Acute aortic dissection type A.

BACKGROUND: Acute aortic dissection type A (AADA) is a life-threatening vascular emergency. Clinical presentation ranges from pain related to the acute event, collapse due to aortic rupture or pericardial tamponade, or manifestations of organ or limb ischaemia. The purpose of this review was to clarify important clinical issues of AADA management, with a focus on diagnostic and therapeutic challenges. METHODS: Based on a MEDLINE search the latest literature on this topic was reviewed. Results from the German Registry for Acute Aortic Dissection Type A (GERAADA) are also described. RESULTS: Currently, the perioperative mortality rate of AADA is below 20 per cent, the rate of definitive postoperative neurological impairment approaches 12 per cent and the long-term prognosis after surviving the acute phase of the disease is good. Many pathology- and therapy-associated factors influence the outcome of AADA, including prompt diagnosis with computed tomography and better cerebral protection strategies during aortic arch reconstruction. Endovascular technologies are emerging that may lead to less invasive treatment options. CONCLUSION: AADA is an emergency that can present with a wide variety of clinical scenarios. Advances in the surgical management of this complex disease are improving outcomes.

Management of the heartbeating brain-dead organ donor.

The main factor limiting organ donation is the availability of suitable donors and organs. Currently, most transplants follow multiple organ retrieval from heartbeating brain-dead organ donors. However, brain death is often associated with marked physiological instability, which, if not managed, can lead to deterioration in organ function before retrieval. In some cases, this prevents successful donation. There is increasing evidence that moderation of these pathophysiological changes by active management in Intensive Care maintains organ function, thereby increasing the number and functional quality of organs available for transplantation. This strategy of active donor management requires an alteration of philosophy and therapy on the part of the intensive care unit clinicians and has significant resource implications if it is to be delivered reliably and safely. Despite increasing consensus over donor management protocols, many of their components have not yet been subjected to controlled evaluation. Hence the optimal combinations of treatment goals, monitoring, and specific therapies have not yet been fully defined. More research into the component techniques is needed.

Epicardial adipose tissue as a source of nuclear factor-kappaB and c-Jun N-terminal kinase mediated inflammation in patients with coronary artery disease.

CONTEXT: Visceral adipose tissue (AT) is known to confer a significantly higher risk of type 2 diabetes and cardiovascular disease. Epicardial AT has been shown to be related to cardiovascular disease and myocardial function through unidentified mechanisms. Epicardial AT expresses an inflammatory profile of proteins; however, the mechanisms responsible are yet to be elucidated. OBJECTIVES: The objectives of the study were to: 1) examine key mediators of the nuclear factor-kappaB (NFkappaB) and c-Jun N-terminal kinase (JNK) pathways in paired epicardial and gluteofemoral (thigh) AT from coronary artery disease (CAD) and control patients and 2) investigate circulating endotoxin levels in CAD and control subjects. DESIGN: Serums and AT biopsies (epicardial and thigh) were obtained from CAD (n = 16) and non-CAD (n = 18) patients. Inflammation was assessed in tissue and serum samples through Western blot, real-time PCR, ELISAs, and activity studies. RESULTS: Western blotting showed epicardial AT had significantly higher NFkappaB, inhibitory-kappaB kinase (IKK)-gamma, IKKbeta, and JNK-1 and -2 compared with thigh AT. Epicardial mRNA data showed strong correlations between CD-68 and toll-like receptor-2, toll-like receptor-4, and TNF-alpha. Circulating endotoxin was elevated in patients with CAD compared with matched controls [CAD: 6.80 +/- 0.28 endotoxin unit(EU)/ml vs. controls: 5.52 +/- 0.57 EU/ml; P<0.05]. CONCLUSION: Epicardial AT from patients with CAD shows increased NFkappaB, IKKbeta, and JNK expression compared with both CAD thigh AT and non-CAD epicardial AT, suggesting a depot-specific as well as a disease-linked response to inflammation. These studies implicate both NFkappaB and JNK pathways in the inflammatory profile of epicardial AT and highlight the role of the macrophage in the inflammation within this tissue.

