A multicenter study of primary graft failure after infant heart transplantation: impact of extracorporeal membrane oxygenation on outcomes.

Primary graft failure is the major cause of mortality in infant HTx. The aim of this study was to characterize the indication and outcomes of infants requiring ECMO support due to primary graft failure after HTx. We performed a retrospective review of all infants (<1 yr) who underwent Htx from three institutions. From 1999 to 2008, 92 infants (<1 yr) received Htx. Sixteen children (17%) required ECMO after Htx due to low cardiac output syndrome. Eleven (69%) infants were successfully weaned off ECMO, and 9 (56%) infants were discharged with a mean follow-up of 2.3 ± 2.5 yr. Mean duration of ECMO in survivors was 5.4 days (2-7 days) compared with eight days (2-10 days) in non-survivors (p = NS). The five-yr survival rate for all patients was 75%; however, the five-yr survival rate was 40% in the ECMO cohort vs. 80% in the non-ECMO cohort (p = 0.0001). Graft function within one month post-Htx was similar and normal between ECMO and non-ECMO groups (shortening fraction = 42 ± 3 vs. 40 ± 2, p = NS). For infants, ECMO support for primary graft failure had a lower short-term and long-term survival rate vs. non-ECMO patients. Duration of ECMO did not adversely impact graft function and is an acceptable therapy for infants after HTx for low cardiac output syndrome.

Lung transplantation in infants and toddlers from 1990 to 2004 at St. Louis Children's Hospital.

In a retrospective, single-center cohort study, outcomes of infants and toddlers undergoing lung transplant at St. Louis Children's Hospital between 1990 and 2004 were compared to older children. Patients with cystic fibrosis (exclusively older children) and those who underwent heart-lung, liver-lung, single lung or a second transplantation were excluded from comparisons. One hundred nine lung transplants were compared. Thirty-six were in infants <1 year old, 26 in toddlers 1-3 years old and 47 in children >3 years old. Graft survival was similar for infants and toddlers (p = 0.35 and p = 0.3, respectively) compared to children over 3 years old at 1 and 3 years after transplant. Significantly more infants (p < 0.0001 and p = 0.003) and toddlers (p = 0.002 and p = 0.03) were free from acute rejection and bronchiolitis obliterans compared to older patients. While most infants and toddlers had only minimal lung function impairment, and achieved normal to mildly delayed developmental scores, somatic growth remained depressed 5 years after transplant. Lung transplantation in infants and young children carries similar survival rates to older children and adults. Further insights into the unique immunologic aspects of this group of patients may elucidate strategies to prevent acute and chronic rejection in all age groups.

Quality of life after aortic valve replacement at the age of >80 years.

BACKGROUND: The optimal management of aortic valve disease in patients >80 years old depends on functional outcome as well as operative risks and late survival. METHODS AND RESULTS: We retrospectively identified 133 patients (62 men, 71 women) aged 80 to 91 years (mean 84+/-3 years) who underwent aortic valve replacement alone or in combination with another procedure between January 1, 1993, and April 31, 1998. Demographics included hypertension 68%, diabetes mellitus 17%, and history of stroke 11%. Operative (30 day) mortality rate was 11%. Urgent or emergent surgery, aortic insufficiency, and perioperative stroke or renal dysfunction were risk factors for operative death by multivariable analysis. Intensive care unit and total hospital length of stay were prolonged at 6.2 and 14.7 days, respectively. Late follow-up between July 1, 1998, and November 1, 1999, was 98% complete. Actuarial survival at 1 and 5 years was 80% and 55%, respectively. Predictors of late mortality were preoperative or perioperative stroke, chronic obstructive pulmonary disease, aortic stenosis, and postoperative renal dysfunction. The mean New York Heart Association functional class for 65 long-term survivors improved from 3.1 to 1.7. Quality of life assessed with the Medical Outcomes Study Short Form-36 was comparable to that predicted for the general population >75 years old. CONCLUSIONS: Functional outcome after aortic valve replacement in patients >80 years old is excellent, the operative risk is acceptable, and the late survival rate is good. Surgery should not be withheld from the elderly on the basis of age alone.

Spontaneous atrial flutter in a chronic canine model of the modified Fontan operation.

