The influence of blood pressure management on neurological outcome in endovascular therapy for acute ischaemic stroke.

BACKGROUND: Observational studies have suggested that low blood pressure and blood pressure variability may partially explain adverse neurological outcome after endovascular therapy with general anaesthesia (GA) for acute ischaemic stroke. The aim of this study was to further examine whether blood pressure related parameters during endovascular therapy are associated with neurological outcome. METHODS: The GOLIATH trial randomised 128 patients to either GA or conscious sedation for endovascular therapy in acute ischaemic stroke. The primary outcome was 90 day modified Rankin Score. The haemodynamic protocol aimed at keeping the systolic blood pressure >140 mm Hg and mean blood pressure >70 mm Hg during the procedure. Blood pressure related parameters of interest included 20% reduction in mean blood pressure; mean blood pressure <70 mm Hg, <80 mm Hg, and <90 mm Hg, respectively; time with systolic blood pressure <140 mm Hg; procedural minimum and maximum mean and systolic blood pressure; mean blood pressure at the time of groin puncture; postreperfusion mean blood pressure; blood pressure variability; and use of vasopressors. Sensitivity analyses were performed in the subgroup of reperfused patients. RESULTS: Procedural average mean and systolic blood pressures were higher in the conscious sedation group (P<0.001). The number of patients with mean blood pressure <70-90 mm Hg and systolic blood pressure <140 mm Hg, blood pressure variability, and use of vasopressors were all higher in the GA group (P<0.001). There was no statistically significant association between any of the examined blood pressure related parameters and the modified Rankin Score in the overall patient population, and in the subgroup of patients with full reperfusion. CONCLUSION: We found no statistically significant association between blood pressure related parameters during endovascular therapy and neurological outcome. CLINICAL TRIAL REGISTRATION: NCT 02317237.

Prevalence of cerebral and pulmonary thrombosis in patients with cyanotic congenital heart disease.

BACKGROUND: Patients with cyanotic congenital heart disease (CCHD) have a high prevalence of thrombosis, the most frequently described locations being the cerebral and pulmonary vessels. The reported prevalence of both cerebral infarction and pulmonary thrombosis has been highly variable. The aim of this study was to examine the prevalence of both cerebral and pulmonary thrombosis in CCHD according to medical history and imaging. In addition, the role of known erythrocytosis and haemostatic abnormalities as risk factors was evaluated. METHODS AND RESULTS: A cross-sectional descriptive study examining 98 stable adult patients with CCHD with a medical questionnaire, blood samples, MRI of the cerebrum (n=72), multidetector CT imaging (MDCT) of the thorax (n=76) and pulmonary scintigraphy (ventilation/perfusion/single-photon emission computerised tomography/CT) (n=66). The prevalence of cerebral infarction and pulmonary thrombosis according to imaging were 47% and 31%, respectively. Comparing the findings with previous medical history revealed a large under-reporting of thrombosis with only 22% of the patients having a clinical history of stroke and 25% of pulmonary thrombosis. There was no association between the degree of erythrocytosis or haemostatic abnormalities and the prevalence of thrombosis. CONCLUSIONS: Patients with CCHD have a prevalence of both cerebral and pulmonary thrombosis of around 30%-40%, which is much higher than that reported previously. Furthermore, there is a large discrepancy between clinical history and imaging findings, suggesting a high prevalence of silent thrombotic events. Neither erythrocytosis nor haemostatic abnormalities were associated with the prevalence of thrombosis in patients with CCHD. TRIAL REGISTRATION NUMBER: http://www.cvk.sum.dk/CVK/Home/English.aspx (H-KF-2006-4068).

Arrhythmia and exercise intolerance in Fontan patients: current status and future burden.

