Calculation of lung flow differential after single-lung transplantation: a transesophageal echocardiographic study.

Single-lung transplantation (SLT) is a viable option for patients with end-stage pulmonary disease. After successful SLT, pulmonary blood flow is preferentially shifted to the transplanted lung, creating a flow differential. Lack of flow differential may be indicative of potential vascular complications such as anastomotic stenosis or thrombosis. To assess the ability of transesophageal echocardiography (TEE) in estimating lung flow differential in patients undergoing SLT, biplane TEE was prospectively performed in 18 consecutive patients undergoing SLT early (24 to 72 hours), and in 10 of them late (3 to 6 months) after surgery. Right and left pulmonary vein flow were calculated as Qnu=A. VTI, where A, the pulmonary vein area, was derived as pi.(D/2)(2) and VTI is the velocity time integral of the pulmonary vein spectral display. Lung flow differential was calculated as the ratio of right (RQnu) or left (LQnu) pulmonary vein flow to total pulmonary venous flow (RQnu + LQnu). Lung perfusion imaging scintigraphy (technetium-99m) was used for comparison. Pulmonary vein velocity time integral of transplanted lung was significantly greater than that of native lung (34 +/- 9 vs 18 +/- 8 cm, p <0.001). Percent differential lung flow derived by perfusion imaging scintigraphy and by TEE showed a good correlation (r = 0.67, p <0.001). Pulmonary artery anastomoses were seen in all 12 right-lung recipients, and in 4 of the 6 left-lung recipients; no significant stenosis was noted in the arteries visualized. The pulmonary venous anastomoses were imaged in all patients. Small, nonocclusive pulmonary vein thrombi were seen in 1 patient. In conclusion, TEE is a useful method for calculating lung flow differential in patients undergoing SLT. In addition, TEE provides superb direct visualization of the venous and arterial anastomoses in most patients. Contrary to previous reports, the overall incidence of anastomotic complications is relatively low.

Posttransplant lymphoproliferative disorders in lung transplant recipients: clinical experience at a single center.

OBJECTIVES: Posttransplant lymphoproliferative disorders (PTLD) can be a significant cause of morbidity in lung transplant (LT) recipients. Risk factors include Epstein-Barr virus (EBV) infection, particularly primary infection, and immunosuppression. This article updates the incidence and presentation of PTLD at our lung transplant program. METHODS: We retrospectively reviewed the immunosuppression, EBV serology, and cases of PTLD among 129 lung transplant recipients at risk who survived > 1 month. RESULTS: There were two cases of PTLD among 129 LT patients, 2/129 (1.6%). One of these patients was among the 6 EBV seroconverters, 1/6 (16.7%), and had a typical presentation of PTLD in the allograft resulting in dissemination and death. The second case of PTLD developed in an EBV seropositive recipient who presented 33 months following LT with isolated colonic involvement. He subsequently died from chronic rejection. CONCLUSIONS: The incidence of PTLD in a LT program with a large EBV seropositive population is low, 1.6%. The presentation of PTLD in LT recipients is variable and may present typically with allograft involvement in the first year following transplantation, or late with isolated, extrapulmonic involvement.

A low incidence of posttransplant lymphoproliferative disorder in 109 lung transplant recipients.

STUDY OBJECTIVES: The incidence of posttransplant lymphoproliferative disorder (PTLD) has been reported to range from 6.4 to 20% in lung transplant (LT) recipients. Postulated contributing factors include Epstein-Barr virus (EBV) infection and the use of immunosuppression, particularly muromonab-CD3 (OKT3)(Orthoclone OKT-3; Ortho Biotech; Raritan, NJ). We sought to examine these PTLD risk factors in 109 LT recipients at our institution who survived > 1 month. DESIGN: Retrospective review of EBV serology of all LT recipients at our institution. Our standard transplant protocol includes OKT3 for induction and refractory rejection, as well as lifelong acyclovir for herpes prophylaxis. We do not perform EBV donor-recipient matching. SETTING: A university-based LT center. RESULTS: We found that 5 of 109 patients were serologically negative for EBV prior to lung transplantation, and all of these patients converted following lung transplantation. The mean time to conversion was 151 days (range, 11 to 365 days). One fatal case of PTLD was documented in an EBV seroconverter (one of five patients) 12 weeks status posttransplantation for lymphangioleiomyomatosis. One nonfatal extrathoracic PTLD was documented in a seropositive patient (1 of 104 patients) 33 months posttransplantation. CONCLUSIONS: We conclude the following: (1) PTLD in LT recipients may have a lower incidence (2 of 109 patients; 1.8%) than previously reported, despite an aggressive immunosuppressive regimen; and (2) the incidence of PTLD is higher in patients with primary EBV infection (20% vs 1%).

