Emergency pulmonary autograft mitral valve replacement in a child.

Mitral valve replacement in small children imposes significant clinical difficulties because of the relatively small mechanical prosthetic valves required and the need for lifelong anticoagulation therapy. A child weighing 10.4 kg presented with thrombosis of her 19-mm mechanical mitral prosthesis 4 weeks after implantation despite appropriate oral anticoagulation therapy. An emergency mitral valve replacement with a pulmonary autograft was successfully performed with encouraging short-term results.

Reoperative homograft right ventricular outflow tract reconstruction.

BACKGROUND: Homografts are implanted in the right ventricular outflow tract (RVOT) of children, with the knowledge that reoperation might be required. We reviewed 14 years of homograft RVOT reconstruction to assess the feasibility of homograft replacement and to determine risk factors for homograft survival. METHODS: From February 1985 through March 1999, 223 children (age 5 days to 16.9 years) underwent primary RVOT reconstruction with an aortic or pulmonary homograft. Of these, 35 patients underwent homograft explant at the implanting hospital with insertion of a second homograft from 2 months to 13.3 years after the first implantation. The primary operation and reoperation patient groups were compared with regard to incidence of early death, late death, homograft-related intervention without explant, and homograft explant. RESULTS: Actuarial survival and event-free curves for initial and replacement homografts were not significantly different. Univariable analysis was performed for the following risk factors: weight (p < 0.0001), age (p < 0.003), homograft diameter (p < 0.0001), homograft type (p < 0.01), surgery date (not significant [NS]), gender (NS), Blood Group match (NS), and type of distal anastomosis (NS). Multivariable analysis of significant univariable risks revealed small homograft diameter to be a significant risk factor (p < 0.001) for replacement. CONCLUSIONS: The RVOT homografts eventually require replacement. Patient and homograft survival for replacement homografts is similar to primary homografts. Reoperative homograft RVOT reconstruction is possible, with reasonably low morbidity and mortality.

Utility of extracorporeal membrane oxygenation for early graft failure following heart transplantation in infancy.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is widely used for postcardiotomy cardiogenic shock in children. However, the efficacy of ECMO for early post-heart transplant graft failure in infants has not been reported. Our aims were to determine: (1) the utility of ECMO in infants with severe donor-heart dysfunction, (2) predictors for requiring ECMO, and (3) the long-term outcome of surviving ECMO patients. METHODS: All infants (age < 6 months at listing) undergoing heart transplantation were reviewed. Diagnostic categories were hypoplastic left heart syndrome (HLHS) and non-HLHS (complex congenital heart disease and cardiomyopathies). Continuous and categorical comparisons were by Wilcoxon's rank sum test and Fisher's exact test respectively. RESULTS: 14 (12 HLHS, 2 non-HLHS) of 63 (46 HLHS, 17 non-HLHS) infants were placed on ECMO. Ten patients (71%) were successfully weaned from ECMO and 8 (57%) were discharged alive. All ECMO hospital survivors remain alive (mean follow-up 36.2 +/- 21.4 months, range 13.1-77.6 months). Mean duration of ECMO support was 68 hours in weaned patients vs 144 hours (p = 0.19) in nonweaned patients, and 64 hours in survivors vs 123 hours (p = 0.35) in nonsurvivors. ECMO deaths were due to sepsis (n = 3), intractable pulmonary hypertension (n = 2), and intracranial bleed (n = 1). Neurologic deficits occurred in 2 survivors. Median ICU and hospital stays for ECMO survivors were 29 and 33 days vs 7 (p = 0.0003) and 9 (p = 0.0004) days for non-ECMO patients. Age listed, age transplanted, wait time, body weight, donor/recipient weight ratio, total ischemia time, and diagnosis did not predict the need for ECMO. CONCLUSIONS: (1) ECMO is useful for post-heart transplant circulatory support in infants with early graft failure. (2) All survivors were weaned in fewer than 4 days. (3) Three-year survival of ECMO hospital survivors has been high, but neurologic complications are prevalent.

Pulmonary artery compression by a giant aortocoronary vein graft aneurysm.

Late failure of saphenous vein aortocoronary bypass grafts is predominantly due to vein graft atherosclerotic disease. Rarely, saphenous vein aortocoronary bypass grafts undergo aneurysmal degeneration. We report a case of a giant true aneurysm of a saphenous vein aortocoronary bypass graft producing right heart failure from main pulmonary artery compression.

