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.

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.

Hypertension prophylaxis with omega-3 fatty acids in heart transplant recipients.

OBJECTIVES: This study sought to determine whether omega-3 fatty acids act as hypertension prophylaxis in heart transplant recipients and have an impact on vascular reactivity. BACKGROUND: Cyclosporine-induced hypertension is probably related to endothelial dysfunction. Suggested vasodilatory mechanisms of omega-3 fatty acids may therefore be particularly beneficial in heart transplant recipients. METHODS: Heart transplant recipients were randomized to receive either 4 g of omega-3 fatty acids (treatment group, n = 14) daily or corn oil (placebo group, n = 14) from the fourth postoperative day. Twenty-four hour blood pressure monitoring was performed at day 12 and 1,2,3 and 6 months postoperatively. Microvascular endothelium-dependent vasodilation, evaluated by skin laser Doppler perfusion measurements of postocclusive reactive hyperemia, was determined preoperatively and at the end of the study. RESULTS: With comparable characteristics at the time of randomization, blood levels of cyclosporine did not at any point differ between the groups. After 6 months, systolic blood pressure decreased 2 +/- 4 mm Hg (mean +/- SEM) in the treatment group and increased 17 +/- 4 mm Hg in the placebo group (p < 0.01), whereas diastolic blood pressure increased 10 +/- 3 and 21 +/- 2 mm Hg (p < 0.01), respectively. The decrease in systolic blood pressure was inversely proportional to increases in concentrations of serum eicosapentaenoic and docosahexaenoic acid (p = 0.01). After 6 months, five patients in the treatment group and nine in the placebo group needed additional antihypertensive treatment. Although the endothelial-dependent phase of the reactive hyperemic response remained unchanged in the treatment group, it decreased significantly in the placebo group. CONCLUSIONS: Postoperative daily administration of 4 g of omega-3 fatty acids in heart transplant recipients is effective as hypertension prophylaxis, depending on increases in serum eicosapentaenoic and docosahexaenoic acids. Preservation of microvascular endothelial function, demonstrated by a more pronounced response to forearm skin ischemia in the treatment group, may contribute to the hypotensive role of omega-3 fatty acids.

Transmyocardial revascularization with CO2 laser in patients with refractory angina pectoris. Clinical results from the Norwegian randomized trial.

OBJECTIVES: The purpose of the study was to evaluate clinical effects, exercise performance and effect on maximal oxygen consumption (MVO2) of transmyocardial revascularization with CO2-laser (TMR) in patients with refractory angina pectoris. BACKGROUND: Transmyocardial laser revascularization is a new method to treat patients with refractory angina pectoris not eligible for conventional revascularization. Few randomized studies comparing TMR with conventional treatment have been published. METHODS: One hundred patients with refractory angina not eligible for conventional revascularization were block-randomized in a 1:1 ratio to receive continued optimal medical treatment (MT) or TMR in addition to MT. The patients were evaluated at baseline and at three and 12 months with end points to symptoms, exercise capacity and MVO2. RESULTS: Transmyocardial laser revascularization resulted in significant relief in angina symptoms after three and 12 months compared to baseline. Time to chest pain during exercise increased from baseline by 78 s after three months (p = NS) and 66 s (p < 0.01) after 12 months in the TMR group, whereas total exercise time and MVO2 were unchanged. No significant changes were observed in the MT group. Perioperative mortality was 4%. One year mortality was 12% in the TMR group and 8% in the MT group (p = NS.) CONCLUSIONS: Transmyocardial laser revascularization was performed with low perioperative mortality and caused significant symptomatic improvement, but no improvement in exercise capacity.

Ultrafiltration after cardiopulmonary bypass in children: effects on hemodynamics, cytokines and complement.