Use of balloon-expandable metallic stents in the management of bronchial stenosis and bronchomalacia after lung transplantation.

STUDY OBJECTIVES: Bronchial stenosis (BS) and bronchomalacia (BM) are often associated with lung allograft rejection or infection in lung transplant (LT) recipients. We reviewed our experience using balloon-expandable metallic (Palmaz) stents in the management of BS and BM in LT. DESIGN: Retrospective review of cases. PATIENTS: LT recipients with bronchoscopic and spirometric evidence of BS and BM. INTERVENTIONS: Serial balloon dilation was performed for BS. Stent placement was done for refractory or recurrent BS, or persistent focal BM. RESULTS: Twelve of 129 LT bronchial anastomoses at risk (9.3%) had complications, which included 11 BS and 5 BM. Four BS were accompanied by BM either concurrently or subsequently. The only isolated BM was associated with acute rejection and resolved after appropriate medical therapy. Balloon dilations alone were successful in relieving BS in three cases. Seven patients received a total of 11 stents. Stents were placed under conscious sedation using a flexible bronchoscope. Five of the seven patients had spirometric improvements after stent placements. One patient had no spirometric improvement, and another died before a follow-up study was done. There were no complications during stent placements. However, complications after stent placements included partial dehiscence of the stent from the bronchial wall, stent migration, partial obstruction of a segmental bronchial orifice by a stent in the main bronchus, and longitudinal stent collapse. One stent was successfully removed using a flexible bronchoscope in the endoscopy suite, and two others were removed by rigid bronchoscopy in the operating room. CONCLUSIONS: Endobronchial placement of the Palmaz stent in LT recipients is relatively easy, and it can be removed if needed. However, because there are significant potential complications, the future use of this stent as an airway prosthesis in LT remains unclear.

Testing neonate-infant membrane oxygenators with the University of Texas neonatal pulsatile cardiopulmonary bypass system in vitro.

Neurologic complications are already well documented after cardiopulmonary bypass (CPB) procedures in neonates and infants. Physiologic pulsatile flow CPB systems may be the alternative to the currently used steady-flow CPB circuits. In addition to the pulsatile pump, a membrane oxygenator should be chosen carefully, because only a few membrane oxygenators are suitable for physiologic pulsatile flow. We have tested four different types of neonate-infant membrane oxygenators for physiologic pulsatility with The University of Texas neonate-infant pulsatile CPB system in vitro. Evaluation criteria were based on mean ejection time, extracorporeal circuit (ECC) pressure, and upstroke of dp/dt. The results suggested that the Capiox 308 hollow-fibre membrane oxygenator produced the best physiologic pulsatile waveform according to the ejection time, ECC pressure, and the upstroke of dp/dt. The Minimax Plus and Masterflo Infant hollow-fibre membrane oxygenators also produced adequate pulsatile flow. Only the Variable Prime Cobe Membrane Lung (VPCML) Plus flat-sheet membrane oxygenator failed to reach the criteria for physiologic pulsatility. Depending on the oxygenator used, the lowest priming volume of the infant CPB circuit was 415 ml and the highest 520 ml.

Management of major tracheobronchial injuries: a 28-year experience.

