Obstetric and neonatal outcome of pregnancies fathered by males on immunosuppression after solid organ transplantation.

Immunosuppressive drugs may influence spermatogenesis, but little is known about outcome of pregnancies fathered by transplanted males. We estimated risk of adverse outcomes in pregnancies (with data after the first trimester) fathered by males that had undergone organ transplantation and were treated with immunosuppression. A population-based study, linking data from the Norwegian transplant registry and the Medical Birth Registry of Norway during 1967-2009 was designed. All Norwegian men undergoing solid organ transplantation were included. Odds ratios for major malformations, preeclampsia, preterm delivery (<37 weeks) and small-for-gestational-age were obtained using logistic regression. A total of 2463 transplanted males, fathering babies of 4614 deliveries before and 474 deliveries after transplantation were identified. The risk of preeclampsia was increased (AOR: 7.4, 95% CI: 1.1-51.4,) after transplantation compared to prior to transplantation. No increased risk was found for congenital malformations or other outcomes when compared with pregnancies before transplantation or with the general population (2 511 506 births). Our results indicate an increased risk of preeclampsia mediated through the transplanted and immunosuppressed father. Importantly, no increased risk was found for other adverse obstetric outcomes or malformations, which may reassure male transplant recipients planning to father children.

Central venous catheters may be a potential source of massive air emboli during vascular procedures involving extracorporeal circulation: an experimental study.

Central venous catheters are mandatory during every major procedure involving extracorporeal circulation. Air emboli potentially could enter the circulation through this device when negative pressure is applied in the venous cannula. The following experimental study was initiated by a fatal massive air embolus during a vascular procedure involving cardiopulmonary bypass. An experimental setup was established, simulating a real scenario. The experiment was performed with a 40% glycerol/water mixture which exhibits properties and fluid dynamics close to blood. A heart-lung machine provided circulation of the fluid. The flow was adjusted according to the gravitational status. A triple-lumen central venous catheter with one line open to air was lowered into the liquid. The disconnected lumen of the central venous catheter was manipulated so it approached and was located in close proximity to the venous cannula. An air flow of up to 300 ml/min could be obtained from the central venous catheter with a flow in the cardiopulmonary bypass circuit of 2.3 L/min. A linear relationship was observed between flow in the circuit and air flow. Consecutive measurements proved consistent with acceptable results, proving that a disconnected central venous catheter might, under certain circumstances, be a source of massive air emboli during cardiopulmonary bypass.

Systemic markers of inflammation are associated with cardiac allograft vasculopathy and an increased intimal inflammatory component.

We evaluated an extensive profile of clinical variables and immune markers to assess the inflammatory milieu associated with cardiac allograft vasculopathy (CAV) assessed by intravascular ultrasound (IVUS) and virtual histology (VH). In total, 101 heart transplant (HTx) recipients were included and underwent IVUS/VH examination and measurement of plasma C-reactive protein (CRP), soluble tumor necrosis factor receptor-1, interleukin-6, osteoprotegerin, soluble gp130, von Willebrand factor, vascular cell adhesion molecule-1 (VCAM-1) and neopterin. Mean Maximal Intimal Thickness (MIT) was 0.61 +/- 0.19 mm and mean fibrotic, fibrofatty, dense calcified and necrotic core components were 55 +/- 15, 14 +/- 10, 15 +/- 13 and 17 +/- 9%, respectively. In multivariate analysis, CRP > 1.5 mg/L (OR 4.6, p < 0.01), VCAM-1 > 391 ng/mL (adjusted OR 3.2, p = 0.04) and neopterin > 7.7 nmol/L (OR 3.8, p = 0.02) were independently associated with MIT > 0.5 mm. Similarly, CRP > 1.5 mg/L (OR 3.7, p < 0.01) and VCAM-1 > 391 (OR 2.7, p = 0.04) were independently associated with an increased intimal inflammatory component (dense calcified/necrotic core component > 30%). Advanced CAV is associated with elevated CRP, VCAM-1 and neopterin and the two former biomarkers are also associated with an increased intimal inflammatory component. Forthcoming studies should clarify if routine measurements of these markers can accurately identify HTx recipients at risk of developing advanced CAV and vulnerable lesions.

Extracorporeal membrane oxygenation support for 59 days without changing the ECMO circuit: a case of Legionella pneumonia.

We report the successful use of veno-venous extracorporeal membrane oxygenation (ECMO) in a 53-year-old patient with Legionella pneumonia and acute respiratory distress syndrome (ARDS) with severe barotraumas. The patient was supported for 59 days without any changes in the ECMO circuit. This is probably the longest support ever reported using the same oxygenator.

