Pulmonary thromboendarterectomy in patients with chronic thromboembolic pulmonary hypertension: hemodynamic characteristics and changes

Objective: To see whether degree of pulmonary hypertension or severity of cardiac failure affect the success of pulmonary thromboendarterectomy (PTE) in chronic thromboembolic pulmonary hypertension. Methods: From May 1996 to June 1999, 33 patients, all in New York Heart Association (NYHA) class 3 or 4 were treated with PTE. Preoperative hemodynamic values were: central venous pressure (CVP) 8±6 (1–23), mean pulmonary artery pressure (mPAP) 50±10 (30–69), cardiac output (CO) 3.3±0.9 (1.8–5.2), pulmonary vascular resistance (PVR) 1056±344 (523–1659), and right ventricle ejection fraction (RVEF) 12±5 (5–21). To establish whether some hemodynamic or cardiac variables correlate with surgical failure (early death or functional non-success), these patients were divided into a low risk or a high risk group for each variable: CVP (<9 or ≥9), mPAP (<50 or ≥50), CO (≥3.5 or <3.5), PVR (≥1100 or <1100), and RVEF (≥10 or <10). The duration of 3–4 NYHA class period (<24 or ≥24 months) was also included in the study. Results: Three patients (9.1%) died in hospital, one (3.0%) underwent lung transplant shortly after PTE, and in five cases (15.2%) mPAP and PVR at the 3-month follow-up examination corresponded with our definition of functional nonsuccess (mPAP and PVR decreased by less than 40% of preoperative values). One of the five functional nonsuccess patients underwent lung transplant 3 months after the operation and another died 17 months after the operation from a non-related cause. Thus PTE was successful in 24 patients and unsuccessful in nine. None of the hemodynamic variables considered was found to be associated with the disparate outcomes. At the 3-month examination, all surviving patients were in NYHA class 1 or 2 except for three in NYHA class 3. At 2 years, hemodynamic values were: CVP 2±2 (0–4), mPAP 16±3 (12–21), CO 5.0±1.0 (3.4–6.5), PVR 182±51 (112–282), and RVEF 35±5 (26–40). All differences were significant with respect to baseline values (P<0.001). Preoperative mPAP and RVEF values had a strict linear correlation (R=0.45; P=0.014). Conclusions: None of the variables considered was correlated with early death or functional nonsuccess. Neither preoperative severity of pulmonary hypertension nor degree of cardiac failure influenced the outcome of the operation. PTE leads to hemodynamic recovery even in very compromised patients.     

Prevalence and optimal management strategy for aortic regurgitation in tetralogy of Fallot

Objective: Aortic regurgitation (AR) in the tetralogy of Fallot (TOF) is not frequent, but when present it impacts significantly on surgical management. Furthermore, the incidence of late AR development has been increasing, along with surgical interest in current practices. Methods: Pre- and post-operative studies on 427 patients (TOF, 374; TOF/PA (TOF with pulmonary atresia), 53) who survived corrective operation were reviewed. AR (mild) was detected in 28. Results: Nine had AR preoperatively, while 25 (including six with preoperative AR) exhibited AR post-operatively. In the 19 who developed AR post-operatively, the aortic root diameter (AoRoD) and indexed AoRoD (%AoRoD) were 42±11 mm and 166±36%, increased from the preoperative values of 30±10 mm and 149±24%. AR-free rate at 20 years was 95.1% of all cases studied, 84.3 vs 96.5% in TOF/PA vs classic TOF (P<0.0001), and 82.2 vs 97.0% in bulboventricular VSD vs infracristal VSD (P<0.0001). Older age at repair, and bulboventricular VSD were identified as risk factors for the progression of AR. Aortic valvuloplasty (AVP; n=5) or replacement (AVR; n=4) was performed nine times in eight patients before (n=1), during (n=4), or late after TOF repair (n=4); all showed improvement of NYHA class. Survival- and reoperation-free survival curves showed no significant difference between patients with or without AR. Conclusions: After repair of TOF, careful observation for a late progression of AR is needed for the optimal timing of surgical intervention, especially in patients who repaired at higher age with a dilated aortic root or in patients with bulboventricular VSD.     

Resting hemodynamics after total versus standard orthotopic heart transplantation in patients with high preoperative pulmonary vascular resistance

