AIM:To evaluate foetal left ventricular performance when its preload was increased by banding the pulmonary artery, a study design where a simultaneous change in left ventricular afterload is unlikely. METHODS:Nine ovine foetuses were studied with real-time images and Doppler echocardiography before, 3-4 and 6-8 d after surgery. Seven of these foetuses were also studied during the surgical intervention, immediately before and within 2 min after banding. RESULTS:The immediate effects of a 90-95% reduction of the pulmonary artery cross-sectional area were: a 53 +/- 20% (mean +/- SD) decrease and a 38 +/- 10% increase of right (RvQ) and left ventricular output (LvQ), respectively. Comparing measurements before and 3-4 d after operation, there was a 64 +/- 16% decrease of RvQ and a 64 +/- 25% increase of LvQ. The increase in LvQ was due to an increase in both heart rate (19 +/- 10%) and stroke volume (38 +/- 18%). After an additional 3-4 postoperative days, heart rate remained increased to the same extent, but there was a more pronounced increase of LvQ (93 +/- 19%) and stroke volume (59 +/- 22%). CONCLUSION:The parallel foetal circulation has a capacity to handle a severely increased afterload for the right ventricle by immediately improving and maintaining an increased left ventricular performance. This improvement was in part accomplished by an increase in stroke volume.

BACKGROUND:Tetralogy of Fallot (TOF) and its surgical repair are associated with alterations in right ventricular systolic and diastolic functions. The cardiopulmonary baroreflex describes the peripheral vasoconstriction response to the volume-unloading deactivation of left and possibly right ventricular receptors. Alterations in cardiac geometry or distensibility and pulmonary vasculature of operated TOF may affect the mechanical stimulation of sensitive cardiopulmonary receptors leading to an impaired baroreflex function. There has to date been no report on the integrity of baroreflex function in postoperative TOF.OBJECTIVE:To characterize the combined cardiopulmonary and baroreflex response of patients successfully operated for TOF in early childhood to central volume unloading using graded lower body negative pressure (LBNP) application.METHODS:Fifteen patients operated on for TOF (mean+/-SEM) 15.7+/-1.4 years previously and 13 healthy age-matched control subjects were submitted to four consecutive 5 min LBNP applications at -10, -20, -30 and -40 mmHg. Forearm blood flow and vascular resistance, left ventricle end-diastolic diameter (LVEDD), arterial blood pressure and heart rate were obtained.RESULTS:TOF exhibited a lower LVEDD (42.7+/-1.5 mm) than control subjects (51.9+/-1.6). The forearm vascular resistance to LVEDD relationship was shifted left and upward in TOF compared with that of control subjects, but the slope of the relationship was not different between groups. LBNP -40 mmHg induced a lesser change in heart rate in TOF (+10.6+/-1.5%) than in control subjects (+14.7 +/-2.4%) and an increase (P<0.05) in diastolic blood pressure in TOF (-2.4+/-2.5%), which was not seen in control subjects (+4.3+/-2.9%).CONCLUSIONS:Young adults successfully operated on for TOF in early childhood exhibit a resetting of the cardiopulmonary baroreflex to operate at smaller LVEDD and at a higher level of forearm vascular resistance. The blunted heart rate response to LBNP -40 mmHg is consistent with previous observations pointing to disturbances in the efferent arm of the baroreflex.

Fetuses with pulmonary stenosis and constriction of the ductus arteriosus or the recipient twin in the context of a twin-to-twin transfusion syndrome may present with severe right ventricular myocardial dysfunction. Free O2 radicals are known to be increased in hypertrophied adult myocardium secondary to an increase in endocavitary pressure. This study investigates whether products of reactive O2 species generation are abnormally elevated in the myocardium of fetuses with increased right ventricular pressure. Banding of the main pulmonary artery was performed in five fetal lambs at 90 to 100 days of gestation. Three other animals had a sham intervention and were used as controls. Postoperative observation lasted on average 42 days (range 33–49 days). The levels of hydroperoxides were found to be significantly higher in the right ventricle of the stenosed lambs (6.6 ± 3.5 nmol/mg protein) compared to the left ventricle of the same lambs (0.7 ± 0.7 nmol/mg protein), and compared to the right (0.12 ± 0.1 nmol/mg protein) and the left (0.5 ± 0.8 nmol/mg protein) ventricles of the controls. It is concluded that during fetal life, an increase in right ventricular pressure is associated with a marked accumulation of products of reactive O2 species generation in the right ventricular myocardium.