OBJECTIVES: The purpose of the study was to evaluate the clinical and hemodynamic effect of intraoperative extracorporeal ultrafiltration (UF) and its potential in reducing the plasma concentration of circulating cytokines and complement activation products following open heart surgery in children. METHODS: Eighteen children with congenital heart disease were prospectively randomized into a control group (n = 9) and a group who underwent UF (n = 9). Serial plasma samples for measurements of circulating cytokines (interleukin 6 (IL-6), tumor necrosis factor alpha (TNF), and its soluble receptor (sTNF receptor)), and complement factors (C3 activation products (C3a and C3bc) and terminal complement complex (TCC)) were obtained before, during and up to 48 h after cardiopulmonary bypass (CPB). A pulmonary artery thermodilution catheter was introduced preoperatively for hemodynamic monitoring. RESULTS: Postoperative hemodynamics were similar in both groups. Plasma levels of IL-6, sTNF receptors, C3a, C3bc and TCC increased significantly perioperatively (P < 0.01) in both groups. TNF was detected transiently in 16 patients perioperatively and in 4 of the 9 ultrafiltrate samples in concentrations similar to the plasma levels. Complement activating products were not detected in the ultrafiltration samples except for small amounts of C3a in two cases. Compared to the control group the plasma levels of C3a, C3bc and TCC were unaffected by the ultrafiltration procedure. The level of IL-6 and sTNF receptors increased significantly after 15 min of UF but there was no significant difference between the two groups postoperatively. CONCLUSIONS: In this study no clinical or hemodynamic effect was registered after UF. TNF and C3a were occasionally detected in the ultrafiltrate but we were unable to demonstrate reduction of these or any of the other markers tested in the group subjected to ultrafiltration.

Angiotensin II receptor subtype AT1 and AT2 expression after heart transplantation.

OBJECTIVE: Cardiac hypertrophy appears early after heart transplantation, and may represent a myocardial response to injury. Recent evidence suggests that angiotensin II (Ang II) may promote growth through the AT1 and inhibit growth through the AT2 receptor subtypes. We therefore asked whether hypertrophy after heart transplantation is characterized by alterations in Ang II receptor gene expression. METHODS: The expression of Ang II receptor subtypes. AT1 and AT2, was analyzed in right ventricular endomyocardial biopsies taken from 10 human donor hearts prior to implantation (controls) and from 17 heart transplant recipients, 11 studied during annual evaluation (> 1 year after transplantation) and 6 one week after transplantation. Competitive reverse transcription polymerase chain reaction (RT-PCR) was performed using synthetic RNA internal standards for both receptor subtypes. RESULTS: AT1 and AT2 receptor mRNAs were detected in all samples. AT1 receptor mRNA decreased 4.5 fold (p < 0.01) and AT2 receptor mRNA 4.2 fold (p < 0.001) in transplant patients compared with controls. In the subgroup of patients examined one week after surgery AT1 was reduced relative to AT2 receptor mRNA, resulting in an altered ratio of AT1 to AT2 early after transplantation. There was no correlation between Ang II receptor levels and left ventricular wall thickness, and the decrease in receptor level did not correlate with any hemodynamic parameters, cyclosporine blood levels, or plasma renin, Ang II or pANP, except for a negative correlation between AT2 mRNA and plasma renin (r = -0.49, p = 0.05). CONCLUSIONS: Contrary to our expectations, mRNA for both Ang II receptors was downregulated after heart transplantation. The cause of myocardial hypertrophy after heart transplantation is still unclear, but the hypertrophy does not appear to be driven by increased transcription of the AT1 receptor.

Myocardial expression of CC- and CXC-chemokines and their receptors in human end-stage heart failure.

OBJECTIVES: Chemokines regulate several biological processes, such as chemotaxis, collagen turnover, angiogenesis and apoptosis. Based on the persistent immune activation with elevated circulating levels of chemokines in patients with congestive heart failure (CHF), we have hypothesised a pathogenic role for chemokines in the development of CHF. The objective of this study was to examine mRNA levels and cellular localisation of chemokines and chemokine receptors in human CHF. METHODS: We examined explanted hearts from ten patients with end-stage heart failure (all chambers) and in ten organ donors using an RNase protection assays and immunohistochemical techniques. RESULTS: Our main findings were: (i) expression of eight chemokine and nine chemokine receptor genes in both failing and nonfailing myocardium, (ii) particularly high mRNA levels of monocyte chemoattractant protein (MCP)-1 and CXC-chemokine receptor 4 (CXCR4), in both chronic failing and nonfailing myocardium, (iii) decreased mRNA levels of MCP-1 and interleukin (IL)-8 in the failing left ventricles compared to failing left atria, (iv) decreased chemokine (e.g., MCP-1 and IL-8) and increased chemokine receptor (e.g., CCR2, CXCR1) mRNA levels in failing left ventricles and failing left atria compared to corresponding chambers in the nonfailing hearts and (v) immunolocalisation of MCP-1, IL-8 and CXCR4 to cardiomyocytes. CONCLUSION: The present study demonstrates for the first time chemokine and chemokine receptor gene expression and protein localisation in the human myocardium, introducing a new family of mediators with potentially important effects on the myocardium. The observation of chemokine dysregulation in human end-stage heart failure may represent a previously unknown mechanism involved in progression of chronic heart failure.

