The mode of death in the non-heart-beating donor has an impact on lung graft quality

Objective: We hypothesised that the agonal phase prior to cardiac death may negatively influence the quality of the pulmonary graft recovered from non-heart-beating donors (NHBDs). Different modes of death were compared in an experimental model. Methods: Non-heparinised pigs were divided into three groups (n = 6 per group). Animals in group I [FIB] were sacrificed by ventricular fibrillation resulting in immediate circulatory arrest. In group II [EXS], animals were exsanguinated (45 ± 11 min). In group III [HYP], hypoxic cardiac arrest (13 ± 3 min) was induced by disconnecting the animal from the ventilator. Blood samples were taken pre-mortem in HYP and EXS for measurement of catecholamine levels. After 1 h of in situ warm ischaemia, unflushed lungs were explanted and stored for 3 h (4 °C). Left lung performance was then tested during 60 min in our ex vivo reperfusion model. Total protein concentration in bronchial lavage fluid was measured at the end of reperfusion. Results: Pre-mortem noradrenalin (mcg l⁻¹) concentration (baseline: 0.03 ± 0) increased to a higher level in HYP (50 ± 8) vs EXS (15 ± 3); p = 0.0074. PO₂ (mmHg) at 60 min of reperfusion was significantly worse in HYP compared to FIB (445 ± 64 vs 621 ± 25; p < 0.05), but not to EXS (563 ± 51). Pulmonary vascular resistance (dynes s cm⁻⁵) was initially higher in EXS (p < 0.001) and HYP (NS) vs FIB (15824 ± 5052 and 8557 ± 4933 vs 1482 ± 61, respectively) but normalised thereafter. Wet-to-dry weight ratio was higher in HYP compared to FIB (5.2 ± 0.3 vs 4.7 ± 0.2, p = 0.041), but not to EXS (4.9 ± 0.2). Total protein (g l⁻¹) concentration was higher, although not significant in HYP and EXS vs FIB (18 ± 6 and 13 ± 4 vs 4.5 ± 1.3, respectively). Conclusion: Pre-mortem agonal phase in the NHBD induces a sympathetic storm leading to capillary leak with pulmonary oedema and reduced oxygenation upon reperfusion. Graft quality appears inferior in NHBD lungs when recovered in controlled (HYP) vs uncontrolled (EXS and FIB) setting.     

Mitroflow aortic pericardial bioprosthesis — clinical performance

Objective: Advancing life expectancy with the increased prevalence of aortic valve degenerative disease brings the need for an aortic bioprosthesis with excellent haemodynamic performance and comparable durability. The Mitroflow bioprosthesis has been on the worldwide market, except in the United States, since 1982, while the current model (1991) has only recently gained regulatory approval in the latter country. This study was primarily performed to determine the durability of the current Mitroflow bioprosthesis. Methods: The contemporary Mitroflow bioprosthesis was implanted in 381 patients in three centres. The mean age was 76.4 years (range 53–91 years) and the mean follow-up period was 5.4 ± 3.4 years, a total of 2048.7 years of evaluation. Prosthesis–patient mismatch (PPM) was classified by reference effective orifice area index categories: normal ≥0.85 cm² m⁻² (53.9%), mild 0.84–0.76 cm² m⁻² (33.9%), moderate ≤0.75–0.66 cm² m⁻² (11.7%) and severe ≤0.65 cm² m⁻² (0.5%). Results: The survival, at 10 years, was 39.9 ± 7.9% for 50–69 years, 27.0 ± 3.7% for 70–79 years and 16.6 ± 4.4% for ≥80 years (p = 0.011). There was a trend (p = 0.063) influencing survival for moderate-to-severe PPM. Of the independent predictors influencing survival – moderate-to-severe projected effective orifice area index (pEOAI) (Hazard Ratio (HR) 1.6, p = 0.0142) and left ventricular dysfunction (ejection fraction <35%) (HR 1.9, p = 0.0193) were included. The 10-year freedom from structural valve deterioration (SVD) at explant assessing the same age groups as survival was not different (p = 0.081). The 10-year actual/actuarial freedom from SVD, at explant was for ≥60 years – 94.4 ± 1.4% (85.2 ± 3.9%), for ≥65 years – 94.2 ± 1.4% (85.0 ± 4.0%), for 61–70 years – 97.4 ± 2.6% (95.7 ± 4.3%) and for >70 years – 94.0 ± 1.5% (83.2 ± 4.6%). Conclusions: The Mitroflow external mounted, pericardial aortic bioprosthesis with documented excellent haemodynamics (especially for the small aortic root), demonstrates that prosthesis–patient mismatch in moderate and severe categories can essentially be eliminated, with durability performance comparable to other heterograft (porcine and pericardial) bioprostheses.     

