperation between both fields and has demonstrated encouraging as well as good initial outcomes.

Results of completion arteriography after minimally invasive off-pump coronary artery bypass.

BACKGROUND: The benefits of a minimally invasive approach to off-pump coronary artery bypass remain controversial. The value of completion arteriography in validating this technique has not been investigated. METHODS: From April 2007 to October 2009, fifty-six patients underwent isolated minimally invasive coronary artery bypass grafting through a left thoracotomy without cardiopulmonary bypass. Forty-three of these patients underwent completion arteriography. RESULTS: Sixty-five grafts were performed in these 56 patients, (average, 1.2 grafts per patient; range, 1 to 3). Forty-eight grafts were studied in the 43 patients undergoing completion arteriography. There were 4 findings on arteriogram leading to further immediate intervention (8.3%). These included 3 grafts with anastomotic stenoses or spasm requiring stent placement, and 1 patient who had limited dissection in the left internal mammary artery graft and underwent placement of an additional vein graft. These findings were independent of electrocardiographic changes or hemodynamic instability. The remainder of the studies showed no significant abnormalities. There were no deaths. One patient who did not have a completion arteriogram suffered a postoperative myocardial infarction requiring stent placement for anastomotic stenosis. Patients were discharged home an average of 6.8 days postoperatively. There were no instances of renal dysfunction postoperatively attributable to catheterization. CONCLUSIONS: Minimally invasive coronary artery bypass is safe and effective. Findings of completion arteriography occasionally reveal previously under-recognized findings that, if corrected in a timely fashion, could potentially impact graft patency and clinical outcomes. Our experience validates this minimally invasive technique.

Regulation of thromboxane receptor signaling at multiple levels by oxidative stress-induced stabilization, relocation and enhanced responsiveness.

BACKGROUND: Thromboxane A(2) (TxA(2)) is a major, unstable arachidonic acid metabolite, and plays a key role in normal physiology and control of vascular tone. The human thromboxane receptor (TPß), expressed in COS-7 cells, is located predominantly in the endoplasmic reticulum (ER). Brief hydrogen peroxide exposure increases the efficiency of translocation of TPß from the ER into the Golgi complex, inducing maturation and stabilization of TPß. However, the ultimate fate of this post-ER TPß pool is not known, nor is its capacity to initiate signal transduction. Here we specifically assessed if functional TPß was transported to the plasma membrane following H(2)O(2) exposure. RESULTS: We demonstrate, by biotinylation and confocal microscopy, that exposure to H(2)O(2) results in rapid delivery of a cohort of TPß to the cell surface, which is stable for at least eight hours. Surface delivery is brefeldin A-sensitive, indicating that translocation of this receptor cohort is from internal pools and via the Golgi complex. H(2)O(2) treatment results in potentiation of the increase to intracellular calcium concentrations in response to TPß agonists U46619 and 8-iso PGF(2α) and also in the loss of ligand-dependent receptor internalization. Further there is increased responsiveness to a second application of the agonist. Finally we demonstrate that the effect of H(2)O(2) on stimulating surface delivery is shared with the FP prostanoid receptor but not the EP3 or EP4 receptors. CONCLUSIONS/SIGNIFICANCE: In summary, brief exposure to H(2)O(2) results in an immediate and sustained increase in the surface pool of thromboxane receptor that is capable of mediating a persistent hyper-responsiveness of the cell and suggests a highly sophisticated mechanism for rapidly regulating thromboxane signaling.

Routine intraoperative completion angiography after coronary artery bypass grafting and 1-stop hybrid revascularization results from a fully integrated hybrid catheterization laboratory/operating room.

OBJECTIVES: This study sought to report our experience with a routine completion angiogram after coronary artery bypass surgery (CABG) and simultaneous (1-stop) percutaneous coronary intervention (PCI) at the time of CABG performed in the hybrid catheterization laboratory/operating room. BACKGROUND: The value of a routine completion angiogram after CABG and 1-stop hybrid CABG/PCI remains unresolved. METHODS: Between April 2005 and July 2007, 366 consecutive patients underwent CABG surgery, with (n = 112) or without (n = 254) concomitant 1-stop PCI (hybrid), all with completion angiography before chest closure. Among the 112 1-stop hybrid CABG/PCI patients, 67 (60%) underwent a planned hybrid procedure based on pre-operative assessment, whereas 45 (40%) underwent open-chest PCI (unplanned hybrid) based on intraoperative findings. RESULTS: Among the 796 CABG grafts (345 left internal mammary artery, 12 right internal mammary artery/radial, and 439 veins), 97 (12%) angiographic defects were identified. Defects were repaired with either a minor adjustment of the graft (n = 22, 2.8%), with intraoperative open-chest PCI (unplanned hybrid, n = 48, 6%) or with traditional surgical revision (n = 27, 3.4%). Hybrid patients had clinical outcomes similar to standard CABG patients. CONCLUSIONS: Routine completion angiography detected 12% of grafts with important angiographic defects. One-stop hybrid coronary revascularization is reasonable, safe, and feasible. Combining the tools of the catheterization laboratory and operating room greatly enhances the options available to the surgeon and cardiologist for patients with complex coronary artery disease.

