Craig J. Baker

Prophylactic photopheresis and chronic rejection : effects on graft intimal hyperplasia in cardiac transplantation

Background: Despite the decreased incidence of acute rejection episodes and improvements in short and intermediate term graft survival with current immunosuppressive agents, there has been little progress in decreasing the morbidity and mortality from chronic rejection. This phenomenon may, in part, be related to the development of a humoral immune response with increases in anti‐HLA antibodies, which presents as accelerated graft arteriopathy with intimal hyperplasia. 
Methods: Based on prior experimental work, a pilot, prospective, randomized study was performed in 23 primary cardiac transplant recipients to determine whether the addition of prophylactic photopheresis to a cyclosporine, azathioprine and prednisone regimen was safe and resulted in decreased levels of panel reactive antibodies (PRA) and transplant arteriopathy. 
Results: There was no difference between the two groups in regard to infection or acute rejection incidence. The photopheresis group had a significant reduction in PRA levels at two time points within the first 6 postoperative months. Coronary artery intimal thickness was significantly reduced in the photopheresis group at 1‐yr (0.23 vs. 0.49 mm, p<0.04) and 2‐yr (0.28 vs. 0.46 mm, p<0.02) follow‐up compared with the control group. 
Conclusion: In this small pilot study, photopheresis is a safe, well‐tolerated immunomodulatory technique that is capable of decreasing the severity of chronic rejection manifesting as post‐transplant graft intimal hyperplasia.

A Decade of Living Lobar Lung Transplantation: Perioperative Complications after 253 Donor Lobectomies†

Living lobar lung transplantation places two donors at risk for each recipient. We examined the perioperative outcomes associated with the 253 donor lobectomies performed at our institution during our first decade of living lobar lung transplantation. There have been no perioperative or long‐term deaths. 80.2% of donors (n = 203) had no perioperative complications, while fifty (19.8%) had one or more complication. The incidence of intraoperative complications was 3.6%. Complications requiring reoperation occurred in 3.2% of donors. 15.0% of donors had other perioperative complications; the most serious were two donors who developed pulmonary artery thrombosis, while the most common was the need for an additional thoracostomy tube or a thoracostomy tube for ≥14 d for persistent air leaks and/or drainage. Right‐sided donors were more likely to have a perioperative complication than left‐sided donors (odd ratio 2.02, p = 0.04), probably secondary to right lower and middle lobe anatomy. This experience has shown donor lobectomy to be associated with a relatively low morbidity and no mortality, and is important if this procedure is to be considered an option at more pulmonary transplant centers, given continued organ shortages and differences in philosophical and ethical acceptance of live

Midterm results of the Ross procedure.

BACKGROUND The optimal hemodynamic performance and potential growth of the pulmonary autograft has led to expanded indications for the Ross procedure. We reviewed our institutional experience to assess midterm results with the Ross operation. METHODS In a 7-year period (1992 to 1999), 111 patients with a median age of 15.7 years (range 2 days to 67 years), underwent the Ross procedure. Ninety-five patients had isolated aortic valve disease and 16 pediatric patients had a more complex left ventricular outflow tract obstruction. RESULTS There were 3 early (2.7%) and 3 late deaths over a median follow-up of 3.6 years (range 6 months to 7.6 years). Actuarial survival at 5 years was 94%+/-2%. In pediatric patients, the pulmonary autograft annulus enlarged from 14.7+/-6.2 mm to 22+/-6.3 mm. This growth followed the expected increase in pulmonary valve diameter based on body surface area. Eight reoperations were necessary for autograft insufficiency at a median interval of 14 months (range 2 days to 31 months). Freedom from replacement of the pulmonary autograft was 91%+/-3% at 5 years. Three patients developed important obstruction of the pulmonary homograft requiring reoperation at a median of 29 months (range 9 to 31 months). CONCLUSIONS The Ross procedure can be performed with good midterm results. In pediatric patients, autograft growth has been appropriate. The potential for development of important autograft insufficiency suggests close follow-up through the intermediate and late term.

Platelet activating factor acetylhydrolase decreases lung reperfusion injury.

BACKGROUND Ischemia-reperfusion injury involves free radical production, polymorphonuclear neutrophil chemotaxis/degranulation, and production of proteolytic enzymes, complement components, coagulation factors, and cytokines. Activated polymorphonuclear neutrophils, endothelial cells, and macrophages produce platelet activating factor, which further promotes these inflammatory reactions. The recently cloned plasma form of platelet activating factor-acetylhydrolase (PAF-AH) demonstrates antiinflammatory effects by degrading platelet activating factor. We evaluated the effects of PAF-AH in an isolated perfused rat lung model by adding it to the flush solutions or to the reperfusion blood. METHODS Rat lungs were isolated, flushed with EuroCollins (EC) or University of Wisconsin (UW) solution, stored at 4 degrees C for 6 or 12 hours, and reperfused using a cross-circulating syngeneic support rat. During reperfusion, oxygenation, compliance, and capillary filtration coefficient were calculated. There were four groups in the study; group I (control) had no PAF-AH added, group II had PAF-AH added to the flush solution, group III had PAF-AH added to reperfusion blood, and group IV had PAF-AH added to both flush solution and reperfusion blood. RESULTS After 6 hours of storage, oxygenation, compliance, and capillary filtration coefficient significantly improved for EC in group IV. For UW, oxygenation improved in group IV whereas compliance improved in groups II, III, and IV. After 12 hours of storage, compliance improved for EC in group IV and capillary filtration coefficient improved in groups III and IV. For UW, oxygenation and compliance improved in groups II and IV, whereas capillary filtration coefficient improved in group IV. CONCLUSIONS Addition of PAF-AH to intracellular organ preservation solutions and to the blood reperfusate significantly improves postreperfusion oxygenation and compliance, and reduces lung capillary permeability.