An initial evaluation of post-cardiopulmonary bypass acute kidney injury in swine

Objective: Acute kidney injury (AKI) post-cardiac surgery is associated with mortality rates approaching 20%. The development of effective treatments is hindered by the poor homology between rodent models, the mainstay of research into AKI, and that which occurs in humans. This pilot study aims to characterise post-cardiopulmonary bypass (CPB) AKI in an animal model with potentially greater homology to cardiac surgery patients. Methods and results: Adult pigs, weighing 50–75 kg, underwent 2.5 h of CPB. Pigs undergoing saphenous vein grafting procedures served as controls. Pre-CPB measures of porcine renal function were within normal ranges for adult humans. The effect of CPB on renal function; a 25% reduction in ⁵¹Cr-EDTA clearance (p = 0.068), and a 33% reduction in creatinine clearance (p = 0.043), was similar to those reported in clinical studies. CPB resulted in tubular epithelial injury (median NAG/creatinine ratio 2.6 u mmol⁻¹ (interquartile range (IQR): 0.81–5.43) post-CPB vs 0.48 u mmol⁻¹ (IQR: 0.37–0.97) pre-CPB, p = 0.043) as well as glomerular and/or proximal tubular injury (median albumin/creatinine ratio 6.8 mg mmol⁻¹ (IQR: 5.45–13.06) post-CPB vs 1.10 mg mmol⁻¹ (IQR: 0.05–2.00) pre-CPB, p = 0.080). Tubular injury scores were significantly higher in kidneys post-CPB (median score 2.0 (IQR: 1.0–2.0) relative to vein graft controls (median score 1.0 (IQR 1.0–1.0), p = 0.019). AKI was associated with endothelial injury and activation, as demonstrated by reduced DBA (dolichos biflorus agglutinin) lectin and increased endothelin-1 and vascular cell adhesion molecule (VCAM) staining. Conclusions: The porcine model of post-CPB AKI shows significant homology to AKI in cardiac surgical patients. It links functional, urinary and histological measures of kidney injury and may offer novel insights into the mechanisms underlying post-CPB AKI.     

Minimised versus conventional cardiopulmonary bypass: outcome of high-risk patients

Background: Coronary artery bypass grafting (CABG) with extracorporeal circulation (ECC) is the gold standard for surgical coronary re-vascularisation. Recently, minimised extracorporeal circulation system (MECC) has been postulated a safe and advantageous alternative for multi-vessel CABG. Method: Between January 2004 and December 2007, 244 high-risk patients (logistic EuroScore (ES) > 10%) underwent CABG in our institution. ECC was used in 139 (57%) and MECC in 105 (43%) patients. Demographic data including age (MECC: 73.4 ± 7.4 years; ECC: 73.3 ± 6.4 years), ES (MECC: 19.2 ± 9.8%; ECC: 21.4 ± 11.9%), left-ventricular ejection fraction (MECC: 45.6 ± 16.1%; ECC: 43.1 ± 15.3%), diabetes mellitus (MECC: 14.3%; ECC: 15.1%) and COPD (MECC: 6.7%; ECC: 7.9%) did not differ between the two groups. Preoperative end-stage renal failure was an exclusion criterion. The clinical course and serological/haematological parameters in the ECC and MECC patients were compared in a retrospective manner. Results: Although the numbers of distal anastomoses did not differ between the two groups (MECC: 3.0 ± 0.9; ECC: 2.9 ± 0.9), ECC time was significantly shorter in the MECC group (MECC: 96 ± 33 min; ECC: 120 ± 50 min, p < 0.01). Creatinine kinase (CK) levels were significantly lower 6 h after surgery in the MECC group (MECC: 681 ± 1505 U l⁻¹; ECC: 1086 ± 1338 U l⁻¹, p < 0.05) and the need of red blood cell transfusion was significantly less after MECC surgery (MECC: 3 [range: 1–6]; ECC: 5 [range: 2–9] p < 0.05). Moreover, 30-day mortality was significantly lower in the MECC group as compared to the ECC group (MECC: 12.4%; ECC: 26.6, p < 0.01). Discussion: MECC is a safe alternative for CABG surgery. A lower 30-day mortality, lower transfusion requirements and less renal and myocardial damage encourage the use of MECC systems, especially in high-risk patients.     