Disease-specific survival benefit of lung transplantation in adults: a national cohort study.

The lung transplantation candidate population is heterogeneous and survival benefit has not been established for all patient groups. UK data from a cohort of 1997 adult (aged > or = 16), first lung transplant candidates (listed July 1995 to July 2006, follow-up to December 2007) were analyzed by diagnosis, to assess mortality relative to continued listing. Donor lungs were primarily allocated according to local criteria. Diagnosis groups studied were cystic fibrosis (430), bronchiectasis (123), pulmonary hypertension (74), diffuse parenchymal lung disease (564), chronic obstructive pulmonary disease (COPD, 647) and other (159). The proportion of patients in each group who died while listed varied significantly (respectively 37%, 48%, 41%, 49%, 19%, 38%). All groups had an increased risk of death at transplant, which fell below waiting list risk of death within 4.3 months. Thereafter, the hazard ratio for death relative to listing ranged from 0.34 for cystic fibrosis to 0.64 for COPD (p < 0.05 all groups except pulmonary hypertension). Mortality reduction was greater after bilateral lung transplantation in pulmonary fibrosis patients (p = 0.049), but not in COPD patients. Transplantation appeared to improve survival for all groups. Differential waiting list and posttransplant mortality by diagnosis suggest further use and development of algorithms to inform lung allocation.

Selective antegrade cerebral perfusion attenuates brain metabolic deficit in aortic arch surgery: a prospective randomized trial.

BACKGROUND: Aortic arch surgery has a high incidence of brain injury. This may in part be caused by a cerebral metabolic deficit observed after hypothermic circulatory arrest (HCA). We hypothesized that selective antegrade cerebral perfusion (SACP) would attenuate this phenomenon. METHODS AND RESULTS: In a prospective randomized trial, 42 adult patients were allocated to either HCA (22) or SACP. HCA occurred at a nasopharyngeal temperature of 15 degrees C and SACP at a corporeal temperature of 25 degrees C with cerebral perfusion at 15 degrees C. Paired arterial and jugular venous samples were taken before and after arrest. Continuous transcranial Doppler monitoring of middle cerebral artery velocity (MCAV) was performed. Neuropsychometric testing was performed preoperatively and at 6 and 12 weeks postoperatively. There were 3 hospital deaths (7.1%), 2 strokes (4.8%), and 6 episodes of transient neurological deficit (14.3%). From before to after arrest, jugular bulb pO2 changed by -21.67 mm Hg (26.4) in the HCA group versus +2.27 mm Hg (18.8) in the SACP group (P=0.007). Oxygen extraction changed by +1.7 mL/dL (1.3) in the HCA group versus -1 mL/dL (2.4) in the SACP group (P<0.001). MCAV increased by 6.25 cm/s (9.1) in the HCA group and 19.2 cm/s (10.1) in the SACP group (P=0.001). Incidence of neuropsychometric deficit at 6 weeks was 6/12 (50%) in HCA patients and 8/10 (80%) in SACP patients (P=0.2), and at 12 weeks was 6/16 (38%) in HCA patients and 4/11 (36%) in SACP patients (P=1). CONCLUSIONS: SACP attenuates the metabolic changes seen after HCA. Further studies are required to assess optimal perfusion conditions and clinical outcome.

Insulin resistance in patients with cardiac hypertrophy.