OBJECTIVES: This study sought to 1) establish whether the atrial flutter (AFL) inducible acutely occurs spontaneously in a chronic canine model, and 2) characterize any reentrant circuits present chronically. BACKGROUND: We previously demonstrated, in an acute canine model of the modified Fontan operation, that the lateral tunnel suture line creates a sufficient electrophysiologic substrate for AFL. METHODS: Using cardiopulmonary bypass, a suture line was placed through a right atriotomy in adult dogs (n = 7) to simulate the lateral tunnel of the Fontan operation. Holter recordings were made preoperatively, on the first postoperative day and 2, 4 and 6 weeks postoperatively. At 6 to 8 weeks, through bilateral ventriculotomies, 253-point unipolar atrial electrodes were inserted. AFL was induced using atrial burst pacing, and endocardial activation sequence maps were created. RESULTS: Preoperatively, all dogs were in sinus rhythm. Spontaneous AFL occurred in all dogs postoperatively, with a mean (+/-SD) cycle length of 192 +/- 22 ms. At 6 weeks postoperatively, of six dogs that survived, four had intermittent AFL, and two had incessant AFL. At reoperation, sustained AFL was inducible in six of six dogs, with a mean cycle length of 194 +/- 17 ms. Activation sequence maps demonstrated conduction block at the lateral tunnel suture line, which facilitated unidirectional conduction critical for propagation of the reentrant circuit. The AFL circuit was similar to that observed acutely. CONCLUSIONS: In a chronic canine model of the modified Fontan operation, the lateral tunnel suture line alone, in the absence of atrial stretch or hypertension, provides an electrophysiologic substrate that promotes spontaneous AFL. This model may be useful for evaluating various forms of treatment and prevention of AFL after the Fontan operation.

Deletion within chromosome 22 is common in patients with absent pulmonary valve syndrome.

Interstitial deletions in chromosome 22 and features associated with CATCH-22 syndrome have been reported in patients with conotruncal congenital heart anomalies. Absent pulmonary valve syndrome is characterized by absent or rudimentary pulmonary valve cusps, absent ductus arteriosus, conoventricular septal defect, and massive dilation of the pulmonary arteries. Because absence of the ductus arteriosus is a key element in the pathogenesis of this syndrome and aortic arch malformations are frequently seen in patients with CATCH-22 syndrome, we hypothesized that patients with absent pulmonary valve syndrome would have a high incidence of deletions in the critical region of chromosome 22. Eight patients with absent pulmonary valve syndrome were studied. Metaphase preparations were examined with fluorescent in situ hybridization of the N25 (D22S75) probe to the critical region of chromosome 22q11.2. Deletions were detected in 6 of 8 patients. The presence of deletions in chromosome 22 in most of the patients we have examined with a diagnosis of absent pulmonary valve syndrome supports a specific genetic and embryologic mechanism involving the interaction of the neural crest and the primitive aortic arches as one cause of congenital absence of the pulmonary valve.

Isolated lung transplantation in children: pathological diagnosis and incidence of pulmonary complications.

The pathological findings in the allografts of 14 children who underwent lung transplantation (LT) at St. Louis Children's Hospital, St. Louis, MO, in the period between July 1990 and May 1992 were reviewed. The study is based on histological analysis of 63 transbronchial biopsy (TBB) specimens, eight open lung biopsy specimens, and three pneumonectomy specimens. The mean age at transplantation was 10.5 years (range, 1 to 17 years) and the average follow-up period was 5.7 months. Sufficient tissue for an adequate pathological examination was obtained in 58 (92%) TBB specimens. Each specimen consisted of a mean of 6.12 tissue fragments, but only 4.79 fragments contained actual lung parenchyma for suitable examination. Ten patients (71%) had 23 biopsy-proven episodes of acute rejection with a frequency of 1.64 episodes per patient. The first episode was documented at a mean of 19 days after transplantation. Six patients (42.8%) developed bronchiolitis obliterans (BO). The definitive diagnosis of this condition was made either by open lung biopsy (n = 3) or on allograft pneumonectomy (n = 1), and it was infrequently recognized by TBB. Four of the six patients died less than 9 months after the diagnosis of BO was made, indicating the grave consequences of this complication. Two other deaths were attributed to the development of posttransplantation lymphoproliferative disorders.

Pediatric lung transplantation. Indications, techniques, and early results.