Coronary artery bypass grafting with concomitant cardiac resynchronisation therapy in patients with ischaemic heart failure and left ventricular dyssynchrony

Objective: We have tested the hypothesis that epicardial implantation of cardiac resynchronisation therapy (CRT) system during coronary artery bypass grafting (CABG) may be an additional treatment method, which can decrease the mortality and improve left ventricle (LV) systolic function in patients with ischaemic heart failure (HF) and LV dyssynchrony. Methods: One hundred and seventy-eight consecutive patients with severe ischaemic HF and LV dyssynchrony were enrolled in two groups: CABG alone (n = 87) and epicardial CRT implantation during CABG (n = 91). The primary end point of the study was the comparison of mortality between two groups at 18 months of follow-up. Results: Twenty-three patients (26.1%) in the CABG group died at 18 months of follow-up compared with nine (10%) in CABG + CRT group (log-rank test, p = 0.006). The Cox regression analysis revealed that LV dyssynchrony (hazard ratio (HR) 2.634 (1.206–5.751), p = 0.015) was the independent predictor of all-cause death and HF hospitalisation. LV systolic function, dyssynchrony signs and quality of life did not change significantly post-CABG compared to pre-CABG data in CABG group patients. On the contrary, echocardiography revealed an improved LV ejection fraction (42 ± 1.9 vs 28 ± 2.7; p < 0.001), smaller LV end-systolic volume (120 ± 57.5 vs 164 ± 61.4; p = 0.04) and improved LV synchrony in the CABG + CRT group compared with the CABG group. In the CABG + CRT group, more patients improved by two NYHA classes (NYHA, New York Heart Association; 49 vs 0; p = 0.028), had a longer 6-min-walk test distance (452 ± 65 vs 289 ± 72; p < 0.001) and a better quality of life (22.9 ± 5 vs 46.4 ± 11; p < 0.001) compared with the CABG group. Conclusion: For majority of the patients with ischaemic HF and evidence of LV dyssynchrony, CABG neither eliminates dyssynchrony nor improves systolic function. Epicardial implantation of a CRT system concomitant with CABG facilitates patient management in the early postoperative period, improves LV systolic function and quality of life and is associated with low mortality at 18 months of follow-up.     

The effect of fenoldopam and dopexamine on hepatic blood flow and hepatic function following coronary artery bypass grafting with hypothermic cardiopulmonary bypass

Background: Hypothermic cardiopulmonary bypass is associated with low perfusion state causing a mismatch between demand and supply to various organs such as gut, kidneys and brain. The consequences are thought to be responsible for postoperative complications like systemic inflammatory response, renal failure, neurological injury, etc. Pharmacological agents like dopamine, dopexamine and dobutamine have been used in an attempt to reduce hypoperfusion and hence complications. Fenoldopam, a dopamine analog (DA-1 receptor agonist), has recently been shown to be specific reno-splanchnic vasodilator in animal studies. We studied the haemodynamic effects of fenoldopam and its effect on hepatic blood flow (HBF) during and after cardiopulmonary bypass and compared these with dopexamine. Methods: Ethics committee approval was obtained. Forty-two consecutive patients with good/moderate left ventricular function undergoing either elective/urgent coronary artery bypass grafting were included in the study. Patients were randomised to receive either fenoldopam (0.2 μg/kg min) (F; n = 14) or dopexamine (2.0 μg/kg min) (Dx; n = 14) normal saline (NS; n = 14) continuously after induction of anaesthesia for 24 h following completion of surgery. HBF was measured using the Indocyanine green dye disappearance rate method, before, during and after cardiopulmonary bypass. Data were collected pre-, intra- and postoperatively. Serum liver enzymes were measured during the perioperative period. Repeated measures ANOVA test was used to compare timed samples in both groups. Results: The study groups were comparable in pre- and intraoperative variables. In the fenoldopam and dopexamine groups there was a significant increase in heart rate 15 min following the commencement of the infusion (NS:F:DX::−2.0 ± 7.8 beats/min:13.6 ± 8.1 beats/min (p = 0.007):18.36 ± 20.2 beats/min (p = 0.004)). However the change in mean arterial blood pressure was similar (NS:F:DX::−12.7 ± 14.9:−4.0 ± 23.1 (p = 0.699):−2.6 ± 22.3) (p = 0.235). Cardiac index increased and systemic vascular resistance decreased (requiring noradrenaline infusion) in the fenoldopam group, however this did not reach statistical significance. Hepatic blood flow reduced during CPB and returned to near preoperative levels in all three groups with no statistical difference between groups. Conclusions: Fenoldopam infusion induced transient tachycardia, with no augmentation of hepatic blood flow whereas dopexamine induced tachycardia and did not augment hepatic blood flow. Fenoldopam and dopexamine may have hepato-protective effect.     

Leucocyte filtration of salvaged blood during cardiac surgery: effect on red blood cell function in concentrated blood compared with diluted blood

