Secondary pulmonary hypertension does not adversely affect outcome after single lung transplantation.

OBJECTIVE: Primary and secondary pulmonary hypertension have been associated with poor outcomes after single lung transplantation. Some groups advocate double lung transplantation and the routine use of cardiopulmonary bypass during transplantation in this population. However, the optimal procedure for these patients remains controversial. The goal of our study was to determine the safety of single lung transplantation without cardiopulmonary bypass in patients with secondary pulmonary hypertension. METHODS: We retrospectively reviewed 76 consecutive patients with pulmonary parenchymal disease who underwent single lung transplantation from 1992 to 1998. Recipients were stratified according to preoperative mean pulmonary artery pressure. Secondary pulmonary hypertension was defined as parenchymal lung disease with a preoperative mean pulmonary artery pressure of 30 mm Hg or more. Patients with primary pulmonary hypertension or Eisenmenger's syndrome were excluded from analysis. RESULTS: Eighteen of 76 patients had secondary pulmonary hypertension. No patient with secondary pulmonary hypertension required cardiopulmonary bypass, whereas 1 patient without pulmonary hypertension required bypass. After the operation, no significant differences were seen in lung injury as measured by chest radiograph score and PaO(2)/FIO(2) ratio, the requirement for inhaled nitric oxide, the length of mechanical ventilation, the intensive care unit or hospital length of stay, and 30-day survival. There were no differences in the forced expiratory volume in 1 second or 6-minute walk at 1 year, or the incidence of rejection, infection, or bronchiolitis obliterans syndrome greater than grade 2. Survival at 1, 2, and 4 years after transplantation was 86%, 79%, and 65%, respectively, in the low pulmonary artery pressure group and 81%, 81%, and 61%, respectively, in the group with secondary pulmonary hypertension (P >.2). CONCLUSION: We found that patients with pulmonary parenchymal disease and concomitant secondary pulmonary hypertension had successful outcomes as measured by early and late allograft function and appear to have acceptable long-term survival after single lung transplantation. Our results do not support the routine use of cardiopulmonary bypass or double lung transplantation for patients with this disorder.

Intraoperative prosthetic valve dysfunction: detection by transesophageal echocardiography.

We describe the valuable role of intraoperative transesophageal echocardiography in the detection of immediate prosthetic valve dysfunction. Transesophageal echocardiography accurately diagnosed one leaflet of a St. Jude Medical mitral valve to be stuck. We recommend routine transesophageal echocardiography for mitral valve operations.

The past, present, and future of lung transplantation.

BACKGROUND: The history of lung transplantation from the first human transplant performed in 1963 to the present is reviewed with particular focus on the added challenges because of the contaminated bronchus, exposure of the graft to airborne organisms, the poor blood supply to the bronchus, and the problem of reperfusion pulmonary edema. METHODS: The technical aspects of single and double sequential lung transplantation are reviewed, as are the current indications for single, double sequential, and heart/lung transplantation. Criteria for lung transplant recipients, in addition to their primary disease are noted, as are absolute and relative contraindications. The standard criteria for donor selection are also reviewed. RESULTS: The results of single, double sequential, and heart-lung transplantation over the past 10 years as reported by the International Society for Heart and Lung Transplantation Database are reviewed. In addition, the statistics of the lung and heart-lung transplantation program at the University of Colorado Health Sciences Center are reviewed, including the current immunosuppressive regimens and early and late monitoring for infection and rejection. This experience includes 3 early deaths in the first 53 patients for an operative mortality of 5.6%, with a 1-year actuarial survival of 90%. CONCLUSIONS: During the past decade remarkable improvement in the result of single and double sequential lung transplantation have occurred. As 1-year, actuarial survival is now approaching 90% at some institutions. Living related lobar transplantation, new antirejection agents, chimerism, and xenograft transplantation are areas for continuing and future investigation. The shortage in donor organ supply continues to be a very significant factor in limiting human lung transplantation.

Anesthesia for heart or single or double lung transplantation in the adult patient.

Providing an anesthetic for patients undergoing heart or a single or double lung transplantation may represent a challenge even to the most experienced anesthesiologist. Patients with end-stage cardiac dysfunction have an impaired response to beta-agonist due to receptor downregulation. These patient will have isolated left ventricular dysfunction secondary to ischemic heart disease or present with biventricular failure with or without significant pulmonary hypertension. Increasingly, more patients have undergone prior major cardiac procedures and are at risk for significant perioperative bleeding. Patients undergoing single or double lung are particularly challenging because most of these procedures are performed without the aid of cardiopulmonary bypass. The anesthesiologist must be proficient at the management of one-lung ventilation techniques and have a rational physiologic approach to the management of intraoperative hypoxemia and auto-PEEP.

Segmental regulation of pulmonary vascular permeability by store-operated Ca2+ entry.

