Influence of graft ischemic time on outcomes following lung transplantation.

BACKGROUND: Reperfusion injury is the most common cause of early mortality following lung transplantation. Although cold graft ischemic time has been reported to influence this injury, some lung grafts with short ischemic times develop significant reperfusion injury, whereas other grafts with more prolonged ischemic times do not develop injury. Our hypothesis was that ischemic time did not significantly influence reperfusion injury or other outcomes following lung transplantation. METHODS: Data on 136 patients who had lung transplantation over a 10 year period was used for analysis. RESULTS: Cold graft ischemic time > or = 6 hours did not increase the risk of reperfusion injury, acute rejection, cytomegalovirus infection, bacterial or fungal pneumonia, bronchiolitis obliterans syndrome, 1-month mortality, 1-year mortality, or 5-year mortality compared with ischemic times of either < 4 hours or 4 to 6 hours. The incidence of reperfusion injury was at least 20% for each time group. CONCLUSIONS: At least 20% of all patients will develop reperfusion injury regardless of cold graft ischemic time. Prolonged ischemic times up to 8 hours do not result in a significant increase in adverse short-term, intermediate, or long-term outcomes. Cautious extension of ischemic time beyond the current target of 4 to 6 hours may be warranted for geographic expansion of the donor lung pool.

A technique for the treatment of sternal infections using the Vacuum Assisted Closure device.

BACKGROUND: Sternal infections after median sternotomy remain a serious cause of postoperative morbidity and mortality. The treatment of sternal infections has evolved over the past few decades, and now aggressive surgical debridement with rotational muscle flap closure has provided an acceptable means of managing this complication. However, there are several disadvantages with this approach, mainly related to the morbidity associated with serial debridements with dressing changes and open packing until the wound is closed. Other disadvantages include potential morbidity and mortality associated with the shearing forces between the beating heart and the debrided sternal edges, and the need to paralyze the patient during the period after debridement. METHODS: Our method of managing sternal infections is based on the triad of prompt surgical debridement, serial quantitative wound cultures, and the use of the Vacuum Assisted Closure (VAC) device (KCI International, San Antonio, TX). Following debridement and irrigation, a biopsy of the healthy appearing bone is sent for quantitative culture. If culture results are favorable, the wound is then fitted with the VAC device, which consists of a non-collapsible, open-cell, polyurethane sponge with embedded vacuum tubing, a vacuum pump, and transparent adhesive dressing. When systemic signs of infection and quantitative cultures indicate the resolution of the local infection, regional muscle flap or primary wound closure is performed. CONCLUSIONS: The VAC serves as a bridge to sternal wound closure and is a safe and effective therapeutic strategy for patients with impaired physiologic reserve and/or highly contaminated wounds. We feel that it is also reasonable to consider the VAC as a preventive strategy against right ventricular rupture. Furthermore, because the firmness of the vacuum sponge apparatus acts as an impressive sternal stabilizer, post-debridement extubation is possible, reducing the need for prolonged paralysis and mechanical ventilation. This stabilization also allows early postoperative ambulation with the VAC in place. In summary, we believe that the VAC device offers an effective means of managing patients with sternal infections.

Carotid arteriography impacts carotid stenosis management.

Recent literature advocates carotid endarterectomy on duplex alone. The authors hypothesized that carotid angiography adds information that alters clinical management in a substantial number of patients compared to the use of carotid duplex examination alone. The records of 182 consecutive patients who underwent carotid artery duplex and subsequent carotid/cerebral angiography for suspected carotid artery stenosis between January 1998 and April 1999 were reviewed retrospectively. Carotid artery duplex examinations were stratified based on stenosis: < or =39%, 40% to 59%, 60% to 79% (moderate), 80% to 99% (severe), 100%. Carotid stenosis on angiograms was determined by NASCET criteria. New information found at angiography included vertebral, subclavian, or arch atherosclerosis, intracranial pathosis, or a change in duplex stenosis category to a degree of stenosis not requiring surgery. Clinical importance was attributed to angiograms that altered the patients' management plan. Angiography provided additional information in 53% (97/182) of patients. Vertebral disease was found in 25.1%, subclavian disease in 16.4%, intracranial disease in 15.3%, aortic arch disease in 3.3%. Patient treatment was altered in 30% (55/182). Angiographic findings downgraded the stenosis to medical therapy in 20.9% (38/182). The surgical plan was influenced in 5.5% (10/182). Nine intracranial aneurysms were discovered. Carotid angiography was essential for vascular bypass surgery planning in 3.3% (6/182). Angioplasty was performed in 2.2% (4/182). The accurate determination of stenosis is critical in determining optimal treatment of patients with carotid artery stenosis. Routine carotid angiography remains valuable in the clinical treatment of these patients.