OBJECTIVE: Animal studies suggest that left ventricular hypertrophy might be associated with insulin resistance and alterations in glucose transporters. We have previously demonstrated myocardial insulin resistance in patients with post-ischemic heart failure. The aim was to investigate whether myocardial insulin resistance could be demonstrated in human cardiac hypertrophy in the absence of hypertension, diabetes and coronary artery disease. METHODS: Eleven normotensive nondiabetic patients with cardiac hypertrophy due to aortic stenosis and angiographically normal coronary arteries were compared to 11 normal volunteers. Myocardial glucose uptake (MGU) was measured with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose during fasting (low insulinemia) or during euglycemic-hyperinsulinemic clamp (physiologic hyperinsulinemia). Myocardial biopsies were obtained in order to investigate changes in insulin-independent (GLUT-1) and insulin-dependent (GLUT-4) glucose transporters. RESULTS: During fasting, plasma insulin (7 +/- 1 vs. 6 +/- 1 mU/l) and MGU (0.12 +/- 0.05 vs. 0.11 +/- 0.04 mumol/min/g) were comparable in patients and controls. By contrast, during clamp, MGU was markedly reduced in patients (0.48 +/- 0.02 vs. 0.70 +/- 0.03 mumol/min/g, p < 0.01) despite similar plasma insulin levels (95 +/- 6 vs. 79 +/- 6 mU/l). A decreased GLUT-4/GLUT-1 ratio was shown by Western blot analysis in patients. CONCLUSIONS: Insulin resistance seems to be a feature of the hypertrophied heart even in the absence of hypertension, coronary artery disease and diabetes and may be explained, at least in part, by abnormalities in glucose transporters.

Validation of the conductance catheter method for measurement of ventricular volumes under varying conditions relevant to cardiac surgery.

The development of the conductance catheter method has enabled continuous measurement of intraventricular volume in vivo, thus making assessment of pump performance of the heart in vivo possible using pressure-volume analysis. However, this method has not been validated under conditions where pump rate, conductance, viscosity, and temperature of the fluid in the heart chamber is changed as happens in cardiac surgery. To validate the method, pressure-volume data were measured by conductance catheter in a physical model of the human left ventricle. The volume, salinity, viscosity, and temperature of the fluid inside the model were rigorously controlled. The measured pressure-volume data were compared with the actual values to assess the accuracy and dependence of the conductance-measured volumes on salinity, viscosity, temperature, and pump rate. Conductance-measured volumes were not significantly different over a range of heart rates extending from 60 to 100 beats/min, and they were not significantly different over a salinity range of 0.2 to 2 normal saline, a viscosity range of 2.7 to 3.5 centipoise, or over a temperature range of 20 degrees C to 39 degrees C. The percentage errors between actual stroke volumes and conductance-derived volumes were of the order of 10% on average. Our data shows that for a broad range of conditions normally encountered during cardiac surgery, there is no dependence of conductance-measured volume on heart rate, viscosity, temperature, or salinity, provided the correct value of fluid resistivity is used.

Coronary revascularization in the treatment of moderate and severe postischemic left ventricular dysfunction.

Chronic postischemic left ventricular (LV) dysfunction can improve following coronary revascularization (hibernating myocardium). However, it is not clear whether the severity of LV dysfunction determines functional outcome after revascularization and the accuracy of tests to predict myocardial viability. We studied 47 patients with coronary artery disease and chronic LV dysfunction. Before coronary bypass, patients underwent (18F)2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) during euglycemic hyperinsulinemic clamp to assess viability. Global and regional LV function were assessed before and 4 to 6 months after surgery. Patients were arbitrarily divided into 2 groups with moderate and severe LV dysfunction. Group 1 (n = 26) had an ejection fraction (EF) of < or = 30% and group 2 (n = 21) > 30%. After bypass, the EF (22+/-6% vs 31+/-10%; p <0.0001) and global wall motion score (WMS) (2.05+/-0.39 vs 1.56+/-0.34; p <0.001) improved in group 1, whereas the EF (43+/-9% vs 43+/-12%; p = NS) was unchanged in group 2, although WMS tended to improve (1.42+/-0.38 vs 1.32+/-0.39; p = 0.09). The proportion of dysfunctional segments (72% vs 32%; p <0.0001) and FDG uptake in these segments (0.44+/-0.15 vs 0.34+/-0.15 micromol/g/min, p <0.0001) were greater in group 1 than in group 2. The baseline EF influenced the predictive accuracy of PET, with highest positive predictive accuracy in group 2 and highest negative predictive accuracy in group 1. Thus, coronary revascularization has the potential for greatest benefit in patients with the most severe dysfunction, but with evidence of viability, and the entity of LV dysfunction affects the predictive accuracy of viability studies.

