Two-year carcinogenicity study of tamoxifen in Alderley Park Wistar-derived rats.

Tamoxifen, a nonsteroidal antiestrogen used widely in the treatment of breast cancer, was tested in a conventional 2-year carcinogenicity bioassay in rats, a species in which tamoxifen acts variably as a partial agonist and antagonist on different target tissues. Groups of 51 males and 52 females were given 5, 20, and 35 mg/kg of tamoxifen/day by gastric intubation in 0.5% hydroxypropyl methylcellulose at 5 ml/kg dose volume. There were 102 male and 104 female controls dosed with vehicle alone. Growth rate and food consumption were reduced in all treated groups. The major finding was a dose-related increase in the incidence of hepatocellular tumors which were first observed after 31 weeks of treatment in the top dose group. The majority of the neoplasms were hepatocellular carcinomas showing a well differentiated trabecular pattern. Some tumors were glandular in type. Mortality was increased in the 20 and 35 mg/kg dose groups compared with controls as a result of these tumors. By contrast, survival was greater than controls in rats given 5 mg/kg tamoxifen despite the presence of hepatocellular tumors due to a reduction in the number of pituitary tumors in females and less chronic renal disease in males. The mechanism of hepatic tumor induction by tamoxifen in rats is unclear. In view of the lack of genotoxic activity in conventional genotoxicity studies and lack of similar effect in mice or in humans, the findings may relate to a particular constellation of effects in rats. All other drug-induced changes in this study were nonneoplastic in nature and most appeared to be the result of hormonal perturbation since they were confined to endocrine organs or have been seen previously in rats treated for long periods with tamoxifen.

Closure of hip wound, clips or subcuticular sutures: does it make a difference?

The purpose of this study was to investigate wound healing and complications following surgery for fracture neck of femur. Seventy-one patients were prospectively divided into two groups, according to the method of skin closure: group A had clips; group B had subcuticular vicryl® sutures. There were 41 patients in group A, and 30 patients in group B. There were 13 males and 58 females with an average age of 84.3 years (range 67-100 years). Thirty-seven patients underwent fixation with a dynamic hip screw, while 34 had undergone either a hemi or total hip arthroplasty. The wounds were inspected at days 2, 5, 7, 10 and 14 days, for discharge, redness and infection. There was a statistically significantly greater amount of wound discharge (P<0.002) and redness (P<0.009) in group A (clips) as compared to group B (vicryl). There were three cases of infection; all in patients where clips had been used for skin closure. We concluded that subcuticular vicryl sutures were significantly better than clips in terms of wound healing as well as cost. Except for some decrease in operative time there does not seem to be any advantage in the use of clips for wound closure.

Surgical therapy for atrial tachycardia in adults.

Eighteen adult patients with atrial tachycardia refractory to treatment with a mean of four drugs underwent attempted surgical cure. Atrial tachycardia originated in the right atrium in 17 patients and the left atrium in 1 patient. Tachycardia could be reproducibly induced and terminated by atrial extrastimuli or atrial pacing in 8 patients (44%). Resection of the arrhythmogenic area was performed in 16 patients (89%), and an isolation procedure was performed in 1 patient. In seven cases (39%), the area of isolation or excision included the sinoatrial node. One patient underwent His bundle section because the arrhythmogenic region was too close to the atrioventricular (AV) conduction system to enable resection. The mean duration of clinical follow-up was 56 +/- 34 months. Clinical tachycardia recurred in five patients (28%), but in two patients it did not recur until greater than 1 year after surgery. A permanent pacemaker was implanted in 3 (18%) of the 17 patients whose His-Purkinje system was left intact. One other patient had required permanent pacing before surgery. Only one of the seven patients undergoing sinoatrial node resection or isolation required permanent pacing for symptomatic bradycardia. Apart from the requirement for permanent pacing, no significant complications occurred. Surgical therapy for atrial tachycardia is a safe procedure, but the rate of cure appears to be less than that of supraventricular tachycardias associated with accessory AV connections. Excision or isolation of the sinoatrial node does not necessitate permanent pacing in most patients.

Mechanism, localization and cure of atrial arrhythmias occurring after a new intraoperative endocardial radiofrequency ablation procedure for atrial fibrillation.

