InVERT molding for scalable control of tissue microarchitecture.

Complex tissues contain multiple cell types that are hierarchically organized within morphologically and functionally distinct compartments. Construction of engineered tissues with optimized tissue architecture has been limited by tissue fabrication techniques, which do not enable versatile microscale organization of multiple cell types in tissues of size adequate for physiological studies and tissue therapies. Here we present an 'Intaglio-Void/Embed-Relief Topographic molding' method for microscale organization of many cell types, including induced pluripotent stem cell-derived progeny, within a variety of synthetic and natural extracellular matrices and across tissues of sizes appropriate for in vitro, pre-clinical, and clinical studies. We demonstrate that compartmental placement of non-parenchymal cells relative to primary or induced pluripotent stem cell-derived hepatocytes, compartment microstructure, and cellular composition modulate hepatic functions. Configurations found to sustain physiological function in vitro also result in survival and function in mice for at least 4 weeks, demonstrating the importance of architectural optimization before implantation.

Minimally invasive fetal therapy for hydropic lung masses: three different approaches and review of the literature.

OBJECTIVE: To report three different antenatal therapeutic approaches for fetal lung masses associated with hydrops. METHODS: Three prospectively followed cases are described, and all 30 previously published minimally invasive cases of fetal therapy for hydropic lung masses are reviewed. RESULTS: Three hydropic fetuses with large intrathoracic lung masses presented at 17, 25 and 21 weeks of gestation, respectively. An aortic feeding vessel was identified in each case and thus a bronchopulmonary sequestration (BPS) was suspected. Under ultrasound guidance, the feeding vessel was successfully occluded with interstitial laser (Case 1), radiofrequency ablation (RFA) (Case 2) and thrombogenic coil embolization (Case 3). Complete (Cases 1 and 2) or partial (Case 3) resolution of the lung mass and hydrops was observed. A healthy infant was born at term after laser therapy (Case 1), and the involved lung lobe was resected on day 2 of postnatal life. In Case 2, hydrops resolved completely following RFA, but an iatrogenic congenital diaphragmatic hernia and abdominal wall defect became apparent 4 weeks later. The neonate died from sepsis following spontaneous preterm labor at 33 weeks. In Case 3, despite technical success in complete vascular occlusion with coils, a stillbirth ensued 2 days after embolization. CONCLUSIONS: The prognosis of large microcystic or echogenic fetal chest masses associated with hydrops is dismal. This has prompted attempts at treatment by open fetal surgery, with mixed results, high risk of premature labor and consequences for future pregnancies. We have demonstrated the possibility of improved outcome following ultrasound-guided laser ablation of the systemic arterial supply. Despite technical success, RFA and coil embolization led to procedure-related complications and need further evaluation.

Stenting of the right ventricular outflow tract in the symptomatic infant with tetralogy of Fallot.

BACKGROUND: Repair of neonatal tetralogy of Fallot (TOF) has low mortality. Debate continues regarding the initial management of cyanotic or duct-dependent infants with TOF and adverse risk factors. While repair can and has been performed in these patients, it is associated with increased morbidity. OBJECTIVE: We review the effectiveness of right ventricular outflow tract (RVOT) stenting in the symptomatic young infant with TOF. METHODS: Clinical, echocardiographic, angiographic and haemodynamic data were reviewed for nine patients who underwent 11 RVOT stenting procedures from October 1994 to August 2007. RESULTS: The pulmonary valve was deemed unsalvageable in all patients (median valve diameter 3.7 mm (range 2.7-4.2), Z-score -6.7 (range -9.7 to -5.4). RVOT stenting improved arterial oxygen saturation from a median of 73% (60-85%) to 94% (90-98%) (p = 0.008). Median Z-score for the left pulmonary artery increased from -4.9 (-7.8 to -2.4) before stent implantation to -1.5 (-4.2 to -0.2) (p = 0.02) before surgical repair. Median Z-score for the right pulmonary artery increased from -3.7 (-6.8 to -1.9) to -0.8 (-2.5 to 0.1) (p = 0.008). Median Nakata index increased from 56 mm(2)/m(2) (21-77) to 150 mm(2)/m(2) (123-231) (p = 0.008). There were no procedural complications. Six patients have undergone successful repair. There were no deaths. CONCLUSIONS: In the symptomatic young infant with TOF, stenting of the RVOT provides a safe and effective management strategy, improving arterial oxygen saturation and encouraging pulmonary artery growth.