Objective: Pretransplant pulmonary vascular resistance ≥4 Wood-units predisposes to right ventricular failure after heart transplantation. Total orthotopic heart transplantation with bicaval and pulmonary venous anastomoses offers synchronous contractions of the atria and a normal ventricular filling pattern, but requires longer ischemic time than standard orthotopic heart transplantation. To test if total orthotopic heart transplantation improves resting hemodynamics in pts with high preoperative pulmonary vascular resistance, we analyzed 65 pts with standard and 65 with total orthotopic heart transplantation transplanted between 12/88 and 7/94. Of these, 18 with total and 15 with standard orthotopic heart transplantation had a preoperative pulmonary vascular resistance ≥4 Wood-units. Methods: Right heart catheterization data were obtained at each endomyocardial biopsy. All data from biopsies at both 2 weeks and 1 year posttransplant that were free from humoral or greater than 1A cellular rejection (9 versus 13 pts) were included in a two way ANOVA. Pts with postop pacemakers, atrial fib or β-blocker therapy at the time of biopsy were excluded. Results: Ischemic time was different (172±44 versus 142±28 min, P=0.03). Demographics, NYHA class, pre-TX hemodynamics, donor age and inotropes were similar. Cardiac output and index were higher in the total orthotopic group at 2 weeks (6.5±1.7 versus 5.1±1.0 l/min; 3.4±0.9 versus 2.8±0.6 l/min per m²) and 1 year (7.1±2.0 versus 4.9±1.1 l/min, P=0.002; 3.6±1.1 versus 2.6±0.5 l/min per m², P=0.009). Right atrial and pulmonary arterial mean pressure (mmHg) were lower with total orthotopic heart transplantation at 2 weeks (6±4 versus 9±5, P=0.04; 22±3 versus 25±7, P=0.1) and 1 year (5±2 versus 7±3, P=0.02; 19±4 versus 25±7, P=0.03). Pulmonary capillary wedge pressure (mmHg) was borderline nonsignificant (11±4 versus 13±7 at 2 weeks, 8±3 versus 14±5 at 1 year, P=0.055), as well as pulmonary vascular resistance (1.9±1 versus 2.5±1 at 2 weeks, 1.5±0.6 versus 2.7±1.7 WU at 1 year, P=0.051). Conclusions: Total orthotopic heart transplantation improves cardiac output and index in pts with high preoperative pulmonary vacular resistance. There is a lower mean RA and PA pressure perhaps due to less tricuspid and mitral regurgitation. In view of the frequently observed restrictive filling pattern after cardiac transplantation, total orthotopic heart transplantation can be beneficial until this pattern has subsided by preserving atrioventricular synchrony and offering better atrial transport.     

Impact of mitral insufficiency on reoperative coronary artery surgery in ischemic cardiomyopathy patients

Objective: To determine the impact of mitral insufficiency on survival after reoperative coronary artery bypass grafting (CABG) in ischemic cardiomyopathy patients. Methods: We retrospectively studied 891 (Initial 708, Redo 183) consecutive CABG patients (1993–2002) with ejection fraction (EF) 35% or less. Patient characteristics: mean age=67.0±10.5 yrs, men=77.1%, EF=26.4±7.4%, mean CCS=3.47±0.73, mean NYHA=3.50±0.68. There were 180 (Initial 141, Redo 39) patients with 3/4+mitral regurgitation (MR). Late survival statistics of cohorts were compiled using National Death Index. Results: At a mean follow-up period of 3 years, reoperative CABG with MR (Redo/MR+) survival was 41.7±9.2% (n=39), which was worse than reoperative CABG without MR (Redo/MR−) survival of 71.8±4.1% (n=144, P=0.0003), initial CABG with MR (Initial/MR+) survival of 68.5±4.2% (n=141, P=0.014) and initial CABG without MR (Initial/MR−) survival of 76.2±2.0% (n=567, P<0.0001). By multivariate analysis, congestive heart failure (P=0.029), 3/4+MR (P=0.044) were independent predictors of Redo late mortality. In contrast, renal failure on dialysis, stroke, no angina, age >65 yrs, absence of hypercholesterolemia, EF<26% but not 3/4+MR were independent predictors of Initial late mortality. In subset analysis, adverse impact of 3/4+MR on late survival was greatest in Redo with EF<26%. The 3- and 5-yr late survival were only 44.4 and 26.8% (P=0.041). Concomitant mitral valve repair (MVrep) was performed in 100 (Initial 75, Redo 25) patients. MVrep in Initial/MR+patients achieved similar late survival as Initial/MR− patients. MVrep did not produce the same late survival benefit in Redo/MR+ patients. Conclusions: (1) Mitral insufficiency has a greater survival impact on redo than initial CABG patients with ischemic cardiomyopathy. (2) Mitral insufficiency and congestive heart failure are the primary independent predictors of late survival following redo CABG. (3) Mitral repair has less neutralizing effect on late survival in redo than initial CABG patients.     

Restrictive left atrial outflow adversely affects outcome after the modified Norwood procedure