OBJECTIVES: The purpose of this study was to test a new pattern of radiofrequency ablation for atrial fibrillation (AFib) intended to optimize atrial activation, and to demonstrate the usefulness of catheter techniques for mapping and ablation of postoperative atrial arrhythmias. BACKGROUND: Linear radiofrequency lesions have been used to cure AFib, but the optimal pattern of lesions is unknown and postoperative tachyarrhythmias are common. METHODS: A radial pattern of linear radiofrequency lesions (Star) was made using an endocardial open surgical approach in 25 patients. Postoperative arrhythmias were induced and characterized during electrophysiological studies in 15 patients. RESULTS: The AFib was abolished in most patients (91%), but atrial flutter (AFlut) occurred in 96% of patients postoperatively. At postoperative electrophysiological studies, 37 flutter morphologies were studied in 15 patients (46% spontaneous, cycle length [CL] 223 +/- 25 ms). Seven mechanisms (lesions discontinuity, n = 6; focal mechanism, n = 1) of AFlut were characterized in six patients. In these cases, flutter was abolished using further catheter radiofrequency ablation. In the remaining cases, flutter was usually localized to an area involving the interatrial septum, but no critical isthmus was identified for ablation. After 16 +/-10 months, 15 patients (65%) were asymptomatic with (n = 3) or without (n = 12) antiarrhythmic medications. Eight (35%) patients had persistent arrhythmias. Postoperative atrial electrical activation was near physiological. CONCLUSIONS: The AFib maybe abolished using a radial pattern of linear endocardial radiofrequency lesions, but postoperative AFlut is common even when lesions are made under optimal conditions. Endocardial mapping techniques can be used to characterize the flutter mechanisms, thus enabling subsequent successful catheter ablation.

Effect of fluocarbon exchange transfusion on myocardial infarction size in dogs.

Fluosol DA (20%), a perfluocarbon with high oxygen solubility, was administered by concurrent exchange transfusion (30 ml/kg) to anesthetized open-chested adult greyhounds (n = 9) 1 hour after left anterior descending coronary ligation. Mechanical ventilation using 100% oxygen was used throughout the experiment. A second similar group (n = 9) received 0.9% normal saline solution (30 ml/kg), and a third group (n = 9) received no further intervention. Systemic, right atrial, and left atrial pressures were not altered by the exchange transfusion. Monastryl blue dye was injected through the left atrial line at 6 hours after ligation to define the area of myocardium at risk (AR); the animals were then killed and the heart was excised. The left ventricle was sliced at 5 mm intervals and stained using triphenyltetrazolium chloride, defining areas of necrosis (AN). The ratio of AN/AR and total left ventricular mass were then compared with the use of planimetry. The results were as follows: the AN/AR ratio in the 9 control animals was 90 +/- 2 (mean +/- standard error of the mean); in the 9 animals who received saline solution it was 88 +/- 2; and in the animals who received Fluosol it was 67 +/- 4 (p less than 0.01 compared with control; p less than 0.001 compared with the saline group). Fluocarbon exchange transfusion may reduce infarct size when administered after coronary occlusion.

Minimally invasive management of transposition of the great arteries in the newborn period.

This study reports on a predominantly noninvasive management program for neonatal transposition of the great arteries [TGA] incorporating balloon atrial septostomy [BAS] under echocardiographic control. BAS was performed in 25 consecutive patients presenting with TGA between April 1988 and April 1990. Structural and coronary anatomy was evaluated echocardiographically with angiographic supplementation only when additional data were required. This information was correlated, where possible, with direct anatomic findings and subsequent course. BAS was performed through the umbilicus in 17 patients (85% of patients in whom this approach was attempted). Thirteen patients did not require ventilation during BAS. There were minimal complications and satisfactory septostomies in all cases. Coronary anatomy was correctly predicted in all patients where anatomic correlation was available. Without invasive investigation 9 patients underwent neonatal arterial switch procedures and 2 underwent palliative procedures. BAS under echocardiographic control proved safe, effective, minimally traumatic and mostly possible via the umbilical vein. The umbilical vein, where patent, permitted rapid safe access for BAS. Echocardiographic diagnosis of the coronary artery, and structural and functional anatomy was reliable and allowed minimally invasive preoperative management in many patients.

Aorta-coronary bypass grafting with polytetrafluoroethylene conduits. Early and late outcome in eight patients.

During 1982 and 1983 we performed aorta-coronary bypass grafts on eight patients using 4 mm polytetrafluoroethylene conduits and predominantly the multiple sequential graft technique. Angiography was performed 1 week postoperatively and seven of eight patients had patent grafts and were angina free. At 1 year's follow-up 18 of 28 distal anastomoses were patent and five of eight patients were angina free. At 45 month's follow-up four of 28 distal anastomoses were patent and one of eight patients was angina free.