Percutaneous ultrasound-guided stenting of the atrial septum in fetal sheep.

OBJECTIVES: Hypoplastic left heart syndrome (HLHS) with a restricitive foramen ovale is associated with high mortality related to fetal left atrial hypertension. Fetal atrial balloon septoplasty has largely failed to achieve adequate decompression due to the small size of the holes produced. We attempted to produce larger atrial communications by stenting the atrial septum in fetal sheep using a minimally invasive technique. METHODS: We used a percutaneous, ultrasound-guided transpulmonary or transhepatic approach to attempt deployment of coronary stents (2-5 mm in diameter and 13-23 mm in length) in the atrial septum primum of 10 normal fetal sheep. RESULTS: Coronary stents were deployed in eight of the 10 fetal sheep (119-139 days' gestation). The transhepatic route was unsuccessful (n = 2). Transpulmonary implantation was only possible in prone fetuses, so three initially supine fetuses underwent external version. Small coronary stents (2.0-2.5 mm in diameter) were deployed rapidly without complication via an 18G needle (n = 4). Larger coronary stents (5 mm in diameter) were delivered through a 4F sheath, but a right pleural effusion occurred in three of the four cases, related to inferior vena cava injury by the balloon. One stent dislodged from a floppy septum. Another was partially occluded within a week by endocardial cells. CONCLUSIONS: Percutaneous ultrasound-guided deployment of coronary stents into the septum primum is feasible without laparotomy or uterine exteriorization in fetal sheep. Partial luminal occlusion by rapid proliferation of endocardial cells is a concern.

Cardiac ECMO for biventricular hearts after paediatric open heart surgery.

OBJECTIVE: To delineate predictors of hospital survival in a large series of children with biventricular physiology supported with extracorporeal membrane oxygenation (ECMO) after open heart surgery. RESULTS: 81 children were placed on ECMO after open heart surgery. 58% (47 of 81) were transferred directly from cardiopulmonary bypass to ECMO. Hospital survival was 49% (40 of 81) but there were seven late deaths among these survivors (18%). Factors that improved the odds of survival were initiation of ECMO in theatre (64% survival (30 of 47)) rather than the cardiac intensive care unit (29% survival (10 of 34)) and initiation of ECMO for reactive pulmonary hypertension. Important adverse factors for hospital survival were serious mechanical ECMO circuit problems, renal support, residual lesions, and duration of ECMO. CONCLUSIONS: Hospital survival of children with biventricular physiology who require cardiac ECMO is similar to that found in series that include univentricular hearts, suggesting that successful cardiac ECMO is critically dependent on the identification of hearts with reversible ventricular dysfunction. In our experience of postoperative cardiac ECMO, the higher survival of patients cannulated in the operating room than in the cardiac intensive care unit is due to early effective support preventing prolonged hypoperfusion and the avoidance of a catastrophic cardiac arrest.

Validation and utility of novel volume reduction technique for determination of parallel conductance.

The parallel conductance volume, created by the conductivity of structures surrounding the ventricular blood pool, can be estimated by using a saline dilution technique. This paper examines the use of a novel volume reduction method, during a standard vena caval preload reduction maneuver, as an alternative to the routinely used saline dilution method to calibrate conductance catheter measurements in the left (LV) and right ventricle (RV) of animals and humans. The serial reproducibility of both methods was examined by measurement of percent difference, and by assessing the coefficient of repeatability 1) between two measurements within the same subject, 2) between the two techniques, and 3) interobserver variability. The effect of ventricular size and contractile state on the volume reduction technique was also observed. It was essential to ensure the technique was not affected by inotropic state. The volume reduction technique and saline dilution method were repeated at three different loading states (baseline, 5, and 10 microg x kg(-1) x min(-1) of dobutamine). The coefficient of repeatability between serial measurements was similar for both the volume reduction and saline dilution methods, and good interobserver variability was demonstrated. The volume reduction technique was compared with the saline dilution technique over a large range of ventricular sizes. No significant difference was observed in the RV or LV of adult humans or in the LV of neonatal pigs and children. There was no significant effect on either the saline dilution or the volume reduction technique as the inotropic state increased. In conclusion, the volume reduction technique is neither affected by ventricular size nor contractile state, is repeatable between different observers, and can be used to substitute the saline dilution method when preload reduction of the ventricle is being employed.

Iron overload in paediatrics undergoing cardiopulmonary bypass.