BACKGROUND: Long-term survival after the Fontan procedure shows excellent results but is associated with a persistent risk of arrhythmias and exercise intolerance. We aimed to analyze the current burden of clinically relevant arrhythmia and severe exercise intolerance in Danish Fontan patients and furthermore, to estimate the future burden from analysis of mortality and the current burden related to age. METHODS: All Danish citizens with Fontan completion from 1981 to 2009 were identified (n=235). Surviving patients performed exercise test, Holter monitoring, echocardiography, pulmonary function test, and blood sampling and medical history was retrieved from medical records. RESULTS: Twenty-six (11%) patients died or had heart transplantation (HTx) after a mean (± SD) post-Fontan follow-up of 8.3 ± 5.7 years. Excluding perioperative deaths (n=8), a linear probability of HTx-free survival was observed and estimated to 99.1% per year. Prevalence of clinically relevant arrhythmia and severe exercise intolerance increased significantly with age and was found in 32% and 85% of patients ≥ 20 years, respectively. Thus, from survival data and logistic regression models the future prevalence of patients, clinically relevant arrhythmia and severe exercise intolerance were estimated, revealing a considerable augmentation. Furthermore, resting and maximum cardiac index, resting stroke volume index and pulmonary diffusing capacity decreased significantly with age while diastolic and systolic ventricular function was unchanged. CONCLUSIONS: The prevalence of clinically relevant arrhythmia and severe exercise intolerance increased significantly with age in Danish Fontan patients. The future Fontan burden was estimated showing an increase in the prevalence of older patients, clinically relevant arrhythmia, and severe exercise intolerance.

Endothelial dysfunction, increased inflammation, and activated coagulation in HIV-infected patients improve after initiation of highly active antiretroviral therapy.

OBJECTIVES: Endothelial dysfunction and inflammation have been demonstrated to be markers of cardiovascular risk. We investigated the effects of HIV infection per se and the antiretroviral treatment prescribed on the levels of risk factors of cardiovascular disease. METHODS: This was a prospective study of 20 treatment-naïve, nonsmoking, HIV-positive patients examined before and after 3 months of treatment with a protease inhibitor (PI)-containing regimen followed by 3 months of treatment with nonnucleoside reverse transcriptase inhibitor (NNRTI)-containing therapy. Parameters of inflammation, endothelial function and coagulation were examined. The results were compared with those for an age- and gender-matched, nonsmoking, healthy control group. RESULTS: Compared with controls, treatment-naïve HIV-infected patients exhibited endothelial dysfunction [flow-mediated dilation (FMD) 108 vs. 111% for HIV-infected vs. control groups, respectively; P < 0.05] and activation [von Willebrand factor 2.0 vs. 0.9 U/l; soluble intercellular adhesion molecule (sICAM) 313 vs. 211 ng/L, respectively; P < 0.01]. Inflammation [C-reactive protein (CRP) 24 vs. 8.6 nmol/L; fibrinogen 9.4 vs. 8.6 µmol/L, respectively; P < 0.05] and coagulation/fibrinolysis (D-dimers 0.55 vs. 0.23 µg/mL, respectively; P < 0.01) were increased. Initiating therapy resulted in normalization of FMD and a significant decrease in endothelial activation and CRP. CONCLUSION: Endothelial dysfunction together with increased inflammation and coagulation were more prevalent in untreated HIV-infected patients compared with controls. These cardiovascular risk factors improved with treatment, although not all parameters normalized after 6 months.

The haematocrit--an important factor causing impaired haemostasis in patients with cyanotic congenital heart disease.