Surgical therapy for supraventricular tachycardia, a potentially curable disorder.

One hundred fifty-six patients underwent investigation and operation for supraventricular tachycardia: 145 had attempts at curative operations and 11 had His bundle section. Operative mortality was 0.68% and there were no late deaths among patients having curative operations. One patient died suddenly 1 year after His bundle section. All patients underwent electrophysiologic study before discharge and 6 months postoperatively. A satisfactory result, without supraventricular tachycardia and without medication, was achieved in 96.5% of all patients. Ninety-three percent have no supraventricular tachycardia and no demonstrable reentrant pathway at electrophysiologic study. All free wall accessory atrioventricular connections were divided and 97.7% of the patients were cured. Ninety percent of patients with posterior septal accessory atrioventricular connections had a satisfactory result, with cure demonstrated at late electrophysiologic study in 84%. Fifteen patients with atrioventricular junctional reentrant tachycardia were all cured, with preservation of normal atrioventricular conduction. Eight (88%) of nine patients with right atrial tachycardia were cured, and two patients with nodoventricular fibers and one patient with incessant atrioventricular junctional tachycardia had satisfactory results. Supraventricular tachycardia is now a potentially curable disorder when managed by low risk surgical procedures that offer a high cure rate.

Primary left ventricular rhabdomyosarcoma in a child: noninvasive assessment and successful resection of a rare tumor.

Rhabdomyosarcoma of the heart is a rare tumor, especially in childhood and particularly in the left ventricle. A primary tumor of this type was successfully resected after echocardiographic assessment alone in a young girl exposed prenatally to diphenylhydantoin. The patient is well and free of recurrence 2 1/2 years later.

Transcaval repair of the sinus venosus syndrome.

BACKGROUND: Surgical correction of the sinus venosus syndrome has been associated with sinus node dysfunction and venous obstruction postoperatively. We present the long-term follow-up of a lateral transcaval approach, which closes the atrial communication and corrects the partial anomalous pulmonary venous connection to the superior vena cava with the use of a simple pericardial patch. METHODS: The records of 66 patients undergoing repair between April 1981 and April 1997 were examined. Mean age at repair was 10.2 years (range, 1.5-65 years; median, 5 years). Six patients had a left superior vena cava, 4 had an additional atrial septal defect, and 2 had coronary artery bypass grafts. Immediate and long-term follow-up included physical examination, electrocardiography, transthoracic echocardiography, and use of a 24-hour ambulatory Holter monitor. Sinus node function, incidence of significant arrhythmia, and evidence of mechanical venous obstruction were assessed. RESULTS: Follow-up data were available for 64 (97%) patients for a mean follow-up of 4.1 years (range, 1-9 years). There were no deaths. No evidence of residual atrial septal defect, superior vena cava, or venous obstruction were found by echocardiography. On electrocardiography all patients were in sinus rhythm, with no arrhythmia seen. Holter monitoring was performed at a mean of 7.3 years postoperatively. All patients had normal sinus node function, and no sustained atrial arrhythmia was seen. CONCLUSION: Transcaval repair is a simple technique that does not interfere with sinus node function. There is no evidence to suggest that this approach leads to venous obstruction.

Simplified single patch technique for the repair of atrioventricular septal defect.

OBJECTIVE: Because of the complexity of traditional 1- and 2-patch techniques for the repair of complete atrioventricular septal defect, we modified our repair technique to avoid the use of any ventricular septal patch material. We report our prospective experience with this simplified 1-patch technique. METHOD: Forty-seven consecutive patients between May 1995 and August 1998 underwent repair with the use of this technique without modification. Repair was done in all patients by direct suturing of the common atrioventricular valve leaflets to the crest of the ventricular septum. No division of valve leaflets was necessary. A single pericardial patch was used to close the defect in the atrial septal component. Follow-up included electrocardiography and echocardiographic assessment of ventricular function, atrioventricular valve function, and adequacy of the left ventricular outflow tract. RESULTS: There were 2 deaths (4%), only 1 cardiac related, in the series. There were 17 male patients and 30 female patients. Mean age at repair was 5.6 months (median, 3.4 months). Associated lesions were repaired in 19 patients (40%). Mean follow-up was 1.85 years (median, 1.9 years). There was no heart block. There were no significant residual ventricular septal defects detected and no left ventricular outflow tract obstruction seen on echocardiography in any patient to date. Mitral valve status after operation was assessed as no incompetence in 13 patients (28%), minimal in 19 patients (40%), mild in 12 patients (26%), and moderate in 3 patients (6%). CONCLUSION: The repair of complete atrioventricular septal defect by direct suturing of the atrioventricular valve leaflets to the crest of the ventricular septum with a single-patch technique greatly simplifies the repair and does not lead to left ventricular outflow tract obstruction nor interfere with valve function.