Pathological changes in iron status are known to occur during bypass and will be superimposed upon physiological abnormalities in iron distribution, characteristic of the neonatal period. We have sought to define the severity of iron overload in these patients. Plasma samples from 65 paediatric patients undergoing cardiopulmonary bypass (CPB) were analysed for non-haem iron, total iron binding capacity, transferrin and bleomycin-detectable iron. Patients were divided into four age groups for analysis. Within each age group, patients who were in iron overload at any time point were statistically compared to those who were not. The most significant changes in iron chemistry were seen in the plasma of neonates, with 25% in a state of plasma iron overload. 18.5% of infants and 14.3% of children at 1-5 years were also in iron overload at some time point during CPB. No children over 5 years, however, went into iron overload. Increased iron saturation of transferrin eliminates its ability to bind reactive forms of iron and to act as an antioxidant. When transferrin is fully saturated with iron, reactive forms of iron are present in the plasma which can stimulate iron-driven oxidative reactions. Our data suggest that paediatric patients are at greater risk of iron overload during CPB, and that some form of iron chelation therapy may be advantageous to decrease oxidative stress.

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.

Acute right ventricular restrictive physiology after repair of tetralogy of Fallot: association with myocardial injury and oxidative stress.

BACKGROUND: Acute right ventricular (RV) restrictive physiology after tetralogy of Fallot repair results in low cardiac output and a prolonged stay in the intensive care unit (ICU). However, its mechanism remains uncertain. METHODS AND RESULTS: In the first 24 hours after tetralogy of Fallot repair (n=11 patients), serial prospective measurements were performed of cardiac troponin T, indexes of NO production (NO(2)(-) and NO(3)(-) combined as NOx), and iron metabolism and antioxidants. RV diastolic function was assessed by transthoracic Doppler echocardiography. Patients who had a long stay in the ICU were characterized by restrictive RV physiology (nonrestrictive group [n=7]: 3.0+/-0.6 days [mean+/-SD]; restrictive group [n=4]: 10.7+/-3.1 days). Troponin T peak concentration and the area under its concentration-time curve (AUC) were higher in the restrictive RV group (peak: restrictive group 17. 0+/-2.8 microg/L, nonrestrictive group 10.4+/-4.6 microg/L, P<0.03; AUC: restrictive group 268.8+/-73.6 microg. h(-1). L(-1), nonrestrictive group 136.2+/-48.3 microg. h(-1). L(-1), P<0.03). Plasma NOx/creatinine concentrations were higher in the restrictive group than the nonrestrictive group at 2 hours after bypass (restrictive group 1.3+/-0.4, nonrestrictive group 0.8+/-0.2; P=0. 04) but were similar by 24 hours. Iron loading peaked 2 to 10 hours after bypass and was more severe in the restrictive group (peak transferrin saturation: restrictive group 83.9+/-13.0%, nonrestrictive group 58.3+/-16.2%, P=0.05; minimum total iron-binding capacity: restrictive group 0.59+/-0.21%, nonrestrictive group 0.76+/-0.06%, P=0.04; minimum iron-binding antioxidant activity to oxyorganic radicals: restrictive group 9. 5+/-22.4%, nonrestrictive group 50.6+/-11.4%, P=0.01). CONCLUSIONS: After tetralogy of Fallot repair, acute restrictive RV physiology is associated with greater intraoperative myocardial injury and postoperative oxidative stress with severe iron loading of transferrin.

Modified ultrafiltration improves global left ventricular systolic function after open-heart surgery in infants and children.