Objective: Moderate restrictive foramen ovale in neonates with hypoplastic left heart syndrome (HLHS) is considered to be favourable, reducing pulmonary overcirculation, before modified Norwood operation. However, some newborns with severe restriction of interatrial communication will have pulmonary vascular disease at birth, which correlates with increased perioperative mortality. This article studies the post-Norwood hemodynamic patterns and outcome for the particular group of HLHS newborns with restrictive left atrial outflow compared to other patients. Methods: Restrictive left atrial outflow is defined as mitral and/or aortic atresia with intact ventricular septum, and restrictive foramen ovale, with 3 mm diameter or less with mean interatrial pressure gradient more than 5 mmHg at preoperative echo-Doppler. Four neonates fulfilled these criteriae among 18 consecutive patients, who underwent Norwood procedure from October 2002 to December 2003. Mean arterial pressure, heart rate, mean common atrial pressure, urinary output, central venous and arterial oximetry data, serum lactate levels, and dosages of milrinone, phentolamine and norepinephrine were collected at 0, 6, 12, 18 and 24 h after operation. Data were summarized as mean±SEM. For univariate comparison of different variables, Student's t-test was used. Results: The postoperative hemodynamic pattern of patients with restrictive left atrial outflow was characterized by hypoxemia and low cardiac output. Arterial (66±3.0% vs 76±1.0%, P=0.01) and central venous (37±1.2 vs 52±1.1%, P=0.001) oxygen saturations were much lower than in patients without restriction. Arterio-venous oxygen saturation difference was wider (29±2.4% vs 23±0.9%, P=0.02) and serum lactate levels were higher (10.8±3.0 vs 2.8±0.2 mmol/l, P=0.03). Common atrial pressures were more elevated (12±0.8 vs 8±0.3 mmHg, P<0.001) and higher norepinephrine doses were needed (0.44±0.15 vs 0.06±0.01 μg/kg/min, P=0.03). The difference for the mean arterial pressures did not reach the significance level (48±2.0 vs 51±2.0 mmHg, P=0.2). Operative mortality was higher 75% (3/4) compared to 14.3% (2/14, P=0.04) for the other patients. Conclusions: Restrictive left atrial outflow adversely affects outcome after modified Norwood procedure. Abnormal pulmonary vasculature leading to insufficient pulmonary perfusion is incriminated. To improve outcome, implantation of larger size modified Blalock-Taussig or right ventricle-to-pulmonary artery shunts and routine use of postoperative mechanical assist device should be considered.     

Reduction of pro-inflammatory cytokine levels and cellular adhesion in CABG procedures with separated pulmonary and systemic extracorporeal circulation without an oxygenator

Objective: We have recently shown that a considerable amount of pro-inflammatory cytokines is released during pulmonary passage after aortic declamping in patients undergoing coronary artery bypass grafting. The present study was performed to investigate whether bilateral extracorporeal circulation with the lungs as oxygenators can reduce the inflammatory responses of the lungs. Methods: Eighteen consecutive patients undergoing coronary artery bypass grafting were randomly assigned to routine extracorporeal circulation with cannulation of right atrium and aorta (routine circulation, ten patients) or to a bilateral extracorporeal circulation with additional cannulation of left atrium and pulmonary artery (bilateral circulation, eight patients). Blood was simultaneously drawn from right atrium and pulmonary vein at 1, 10 and 20 min reperfusion. The levels of interleukin (IL)-6 and IL-8 and the adhesion molecules CD41 and CD62 on platelets and CD11b and CD41 on leukocytes were determined. Because of considerable interindividual scatter, the pulmonary venous levels are normalized to percent of the respective right atrial value at each time point. Results: At 1 min reperfusion pulmonary venous levels of IL-6 and IL-8 in routine circulation were +44±15% and +43±28% of the respective right atrial values. The respective values in bilateral circulation were −3±4% and −6±7% (P=0.02 and P=0.05 vs. respective right atrium). Similar increments were found after 10 and 20 min. Platelet–monocyte coaggregates were retained during pulmonary passage at 1 min reperfusion in routine circulation (−21±6%), but washed out in bilateral circulation (+5±8%, P=0.007). At 20 min reperfusion, activated polymorphonuclear neutrophils (PMN) were retained in routine circulation (−16±9%) but washed out in bilateral circulation (+19±29%, P=0.05; all data given as mean±SEM). Conclusions: Bilateral extracorporeal circulation without an artificial oxygenator significantly reduces the inflammatory responses during pulmonary passage after aortic declamping.     

Early and long term outcome of the arterial switch operation for transposition of the great arteries: predictors and functional evaluation

Objectives: The aims of this report were to study the early and late outcome in terms of mortality, freedom from reoperation, predictors for late pulmonary stenosis (PAS) and insufficiency of the neo-aortic valve (AVI) in patients with transposition of the great arteries (TGA) undergoing arterial switch operation (ASO). Materials and methods: Between January 1990 and December 2001, 134 patients with TGA underwent ASO. The patients were divided in Group I (n=88)-TGA with intact ventricular septum and Group II (n=46)-TGA with ventricular septal defect (VSD). The pulmonary artery was reconstructed employing the direct anastomosis technique (PT-I) in 21 (15.7%) patients, the double-patch technique (PT-II) in 41 (30.6%), single pantaloon patch (partial circumference) (PT-III) in 46 (34%) and single pantaloon patch (total circumference) (PT-IV) in 35 (26%) patients. The mean follow-up was 3.4±1.3 years. Results: The hospital mortality was 17 (12.7%) patients. The mortality in Group I was significantly lower than Group II (P=0.002). The overall actuarial survival at 1, 3 and 5 years follow-up resulted to be 98, 93, and 91.5%, resulting to be significantly higher in Group I (P=0.032). The multivariate analysis revealed the complex TGA (P=0.007), VSD (P=0.032), coronary anomalies (P=0.004), aortic coarctation or hypoplastic aortic arch (P=0.021), left ventricular outflow tract obstruction (LVOTO) or moderate PAS (P=0.041) as strong predictors for poor free-reoperation cumulative survival. A strong inverse correlation was found between the mean trans-pulmonary gradient at follow-up and the age at the operation (r=−0.41, P<0.0001). The univariate analysis revealed the PT-I technique (P=0.002), prior moderate PAS (P=0.0001), and age <1 month (P=0.018) as strong predictors for moderate-to-severe PAS. The neo-AVI incidence was significantly higher in Group II (P=0.011). Predictors for neo-AVI were male sex (P=0.003), preoperative neo-AV Z-score >1 (P<0.001), prior or concomitant operation for aortic coarctation or hypoplastic aortic arch (P=0.001), LV retraining (P=0.003). Conclusion: ASO remains the procedure of choice for the treatment of various forms of TGA with acceptable early and later outcome in terms of overall survival and free reoperation. Strong predictors for poor overall free-reoperation survival are complex TGA, VSD, coronary anomalies, aortic coarctation and LVOTO or moderate PAS. The pulmonary artery reconstruction using a single ‘pantaloon patch’ seems to offer less residual stenosis. Patients with a VSD and a significant mismatch between the neo-aortic root and distal aorta are at a higher risk for developing postoperative neo-AVI.     