Dural ectasia in Marfan syndrome: a case control study.

BACKGROUND AND PURPOSE: Dural ectasia (DE) is one of the major criteria of Marfan syndrome (MFS). Our aim was to establish the prevalence of DE in an adult population fulfilling the Ghent criteria for MFS and to assess definitions of DE. MATERIALS AND METHODS: One hundred five adults with suspected MFS were included. MR imaging at 1.5T was performed unless contraindicated; then CT was obtained. Lumbosacral anteroposterior vertebral body diameters (VBD) and dural sac diameters (DSD) were measured. Dural sac ratios (DSR = DSD/VBD) at levels L3 through S1 were calculated. Anterior meningoceles, herniations of nerve root sleeves, and scalloping were characterized. One hundred one sex- and age-matched patients were included as controls. RESULTS: We identified 3 patient groups: 1) fulfilling Ghent criteria independent of DE (n = 73), 2); fulfilling Ghent criteria dependent on DE (n = 14), and 3); and suspected MFS, not fulfilling Ghent criteria (n = 18). DE was found in 86% of group 1. At levels L4-S1, mean DSRs were significantly higher in group 1 than in group 3 and controls (P < .001). Herniations of the nerve root sleeves were present in 73% in group 1 versus 1% in controls. Anterior meningoceles were found in 37% and 14% in groups 1 and 2, respectively, but not in group 3 or controls. CONCLUSIONS: The diagnosis of DE on MR imaging or CT should be based on the presence of at least 1 of the following criteria: anterior meningoceles or nerve root sleeve herniation, DSD at S1 or below larger than DSD at L4, and DSR at S1 >0.59.

Severe chronic obstructive pulmonary disease: association with marginal bone loss in periodontitis.

An association between chronic marginal periodontitis and chronic obstructive pulmonary disease (COPD) has been suggested. The aim of this study was to investigate whether chronic marginal periodontitis is more prevalent in very severe COPD than in other very severe respiratory diseases, and whether periodontitis in COPD is related to risk factors for periodontitis that are often present in COPD subjects. Orthopantomograms were collected from 130 patients with COPD and 50 patients with non-COPD evaluated for lung transplantation. Chronic marginal periodontitis was defined as a general marginal bone level > or = 4 mm. The prevalence of periodontitis was 44% in the COPD group vs. 7.3% in the non-COPD group. All oral measurements differed significantly between the groups. The difference in mean marginal bone level remained statistically significant when adjusting for age, gender and pack years smoked. In logistic regression analysis mean marginal bone level > or = 4 mm was identified as a factor significantly associated with severe COPD. This study demonstrates that chronic marginal periodontitis is common in patients with severe COPD. The high prevalence of periodontitis in COPD patients appears to be independent of possible risk factors for periodontitis such as age, pack years smoked, body mass index, use of corticosteroids and bone mineral density.

Renal function after cardiopulmonary bypass surgery in patients with impaired renal function. A randomized study of the effect of nifedipine.

BACKGROUND AND OBJECTIVES: Postoperative acute renal failure predicts morbidity and mortality. We investigated the effect of nifedipine infusion on glomerular filtration rate in patients with impaired renal function undergoing cardiopulmonary bypass surgery. METHODS: Twenty patients accepted for coronary bypass and/or heart valve surgery were enrolled prospectively and randomized to nifedipine infusion or no treatment. Males and females with creatinine 150 micromol L(-1) and 130 micromol L(-1), respectively, were included. Patients with unstable angina pectoris, ejection fraction 35% and those on dialysis were excluded. Glomerular filtration rate was measured preoperatively and 48 h postoperatively. Creatinine clearance was measured preoperatively and 0-4, 20-24 and 44-48 h postoperatively. There were no statistically significant differences in patient characteristics. Biochemical markers in plasma and urine were measured before and 48 h after surgery. RESULTS: The mean +/- SD preoperative glomerular filtration rates were 32.2 +/- 11.5 and 31.4 +/- 17.0 mL min-1 per 1.73 m2 in the nifedipine and control groups (P = 0.90), respectively. There was no statistically significant change in the glomerular filtration rate or in creatinine clearance over time within or between groups. A linear mixed model showed no effect of nifedipine (P = 0.44), time (P = 0.97) or interaction of nifedipine and time (P = 0.99) on creatinine clearance. Perioperative arterial pressure was kept within predefined targets. Three patients received dialysis postoperatively, all in the control group (P = 0.21). There were no statistically significant differences between groups in changes of urinary or plasma biochemistry. CONCLUSIONS: Renal function was well preserved after cardiopulmonary bypass surgery in patients with impaired renal function when maintaining thorough intensive care surveillance. Nifedipine did not influence early postoperative renal function.