This study compares the autonomic responses of 9 adolescents (mean ± SEM: 17±1 years) successfully operated for tetralogy of Fallot (TOF) in early childhood and 8 age-matched healthy controls (CTRL) using R-R and blood pressure variability. Continuous ECG and BP recordings were obtained during spontaneous and controlled respiration (CR) at 0.20 Hz as well as after an 85° head-up tilt (HUT) and during steady-state cycling at heart rates of 100 and 120 bpm, selected to reflect partial and complete cardiac vagal withdrawal. TOF exhibited total R-R variance and HF power (ms2) lower than CTRL under both spontaneous (938 ± 322 vs. 1,714 ± 296) and CR (1,541 ± 527 vs. 4,725 ± 1,207; p < .05), which may be indicative of a lower cardiac vagal activity. HUT decreased the R-R HF component, which remained lower in TOF than CTRL and increased the diastolic BP LF component in TOF but not in CTRL. Exercise decreased the R-R HF power more in TOF than CTRL. The exaggerated diastolic BP and limited heart rate responses to tilting and the more marked vagal withdrawal at Ex120 in TOF may be suggestive of a disturbance in the cardiac sympathetic response. Further studies are needed to confirm these observations on larger groups of young adults successfully operated for TOF.

Lipid peroxidation due to oxygen free radicals (OFR) seems to play a major role in loss of liver graft viability after warm ischemia, preservation, and transplantation. N-acetylcysteine (NAC) is an antioxidant that has a direct effect on OFR, and is also a glutathione precursor, another antioxidant. This study was designed to evaluate the efficacy of NAC in preventing ischemia-reperfusion damage of liver grafts harvested from non-heart-beating donors. Liver transplantation was performed on pigs divided into five groups: group 1 (control group; n=5) received livers from heart-beating donors; livers were subjected to 30 min of warm ischemia in groups 2 (n=3, no NAC) and group 3 (n=3; NAC treatment); warm ischemia time lasted 60 min in groups 4 (n=4; no NAC) and 5 (n=5; NAC treatment). Studied parameters included graft survival for more than 3 days, aspartate aminotransferase plasma levels, liver histology, and hepatic total glutathione concentrations. Graft survival was 100% in groups 1, 2, and 3, 0% in group 4, and 20% in group 5. NAC treatment did not influence initial mean aspartate aminotransferase release which was greater in warm ischemic livers than in controls. NAC treatment had no effect on liver hepatic total glutathione after reperfusion of animals receiving warm ischemic grants. Finally, no effect on liver histology was observed with NAC treatment. Our study suggests that in liver transplantation from non-heart-beating donors, NAC has no effect in both graft viability and lipid peroxidation. The role of OFR in primary dysfunction of transplanted warm ischemic livers remains controversial.

Toxic oxygen free radicals (OFRs) are produced after ischemia-reperfusion injury, which can be observed during cardiopulmonary bypass (CPB). In a pilot study conducted in a tertiary care pediatric intensive care unit, we sought to determine plasma malondialdehyde (MDA) levels, a marker of OFR production, in children undergoing CPB, and to relate the findings to gastric intramucosal pH and PCO2 (pHi, PiCO2) and serum lactate. Thirteen nonconsecutive children (age: 56 ± 58 months) were included in the study. After induction of general anesthesia and endotracheal intubation, a tonometer nasogastric tube was positioned in the stomach; gastric pHi and PiCO2, arterial PCO2 (PaCO2), MDA, and lactate were measured 1 hour later (time 0) and 1 to 48 hours after initiation of CPB (times 1, 4, 8, 12, 16, 20, 24, 32, 40, and 48). Data for each variable were compared with baseline values for statistical significance. Free MDA levels increased by more than 50% in 11 patients (85%) and a statistically significant difference was found between the highest and the baseline free MDA concentrations (p < .0025). Low gastric pHi after the first 8 hours post-CPB was significantly associated with a late rise in MDA levels. A stepwise multivariate regression analysis showed that the highest PiCO2:PaCO2 ratio was correlated to the highest MDA level (p < .0001). A low gastric pHi later than 8 hours after CPB or a high PiCO2: PaCO2 ratio, as observed in this study, may indicate secondary splanchnic hypoperfusion with increased OFR production.