From July 1990 to April 1993, 36 lung transplantations in 33 patients were performed in our pediatric transplant program (0.25 to 23 years, mean age 10.3 years). Eight children had been continuously supported with a ventilator for 3 days to 4.5 years before transplantation and three were supported by extracorporeal membrane oxygenation. Indications for lung transplantation in this pediatric population included the following: cystic fibrosis (n = 13), pulmonary hypertension, and associated congenital heart disease (n = 10), pulmonary atresia, ventricular septal defect and nonconfluent pulmonary arteries (n = 3), pulmonary fibrosis (n = 6), and acute respiratory distress syndrome (n = 1). Three children underwent retransplantation for acute graft failure (n = 2) or chronic rejection (n = 1). Pulmonary fibrosis was related to complications of treatment of acute of myelogenous leukemia with bone marrow transplantation in two children and to bronchiolitis obliterans, bronchopulmonary dysplasia, interstitial pneumonitis, and Langerhans cell histiocytosis in four others. Thirteen children underwent lung transplantation and concomitant cardiac repair. Bilateral lung transplantation, ventricular septal defect closure and pulmonary homograft reconstruction of the right ventricular outflow tract to the transplanted lungs was performed in three children by means of a new technique that avoids the need for combined heart-lung transplantation. Two patients had ventricular septal defect closure and single lung transplant for Eisenmenger's syndrome, two had ligation of a patent ductus arteriosus and transplantation, three additional children underwent atrial septal defect closure and lung transplantation, and two underwent lung transplantation for congenital pulmonary vein stenosis. Eight early deaths and three late deaths occurred (actuarial 1-year survival 62%). Lung transplantation in children has been associated with acceptable early results, although modification of the adult implantation technique has been necessary. Lung transplantation and repair of complex congenital heart defects is possible; heart-lung transplantation may only be required for patients with severe left heart dysfunction and associated pulmonary vascular disease. Bronchiolitis obliterans remains a major concern for long-term graft function in pediatric lung transplant recipients.

Repair of long-segment tracheal stenosis in infancy.

Long-segment stenosis of the trachea in infancy is a considerable surgical challenge because the infants are generally extremely ill and the airway is small. The optimal type of repair is not clearly defined. This report summarizes our experience with rib cartilage tracheoplasty done with cardiopulmonary bypass. Six patients underwent repair of long-segment tracheal stenosis between September 1987 and September 1994. The mean age was 14 weeks (range 1 to 58 weeks). Patients had stenosis of at least 70% of the tracheal length, typically with complete cartilaginous rings. In all patients stenosis was repaired by placement of a section of rib cartilage as an augmentation patch into the anterior surface of the trachea, which had been incised through the entire length of the stenosis. To avoid distal airway intubation, we used cardiopulmonary bypass for all procedures, with a mean bypass duration of 110 minutes (range 54 to 175 minutes). Mechanical ventilation was required for a median of 11 days after the operation (range 7 to 81 days), and the median postoperative hospital stay was 17 days (range 12 to 180 days). All patients are long-term survivors. Complications included the need for extracorporeal membrane oxygenation to treat ventricular dysfunction in one patient and graft dehiscence requiring revision of the distal graft in another. The latter patient has required several treatments with a bronchoscope for removal of granulation tissue. All other patients are free of symptoms and have normal growth with a mean follow-up of 4.7 years (range 5 months to 7.6 years). We conclude that rib cartilage tracheoplasty for long-segment tracheal stenosis provides excellent results in short and intermediate follow-up. In addition, the use of cardiopulmonary bypass allows an unobstructed view of the tiny infant airway and thus permits a precise repair.

Atrial flutter: a newly recognized complication of pediatric lung transplantation.