Compensatory cardiac mechanisms evoked by septal ischemia in dogs.

To examine the cardiac responses to selective septal ischemia, the septal artery was occluded intermittently in anesthetized open-chest dogs. Myocardial segment length was recorded continuously by an ultrasonic technique in the interventricular septum and the right and left ventricular free walls. At left ventricular end-diastolic pressure of 3.0 +/- 0.6 mm Hg, occlusion of the septal artery increased left ventricular end-diastolic segment length by 3.9 +/- 0.9% and stroke volume was maintained. After blood volume expansion to a left ventricular end-diastolic pressure of 7.2 +/- 1.4 mm Hg, occlusion of the septal artery did not increase end-diastolic dimensions and stroke volume decreased significantly but by less than 10%. At all levels of blood volume expansion, occlusion of the septal artery did not alter significantly the end-systolic segment length of the free wall of the left ventricle and the dimensions of the free wall of the right ventricle. The distance between the septum and the right ventricular free wall was unchanged in end-diastole and reduced in end-systole after occlusion of the septal artery. These observations indicate paradoxical movement of the ischemic septum. The ischemic septum seems to act as a passive diaphragm pump on the right ventricle without activation of the Frank-Starling mechanism in uninjured areas. In the left ventricle, the Frank-Starling mechanism is fully exploited with unaltered end-systolic dimensions of the uninjured myocardium because of the systolic bulging of the ischemia septum.

Possible role of proinflammatory cytokines in heart allograft coronary artery disease.

Transplant coronary artery disease (Tx-CAD) is the main determinant of long-term prognosis after heart transplantation. Immunologic processes may play a central role in the development of Tx-CAD, but the pathogenesis has not been fully clarified. We examined plasma levels of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukins (IL)-1beta and IL-6, and the CC-chemokine macrophage chemoattractant protein-1 (MCP-1) in 62 cardiac allograft recipients undergoing yearly heart catherization with coronary angiography for evaluation of graft disease. In this cross-sectional study, we found significantly increased levels of IL-1beta, IL-6, TNF-alpha, and MCP-1 compared with healthy controls even several years (median 7 years) after transplantation in periods with no intercurrent illness. Although no significant differences were found in plasma levels of IL-1beta and TNF-alpha between patients with (n = 25) and without (n = 37) Tx-CAD, the Tx-CAD group had significantly increased levels of IL-6 and MCP-1 compared with both controls and transplant recipients without Tx-CAD. Increased IL-6 levels compared with controls were found only in patients with Tx-CAD. Finally, while there was no significant relation between Tx-CAD and altered lipid status, the combination of high plasma concentrations of IL-6 or MCP-1 and high low-density lipoprotein cholesterol was strongly associated with increased occurrence of Tx-CAD. These findings indicate that cardiac allograft recipients have a persistent immune activation long term after transplantation. This activation, as particularly reflected in increased MCP-1 and IL-6 levels, may be related to the development of Tx-CAD.

Complement activation during extracorporeal circulation. In vitro comparison of Duraflo II heparin-coated and uncoated oxygenator circuits.

The degree of complement activation during cardiopulmonary bypass is considered a valuable parameter of biocompatibility of the extracorporeal circuit. In an in vitro setting with a heart-lung machine primed with fresh whole blood and saline solution, the C3 activation products C3b, iC3b, and C3c and the terminal complement complex were measured in double-antibody enzyme immunosorbent assays. No differences were found between seven sets treated with Duraflo II heparin coating and seven uncoated sets after 2 hours of circulation. C3 activation products (expressed as median and 95% confidence intervals) increased from 4.5 AU (2.8 to 12.3 AU) to 16.5 AU (10.0 to 19.4 AU) in the uncoated sets (p = 0.02) and from 4.6 AU (2.2 to 5.8 AU) to 19.3 AU (3.5 to 27.1 AU) in the coated sets (p = 0.02). Terminal complement complex increased from 5.7 AU (2.7 to 11.3 AU) to 13.6 AU (8.2 to 17.8 AU) in the uncoated sets (p = 0.02) and from 7.9 AU (4.6 to 11.4 AU) to 17.3 AU (9.4 to 35.1 AU) in the coated sets (p = 0.02). A significant drop in thrombocyte levels was observed in both coated and uncoated sets. In a supplementary series, the sterilization process did not influence the results. Although Duraflo II heparin coating is considered highly effective in preventing coagulation, it did not prevent complement activation in the present in vitro study. We hypothesize that the mode by which the heparin molecule is bound to the surface may be essential to obtain effects on both coagulation and complement system.