Secondary pulmonary hypertension does not adversely affect outcome after single lung transplantation.

OBJECTIVE: Primary and secondary pulmonary hypertension have been associated with poor outcomes after single lung transplantation. Some groups advocate double lung transplantation and the routine use of cardiopulmonary bypass during transplantation in this population. However, the optimal procedure for these patients remains controversial. The goal of our study was to determine the safety of single lung transplantation without cardiopulmonary bypass in patients with secondary pulmonary hypertension. METHODS: We retrospectively reviewed 76 consecutive patients with pulmonary parenchymal disease who underwent single lung transplantation from 1992 to 1998. Recipients were stratified according to preoperative mean pulmonary artery pressure. Secondary pulmonary hypertension was defined as parenchymal lung disease with a preoperative mean pulmonary artery pressure of 30 mm Hg or more. Patients with primary pulmonary hypertension or Eisenmenger's syndrome were excluded from analysis. RESULTS: Eighteen of 76 patients had secondary pulmonary hypertension. No patient with secondary pulmonary hypertension required cardiopulmonary bypass, whereas 1 patient without pulmonary hypertension required bypass. After the operation, no significant differences were seen in lung injury as measured by chest radiograph score and PaO(2)/FIO(2) ratio, the requirement for inhaled nitric oxide, the length of mechanical ventilation, the intensive care unit or hospital length of stay, and 30-day survival. There were no differences in the forced expiratory volume in 1 second or 6-minute walk at 1 year, or the incidence of rejection, infection, or bronchiolitis obliterans syndrome greater than grade 2. Survival at 1, 2, and 4 years after transplantation was 86%, 79%, and 65%, respectively, in the low pulmonary artery pressure group and 81%, 81%, and 61%, respectively, in the group with secondary pulmonary hypertension (P >.2). CONCLUSION: We found that patients with pulmonary parenchymal disease and concomitant secondary pulmonary hypertension had successful outcomes as measured by early and late allograft function and appear to have acceptable long-term survival after single lung transplantation. Our results do not support the routine use of cardiopulmonary bypass or double lung transplantation for patients with this disorder.

Infant heart transplantation: improved intermediate results.

OBJECTIVES: Our objectives were to (1) review our experience with heart transplants in infants (age < 6 months), (2) delineate risk factors for 30-day mortality, and (3) compare outcomes between our early and recent experience. METHODS: Records of all infants listed for transplantation in our center before September 1996 were analyzed. Early and recent comparisons were made between chronologic halves of the accrual period. Univariate analysis was used to analyze potential risk factors for 30-day mortality (categorical variables, Fisher's exact test; continuous variables, nonparametric Wilcoxon rank-sum test). Multivariable analysis included univariate variables with p values < or = 0.10. Actuarial survivals were estimated (Kaplan-Meier) and compared by the log-rank test. RESULTS: Fifty-one of the 60 infants listed for transplantation were operated on (waiting list mortality 15%). Thirty-day mortality was 18% overall, 30% in the first 3 years and 10% in the last 3 years (p = 0.07). Sepsis was the commonest cause of early death (4/9). Univariate analysis suggested four potential risk factors for early death: preoperative mechanical ventilation (p = 0.01), prior sternotomy (p = 0.002), preoperative inotropic drugs (p = 0.08), and warm ischemia time (p = 0.08). Multivariable analysis indicated that prior sternotomy (p = 0.01) was an independent risk factor for 30-day mortality. Actuarial survivals were 80%, 78%, and 70% at 1, 2, and 3 years, and these figures improved between early and recent groups (p = 0.05). Late deaths were most commonly due to acute rejection (3/5). CONCLUSIONS: Results of heart transplantation in infancy improve with experience. Prior sternotomy increases initial risk. Intermediate-term survival for infants with end-stage heart disease is excellent.

Cardiac entrapment during minimally invasive aortic valve replacement.

Reduced exposure during minimally invasive valve operations poses new difficulties in intraoperative management. Transesophageal echocardiography improves intraoperative management. During a minimally invasive aortic valve replacement, we encountered unexpected hypotension due to mechanical compression of the right ventricle against the sternum. Transesophageal echocardiography facilitated rapid diagnosis of this problem. Surgeons performing these procedures should be aware of this potential problem.