BACKGROUND: Tracheobronchial injuries are rare but potentially life threatening. Their successful diagnosis and treatment often require a high level of suspicion and surgical repairs unique to the given injury. METHODS: We reviewed our experience with 32 patients with tracheobronchial injuries treated over the past 28 years. RESULTS: Forty-one percent (13/32) of the injuries were due to blunt trauma and 59% (19/32), to penetrating trauma. Most penetrating injuries were located in the cervical trachea (74%), whereas blunt injuries were more commonly located close to the carina (62%). Fifty-nine percent of the patients required urgent measures to secure the airway. Penetrating injuries were usually diagnosed by clinical findings or at surgical exploration. The diagnosis of blunt injuries was more difficult and required a high index of suspicion and the liberal use of bronchoscopy. The majority of the injuries were repaired primarily using techniques specific to the injury, and most patients returned to their normal activity soon after discharge. CONCLUSIONS: A high level of suspicion and the liberal use of bronchoscopy are important in the diagnosis of tracheobronchial injury. A tailored surgical approach is often necessary for definitive repair.

Monoamine oxidase inhibitors and cardiac anesthesia revisited.

There are well-recognized adverse interactions between the monoamine oxidase inhibitors and anesthetic drugs, particularly narcotics. Patients having cardiopulmonary bypass procedures are commonly anesthetized using high-dose narcotic techniques. We describe an uneventful perioperative course in a parkinsonian patient who required urgent coronary artery bypass graft surgery while he was taking selegiline, a selective inhibitor of monoamine oxidase type B.

Abdominal operations after lung transplantation. Indications and outcome.

OBJECTIVE: To assess the outcomes of abdominal operations in patients with lung transplants and identify adverse risk factors. DESIGN: Matched cohort study. SETTING: University referral center. PARTICIPANTS: Twelve lung transplant recipients who required abdominal operations (hereafter referred to as case patients) and 12 age-, sex-, and pulmonary diagnosis-matched lung transplant recipients who had not undergone an abdominal procedure (hereafter referred to as control patients). INTERVENTIONS: Elective abdominal operations including laparoscopic cholecystectomies (n = 5), laparoscopic repair of a colovaginal fistula (n = 1), and open colectomy for a benign colovesical fistula (n = 1) and urgent operations including bowel resections (n = 3), subtotal pancreatectomy (n = 1), and hepatorrhaphy for an iatrogenic liver injury (n = 1). MAIN OUTCOME MEASURES: Morbidity and mortality. RESULTS: Abdominal operations were performed in 12 (11%) of the patients undergoing lung transplantation at the university referral center since 1987, with an associated mortality rate of 25%. Morbidity and mortality rates of electively performed procedures were 28% and 14%, respectively. An urgent indication for abdominal procedure was associated with 100% morbidity and 40% mortality. Compared with a matched group of 12 control patients, the long-term survival of the case patients was reduced (18% vs 64% at 4 years). Case patients undergoing an abdominal procedure in the posttransplantation period tended to have a higher prevalence of previous rejection (67% vs 25%), a higher perioperative steroid dosage (53 mg/d vs 36 mg/d), and a significantly lower posttransplantational forced expiratory volume in 1 second (FEV1, 1.23 L vs 1.91 L; P < .05). CONCLUSIONS: Elective abdominal operations are relatively safe in properly prepared lung transplant recipients. However, laparotomy for urgent surgical conditions is associated with increased morbidity and mortality rates caused in part by the magnitude of the abdominal operation and influenced by the status of the lung transplant as manifested by previous rejection episodes, perioperative steroid dosages, and FEV1 values.

Dual-inflow great vessel aneurysm: delayed presentation after penetrating trauma.

Aneurysms constitute uncommon sequelae of injuries to the thoracic outlet. Most such aneurysms are secondary to blunt trauma and usually involve the great vessels at their take-off from the aortic arch. Penetrating injuries are more often identified in the more distal vessels and only very rarely present as pseudoaneurysms. Reported here is a single case of a chronic posttraumatic pseudoaneurysm arising from both the right common carotid artery and the right subclavian artery. The workup and surgical approach provide practical lessons, complemented with illustrations that aid in the understanding of the case. It is an unusual case because of the dual-inflow nature of the aneurysm.

Systemic availability of itraconazole in lung transplantation.