OBJECTIVES: Modified ultrafiltration increases blood pressure and cardiac index following open-heart surgery in children, but it is unclear if this is secondary to an improvement in global left ventricular function. A previous report has suggested that left ventricular systolic function as assessed in a single chord is improved by ultrafiltration (Davies MJ, Nguyen K, Gaynor JW, Elliott MJ. Modified ultrafiltration improves left ventricular systolic function in infants after cardiopulmonary bypass. J Thorac Cardiovasc Surg 1998;115:361--370). The prominent vascular actions of modified ultrafiltration necessitate left ventricular assessment using load-independent indices of systolic and diastolic function. METHODS: In 22 consecutive infants and children undergoing open-heart surgery, left ventricular function was assessed following bypass and then 10 min later. Sixteen children (median weight 8.1 kg) underwent modified ultrafiltration during this period, the remainder (median weight 7.3 kg) were controls for spontaneous recovery without ultrafiltration. Real-time pressure-volume loops, with transient inferior caval vein snaring were generated from conductance and microtip pressure catheters inserted through the LV apex. From these, load-independent (slope of the end-systolic pressure-volume [Ees] and end-diastolic pressure-volume [Eed] relationships) and load-dependent (Pmax, maximum LV pressure; Ped, end-diastolic LV pressure; maximum [dP/dtmax] and minimum [dP/dtmax] time derivatives of LV pressure; tau, time constant of isovolumic relaxation) indices of left ventricular function were measured. RESULTS: Haemoconcentration was achieved in all modified ultrafiltration patients, median increase in haematocrit 34% (interquartile range 21%, 42%), final haematocrit 0.40 (0.35, 0.41). Ees increased 58% (9, 159, P = 0.005). The changes in Eed, Pmax, Ped, dP/dtmax, dP/dtmin, and tau were not significantly different from the control group. CONCLUSION: Modified ultrafiltration improves global left ventricular systolic function in infants and children following open-heart surgery.

The effect of changing excitation frequency on parallel conductance in different sized hearts.

OBJECTIVE: An important component of the ventricular volume measured using the conductance catheter technique is due to parallel conductance (Vc), which results from the extension of the electric field beyond the ventricular blood pool. Parallel conductance volume is normally estimated using the saline dilution method (Vc(saline dilution)), in which the conductivity of blood in the ventricle is transiently increased by injection of hypertonic saline. A simpler alternative has been reported by Gawne et al. [12]. Vc(dual frequency) is estimated from the difference in total conductance measured at two exciting frequencies and the method is based on the assumption that parallel conductance is mainly capacitive and hence is negligible at low frequency. The objective of this study was to determine whether the dual frequency technique could be used to substitute the saline dilution method to estimate Vc in different sized hearts. METHODS: The accuracy and linearity of a custom-built conductance catheter (CC) system was initially assessed in vitro. Subsequently, a CC and micromanometer were inserted into the left ventricle of seven 5 kg pigs (group 1) and six 50 kg pigs (group 2). Cardiac output was determined using thermodilution (group 1) and an ultrasonic flow probe (group 2) from which the slope coefficient (alpha) was determined. Steady state measurements and Vc estimated using saline dilution were performed at frequencies in the range of 5-40 kHz. All measurements were made at end-expiration. Finally, Vc was estimated from the change in end-systolic conductance between 5 kHz and 40 kHz using the dual frequency technique of Gawne et al. [12]. RESULTS: There was no change in measured volume of a simple insulated cylindrical model when the stimulating frequency was varied from 5-40 kHz. Vc(saline dilution) varied significantly with frequency in group 1 (8.63 +/- 2.74 ml at 5 kHz; 11.51 +/- 2.65 ml at 40 kHz) (p = 0.01). Similar results were obtained in group 2 (69.43 +/- 27.76 ml at 5 kHz; 101.24 +/- 15.21 ml at 40 kHz) (p < 0.001). However, the data indicate that the resistive component of the parallel conductance is substantial (Vc at 0 Hz estimated as 8.01 ml in group 1 and 62.3 ml in group 2). There was an increase in alpha with frequency in both groups but this did not reach significance. The correspondence between Vc(dual frequency) and Vc(saline dilution) methods was poor (group 1 R2 = 0.69; group 2 R2 = 0.22). CONCLUSION: At a lower excitation frequency of 5 kHz a smaller percentage of the electric current extends beyond the blood pool so parallel conductance is reduced. While parallel conductance is frequency dependent, it has a substantial resistive component. The dual frequency method is based on the assumption that parallel conductance is negligible at low frequencies and this is clearly not the case. The results of this study confirm that the dual frequency technique cannot be used to substitute the saline dilution technique.

Left ventricular dysfunction after open repair of simple congenital heart defects in infants and children: quantitation with the use of a conductance catheter immediately after bypass.

