Effects of inhaled nitric oxide following lung transplantation.

BACKGROUND: Lung transplantation offers an established therapeutic option for end-stage lung disease. It is associated with several complications, and early allograft failure is one of the most devastating among all. Different studies are focused on an attempt to minimize these complications, especially transplant failure. We aimed to evaluate the effects of inhaled nitric oxide (iNO) treatment in patients receiving lung transplantation. METHODS: Nine patients (six female, three male; mean age 42.9 +/- 15.8) requiring lung transplantation for end-stage pulmonary disease--chronic obstructive pulmonary disease (three patients), cystic fibrosis (three patients), scleroderma and systemic sclerosis (two patients), Eisenmenger's syndrome (one patient), and treated with iNO were included in this retrospective study. Hemodynamic data (mean arterial pressure, mean pulmonary arterial pressure, heart rate) and respiratory parameters were analyzed. Pretreatment data were compared with the post-iNO treatment data at 6-8 hours and 12-14 hours. RESULTS: The inhalation of nitric oxide was started with an initial dose of 40 parts per million (ppm) and the dose was gradually decreased until hemodynamic and pulmonary stability was achieved. Six patients underwent double-lung transplantation and three single-lung transplantations were performed. Cardiopulmonary bypass was used in seven patients. The iNO therapy was started before transplantation in five patients, after the procedure in four patients. Mean iNO therapy duration was 83.2 +/- 74.4 hours. The administration of iNO resulted in a significant reduction in mean pulmonary arterial pressure (36.8 +/- 15.8 mm Hg to 22 +/- 6.8 mm Hg at 6-8 hours and 22.8 +/- 7.96 mm Hg at 12-14 hours). Mean systemic arterial pressure slightly increased at 6-8 hours and significantly increased at 12-14 hours (70.2 +/- 6.3 mm Hg to 90.1 +/- 11.96 mm Hg). Heart rate was not significantly affected with the treatment. Arterial oxygenation improved with the treatment. All patients except one showed improvement of overall respiratory functions. The mean duration of mechanical ventilation was 12.8 +/- 10.9 days. Mortality occurred in one patient due to neurologic injury. NO(2) and methemoglobin levels were closely monitored during the treatment. Methemoglobinemia did not occur and NO(2) levels remained between 0.1 and 0.4 ppm. CONCLUSION: Nitric oxide inhalation for the prevention and treatment of early allograft failure in lung transplant recipients is encouraging. It is superior to other vasodilators with its selectivity to the pulmonary vasculature, while having no significant side effects on systemic circulation. It appears to improve gas exchange and oxygenation properties. Further prospective randomized studies will aid to standardize inhalation nitric oxide therapy.

Surgery for aortic root aneurysm in children: a 21-year experience in 50 patients.

BACKGROUND: Ascending aortic aneurysms are unusual in children and have received little attention to develop guidelines for management. This study reviewed our experience with 50 children who have undergone aortic root replacement for ascending aortic aneurysm. METHODS: A retrospective clinical review was conducted using hospital charts and office records. Patients or their physicians were contacted for follow-up and recent echocardiograms were obtained and reviewed. RESULTS: There was no operative or hospital mortality. Twenty-six children had aortic root replacement with a composite graft, 10 patients had replacement with a homograft aortic root, and 14 patients had a David II valve-sparing procedure. Factors related to late morbidity and mortality were analyzed. Long-term results were excellent in the 26 children receiving a composite graft. Twenty-three of these children were New York Heart Association class I (19) or II (4) at study closure. There were 3 late deaths (11, 16, and 17 years postoperative). Seven of 10 children receiving a homograft aortic root are long-term survivors and all 14 children having a valve-sparing procedure are alive. Generally, late results with the David II remodeling procedure have been good although 3 patients developed late aortic insufficiency and two required valve replacement. CONCLUSIONS: Aortic root replacement in children with aneurysms has low operative risk and good long-term results. Composite grafts in particular carry a low risk of endocarditis, thromboembolism, and hemorrhagic events. Homografts are suitable for small patients but lack durability. Late results with the David II remodeling valve-sparing procedure in children have been compromised by late root dilatation.