A technique for adequate coverage of the proximal suture line during abdominal aortic aneurysm repair.

The proximal suture line is a vulnerable area after abdominal aortic aneurysm repairs. This area has been implicated in various postoperative complications, such as pseudoaneurysm formation, graft-enteric fistula, and suture line disruption. We present a technique that provides safe and adequate coverage of this suture line by using the aneurysm sac. This technique is derived from the z-plasty technique used for scar revision. The technique is illustrated with detailed line drawings. None of the patients in whom we used this technique have had any complications related to the proximal suture line.

Epidermal growth factor receptor up-regulation is associated with lung growth after lobectomy.

BACKGROUND: We hypothesized that compensatory lung growth after lobectomy is characterized by a combination of cellular hyperplasia and hypertrophy and that up-regulation of epidermal growth factor receptor (EGFR) is involved in these processes. METHODS: Age-matched mature pigs were divided into four groups. The control group (group C) did not have operation. Two groups underwent left upper lobectomy and were studied 2 weeks (group L2) or 3 months (group L3) later. The last group underwent a sham left thoracotomy, and the left lower lobe was harvested 2 weeks later for EGFR analysis. Left lower lobes were studied using wet weight, cell proliferation index through immunostaining for 5-bromo-2'-deoxyuridine, morphometry, and Western blot analysis for EGFR. Content of protein and DNA (deoxyribonucleic acid) in the lung tissue was also determined. RESULTS: Left lower lobe weights were elevated in both groups L2 and L3 compared with group C. We noted a significant rise in the proliferation index, with a concomitant increase in EGFR expression, in group L2 compared with group C. In group L3, there was an increase in the protein to DNA ratio compared with group C. CONCLUSIONS: We conclude that compensatory lung growth after lobectomy comprises an early increase in the cell proliferation index (ie, cellular hyperplasia) and a late increase in the protein to DNA ratio (ie, cellular hypertrophy). The early proliferative phase is associated with EGFR up-regulation.

Adenosine analogue reduces spinal cord reperfusion injury in a time-dependent fashion.

BACKGROUND: We hypothesized that inflammation during spinal cord reperfusion worsens ischemic injury. ATL-146e, an adenosine A(2A) agonist with known anti-inflammatory properties, was used to test this hypothesis at varied intervals to determine the time course of reperfusion injury. METHODS: Forty rabbits underwent cross-clamping of the infrarenal aorta for 45 minutes. One group (n = 14 animals) received 0.06 microg/kg/min systemic ATL-146e over 3 hours, beginning after 30 minutes of ischemic time. A second group (n = 6 animals) received ATL-146e over 1.5 hours. A third group (n = 3 animals) received ATL-146e over 1 hour, and a fourth group (n = 17 animals) received saline solution. All animals were assessed at 48 hours for hind limb motor function (Tarlov scale, 0-5). RESULTS: Animals that received ATL-146e for 3 hours (Tarlov score, 4.3 +/- 0.22; P <.001) or 1.5 hours (Tarlov score, 2.7 +/- 0.6; P <.05) had improved neurologic outcomes compared with rabbits that received saline solution (Tarlov score, 0.6 +/- 0.29). Animals that received ATL-146e for 1 hour (Tarlov score, 0.7 +/- 0.8) were not significantly different from those animals that received saline solution. CONCLUSIONS: Systemic ATL-146e, given during reperfusion, results in time-dependent improvement in spinal cord function after ischemia. This implies that the mechanism of spinal reperfusion injury includes leukocyte-mediated inflammation at a critical post-ischemic time interval.

Early intervention after severe oxygenation index elevation improves survival following lung transplantation.