Inhaled iloprost to control residual pulmonary hypertension following pulmonary endarterectomy

Objective: Pulmonary endarterectomy (PEA) is the standard therapy for patients with chronic thromboembolic pulmonary hypertension (CTEPH). In the immediate postoperative period, persistent pulmonary hypertension increases the risk of acute respiratory or right heart failure. In pulmonary arterial hypertension, prostanoid inhalation has been found to improve pulmonary hemodynamics, right ventricular function, gas exchange, and clinical outcome. We report the results of a double-blinded randomized trial with the aerosolized prostacyclin analogue iloprost in patients with residual pulmonary hypertension after PEA. Methods: Twenty-two patients (age, 55 ± 13 years; 8 females; propofol- and sufentanil-based anesthesia; pressure-controlled mechanical ventilation) were randomized to receive either a single dose of 25 μg aerosolized iloprost (iloprost group; n = 11) or normal saline (placebo group; n = 11) immediately after postoperative ICU admission. Primary endpoints were changes in gas exchange, pulmonary and systemic hemodynamics, and clinical outcome. Results: Iloprost significantly enhanced cardiac index (CI) and reduced mean pulmonary arterial pressure (mPAP) and pulmonary vascular resistance [PVR (dyn s cm⁻⁵)] in contrast to placebo. Placebo: pre-inhalation 413 ± 195 versus post-inhalation 404 ± 196 at 30 min (p = 0.051), 415 ± 189 at 90 min (p = 0.929). Iloprost: pre-inhalation 503 ± 238 versus post-inhalation 328 ± 215 at 30 min (p = 0.001), 353 ± 156 at 90 min (p = 0.003). Blood oxygenation remained unchanged. Conclusion: In addition to the effect of PEA, iloprost reduces residual postoperative pulmonary hypertension, decreases right ventricular afterload and may facilitate the early postoperative management after PEA.     

Right ventricle-to-pulmonary artery shunt and modified Blalock–Taussig shunt in preparation to hemi-Fontan procedure in children with hypoplastic left heart syndrome

Objective: The advantageous effect of right ventricle-to-pulmonary artery shunt (RV–PA) on the early postoperative hemodynamics in the Norwood procedure for hypoplastic left heart syndrome (HLHS) is well known. Numerous controversies still exist with respect to the late consequences of this new palliation method in preparation for the second stage procedure. Methods: Between September 1997 and September 2004, a consecutive series of 78 children with HLHS from a single institution underwent the hemi-Fontan procedure: Group 1 (n=27) after Blalock–Taussig shunt (BT), and Group 2 (n=51) after RV–PA. Hemodynamic, echocardiographic and clinical perioperative data were analyzed. Results: There were no significant differences in the age and operative weight (Group 1: 6.9±1.04 months, 6.22±0.99 kg; Group 2: 6.57±1.12 months, 6.36±0.86 kg). Children after RV–PA were characterized by a significantly higher preoperative hematocrit value (P=0.014), lower aortic and superior vena cava oxygen blood saturation (P<0.001, P=0.024), severe right ventricle hypertrophy more rarely diagnosed in echocardiography (P<0.004), lower Qp:Qs ratio (P=0.011), larger right (P=0.001) and left (P=0.006) pulmonary artery index and a shorter intensive care unit stay after the hemi-Fontan procedure (P=0.004). Conclusions: The Norwood procedure with the RV–PA shunt provides satisfactory late hemodynamics and improves the development of the pulmonary arteries. Children with hypoplastic left heart syndrome subjected to this new method of palliation are good candidates for the hemi-Fontan procedure.     