Systemic availability of itraconazole in lung transplantation was evaluated by serially measuring the bioactivity of itraconazole in lung transplant patients who received itraconazole for prophylaxis (n = 12) or therapy (n = 5). These patients also received concomitant antacid and H2 blocker therapy. In patients receiving itraconazole at 200 and 400 mg/day, the median concentrations in serum were 0.5 microgram/ml (range, < 0.05 to 2.7) and 3.5 micrograms/ml (< 0.5 to 14), respectively. The concentration following administration of 400 mg/day was > 2.5 micrograms/ml in 56% of samples, while only 4% of samples from patients who were administered 200 mg/day had levels over 2.5 micrograms/ml. This study documents that itraconazole can be absorbed in patients receiving concomitant antacid and H2 blocker therapy. However, the reduced and variable absorption suggests the importance of confirming drug delivery by measurement of concentrations in serum.

Twelve-hour canine heart preservation with a simple, portable hypothermic organ perfusion device.

BACKGROUND: Cardiac transplantation is limited to an ischemic time of around 6 hours by available preservation solution and technique. Complex organ preservation devices have been developed that extend this time to 24 hours or more, but are clinically impractical. This study evaluates a portable oxygen-driven organ perfusion device weighing approximately 13.5 kg. METHODS: Organs are perfused with the University of Wisconsin solution at low perfusion pressure using less than 400 L of oxygen per 12 hours. Left ventricular parameters were measured in anesthetized adult beagles to establish control values (n = 5). Hearts were procured after cardioplegia with 4 degrees C University of Wisconsin solution, weighed, then stored for 12 hours in University of Wisconsin solution at 4 degrees C. Hearts were perfused (n = 3) or nonperfused (n = 2) during storage. Organ temperature, partial pressure of oxygen in the aorta and right atrium, perfusion pressure, and aortic flow were recorded hourly in perfused hearts. After 12 hours, hearts were transplanted into littermates and left ventricular parameters measured after stabilization off bypass. RESULTS: Organ weight for both groups was unchanged. Nonperfused hearts required both pump and pharmacologic support with significantly depressed left ventricular function. Perfused hearts needed minimal pharmacologic support, with left ventricular end-diastolic pressure, cardiac output, and rate of change of left ventricular pressure showing no statistical difference from control. CONCLUSIONS: These findings confirm the potential for extended metabolic support for ischemia-intolerant organs in a small, lightweight, easily portable preservation system.

Penetrating intrapericardial wounds: clinical experience with a surgical protocol.

BACKGROUND: From 1972 to 1977, a treatment protocol was developed at our institution for patients with suspected penetrating intrapericardial wounds. It consists of immediate transport to the operating room, pericardial decompression by subxiphoid pericardial window under local or light general anesthesia in patients in stable condition, and median sternotomy and operative repair with limited use of cardiopulmonary bypass. METHODS: The records of 79 consecutive patients with acute penetrating intrapericardial injury who underwent operation from March 1978 to July 1991 were reviewed. There were 59 patients (75%) with stab wounds and 20 (25%) with gunshot wounds. Wound location was as follows: right ventricle, 33 (42%); left ventricle, 28 (35%); multiple sites, 8 (10%); atrium, 5 (6%); and great vessels, 5 (6%). RESULTS: Subxiphoid pericardial window was performed under local or light general anesthesia in 53 patients (67%). Cardiopulmonary bypass was required in only 4 patients. Overall mortality was 6%. CONCLUSION: Approach to a trauma victim must be systematic. We believe one treatment protocol for patients with suspected penetrating intrapericardial wounds is effective.

Homograft patch repair for hemorrhagic mediastinitis.

Hemorrhage from the heart and great vessels is a potentially lethal complication of post-sternotomy mediastinitis. We report 2 cases in which a cryopreserved descending thoracic aortic homograft was used successfully to repair defects of the ascending aorta and right ventricle in the setting of active mediastinal infection. An overview of mediastinitis and management strategies for life-threatening mediastinal bleeding is included.

Medium term functional results of single-lung transplantation for endstage obstructive lung disease.