This study was designed to determine (1) the value of Doppler echocardiography in depicting the presence of a fetal pulmonary stenosis, (2) its reliability in the assessment of the severity of the lesion, and (3) the usefulness of additional markers from the left side of the heart as criteria of severity. Fourteen pregnant ewes were included in this study (gestational age, 90 to 120 days). Banding of the fetal main pulmonary artery created mild (n = 3), moderate (n = 3), and severe (n = 5) stenosis. Three lambs were sham operated. Intrauterine fetal Doppler echocardiographic data obtained 15 days after surgery were compared with preoperative values. Peak velocities recorded through the band increased linearly from baseline in the groups with mild and moderate stenosis but did not show any further increase in the group with severe stenosis. Compared with the sham-operated group, right ventricular output in the group with stenosis was either similar or reduced significantly. The increase in right ventricular free wall thickness was significantly greater in the groups with stenosis compared with that of the sham-operated group; the correlation with the degree of severity was r = 0.65 and p < 0.05. A A stronger positive correlation was found between the severity of stenosis and aortic valve diameters: r = 0.82 and p < 0.01. The strongest correlation was found for right ventricular/left ventricular outputs (r = 0.92; p < 0.001). Thus Doppler peak velocities through the obstruction can help detect pulmonic stenosis but are not reliable for the assessment of its severity during fetal life. Other ultrasound measurements such as the size of the aortic anulus and especially the ratio of right ventricular/left ventricular output could be used as sensitive markers of the severity of stenosis.

In our attempt to band the main pulmonary artery above the valve in a 4-month-old prematurely born infant, we erroneously banded only the left pulmonary artery, owing to the unusually low origin of the right pulmonary artery (which arose partially in the sinus of Valsalva). When severe cardiac failure recurred, the anomaly was noted upon reoperation and the band was repositioned at the level of the pulmonary valve. Since this revision, the postoperative course has been good. Low origin of the right pulmonary artery is normal in premature infants. However, origin of the right pulmonary artery from the sinus of Valsalva is a sufficiently extreme variant to constitute a surgically important anomaly. Our postmortem studies of the pulmonary arteries of 25 premature infants born without cardiac malformation showed that while the right pulmonary artery was lower than the left, it never originated from the sinus of Valsalva. This anomalous configuration of the pulmonary arteries has, to our knowledge, never been found in an infant as old as 4 months; yet we believe it should be taken into account when banding pulmonary arteries in infants.

In order to assess the influence of acetylsalicylic acid (ASA) on function and patency of Gore-Tex shunts, angiographic features of 62 Gore-Tex shunts were assessed, 31 without and 31 with postoperative ASA. Groups were selected on the basis of similar angiographic follow-up duration. Mean follow-up was 709 days for the group without ASA and 739 days for the group with it. The average daily dose of ASA was 4.5 mg/kg/day started a mean of 6.7 days after surgery. Clinical characteristics were similar between the two groups except for age at surgery which was 581 days in the group without ASA (operated between 1983 and 1987) and 303 days in the group with (operated between 1987 and 1991), reflecting the fact that patients were operated upon earlier after 1987. Preoperative Gore-Tex diameter was similar between the two groups, but three patients in the group with ASA had a Gore-Tex shunt as small as 4 mm. At angiography, four conduits were diagnosed as nonpatient (two in each group), 20 had a localized stenosis (11 of 28 in the group without ASA and nine of 23 in the group with ASA). Patency index (angiographic Gore-Tex diameter/preoperative Gore-Tex diameter) was similar in the two groups: 68.5% in the group without ASA and 69.7% in the group with ASA. Pulmonary artery growth index was 57% in the group without ASA and 91% in the group with ASA. No risk factor for thrombosis or decreased patency was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Atriopulmonary anastomosis results in a chronic right atrial pressure-volume overload. Water and salt retention is a frequent clinical observation in patients after atriopulmonary anastomosis. The purpose of this study was to examine if this could be related to an inability to increase already elevated circulating atriopeptin (ANP) in response to central volume-overloading conditions. Eighteen patients (mean age 16 ± 6 years) with an atriopulmonary anastomosis underwent routine cardiac catheterization during which a 5-minute head-down 10 ° tilt was performed. Peripheral venous and right atrial blood samples were obtained under basal conditions, and after tilting and angiography for determination of ANP concentrations. At a different time, circulating ANP levels were measured during a maximal graded exercise protocol. Increased circulating ANP concentrations were found under basal conditions (114 ± 10 μg/ml). Tilting and cardioangiography resulted in significant increases in mean atrial pressure (basal: 12 ± 0.7 mm Hg; tilt: 13.4 ± 0.63 mm Hg; after angiography: 15.8 ± 0.8 mm Hg), but not in atrial or peripheral ANP. Compared with the expected threefold increase in plasma ANP induced by maximal exercise in healthy control subjects, only a slight (0.25-fold) increase was found in patients. These observations suggest a reduced stimulus-release response after atriopulmonary anastomosis, which could be related to a loss of atrial stretch receptor sensitivity, achievement of the limit for maximal right atrial secretion, or an alteration in right atrial compliance, or a combination.