An intact endothelial cell barrier maintains normal gas exchange in the lung, and inflammatory conditions result in barrier disruption that produces life-threatening hypoxemia. Activation of store-operated Ca2+ (SOC) entry increases the capillary filtration coefficient (Kf,c) in the isolated rat lung; however, activation of SOC entry does not promote permeability in cultured rat pulmonary microvascular endothelial cells. Therefore, current studies tested whether activation of SOC entry increases macro- and/or microvascular permeability in the intact rat lung circulation. Activation of SOC entry by the administration of thapsigargin induced perivascular edema in pre- and postcapillary vessels, with apparent sparing of the microcirculation as evaluated by light microscopy. Scanning and transmission electron microscopy revealed that the leak was due to gaps in vessels >/= 100 micrometer, consistent with the idea that activation of SOC entry influences macrovascular but not microvascular endothelial cell shape. In contrast, ischemia and reperfusion induced microvascular endothelial cell disruption independent of Ca2+ entry, which similarly increased Kf,c. These data suggest that 1) activation of SOC entry is sufficient to promote macrovascular barrier disruption and 2) unique mechanisms regulate pulmonary micro- and macrovascular endothelial barrier functions.

Signal transduction and regulation of lung endothelial cell permeability. Interaction between calcium and cAMP.

Pulmonary endothelium forms a semiselective barrier that regulates fluid balance and leukocyte trafficking. During the course of lung inflammation, neurohumoral mediators and oxidants act on endothelial cells to induce intercellular gaps permissive for transudation of proteinaceous fluid from blood into the interstitium. Intracellular signals activated by neurohumoral mediators and oxidants that evoke intercellular gap formation are incompletely understood. Cytosolic Ca2+ concentration ([Ca2+]i) and cAMP are two signals that importantly dictate cell-cell apposition. Although increased [Ca2+]i promotes disruption of the macrovascular endothelial cell barrier, increased cAMP enhances endothelial barrier function. Furthermore, during the course of inflammation, elevated endothelial cell [Ca2+]i decreases cAMP to facilitate intercellular gap formation. Given the significance of both [Ca2+]i and cAMP in mediating cell-cell apposition, this review addresses potential sites of cross talk between these two intracellular signaling pathways. Emerging data also indicate that endothelial cells derived from different vascular sites within the pulmonary circulation exhibit distinct sensitivities to permeability-inducing stimuli; that is, elevated [Ca2+]i promotes macrovascular but not microvascular barrier disruption. Thus this review also considers the roles of [Ca2+]i and cAMP in mediating site-specific alterations in endothelial permeability.

Inhaled nitric oxide pretreatment but not posttreatment attenuates ischemia-reperfusion-induced pulmonary microvascular leak.

BACKGROUND: Ischemia-reperfusion (I/R) pulmonary edema probably reflects a leukocyte-dependent, oxidant-mediated mechanism. Nitric oxide (NO) attenuates leukocyte-endothelial cell interactions and I/R-induced microvascular leak. Cyclic adenosine monophosphate (cAMP) agonists reverse and prevent I/R-induced microvascular leak, but reversal by inhaled NO (INO) has not been tested. In addition, the role of soluble guanylyl cyclase (sGC) activation in the NO protection effect is unknown. METHODS: Rat lungs perfused with salt solution were grouped as either I/R, I/R with INO (10 or 50 ppm) on reperfusion, or time control. Capillary filtration coefficients (Kfc) were estimated 25 min before ischemia (baseline) and after 30 and 75 min of reperfusion. Perfusate cell counts and lung homogenate myeloperoxidase activity were determined in selected groups. Additional groups were treated with either INO (50 ppm) or isoproterenol (ISO-10 microM) after 30 min of reperfusion. Guanylyl cyclase was inhibited with 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ-15 microM), and Kfc was estimated at baseline and after 30 min of reperfusion. RESULTS: (1) Inhaled NO attenuated I/R-induced increases in Kfc. (2) Cell counts were similar at baseline. After 75 min of reperfusion, lung neutrophil retention (myeloperoxidase activity) and decreased perfusate neutrophil counts were similar in all groups. (3) In contrast to ISO, INO did not reverse microvascular leak. (4) 8-bromoguanosine 3',5'-cyclic monophosphate (8-br-cGMP) prevented I/R-induced microvascular leak in ODQ-treated lungs, but INO was no longer effective. CONCLUSIONS: Inhaled NO attenuates I/R-induced pulmonary microvascular leak, which requires sGC activation and may involve a mechanism independent of inhibition of leukocyte-endothelial cell interactions. In addition, INO is ineffective in reversing I/R-induced microvascular leak.

Ca(2+)-inhibitable adenylyl cyclase and pulmonary microvascular permeability.

Intracellular mechanisms responsible for endothelial cell disruption are unknown, although either elevated cytosolic Ca2+ ([Ca2+]i) or decreased adenosine 3',5'-cyclic monophosphate (cAMP) promotes permeability. Recent identification that Ca(2+)-inhibitable adenylyl cyclase establishes an inverse relationship between [Ca2+]i and cAMP in macrovascular endothelial cells provided a possible mechanism of development of permeability. However, these data utilized an in vitro model; lacking was evidence supporting 1) expression of Ca(2+)-inhibitable adenylyl cyclase in pulmonary microvascular endothelium and 2) Ca2+ inhibition of adenylyl cyclase and cAMP content as a paradigm for inflammatory mediator-induced permeability in the intact circulation. We therefore addressed these issues in microvascular endothelial cells derived from rat lung and in an isolated perfused rat lung preparation. Results demonstrate expression of a Ca(2+)-inhibitable adenylyl cyclase in microvascular endothelial cells. Furthermore, data suggest that Ca2+ inhibition of adenylyl cyclase is necessary for development of microvascular permeability in the intact circulation. We conclude Ca2+ inhibition of cAMP represents a critical step in genesis of microvascular permeability in the intact pulmonary circulation.