Pulmonary resection following lung transplantation.

BACKGROUND: The morbidity of lung transplantation is higher than other solid organ transplants. Little is known about the outcomes of patients who require pulmonary resection following lung transplantation. We reviewed our experience to evaluate and discern any variables affecting outcome of pulmonary resections performed following lung transplantation. METHODS: A retrospective review of the lung transplant database was performed. Data are presented as mean +/- standard error (median). RESULTS: A total of 136 lung transplants (80 single lung transplants [SLT], 55 bilateral lung transplants [BLT], and 3 heart-lung transplants [HLT]) were performed from August 1995 to February 2002. Twelve pulmonary resections, 7 lobectomies, and 5 wedge resections were performed on 11 patients. The indication for lobectomy was infection in 5 of 7 lobectomies (3 fungal, 2 bacterial), mass in 1 of 7, and infarction in 1 of 7. The indication for wedge resection was native lung hyperinflation in 4 of 5 wedge resections and mass in 1 of 5. The native lung was resected in 3 of 7 lobectomies and 4 of 5 wedge resections. An allograft lobectomy was performed following 1 SLT and 3 BLT and a wedge resection was performed after 1 SLT. The mean time to pulmonary resection was 12.4 +/- 3.9 (9.1) months. Survival postresection was 17.2 +/- 5.8 (8.3) months and 5 of 11 patients are still alive. There were no bronchial stump leaks following lobectomy. CONCLUSIONS: Major pulmonary resections can safely be performed following lung transplant. We recommend early intervention to optimize outcomes.

Pharmacological preconditioning ameliorates neurological injury in a model of spinal cord ischemia.

BACKGROUND: Pharmacological openers of mitochondrial ATP-sensitive potassium (mitoKATP) channels have been shown to mimic ischemic preconditioning (IPC) in both the brain and myocardium. We hypothesized that similar endogenous mechanisms exist in the spinal cord and that diazoxide, a potent mitoKATP opener, could reduce neurologic injury after aortic cross-clamping in a model of spinal cord ischemia. METHODS: The infra-renal aorta was cross-clamped in 45 male New Zealand white rabbits for 20 minutes. Control animals received no pretreatment. Diazoxide-treated animals were dosed (5 mg/kg) 15 minutes before cross-clamp. A third group underwent 5 minutes of IPC 30 minutes before cross-clamp. Two groups received KATP antagonists, 5-hydroxydecanoic acid (5-HD, 20 mg/kg) or glibenclamide (1.0 mg/kg), before diazoxide administration. Systemic hypotension was induced in a final group with excess isoflurane. Tarlov Scoring was used to assess neurologic function at 24 and 48 hours, after which, the spinal cords were procured for histopathological analysis. RESULTS: Tarlov scoring demonstrated marked improvement in the Diazoxide group compared with control at 24 hours (p < 0.02) and 48 hours (p < 0.009). Moreover, no further neurologic injury occurred in this group at 7 days. IPC-treated animals showed neurologic improvement but were not significantly different from controls. Further, administration of glibenclamide was effective in antagonizing diazoxide's protective effect. CONCLUSIONS: Administration of diazoxide resulted in significant improvement in neurologic outcome in this model. This protective effect improved outcome at both early and late time points. Further, the antagonistic effect of glibenclamide implicates diazoxide's ATP-dependent potassium channel agonism as the mechanism of protection. Overall, this study suggests that diazoxide may be useful in the prevention of neurologic injury after thoracic aneurysm surgery.

Application of haptic feedback to robotic surgery.

Robotic surgical systems have greatly contributed to the advancement of minimally invasive endoscopic surgery. However, current robotic systems do not provide tactile or haptic feedback to the operating surgeon. Under certain circumstances, particularly with the manipulation of delicate tissues and suture materials, this may prove to be a significant irritation. We hypothesize that haptic feedback, in the form of sensory substitution, facilitates the performance of surgical knot tying. This preliminary study describes evidence that visual sensory substitution permits the surgeon to apply more consistent, precise, and greater tensions to fine suture materials without breakage during robot-assisted knot tying.