Objective: Leucocyte filtration of salvaged blood has been suggested to prevent patients from receiving activated leucocytes during auto-transfusion in cardiac surgery. This study examines whether leucocyte filtration of salvaged blood affects the red blood cell (RBC) function and whether there is a difference between filtration of the concentrated and diluted blood on RBC function. Methods: Forty patients undergoing cardiac surgery with cardiopulmonary bypass were randomly divided into a group receiving leucocyte filtration of concentrated blood (High-Hct, n = 20) and another group receiving leucocyte filtration of the diluted blood (Low-Hct, n = 20). During operation, all the salvaged blood, as well as the residual blood, from the heart–lung machine was filtered. In the High-Hct group, blood was concentrated with a cell saver prior to filtration, whereas in the Low-Hct group, blood was filtered without concentration. RBC function was represented by RBC aggregation and deformability measured by a laser-assisted optical rotational cell analyser and by the RBC 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP) contents with conventional biochemical tests. Results: Leucocyte filtration of diluted blood with a low haematocrit (14 ± 4%) did not affect RBC function. However, when the concentrated blood with a high haematocrit (69 ± 12%) was filtered, there was a reduction of ATP content in RBCs after passing through the filter (from 1.45 ± 0.57 μmol g⁻¹ Hb to 0.92 ± 0.75 μmol g⁻¹ Hb, p < 0.05). For patients who received the concentrated blood, their in vivo RBC function did not differ from those who received diluted blood. Conclusions: Leucocyte filtration of the diluted salvaged blood during cardiac surgery does not affect RBC function, but it tends to deplete the ATP content of RBCs as the salvaged blood has been concentrated prior to filtration.     

Postoperative autotransfusion of mediastinal shed blood does not influence haemostasis after elective coronary artery bypass grafting

Objectives: The rationale of using autotransfusion of mediastinal shed blood after cardiac surgery is to preserve haemoglobin levels and reduce the need for allogenic blood transfusions. However, the method is controversial and its clinical value has been questioned. We hypothesised that re-transfusion of mediastinal shed blood instead impairs haemostasis after routine coronary artery bypass grafting and thus increases postoperative bleeding. Methods: Seventy-seven consecutive elective coronary artery bypass surgery patients (mean age 67 ± 9 years, 77% men) were included in a prospective, randomised controlled study. The patients were randomised to postoperative re-transfusion of mediastinal shed blood (n = 39) or to a group where mediastinal shed blood was discarded (n = 38). Primary end point was bleeding during the first 12 postoperative hours. Secondary end points were postoperative transfusion requirements, haemoglobin levels, thrombo-elastometric variables and plasma concentrations of interleukin-6, thrombin–anti-thrombin complex and D-dimer. Results: Mean re-transfused volume in the autotransfusion group was 282 ± 210 ml. There was no difference in postoperative bleeding (median 394 ml (interquartile range 270–480) vs 385 (255–430) ml, p = 0.69), proportion of patients receiving transfusions of blood products (11/39 vs 11/38, p = 0.95), haemoglobin levels 24 h after surgery (116 ± 13 vs 116 ± 14 g l⁻¹, p = 0.87), thrombo-elastometric variables, interleukin-6 (219 ± 144 vs 201 ± 144 pg ml⁻¹, p = 0.59), thrombin–anti-thrombin complex (11.0 ± 9.1 vs 14.8 ± 15, p = 0.19) or D-dimer (0.56 ± 0.49 vs 0.54 ± 0.44, p = 0.79) between the autotransfusion group and the no-autotransfusion group. Conclusions: Autotransfusion of small-to-moderate amounts of mediastinal shed blood does not influence haemostasis after elective coronary artery bypass grafting.     

Intracardiac allogeneic mesenchymal stem cell transplantation elicits neo-angiogenesis in a fully immunocompetent ischaemic swine model

Objectives: Autologous mesenchymal stem cell transplantation has been shown to improve myocardial function in ischaemic cardiomyopathy. We studied one hypothetical mechanism, neo-angiogenesis, using allogeneic mesenchymal stem cell transplantation in an ischaemic swine model. Methods: Allogeneic mesenchymal stem cells were injected in the peri-infarct area (1 × 10⁶ cells kg⁻¹) 2 weeks after myocardial infarction. Myocardial infarction alone (n = 3) served as a control group. In the myocardial infarction–mesenchymal stem cells group (n = 6), tacrolimus was given from day 0 to day 12. Capillary density and inflammatory/rejection processes (anti-factor VIII and anti-CD3/CD68 monoclonal antibodies, respectively) were compared between groups. Results: In scarred myocardium, capillary density was similar between both ischaemic groups: 15.4 (±15.3) and 14.7 (±15.2) vessel/field in myocardial infarction–mesenchymal stem cells and myocardial infarction-alone groups (non-significant). In viable myocardium adjacent to the infarction, capillary density was significantly increased in the myocardial infarction–mesenchymal stem cells group than in the myocardial infarction-alone group (p = 0.002). The number of infiltrating CD3+ cells was equivalent in both myocardial infarction-alone and myocardial infarction–mesenchymal stem cells groups (CD3+: 8.6% vs 9.3%, non-significant). However, CD68+ cell infiltration was more prominent after mesenchymal stem cell transplantation (4.7% vs 2% in myocardial infarction alone, p < 0.01). Conclusions: Allogeneic mesenchymal stem cell transplantation enhances angiogenesis after myocardial infarction. This effect is limited to the viable myocardium. Using a concomitant 12-day course of tacrolimus, no mesenchymal stem cell-specific cellular immune response was demonstrated.     