BACKGROUND AND METHODS: Atrial flutter after pediatric lung transplantation has not previously been reported. We reviewed the records of 78 children who underwent lung transplantation at our institution to characterize the incidence and clinical course of postoperative atrial flutter. The diagnosis was based on either a surface or transesophageal electrocardiogram that demonstrated a fixed cycle length atrial tachycardia that did not require ventricular participation. RESULTS: Atrial flutter occurred in seven of 62 (11.3%) patients who underwent bilateral sequential lung transplantation, zero of 10 patients after single lung transplantation, and zero of six patients after heart-lung transplantation. Ages of the patients with atrial flutter ranged from 2.5 months to 14 years. Electrocardiographic findings among patients varied with respect to p-wave morphology and atrioventricular conduction. No patient had a prior atrial arrhythmia or coexisting structural cardiac disease. None had atrial flutter in relation to a rejection episode. Two patients had atrial flutter transiently during the first postoperative day, but it resolved spontaneously. Five patients had recurrent atrial flutter that began 13 +/- 7 days after the operation. The mean cycle length of atrial flutter was 196 +/- 65 msec. The arrhythmia was unresponsive to digoxin in four patients to whom it was administered. It was controlled with procainamide in four patients and with flecainide in one. At 1 and 6 months after lung transplantation, procainamide was discontinued in two patients without recurrence. One patient died of bronchiolitis obliterans 6 months after the operation while still receiving flecainide. Two patients continue to receive procainamide 4 and 7 months after transplantation. CONCLUSIONS: (1) Atrial flutter commonly occurs after bilateral lung transplantation in children. (2) Electrocardiographic manifestations are variable. (3) Type 1 antiarrhythmic agents provide satisfactory control.

Lung transplantation in very young infants.

INTRODUCTION: Established successes with adult lung transplantation have laid the foundation for extension of this therapeutic modality to infants and children dying of end-stage pulmonary disease. The purpose of this report is to convey our experience with 19 infants undergoing lung transplantation before the age of 6 months. METHODS: Six patients with predominantly pulmonary vascular disease and 13 patients with primarily pulmonary parenchymal disease have undergone bilateral sequential lung transplantation at our institution since 1990. Mean age at transplant was 104 +/- 44 days, and mean weight was 4.9 +/- 1.6 kg. RESULTS: Although early mortality (32%, 6/19) was higher than that previously reported for older pediatric age groups, long-term survival was similar (44% at a maximum follow-up of 6 years). Although anastomotic complications and infections occurred at a rate approximating that seen in older pediatric age groups, episodes of acute rejection appear to occur with decreased frequency. Similarly, at a mean follow-up of 3 years, only 2 (15%) of 13 long-term survivors have evidence of bronchiolitis obliterans. The functional residual capacity, as measured on infant pulmonary function tests, has gradually increased as the children have grown, suggesting that lung growth is occurring. CONCLUSIONS: Bilateral lung transplantation is a viable alternative in infants dying of end-stage pulmonary disease. Efforts directed toward avoiding the complications that lead to early posttransplant mortality combined with the seemingly lower incidence of early and late rejection may provide long-term results better than those in other age groups.

Response of the hypertrophied left ventricle to global ischemia. Comparison of hyperkalemic cardioplegic solution with and without verapamil.

The hypertrophied left ventricle is at considerably greater risk for injury when subjected to global ischemia than is an otherwise normal heart. We evaluated the efficacy of verapamil, a calcium-channel blocking agent, as an adjunct to standard crystalloid cardioplegic solution in animals with left ventricular hypertrophy subjected to myocardial ischemia during cardiopulmonary bypass. Infracoronary aortic stenosis was produced in 15 mongrel puppies by plication of the noncoronary cusp of the aortic valve. Studies were conducted 3 to 4 months later. Left ventricular catheter-tip pressure transducers and major and minor axis ultrasonic dimension crystals were inserted, and the animals were then supported by cardiopulmonary bypass with 30 minutes of normothermic ischemia. Animals were randomized to receive either standard hyperkalemic crystalloid cardioplegic solution (n = 8) or the same solution with verapamil, 0.1 mg/kg (n = 7). After the 30 minutes of ischemia, the animals were supported on cardiopulmonary bypass for an additional 30 minutes and then separated from bypass. They were then studied for another 2 hours by measurement of myocardial adenosine triphosphate content, myocardial blood flow, systolic function with use of the end-systolic pressure/volume ratio, and compliance with use of the natural strain coefficient of the minor axis at 15 mm Hg end-diastolic pressure. There was a better recovery of systolic function in the animals treated with verapamil (89.2% versus 63.3%). The compliance as measured with use of the minor axis natural strain coefficient returned essentially to baseline in the group of animals treated with verapamil (0.236 +/- 0.038 before ischemia and 0.254 +/- 0.043 2 hours after ischemia), but it fell markedly in the control animals (0.219 +/- 0.027 before ischemia and 0.153 +/- 0.016 2 hours after ischemia). Myocardial adenosine triphosphate levels were not significantly different at any time during the study. Likewise, myocardial blood flow was not significantly different between groups. We conclude that the addition of verapamil to hyperkalemic cardioplegic solution improves recovery of both systolic and diastolic function after global ischemia in dogs with left ventricular hypertrophy resulting from aortic stenosis. The precise mechanism for this is unknown.