OBJECTIVE: Quantification of myocardial injury after the simplest pediatric operations by load-independent indices of left ventricular function, using conductance and Mikro-Tip pressure catheters (Millar Instruments, Inc., Houston, Tex.) inserted through the left ventricular apex. METHODS: Sixteen infants and children with intact ventricular septum undergoing cardiac operations had left ventricular function measured, immediately before and after bypass. Real-time pressure-volume loops were generated by conductance and Mikro-Tip pressure catheters placed in the long-axis via the left ventricular apex, and preload was varied by transient snaring of the inferior vena cava. RESULTS: Good quality pressure-volume loops were generated in 13 patients (atrial septal defects, n = 11; double-chambered right ventricle, n = 1; supravalvular aortic stenosis, n = 1; age 0.25 to 14.4 years, weight 3.1 to 46.4 kg). Their mean bypass time was 41 +/- 14 minutes and mean aortic crossclamp time 27 +/- 11 minutes. End-systolic elastance decreased by 40.7% from 0.34 +/- 0.17 to 0.21 +/- 0.15 mm Hg-1.ml-1.kg-1 (p < 0.001). There were no significant changes in the slope of the stroke work-end-diastolic volume relationship, end-diastolic elastance, time constant of isovolumic relaxation, and normalized values of the maxima and minima of the first derivative of developed left ventricular pressure. CONCLUSION: Load-independent indices of left ventricular function can be derived from left ventricular pressure-volume loops generated by conductance and Mikro-Tip pressure catheters during the perioperative period in infants and children undergoing cardiac operations. Incomplete myocardial protection was demonstrated by a deterioration in systolic function after even short bypass and crossclamp times.

Left ventricular parallel conductance during cardiac cycle in children with congenital heart disease.

This study examines the accuracy of the conductance catheter technique and, in particular, parallel conductance [expressed as offset volume (Vc)] changes during the cardiac cycle in the human left ventricle. Two groups of patients were assessed: group 1, with an open atrial septal defect, and group 2, with an interventricular communication. In a subgroup, pre- and postoperative data were compared to assess the possible impact of shunting or anatomic considerations on our measurements. Vc is normally obtained by a saline-dilution technique previously described by Baan et al. [Vc(Baan); J. Baan, E. T. Van der velde, H. G. Debruin, G. J. Smeenk, J. Koops, A. D. Van Dijk, D. Temmerman, P. J. Senden, and B. Buis. Circulation 70: 812-823, 1984]. This does not take into account potential changes during the cardiac cycle. Four cardiac cycles were taken from the hypertonic saline washin and were divided into six equal isochrones between the maximum and minimum first derivatives of left ventricular pressure (dP/dtmax and dP/dtmin, respectively). The apparent ventricular volume was regressed against stroke volume for the corresponding cardiac cycle. The volume at the gamma-intercept corresponds to the Vc at each time interval [Vc(t)]. In group 1, there was a variation in Vc(t) during systole, but the temporal changes were quite small, on the order of 4.28% (SD = 5.18%) of total corrected end-diastolic volume (mean maximal variation of 2.60 ml). Furthermore, the value of Vc obtained at dP/dtmax was not significantly different from that obtained at dP/dtmin. For group 2 as a whole, mean Vc(Baan) did not change significantly with ventricular septal defect closure (preoperative, 8.85 +/- 11.1 ml; postoperative, 9.82 +/- 11.84 ml). Group 2 children also exhibited a systolic cyclical variation in Vc(t) similar to group 1. Finally, Vc(t) as a percentage of end-diastolic volume was no different when group 1 and group 2 were compared. We conclude that in the left ventricle, even in the presence of a left-to-right shunt, there is a small but insignificant difference in parallel conductance during ventricular ejection. The magnitude of this cyclical change does not preclude ventricular volume measurement in congenital heart disease by the conductance catheter technique.

Increased airway pressure and simulated branch pulmonary artery stenosis increase pulmonary regurgitation after repair of tetralogy of Fallot. Real-time analysis with a conductance catheter technique.