Pulmonary preservation with Bretscheider''s HTK and Celsior solution in minipigs

Background: Pulmonary preservation with high potassium/low oncotic pressure Euro-Collins (EC) solution is associated with endothelial dysfunction and reduced surfactant function. We compared two low potassium solutions, histidine-tryptophane-ketoglutarate (HTK) and Celsior, to EC in lung ischemia-reperfusion injury. Methods: In 19 minipigs, the left lung was perfused in situ with cold preservation solution (EC, n=6; HTK, n=6; Celsior, n=7). Reperfusion was started after 90 min of warm ischemia. The right pulmonary artery and main bronchus were clamped. Bronchoalveolar lavage (BAL) was obtained before ischemia and after 2 h of reperfusion. Surfactant activity was determined from the BAL in a pulsating bubble surfactometer. Results: Animals in the EC group survived 3.7±1.4 h. Six Celsior and five HTK treated animals survived the observation period of 7 h (P<0.001). Compliance of the reperfused lung deteriorated less in both Celsior and HTK groups (P<0.001). In EC and HTK animals, the pO₂/FiO₂ ratio was lower (P=0.002), and pulmonary vascular resistance was higher (P=0.02) than in Celsior animals. Surfactant function was impaired after reperfusion in all groups. Conclusions: Compared to EC, HTK solution showed moderate and Celsior distinct improvement of post-ischemic pulmonary function. However, surfactant function was not well preserved in any group.     

Microwave and radiofrequency ablation yield similar success rates for treatment of chronic atrial fibrillation

Objective: To evaluate the influence of two different ablation devices (microwave AFx^® and radiofrequency Medtronic^®), designed to create linear lesion lines, with respect to efficacy and restoration of sinus rhythm (SR). Methods: Between February 2001 and December 2002, 42 patients with chronic, persistent atrial fibrillation (AF) >6 months were submitted to different combinations of valve surgery (mitral±tricuspid, n=30; mitral and aortic±tricuspid reconstruction, n=6; aortic±tricuspid, n=8) and concomitant Maze procedure. The biatrial Maze followed the concept of the Cox III procedure, using either microwave energy (AFx Lynx) (group I: age 65.8±11.9 years, mean duration of AF 61.9±28.9 months, n=23) or radiofrequency (Medtronic Cardioblate) (group II: age 64.1±11.1 years, mean duration of AF 53.5±49 months, n=19). Results: There was one death with group I (4%), due to liver failure. Both groups were comparable with regard to Euro Score, ejection fraction, cross clamp time, cardiopulmonary bypass time, ICU (median 1 day in both groups) and hospital stay, and type of indication. The preoperative diameter of the left atrium was 69.7±10.8 and 74.0±14.3 mm in groups I and II, respectively (P=0.359). The Maze procedure resulted in 23±2 and 17±1 min additional cross clamp time in groups I and II, respectively (P=0.013). At the 12-month follow up, freedom from AF was 81 and 80% in groups I and II, respectively. Twenty percent in group I and 21% in group II needed a pacemaker (PM), due to sick sinus syndrome (2 versus 2 cases), AV bloc (2 versus 1 case) and preoperative bradycardia (0 versus 1 case), respectively. Conclusions: The combination of complex valve surgery and Maze procedure was safe and reproducible. Following the Cox Maze III line concept, microwave and radiofrequency ablation gave similar results even in patients with more complex double or triple valve procedures.     

Extracardiac conduit Fontan procedure: early and intermediate results

Objective: The extracardiac Fontan procedure, as compared with classic atriopulmonary connections, may have the potential for optimizing ventricular and pulmonary vascular function by maximizing the laminar flow principle, by the avoidance of intra-atrial suture lines and cardiac manipulation, and by minimizing cardiopulmonary bypass time. In this study the clinical results of this procedure are assessed. Methods: From January 1990 until January 1997, 45 patients (33 males and 12 females) with a median age of 4.0 years (range 2.7–38 years) underwent an extracardiac Fontan procedure for univentricular physiology. The underlying diagnoses included tricuspid atresia (n=19), double-inlet left ventricle (n=11), and complex anomalies (n=15). Forty patients (89%) were in sinus rhythm. The median ventricular ejection fraction was 60%. In 37 patients (82%) the procedure was staged. Results: Median cardiopulmonary bypass time was 72 min, with a decrease to a median time of 24 min in the last ten patients. Aortic cross-clamping was avoided in 33 patients (73%). The intraoperative Fontan pressure and transpulmonary gradient were low: 13.6±3.2 and 8.5±3.9 mmHg, respectively. Transient supraventricular tachyarrhythmias were observed in six patients (13%). There was no early or late mortality. At a median follow-up of 64 months (range 26–105 months), 39 patients (87%) were in NYHA class I, four (9%) were in NYHA class II, and two (4%) were in class III. Forty patients (89%) remained in sinus rhythm. The median ventricular ejection fraction was 59%. The median arterial oxygen saturation raised from 82% preoperatively to 97%. Functional class (P=0.02), maintenance of sinus rhythm (P=0.04), and preservation of ventricular function (P=0.05) was superior in patients who were appropriately staged. None of the patients had atrial thrombus, chronic pleural effusions, or protein losing enteropathy. Conclusions: In the majority of patients, the extracardiac Fontan procedure, when performed as a staged procedure, provides excellent early and midterm results in terms of quality of life, maintenance of sinus rhythm, and preservation of ventricular function.     