Regional topical hypothermia of the beating heart: preservation of function and tissue

BACKGROUND Protection of the myocardium during beating heart operations is paramount. The goal of this study is to determine if regional topical hypothermia (RTH) preserves myocardial viability and function during periods of temporary coronary artery occlusion. METHODS Sixteen pigs were divided into two groups (RTH and control). Each group received 40 minutes of midleft anterior descending coronary occlusion followed by 3 hours of reperfusion. The RTH group (n = 10) received RTH and the control group (n = 6) received no cooling. Myocardial and core temperatures were measured with thermistors. Sonomicrometers and micromonameters were used to determine load independent indices of myocardial function. These indices were measured at base line, during coronary occlusion, and at 3 hours of reperfusion. The myocardium at risk and the infarct area were determined with monastral blue dye and triphenyl tetrazolium chloride staining. RESULTS The mean myocardial temperature in the risk zone during coronary occlusion was significantly less in the RTH group (29.4 degrees C +/- 5.6 degrees C versus 35.7 degrees C +/- 1.1 degrees C, p < 0.05). After 40 minutes of coronary occlusion, both the RTH group and control had a significant reduction in regional elastance (9.38 +/- 3.54 and 11.05 +/- 1.67 mm Hg/mm) compared with base line measurements (14.70 +/- 2.42 and 16.80 +/- 4.79 mm Hg/mm), p < 0.05. However, after 3 hours of reperfusion, the elastance returned to base line levels in the RTH group (15.83 +/- 3.06 mm Hg/mm) but remained significantly depressed in the control group (9.97 +/- 3.63 mm Hg/mm, p < 0.04). Myocardial necrosis as a percentage of the risk zone was significantly less in the hypothermia group (25% +/- 2% versus 62% +/- 5%, p < 0.001). CONCLUSIONS Regional topical hypothermia during isolated temporary coronary occlusion provides regional myocardial protection expressed as a return of function and decreased necrosis. Regional topical hypothermia may be clinically applicable to myocardial preservation during beating heart operations.

Hemidiaphragm plication after repair of congenital heart defects in children : Quantitative return of diaphragm function over time

OBJECTIVE Phrenic nerve injury resulting in hemidiaphragm paresis leads to morbidity in children undergoing repair of congenital heart defects. Previous studies have documented short-term benefits of diaphragm plication, but little is known about the return of diaphragm function. METHODS We reviewed 46 consecutive patients undergoing hemidiaphragm plication after repair of congenital heart defects. The function of plicated diaphragms was measured at follow-up fluoroscopy using excursion of the unplicated side as a control. RESULTS The median age at the procedure resulting in phrenic nerve injury was 6.4 months (0-62 months). Among the 46 patients, 29 (63%) and 17 (37%) had repair for single and 2-ventricle defects, respectively. Hemidiaphragm paresis occurred on the left side in 32 patients (70%). Phrenic nerve injury was documented at a median of 8 days (1-84 days) after operation. The median time from diagnosis to plication was 2 days (0-21 days). Five patients required prolonged ventilation after plication. One patient died 10 weeks later, and 4 patients required tracheostomy. The remaining 41 patients were extubated within 2 days (0-19 days). In 17 patients, fluoroscopy assessing diaphragm motion was performed at a mean interval of 16.4 months after plication. Excursion of the plicated diaphragm was 77% of the contralateral side. There was a trend toward improved function over time. CONCLUSIONS Hemidiaphragm paresis results in significant morbidity after repair of congenital heart defects. Early diagnosis and plication result in timely extubation. The plicated diaphragm demonstrates return of function that may improve over time. This is the first study to numerically quantitate the degree of diaphragm recovery.