Plasma exchange and heart-liver transplantation in a patient with homozygous familial hypercholesterolemia.

A female patient born in 1950 underwent plasma exchange and concomitant drug therapy for 20 yr due to homozygous familial hypercholesterolemia. Plasma exchange reduced total cholesterol levels from 25-30 mmol/L (967-1160 mg/dL) before treatment to 9.5 mmol/L (363 mg/dL) with regression of xanthomas and no side effects of long-term treatment. Due to end-stage calcific left ventricular outflow tract obstruction not amenable to standard valve reconstructive surgery, a combined heart-liver transplantation was successfully performed in 1996. She is without symptoms and living a normal life 4 yr after transplantation. Total cholesterol value is normal (4.7 mmol/L [182 mg/dL]) using a moderate dose of statins. Selective coronary angiography is without signs of graft vascular disease and the liver function is normal.

Graft control by transit time flow measurement and intraoperative angiography in coronary artery bypass surgery.

BACKGROUND: The aim of this study was to compare the relationship between intraoperative transit time flow measurements and angiographic findings with long-term graft patency in 72 patients who underwent coronary artery bypass surgery. METHODS: Transit time flow measurements with recording of mean flow and pulsatility indexes were performed after completion of the anastomoses. Coronary angiography was performed on-table while the patients were still in general anesthesia, and then at follow-up three months and 12 months after surgery. Based on angiography, the grafts were graded as type A (fully patent), type B (having more than 50% diameter reduction), or type O (occluded). RESULTS: Of the 67 left internal mammary artery (LIMA) grafts, 51 (76%) were type A on-table, 14 (21%) were type B, and two (3%) were type O. Of the 57 saphenous vein grafts, 49 (86%) were type A, 7 (12%) were type B, and one (2%) was type O. For both LIMA and vein grafts, there were no differences in flow (p = 0.69 and 0.47, respectively) or pulsatility index (p = 0.79 and 0.83) between type A and B. There were also no differences in flow (p = 0.37 and 0.7) or pulsatility index (p = 0.37 and 0.24) between type B on-table that either normalized or persisted occluded at the follow-up. Transit time flow measurement failed to detect an occluded LIMA graft as shown by intraoperative angiography. CONCLUSIONS: Blood flow measurements performed intraoperatively could not identify significant lesions in arterial or vein grafts, and could not predict graft patency. We have become cautious in interpreting flow measurements alone and combine blood flow recordings with intraoperative angiography in the assessment of graft quality.

Regional cardiac expression and concentration of natriuretic peptides in patients with severe chronic heart failure.

The purpose of this study was to examine the regional cardiac mRNA expression and concentration of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in relation to the circulating peptide concentrations in patients with chronic heart failure (CHF). The myocardial mRNA levels and peptide concentrations of BNP and ANP were analysed in seven different regions of the heart from patients undergoing cardiac transplantation. Autopsy samples from individuals without known cardiovascular disease were used as controls. The plasma levels of natriuretic peptides and their N-terminal propeptides, Nt-proBNP and Nt-proANP, were measured in the CHF patients and healthy volunteers. In the autopsy specimens, the atrial regions appeared to contain the highest peptide levels for BNP as well as ANP, the atrioventricular ratio being 12-262 and 72-637-fold, respectively. In the CHF patients there was a relative shift towards the ventricle for BNP, reducing the atrioventricular ratio to 6-16-fold. The circulating concentrations of BNP/Nt-proBNP in the CHF patients correlated closely to the BNP mRNA expression in most myocardial regions including the left ventricle (r = 0.72, P < 0.001). For circulating concentrations of ANP/Nt-proANP, such correlation were limited to the left atrium free wall (r = .66, P < 0.002). Thus, of the two natriuretic peptides, BNP/Nt-proBNP may be a better reflector of left ventricular overload.

Differential effects of cocaine on the positive inotropic effect of noradrenaline mediated by alpha1- and beta-adrenoceptors in failing human myocardium.

Electrically driven (1 Hz) ventricular trabeculae from explanted failing human myocardium were indirectly examined for the localization of the alpha1-adrenoceptor population and the beta-adrenoceptor population in relation to sympathetic nerve endings. We examined the influence of neuronal uptake blockade by cocaine upon the horizontal position of the concentration-response curves for the inotropic effects exerted by noradrenaline in the presence and absence of appropriate adrenoceptor antagonists. Cocaine shifted the concentration-response curve for alpha1-adrenoceptor stimulation, but not that for beta-adrenoceptor stimulation, to lower concentrations of noradrenaline in a parallel manner. The concentration-response curve for combined adrenoceptor stimulation was shifted by cocaine to lower concentrations of noradrenaline in a nonparallel manner. In explanted allograft heart, cocaine had no effect upon the position of the concentration-response curve to alpha1-adrenoceptor stimulation. The data indicate that in the explanted native hearts the alpha1-adrenoceptor population is located close to or within the synaptic cleft, while the beta-adrenoceptor population remaining in the failing myocardium is located more distantly to the neuronal release sites.

