Inhaled nitric oxide for pulmonary hypertension after heart transplantation.

BACKGROUND: Recipient pulmonary hypertension due to chronic congestive heart failure is a major cause of right ventricular (RV) dysfunction after heart transplantation. We hypothesized that inhaled nitric oxide (NO), in the postoperative period, would a) selectively reduce pulmonary vascular resistance and improve RV hemodynamics and b) reduce the incidence of RV dysfunction compared with a matched historical group. METHODS: Sixteen consecutive adult heart transplant recipients with lowest mean pulmonary artery (PA) pressures >25 mmHg were prospectively enrolled. Inhaled NO at 20 parts per million (ppm) was initiated before termination of cardiopulmonary bypass (CPB). At 6 and 12 hours after CPB, NO was stopped for 15 minutes and systemic and pulmonary hemodynamics were measured. RV dysfunction was defined as central venous pressure >15 mmHg and consistent echocardiographic findings. The incidence of RV dysfunction and 30-day survival in this group was compared with a historical cohort of 16 patients matched for pulmonary hypertension. RESULTS: Discontinuation of NO for 15 minutes at 6 hours after transplantation resulted in a significant rise in mean PA pressure, pulmonary vascular resistance (PVR), and RV stroke work index. Systemic hemodynamics were not affected by NO therapy. One patient in the NO-treated group, compared with 6 patients in the historical cohort group, developed RV dysfunction (P< .05). The 30-day survival in the NO-treated group and the historical cohort group were 100% and 81%, respectively (P> .05). CONCLUSION: In heart transplant recipients with pulmonary hypertension, inhaled NO in the postoperative period selectively reduces PVR and enhances RV stroke work. Furthermore, NO reduces the incidence of RV dysfunction in this group of patients when compared with a historical cohort matched for pulmonary hypertension. Inhaled NO is a useful adjunct to the postoperative treatment protocol of heart transplant patients with pulmonary hypertension.

Does the addition of albumin to the prime solution in cardiopulmonary bypass affect clinical outcome? A prospective randomized study.

Colloid solution is commonly used to increase the oncotic pressures of priming solutions used in the cardiopulmonary bypass circuit. To study the effectiveness of this practice, we prospectively randomized 100 adult patients undergoing cardiac operations to receive Ringer's lactate solution plus 50 gm of albumin (group A) or Ringer's lactate solution alone (group B) as the prime solution for the bypass circuit. Personnel involved in the management of these patients were blinded concerning the group to which the patients had been randomized. Forty clinical parameters related to perioperative fluid balance, cardiopulmonary function, and renal function were studied. Although group B received a larger volume of crystalloid solution intraoperatively (p less than 0.05), had a lower mean cardiac filling pressure (p less than 0.05), and had a higher hematocrit value (p less than 0.05) in the immediate postoperative period, all mean values for both groups were within the normal range. There were no differences between the two groups with regard to postoperative clinical parameters of cardiopulmonary and renal function, nor was outcome affected by the addition of albumin to the prime solution. We conclude that there is no clinically detectable advantage for the practice of adding 50 gm of albumin to the priming solution of bypass circuits in adults undergoing cardiac operations. Routinely supplementing the bypass prime solution with albumin adds significant cost, estimated to be approximately $10,000 per 100 cases, without demonstrable clinical benefits. Whether this practice can be of value in selected cases needs to be further studied.

The reversibility of impaired mucociliary function after lung transplantation.

Impairment of mucociliary function occurs after lung transplantation and may predispose patients to repeated pulmonary infections. The purpose of this study is to determine whether and how soon such mucociliary function may recover. Ten dogs underwent left lung autotransplantation. Within 3 weeks five of these dogs underwent study for proximal airway clearance by observation through a bronchoscope of the movement of carbon particles placed at different locations on the tracheobronchial mucosa. The mechanical properties of collected mucus from specific sites were determined by magnetic rheometry. The right lung, which was not operated on, served as a paired control. Similar studies were conducted in the remaining five dogs at 12 weeks after autotransplantation. Lung autotransplantation caused significant depression of proximal airway clearance and a 35% increase in mucous rigidity (p = 0.05) soon after operation. At 12 weeks after operation, there was a partial recovery of proximal airway clearance. Mucous changes were no longer consistent. Histologic and electron microscopic examinations initially revealed focal denudation of ciliated cells and loss of the bronchial glands. At 12 weeks there was a regeneration of cilia and a reappearance of the bronchial glands. We conclude that the mucociliary function, observed to be depressed early after lung autotransplantation, recovers partially during the late postoperative period. Thus the mucociliary functional recovery should be attributed to revascularization rather than to reinnervation, since the latter is unlikely to occur during this period.