Aprotinin reduces postoperative bleeding and the need for blood products in thoracic surgery: results of a randomized double-blind study

Objective: Bleeding complications have been a major concern in certain thoracic surgery operations, especially decortication and pulmonary resection for inflammatory pulmonary infection. Prevention of plasminogen activation and fibrinolysis by aprotinin administration has been shown to reduce perioperative bleeding during operations associated with high blood consumption. Methods: Use of blood products (packed red cells, whole blood), chest tube drainage, analgesic requirement, chest tube duration for the patients undergoing major thoracic operations were recorded. In a double blind randomized fashion, patients were assigned to two groups receiving aprotinin (n=51) at a loading dose of 10⁶ kallikrein inhibitory units (KIU) followed by an infusion of the same dose during chest closure or receiving placebo (n=52). On a daily basis, red-cell percentages of total fluid from drainage bottles were recorded and using the blood hematocrit level of the patient of the day before, the corrected value for the patient's blood volume equivalent of daily drainage was calculated. Results: There was a significant reduction in perioperative use of donor blood (0.98±0.92 vs. 0.45±0.32 unit; P=0.0026), and total chest tube drainage (corrected value for the corresponding blood volume) (28.2±36.9 vs. 76.9±53.3 ml, P=0.0004) (mean±standard deviation) in the aprotinin group. However, aprotinin did not reduce postoperative transfusion or decrease in hematocrit level due to thoracic operations. In high transfusion-risk thoracic surgery patients (patients who underwent decortication, pulmonary resection for inflammatory lung disease and chest wall resection), the perioperative transfusion was only 0.50±1.08 units in aprotinin group, compared with 1.94±0.52 units in control group (P=0.003). Postoperative transfusion was also reduced in aprotinin administrated group (0.53±0.56 vs. 1.38±0.97 units; P=0.02). The mean total blood loss was decreased to nearly one third of the blood loss of the control group (41±28 ml vs. 121±68 ml; P=0.001). Conclusion: Aprotinin significantly reduced perioperative transfusion requirement and postoperative bleeding during major thoracic operations. Aprotinin decreased perioperative transfusion needs. Moreover, patients who were at risk of greater blood loss during and after certain thoracic operations had a greater potential to benefit from prophylactic perioperative aprotinin treatment.     

Valvular heart operation in patients with previous mediastinal radiation therapy

Background. The outcome of valvular heart operations in patients with previous mediastinal radiation therapy was studied.

Methods. This is a single center retrospective study of 60 patients (37 females, 23 males) with a mean age of 62 ± 15 years (28 to 88 years old) operated on from January 1976 to December 1998. Valvular heart operations performed included aortic valve replacements (n = 26), mitral valve procedures (n = 16), tricuspid valve procedures (n = 6), and multiple valve procedures (n = 12). A total of 264 clinical, hemodynamic, electrocardiographic and echocardiographic variables were analyzed.

Results. Total follow-up was 199 patient-years with a mean of 3.3 ± 3.1 years and a range of 0 to 12.4 years old. Early mortality was 7 patients (12%). Early mortality in patients with constrictive pericarditis was 40% (4 of 10) compared with 6% (3 of 50) in patients without constrictive pericarditis. By univariate analysis, early mortality was associated with constrictive pericarditis (p = 0.011), reduced preoperative ejection fraction (p = 0.015), and longer cardiopulmonary bypass times (p = 0.037). A total of 14 patients (23%) required permanent pacemaker placement before (n = 7), during (n = 1), or early (n = 6) after valvular heart operations. There were 19 late deaths (malignancies, 7; heart failures, 5; other cardiac, 4; and other noncardiac, 3). Overall survival and freedom from late cardiac death and cardiac reoperation at 5 years for hospital survivors were 66% ± 8%, 82% ± 7%, and 93% ± 4%, respectively. By univariate analysis, late cardiac death was associated with low ejection fraction (p = 0.002), New York Heart Association (NYHA) functional class IV (p = 0.004), preoperative congestive heart failure (p = 0.02), and preoperative atrial fibrillation (p = 0.038). Eighty-five percent of the discharged patients were in NYHA functional class I or II at follow-up.

Conclusions. Early results of valve replacement after mediastinal radiation therapy were good except in the presence of constrictive pericarditis. Long-term outcome was limited by malignancy and heart failure. Early surgical intervention is recommended before the development of risk factors for late death, namely, severe symptoms, left ventricular dysfunction, and atrial fibrillation.     

Anaphylactic/anaphylactoid reactions during cardiac surgery

Over a 12-month period, 1,743 patients were retrospectively evaluated for anaphylactic/anaphylactoid reactions during cardiac surgery. Reactions to protamine, vancomycin, blood, and metocurine were observed in eight patients (0.46%). Base-line to reaction mean arterial pressures decreased from 81 ± 9 mmHg to 50 ± 7 mmHg (mean ± SD; p < 0.001), cardiac output increased from 4.6 ± 0.6 L/min to 6.5 ± 1.2 L/min (p < 0.005), stroke volume increased from 49 ± 11 to 83 ± 22 ml/beat (p < 0.02), and systemic vascular resistance decreased from 1,294 ± 137 to 563 ± 127 dyne/sec/cm⁻⁵ (p < 0.001). Two patients developed pulmonary artery hypertension, while only one patient developed bronchospasm. Initial hypertnsion during anaphylacticlanaphylactoid reactions is due to decreased systemic vascular resistance, not myocardial depression.     