Reduction of endothelial injury after hypothermic lung preservation by initial leukocyte-depleted reperfusion.

OBJECTIVES: Leukocyte depletion has been shown to ameliorate the effects of reperfusion injury in many organ systems. The aim of this study was to investigate the effects of leukocyte depletion on functional and endothelial markers of pulmonary performance after cold ischemic injury. METHOD: Groups of 6 rat lungs were flushed with University of Wisconsin solution and then stored at 4 degrees C for 4 hours. They then underwent sanguine reperfusion for 30 minutes, during which time functional measures (gas exchange, pulmonary artery, and airway pressures) were made and after which the lungs underwent estimation of endothelial permeability by measurement of the capillary filtration coefficient (in grams per centimeter of water per minute per grams of wet lung tissue) by a gravimetric technique. Four groups were studied: group 1 underwent no reperfusion, group 2 underwent 30 minutes of reperfusion, group 3 underwent 30 minutes of leukocyte-deplete reperfusion with an in-line leukocyte filter (PALL), and group 4 underwent 10 minutes of leukocyte-depleting reperfusion followed by 20 minutes of normal reperfusion. RESULTS: The capillary filtration coefficient increased between group 1 and group 2 animals (1.05 +/- 0.32 to 3.07 +/- 0.47 [mean +/- SEM]; P <.01). Complete leukocyte depletion caused the greatest diminution in the capillary filtration coefficient (0.392 +/- 0.07, P <.001), but initial leukocyte depletion (group 4) also showed a significant diminution (0.74 +/- 0.3, P <.01). Complete or initial leukocyte depletion caused no significant change in functional measures of pulmonary performance. Complete leukocyte depletion produced less pulmonary leukostasis, as assessed by means of myeloperoxidase activity. CONCLUSION: Initial and continued leukocyte depletion are associated with amelioration of reperfusion-induced endothelial injury after cold ischemic injury.

Coronary artery bypass surgery as treatment for ischemic heart failure: the predictive value of viability assessment with quantitative positron emission tomography for symptomatic and functional outcome.

OBJECTIVES: To determine the predictive value of quantitative evaluation of myocardial viability on changes in left ventricular function, exercise capacity, and quality of life after coronary artery bypass grafting in patients with ischemic heart failure (congestive heart failure, New York Heart Association class > or = III) with and without angina. METHODS: Thirty-five patients, 14 with congestive heart failure and angina (CHF-angina) and 21 with congestive heart failure without angina (CHF-no angina) were studied at baseline and 6 months after coronary bypass grafting. Left ventricular function was evaluated with transthoracic echocardiography and radionuclide ventriculography. Myocardial viability was assessed with [18F]-2-fluoro-2-deoxy-D-glucose using positron emission tomography. Peak aerobic capacity (peak oxygen consumption) and anaerobic threshold were assessed with treadmill exercise test and quality of life with a questionnaire. RESULTS: A total of 286 of 336 dysfunctional left ventricular segments were viable. There were two perioperative deaths (5.7%) and three late deaths. Left ventricular ejection fraction increased from 23% +/- 7% to 32% +/- 9% (p < 0.0001), and a linear correlation was found between the number of viable segments and the changes in ejection fraction (r = 0.65; p = 0.0001). Receiver operating characteristics curve identified eight viable segments as the best predictor for increase of ejection fraction more than 5 percentage points. Peak oxygen consumption increased from 15 +/- 4 to 22 +/- 5 ml/kg per minute (p < 0.0001). Preoperatively, anaerobic threshold was identified in one patient from the CHF-angina group and in all from the CHF-no angina group and increased from 13 +/- 4 to 19 +/- 4 ml/kg per minute (p < 0.0001). Quality of life scores improved significantly in both groups. No correlation was found between the amount of viable dysfunctional myocardium and changes in exercise capacity or quality of life. CONCLUSIONS: In patients with postischemic congestive heart failure the amount of viable myocardium dictates the degree of improvement in left ventricular function after revascularization.