Effect of sensory substitution on suture manipulation forces for surgical teleoperation.

Bilateral telemanipulation, which applies haptic feedback to the operator, is not yet available in most commercial robot-assisted surgical systems. We have shown in previous work that the lack of haptic (force or tactile) feedback is detrimental in applications requiring fine suture manipulation. In this paper, we study the effect of substituting direct haptic feedback with visual and auditory cues. Using the da Vinci robot from Intuitive Surgical, we observed the difference between applied forces during a knot tying procedure for four different sensory feedback substitution scenarios: no feedback, auditory feedback, visual feedback, and a combination of auditory and visual feedback. Our results indicate that visual feedback, which provides continuous force information, would improve robot-assisted performance during complex surgical tasks such as knot tying with fine sutures. Discrete auditory feedback gives additional useful support to the surgeon.

Effect of pulsatile and nonpulsatile flow on cerebral perfusion in patients with left ventricular assist devices.

BACKGROUND: Insertion of a left ventricular assist device (LVAD) is an accepted therapy for advanced heart failure patients. However, the effects on end-organ perfusion, including cerebral autoregulation, are unclear in the presence of reduced pulsatility. Therefore, the objective of this study was to determine whether cerebral autoregulation is impaired in patients with continuous-flow (CF) LVADs. METHODS: Dynamic cerebral autoregulation was assessed in both time-domain (autoregulatory index) and frequency-domain (transfer function analysis) analyses in 9 CF-LVAD subjects, 5 pulsatile LVAD subjects and 10 healthy controls, by evaluating mean arterial pressure (MAP) and cerebral blood flow velocity (CBFV) during a sit-stand maneuver at 0.05 Hz (10-second sit, 10-second stand). The autoregulatory index was calculated as the percent change in mean CBFV per mm Hg change in MAP. RESULTS: The magnitude of oscillation in MAP and CBFV was greater in subjects with pulsatile LVADs than either CF-LVADs or healthy controls (p = 0.065 for MAP, p = 0.004 for CBFV). The autoregulatory index and transfer function gain were similar among groups, indicating that dynamic cerebral autoregulation is preserved among patients with CF-LVADs. CONCLUSIONS: Cerebral blood flow in patients with CF-LVADs is comparable to that of healthy controls across a range of blood pressures. Patients with pulsatile devices have greater oscillations in MAP and CBFV. However, dynamic cerebral autoregulation is preserved among subjects with either type of device. Thus, the reduction in pulsatility afforded by CF-LVADs does not impair normal autoregulatory processes.

Sympathetic neural and hemodynamic responses to upright tilt in patients with pulsatile and nonpulsatile left ventricular assist devices.

BACKGROUND: Left ventricular assist devices (LVADs) are now widely accepted as an option for patients with advanced heart failure. First-generation devices were pulsatile, but they had poor longevity and durability. Newer generation devices are nonpulsatile and more durable, but remain associated with an increased risk of stroke and hypertension. Moreover, little is understood about the physiological effects of the chronic absence of pulsatile flow in humans. METHODS AND RESULTS: We evaluated patients with pulsatile (n=6) and nonpulsatile (n=11) LVADs and healthy controls (n=9) during head-up tilt while measuring hemodynamics and muscle sympathetic nerve activity. Patients with nonpulsatile devices had markedly elevated supine and upright muscle sympathetic nerve activity (mean±SD, 43±15 supine and 60±21 bursts/min at 60° head-up tilt) compared with patients with pulsatile devices (24±7 and 35±8 bursts/min; P<0.01) and controls (11±6 and 31±6 bursts/min; P<0.01); however, muscle sympathetic nerve activity was not different between patients with pulsatile flow and controls (P=0.34). Heart rate, mean arterial pressure, and total peripheral resistance were greater, whereas cardiac output was smaller, in LVAD patients compared with controls in both supine and upright postures. However, these hemodynamic variables were not significantly different between patients with pulsatile and nonpulsatile flow. CONCLUSIONS: Heart failure patients with continuous, nonpulsatile LVADs have marked sympathetic activation, which is likely due, at least in part, to baroreceptor unloading. We speculate that such chronic sympathetic activation may contribute to, or worsen end-organ diseases, and reduce the possibility of ventricular recovery. Strategies to provide some degree of arterial pulsatility, even in continuous flow LVADs may be necessary to achieve optimal outcomes in these patients.