Global ischemia in the immature canine ventricle. Enhanced protective effect of verapamil and potassium.

The efficacy of the addition of verapamil to a cardioplegic solution was evaluated in immature canine hearts subjected to normothermic global ischemia. Two groups of mongrel puppies less than 10 weeks old were subjected to 30 minutes of global myocardial ischemia while on cardiopulmonary bypass. One group (Group K) was arrested with cardioplegic solution containing 20 mEq/L of KCl; the other group (Group K + V) was arrested with the same solution containing 0.2 mg/kg of verapamil. Ultrasonic crystals were placed for measurement of left ventricular dimensions, and micromanometers measured left ventricular pressures. Functional measurements included left ventricular strain, first derivative of left ventricular pressure (dP/dt), and the end-systolic pressure/volume ratio (Emax). Metabolic recovery was assessed by measuring myocardial adenosine triphosphate (ATP) content. Ninety minutes following ischemia, Group K + V exhibited greater minor axis strain at a left ventricular end-diastolic pressure of 15 and 20 mm Hg (p less than 0.05), greater dP/dt (p less than 0.05 to 0.001), and greater Emax (p less than 0.05) than Group K. ATP content in Group K + V was greater at 60 minutes (Group K + V: 12.74 +/- 1.60 mumol/gm; Group K: 8.39 +/- 1.30, p less than 0.05) and 90 minutes (Group K + V: 10.34 +/- 0.46; Group K: 7.55 +/- 1.42, p less than 0.05) after ischemia. The addition of verapamil to a cardioplegic solution containing potassium enhances the recovery of function and high-energy phosphate stores in the immature myocardium following normothermic global ischemia.

Atrial flutter after lateral tunnel construction in the modified Fontan operation: a canine model.

Intraatrial reentrant tachycardia, or atrial flutter, is a common postoperative problem after Fontan repair, which involves an atriopulmonary connection. A modification of Fontan repair, total cavopulmonary connection, minimizes the portion of the right atrium exposed to stretch and hypertension; however, atrial flutter continues to occur after this procedure. We postulated that the intraatrial lateral tunnel suture line of total cavopulmonary connection, in the absence of physiologic alterations such as atrial hypertension or stretch, provides the necessary electrophysiologic substrate for atrial flutter. The purpose of this study was to produce a canine model of total cavopulmonary connection (1) to establish that the intraatrial suture line alone is sufficient to permit sustained atrial flutter and (2) to characterize the pathways of resulting reentrant arrhythmias. After induction of general anesthesia, 25 to 30 kg dogs (n = 17) underwent median sternotomy, cradling of the pericardium, and placement of a pacing electrode on the right atrial appendage. Normothermic cardiopulmonary bypass was initiated. The total cavopulmonary connection suture line was placed through a standard right atriotomy,simulating construcion of the lateral tunnel. After closure of the atriotomy, 253 point unipolar atrial endocardial form-fitting electrodes were placed through bilateral ventriculotomies. By means of atrial burst pacing and programmed extrastimulation, induction of atrial flutter was attempted. If atrial flutter could not be induced, isoproterenol was infused and the stimulation protocol was repeated. After induction of atrial flutter, mapping of the activation sequence was performed. Before suture line placement, no dog had inducible atrial flutter. After placement of the suture line, sustained atrial flutter was reproducibly induced in every dog, although isoproterenol was required for this in three (17.6%). The mean flutter cycle length was 177 +/- 30 msec. In each case, the atrial flutter circuit was limited to the right atrium, with the left atrium being passively activated. The atrial flutter circuit was dependent on a corridor of myocardium that resulted from conduction block on the free wall, created by the lateral margin of the total cavopulmonary connection. In no case was the atriotomy integral to the atrial flutter circuit. This study establishes that the total cavopulmonary connection baffle suture line alone, without alteration in circulatory physiology, creates a sufficient anatomic substrate for atrial flutter in a short-term canine model. Delineation of the anatomic boundaries of the reentrant circuit raises the possibility of targeting areas within the circuit that could be modified, potentially reducing the incidence of postoperative atrial flutter after total cavopulmonary connection.