Controversy has surrounded the use of single-lung transplantation (SLT) for the treatment of endstage obstructive lung disease. In recent years, several transplant centers have performed SLT for such indications. In this report, we describe functional results in patients undergoing SLT for obstructive lung disease, twenty-two followed over one year and 10 over two years. Data include pulmonary function testing, gas exchange, quantitative ventilation and perfusion to the lung graft, and results of symptom-limited graded cycle exercise testing after SLT. Our results show improvement in obstructive dysfunction FEV1 0.49 +/- 0.13 L (16 +/- 4% predicted) pre-SLT to 1.71 +/- 0.43 L (57 +/- 12% predicted) 3 mo after SLT, FEV1/FVC 0.30 +/- 0.07 pre-SLT to 0.75 +/- 0.09 3 mo after SLT, and improvement in arterial oxygenation, PaO2 58 +/- 10 mm Hg pre SLT to PaO2 86 +/- 13 mm Hg 3 mo post-SLT. In addition, these improvements were sustained up to 1 to 2 yr post-SLT. The majority of ventilation and perfusion go to the new lung graft. After SLT, patients have reduced maximum oxygen consumption (VO2max 40 to 60% predicted) but do not have ventilatory limitation to exercise and can carry out daily activities without compromise. We conclude that SLT is a viable medium-term therapeutic option for endstage obstructive lung disease. The long-term future of this technique remains to be determined.

Ischemic contracture begins when anaerobic glycolysis stops: a 31P-NMR study of isolated rat hearts.

The relationships among myocardial ATP, intracellular pH, and ischemic contracture in Langendorff-perfused rat hearts were investigated by 31P nuclear magnetic resonance spectroscopy during total global normothermic ischemia while the left ventricular pressure was recorded continuously via an intraventricular balloon. Glucose-perfused hearts (n = 63) were divided into five groups based on the time of onset of contracture (TOC), and three other groups of hearts were treated to vary the ischemic glycogen availability. ATP levels, which showed no evidence of accelerated ATP depletion during contracture, were significant and variable at TOC. Intracellular pH initially declined and then leveled off at TOC, with lower final pH in hearts with later TOC. We conclude that contracture began when anaerobic glycolysis (and thus glycolytic ATP synthesis) stopped. These results, though consistent with the concept that ischemic contracture in normal hearts results from rigor bond formation due to low ATP levels at the myofibrils, suggest that TOC is more closely related to glycolytic ATP production than to total cellular ATP content, thus providing evidence of some degree of subcellular compartmentation or metabolite channeling. In glycolytically inhibited hearts, the quite early contracture may have a Ca2+ component.

31P NMR measurement of mitochondrial uncoupling in isolated rat hearts.

Mitochondrial uncoupling is often invoked as a mechanism underlying cellular dysfunction; however, it has not been possible to study this phenomenon directly in intact cells and tissues. In this paper, we report direct evaluation of mitochondrial uncoupling in the intact myocardium using 31P NMR magnetization transfer techniques. Langendorff perfused rat hearts were exposed to either a known uncoupler, 2,4-dinitrophenol (DNP), or a potential uncoupler, octanoate. Both DNP and octanoate decreased mechanical function as measured by the rate pressure product and caused an increase in the oxygen consumption rate (MVO2); with DNP this increase in MVO2 was dose-dependent. The ATP synthesis rate measured by 31P NMR, however, was not elevated commensurately with MVO2; instead, the P/O ratio declined. In contrast, the linear relationship between the ATP synthesis rate and rate pressure product was not altered by the uncoupling agents. These data demonstrate that 1) 31P NMR magnetization transfer can be utilized to measure uncoupling of oxidative phosphorylation in intact organs, 2) octanoate does not induce excess ATP utilization in the intact heart, and 3) high levels of octanoate induce mitochondrial uncoupling in the intact myocardium; and this may, in part, be the cause of the toxic effects associated with fatty acid exposure.

A comparison of different carbohydrates as substrates for the isolated working heart.