Aortic root replacement in 372 Marfan patients: evolution of operative repair over 30 years.

BACKGROUND: We reviewed the evolution of practice and late results of aortic root replacement (ARR) in Marfan syndrome patients at our institution. METHODS: A retrospective clinical review of Marfan patients undergoing ARR at our institution was performed. Follow-up data were obtained from hospital and office records and from telephone contact with patients or their physicians. RESULTS: Between September 1976 and September 2006, 372 Marfan syndrome patients underwent ARR: 269 had a Bentall composite graft, 85 had valve-sparing ARR, 16 had ARR with homografts, and 2 had ARR with porcine xenografts. In the first 24 years of the study, 85% received a Bentall graft; during the last 8 years, 61% had a valve-sparing procedure. There was no operative or hospital mortality among the 327 patients who underwent elective repair; there were 2 deaths among the 45 patients (4.4%) who underwent emergent or urgent operative repair. There were 74 late deaths (70 Bentalls, 2 homograft, and 2 valve-sparing ARRs). The most frequent causes of late death were dissection or rupture of the residual aorta (10 of 74) and arrhythmia (9 of 74). Of the 85 patients who had a valve-sparing procedure, 40 had a David II remodeling operation; there was 1 late death in this group, and 5 patients required late aortic valve replacement for aortic insufficiency. A David I reimplantation procedure using the De Paulis Valsalva graft has been used exclusively since May 2002. All 44 patients in this last group have 0 to 1+ aortic insufficiency. CONCLUSIONS: Prophylactic surgical replacement of the ascending aorta in patients with Marfan syndrome has low operative risk and can prevent aortic catastrophe in most patients. Valve-sparing procedures, particularly using the reimplantation technique with the Valsalva graft, show promise but have not yet proven as durable as the Bentall.

Valve-sparing aortic root replacement: early experience with the De Paulis Valsalva graft in 51 patients.

BACKGROUND: Valve-sparing aortic root replacement for treatment of aortic sinus disease avoids the problems of prosthetic valves, but some patients suffer late valve incompetence as a result of leaflet distortion or annular dilatation. The reimplantation technique using the De Paulis Valsalva graft might improve late results of valve-sparing aortic root replacement by maintaining annular stability and re-creating sinuses that minimize leaflet stress. METHODS: Retrospective review was conducted of all patients at our institution who underwent valve-sparing aortic root replacement using the Valsalva graft. Clinical data were obtained from hospital and clinic charts and patient contacts; echocardiograms were analyzed for aortic root dimensions and valve function. RESULTS: Between May 2002 and June 2005, 51 patients underwent valve-sparing aortic root replacement using the reimplantation technique with the Valsalva graft. Mean age was 33 +/- 15 years; 22% (11 of 51) were children, and 80% (41 of 51) were male. Primary indication for surgery was root aneurysm in all patients. Preoperative mean root diameter was 5.0 +/- 0.5 cm. Marfan syndrome was present in 67% (34 of 51), and 10% (5 of 51) had the newly described Loeys-Dietz syndrome. There were no operative or late deaths, and no patient required reoperation for bleeding. At mean follow-up of 1.8 years, there were no episodes of endocarditis or thromboembolism. Echocardiograms showed stability of the annulus and root dimensions on follow-up. No patient had more than 0 to 1+ aortic insufficiency or progression of aortic insufficiency. All were in New York Heart Association class I. CONCLUSIONS: Valve-sparing aortic root replacement using the Valsalva graft and reimplantation technique has excellent early results. Preservation of valve competence is encouraging, but long-term results will determine whether the anatomic design of this aortic root prosthesis is superior for preservation of valve integrity.