Anatomically based ablation of atrial flutter in an acute canine model of the modified Fontan operation.

BACKGROUND: Lateral tunnel total cavopulmonary connection, also called the modified Fontan operation, uses a baffle through the right atrium. We established, in an acute canine model, that atrial flutter after total cavopulmonary connection revolves around a line of conduction block imposed by the free wall lateral tunnel suture line. We hypothesized that a line of conduction block between the free wall total cavopulmonary connection suture line and the tricuspid anulus would interrupt atrial flutter in this model. OBJECTIVE: Our objective was to determine whether a cryolesion placed between the free wall total cavopulmonary connection suture line and the tricuspid anulus would terminate atrial flutter in an acute canine model. METHODS: Seven adult dogs underwent median sternotomy and institution of cardiopulmonary bypass. A suture line was placed through a right atriotomy to simulate total cavopulmonary connection lateral tunnel construction. Form-fitting 253-point biatrial endocardial mapping electrodes were placed via bilateral ventriculotomies. Atrial flutter was induced by atrial burst pacing. A cryothermal lesion was then placed between the free wall total cavopulmonary connection suture line and the tricuspid anulus in the low lateral right atrium (i.e., CRYO 1 procedure), and reinduction of atrial flutter was attempted. If atrial flutter was reinduced, the cryolesion was modified superiorly to include the caudal portion of the atriotomy (i.e., CRYO 2 procedure). Activation sequence maps were generated for sinus rhythms before and after the cryolesions were placed and for induced arrhythmias. RESULTS: In all seven cases, atrial flutter was inducible after suture line placement, before placement of a cryolesion. The reentrant circuit incorporated both caval orifices in five of seven cases and was successfully ablated by the CRYO 1 approach in each case. Atrial flutter was not inducible after placement of the CRYO 2 lesion in the remaining two cases, in which breakthrough of the wave front occurred across the lateral tunnel suture line in the intercaval region. Activation sequence maps of sinus rhythm after placement of the cryolesions demonstrated a conduction block at the site of the lesion. CONCLUSIONS: A linear cryothermal lesion placed between the free wall aspect of the total cavopulmonary connection suture line and the tricuspid anulus created a line of conduction block that successfully ablates atrial flutter in the canine model.

Left-sided atrial flutter: characterization of a novel complication of pediatric lung transplantation in an acute canine model.

BACKGROUND: Postoperative atrial flutter has been observed in approximately 10% of children undergoing lung transplantation at our institution. We hypothesized that the left atrial anastomoses made to establish pulmonary venous continuity provide the primary electrophysiologic substrates for atrial flutter. OBJECTIVES: Our objectives were (1) to determine whether the left atrial suture lines alone are sufficient to produce atrial flutter in an acute canine model of lung transplantation and (2) to characterize any resulting reentrant circuits to surgically ablate the atrial flutter. METHODS: Supported by cardiopulmonary bypass, adult dogs (n = 10) underwent bilateral pneumonectomies. The left atrial anastomotic suture lines were simulated by dividing the tissue between the ostia of the transected superior and inferior pulmonary veins and closing the resulting defects. Bilateral suture lines were placed in group 1 (n = 6) to simulate bilateral lung transplantation. In group 2 (n = 4), only a left-sided suture line was placed to represent single lung transplantation. Unipolar 253-point biatrial endocardial mapping electrodes were inserted via bilateral ventriculotomies. Atrial flutter was induced by atrial burst pacing, and activation sequence maps were generated. In five of six cases in group 1, a T-incision connecting the two suture lines and the mitral anulus was then made. In group 2, a single incision from the suture line to the mitral anulus was performed in each case. Burst pacing was subsequently repeated. RESULTS: Atrial flutter could not be induced after bypass alone in any case. After simulated lung transplantation, sustained atrial flutter was reproducibly induced in 10 of 10 dogs. The mean cycle length in all dogs was 133 +/- 7 msec. There was no significant difference in mean cycle length or activation sequence patterns between groups 1 and 2. The reentrant circuit was confined to the left atrium. Each simulated left atrial anastomosis created a zone of conduction block around which circus movement could occur. In group 1, either suture line functioned as the central obstacle. Atrial flutter was terminated in five of five dogs in group 1 by means of the T-incision and in all four dogs in group 2 with the incision connecting the suture line to the mitral anulus. CONCLUSIONS: (1) In an acute canine model of lung transplantation, each left atrial suture line alone provides an electrophysiologic substrate for atrial flutter by creating a zone of conduction block around which circus movement can occur. (2) Extending this zone of block to the mitral anulus, together with interruption of the isthmus of tissue between the two suture lines present after bilateral lung transplantation, terminates the atrial flutter in this model and may have an application prophylactically at the time of lung transplantation in children to prevent postoperative atrial flutter.