Ribose has been shown to greatly enhance ATP recovery in situations such as postischemia when total adenine nucleotides have been depleted by catabolism. In addition, metabolic studies have reported that both five carbon sugars and alcohols (ribose and xylitol) can support energy metabolism presumably after conversion to substrates for glycolysis. Because of the importance of these two aspects of energy metabolism to myocardial function, we compared the ability of ribose and xylitol with glucose and pyruvate as exclusive substrates for the isolated working rat heart. Our studies revealed, however, that the utilization of ribose or xylitol as substrates by the myocardium is not sufficiently rapid to rely on these as exclusive oxidizable substrates. In fact, ribose or xylitol are no more effective than substrate-free medium in this regard. Myocardial glycogen was depleted in these groups and after a lag period consumption of oxygen also decreased. In contrast to the postischemic situation the total adenine nucleotide levels were preserved during ribose, xylitol or substrate-free perfusion. Consequently, the energy charge in these hearts fell significantly. In hearts perfused with ribose, xylitol or no substrate, the rate pressure product and the stroke volume rapidly declined after an initial brief stable period corresponding to glycogen depletion. Glycogen levels were 6% of the average control value in ribose- and xylitol-perfused hearts and were undetectable in substrate-free perfused hearts. In contrast, either glucose or pyruvate supported steady levels of ATP and myocardial oxygen consumption; maintained the energy charge; and supported the stroke volume, rate pressure product, and cardiac work. In glucose-perfused hearts the glycogen was reduced to 21% of control values, while in pyruvate-perfused hearts the average glycogen levels were 76% of control. Thus, although the heart is able to metabolize ribose and xylitol through the hexose monophosphate pathway, the rate of utilization through glycolysis and presumably the TCA cycle is not sufficient for these compounds to serve as exclusive substrates for the isolated working heart.

ATP synthesis kinetics and mitochondrial function in the postischemic myocardium as studied by 31P NMR.

The effects of ischemia on mitochondrial function and the unidirectional rate of ATP synthesis (Pi----ATP rate) were studied using a Langendorff-perfused heart preparation and 31P NMR spectroscopy. There was significant postischemic depression of mechanical function assessed as the heart rate pressure product, and the myocardial oxygen consumption rate at a given rate pressure product was elevated. Experiments performed on glucose- and pyruvate-perfused hearts demonstrated the presence of a large contribution to the unidirectional Pi----ATP rate catalyzed by glyceraldehyde-3-phosphate dehydrogenase and phosphoglycerate kinase. This rate was much greater than the maximal glucose utilization rate in the myocardium, demonstrating that the glyceraldehyde-3-phosphate dehydrogenase/phosphoglycerate kinase reactions are near equilibrium both before and after ischemia. In the pyruvate-perfused postischemic hearts, the glycolytic contribution was eliminated and the net rate of ATP synthesis by oxidative phosphorylation was measurable. Despite the reduced mechanical function and increased myocardial oxygen consumption rate, the ratio of the net rate of ATP synthesis by oxidative phosphorylation to oxygen consumption rate (the P:O ratio) was not altered subsequent to ischemia (2.34 +/- 0.12 and 2.36 +/- 0.09 in normal and postischemic hearts, respectively). Therefore, mitochondrial uncoupling cannot be the cause of postischemic depression in mechanical function; instead, the data suggest the existence of ischemia-induced inefficiency in ATP utilization.

Substrate effects in the post-ischemic myocardium.

A study was undertaken to examine the effects of glucose versus pyruvate as the sole substrate following severe myocardial ischemia. Glycolysis usually contributes only a small amount to total ATP production and may be rate limiting in providing tricarboxylic acid (TCA) cycle substrates. Consequently, pyruvate may be a more effective substrate by bypassing glycolysis to feed directly to the TCA cycle and oxidative phosphorylation. Isolated rat hearts were studied in a retrograde (Langendorff) perfusion apparatus while in an NMR spectrometer. Rate pressure product (RPP), myocardial oxygen consumption (MVO2), and the unidirectional Pi----ATP rate were measured in control and postischemic hearts with or without the inotrope dobutamine. The undirectional Pi----ATP rate was higher in the glucose than the pyruvate hearts and the difference increased further postischemia. This increase over that of the pyruvate hearts has been attributed to a glycolytic component of ATP metabolism. Oxygen consumption was higher in pyruvate hearts at equivalent levels of performance. It thus appears that the glycolysis rate is significant and may be elevated following severe myocardial ischemia. Perfusion with pyruvate requires increased rates of oxidative phosphorylation to make up for the loss of glycolytically produced ATP. Optimal postischemic substrate delivery may require several compounds, one of which should be glucose.