Mucociliary function in autotransplanted, allotransplanted, and sleeve resected lungs.

Tracheobronchial mucociliary function in dogs that underwent left upper sleeve lobectomy was compared with that of dogs that underwent left lung autotransplantation or allotransplantation (n = 5 each). Proximal airway clearance was measured by observing the movement of carbon particles through a bronchoscope. Preoperative and postoperative clearance rates for the right lungs in these dogs were unchanged. Although preoperative clearance rates in the transplanted left lungs were comparable with those of the right lungs, these left lungs were unable to clear the carbon particles during a 15-minute observation period 3 weeks postoperatively. In contrast, preoperative and postoperative clearance rates for the dogs that underwent sleeve resection were unchanged for both lungs. Mucus rigidity was studied by microrheometry and was found to be significantly increased postoperatively for samples collected from the autotransplanted and allotransplanted lungs than for samples collected from the untreated right lungs. These changes in mucus were noted for forces representing both normal ciliary beat and coughing. Viscoelastic properties of mucus were not significantly altered after sleeve lobectomy. Microscopic study showed squamous cell metaplasia and relative disappearance of bronchial glands distal to the anastomosis in all transplanted lungs. These changes were less pronounced in the sleeve resected bronchi. We conclude that changes in rheologic characteristics of mucus can impair mucociliary clearance and may be related to denervation after lung transplantation. Bronchial devascularization may have an additional effect of altering mucosal structures and function in the early postoperative period after lung transplantation. These effects are avoided by preserving peribronchial tissue in sleeve resection.

The use of donor hearts with left ventricular hypertrophy.

BACKGROUND: We reviewed 37 patients who received donor hearts with left ventricular hypertrophy (LVH) to determine which factors affected outcomes. METHODS: Thirty-seven patients underwent orthotopic heart transplantation (1994 through 1998) with donor hearts qualified as having LVH by echocardiography (EC) and/or electrocardiogram (ECG). We performed univariate analysis on 18 donor and recipient risk factors for mortality. We calculated 12-month survival curves using Kaplan-Meier estimates and compared them using the log-rank test. A contemporaneous cohort of 221 patients who received optimal hearts within the same institution served as a control for survival. RESULTS: Median follow-up was 18 months (1 to 53). Median recipient age was 58 ye ars (25 to 75), and median donor age was 47 years (12 to 63). Median donor/recipient height and weight ratios were 1.01 (0.9 to 1.19) and 1.16 (0.77 to 2.02), respectively. Two-month survival was 86.4%, and 12-month survival was 73.0%. Survival for the control group was 91. 6% at 2 months and 86.9% at 12 months. Clinically inferior survival curves were observed when donors had known hypertension (n = 17, 95% vs 71% at 2 months, 76% vs 65% at 12 months), ischemia > 180 minutes (n = 18, 95% vs 72% at 2 months, 78% vs 65% at 12 months), LVH by ECG (n = 10, 85% vs 80% at 2 months, 77% vs 56% at 12 months), and greater than mild or unknown ECHO grade (n = 18, 89% vs 72% at 2 months, 84% vs 59% at 12 months, p = 0.11). CONCLUSIONS: Donor hearts with mild LVH may be used selectively, particularly if there are no ECG criteria and if ischemia time is short. Caution is indicated for donors with documented history of hypertension. Precise measurement of LV wall thickness by EC is needed in all donors to estimate severity and to complement ECG interpretation.

Use of OKT3 for acute myocarditis in infants and children.

Acute viral myocarditis triggers an autoimmune phenomenon that aggressive immunosuppressive therapy with monoclonal OKT3 may suppress. We treated 5 patients, aged 15 months to 16.5 years, who had acute viral myocarditis and left ventricular ejection fraction (LVEF) of 5% to 20%, with a combination immunosuppressive regimen that included OKT3, intravenous immunoglobulin, methylprednisone, cyclosporine, and azathioprine. Within 2 weeks of therapy, all patients demonstrated normalization of LVEF to 50% to 74%, and on mid-term follow-up, we have found no recurrence of heart failure or progression to dilated cardiomyopathy. In patients with severe acute myocarditis, aggressive immunosuppressive regimen based on OKT3 is safe and may inhibit or reverse the immune response, resulting in dramatic improvement in myocardial function.