Amelioration of the deleterious effects of platelets activated during cardiopulmonary bypass. Comparison of a thromboxane synthetase inhibitor and a prostacyclin analogue.

Thrombocytopenia and platelet dysfunction are commonly seen after cardiopulmonary bypass. In addition, the microvascular bed of ischemic myocardium is a potent stimulus for platelet deposition and microvascular plugging. Thus, it would appear theoretically advantageous to provide pharmacologic protection of platelets by inhibiting their response to activating agents and thereby preventing their loss into the extracorporeal circuit; this would further inhibit myocardial platelet deposition and the deleterious effects therein. Twenty-one mongrel dogs were placed on cardiopulmonary bypass with 30 minutes of normothermic global ischemia. They were randomly assigned to receive pretreatment with an infusion of saline (control, n = 8), a thromboxane synthetase inhibitor (RO-22-4679, n = 5), or a prostacyclin analogue that does not produce hypotension (ZK 36,374, n = 8). The platelet count in those animals treated with ZK 36,374 was significantly higher at the end of the experiment than in the control group (102.8 +/- 10.7 X 10(3) versus 69.7 +/- 10.6 X 10(3), p less than 0.01); the animals treated with RO-22-4679 had a platelet count between the other two groups (92.8 +/- 14.8 X 10(30)), which was not significantly different from either. Myocardial platelet deposition was measured with indium 111-labeled platelets. Those animals treated with ZK 36,374 had a much lower level of platelet deposition than the group of controls; again the RO-22-4679 group had values between the other two. Finally, myocardial blood flow after global ischemia and cardiopulmonary bypass, measured with radioactive microspheres, was significantly higher in the ZK 36,374 group than in the control group. We conclude that ZK 36,374 prevents platelet consumption during cardiopulmonary bypass over and above that seen with inhibition of thromboxane synthesis alone. It also prevents deposition of platelets into the myocardium after global ischemia and we presume by that mechanism increases myocardial blood flow.

Pathophysiology of chronic cyanosis in a canine model. Functional and metabolic response to global ischemia.

To investigate the pathophysiology of chronic cyanosis, we subjected 14 adult mongrel dogs to diversion of the inferior vena cava to the right inferior pulmonary vein. This produced a mean oxygen tension of 42 +/- 2 mm Hg and a calculated right-to-left shunt of 52.0% +/- 3.9%. These animals (Group C) and 15 normal dogs (Group N) were subjected to cardiopulmonary bypass with 20 minutes of normothermic global ischemia. Functional indices studied were rate of rise of left ventricular pressure and the end-systolic pressure/volume ratio. Metabolic status was assessed by obtaining transmural myocardial biopsy specimens for measurement of adenosine triphosphate content. Myocardial blood flow was measured with radiolabeled microspheres. There were no significant differences between Group C and Group N in either functional index or blood flow measurement prior to global ischemia. At 45 minutes after ischemia, Group N animals had a significantly greater rate of rise of left ventricular pressure (at a left ventricular end-diastolic pressure of 0, 5, 10, and 15 mm Hg, p less than 0.025 to 0.05) and subendocarial perfusion (endocardial/epicardial flow ratio 0.961 +/- 0.037 versus 0.815 +/- 0.021, p less than 0.01). At 90 minutes after ischemia, Group N animals exhibited a significantly higher end-systolic pressure/volume ratio (4.9 +/- 0.7 versus 3.0 +/- 0.4 mm Hg/ml, p less than 0.05), rate of rise of left ventricular pressure (at an end-diastolic pressure of 0 to 20 mm Hg, p less than 0.005 to 0.05), and endocardial/epicardial flow ratio (1.065 +/- 0.046 versus 0.829 +/- 0.059, p less than 0.01). No differences in adenosine triphosphate content were found at any sampling period. The Group C left ventricles exhibited no hypertrophy but were significantly dilated compared to Group N (38.8 +/- 0.3 versus 30.1 +/- 0.2 mm, p less than 0.05). Inferior vena cava to pulmonary vein diversion produces cyanosis with left ventricular dilatation but without hypertrophy. It is proposed that abnormal loading characteristics of the left ventricle are responsible for the functional derangements that result from global ischemia.