Development of a cardiac surgery simulation curriculum: From needs assessment results to practical implementation

OBJECTIVE A paradigm shift in surgical training has led to national efforts to incorporate simulation-based learning into cardiothoracic residency programs. Our goal was to determine the feasibility of developing a cardiac surgery simulation curriculum using the formal steps of curriculum development. METHODS Cardiothoracic surgery residents (n = 6) and faculty (n = 9) evaluated 54 common cardiac surgical procedures to determine their need for simulation. The highest scoring procedures were grouped into similarly themed monthly modules, each with specific learning objectives. Educational tools consisting of inanimate, animate, and cadaveric facilities and a newly created virtual operating room were used for curriculum implementation. Resident satisfaction was evaluated by way of a 5-point Likert scale. Perceived competency (scale of 1-10) and pre-/post-self-confidence (scale of 1-5) scores were collected and analyzed using cumulative mean values and a paired t-test. RESULTS Of the 23 highest scoring procedures (mean score, ≥ 4.0) on the needs assessment, 21 were used for curriculum development. These procedures were categorized into 12 monthly modules. The simulation curriculum was implemented using the optimal simulation tool available. Resident satisfaction (n = 57) showed an overwhelmingly positive response (mean score, ≥ 4.7). The perceived competency scores highlighted the procedures residents were uncomfortable performing independently. The pre-/post-self-confidence scores increased throughout the modules, and the differences were statistically significant (P < .001). CONCLUSIONS It is feasible to develop and implement a cardiac surgery simulation curriculum using a structured approach. High-fidelity, low-technology tools such as a fresh tissue cadaver laboratory and a virtual operating room could be important adjuncts.

A comparison of aortic valve replacement via an anterior right minithoracotomy with standard sternotomy: a propensity score analysis of 492 patients

OBJECTIVES Right anterior minithoracotomy with central arterial cannulation is our preferred technique of minimally invasive aortic valve replacement (AVR). We compared perioperative outcomes with this technique to those via sternotomy. METHODS Between March 1999 and December 2013, 492 patients underwent isolated AVR via either sternotomy (SAVR, n = 198) or minimally invasive right anterior thoracotomy (MIAVR, n = 294) in our institution. Univariate comparisons between groups were made to evaluate overall outcomes and adverse events. To control treatment selection bias, propensity scores were constructed from core patient characteristics. A propensity score-stratified analysis of outcome and adverse events was then performed. RESULTS Overall mortality was 2.5 and 1.0% in the SAVR and MIAVR groups, respectively. Hospital and ICU stays were shorter, there was less intraoperative blood product usage, and fewer wound infections in the MIAVR group. There were no differences in other adverse events, including strokes. The composite end-point of alive and adverse event-free was significantly more common in the MIAVR group (83 vs 74%, P = 0.002). After adjusting for the propensity score, hospital and ICU stays remained shorter and intraoperative blood product usage remained less in the MIAVR group. There was no difference in mortality, stroke or other adverse events between groups. CONCLUSION Minimally invasive AVR via an anterior right thoracotomy with predominately central cannulation can be performed with morbidity and mortality similar to that of a sternotomy approach. There appear to be advantages to this minimally invasive approach when compared with sternotomy in terms of less intraoperative blood product usage, lower wound infection rates and decreased hospital stays. If mortality and the occurrence of adverse events are taken together, MIAVR may be associated with better outcomes. As minimally invasive AVR becomes more common, further long-term follow-up is needed and a prospective multicentre randomized trial would be warranted.

Depopulated vena caval homograft: A new venous conduit

OBJECTIVE Completion of the Fontan procedure is frequently performed by using an extracardiac conduit between the inferior vena cava and the pulmonary artery. Most centers use a polytetrafluoroethylene graft for the extracardiac conduit, and because re-endothelialization is unlikely, anticoagulation is used for a variable period. This study explores the use of an alternate large-caliber venous conduit. METHODS The superior vena cava was replaced in 8 minipigs with either a polytetrafluoroethylene interposition graft (2 pigs) or a depopulated (acellular), cryopreserved superior vena caval homograft (6 pigs). After 6 months, the animals were killed, and the grafts were examined for patency and histology, including immunostaining. No anticoagulation was used. RESULTS Polytetrafluoroethylene grafts have a cross-sectional luminal narrowing, ranging from 16% to 40%. Histology showed only partial intimal ingrowth, with excessive subendothelial fibrosis and early calcification. In contrast, the depopulated venous homografts showed minimal luminal narrowing, ranging from 2% to 9%. These grafts were completely repopulated by the recipient with an endothelial lining, which stained positively for factor VIII, and a subendothelial region appropriately recellularized by myofibroblasts, which stained positively for smooth muscle actin and procollagen. There was no evidence of an immune response to the venous homografts, as judged by staining for T-cell surface antigen, CD4, and CD8. Thrombus was not seen in any of the grafts. CONCLUSION Depopulated, cryopreserved vena caval homografts might be superior conduits for cavopulmonary connection during completion of the Fontan operation by using the extracardiac conduit technique.

Resection of Giant Coronary Artery Aneurysms in a Takayasu's Arteritis Patient

Takayasus arteritis is a chronic vasculitis of unknown cause. Coronary arteries are affected in approximately 10% of cases with aneurysm formation being extremely rare. Coronary aneurysms (not related to Takayasus arteritis) have been surgically treated with aneurysm resection and coronary bypass. We describe the case of a young woman found to have giant coronary artery aneurysms. She underwent resection of the aneurysms and short segment saphenous vein bypass to the right and left coronary arteries. In reviewing the literature, this seems to be the first case of Takayasus arteritis related to coronary artery aneurysm treated surgically with a good result.