BACKGROUND: Patients with cyanotic congenital heart disease(CCHD) have haemostatic abnormalities, which result in an increased risk of bleeding. The cause is unknown, but recent studies have indicated that an elevated haematocrit, which is present in cyanotic patients, could be an important factor. The aim of this study was to characterize the haemostatic profile, examine how changes in haematocrit affect the haemostatic profile, and whether a haematocrit reduction could terminate bleeding in CCHD patients. METHODS: This was a prospective, multicenter study. The haemostatic profile consisting of haematocrit, platelet count and thrombelastography(TEG) was characterized in ninety-eight CCHD patients. To evaluate the influence of haematocrit on the haemostatic profile, 21 of the patients underwent phlebotomy and 16 patients received treatment with an iron supplement. Furthermore ten patients with haemoptysis underwent phlebotomy. The haemostatic profile was reevaluated after interventions. RESULTS: TEG revealed that patients with CCHD and elevated haematocrit were hypocoagulable due to reduced clot formation and strength. Furthermore a positive correlation between elevated haematocrit and hypocoagulability was present. Interventions such as phlebotomy and treatment with supplemental iron causing significant haematocrit changes confirmed the correlation between haematocrit and the haemostatic profile. Finally a haematocrit reduction by phlebotomy successfully terminated haemoptysis in ten CCHD patients. CONCLUSION: Patients with CCHD and elevated haematocrit are hypocoagulable. The hypocoagulable haemostatic profile is positively correlated to increasing haematocrit. An intervention, which increases or decreases haematocrit, changes the haemostatic profile. A haematocrit reduction seems to improve the haemostatic profile, and may thereby terminate bleeding. However, these results warrant further studies.

Thromboembolic complications in Fontan patients: population-based prevalence and exploration of the etiology.

After the Fontan procedure, patients face an increased risk for thromboembolic events (TE). The etiology for this increased thrombogenecity is incompletely understood. This study aimed to determine the prevalence of TE in Danish Fontan patients and to bring new insights into the etiology of TE. Using a population-based design, we retrospectively identified all TEs in 210 Fontan patients. Whole blood assays (thromboelastography, thromboelastography functional fibrinogen and Multiplate) reflecting global hemostasis, clot strength and platelet aggregation were analyzed prospectively in 112 patients and plasma was analyzed in 76 patients for biomarkers reflecting endothelial-, glycocalyx-, platelet-, and fibrinolysis function (histone-complexed DNA fragments, Protein C, soluble CD40 ligand, soluble thrombomodulin, syndecan-1, tissue-type plasminogen activator). The results were compared in groups stratified according to age, antithrombotic therapy, TE, and glycocalyx degradation (syndecan-1 < or ≥ median). Correlation between biomarkers and demographic-, anatomical-, clinical- and biochemical parameters was investigated. The prevalence of TE was 8.1 % after a mean follow-up of 8.4 years. None of the stratified groups demonstrated evidence of hypercoagulability in the whole blood assays and no unexpected significant differences were found between the groups. All biomarkers, except protein C, correlated with one another and after stratification of glycocalyx degradation only syndecan-1 levels ≥ median correlated with other biomarkers. The prevalence of TEs was 8.1 % after mean follow-up of 8.4 years. Overall, the hemostatic profile appeared normal, however, in a subset of patients, evidence of some endothelial activation/damage including glycocalyx degradation and fibrinolysis was found, identifying a potentially more thrombogenic group.

Protein expression studies of desmoplakin mutations in cardiomyopathy patients reveal different molecular disease mechanisms.

Mutations in the gene for desmoplakin (DSP) may cause arrhythmogenic right ventricular cardiomyopathy (ARVC) and Carvajal syndrome (CS). Desmoplakin is part of all desmosomes, which are abundantly expressed in both myocardial and epidermal tissue and serve as intercellular mechanical junctions. This study aimed to investigate protein expression in myocardial and epidermal tissue of ARVC and CS patients carrying DSP mutations in order to elucidate potential molecular disease mechanisms. Genetic investigations identified three ARVC patients carrying different heterozygous DSP mutations in addition to a homozygous DSP mutation in a CS patient. The protein expression of DSP in mutation carriers was evaluated in biopsies from myocardial and epidermal tissue by immunohistochemistry. Keratinocyte cultures were established from skin biopsies of mutation carriers and characterized by reverse transcriptase polymerase chain reaction, western blotting, and protein mass spectrometry. The results showed that the mutation carriers had abnormal DSP expression in both myocardial and epidermal tissue. The investigations revealed that the disease mechanisms varied accordingly to the specific types of DSP mutation identified and included haploinsufficiency, dominant-negative effects, or a combination hereof. Furthermore, the results suggest that the keratinocytes cultured from patients are a valuable and easily accessible resource to elucidate the effects of desmosomal gene mutations in humans.