Anesthésie pour sténose du pylore. Evaluation de l'association propofol-anesthésiques halogénés

This study was aimed at evaluating haemodynamic changes during an anaesthetic sequence for full stomach, using propofol as induction agent and volatile anaesthetics for maintenance of anaesthesia in infants scheduled for surgical cure of hypertrophic pyloric stenosis. After correction of preoperative blood electrolyte and metabolic disturbances with appropriate i.v. hydrating solutions, anaesthesia was induced with propofol and suxamethonium. Infants were divided in two groups according to the volatile anaesthetic agent used for maintenance of anaesthesia after tracheal intubation : halothane (n = 16) or isoflurane (n = 15). The two groups were identical regarding weight (4.28 ± 0.6 vs 4.14 ± 0.76 kg), age (1.6 ± 0.9 vs 1.5 ± 0.6 months), preinduction heart rate (155 ± 22 vs 151 ± 22 b · min⁻¹) and systolic-diastolic arterial pressure (96 ± 18/58 ± 12 vs 105 ± 16/67 ± 15 mmHg). Propofol and suxamethonium doses were identical, 3.9 ± 1 mg · kg⁻¹ and 1.3 ± 0.6 mg · kg⁻¹ respectively in halothane groupe, vs 4.3 ± 0.8 mg · kg⁻¹ and 1.3 ± 0.4 mg · kg⁻¹ in isoflurane group. Heart rate did not change after induction of anaesthesia, while arterial blood pressure decreased significantly (p < 0.001). However, blood pressure remained within the normal range for age throughout the procedure. Mean duration of surgery was shorter in halothane group (64 ± 16 vs 79 ± 17 min, p < 0.05), however time-interval from the end of surgery to tracheal extubation (12 ± 6 vs 15 ± 8 min) was short and identical in the two groups. It is concluded that propofol seems to be appropriate for infants requiring a rapid i.v. sequence induction for “full-stomach”, as haemodynamic changes remain minimal.     

The impact of the lung allocation scoring system at the single national Veterans Affairs Hospital lung transplantation program

Objective: The lung allocation score (LAS) has changed the distribution of donor lungs for transplantation. This study was undertaken to evaluate the impact of the LAS on a unique patient population undergoing lung transplantation (LTX) at the single national Veterans Affairs (VA) LT center. Methods: One hundred and ten consecutive VA patients underwent LTX between 1994 and 2007. Patients transplanted using the LAS (LAS, n = 26) were compared to patients transplanted prior to introduction of the LAS (pre-LAS, n = 84). Results: Waiting time decreased from 353.8 ± 254.7 (pre-LAS) to 238.0 ± 306.6 (LAS) days (p < 0.01). Recipient diagnoses have changed with an increase in idiopathic pulmonary fibrosis [11% (9/84) pre-LAS vs 46% (12/26) LAS, p < 0.01] and a decrease in emphysema [57% (48/84) pre-LAS vs 35% (9/26) LAS, p < 0.01]. Mean LAS calculation was 33.1 ± 2.9 for pre-LAS versus 41.9 ± 9.8 for the LAS (p < 0.01). Postoperative complications did not differ between the groups. Length of hospital stay decreased from 44.3 ± 42.9 (pre-LAS) to 18.1 ± 12.3 (LAS) days (p < 0.01). Hospital mortality and 1-year survival did not differ between the pre-LAS and LAS groups (7% vs 8%; p = 0.72 and 92% [95% confidence interval (CI) 86–98] vs 92% [CI 82–100]; p = 0.23, respectively). Conclusions: The LAS appears to be achieving its objectives by reducing waitlist time and altering the distribution of lung disease being transplanted on the basis of medical necessity in the U.S. VA population. In addition, the LAS does not appear to have adversely affected short-term post-transplant outcomes in our recipient cohort.     

A novel protamine variant reversal of heparin anticoagulation in human blood in vitro