Use of leukocyte depletion to decrease injury after lung preservation and rewarming ischemia: an experimental model.

BACKGROUND: Hypothermia is critical for proper lung preservation. Ideally, the lungs should be maintained at the optimal preservation temperature during the entire ischemic interval. Lung rewarming during implantation is commonly observed. This study was undertaken to investigate the severity of rewarming ischemia on preservation injury and the possibility of minimizing this by use of leukocyte depletion during initial reperfusion. METHODS: Four experimental groups were tested as follows: neonatal piglet heart-lung blocks were either (1) placed on an isolated, blood-perfused, working heart-lung circuit without intervening ischemia (control, n = 6), (2) reperfused on the circuit with whole blood (WB, n = 6) after 13 hours of preservation, (3) reperfused with WB after 12 hours of preservation and 1 hour of rewarming (RWB, n = 5), or (4) reperfused with leukocyte-depleted blood for an initial 10 minutes followed by WB, after 12 hours of preservation and 1 hour of rewarming (n = 6). All groups were studied for 4 hours. RESULTS: The partial pressure of arterial oxygen and lung compliance were significantly lower in the RWB group than in controls (113.8+/-33.1 vs 417.3+/-6.2 mm Hg, p < 0.01; and 0.8+/-0.2 vs 2.9+/-0.4 ml/cm H2O, p < 0.05, respectively). Pulmonary vascular resistance and lung wet/dry weight ratios were significantly higher in the RWB group than in controls (15884.1+/-11354.8 vs 6108.3+/-1309.9 dyne x sec x cm[-5], p < 0.05; and 7.13+/-0.24 vs 5.82+/-0.35, p < 0.05, respectively). The WB and leukocyte-depleted groups did not differ significantly from controls for any measured parameter. CONCLUSIONS: This model confirms that rewarming ischemia during lung implantation exacerbates reperfusion injury. Leukocyte-depleted reperfusion as tested for a short period of time (10 minutes) ameliorates this injury and therefore should be considered for clinical lung transplantation.

Improved survival in patients with acute myocarditis using external pulsatile mechanical ventricular assistance.

BACKGROUND: Acute myocarditis remains a disease with a variable clinical course, from full ventricular recovery to complete heart failure; to date, few cases have been reported that describe the efficacy of temporary mechanical ventricular assistance for its treatment. METHODS: We evaluated the voluntary world registry with the use of an external pulsatile ventricular assist device (the ABIOMED BVS 5000 [BVS]) for acute myocarditis to determine the impact of mechanical ventricular assistance on outcome. Variables analyzed included patient demographics, serum chemistries, and overall hemodynamics prior to BVS, while on BVS support, and after BVS explanation. Postoperative parameters included re-operation, bleeding, respiratory failure, renal failure, and infections, neurologic, or embolic events. RESULTS: Eighteen patients in the ABIOMED world registry underwent BVS implantation for myocarditis; 11 (61.1%) had complete pre-operative and hemodynamic data for analysis. Patients were supported for 13.2 +/- 17.0 days, after which time 7 (63.6%) patients survived to explanation of the device and 2 (18.2%) underwent transplantation. Elevated admission serum chemistries (blood ureanitrogen [BUN], creatinine, transaminases) and hemodynamics (central venous pressure [CVP], mean pulmonary arterial pressure [PAP], pulmonary capillary wedge pressure [PCW], cardiac index [CI], all normalized during the period of device support. Estimated ejection fractions in the 7 explanted patients ranged between 50 to 60% at routine evaluation 3 years after device removal. CONCLUSIONS: Temporary mechanical ventricular assistance represents an efficacious therapy for acute myocarditis in patients with hemodynamic decompensation despite maximal medical therapy. Failure to achieve full ventricular recovery while on device support still allows for other surgical alternatives, including implantation of a long-term implantable ventricular assist device, or cardiac transplantation.

Cell transplantation for myocardial repair: an experimental approach.