Transthoracic intra-aortic balloon pump in open heart operations: techniques and outcome.

OBJECTIVE: During open heart surgery, direct transthoracic insertion of the intra-aortic balloon pump (IABP) is an alternative to the routine transfemoral insertion especially in the presence of severe peripheral vascular disease. METHODS: Over 19 years (1980-1998), 646 patients were treated with IABP. In 24 of them, the balloon was inserted transthoracic (TIABP) due to failure of transfemoral insertion in 13 or extensive occlusive aorto-iliac disease in 11 cases. RESULTS: Early mortality was 58.3% in patients having TIABP compared to 46.1% in patients with transfemoral IABP insertion (p > 0.2). Of the 24 patients receiving IABP transthoracic, none suffered vascular injury (i.e. perforation or dissection). Complications which could be related to TIABP occurred in 10 patients: 3 balloon ruptures, 1 mediastinal haemorrhage, 3 cerebrovascular accidents, 1 post-operative mediastinitis, and 2 late graft infections. CONCLUSIONS: TIABP is a useful alternative when transfemoral insertion of IABP is not feasible or hazardous because of occluded or severely diseased ilio-femoral arteries. Being a second choice and a more invasive treatment, transthoracic IABP is associated with increased mortality.

Myocardial gene expression of leukaemia inhibitory factor, interleukin-6 and glycoprotein 130 in end-stage human heart failure.

BACKGROUND: Studies in different animal models and plasma analyses in humans suggest that members of the interleukin-6 (IL-6) cytokine family may be involved in the pathogenesis of congestive heart failure (CHF). Accordingly, we have examined IL-6-related cytokines in chronic CHF in humans by analysing gene and protein expression in myocardium derived from patients with end-stage heart failure and donor hearts. METHODS: Gene expression of cytokines/receptors of the IL-6 family was documented in myocardial samples using cDNA array hybridization and RNase protection assays. Immunohistochemistry was used to detect leukaemia inhibitory factor (LIF), IL-6 and glycoprotein 130 (gp130) in myocardial tissues. RESULTS: Myocardial gene activity was documented for the majority of IL-6 family cytokines and their receptors. Immunohistochemical analysis localized IL-6, LIF and their common receptor subunit gp130 to myocytes and vascular smooth muscle cells. LIF mRNA levels were enhanced in the left ventricles of CHF patients relative to the left ventricles of donor hearts (patients 4.6 +/- 4.7 vs. donors 0.3 +/- 0.3, P < 0.005). Myocardial IL-6 and gp130 mRNA levels were not statistically different between patients and donors, but in contrast to LIF mRNA expression in heart explants, gp130 mRNA levels were significantly higher in left atrium compared with left ventricle in both patients and donors. CONCLUSIONS: Both mRNA and proteins of gp130 and its ligands IL-6 and LIF are expressed in both nonfailing and failing human myocardium. The elevated LIF mRNA levels in left ventricles from patients with end-stage heart failure suggest a role for LIF in the pathogenesis of CHF.

[Surgery in chronic pulmonary embolism]. / Kirurgi ved kronisk lungeemboli.

BACKGROUND: Chronic lung thromboembolism may develop after episodes of acute lung emboli. Instead of being resoluted, the thromboembolic material is incorporated into the walls of the lung arteries causing obstruction of the blood flow. Secondarily, pulmonary hypertension develops and patients experience increasing dyspnoea on exertion. In chronic pulmonary thromboembolism, drug therapy is of little benefit. Surgical thromboendarterectomy of lung arteries has emerged as an effective treatment for these very sick patients. MATERIALS AND METHODS: This paper discusses our experience with seven patients who underwent pulmonary thromboendarterectomy during the five-year period 1995-99 at our institution. The preoperative and postoperative haemodynamic evaluation of all patients were similar. RESULTS: For five patients the working capacity was significantly improved, one had limited symptomatic effect, and one died perioperatively due to massive surgical bleeding. INTERPRETATION: Pulmonary thromboendarterectomy may be indicated in selected patients with severe dyspnoea due to pulmonary hypertension secondary to chronic pulmonary thromboembolism.