Purpose: Protamine reversal of heparin anticoagulation during cardiovascular surgery may cause severe hypotension and pulmonary hypertension. A novel protamine variant, [+18RGD], has been developed that effectively reverses heparin anticoagulation without toxicity in canine experiments. Heretofore, human studies have not been undertaken. This investigation hypothesized that [+18RGD] would effectively reverse heparin anticoagulation of human blood in vitro. Methods: Fifty patients who underwent anticoagulation therapy during vascular surgery had blood sampled at baseline and 30 minutes after receiving heparin (150 IU/kg). Activated clotting times were used to define specific quantities of [+18RGD] or protamine necessary to completely reverse heparin anticoagulation in the blood sample of each patient. These defined amounts of [+18RGD] or protamine were then administered to the heparinized blood samples, and percent reversals of activated partial thromboplastin time, thrombin clotting time, and antifactor Xa/IIa levels were determined. In addition, platelet aggregation assays, as well as platelet and white blood cell counts were performed. Results: [+18RGD] and protamine were equivalent in reversing heparin as assessed by thrombin clotting time, antifactor Xa, antifactor IIa levels, and white blood cell changes. [+18RGD], when compared with protamine, was superior in this regard, as assessed by activated partial thromboplastin time (94.5 ± 1.0 vs 86.5 ± 1.3%δ, respectively; p < 0.001) and platelet declines (–3.9 ± 2.9 vs –12.8 ± 3.4 per mm³, respectively; p = 0.048). Platelet aggregation was also decreased for [+18RGD] compared with protamine (23.6 ± 1.5 vs 28.5 ± 1.9%, respectively; p = 0.048). Conclusions: [+18RGD] was as effective as protamine for in vitro reversal of heparin anticoagulation by most coagulation assays, was statistically more effective at reversal than protamine by aPTT assay, and was associated with lesser platelet reductions than protamine. [+18RGD], if less toxic than protamine in human beings, would allow for effective clinical reversal of heparin anticoagulation. (J Vasc Surg 1997;26:1043-8.)     

Epoxyeicosatrienoic acids (EET11,12) may partially restore endothelium-derived hyperpolarizing factor–mediated function in coronary microarteries

Background. Endothelial cells derive nitric oxide, prostacyclin, and endothelium-derived hyperpolarizing factor (EDHF). The cytochrome P-450–monooxygenase metabolites of arachidonic acid (epoxyeicosatrienoic acids [EETs]) have been suggested to be EDHF. This study was designed to examine the effect of EET_11,12 with regard to the possibility of restoring EDHF function when added into hyperkalemic cardioplegic solution.Methods. Porcine coronary microartery rings were studied in a myograph. In groups 1 and 2, paired arteries were incubated in either hyperkalemic solution (K⁺ 20 mmol/L) or Krebs’ solution (control). In group 3, the paired arteries were incubated in hyperkalemia plus EET_11,12 (1 × 10^−6.5 mol/L) or hyperkalemia alone (control) at 37°C for 1 hour, followed by Krebs’ washout and then precontracted with 1 × 10^−8.5 mol/L U46619. The EDHF-mediated relaxation to EET_11,12 (group 1) or bradykinin (groups 2 and 3) was studied in the presence of N^G-nitro-l-arginine, indomethacin, and oxyhemoglobin.Results. After exposure to hyperkalemia, the EDHF-mediated maximal relaxation by bradykinin (72.5% ± 7.8% versus 41.6% ± 10.6%; p < 0.05), but not by EET_11,12 (18.4% ± 3.3% versus 25.1% ± 4.9%; p > 0.05) was significantly reduced. Incubation with EET_11,12 partially restored EDHF function (33.3% ± 9.5% versus 62.0% ± 8.5%; p < 0.05).Conclusions. In coronary microarteries, hyperkalemia impairs EDHF-mediated relaxation, and EET_11,12 may partially mimic the EDHF function. Addition of EET_11,12 into cardioplegic solution may partially restore EDHF-mediated function reduced by exposure to hyperkalemia.     

Long-term outcome after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: a single institution experience

Objective: Pulmonary endarterectomy (PEA) for chronic thromboembolic pulmonary hypertension (CTEPH) is the first treatment of choice with good short-term results. Only limited data are available concerning the long-term outcome after PEA. The purpose of this study is to evaluate the long-term survival and functional outcome after PEA with nearly 10 years experience. Method: In the period of December 1998 and December 2007 120 patients with CTEPH were referred to the St Antonius Hospital (Nieuwegein, The Netherlands) of whom 72 underwent PEA. The clinical data are collected retrospectively. Results: In-hospital mortality was (5/72) 6.9%. Since 2004 one patient died in the hospital (1/38, 2.9%). Two patients died during long-term follow-up with a median observation of 3 years. The overall 1-, 3- and 5-year survival rates were 93.1%, 91.2% and 88.7% respectively. Prior to surgery patients were in New York Heart Association functional class III (58) and IV (14) with a mean pulmonary vascular resistance of 572 ± 313 dynes s cm⁻⁵. The following data were compared before and after operation: mean pulmonary artery pressure (mPAP) decreased from 42 ± 11 to 22 ± 7 mmHg (p = 0.0001), NT-pro BNP improved from 1527 ± 1652 to 160 ± 3 pg/ml (p = 0.0001), 6 min walk distance (6MWD) from 359 ± 124 to 518 ± 11 m (p = 0.0001), and almost all patients returned to functional class I or II (p = 0.0001). Conclusion: Pulmonary endarterectomy for patients with CTEPH has shown a dramatic improvement of clinical status with excellent long-term survival.     