Fibrinogen function is impaired in whole blood from patients with cyanotic congenital heart disease.

BACKGROUND: Patients with cyanotic congenital heart disease (CCHD) have haemostatic abnormities associated with bleeding and thrombo-embolic events. The haemostatic abnormalities are not fully understood, but recent studies indicate that elevated haematocrit and fibrinogen function may be of importance. The aim of this study was to characterise the haemostatic profile and examine the potential role of haematocrit on clot formation and strength in CCHD patients. Furthermore to examine whether CCHD patients with history of haemoptysis have diminished fibrinogen function compared to those without haemoptysis. METHODS: In a prospective study 75 adult CCHD patients had haematocrit, platelet count, and plasma fibrinogen concentration examined. Furthermore thrombelastography(TEG) as well as TEG Functional Fibrinogen(TEG FF) assay evaluating fibrinogen function(FLEV) was performed. Data were compared with historical data regarding previous haemoptysis in CCHD patients. RESULTS: Haematocrit was 57 ± 8% and platelet counts in the lower normal range. TEG revealed a hypocoagulable condition with impaired clot formation. TEG values were correlated to haematocrit, indicating that elevated haematocrit causes impaired clot formation and strength. Despite high levels of plasma fibrinogen, TEG FF demonstrated that FLEV was diminished and negatively correlated to haematocrit. Furthermore CCHD patients with previous history of haemoptysis had significantly lower FLEV compared to CCHD patients without haemoptysis. CONCLUSION: Patients with CCHD are hypocoagulable mainly due to impaired fibrinogen function. Despite a low platelet count, platelet function does not seem to be severely affected in CCHD patients. Haemostasis, and especially fibrinogen function, is negatively affected by elevated haematocrit, and fibrinogen function is diminished in CCHD patients with haemoptysis.

The neonatal but not the mature heart adapts to acute tachycardia by beneficial modification of the force-frequency relationship.

The force-frequency relationship (FFR) reflects alterations in intracellular calcium cycling during changing heart rate (HR). Tachycardia-induced heart failure is associated with depletion of intracellular calcium. We hypothesized (1) that the relative resistance to tachycardia-induced heart failure seen in neonatal pigs is related to differences in calcium cycling, resulting in different FFR responses and (2) that pretreatment with digoxin to increase intracellular calcium would modifies these changes. LV +dP/dt was measured during incremental right atrial pacing in 16 neonatal and 14 adult pigs. FFR was measured as the change in +dP/dt as HR was increased. Animals were randomized to control or intravenous bolus digoxin (n = 8 neonate pigs in the 0.05 mg/kg group and n = 7 adult pigs in the 0.025 mg/kg group) and paced for 90 min at 25 bpm greater than the rate of peak +dP/dt. Repeat FFR was then obtained. The postpacing FFR in neonatal control pigs shifted rightward, with peak force occurring 30 bpm greater than baseline (P < 0.03). There was no vertical shift; thus, force at 150 bpm decreased (P < 0.03) and force at 300 beats/min increased (P < 0.08). In adult control pigs, FFR shifted downward (P < 0.01), with decreased force generation at all HRs. In both neonates and adult pigs, digoxin increased +dP/dt at all HRs; however, in neonate pigs digoxin decreased the contractile reserve by abrogation of the rightward shift of FFR. An adaptive response to tachycardia in the neonate pig leads to improved force generation at greater HRs. Conversely, the response of the mature pig heart is maladaptive with decreased force generation. Pretreatment with digoxin modifies these responses.

Maternal hyperglycemia improves fetal cardiac function during tachycardia-induced heart failure in pigs.