Determining the utility of temporary pacing wires after coronary artery bypass surgery.

BACKGROUND: Temporary epicardial pacing wires are used routinely after coronary artery bypass graft (CABG) surgery and can cause rare, catastrophic complications. This study's purpose was to identify patient characteristics predicting the need for pacing after CABG surgery with the potential to limit their utilization. METHODS: This prospective observational study involved 290 consecutive patients undergoing CABG at our institution from August 2000 to January 2001. Sixty-eight patients were excluded for the following reasons: off-pump CABG, preoperative pacemaker, no pacing wire placement, or incomplete follow-up. Among the remaining 222 patients, the incidence of pacing during the postoperative period was recorded. Univariate and independent multivariate predictors for postoperative pacing were determined using medical records, the Johns Hopkins Hospital cardiac surgery database and the Society of Thoracic Surgery database. RESULTS: In the postoperative period, 19 of 222 patients (8.6%) required pacing. Univariate analysis identified age, cardiomegaly, preoperative antiarrhythmic therapy, diabetes mellitus, preoperative arrhythmia, inotropic agents leaving the operating room, and pacing initialized at the separation from cardiopulmonary bypass as predictors of the need for postoperative pacing. Only diabetes mellitus, preoperative arrhythmia, and pacing utilized to separate from bypass were found to be significant on multivariate analysis. Using this model, if we exclude the patients with any of these three risk factors, only 2.6% of them would have required pacing. CONCLUSIONS: Few patients require temporary epicardial pacing after routine CABG. This study identified specific predictors for postoperative pacing requirements and provides criteria for the selective use of epicardial pacing wires after CABG.

Impact of 24 h continuous hypothermic perfusion on heart preservation by assessment of oxidative stress.

INTRODUCTION: Despite investigating numerous solutions, additives, and techniques over the last two decades, extending donor heart preservation beyond 4-6 h has not been achieved. Hypothermic heart preservation (HP) induces oxidative stress (OS) with reactive oxygen species (ROS) production, causing DNA cleavage and impairing repair. Quantification of cardiomyocyte concentrations of DNA damage by-products (8-oxoG) and mismatch repair enzymes (MYH, OGG-1, MSH2) reflects the severity of OS. If increased repair enzyme production is insufficient to repair injury, cell death occurs and functional outcomes are impacted. We investigated continuous hypothermic perfusion (CHP), a new form of HP, and the mechanism of injury associated with hypothermic storage, by assessing functional outcome and OS after allotransplantation of canine hearts. METHODS: Fourteen canine hearts were harvested using standard techniques after baseline echocardiograms and haemodynamic parameters were obtained. The hearts were implanted after 24 h CHP (n = 10) or 4 h static preservation (SP; n = 4). After weaning from cardiopulmonary bypass (CPB), recipients were kept alive for 6 h. Repeat echocardiograms and haemodynamic parameters were obtained. Quantification of MYH, OGG-1, and MSH2 concentrations were performed on biopsies using immunohistochemistry and Western blot analysis. RESULTS: Twelve out of 14 hearts (8/10 CHP; 4/4 SP) were successfully weaned on moderate inotropic support. Post-implant echocardiogram, completed in 6/10 CHP and 2/4 SP hearts, demonstrated hyperdynamic function and normal wall motion. The expression and activity of DNA repair enzymes was identical between normal baseline and CHP hearts. CONCLUSION: CHP reduces OS associated with prolonged hypothermic preservation and may allow longer preservation periods without compromising function. CHP offers several potential advantages: (1) resuscitation of non-beating heart donor organs, (2) time for HLA tissue typing, (3) facilitate interventions improving graft function, and (4) increased organ sharing.

Effect of bronchial artery blood flow on cardiopulmonary bypass-induced lung injury.

