Claude Chartrand

Pediatric cardiac transplantation despite atrial and venous return anomalies

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.

Electrophysiologic effects of sotalol on the immature mammalian heart.

Sotalol is a beta-blocker with class III antiarrhythmic properties that has recently been used in children for the treatment of supraventricular and ventricular arrhythmias. However, little is known about its electrophysiologic effects on the immature heart. Using intracardiac electrocardiographic recordings and stimulation techniques, 15 canine neonates (8-15 days) and 15 adult mongrel dogs were studied with cumulative doses of sotalol (0.5, 1, 2, and 4 mg/kg plus an additional dose of 8 mg/kg for neonates). Heart rate decreased significantly in the two groups, but more in adult dogs (-43% in adult dogs versus -25% in neonates, p less than 0.05). There was no significant change for QRS duration and His-Purkinje system conduction time interval. QT and atrioventricular nodal conduction time intervals increased in adult dogs and neonates. Sinus node recovery time increased significantly in the two groups, but more in adult dogs. Refractory periods of the atrioventricular (AV) node increased significantly in neonates. Atrial flutter was no longer inducible in 12 of 15 neonates after the 2 mg/kg dose. Atrial effective refractory period increased significantly more in neonates (96%, p less than 0.001) than in adult dogs (58%, p less than 0.001). Ventricular effective refractory periods increased significantly both in neonates (46%) and adult dogs (50%), in a similar way. In conclusion, sotalol has greater electrophysiologic effects on the immature heart at the atrial level when compared to the adult, and similar effects on the refractory period of AV node and ventricle.

True Diverticulum of the Right Ventricle: Two Cases Associated with Tetralogy of Fallot

A true right ventricular diverticulum is a rare malformation consisting of an accessory ventricular outpouching communicating with the right ventricle through a muscular annulus and located at the right superior margin of the right ventricle. Its normal myocardial structure causes it to function as normal ventricle and in itself does not cause functional disturbances. In all reported instances, the malformation was associated with a ventricular septal defect and obstructive lesions of the right ventricular outflow tract. The 2 patients we describe had partial resection at the time of repair of tetralogy of Fallot and are doing well one and four years postoperatively.

Assessment of fetal pulmonic stenosis by ultrasonography

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.

Long-term daily study of blood volume in cardiac autotransplanted dogs.

Cardiac transplantation is followed by the interruption of afferent nerves to the heart. Knowing that some of the afferent nerves are responsible for the homeostasis of the blood volume, we undertook a serial and long-term study of the blood volume in 25 dogs with denervated hearts. The animals were autotransplanted in order to eliminate repercussions linked to rejection and to its treatment. To discern the effects of surgery and of extracorporeal circulation from those of denervation, a group of 11 control dogs was operated upon and subjected to a period of extracorporeal circulation. In both groups, serial and long-term studies of blood volume were carried out daily with 131I-labeled albumin. Analysis of the results demonstrated that in the hours following surgery, blood volume is significantly decreased by 11% in the control group and by 22% in group 2. By the 5th postoperative day, the blood volume had increased gradually to attain normal values in both groups. At the 2nd postoperative week, the total blood volume remained normal in the control group, whereas blood volume had increased by 5.7% in the autotransplanted dogs, this being due to a 38% increase of the plasmatic phase. This increment persisted from the 14th to the 42nd postoperative day and attained 7.4%. Our conclusion is that the variations in blood volume during the 1st postoperative week in the autotransplanted heart are inherent in surgery and in extracorporeal circulation. Afterwards, the hypervolemia shown in the transplanted dogs is secondary to cardiac denervation.

Peroperative Myocardial Ischemia and Citrate Administration: Cardiovascular Adaptability in Conscious Dogs

Since the hemodynamic response elicited by the administration of citrate is sensitive to alterations in the baseline cardiovascular status, we have investigated the consequences of peroperative myocardial ischemia upon this hemodynamic response. 19 dogs equipped with an electromagnetic flow probe positioned around the ascending aorta served as control (group I). 16 dogs were equipped similarly and in addition submitted to 1 h of myocardial ischemia combined with topical cardiac hypothermia (group II). Hemodynamic studies were carried out 3 h postoperatively and then daily for 1 month, before and during rapid intravenous administration of citrate. From baseline hemodynamic data, cardiac failure was only evident 3 h postoperatively in group II. Transient hypotension and myocardial depression resulted from administration of citrate in both groups with no evidence of peripheral vasodilation. Hypotension and the negative inotropic response were more pronounced in the presence of cardiac failure following peroperative myocardial ischemia. Long-term studies indicate that global myocardial ischemia did not interfere with the cardiovascular adaptability to this pharmacologic interference.