BACKGROUND: Pulmonary regurgitation (PR) is an important determinant of outcome after repair of tetralogy of Fallot. Baseline PR was measured by magnetic resonance (MR) phase velocity mapping and from real-time right ventricular pressure-volume loops with a conductance catheter. Subsequently, the impact of two loading maneuvers (increased airway pressure, simulated branch pulmonary artery stenosis) on PR was assessed by the conductance catheter method. METHODS AND RESULTS: Thirteen patients, 3 to 35 years after tetralogy of Fallot repair or pulmonary valvotomy, had PR measured by MR phase velocity mapping while breathing spontaneously. During catheterization under general anesthesia. PR was estimated from right ventricular pressure-volume loops generated by conductance and microtip pressure catheters. The effect of increased airway pressure (continuous positive airway pressure, 20 cm H2O; n = 12) and simulated branch pulmonary artery stenosis (transient balloon occlusion of a branch pulmonary artery, n = 7) was measured. Basal PR fraction derived by MR and from right ventricular pressure-volume loops had a correlation coefficient of .76 and mean of differences of 2.0 +/- 18.2% (95% limits of agreement). Increased airway pressure increased PR (16.3 +/- 11.4% to 25.7 +/- 17.3%, P < .01). Simulated branch pulmonary artery stenosis increased right ventricular end-systolic pressure (69.1 +/- 21.4 to 78.7 +/- 23.1 mm Hg, P < .05) and PR (27.5 +/- 11.3% to 36.9 +/- 12.8%, P < .05). CONCLUSIONS: There was reasonable agreement between MR phase velocity-derived PR fraction and that obtained from right ventricular pressure-volume loops generated by use of conductance and pressure-microtip catheters. Exacerbation of PR by increased airway pressure and branch pulmonary stenosis may be relevant to the acute postoperative and long-term management, respectively, of patients after repair of tetralogy of Fallot.

Does parallel conductance vary during systole in the human right ventricle?

OBJECTIVES: Right ventricular (RV) contractile performance remains poorly characterised, particularly in humans. Conductance catheter techniques have the potential to overcome the geometric difficulties in RV volume measurement that have hindered systematic studies of RV pressure volume relations. The present study examines changes in parallel conductance (Vc) that may occur during the cardiac cycle in the human right ventricle. METHODS: Using signals obtained from custom-built conductance catheters, six isochronal systolic values of Vc (Vc(t)) were measured during hypertonic saline wash-in. Studies were performed in nine patients undergoing right heart catheterisation. Their ages ranged from 7 to 39 years (median = 16) and their weights ranged from 20.3 to 84.7 kg (median = 50.0 kg). Measurements of mean Vc and isochronal Vc(t) and its variability during systole were assessed. Mean Vc was measured using the Baan technique (Vc(Baan)), Vc(t) was measured from six systolic isochrones obtained during the same period of hypertonic saline wash-in. RESULTS: The temporal changes in Vc(t) were small (mean 5.8%, median = 4.4%, range = 0.6-17.9%) of total corrected end-diastolic volume (mean maximal variation of 7.7 ml). The value of Vc(t) obtained at dp/dtmax (mean = 99.1 ml; median = 104.75 ml; range 20.15-196.7 ml) was not significantly different to that obtained at dp/dtmin (mean = 100.0 ml; median = 110.87 ml; range = 20.0-204.2 ml) (P > 0.05), but both were higher than the single Vc measurement (Vc(Baan)) obtained using the standard approach (P = 0.02). The correlation between Vc(Baan) and Vc(t) for group data; (Vc(Baan) = 89.69 ml, s.d. = 43.73 ml; Vc(t) = 98.16 ml, s.d. = 50.16 ml) produces a regression slope of 0.99 for all studies (P = 0.02). CONCLUSION: We conclude that parallel conductance does vary during systole in the human right ventricle of adults and older children after repair of congenital abnormalities but there is no significant difference in Vc(t) at dp/dtmin and dp/dtmax. However, there was a significant difference when the isochronal Vc(t) measurement is compared with the standard single value technique (Vc(Baan)) obtained using the hypertonic saline wash-in method. The excellent correlation between Vc(t) and Vc(Baan) suggests that the correction of Vc for the phase of the cardiac cycle is unnecessary for most purposes when studying the human right ventricle.

Intraoperative apical ventricular septal defect closure using a modified Rashkind double umbrella.

OBJECTIVE: To demonstrate the safety and efficacy of intraoperative apical ventricular septal defect (VSD) closure using a modified Rashkind double umbrella. DESIGN: Descriptive study of all patients in whom intraoperative device closure of apical VSDs was attempted. SETTING: A tertiary referral centre. PATIENTS: Four patients with an apical VSD requiring closure, during the period January 1993 to May 1995. INTERVENTIONS: Intraoperative placement of a modified Rashkind umbrella. RESULTS: Four successful placements resulting in apical VSD closure, as judged by transoesophageal colour flow mapping. Three patients received a 17 mm and one a 12 mm umbrella. Early complete closure was achieved in three patients. There was a small residual leak around the 12 mm device that had resolved at 5 month follow up. There was one early death, which was unrelated to VSD closure. CONCLUSION: Apical ventricular septal defects can be closed safely and effectively with intraoperative use of a modified Rashkind umbrella.