A disturbance in the chronotropic response to exercise has well documented following surgical repair of a congenital heart defect. Observations of a similar dysfunction following correction of simple atrial as well as ventricular septal defect suggest that its occurrence might be linked to a common denominator in the surgical procedures. Since cardiopulmonary bypass (CPB) is used for all initacardiac surgeries, the contribution of this factor to the abnormal response was examined. Three groups of patients von; evaluated: VSDop: operated on for a ventricular septal defect, CPB required; VSDnon-op: spontaneous closure of a congenital 73D, no surgery; and PDAoperated on for a patent ductus arteriosus, no CPB required. They were compared io a control group of healthy adolescents (C). The main, finding was that of lower submax final and maximal heart rates in VCDop disc in any other group. These results suggest that placement of cannulae resulting from-CPB could alter the control of heart rate during exercise and contribute to the abnormal chronotropic response following intracardiac repair of a congenital heart defect.

In this presentation the author updates the progress made in pediatric cardiac transplantation through a review of the results obtained at Ste-Justine Hospital (SJH) and of the recent literature. Of 56 children referred to SJH for cardiac transplantation, 27 met the selection criteria; 10 died before receiving a new heart and 2 are still awaiting transplantation. Fifteen children, aged 3 to 16 years, have received a transplant. Ten of them had 32 birth defects, all of which were repaired at the time of transplantation thanks to improved graft removal methods and innovative surgical techniques. This study demonstrates that birth defects are not a contraindication to cardiac transplantation in children. Triple-drug immunosuppression was used, and the cyclosporine blood levels were maintained in the range of 100 to 200 ng/mL. Survival at 2 years was 78%. Episodes of acute rejection occurred at a rate of 0.5 per patient, 85% of them within the first 3 months after transplantation. Adequate renal function was preserved (creatinine clearance between 89 and 102 mL/min.m-2). The use of low-dose cyclosporine might explain in part the lack of significant nephrotoxicity. Reversible high blood pressure was observed in 5 of 13 patients during the first 6 months postoperatively. Multifactorial analysis identified, as a likely cause, a higher dose of steroids and cyclosporine during this period. Annual coronary angiography did not reveal any lesion, and apart from the acute rejection episodes, cardiac function was normal at rest, and the transplanted children have maintained an excellent level of activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Seven patients underwent cardiac transplantation at Ste‐Justine Hospital between June 1984 and October 1988 (age 3‐16 years). Indices derived from M‐mode echocardiography – left ventricular mass (LVM), isovolumetric relaxation time (IRT), shortening fraction (SF), velocity of circumferential fiber shortening (VCF), ejection fraction (EF), LV pre‐ejection period/ejection time (PEP/ET), isometric contraction time (ICT) – and electrocardiography – summation of potentials (Sum Pot) – were used as non‐invasive markers of rejection (367 studies), while rejection status was monitored by serial endomyocardial biopsy (55 biopsies). Spontaneous variation of such indices, as defined by the 90% distribution interval of their variation when biopsy was unchanged, was found to be important: –20% to +28% for IRT, –30% to +28% for LVM, –30% to 32% for Sum Pot, –32% to 42% for PEP/ET, etc. Using limits of spontaneous variation such as thresholds, none of the studied indices could consistently predict the 2 biopsy‐documented episodes of rejection or the 7 episodes of improvement. Among all the studied indices. IRT was the most promising, correctly predicting 1 of the episodes of rejection and almost predicting the 2nd. Remeasurement of all M‐mode tracings by an unique observer, following strict rules to maximize reproducibility, did not decrease the spontaneous variation of these indices, nor did it improve their performance as predictors of changes in the rejection status. These results warrant the continuing search for other non‐invasive methods for accurate monitoring of the rejection status.