Reversible hyperinflation in emphysema.

Pulmonary emphysema results in hyperinflation of the lungs and concomitant changes in the configuration of the thoracic cavity. We describe a patient who underwent bilateral lung transplantation for emphysema due to alpha 1 antitrypsin deficiency. Dramatic changes in chest dimensions and configuration occurred following transplantation, demonstrating the dynamic and reversible nature of the thoracic cavity abnormalities of emphysema.

Failure of retrograde cerebral perfusion to attenuate metabolic changes associated with hypothermic circulatory arrest.

OBJECTIVES: Although retrograde cerebral perfusion has become a popular adjunctive technique and may improve cerebral ischemic tolerance during hypothermic circulatory arrest, direct cerebral metabolic benefit has yet to be demonstrated in human subjects. We investigated the post-arrest metabolic phenomena with and without retrograde cerebral perfusion in patients. METHODS: In a prospective randomized trial, 42 patients undergoing aortic surgery requiring hypothermic circulatory arrest were allocated to receive hypothermic circulatory arrest alone (n = 21) or hypothermic circulatory arrest with additional retrograde cerebral perfusion (n = 21). Circulatory arrest was commenced at 15 degrees C, and retrograde perfusion was instituted through the superior vena cava at a maximum jugular bulb pressure of 25 mm Hg. Transcranial, paired, repeated samples of the arterial and jugular bulb blood were analyzed for oxygen and glucose. Velocity in the right middle cerebral artery was also measured simultaneously. RESULTS: There were 3 (7.1%) deaths and 3 (7.1%) episodes of neurologic deficit. Mean bypass and circulatory arrest duration (in minutes) were similar between groups (P =.4 and.14). The mean retrograde perfusion duration was 23 minutes. Post-arrest nasopharyngeal temperature was similar (15.3 degrees C vs. 15.3 degrees C). Retrograde perfusion did not affect post-arrest oxygen extraction, glucose extraction, or jugular bulb Po(2). There was no immediate lactate release immediately after hypothermic circulatory arrest. CONCLUSIONS: Retrograde cerebral perfusion did not influence immediate post-arrest nasopharyngeal temperature or cerebral metabolic recovery. The low jugular bulb Po(2) suggests equivalent ischemia. These findings cast doubt on the effectiveness of retrograde cerebral perfusion as a metabolic adjunct to hypothermic circulatory arrest.

Neuropsychometric outcome following aortic arch surgery: a prospective randomized trial of retrograde cerebral perfusion.

BACKGROUND: Aortic surgery requiring hypothermic circulatory arrest is associated with a high incidence of brain injury. However, knowledge of neuropsychometric outcome is limited. Retrograde cerebral perfusion has become a popular adjunctive technique to hypothermic circulatory arrest. The aim of this study was to assess neuropsychometric outcome and compare the 2 techniques. METHODS: In a prospective randomized trial, 38 patients requiring elective aortic arch surgery were allocated to either hypothermic circulatory arrest plus retrograde cerebral perfusion or hypothermic circulatory arrest alone. Neuropsychometric testing was performed preoperatively, and at 6 weeks and 12 to 24 weeks postoperatively. Deficit was defined as a 20% decline in 2 tests or more. Standardized Z scores were calculated for each patient and test. Eighteen patients underwent hypothermic circulatory arrest and 20 patients underwent hypothermic circulatory arrest plus retrograde cerebral perfusion. The mean cardiopulmonary bypass, hypothermic circulatory arrest, and retrograde cerebral perfusion durations were 169, 30, and 25 minutes, respectively. RESULTS: There were 2 deaths and 2 neurological deficits. At 6 weeks postoperatively, 77% of the hypothermic circulatory arrest group and 93% of the hypothermic circulatory arrest plus retrograde cerebral perfusion group had a deficit (P =.22). At 12 weeks this was reduced to 55% and 56%, respectively (P =.93). There was a worse total Z test score in the hypothermic circulatory arrest plus retrograde cerebral perfusion group at 12 weeks (P =.05). Neuropsychometric change did not correlate with hypothermic circulatory arrest duration, presence of aortic atheroma, cannulation technique, or procedure. CONCLUSIONS: Hypothermic circulatory arrest plus/minus retrograde cerebral perfusion is associated with a high incidence of neuropsychometric change despite ostensibly normal clinical outcomes and apparently safe arrest duration. Retrograde cerebral perfusion did not improve outcome in this small study.