Pediatric and adult lung transplantation for cystic fibrosis.

OBJECTIVE: This paper was undertaken to review the experience at our institution with bilateral sequential lung transplantation for cystic fibrosis. METHODS: Since 1989, 103 bilateral sequential lung transplants for cystic fibrosis have been performed (46 pediatric, 48 adult, 9 redo); the mean age was 21 +/- 10 years. Cardiopulmonary bypass was used in all but one pediatric (age <18) transplant, and in 15% of adults. RESULTS: Hospital mortality was 4.9%, with 80% of early deaths related to infection. Bronchial anastomotic complications occurred with equal frequency in the pediatric and the adult populations (7.3%). One- and 3-year actuarial survival are 84% and 61%, respectively (no significant difference between pediatric and adult age groups; average follow-up 2.1 +/- 1.6 years). Mean forced expiratory volume in 1 second increased from 25% +/- 9% before transplantation to 79% +/- 35% 1 year after transplantation. Acute rejection occurred 1.7 times per patient-year, with most episodes taking place within the first 6 months after transplantation. The need for treatment of lower respiratory tract infections occurred 1.2 times per patient in the first year after transplantation. Actuarial freedom from bronchiolitis obliterans was 63% at 2 years and 43% at 3 years. Redo transplantation was performed only in the pediatric population and was associated with an early mortality of 33%. Eight living donor transplants (four primary transplants, four redo transplants) were performed with an early survival of 87.5%. CONCLUSION: Patients with end-stage cystic fibrosis can undergo bilateral lung transplantation with morbidity and mortality comparable to that seen in pulmonary transplantation for other disease entities.

Use of aprotinin in pediatric lung transplantation.

BACKGROUND: Aprotinin has been shown to decrease perioperative bleeding in adults undergoing cardiac surgery. We evaluated its efficacy in reducing blood loss in pediatric lung transplantation. METHODS: Aprotinin was given to a group of pediatric lung transplant recipients (n = 24) identified as being at high risk for bleeding by virtue of preoperative diagnosis of cystic fibrosis or previous cardiothoracic operation (group 1). Comparison was made to a group of pediatric recipients (n = 19) believed to be at low risk for bleeding who did not receive aprotinin (group 2). All transplantations were accomplished with the use of cardiopulmonary bypass. RESULTS: No difference in intraoperative blood requirement was identified between groups (18 +/- 3 cc/kg [group 1] versus 30 +/- 8 cc/kg [group 2], p = 0.16). Neither postoperative blood transfusion requirement (12 +/- 5 cc/kg [group 1] versus 16 +/- 6 cc/kg [group 2], p = 0.55) nor chest tube output in the first 24 postoperative hours (43 +/- 9 cc/kg [group 1] versus 53 +/- 13 cc/kg [group 2], p = 0.55) was significantly different between groups. Reexploration for bleeding was required in 8% (2 of 25) in group 1 and 16% (3 of 19) in group 2 (p = 0.64). CONCLUSIONS: Aprotinin reduced the amount of perioperative hemorrhage in a group of pediatric patients at high risk for bleeding after lung transplantation. The magnitude of the effect could not be quantified but was sufficient to normalize the transfusion requirement to that of a low risk group of patients.

Long-term prostacyclin infusion to reduce pulmonary hypertension in a pediatric cardiac transplant candidate prior to transplantation.

Pulmonary hypertension represents a significant risk factor for peri-operative death in patients undergoing cardiac transplantation. Heart-lung transplantation is generally the only procedure available for patients whose pulmonary hypertension can not be reversed by conventional pharmacologic means. We present a pediatric patient with end-stage cardiac disease and refractory pulmonary hypertension who was treated with long-term intravenous prostacyclin. This resulted in a significant enough improvement in her hemodynamics to allow for successful cardiac transplantation alone.