Muscle Mass Is More Strongly Related to Hip Bone Mineral Density Than Is Quadriceps Strength or Lower Activity Level in Adults Over Age 50 Year

This cross-sectional study examined whether reduced hip bone mineral density (BMD) is better explained by isokinetic knee extensor strength (KES), lower limb lean body mass (L-LBM), or Physical Activity Scale for the Elderly (PASE). Through population-based recruitment, 1543 adults without knee osteoarthritis were recruited. For men and women respectively, means ± SD were age 60.8 ± 8.0 and 61.1 ± 7.9 yr; body mass index 29.6 ± 4.6 and 29.1 ± 5.4 kg/m²; hip BMD 1.025 ± 0.138 and 0.895 ± 0.128 g/cm²; KES 124.9 ± 41 and 72.7 ± 22.9 N·m; L-LBM 10.3 ± 1.5 and 7.0 ± 1.2 kg; and PASE 206.4 ± 99.7 and 163.8 ± 77.0. The relationship between BMD and KES in men (r² = 0.21, p ≥ 0.002) and women (r = 0.23, p < 0.001) was significant before adjustment. However, this association was no longer significant after controlling for L-LBM. Even after controlling for age, race, and sex, the association between BMD and KES was better explained by L-LBM (partial R² = 0.14, p < 0.001) than by PASE (partial R² = 0.00). Allometric scaling of KES to body size attenuated the association of BMD with KES (Std Beta = 0.03). The significant association between BMD and L-LBM (Std Beta = 0.36) remained stronger than that between BMD and weight (Std Beta = 0.21). Therefore, muscle mass accounted for a greater proportion of the variance in hip BMD than KES or activity level and explained a significant proportion of the association between weight and BMD.     

Urodynamic Characterisation of Women with Naive Urinary Incontinence: A Population-Based Study in Subjectively Incontinent and Healthy 53–63 Years Old Women

Objectives: To compare the urodynamic characteristics in a group of middle-aged women with untreated urinary incontinence with the findings in a control group of healthy women.Methods: Sixty women with mild-to-moderate urinary incontinence and 28 symptom-free women, 53–63 years old, were randomly chosen out of a large health questionnaire study. All were investigated with a detailed history, gynaecological examination, urinalysis, frequency–volume chart, and urodynamics including cystometry and pressure-flow analysis.Results: The maximum urinary flow was significantly higher in the incontinent group of women, 22±1 ml/s, than in the healthy controls, 16±2 ml/s (p<0.01). The acceleration of flow, with a theoretical maximum of 0°, was also significantly faster in the incontinent, 20°, than in the healthy women, 32° (p=0.01). In the five women with urge incontinence only, maximum urinary flow was 26±2.4 ml/s and the flow acceleration 7°. In incontinent women, both a lower opening pressure and detrusor pressure at maximum flow were seen compared with the healthy women, though the difference did not reach statistical significance. The incontinent and the healthy women did not differ regarding bladder volumes or pressures during filling.Conclusion: The findings of this study indicate the presence of an increased efficiency of the urethral opening mechanism in incontinent women compared to normal, irrespective of the type(s) of symptoms present.     

Tricuspid valve surgery: a thirty-year assessment of early and late outcome

Objective: Tricuspid valve (TV) surgery is usually performed as a concomitant reconstruction procedure in addition to the correction of other cardiac pathologies. Isolated tricuspid procedures are exceptionally rare. Prosthetic valve replacement is also seldom required. Generally, these patients face a high risk of operative mortality and long-term outcome is poor. In this study we reviewed our experience with TV surgery focusing on risk factors for operative mortality, long-term outcome and incidence of valve related complications Methods: Retrospective analysis of 416 consecutive patients >18 years with acquired TV disease operated on between 1974 and 2003. The follow-up is 97% complete (mean 5.9 ± 6.3 years). Three hundred and sixty-six patients (88%) underwent TV surgery with concomitant mitral (n = 340) or aortic (n = 100) valve surgery. The tricuspid valve was repaired in 310 patients (74.5%) and replaced in 106 (25.5%). A biological prosthesis was used in 68 patients (64%). Mean age at repair and replacement was 61 ± 12.5 and 50 ± 11.3 years, respectively (p < 0.001). Results: Overall 30-day mortality was 18.8% (78/416) and decreased from 33.3% (1974–1979) to 11.1% (2000–2003) (p ≤ 0.0001). Thirty-day mortality after TV repair and replacement was 13.9% (43/310) and 33% (35/106), respectively (p ≤ 0.001). Cox regression analysis revealed TV replacement as an independent predictor of 30-day mortality. Ten-year actuarial survival after TV repair and replacement was 47 ± 3.5% and 37 ± 4.8%, respectively (p = 0.002). Forty-five patients (10.8%) required a TV re-operation after 7.7 ± 5.1 years. Freedom from TV re-operation 10 years after TV repair and replacement was 83 ± 3.6% and 79 ± 6.1%, respectively (p = 0.092). Conclusions: Patients who require tricuspid valve surgery constitute a high-risk group. Tricuspid valve repair is associated with better perioperative and long-term outcome than valve replacement. However, patients undergoing replacement showed a significant higher incidence of risk factors for operative mortality. The incidence of re-operation is low with no significant difference when the tricuspid valve has been repaired or replaced. When valve replacement is necessary we recommend the use of a biological prosthesis considering the poor long-term survival.     