BACKGROUND: Reperfusion injury and technical problems following lung transplantation may result in life-threatening pulmonary dysfunction that requires intervention with either extracorporeal membrane oxygenation or reoperation. Early intervention in these patients could prevent complications associated with delayed or emergent intervention and may improve survival. The oxygenation index [(mean airway pressure x percent of inspired oxygen)/partial pressure of arterial oxygen] provides a rapid assessment of pulmonary function in the critical phase of reperfusion. Our hypothesis was that the oxygenation index could be used as an early predictor for severe respiratory failure requiring acute intervention. METHODS: Analysis of 136 consecutive lung transplant operations revealed 18 patients (reperfusion injury in 16 and technical complications in 2) with an oxygen index of > or = 30. Of those patients with reperfusion injury, 9 had fibrotic lung disease, 4 had obstructive lung disease, and 3 had primary pulmonary hypertension. RESULTS: Patients undergoing transplantation for fibrotic lung diseases were more likely to develop severe reperfusion injury (oxygenation index > or = 30) compared to patients with obstructive lung diseases (9 of 42 or 21% vs 4 or 80 or 5%, p = 0.005). The 5 patients with early intervention (< or = 2 hours) after an oxygenation index elevation above 30 had significantly improved survival compared to the 13 with no or late intervention (80% vs 15% survival, p = 0.02). CONCLUSION: Oxygenation index elevation > or = 30 following lung transplantation is an early predictor of severe respiratory failure requiring acute intervention. Early intervention in these patients improves survival.

Lung transplant reperfusion injury involves pulmonary macrophages and circulating leukocytes in a biphasic response.

OBJECTIVE: Both donor pulmonary macrophages and recipient circulating leukocytes may be involved in reperfusion injury after lung transplantation. By using the macrophage inhibitor gadolinium chloride and leukocyte filters, we attempted to identify the roles of these two populations of cells in lung transplant reperfusion injury. METHODS: With our isolated, ventilated, blood-perfused rabbit lung model, all groups underwent lung harvest followed by 18-hour cold storage and 2-hour blood reperfusion. Measurements of pulmonary artery pressure, lung compliance, and arterial oxygenation were obtained. Group I (n = 8) served as a control. Group II (n = 8) received gadolinium chloride at 14 mg/kg 24 hours before lung harvest. Group III (n = 8) received leukocyte-depleted blood reperfusion by means of a leukocyte filter. RESULTS: The gadolinium chloride group had significantly improved arterial oxygenation and pulmonary artery pressure measurements compared with control subjects and an improved arterial oxygenation compared with the filter group after 30 minutes of reperfusion. After 120 minutes of reperfusion, however, the filter group had significantly improved arterial oxygenation and pulmonary artery pressure measurements compared with the control group and an improved arterial oxygenation compared with the gadolinium chloride group. CONCLUSIONS: Lung transplant reperfusion injury occurs in two phases. The early phase is mediated by donor pulmonary macrophages and is followed by a late injury induced by recipient circulating leukocytes.

Retinoic acid enhances lung growth after pneumonectomy.

BACKGROUND: We sought to identify the role of retinoic acid (RA) upon lung growth. RA has a role in perinatal lung development, and we hypothesized that exogenous RA would enhance postpneumonectomy compensatory lung growth. METHODS: Utilizing the postpneumonectomy rat model, we studied the impact of RA upon contralateral lung growth. Adult Sprague-Dawley rats were divided into three groups. Group S underwent a sham left thoracotomy, group P underwent left pneumonectomy, and group R underwent left pneumonectomy with administration of exogenous RA (0.5 microg/g/day intraperitoneally). We then quantitated right lung growth after 10 and 21 days. Lung weight and volume were expressed as a ratio to the final body weight (lung weight and volume indices, LWI and LVI). Epidermal growth factor receptor (EGFR) expression was quantitated using Western blot analysis. Cellular proliferation index (CPI) was determined using BrdU immunostaining. RESULTS: LWI, LVI, CPI, and EGFR expression at 21 days were significantly higher in group R versus S and P. At the 10-day interval, both LWI and LVI were significantly higher in group R versus S and P. CONCLUSIONS: RA administration markedly enhances lung growth after pneumonectomy, as evidenced by increases in LWI, LVI, and CPI. Upregulation of EGFR expression was associated with these effects.

Cardiac reoperation in the intensive care unit.

BACKGROUND: At our institution, cardiac reoperations are routinely performed in the cardiac intensive care unit, as opposed to taking these patients back to the operating room. Our hypothesis was that reoperation in a cardiac intensive care unit does not increase sternal infection rate. METHODS: A retrospective analysis was performed on 6,908 adult patients undergoing cardiac operation over a 9-year period. Excluding those in cardiac arrest, 340 (4.9%) patients underwent reoperation in the cardiac intensive care unit, of which 289 survived (85%). RESULTS: Of the 289 patients who survived reoperation in the intensive care unit, 6 developed wound infections that required operative debridement (2.1%), which was not significantly different from those patients not requiring reoperation (1.9%, 121 of 6,497, p = 0.70). Hospital charges for a 2-hour reoperation in the intensive care unit and operating room are approximately $1,972/patient and $5,832/patient, respectively. CONCLUSIONS: Reoperation in the intensive care unit does not increase wound infection rate compared to those without reoperation. Decreased charges, avoiding transport of potentially unstable patients, quicker time to intervention, and convenience are advantages of reoperation in an intensive care unit.