BACKGROUND: Fetal tachycardia often leads to cardiac failure, which in experimental settings can be prevented by direct fetal glucose-insulin administration. In this study, we hypothesize that similar effects can be obtained indirectly by inducing maternal hyperglycemia. METHODS AND RESULTS: Systolic and diastolic indices (dP/dt(max) and tau) of left ventricular function were measured by use of high-fidelity catheters during 180 minutes of aggressive atrial pacing ( approximately 300 bpm) in 12 preterm porcine fetuses. In 6 fetuses, maternal hyperglycemia (15 mmol/L) was induced for the last 120 minutes of pacing. The remaining fetuses served as controls. Glucose, insulin, and free fatty acid levels were determined, as was fetal myocardial glycogen content. Maternal glucose infusion led to significant fetal hyperglycemia and hyperinsulinemia but did not change the inherently low fetal levels of free fatty acids. There were no differences between groups with regard to dP/dt(max) (1025+/-226 and 1037+/-207 mm Hg, P=NS) and tau (20.6+/-2.0 and 21.4+/-1.6 ms, P=NS) at baseline (100%). During the 180 minutes of pacing, systolic function (dP/dt(max)) and diastolic function (tau) deteriorated more in the control group than in the hyperglycemic group (P<0.001 for both). At 180 minutes, dP/dt(max) was 62+/-18% of baseline in controls and 85+/-11% in hyperglycemic fetuses (P=0.03), and tau was 117+/-12% and 98+/-4%, respectively (P=0.004). CONCLUSIONS: Induced maternal hyperglycemia improves fetal cardiac function during fetal tachycardia and suggests a possible additional therapeutic option to improve the function of the failing fetal heart before or during antiarrhythmic therapy. The findings may be relevant in fetal heart failure in general.

Flow during exercise in the total cavopulmonary connection measured by magnetic resonance velocity mapping.

OBJECTIVE: To measure caval and pulmonary flows at rest and immediately after exercise in patients with total cavopulmonary connection (TCPC). DESIGN: An observational study using the patients as their own controls. SETTING: Using a combination of magnetic resonance (MR) phase contrast techniques and an MR compatible bicycle ergometer, blood flow was measured in the superior vena cava, the tunnel from the inferior vena cava, and in the left and right pulmonary arteries during rest and on exercise (0.5 W/kg and 1.0 W/kg). PATIENTS: Eleven patients aged 11.4 (4.6) years (mean (SD)) were studied 6.3 (3.8) years after TCPC operation. MAIN OUTCOME MEASURES: Volume flow measured in all four branches of the TCPC connection during rest and exercise. RESULTS: Systemic venous return (inferior vena cava plus superior vena cava) increased from 2.5 (0.1) l/min/m2 (mean (SEM)) to 4.4 (0.4) l/min/m2 (p < 0.05) during exercise, with even distribution to the two pulmonary arteries. At rest, inferior vena caval flow was higher than superior vena caval flow, at 1.4 (0.1) v 1.1 (0.1) l/min/m2 (p < 0.05). During exercise, inferior vena caval flow doubled (to 3.0 (0.3) l/min/m2) while superior vena caval flow only increased slightly (to 1.4 (0.1) l/min/m2) (p < 0.05). The increased blood flow mainly reflected an increase in heart rate. The inferior vena caval to superior vena caval flow ratio was 1.4 (0.1) at rest and increased to 1.8 (0.1) (p < 0.05) at 0.5 W/kg, and to 2.2 (0.2) at 1.0 W/kg (p < 0.05). CONCLUSIONS: Quantitative flow measurements can be performed immediately after exercise using MR techniques. Supine leg exercise resulted in a more than twofold increase in inferior vena caval flow. This was equally distributed to the two lungs, indicating that pulmonary resistance rather than geometry decides flow distribution in the TCPC circulation.

Transoesophageal echocardiographic monitoring during paediatric cardiac surgery: obtainable information and feasibility in 532 children.