Successful human double-lung transplantation after five and one-half hours of preservation.

Successful clinical double-lung transplantation after 5 1/2 hours of pulmonary ischemia is reported. Static hypothermic preservation with a high-volume, high flow rate-modified Collin's solution pulmonary artery flush was used. Excellent early and late pulmonary function demonstrates the efficacy of the technique that is described in detail. Lung transplantation remains limited by the lack of reliable methods of long-term storage of donor organs, but refinement of current techniques may soon allow its wider application.

Replacement of the proximal aorta and aortic valve using a composite bileaflet prosthesis and gelatin-impregnated polyester graft (Carbo-Seal): early results in 143 patients.

OBJECTIVE: We report the combined early results from two centers in the United Kingdom using a composite conduit consisting of a bileaflet mechanical valve incorporated into a gelatin-impregnated, ultra-low porosity, woven polyester graft (Carbo-Seal; Sulzer Carbomedics, Inc, Austin, Tex). METHODS: Between August 1992 and March 1997, 143 patients underwent aortic root replacement with the Carbo-Seal composite prosthesis. The indication for surgery was acute type A dissection in 31 (22%), chronic type A dissection in 9 (6%), ascending aortic aneurysm without dissection in 100 (70%), and false aneurysm of the ascending aorta in 3 (2%). Twenty-seven patients (19%) had undergone previous sternotomy, and 40 (28%) were seen as emergencies. Concomitant procedures were performed in 38 (27%), including 18 aortic arch or hemiarch replacements. Total follow-up is 270 patient-years. Follow-up is 100% complete. RESULTS: The early (30-day) mortality was 7% (10 patients). Permanent neurologic events occurred in 2%. At a mean follow-up of 23 months, 94% of survivors were in New York Heart Association functional class I. Freedom from reoperation was 97.2% +/- 1.6% (1 standard error [1 SE]) at 12 months and 95.7% +/- 2.2% at 48 months. Including early mortality, survival was 90.1% +/- 2.6% at 12 months and 83.1% +/- 3. 5% at 48 months. CONCLUSIONS: Aortic root replacement with use of the Carbo-Seal prosthesis can be undertaken with a relatively low early mortality and morbidity. A low reoperation rate and high intermediate-term survival can be expected, but continued follow-up is needed to determine the long-term efficacy of this prosthesis.

Heart-lung transplantation.

Since the successful clinical reintroduction of heart and lung transplantation in 1981, more than 350 of these procedures have been performed worldwide. Although survival following this operation is less than that reported for heart transplantation, the results are improving. It is clear that the increased technical difficulty of the procedure combined with the exquisite susceptibility of the transplanted lung to postoperative injury from infection, rejection or other causes account for these differences. In this report we provide an overview of the experience in heart-lung transplantation and discuss recent advances. The late complication of chronic obliterative bronchiolitis, which may progress inexorably, has cast a shadow over the potential long-term success of this therapeutic procedure. Current research efforts are directed toward the cause, diagnosis, and treatment of this complication.

Sudden infant death syndrome in Cardiff, association with epidemic influenza and with temperature - 1955-1974.

The effects of social class, season, low temperature and sudden falls in temperature are investigated in 286 cases of Sudden Infant Death Syndrome in Cardiff in the years 1955--1974. The association with low temperature was striking: unsuspected hypothermia may be an important feature of these deaths. Sudden infant death incidence was associated with influenza A but not influenza B epidemics.

The heart failure revascularisation trial (HEART): rationale, design and methodology.