Myocardium lacks the ability to regenerate following injury. This is in contrast to skeletal muscle (SKM), in which capacity for tissue repair is attributed to the presence of satellite cells. It was hypothesized that SKM satellite cells multiplied in vitro could be used to repair injured heart muscle. Fourteen dogs underwent explantation of the anterior tibialis muscle. Satellite cells were multiplied in vitro and their nuclei were labeled with tritiated thymidine 24 h prior to implantation. The same dogs were then subjected successfully to a myocardial injury by the application of a cryoprobe. The cells were suspended in serum-free growth medium and autotransplanted within the damaged muscle. Medium without cells was injected into an adjacent site to serve as a control. Endpoints comprised histology using standard stains as well as Masson trichrome (specific for connective tissue), and radioautography. In five dogs, satellite cell isolation, culture, and implantation were technically satisfactory. In three implanted dogs, specimens were taken within 6-8 wk. There were persistence of the implantation channels in the experimental sites when compared to the controls. Macroscopically, muscle tissue completely surrounded by scar tissue could be seen. Masson trichrome staining showed homogeneous scar in the control site, but not in the test site where a patch of muscle fibres containing intercalated discs (characteristic of myocardial tissue) was observed. In two other dogs, specimens were taken at 14 wk postimplantation. Muscle tissue could not be found. These preliminary results could be consistent with the hypothesis that SKM satellite cells can form neo-myocardium within an appropriate environment. Our specimens failed to demonstrate the presence of myocyte nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Short-term bridge to transplant using the BVS 5000 in a 22-kg child.

The availability of pulsatile mechanical assist devices for bridge to transplant in pediatric patients is limited owing to the patients' small sizes. Pulsatile devices offer potential advantages over nonpulsatile devices but the risk of hypertensive bleeding must be balanced against that of device thrombosis. We describe our experience using the BVS 5000 external pulsatile device in an 8-year old patient with a body surface area of 0.88 m2.

Minimally invasive mechanical cardiac support without extracorporeal membrane oxygenation in children awaiting heart transplantation.

BACKGROUND: Mechanical cardiac assist for small children (< 30 kg) requiring bridge strategy to orthotopic heart transplantation often requires sternotomy for cannulation access to ensure perfusion to the aortic arch. Extracorporeal membrane oxygenation (ECMO) through neck cannulation is an option in very small (< 10 kg) patients, but the risk of stroke is increased in larger children. Another disadvantage is poor decompression of the left atrium, which can cause persistent pulmonary edema. METHODS: Two cases are used to illustrate two methods of avoiding sternotomy during mechanical assist in children with dilated cardiomyopathy. One of these approaches avoids the need for extracorporeal oxygenation. RESULTS: Decompression of the left-sided chambers with a left atrial cannula decreased pulmonary edema and improved pulmonary function. CONCLUSIONS: Pediatric patients with dilated cardiomyopathy may benefit from a left ventricular assist technique using a centrifugal pump, which avoids the neck vessels and sternotomy, as well as ECMO.

Percutaneous endoscopic tracheostomy.

Bedside percutaneous tracheostomies are increasingly performed. This avoids patient transport to the operating room. Complications of this procedure are largely related to the blind nature of the technique. After laboratory studies, 4 patients underwent percutaneous endoscopic guided tracheostomy in a selective clinical trial. There were no procedure-related complications. Endoscopic guidance ensures precise low tracheostomy position, prevents paratracheal tube misplacement, and avoids inadvertent injuries.

Institutional experience with a protocol of early primary repair of double-outlet right ventricle.