BACKGROUND: We hypothesized that transoesophageal echocardiography (TOE) performed by the anaesthesiologists would be beneficial for monitoring purposes during paediatric cardiac surgery. We present the results for the first 5 years in 532 consecutive children. METHODS: The probe was successfully inserted in 99% of cases and remained in the oesophagus for 211 min on average (range 10-555 min). RESULTS: Insignificant valve leak, single- or biventricular failure and volume depletion were the most common new findings due to TOE. Changes in inotropic strategy and volume replacement were the most frequent interventions. In 45% of the cases, new information was disclosed and, in a total of 8% of cases, decisive information was provided. Except for tracheal extubation in one child who was uneventfully reintubated, no severe complications were identified. CONCLUSIONS: These data stress the safety and ease of performing TOE in children undergoing cardiac surgery. There is evidence for benefit from TOE findings to potentially enhance the therapeutic basis.

Glaucoma in East Greenlandic Inuit--a population survey in Ittoqqortoormiit (Scoresbysund).

PURPOSE: To determine the prevalence of primary angle-closure glaucoma (PACG) in an isolated Greenlandic Inuit community and to examine the anatomical risk factors for this disease. METHODS: All individuals aged > or =40 years were examined. Visual acuity, refractive error, anterior chamber depth (ACD), intraocular pressure (IOP), gonioscopy, and optic disc characteristics were recorded. RESULTS: Seventy-nine individuals (65% response rate) were examined. Mean IOP was 12.0 mmHg. ACD was shallow and decreased with age and hypermetropia. ACD was deeper than observed in the same community in 1981 and another East Greenland population in 1970. Two subjects had definite PACG (2.5 %). CONCLUSION: This is the first study to use applanation tonometry in a Greenland population and confirms a low IOP as found in other populations of Inuit and Mongolians. ACD measured in 1998 was deeper than in 1981 in the same community which may represent a cohort effect indicating a secular change.

Increased platelet reactivity and significant changes in coagulation markers after cavopulmonary connection.

OBJECTIVE: To evaluate platelet reactivity and coagulation markers after surgical palliation of univentricular hearts. DESIGN AND PATIENTS: Cross sectional survey of 24 patients, median age 11 (range 4-22) years, at 2 (range 0.5-6) years after a total cavopulmonary connection (TCPC; n = 14) or a bidirectional Glenn anastomosis (Glenn; n = 10). MAIN OUTCOME MEASURES: Platelet reactivity and/or coagulation markers were measured in 20 patients (four excluded because of anticoagulant treatment) and compared with 33 healthy controls, median age 12 (range 6-16) years. RESULTS: None of the patients had clinically apparent thromboembolic events. However, increased platelet reactivity was observed ex vivo both after collagen induced platelet aggregation (median 73% (interquartile range 61-84%) in patients, and 61% (47-69%) in controls; p < 0.01), and after ADP induced platelet aggregation (69% (53-77%) in patients, and 56% (40-66%) in controls; p < 0.05). Concentrations of protein S antigen, antithrombin III, and protein C activity were reduced after both TCPC and Glenn. A concomitant decrease was seen in coagulation factor II, VII, X, and factor VII clot activity. CONCLUSIONS: Several abnormalities in the coagulation system were observed after bidirectional Glenn anastomosis, similar to alterations previously described in Fontan operated and TCPC patients. Antithrombotic treatment in these patients is still an unresolved issue, but aspirin is often recommended. This study shows that such a strategy is rational and the results suggest that antiplatelet treatment may be advantageous, either alone or in combination with oral anticoagulant treatment.

Improvement in growth, and levels of insulin-like growth factor-I in the serum, after cavopulmonary connections.