Cardioprotective effects of diltiazem during acute rejection on heterotopic heart transplants.

In the presence of severe rejection, cardiac allograft perfusion has been shown to be impaired. Since a functionally reversible vasoconstrictor component has been identified in this condition and rejection does not reverse if ischemia does not, we hypothesized that diltiazem may be beneficial in this condition. Experiments were performed on dogs with heterotopic heart transplants and chronic instrumentation for the assessment of allograft perfusion. Two groups of cardiac allograft recipients were studied: untreated recipients and recipients treated with the calcium antagonist diltiazem (180 mg twice daily, orally). Allograft blood flow was monitored daily along with plasma diltiazem levels. The lymphoproliferative response to mitogens was studied at selected intervals until terminal rejection. Contractile function of the graft was assessed daily by palpation. Without immunosuppression, terminal rejection was observed within 7 days. Rejection was confirmed by histology; cellular infiltration and myocyte necrosis were present in all cardiac allografts but to a significantly lesser degree in diltiazem-treated recipients. The mean blood flow of heterotopically implanted hearts was in the range of 35-50 ml/min, which decreased steadily in untreated recipients. In contrast, significant improvement of allograft perfusion was observed in diltiazem-treated recipients at days 4-6 after transplantation. Diltiazem also significantly attenuated mitogen-induced lymphocyte proliferation at peak sensitivity (2 days after transplantation). Diltiazem plasma concentrations were in the therapeutic range (30-60 ng/ml) before and after cardiac transplantation. Results of the present study demonstrate beneficial effects of diltiazem in the course of severe cardiac rejection. Such findings support its use during rejection when maintenance of graft blood flow and myocyte protection may be important for myocardial function and viability.

Surgical Repair of Superoinferior Ventricles: Experience with 3 Patients

Superoinferior ventricles are a rare anomaly characterized by a horizontal ventricular septum and a hypoplastic right ventricular sinus localized anterosuperiorly to the left ventricle. This anomaly frequently is accompanied by malformation of the atrioventricular valves. A large ventricular septal defect is always present, and anomalies of the ventriculoarterial relations are common. The results of surgical repair of this complex lesion have been poor. Our recent surgical experience with 3 patients, 2 of whom are well 36 and 38 months postoperatively, suggests a hopeful outcome for the repair of this complex anomaly. The surgical approach was different in each of the 3 patients, demonstrating the need for a precise echocardiographic and angiocardiographic preoperative description of the cardiac anatomy to appropriately repair the multiple variants of this complex anomaly.

Generation of Reactive O2 Species in the Myocardium of Newborn Lambs Following Intrauterine Increase in Right Ventricular Pressure

Abstract. 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.

Intravenous infusion of phentolamine: effects on cardiovascular dynamics and regional blood flow distribution in conscious dogs.

We have studied hemodynamic changes induced by infusion of phentolamine (100μg/kg/min) over 15 min in conscious dogs in order to clarify its mechanism of action. Dogs were prepared with an electromagnetic flow probe, and microspheres (9 μm) were used to measure regional blood flow distribution before and after 15 min of infusion of phentolamine. Controlled hypotension (15–20%) was maintained throughout the infusion, and this hypotensive state was associated with the following significant changes: heart rate increased by 50–70%, stroke volume decreased by 35–42%, left ventricular power and work fell by 15–19% and by 49–56%, respectively, maximum acceleration increased by 26–34%, and total peripheral resistance decreased by 20% while cardiac index was unaffected. Regional blood flow studies showed that phentolamine at the 15th min of infusion induced a significant increase in blood perfusion to all components of the myocardium (range 30–51%) while their vascular resistances showed a significant decrease (35–41%). Blood flow to liver (hepatic artery), spleen, and intestine was also modified (−14, −14, and −15%, p < 0.05) while their vascular resistances were only slightly decreased. At the time measurements were made, blood flow to cerebral and renal tissues was not affected while their local vascular resistances decreased significantly (15–20%). For each organ studied blood perfusion was uniform. These results indicate that phentolamine elicits both central and peripheral hemodynamic changes and that in most vascular beds studied the vasodilator effect of phentolamine can still be observed at the 15th minute of infusion.