BACKGROUND: Our institution has adopted a protocol of primary repair for all patients with double-outlet right ventricle. METHODS: Since May 1989, 24 consecutive neonates and infants with double-outlet right ventricle and atrioventricular concordance (median age, 4 months) underwent anatomic biventricular repair. One patient (4%) received prior pulmonary artery banding but was still repaired as a neonate at 22 days of age. Twelve patients had a subaortic ventricular septal defect (VSD), 5 patients a subpulmonary VSD, 3 patients doubly committed VSD, and 4 patients a noncommitted VSD. Sixty-nine of 72 associated lesions were repaired simultaneously. Four types of repairs were used: intraventricular rerouting in 16 patients, arterial switch operation with VSD closure into the pulmonary artery in 4 patients, Rastelli-type repair with extracardiac conduit in 3 patients, and the Damus-Kaye-Stansel repair with concomitant repair of aortic arch obstruction in 1 patient. Ventricular septal defect enlargement was necessary in 15 patients. Repair of subpulmonary stenosis and of subaortic stenosis was carried out in 13 and 4 patients, respectively. Three patients underwent simultaneous repair of aortic arch obstruction with no mortality. Two of the patients with noncommitted VSD had simultaneous repair of complete atrioventricular canal and repair of severe pulmonary venous obstruction. RESULTS: The perioperative mortality was 8% (2 patients, and there was one late death (4%). Two patients (9%) underwent early successful reoperations (5 and 8 weeks postoperatively). The two reoperations were for residual VSD (1 patient) and severe mitral regurgitation (1 patient). All 21 survivors are alive at a mean follow-up of 40 months (range, 7 months to 6 years). The estimated 5-year actuarial survival is 88%, with no deaths after 2 months postoperatively. Ninety-five percent of long-term survivors have no restriction of physical activities because of cardiac status and are receiving no cardiac medications. CONCLUSIONS: An institutional protocol of early anatomic biventricular repair of double-outlet right ventricle in infants and neonates achieves excellent survival, making palliative operations unnecessary. Associated lesions should be repaired simultaneously. The complexity of these malformations requires a highly individualized and flexible surgical approach.

Mechanical assist strategy using the BVS 5000i for patients with heart failure.

BACKGROUND: The BVS 5000i external pulsatile assist device is used to support patients with reversible cardiogenic shock. Its low cost and potential for insertion without cardiopulmonary bypass make it an attractive option. METHODS: Nineteen status I patients failing inotropic support were treated with the BVS 5000i with the intention of short-term bridge to transplant. Fourteen patients received left ventricular support whereas 5 received biventricular support. Cardiopulmonary bypass was used in less than 50% of patients. RESULTS: Median support time was 7 days. The 2 myocarditis patients were weaned from support. Twelve patients were transplanted and there were 5 deaths on support. Overall 14 of 19 were transplanted or weaned. One-year survival was 79%. Median hospital stay was 31 days. CONCLUSIONS: The BVS 5000i can be used for short-term mechanical assist toward transplantation in selected patients for whom a donor can be expected soon. The device may provide a cost-effective, short-term strategy to optimize end-organ function before orthotopic heart transplant, particularly for patients who are predictably not ideal to be discharged with implantable left ventricular assist device treatment.

Extracorporeal membrane oxygenation for cardiac support in pediatric patients.

Extracorporeal membrane oxygenation (ECMO) has been used for pediatric cardiac support in settings of expected mortality due to severe myocardial dysfunction. We reviewed the records of 34 children (<18 years) placed on ECMO between March 1995 and May 1999. Demographic, cardiac, noncardiac, and outcome variables were recorded. Data were subjected to univariate analysis to define predictors of outcome. Eighteen patients were placed on ECMO after cardiac surgery (Group A); seven of 18 were weaned off ECMO, and four survived to discharge (22%). Thirteen patients were placed on ECMO as a bridge to cardiac transplantation (Group B), six of 13 received a heart transplant, one recovered spontaneously, and six survived to discharge (46%). Three patients were placed on ECMO for failed cardiac transplantation while awaiting a second transplant (Group C); one recovered graft function, two received a second heart transplant, and two of three survived (66%). The primary cause of death was multiorgan system failure (68%). Group A patients supported on ECMO for more than 6 days did not survive. Mediastinal bleeding complications and renal failure requiring dialysis were associated with nonsurvival. We conclude that ECMO as a bridge to cardiac transplant was more successful than ECMO support after cardiotomy. Mediastinal bleeding and renal failure were associated with poor outcome. Recovery of cardiac function occurred within the first week of ECMO support if at all. Longer support did not result in survival without transplantation.

[Psycho-affective and relational aspects of children with congenital cardiopathy]. / Aspetti psico-affettivi e relazionali nei bambini affetti da cardiopatia congenita.

The psychological and relational problems present in pediatric patients with congenital cardiac anomalies and in their families are reviewed based on an analysis of the current literature and on the personal experience of the authors. The need for all caretakers, especially the cardiologist and the cardiac surgeon, to be aware of these critical aspects is emphasized. The psychological experience of the patient and of his family is thoroughly addressed. Moreover, the complex relationship that developed between the family and the physician as a result of the family's expectations, requests and unconscious projections are discussed.