Safety of minimally invasive mitral valve surgery without aortic cross-clamp.

BACKGROUND: We developed a technique for open heart surgery through a small (5 cm) right-anterolateral thoracotomy without aortic cross-clamp. METHODS: One hundred and ninety-five consecutive patients (103 male and 92 female), age 69 +/- 8 years, underwent surgery between January 2006 and July 2007. Mean preoperative New York Heart Association function class was 2.2 +/- 0.7. Thirty-five patients (18%) had an ejection fraction 0.35 or less. Cardiopulmonary bypass was instituted through femoral (176 of 195, 90%), axillary (18 of 195, 9%), or direct aortic (1 of 195, 0.5%) cannulation. Under cold fibrillatory arrest (mean temperature 28.2 degrees C) without aortic cross-clamp, mitral valve repair (72 of 195, 37%), mitral valve replacement (117 of 195, 60%), or other (6 of 195, 3%) procedures were performed. Concomitant procedures included maze (45 of 195, 23%), patent foramen ovale closure (42 of 195, 22%) and tricuspid valve repair (16 of 195, 8%), or replacement (4 of 195, 2%). RESULTS: Thirty-day mortality was 3% (6 of 195). Duration of fibrillatory arrest, cardiopulmonary bypass, and "skin to skin" surgery were 88 +/- 32, 118 +/- 52, and 280 +/- 78 minutes, respectively. Ten patients (5%) underwent reexploration for bleeding and 44% did not receive any blood transfusions. Six patients (3%) sustained a postoperative stroke, eight (4%) developed low cardiac output syndrome, and two (1%) developed renal failure requiring hemodialysis. Mean length of hospital stay was 7 +/- 4.8 days. CONCLUSIONS: This simplified technique of minimally invasive open heart surgery is safe and easily reproducible. Fibrillatory arrest without aortic cross-clamping, with coronary perfusion against an intact aortic valve, does not increase the risk of stroke or low cardiac output. It may be particularly useful in higher risk patients in whom sternotomy with aortic clamping is less desirable.

Concanamycin and indolyl pentadieneamide inhibitors of the vacuolar H+-ATPase bind with high affinity to the purified proteolipid subunit of the membrane domain.

The macrolide antibiotic concanamycin is a potent and specific inhibitor of the vacuolar H(+)-ATPase (V-ATPase), binding to the V(0) membrane domain of this eukaryotic acid pump. Although binding is known to involve the 16 kDa proteolipid subunit, contributions from other V(0) subunits are possible that could account for the apparently different inhibitor sensitivities of pump isoforms in vertebrate cells. In this study, we used a fluorescence quenching assay to directly examine the roles of V(0) subunits in inhibitor binding. Pyrene-labeled V(0) domains were affinity purified from Saccharomyces vacuolar membranes, and the 16 kDa proteolipid was subsequently extracted into chloroform and methanol and purified by size exclusion chromatography. Fluorescence from the isolated proteins was strongly quenched by nanomolar concentrations of both concanamycin and an indolyl pentadieneamide compound, indicating high-affinity binding of both natural macrolide and synthetic inhibitors. Competition studies showed that these inhibitors bind to overlapping sites on the proteolipid. Significantly, the 16 kDa proteolipid in isolation was able to bind inhibitors as strongly as V(0) did. In contrast, proteolipids carrying mutations that confer resistance to both inhibitors showed no binding. We conclude that the extracted 16 kDa proteolipid retains sufficient fold to form a high-affinity inhibitor binding site for both natural and synthetic V-ATPase inhibitors and that the proteolipid contains the major proportion of the structural determinants for inhibitor binding. The role of membrane domain subunit a in concanamycin binding and therefore in defining the inhibitor binding properties of tissue-specific V-ATPases is critically re-assessed in light of these data.

Prevalence and clinical course of pleural effusions at 30 days after coronary artery and cardiac surgery.

The present prospective study was designed to determine the prevalence of pleural effusion at approximately 28 days after cardiac surgery and their subsequent course. This consecutive case study included 389 patients; 312 had only coronary artery bypass graft surgery (CABG) surgery, 37 had both valve and CABG surgery, and 40 had only valve surgery. Chest radiographs were obtained approximately 28 days postoperatively. Patients were subsequently contacted by telephone 3, 6, and 12 months postoperatively and questioned about the presence of fluid in their chest and related symptoms. The prevalence of pleural effusions in the patients undergoing only CABG surgery (63%) or CABG surgery plus valve surgery (62%) was significantly (p = 0.05) higher than that in the patients undergoing valve surgery only (45%). The prevalence of effusions occupying more than 25% of the hemithorax was 9.7%. The primary symptom associated with these larger effusions was dyspnea. Chest pain and fever were uncommon. Over the 12-month follow-up, the effusions tended to resolve. In conclusion, the prevalence of pleural effusions occupying more than 25% of the hemithorax is approximately 10%, 28 days postoperatively. These larger pleural effusions produce dyspnea but not chest pain or fever, and most of the effusions disappear gradually over the subsequent months.