Internal mammary artery grafting in a neonate for coronary hypoperfusion after arterial switch.

Coronary hypoperfusion may occur after the arterial switch operation, especially when coronary anatomy is complicated. We report successful use of the left internal mammary artery graft for a neonate with coronary hypoperfusion after the arterial switch operation for transposition of great arteries with intramural left coronary artery. Internal mammary arteriography showed a patent graft 19 months after operation.

Use of the Medtronic Freestyle valve as a right ventricular to pulmonary artery conduit.

BACKGROUND: We have used the Medtronic Freestyle bioprosthesis as a right ventricular to pulmonary artery conduit recently in an attempt to overcome some of the problems associated with homografts and stented xenografts. The aim of this study was to review the performance of this prosthesis. METHODS: Prospectively collected data for patients having Freestyle bioprostheses implanted as a right ventricular to pulmonary artery conduit were reviewed to assess clinical outcome and echocardiographic results. RESULTS: Thirteen patients aged 13 days to 22.5 years (median, 7.9 years) underwent either primary repair (n = 5) or change of conduit (n = 8) using the Freestyle bioprosthesis. One neonate with truncus arteriosus died postoperatively of pulmonary hypertension. One conduit was explanted 27 months after repair of neonatal truncus arteriosus. There has been no incidence of significant prosthetic regurgitation, thromboembolism, or endocarditis at mean follow-up of 10.1 months (range, 2 weeks to 29 months). CONCLUSIONS: The Medtronic Freestyle valve is a reliable pulmonary valve substitute in the short term. Early results justify continued clinical use of the device in this setting with close follow-up.

Reoperation and coarctation of the aorta: the need for lifelong surveillance.

BACKGROUND: We report a series of reoperations in 23 patients who had undergone previous aortic coarctation repair. METHODS: The medical records of these patients were reviewed, and the patients were followed up by telephone interview. Mean age at reoperation was 25 years. There was a mean of 18 years between initial coarctation repair and reoperation. Indications for reoperation included recoarctation (9 patients), aortic aneurysm (8), aortobronchial fistulas with exsanguinating hemorrhage (2), subaortic stenosis (1), ruptured thoracic aneurysm (1), ruptured sinus of Valsalva aneurysm (1), and supramitral stenosing ring (1). RESULTS: There were no specific intraoperative complications. Three patients required reexploration for bleeding. An acutely ischemic lower limb developed in 1 patient secondary to a common femoral artery embolus, which necessitated embolectomy. CONCLUSIONS: Reoperation for postcoarctation repair patients can be performed with good results. Sudden life-threatening hemorrhage due to aortobronchial fistulas in patients having undergone Dacron patch aortoplasty, as well as long-term obstructive phenomena seen anywhere along the left ventricular outflow tract, make lifelong surveillance of these patients mandatory.

Ventricular assist devices in pediatric cardiac surgery.

BACKGROUND: Early experience in other centers with pediatric assist devices has been favorable. METHODS: Prospectively we examined our first 13 patients between January 1992 and September 1994. RESULTS: Thirteen children underwent ventricular assistance at Royal Alexandra Hospital for Children. Age ranged from 4 days to 30 months, weight from 2.9 kg to 17 kg. Ventricular assistance was employed from 1.5 hours to 190 hours. Of 12 surgical patients, 8 required left ventricular assistance to be weaned from cardiopulmonary bypass after correction of congenital defects, and 4 required support in the postoperative period for refractory low cardiac output. A child was supported after a kick to the chest by a horse caused cardiogenic shock. All 13 patients initially responded to ventricular assistance and 7 remain alive. Of the deaths, 2 were neurologic, 2 due to myocardial failure, and 2 to sepsis. The major complications in the first days were hemorrhage and tamponade. Later problems included thrombosis of the circuit despite systemic heparinization, and a cannula-related tear to the anterior mitral leaflet. The 7 survivors are well after 3 to 32 months. CONCLUSIONS: Despite the mortality and complications, we are encouraged by these results, in the light of almost certain death for all 13 patients without ventricular assistance.

Surgery for supraventricular tachycardia (SVT).