The authors report on 4 infants with the diagnosis of pulmonary sling who were operated in their hospital, and they subsequently review the literature. Considering the poor prognosis of the anomaly, especially when associated with tracheobronchial abnormalities, controversies persist about its management. The authors believe that a conservative approach to these patients cannot improve its prognosis, whereas new surgical technics show promise, and to this end they propose a more aggressive treatment algorithm.

Seven patients underwent cardiac transplantation at Ste-Justine Hospital between June 1984 and October 1988 (age 3-16 years). Indices derived from M-mode echocardiography--left ventricular mass (LVM), isovolumetric relaxation time (IRT), shortening fraction (SF), velocity of circumferential fiber shortening (VCF), ejection fraction (EF), LV pre-ejection period/ejection time (PEP/ET), isometric contraction time (ICT)--and electrocardiography--summation of potentials (Sum Pot)--were used as non-invasive markers of rejection (367 studies), while rejection status was monitored by serial endomyocardial biopsy (55 biopsies). Spontaneous variation of such indices, as defined by the 90% distribution interval of their variation when biopsy was unchanged, was found to be important: -20% to +28% for IRT, -30% to +28% for LVM, -30% to 32% for Sum Pot, -32% to 42% for PEP/ET, etc. Using limits of spontaneous variation such as thresholds, none of the studied indices could consistently predict the 2 biopsy-documented episodes of rejection or the 7 episodes of improvement. Among all the studied indices, IRT was the most promising, correctly predicting 1 of the episodes of rejection and almost predicting the 2nd. Remeasurement of all M-mode tracings by an unique observer, following strict rules to maximize reproducibility, did not decrease the spontaneous variation of these indices, nor did it improve their performance as predictors of changes in the rejection status. These results warrant the continuing search for other non-invasive methods for accurate monitoring of the rejection status.

Operative mortality for critical aortic stenosis in newborn having been reported as high as 20-80%, the percutaneous aortic valvuloplasty is looked upon as an alternative therapy. We elected to review our surgical experience in the last 25 years before changing. our therapeutic approach. Among 37 infants included in the study, 28 were boys and 9 girls. Mean age at diagnosis was 14.5 days (1 to 113 days) and decreased to 4.1 days in the last 5 years. Surgery was done at a mean of 37.2 days 22 infants were operated on before one month of age and 9 in their first week of like. Five died from ventricular fibrillation at incision. Trans-ventricular valvulotomy was attempted in 4 and remaining 28 had trans aortic valvuloplasty. The overall survival of 40 % had improved in last five years to 75 %. All patients with trans-ventricular approach died and also did the only child with percutaneous angioplasty. Only 13 % patients weighing less than 3 kg survived the operation. Follow-up was of 93.3 % with a mean time of 66 months. All but one are in NYHA class 1 or 2. Our study identified the following risk factors : preoperative hemodynamic state, surgical weight, associated anomalies of the left ventricle, transventricular valvulotomy and the year of surgery. In view of improved survival, surgery remains a good therapeutic choice.