INTRODUCTION: The total cavopulmonary connection, and the bidirectional Glenn anastomosis, are widely used for palliation of patients with complex functionally univentricular hearts. Little attention has been paid to the potential for postoperative growth in children after these operations, which are now performed at increasingly younger age. MATERIAL AND RESULTS: Physical growth, and levels of insulin-like growth factor I in the serum, were measured in 20 patients, aged 11.5 +/- 5.6 years, 2 (0.5-6) years after a total cavopulmonary connection in 12, or a Glenn anastomosis in 8. All patients were in functional class I or II of the categorisation of the New York Heart Association, with excellent haemodynamic and angiographic findings. None of the patients had clinical signs of protein losing enteropathy. Controls included 33 healthy children, aged 11.5 +/- 2.7 years. Preoperatively, the mean Z-scores for weight and height were negative, -1.1 +/- 0.8 and -0.5 +/- 1.5. At follow-up, both parameters had improved significantly by 1.1 +/- 0.9 and 0.8 +/- 1.2 percentiles, and Z-scores were comparable between the two groups (p=0.81 for weight and p=0.88 for height). No correlations were found between haemodynamics and the improvement in growth noted during follow-up. Increases equal to, or greater than 2 standard deviations for weight and height were seen only in children undergoing surgery before the age of 5 years. A significant correlation between age at operation and improvement in growth, however, could not be found. Levels of growth factor measured in the serum were not statistically different from levels in healthy children for either group of patients (p=0.07 for girls and p=0.37 for boys). CONCLUSION: Physical growth improved significantly following the surgical procedures. The concentrations of the growth factor measured in the serum were not different from levels in healthy children, suggesting normal nutritional status in both palliative situations.

Neurohormonal activation late after cavopulmonary connection.

OBJECTIVE: To determine whether patients with cavopulmonary connection have higher levels of vasoactive/water-salt regulating hormones and if so, whether hormone levels are related to postoperative haemodynamics and postoperative follow up. DESIGN: Cross sectional study. SETTING: University hospital. PATIENTS: 20 patients (New York Heart Association functional class I-II), mean age 11 years (range 4 to 22), were studied at a mean of 2 years (0.5 to 6) after a total cavopulmonary connection (TCPC, n = 12) or a bidirectional Glenn anastomosis (BDG, n = 8). INTERVENTIONS: Cardiac catheterisation was performed and blood samples were drawn. Control blood samples were drawn from 33 healthy children, mean age 12 years (6 to 16). MAIN OUTCOME MEASURES: Plasma levels of angiotensin II, renin, aldosterone, arginine, vasopressin, atrial natriuretic factor (ANF), brain natriuretic peptide (BNP). RESULTS: All neurohormones were significantly increased in both TCPC and BDG patients (p < 0. 05), with a fourfold increase in angiotensin II, renin, and aldosterone, and a twofold increase in vasopressin, ANF, and BNP (compared with healthy controls). There was no correlation between haemodynamic variables and hormone levels. Angiotensin II and renin were inversely correlated with time to follow up. All subjects over 15 years (n = 5) had normal neurohormonal levels. CONCLUSIONS: Neurohormones were raised for years after successful cavopulmonary operations but lower levels were observed with time on follow up. This supports the hypothesis that neurohormonal activation is primarily related to altered postoperative physiology and that adaptation takes place over time.

Inhibition of nitric oxide synthesis improves left ventricular contractility in neonatal pigs late after cardiopulmonary bypass.