Pulmonary macrophages are involved in reperfusion injury after lung transplantation.

BACKGROUND: Reperfusion injury is a perplexing cause of early graft failure after lung transplantation. Although recipient neutrophils are thought to have a role in the development of reperfusion injury, some researchers have shown that neutrophils are not involved in its earliest phase. Intrinsic donor pulmonary macrophages may be responsible for this early phase of injury. Using the macrophage inhibitor gadolinium chloride, we attempted to investigate the role of pulmonary macrophages in reperfusion injury after lung transplantation. METHODS: Using our isolated, ventilated, blood-perfused rabbit lung model, all groups underwent lung harvest followed by 18-hour storage (4 degrees C) and blood reperfusion for 30 minutes. Group I served as a control. Group II received gadolinium chloride at 7 mg/kg 24 hours before harvest. Group III received gadolinium chloride at 14 mg/kg 24 hours before harvest. RESULTS: Group III had significantly improved arterial oxygenation and pulmonary artery pressures compared with groups I and II after 30 minutes of reperfusion. CONCLUSIONS: The earliest phase of reperfusion injury after lung transplantation involves donor pulmonary macrophages.

When to discontinue extracorporeal membrane oxygenation for postcardiotomy support.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has demonstrated limited success in adult postcardiotomy shock. The goal of this study was to determine when to discontinue ECMO for postcardiotomy support. METHODS: During a 7-year period ECMO was used in 51 postcardiotomy patients, of whom 16 (31%) weaned and 8 (16%) survived. RESULTS: Patients in the heart transplant group were more likely to wean compared with patients in the non-heart transplant group (p = 0.03). Patients aged greater than 65 years (p = 0.04) or with ejection fractions of less than 30% after 48 hours of ECMO (p < 0.001) were less likely to wean. Time on ECMO was significantly longer for survivors in the heart transplant group (101.3 +/- 7.5 hours) compared with survivors in the non-heart transplant group (28.3 +/- 11.9 hours, p < 0.001). CONCLUSIONS: After 48 to 72 hours, consideration should be given to discontinuing ECMO, either by moving to an implantable ventricular assist device or by withdrawal of support, except in those patients with heart transplants. In the latter, both severe postoperative pulmonary hypertension and reperfusion injury may take as long as 120 hours to reverse.

Material properties for modeling traumatic aortic rupture.

Traumatic aortic rupture is a significant cause of fatalities in frontal automobile crashes. However, such ruptures are difficult to reproduce experimentally in cadaveric surrogates, and it is difficult to observe dynamic aortic response in situ. So, the aortic injury mechanism or mechanisms remains in dispute. This study is a staged investigation of the physical parameters and mechanisms of human aortic rupture. The investigation includes both experimental study of local and global viscoelastic properties and failure properties of aortas using aortic tissue samples, excised aortas in vitro, and whole human aortas in situ in cadaver thoraxes. This study is the first phase in a staged programme to develop a finite element computer model of aorta injury to examine the mechanisms of aorta injury in automobile crashes. The high-rate local biaxial properties of porcine aorta tissue are determined from samples taken from the isthmus region, the most common area of failure in traumatic aorta injury. Using porcine aortas, similar in structure and physical characteristics to human aortic tissue, biaxial oscillatory response is determined at large strains and high strain rates. From this data, a hyperelastic material model with a failure threshold is developed that is in good agreement with local property data determined from oscillatory tests at 20 Hz and 65 Hz. Further, whole aorta tests are performed using pressure application with aortic pressure time histories similar in onset rate to those seen in cadaveric sled testing. These tests establish the ultimate stretch ratio and strain to failure for human aorta specimens. The specimens show no significant difference in response between the in situ tests and the in vitro tests. This indicates either that the internal thoracic boundary conditions may not be important in the stress and strain level of aorta failure or that the number of in situ tests (3) was too small to establish a difference. A Weibull survival analysis of the whole aorta failure tests shows significant dependence of aortic ultimate stretch ratio on age. A 50% risk of failure is 852 kPa in the circumferential direction and 426 kPa in the longitudinal direction. For pressure, the 50% risk of failure for all the tests is approximately 101 kPa. This increases to greater than 120 kPa for subjects below 68 years.