Serum levels of osteoprotegerin increase with age in a healthy adult population

Regulation of the balance of osteoblastic and osteoclastic activity is critical for the understanding of normal cell biology and forms the basis of metabolic bone diseases. Our study reports about influences of age and gender on serum levels of osteoprotegerin (OPG) and its association to other clinical parameters of bone metabolism in a precisely determined cohort of 1134 healthy subjects at 17 Austrian outpatient bone clinics, aged between 19 and 96 years (females n = 687, 50 ± 21 years, 19–94, and males n = 447, 52 ± 13.5 years, 24–96). Mean OPG serum levels for all participants were 50.83 ± 51.47 pg/ml (n = 1134; median 36, 2–584) and we observed a sharp increase in females after 60 years and in males after 70 years of age. OPG serum levels increased significantly by age, 2.1 pg/ml in females and 1.9 pg/ml in males for every year (P < 0.0001). Correlation of OPG serum levels and several bone parameters of bone metabolism showed that OPG negatively correlated with serum iPTH (r = −0.14; P < 0.001) and with serum estradiol in females (r = −0.16, P < 0.0001). Bone mineral density measured by DXA method at the spine and at the hip did not correlate with OPG serum levels, except a borderline negative correlation at the trochanteric region (r = −0.1, P < 0.05) in females only. Our results show a significant increase of osteoprotegerin with age in healthy females and males but fluctuations do not predict bone mineral density under in vivo conditions.     

Is long-term functional outcome after lung volume reduction surgery predictable?

Objective: The aim of this retrospective study was to analyze which preoperative parameters might predict a persistent improvement in forced expiratory volume in 1 s (FeV1) 1 year after surgery. Methods: Seventy consecutive lung volume reduction surgery (LVRS) patients (age, 56.5±1.2 years) with a follow-up period of at least 1 year were analyzed (from September 1994 to September 1997). The patients were described by lung function tests, blood gas analysis, ventilatory mechanics (intrinsic positive endexpiratory pressure (PEEP)) and morphometric data (degree of heterogeneity, DHG; degree of hyperinflation, DHI; severity of parenchymal destruction, SPD) preoperatively. Based on the postoperative course of FeV1 (percentual increase compared with preoperative values, % increase), patients were divided into four groups: group A, (n=21) no improvement (FeV1≤20% increase); group B, (n=10) FeV1≥20% increase, which declined to preoperative values after 1 year; group C, (n=18) FeV1, 20–40% increase, sustaining at 1 year; group D, (n=21) FeV1≥40% increase, sustaining at 1 year. The statistics comprised of analysis of variance (ANOVA) and chi-square testing, with values presented as means±SEM. Results: No differences were found for lung function parameters (FeV1: 27.7±2.7, 26.0±2.5, 23.9±2.2 and 23.9±1.9% predicted, in groups A, B, C and D, respectively). Arterial blood gas levels preoperatively revealed significant differences between the groups; the arterial pO₂ was 66.2±1.2 mmHg in groups A+B compared with 61.8±1.5 mmHg in groups C+D (P=0.030). The arterial pCO₂ was 39.2±1.1 mmHg in groups A+B compared with 43.3±1.5 mmHg in groups C+D (P=0.038). The morphometric data had a strong trend towards higher heterogeneity in groups C and D. Marked DHI was found in 59 and 81% of patients in groups A+B versus C+D, respectively (P=0.121). Marked DHG was present in 22 and 54% of patients in groups A+B versus C+D, respectively (P=0.010). Conclusion: Preoperative arterial pO₂ and pCO₂, and the DHG are predictors for long-term benefit after LVRS with regard to the FeV1, 1 year postoperatively.     