Role of fluorine-flurodeoxyglucose positron emission tomography/computed tomography in preoperative assessment of anterior mediastinal masses

Objective: The purpose of the study was to explore the usefulness of fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG PET-CT) in the preoperative assessment of isolated anterior mediastinal lesions, especially in the planning of operative strategy (biopsy or upfront resection). Methods: During the last 36 months, 19 consecutive patients (10 males, mean age 54 ± 16 years) underwent PET-CT in the preoperative work-up of isolated anterior mediastinal diseases. Maximal transverse diameter at CT and the postoperative histology and Masaoka staging for thymomas were collected and related to the maximum standardised uptake values (SUVs). Thymomas were divided into low-risk thymoma (LRT = A, AB and B1) and high-risk thymoma (HRT = B2, B3 and C). Results: There were 13 thymomas (six LRT and seven HRT), three lymphomas and three other primitive thymic tumours (one paraganglioma, two non-seminomatous germ cell tumours). In LRT, the mean SUV was 3.3 ± 0.5 resulting significantly lower than HRT, 13.5 ± 7 (p = 0.009). The SUV in LRT was also significantly lower with respect to lymphoma, 12.4 ± 4 (p = 0.001), and the other primitive anterior mediastinal tumours, 8 ± 0.8 (p = 0.001). Between thymomas we found a significant correlation between Masaoka stage and SUV, r = 0.718, p = 0.006. No correlation was found between transverse diameters and SUV, r = 0.141, p = 0.6. Conclusions: In our experience, low SUV (<5) is associated with LRT and minimal invasive thymoma (Masaoka stages I–II) and, therefore, susceptible to upfront surgery. For lesions with an infiltrative aspect on CT scan associated with a higher SUV (>5), an open biopsy is mandatory to exclude mediastinal lymphomas or, in case of HRT, to address a neoadjuvant treatment.     

Synergistic interaction of 3 M KCl-extracted donor antigens (e-HAg) with cyclosporine or cyclosporine/sirolimus for prolongation of rat heart allograft survival

Extracted donor histocompatibility antigens (e-HAg) may potentiate the effects of drugs to protect organ allografts from rejection. We examined the capacity of e-HAg when combined with cyclosporine (CsA) alone, sirolimus (rapamycin, RAPA) alone, or CsA/RAPA combinations to prolong heart allograft survival in rats. Wistar-Furth (WF: RT1^u) rats that received CsA (10 mg/kg/day) by oral gavage for 3 (days 0, 1 and 2) or 7 (days 0, 1, 2, 3, 4, 5 and 6) consecutive days displayed modest prolongation of Brown Norway (BN; RT1ⁿ) heart allograft survival from a mean survival time of 7.2 ± 0.8 days in untreated controls to 12.2 ± 1.1 days and 18.6 ± 2.7 days, respectively (p < 0.01). Although administration on the day of transplantation (day 0) of a single intravenous (i.v.) dose of BN e-HAg (5 mg/kg) failed to affect allograft survival, both three (days 0, 1 and 2) and five (days 0, 1, 2, 3 and 4) injections significantly potentiated the effect of a 3-day course of oral CsA (18.6 ± 1.3 days (p < 0.01) and 20.0 ± 1.4 days (p < 0.01), respectively) and of a 7-day course of oral CsA (25.3 ± 4.4 days (p < 0.05) and 33.5 ± 9.3 days (p < 0.01), respectively). Median-effect analysis confirmed a synergistic interaction between CsA (0.5 mg/kg × 7 days, i.v.) and e-HAg with combination index (CI) values less than 0.7 (CI = 1 shows additive interactions, CI < 1 synergistic, and CI> 1 antagonistic, interactions). In contrast, e-HAg failed to affect the immunosuppressive effect of RAPA. However, e-HAg (5.0 mg/kg × 3 days) significantly potentiated the effects of a 7-day or 14-day course of RAPA (0.01 mg/kg)/CsA (0.5 mg/kg) combination therapy, namely from 26.0 ± 4.8 days with a 7-day treatment of CsA/RAPA alone to 32.6 ± 3.6 days (p < 0.01) and from 28.2 ± 2.7 days with a 14-day course of CsA/RAPA alone to 42.0 ± 4.9 days (p < 0.05), respectively (CI = 0.2–0.5). Thus, e-HAg potentiates the immunosuppressive effects of CsA alone and of the CsA/RAPA combination, but not of sirolimus alone.