BACKGROUND: Following neonatal open heart surgery a nadir occurs in left ventricular function six to 12 hours after cardiopulmonary bypass. Although initiated by intraoperative events, little is known about the mechanisms involved. OBJECTIVE: To evaluate the involvement of nitric oxide in this late phase dysfunction in piglets. DESIGN: Piglets aged 2 to 3 weeks (4-5 kg) underwent cardiopulmonary bypass (1 h) and cardioplegic arrest (0.5 h) and then remained ventilated with inotropic support. Twelve hours after bypass, while receiving dobutamine (5 microg/kg/min), the left ventricular response to non-selective nitric oxide synthase inhibition (l-N(G)-monomethylarginine (l-NMMA)) was evaluated using load dependent and load independent indices (E(es), the slope of the end systolic pressure-volume relation; M(w), the slope of the stroke work-end diastolic volume relation; [dP/dt(max)](edv), the slope of the dP/dt(max)-end diastolic volume relation), derived from left ventricular pressure-volume loops generated by conductance and microtip pressure catheters. RESULTS: 10 pigs received 7.5 mg l-NMMA intravenously and six of these received two additional doses (37.5 mg and 75 mg). E(es) (mean (SD)) increased with all three doses, from 54.9 (40.1) mm Hg/ml (control) to 86.3 (69.5) at 7.5 mg, 117.9 (65.1) at 37.5 mg, and 119 (80.4) at 75 mg (p < 0.05). At the two highest doses, [dP/dt(max)](edv) increased from 260.8 (209.3) (control) to 470.5 (22.8) at 37.5 mg and 474.1 (296.6) at 75 mg (p < 0.05); and end diastolic pressure decreased from 16.5 (5.6) mm Hg (control) to 11.3 (5.0) at 37.5 mg and 11.4 (4.9) at 75 mg (p < 0. 05). CONCLUSIONS: In neonatal pigs 12 hours after cardiopulmonary bypass with ischaemic arrest, low dose l-NMMA improved left ventricular function, implying that there is a net deleterious cardiac action of nitric oxide at this time.

[Transcatheter occlusion of patent ductus arteriosus]. / Kateterbaseret lukning af persisterende ductus arteriosus.

Percutaneous closure of a patent arterial duct was performed in 58 patients. A Rashkind double umbrella was inserted in 20 patients. A supplementary double umbrella or coils were implanted in four who had residual leaks after 12 months. Three complications: embolization, haemolysis and late bacteriaemia were managed successfully without surgery. A detachable PDA coil was inserted in 38 patients. Three coils embolized and one could not be retrieved. At complete follow-up of 28 patients the duct was closed in all. Median procedure duration and fluoroscopy time was 60 min. and 12 min. respectively for double umbrella implantation, and 20 min. and 5 min. for coil insertion. Transcatheter occlusion of the patent duct is effective and carries little morbidity.

Pulmonary and caval flow dynamics after total cavopulmonary connection.

OBJECTIVE: To assess flow dynamics after total cavopulmonary connection (TCPC). DESIGN: Cross-sectional study. SETTING: Aarhus University Hospital. PATIENTS: Seven patients (mean age 9 (4-18) years) who had previously undergone a lateral tunnel TCPC mean 2 (0. 3-5) years earlier. INTERVENTIONS: Pressure recordings (cardiac catheterisation), flow volume, and temporal changes of flow in the lateral tunnel, superior vena cava, and right and left pulmonary arteries (magnetic resonance velocity mapping). RESULTS: Superior vena cava flow was similar to lateral tunnel flow (1.7 (0.6-1.9) v 1. 3 (0.9-2.4) l/min*m2) (NS), and right pulmonary artery flow was higher than left pulmonary artery flow (1.7 (0.6-4.3) v 1.1 (0.8-2. 5) l/min*m2, p < 0.05). The flow pulsatility index was highest in the lateral tunnel (2.0 (1.1-8.5)), lowest in the superior vena cava (0.8 (0.5-2.4)), and intermediate in the left and right pulmonary arteries (1.6 (0.9-2.0) and 1.2 (0.4-1.9), respectively). Flow and pressure waveforms were biphasic with maxima in atrial systole and late ventricular systole. CONCLUSIONS: Following a standard lateral tunnel TCPC, flow returning via the superior vena cava is not lower than flow returning via the inferior vena cava as otherwise seen in healthy subjects; flow distribution to the pulmonary arteries is optimal; and some pulsatility is preserved primarily in the lateral tunnel and the corresponding pulmonary artery. This study provides in vivo data for future in vitro and computer model studies.