Omega-3 fatty acids improve blood pressure control and preserve renal function in hypertensive heart transplant recipients.

BACKGROUND: Hypertension and cyclosporine-induced nephrotoxicity are common complications in heart transplant recipients. Omega-3 fatty acids may prevent blood pressure rise early, but have not been studied long-term after heart transplantation. METHODS AND RESULTS: Forty-five clinically stable hypertensive heart transplant recipients were studied 1-12 years after transplantation and randomized in a double-blind fashion to receive either 3.4 g of omega-3 fatty acids daily or placebo for 1 year. Ambulatory 24 h blood pressure monitoring and haemodynamic studies were performed before randomization and at the end of the study. Systolic blood pressure increased by 8+/-3 mmHg (P<0.01) in the placebo group, with a non-significant increase in diastolic blood pressure of 3+/-2 mmHg (P=0.10), accompanied by a 14% increase in systemic vascular resistance (P<0.05). In contrast, no change in blood pressure or systemic vascular resistance was recorded in the omega-3 group. Plasma creatinine increased (P<0.01) and glomerular filtration rate decreased (P<0.05) in the placebo group, while no changes were observed in the omega-3 group. The antihypertensive effect was related to an increase in serum eicosapentaenoic and docosahexaenoic acid. CONCLUSION: Treatment with omega-3 fatty acids may reduce the long-term continuous rise in blood pressure after heart transplantation and may offer a direct or indirect renoprotective effect, making these fatty acids a potentially attractive treatment for post-transplant hypertension.

Cardiac surgery in a girl with trisomy 13.

We describe a profoundly retarded infant girl with multiple anomalies caused by trisomy 13. Due to heart failure, which was resistant to medical treatment, we closed successfully a ventricular septal defect at three months of age. She died at 10 months of age. Despite the short survival, we believe that the patient benefitted significantly from the surgical repair of her cardiac defect.

Are heart transplant recipients more likely to develop skin cancer than kidney transplant recipients?

Non-melanoma skin cancer is frequent in organ transplant recipients. The risk of posttransplant cutaneous squamous cell carcinoma in Norwegian heart transplant recipients (n = 148) and kidney transplant recipients (n = 1020) on triple immunosuppressive therapy with cyclosporine, azathioprine, and prednisolone, transplanted between 1983 and 1992, were studied. After adjustment for age at transplantation in multivariable Cox models, heart transplant recipients had a significantly 2.8-times higher risk of developing squamous cell carcinoma relative to kidney transplant recipients. The risk relative to the general population (standardized incidence ratio) was higher in heart transplant recipients than in kidney transplant recipients. The results indicate that heart transplant recipients are more likely to be diagnosed with skin cancer than kidney transplant recipients, probably due to the higher doses of cyclosporine and azathioprine after heart transplantation used at our center in the study period.

Intraaortic balloon pumping for predominantly right ventricular failure after heart transplantation.

BACKGROUND: Right ventricular failure from elevated pulmonary vascular resistance in the recipient is a main cause of early mortality after heart transplantation. When pharmacologic treatment is insufficient, mechanical circulatory assistance has been used to support the failing right ventricle. Considering right and left ventricular interdependence, we investigated whether intraaortic balloon counterpulsation (IABP) might also alleviate predominantly right ventricular dysfunction after heart transplantation. METHODS: Among 278 cardiac recipients, 12 adult patients underwent mechanical circulatory support for cardiac allograft dysfunction. Five patients were treated with percutaneous IABP for early postoperative low cardiac output syndrome characterized by predominantly right ventricular failure. Clinical data and hemodynamic variables were recorded before and during IABP treatment. RESULTS: Cardiac index (CI) and mean arterial pressure (MAP) increased (CI 1.7 +/- 0.1 to 2.5 +/- 0.2, MAP 53 +/- 12 to 71 +/- 7, p < 0.05) within 1 hour after IABP, whereas central venous pressure (CVP) and pulmonary artery wedge pressure (PAWP) decreased (CVP 21.6 +/- 1.7 to 13.8 +/- 3.1, p < .05; PAWP 14.8 +/- 4.9 to 12.4 +/- 3.7, nonsignificant). Within the next 12 hours, CI and mixed venous oxygen saturation increased (p < 0.05) and pulmonary artery pressure decreased (p < 0.05). All 5 patients were weaned successfully and 4 are long-term survivors with adequate cardiac performance at 1 year follow-up. CONCLUSIONS: Intraaortic balloon pumping is a minimally invasive circulatory assist device with proved efficiency in low cardiac output syndromes. This report shows that low output syndrome caused by predominantly right ventricular allograft failure may be an additional indication for IABP.