Single lung transplantation. Morphological surveillance by transbronchial biopsy.

Seven cases of single lung transplantation are reported. The recipients were all below 60 years of age and severely disabled with end-stage lung disease. Transplantation was performed according to ABO blood group compatibility and negative lymphocytotoxic cross-match between donor and recipient irrespective of HLA mismatch. Recipients' diagnoses were sarcoidosis (3), alfa-1 antitrypsin deficiency (3), and idiopathic emphysema (1). Mean recipient age was 48 +/- 2.4 years (range 45-52). Donor age was 29.7 +/- 5.6 years (range 16-49). The immunosuppressive regimen included cyclosporin A, azathioprine, steroids and rabbit antithymocyte globulin. Excellent graft function was achieved. Six patients survived the postoperative period and are alive 4-18 months posttransplant. One patient died after the operation due to pneumonia with respiratory distress syndrome. Graft function was also monitored by transbronchial biopsy, and 57 biopsy procedures were performed without fatal complications. Acute cellular rejection was seen in 16 biopsy specimens from 5 recipients (grade 1 and 2 rejection in 14, grade 3 rejection in 2). Neither severe rejection with septal necrosis (grade 4) nor obliterative bronchiolitis was seen. The rejection rate was 0.03 episodes per patient/month. In contrast to other reports, episodes of cellular rejection occurred throughout the observation period, and were not mainly limited to the first 4 months posttransplant. Graft vascular occlusive disease or chronic vascular rejection was found in 6 biopsy specimens from one recipient. Five patients experienced 7 episodes of cytomegalovirus infection. The cytomegalovirus infection rate was 0.01 episodes per patient/month. The incidence of infection was significantly lower compared to previous studies of rejection in other lung graft combinations. Both infections and rejection episodes may contribute to the development of obliterative bronchiolitis. Almost one third of the specimens (30%) showed lymphocytic bronchitis without perivascular inflammation. The absence of perivascular infiltrates and exclusion of infectious agents leaves in question the aetiology of this inflammation. The lymphocytic bronchitis could be ischaemic, related to aspiration, or represent recurrent sarcoidosis, or, in fact, express bronchial rejection. All biopsy specimens regarded as rejection with cellular infiltrates in the lung parenchyma also showed a lymphocytic bronchitis. The impact of HLA mismatch on cellular and vascular rejection is unclear. Transbronchial biopsy is a reasonably safe and reliable method in the diagnosis of rejection and infection in single lung transplantation.

Single lung transplantation as treatment for end-stage pulmonary sarcoidosis: recurrence of sarcoidosis in two different lung allografts in one patient.

Three patients have undergone single lung transplantation in our hospital because of respiratory failure as a result of sarcoidosis. Two patients survived the postoperative period. Obliterative bronchiolitis developed in one of these patients, and recurrence of sarcoidosis in the transplanted lung necessitated contralateral single lung transplantation. Nine months later the first transplant became necrotic and infected and had to be removed. The postoperative course was uncomplicated. However, transbronchial biopsy specimens 10 months after retransplantation show sarcoid changes also in the second transplant, but without any signs of cellular rejection.

Exercise capacity of heart transplant recipients: the importance of chronotropic incompetence.

BACKGROUND: Maximal exercise capacity is limited in patients after heart transplantation. The extent to which chronotropic incompetence contributes to this intolerance has not been well defined. METHODS: This prospective cross-sectional study examined the heart rate response to exercise and its relation to exercise capacity in 159 heart transplant recipients during progressive, symptom-limited, upright exercise. All prior exercise studies of heart transplant recipients that reported peak oxygen uptake and peak heart rate were also evaluated. RESULTS: Peak oxygen uptake was closely correlated with peak heart rate (r = 0.39, p < 0.001) and maximum increase in heart rate (r = 0.49, p < 0.001) during exercise by our patients. Similar correlations were found in the published studies for peak oxygen uptake versus maximal heart rate (r = 0.54, p < 0.05) and peak oxygen uptake versus increase in heart rate (r = 0.63, p < 0.02). The current study showed that the increase in heart rate from rest to peak exercise was significantly higher and the decline in heart rate after exercise significantly faster for patients 2 or more years after transplantation than for patients less than 2 years after transplantation (46 +/- 2 versus 38 +/- 1.9 beats/min, p < 0.05); the decline in heart rate 4 minutes after exercise was 27 +/- 1.8 versus 16 +/- 1.8 beats/min, respectively ( p < 0.001). CONCLUSION: The reduction in peak oxygen consumption, particularly during the first 2 years, appears to be related in part to chronotropic incompetence. Late after transplantation the heart rate response to exercise is greater and the decline in heart rate after exercise faster, suggesting possible autonomic reinnervation in some patients. Chronotropic incompetence may be an inadequate explanation of oxygen uptake impairment seen late after transplantation, when other factors such as myocardial dysfunction and intrinsic skeletal muscle abnormalities are of increasing importance.