BACKGROUND: Most patients with heart failure due to left ventricular systolic dysfunction (LVSD) secondary to coronary artery disease (CAD) have evidence of myocardium in jeopardy (reversible ischaemia and/or stunning hibernation). It is not known whether revascularisation in such cases is safe or beneficial. AIMS: To determine whether revascularisation will improve the survival of patients with LVSD and heart failure secondary to CAD and myocardium in jeopardy. METHODS: This is a randomised controlled trial comparing revascularisation or not, in addition to optimal medical therapy with ACE inhibitors, beta-blockers, aldosterone antagonists and an anti-thrombotic agent. Patients must have heart failure requiring treatment with diuretics, a left ventricular ejection fraction <35% and evidence of coronary disease. Myocardial viability and ischaemia are assessed by a broad range of techniques including stress echocardiography and nuclear imaging. All imaging tests are reviewed in core laboratories to ensure uniform reporting. Any conventional revascularisation technique is permitted. The primary outcome measure is all cause mortality. Symptoms, quality of life and health economic issues will also be explored. Assuming an annual mortality of 10% in the control group and allowing for substantial cross-over rates, a study of 800 patients followed for 5 years has 80% power with an alpha of 0.05 (two-sided) to show a 25% reduction in mortality with revascularisation. RESULTS: At the time of writing 180 patients have been screened for inclusion, 111 have consented to participate and 70 have been randomised. The results of viability testing are awaited in 22 patients. Twenty-six patients had been investigated for myocardial viability and/or by angiography prior to consent, as part of the routine practice in that cardiology department. Of 68 patients who have completed assessment only after consent, 47 (69%) were included. The principal reason for drop-out between consent and randomisation was lack of evidence of myocardial ischaemia or hibernation. CONCLUSION: The HEART trial will help to determine whether investigation of myocardial ischaemia and/or viability with a view to revascularisation should become part of the routine care of patients with heart failure due to LVSD and CAD.

Conservation of small-airway function by tacrolimus/cyclosporine conversion in the management of bronchiolitis obliterans following lung transplantation.

We studied serial lung function in 11 patients with bronchiolitis obliterans syndrome who were treated with tacrolimus conversion following lung or heart-lung transplantation. Our results show that tacrolimus conversion slows the decline of lung function in bronchiolitis obliterans syndrome. The attenuation continues for at least 1 year following conversion.

Differential time scale of fluid and solute permeability following hypothermic lung preservation.

BACKGROUND: Assessment of the quality of lung graft preservation by simple functional measures in some laboratory models may fail to detect endothelial injury. The effects of hypothermic preservation in isolation were investigated by measuring the pulmonary capillary filtration coefficient (Kf) and the albumin surface area product (PS) at various cold ischemic intervals. METHODS: Rat lungs were flushed with University of Wisconsin solution at 4 degrees C. Following storage at 4 degrees C, lungs for Kf measurement were subjected to a change in pulmonary arterial pressure. Kf was calculated from the change in rate of weight gain as a function of hydrostatic stress. PS lungs were exposed to Tris buffered Ringer's solution containing 1125 albumin (20 microM) in an isogravimetric state. Following a vascular flush the lungs were homogenized and underwent scintillation counting. Using the Kedem-Katchalsky equation PS was calculated. RESULTS: The Kf for the control, 4-hour, and 7-hour groups were 0.778, 1.816, 4.853 g/ cm H2O/min/100 g wet lung tissue, respectively. There was a significant increase in Kf with each time increment (P,0.01). The Kf for the 24-hour group was 5.587 g/cm H2O/min/100 g wet lung tissue; not an additional significant increase. PS for the control and 4-hour groups (0.0115 and 0.0101 cm3/g wet lung tissue/minute, respectively) were not significantly different. After 7 hours there was a significant increase to 0.171 cm3/g wet lung tissue/min. PS could not be measured after 24 hours. CONCLUSIONS: Significant endothelial injury occurs after 4 hours of cold ischemic preservation. There is progressive injury with time. Increase in water permeability is not secondary to increase in albumin permeability.