Cardiovascular surgery requiring cardiopulmonary bypass (CPB) is frequently complicated by postoperative lung injury. Bronchial artery (BA) blood flow has been hypothesized to attenuate this injury. The purpose of the present study was to determine the effect of BA blood flow on CPB-induced lung injury in anesthetized pigs. In eight pigs (BA ligated) the BA was ligated, whereas in six pigs (BA patent) the BA was identified but left intact. Warm (37 degrees C) CPB was then performed in all pigs with complete occlusion of the pulmonary artery and deflated lungs to maximize lung injury. BA ligation significantly exacerbated nearly all aspects of pulmonary function beginning at 5 min post-CPB. At 25 min, BA-ligated pigs had a lower arterial Po(2) at a fraction of inspired oxygen of 1.0 (52 +/- 5 vs. 312 +/- 58 mmHg) and greater peak tracheal pressure (39 +/- 6 vs. 15 +/- 4 mmHg), pulmonary vascular resistance (11 +/- 1 vs. 6 +/- 1 mmHg x l(-1) x min), plasma TNF-alpha (1.2 +/- 0.60 vs. 0.59 +/- 0.092 ng/ml), extravascular lung water (11.7 +/- 1.2 vs. 7.7 +/- 0.5 ml/g blood-free dry weight), and pulmonary vascular protein permeability, as assessed by a decreased reflection coefficient for albumin (sigma(alb); 0.53 +/- 0.1 vs. 0.82 +/- 0.05). There was a negative correlation (R = 0.95, P < 0.001) between sigma(alb) and the 25-min plasma TNF-alpha concentration. These results suggest that a severe decrease in BA blood flow during and after warm CPB causes increased pulmonary vascular permeability, edema formation, cytokine production, and severe arterial hypoxemia secondary to intrapulmonary shunt.

Results of aortic valve-sparing operations: experience with remodeling and reimplantation procedures in 65 patients.

BACKGROUND: Valve-sparing operations for aortic root aneurysms are increasing in frequency, but techniques and results are still in evolution. We reviewed our experience with 65 patients (adults and children) who had this operation at our institution to determine early and late outcomes. METHODS: A retrospective clinical review was undertaken using hospital records, clinical and echocardiographic, computed tomography, magnetic resonance imaging data, and telephone interviews with patients and their physicians. RESULTS: Between July 1994 and December 2002, 65 patients (46 adults and 19 children) underwent a valve-sparing operation for aortic root aneurysm. Forty-four of the patients had the Marfan syndrome; the remaining 21 had either a nonspecific connective tissue disorder (14 patients) or a miscellaneous disease process such as Ehlers-Danlos syndrome (7 patients). Fifty-eight (89%) had a David II (remodeling) procedure and 7 had a David I (reimplantation) procedure. The DePaulis "Valsalva graft" was used in six of the David I patients. There were no operative or hospital deaths; only one late death occurred in an adult due to salmonella meningitis. Overall, survival was 100% at one year and 98% at 3 and 5 years. Ten patients (7 adults and 3 children) developed significant late aortic insufficiency (AI). Nine of these patients had a David II procedure and in 8 of these cases, AI was secondary to significant late annular dilatation. One of the 10 patients developed late AI 8.2 years after a David I procedure; his AI was secondary to aortic leaflet extension and prolapse. Six of the 10 patients who developed significant late AI required aortic valve replacement (4 adults and 2 children). Freedom from late aortic valve replacement (AVR) in this series of 65 patients was 91% at 3 and 84% at 5 years. At the close of this study, 58 patients were New York Heart Association (NYHA) class I and 6 were NYHA class II; no patients were class III or IV. There were no episodes of endocarditis or clinically significant thromboembolism. CONCLUSIONS: Valve-sparing operations provide satisfactory results for many patients with an aortic root aneurysm, but the David II remodeling procedure has a greater risk of late annular dilatation and AI. The David I reimplantation procedure utilizing the DePaulis Valsalva graft may obviate this problem.