Re-operation for bioprosthetic aortic structural failure – risk assessment

Objective: The predominant complication of bioprostheses is structural valve deterioration and the consequences of re-operation. Prosthesis choice for aortic valve replacement surgery (bioprostheses and mechanical prostheses), is influenced by valve-related complications (mortality and morbidity) of the prosthesis type chosen. The purpose of the study is to determine the mortality and risk assessment of that mortality for aortic bioprosthetic failure. Methods: From 1975 to 1999, 3356 patients received a heterograft bioprosthesis in 3530 operations. The procedures were performed with concomitant coronary artery bypass (CAB) in 1388 procedures and without in 2142 procedures. Three hundred twenty-two re-operations for structural valve deterioration were performed in 312 patients with 22 fatalities (6.8%). Of the 322 re-replacements, 36 had CAB and 286 had isolated replacement; the mortality was 8.3% (3) and 6.6% (19), respectively. Eleven predictive factors inclusive of age, concomitant CAB, urgency status, New York Heart Association (NYHA) at Re-op and year of Re-op (year periods) were considered. Results: The mortality for 1979–1986 was 6.1% (2/33); 1987–1992, 7.7% (8/104); and 1993–2000, 6.5% (12/185) (pNS). The mortality by urgency status for elective/urgent was 6.4% (19/299); and emergent, 13.0% (3/23) (pNS). The mortality for NYHA I/II was 2.0% (1/50), III 4.2% (8/191) and IV 16.0% (13/81) (P=0.00063), for gender was male 4.6% and female 13.3% (P=0.011), for age at implant ‘No’ (no re-operation) 51.6±12.2 years and ‘Yes’ (yes re-operation) 59.9±7.3 years (P=0.00004), for age at explant ‘No’ 62.6±12.7 years and ‘Yes’ 70.6±6.5 years (P=0.00001), and for age at explant <60 years 0.0% (0/110), 60–70 years 8.5% (10/117) and >70 years 12.6% (12/95) (P=0.0011). The predictive risk factor assessment by multivariate regression analysis revealed only NYHA III Odds Ratio 1.7 and IV 7.8 P=0.0082. For the period 1993–2000 of re-operations only gender was significant; age at implant, age at explant, CAB pre-Re-op, CAB concomitant with Re-op, urgency at Re-op, ejection fraction, valve lesion and NYHA at Re-op were not significant. Conclusions: Bioprosthetic aortic re-operative mortality can be lowered by re-operation in low rather than medium to severe NYHA functional class. The routine evaluation of patients can achieve earlier low risk re-operative surgery.     

Risk factors and outcome in European cardiac surgery: analysis of the EuroSCORE multinational database of 19030 patients

Objective: To assess risk factors for mortality in cardiac surgical adult patients as part of a study to develop a European System for Cardiac Operative Risk Evaluation (EuroSCORE). Methods: From September to November 1995, information on risk factors and mortality was collected for 19030 consecutive adult patients undergoing cardiac surgery under cardiopulmonary bypass in 128 surgical centres in eight European states. Data were collected for 68 preoperative and 29 operative risk factors proven or believed to influence hospital mortality. The relationship between risk factors and outcome was assessed by univariate and logistic regression analysis. Results: Mean age (± standard deviation) was 62.5±10.7 (range 17–94 years) and 28% were female. Mean body mass index was 26.3±3.9. The incidence of common risk factors was as follows: hypertension 43.6%, diabetes 16.7%, extracardiac arteriopathy 2.9%, chronic renal failure 3.5%, chronic pulmonary disease 3.9%, previous cardiac surgery 7.3% and impaired left ventricular function 31.4%. Isolated coronary surgery accounted for 63.6% of all procedures, and 29.8% of patients had valve operations. Overall hospital mortality was 4.8%. Coronary surgery mortality was 3.4% In the absence of any identifiable risk factors, mortality was 0.4% for coronary surgery, 1% for mitral valve surgery, 1.1% for aortic valve surgery and 0% for atrial septal defect repair. The following risk factors were associated with increased mortality: age (P=0.001), female gender (P=0.001), serum creatinine (P=0.001), extracardiac arteriopathy (P=0.001), chronic airway disease (P=0.006), severe neurological dysfunction (P=0.001), previous cardiac surgery (P=0.001), recent myocardial infarction (P=0.001), left ventricular ejection fraction (P=0.001), chronic congestive cardiac failure (P=0.001), pulmonary hypertension (P=0.001), active endocarditis (P=0.001), unstable angina (P=0.001), procedure urgency (P=0.001), critical preoperative condition (P=0.001) ventricular septal rupture (P=0.002), non-coronary surgery (P=0.001), thoracic aortic surgery (P=0.001). Conclusion: A number of risk factors contribute to cardiac surgical mortality in Europe. This information can be used to develop a risk stratification system for the prediction of hospital mortality and the assessment of quality of care.     

The effects of thermal injury on transcellular permeability and intestinal P-glycoprotein in rats

This study was designed to assess intestinal drug transport via transcellular absorption and intestinal P-glycoprotein content following thermal injury in rats using propranolol as a marker substrate. Male, Sprague Dawley rats (n=30) underwent either a 30% total body surface area full thickness burn or sham treatment. Twenty-four hours later, animals were anesthetized, underwent laparotomy and the proximal jejunum was cannulated. The jejunal segment was perfused with buffer containing [³H] propranolol. Following euthanasia, jejunal tissue was harvested for Western immunoblotting of P-glycoprotein and villin, and immunohistochemical analysis of P-glycoprotein. Dramatic structural changes in jejunal integrity were observed following thermal injury; however, no significant differences in the absorption characteristics of propranolol following thermal injury were observed. Mean effective permeability of propranolol was 5.67±1.79 and 5.85±1.67 cm/s×10⁻⁵ for burn and sham groups, respectively (P>0.05). P-glycoprotein and villin content in the jejunum were significantly decreased in burn animals. The transcellular transport of propranolol is unaffected 24 h following thermal injury in rats, despite alterations in intestinal P-glycoprotein content. The decrease in P-glycoprotein and villin content in thermally injured animals may reflect loss of mature enterocytes at the villus tips.