Five years' follow-up of renal glomerular and tubular functions in heart transplant recipients.

BACKGROUND: Many studies have shown that cyclosporine A may have detrimental long-term effect on kidney function. However, few prospective long-term studies have assessed both glomerular and tubular functions of the kidneys in heart transplant recipients METHODS: We examined 10 heart transplant recipients prospectively for 5 years. Hemodynamic data were obtained by standard heart catheterization technique, and glomerular filtration rate and blood flow were calculated as clearance of inulin and paraaminohippuran, respectively. Tubular functions were assessed by renal excretion of enzymes and albumin and by the lithium clearance method. All patients received cyclosporine A, azathioprine, and prednisolone as immunosuppressive regimen. The dose of cyclosporine averaged 3.9 +/- 0.3 during the first year and 3.2 +/- 0.3 mg/kg up to 5 years. RESULTS: All patients completed the study. Four received rejection therapy. Six were treated for hypertension. Cardiac output remained unchanged and averaged 5.5 +/- 0.9 L/min at baseline. No change ws found in any of the measured or calculated central hemodynamic parameters except a tendency toward an increased systemic peripheral resistance with time. Glomerular filtration remained constant at 66 +/- 22 ml/min, renal plasma flow showed a tendency to decline averaging 361 +/- 133 at baseline and 254 +/- 68 ml/min at 5 years (p = 0.08). Albumin excretion rate increased from 22 +/- 27 to the 102 +/- 100 micrograms/min between 1 and 5 years ( p < 0.05). The excretion of tubular enzymes, N-acetyl-6-glucosaminidase and alkaline phosphatase, and the renal handling of lithium remained unchanged. CONCLUSIONS: Cyclosporine therapy over 5 years did not progressively impair glomerular or tubular functions. However, the occurrence of microalbuminuria may be caused by therapy with cyclosporine itself or associated hypertension.

Minimally invasive direct coronary artery bypass grafting without cardiopulmonary bypass in combination with intraoperative percutaneous transluminal coronary angioplasty for palliative coronary revascularization in a heart transplant recipient.

The use of minimally invasive direct coronary artery bypass grafting without cardiopulmonary bypass in combination with intraoperative percutaneous transluminal coronary angioplasty for myocardial revascularization in a heart transplant recipient is reported.

Nonoperative internal drainage of obstructive common bile ducts.

A new nonoperative method for internal drainage of common bile duct obstructions by endoscopic retrograde cannulation of the papilla of Vater is described. After introduction of a tube in the common bile duct, a substantial decrease in serum activity of bilirubin, alkaline phosphatase, and gamma-glutamyl transferase was found. In addition, a rapid improvement of the clinical condition could be observed. No serious complications occurred. It is concluded that internal drainage of common bile duct obstructions might be of great value in the preoperative treatment of patients with common bile duct obstructions.

Impairment in right ventricular performance after left ventricular aneurysm surgery.

To study the effect of operation for left ventricular (LV) aneurysm on right ventricular (RV) performance, we studied 50 patients before operation with right heart catheterization, RV angiography, and radionuclide ventriculography. Forty patients were followed up and underwent the same investigations 10 +/- 4 months after operation. At baseline, regional RV dysfunction was observed in 89% of the patients whereas global RV dysfunction was present in approximately a third. After operation, no changes in RV regional dysfunction or RV pressures were observed. However, a significant increase in RV end-diastolic (p less than 0.03) and end-systolic volume indices (p less than 0.02) along with a significant decrease in resting and exercise RV ejection fractions (p less than 0.05) was found. We were unable to demonstrate any significant relationship between preoperative RV dysfunction and surgical outcome. We conclude that RV dysfunction is common in patients with LV aneurysm. Current techniques of operative intervention for this type of aneurysm seem to be followed by RV dilatation and impairment in RV function.