Operative mortality for critical aortic stenosis in newborn having been reported as high as 20-80%, the percutaneous aortic valvuloplasty is looked upon as an alternative therapy. We elected to review our surgical experience in the last 25 years before changing our therapeutic approach. Among 37 infants included in the study, 28 were boys and 9 girls. Mean age at diagnosis was 14.5 days (1 to 113 days) and decreased to 4.1 days in the last 5 years. Surgery was done at a mean of 37.2 days; 22 infants were operated on before one month of age and 9 in their first week of life. Five died from ventricular fibrillation at incision. Trans-ventricular valvulotomy was attempted in 4 and remaining 28 had trans aortic valvuloplasty. The overall survival of 40% had improved in last five years to 75%. All patients with trans-ventricular approach died and also did the only child with percutaneous angioplasty. Only 13% patients weighing less than 3 kg survived the operation. Follow-up was of 93.3% with a mean time of 66 months. All but one are in NYHA class 1 or 2. Our study identified the following risk factors: preoperative hemodynamic state, surgical weight, associated anomalies of the left ventricle, transventricular valvulotomy and the year of surgery. In view of improved survival, surgery remains a good therapeutic choice.

We evaluated the relationship between the cardiovascular effects of clentiazem (TA-3090), a new 1,5-benzothiazepine calcium antagonist with high lipophilicity, and both its plasma and myocardial concentrations. Anesthetized, open-chest dogs, instrumented for hemodynamic data recording and blood sampling, were divided into three groups treated with 15, 50, or 200 μg/kg of clentiazem, respectively, as an intravenous bolus. At the end of the protocol (240 minutes), myocardial samples were tested for clentiazem. The results indicated that the peripheral and coronary vasodilator effects of clentiazem were dose dependent and closely related to its plasma concentrations. It was also observed that the minimal effective plasma concentration was in the range of 15–20 ng/ml. Sustained negative chronotropic effects were recorded at the highest dose only and were best related to the amount of clentiazem detectable in the myocardium, suggesting that myocardial clentiazem retention is a major factor governing its depressant cardiac impact.

Congenital anomalies of the atrium, pulmonary venous return, and systemic venous return are often regarded as anatomical contraindications to orthotopic cardiac transplantation. Among our pediatric transplant patients, 10 children aged 3 to 15 years, weighing 9 to 45 kg, and all previously operated on for a total of 18 interventions had 32 anomalies needing correction at the time of transplantation. Besides the 18 instances of great vessel abnormalities, 14 anomalies of the atrium and of the venous return were encountered either alone or in combination: single atrium or previous septectomy (4), hypoplastic left atrium (2), previous Mustard procedure (1), cor triatriatum (1), anomalous pulmonary venous return (3), and anomalous systemic venous return (3). The preparation of the donor heart was modified in four ways: right atrial paraseptal incision, left atrial flap technique, full-length mobilization of the pulmonary arteries, and aortic arch incision. Correction of the atrial and venous return anomalies was carried out at the time of orthotopic transplantation with the following techniques: atrial septation, atrial enlargement, superior systemic venous return reroofing, inferior systemic venous return reroofing, double venous rerouting (pulmonary and systemic), and septal realignment. One child died of pulmonary hypertension in the early postoperative period. After a follow-up ranging from 1 month to 52 months, all survivors are asymptomatic. Based on echocardiography, heart catheterization, and angiography, there are no stenoses and no shunts, and the atrial dimensions are good. Based on the results achieved with these surgical techniques, we conclude that most atrial lesions, anomalous pulmonary venous returns, and anomalous systemic venous returns are correctable at the time of orthotopic transplantation and do not preclude a successful outcome in children.

In most instances of anomalous left coronary artery originating from the pulmonary artery, surgical treatment is recommended. Because establishment of a direct systemic to coronary blood flow is expected to provide the best recovery of left ventricular function, various corrective procedures have been proposed. Subclavian-left coronary artery anastomosis appears to be a logical approach. Four patients operated on at Sainte-Justine Hospital, at an average age of 33 months (27 to 44), with an end-to-end subclavian-left coronary artery anastomosis were evaluated 6 to 46 months postoperatively. The anastomosis was patent in all cases. End-diastolic volume index (74.6 +/- 24.7 versus 122.7 +/- 15.3 ml/m2) and ejection fraction (0.58 +/- 0.07 versus 0.33 +/- 0.06) were improved significantly. Subclavian-left coronary artery anastomosis appears to meet the main criteria for an optimal physiologic correction of anomalous left coronary artery: restoration of a two-coronary artery system, improvement of left ventricular function, and likelihood of long-term patency.