All forms of supraventricular tachycardia (SVT) are now potentially curable by surgery and we believe that patients should be offered surgery as an initial therapeutic option. At Westmead Hospital, 311 patients have undergone surgery for SVT, 13 having AV node ablation, a procedure now rarely performed, and 298 have had attempts at curative surgery. One hundred and ninety-nine patients were diagnosed primarily as having a Wolff-Parkinson-White syndrome (WPW) and 139 had free wall or anterior septal connections with a clinical cure rate of 98.0%. The failures were entirely due to unrecognised posterior septal connections. Sixty patients had primarily posterior septal connections with a clinical cure rate of 96%. Atrioventricular junctional re-entry tachycardia may now be cured, probably by dividing an extra nodal His-to-atrial connection. Seventy-eight patients have undergone surgery with a clinical cure rate of 92%. Fifteen patients with right atrial tachycardias, 4 patients with nodo-ventricular fibres and 2 with incessant AV tachycardia have undergone surgery. The overall clinical cure rate for all patients is 95% and 92% at late electro-physiological study (EPS).

Radiofrequency lesions produced by handheld temperature controlled probes for use in atrial fibrillation surgery.

OBJECTIVES: Detailed analysis of the size and shape of lesions produced by handheld radiofrequency ablation devices at open heart surgery has not been reported previously. METHODS: Radiofrequency lesions were made from the epicardial surface of the cardiac ventricles in open-chested dogs. The effects of electrode size, electrode temperature and duration of ablation were studied. In a second group of experiments simultaneous multielectrode ablation was performed on the ventricular epicardium after cold cardioplegia. RESULTS: Using a single 12 x 2.5 mm electrode and a target temperature of 80 degrees C the lesion depth increased from 3.8+/-0.9 mm at 15 s, to 6.1+/-0.9 mm at 120 s (P=0.01). Increasing the target temperature from 70 to 90 degrees C (for 60 s) increased lesion depth from 5.0+/-1.2 to 5.6+/-1.7 mm (P=0.2). There was no difference in depth of lesions with the two electrode widths (4.0+/-0.5 mm (large) vs. 3.9+/-1.0 mm (small)). Lesions produced using the multielectrode probe (80 degrees C, 60 s) were 30-35 mm long with even penetration into the tissue. The mean depth of these lesions on microscopic sections was 3.9 mm. The mean width was 7.1 mm. CONCLUSIONS: Handheld probes can be used to make deep linear lesions in the myocardium. Lesions expand rapidly and are wider than they are deep. A multielectrode ablation device allows rapid formation of linear lesions.

Evaluation of synthetic and biosynthetic conduits used as aorto-pulmonary shunts in growing pigs.

Synthetic and biosynthetic conduits 6 mm in internal diameter and 3 cm long were implanted as aorto-pulmonary shunts in 4 week old piglets. The synthetic conduit was made of Polytetrafluoroethylene (P.T.F.E.) manufactured by Gore-Tex; the biosynthetic graft was prepared by tanning bovine ureters and covering it with a polyester mesh. Two groups of six animals for each conduit underwent operation. Following implantation, when the animals were physiologically stable, the pressure and blood flow were measured in the pulmonary artery, conduit and aorta, and at the same time blood gases were obtained. These measurements were repeated four weeks later, following which the grafts were excised and processed for histological studies. All the conduits were patent, 4 weeks after implantation, but whereas there was little difference in the flows through the bovine grafts (506 ml/min) there was a marked reduction in the flow through the Gore-Tex conduit (235 ml/min). These differences could be related to the changes seen histologically. No drugs were used to affect patency of the conduits in this study.

The surgical management of aortopulmonary window using the anterior sandwich patch closure technique.

Between 1969 and June, 1986, 13 patients with aortopulmonary window were evaluated and operated upon with eleven survivors. All were children with ages ranging from 2 weeks to 2 1/2 years and had a typical aortopulmonary window (Type 1) with a connection between the ascending aorta and main pulmonary artery. Six of them also had associated cardiac anomalies. Operative techniques included both closed and open procedures. Simple ligation was carried out in two, while the remaining 11 patients were operated upon with the aid of extracorporeal circulation. "Sandwich" patch closure was the preferred method which was employed in 7 patients.

Spontaneous convulsions in Charles River Wistar rats.

Spontaneous clonic convulsions in the Charles River Wistar rat have been observed at an incidence of 1.5%. Females (2.3%) are more susceptible than males (0.7%). These convulsions are not seen in rats of less than approximately 16 weeks of age. Some animals have exhibited single convulsions whilst others have convulsed on numerous occasions. No histopathological abnormalities of the brain have been recorded for these animals following routine examination.