Facilitative interactions between noradrenergic and purinergic signaling during preconditioning of the rat heart.

Recent developments in cardiac physiology have focused on the mechanisms underlying preconditioning against ischemia-reperfusion injury. Sensing, transduction and cardioadaptation to the initial stimulus suggests species-specific differences in strategy. We and others have found that ischemic stress can trigger catecholamine (alpha1-adrenoreceptor)-dependent mechanisms of preconditioning. However, in rabbits and dogs, adenosine receptor mechanisms appear to predominate. In contrast, the role of the adenosine receptors in rat remains controversial. Anticipating a minor role for this metabolite, we examined its ability to induce protection in rat heart against a modest ischemic injury and also its relationship to the noradrenergic alpha1 pathway. Although redundant pathways for inducing adaptation to stress are possible, single transient ischemic stress surprisingly utilizes both alpha1-adrenoreceptors and adenosine P1 receptors in obligate roles. Thus blockade of either purinergic P1 or alpha1-adrenergic receptors abolished functional protection induced by single transient ischemic stimulus. Selective noradrenergic alpha1-adrenoreceptor stimulation was sufficient to protect cardiac recovery after modest ischemic injury, and was unaffected by purinergic blockades, suggesting that this is the primary stress adaptation pathway for rat. However, exogenous purinergic P1 stimulated protection was abolished in either reserpine pretreated, or alpha1-adrenoreceptor blockaded hearts. Therefore the cardioadaptive ischemic preconditioning mechanisms in rat may involve facilitative modulation of a primary pathway rather than redundancy.

Constructive priming of myocardium against ischemia-reperfusion injury.

Ischemia and ischemic stress hormones induce endogenous cardiac protection against ischemia-reperfusion (I/R) injury. Although ischemia and ischemic stress hormones are accompanied by increased [Ca2+], it is unknown whether either opening of the sarcoplasmic reticular ryanodine Ca2+ channel (SR RyR) or inhibition of Ca2+ uptake by the sarcoendoplasmic reticular Ca(2+)-ATPase (SERCA) prior to I/R can similarly induce post-I/R functional protection. To study this, isolated, crystalloid perfused Sprague-Dawley rat hearts were used to assess the effects of inducing a pre-ischemic [Ca2+]i load by either priming the SR RyR with ryanodine (Ry, 5 nM/2 min) or by transient blockade of the SERCA 10 min prior to global I/R (20 min). A pre-ischemic Ca2+ load by either SR RyR activation or SERCA blockade improved post-ischemic myocardial functional recovery (developed pressure, end diastolic pressure, coronary flow, heart rate, and left ventricular creatine kinase activity). We conclude that 1) Ca(2+)-induced myocardial functional protection involves the SR Ca2+ source, 2) a pre-ischemic Ca2+ load induced with either Ry or thapsigargin constructively primes against myocardial I/R injury, and 3) Ca(2+)-induced cardioadaptation to I/R injury may have important therapeutic implications prior to planned ischemic events such as cardiac allograft preservation and cardiac bypass surgery.

Protein kinase C mediates Ca2(+)-induced cardioadaptation to ischemia-reperfusion injury.

Although protein kinase C (PKC)-mediated cardioadaptation to ischemia-reperfusion (IR) is accompanied by increased intracellular Ca2+ concentration, it is unknown whether a preischemia sarcoplasmic reticulum (SR) Ca2+ release affects PKC-mediated post-IR functional protection. To study this, crystalloid-perfused (Langendorff) Sprague-Dawley rat hearts were used to assess the effects of a ryanodine (Ry)-induced preischemia Ca2+ load (Ry, 5 nM/2 min, retrograde coronary) 10 min before global IR (20 min). Ry was administered with and without each of two different PKC inhibitors (20 microM chelerythrine and 150 nM bisindolylmaleimide I-HCl). Ry improved myocardial functional recovery (developed pressure, end-diastolic pressure, coronary flow, and creatine kinase activity), which was eliminated after PKC inhibition. Immunohistochemical staining for PKC isoforms demonstrated that Ry induces specific PKC translocation of alpha-, delta-, and zeta-isoforms. We conclude that 1) a preischemia Ca2+ load from the SR results in post-IR myocardial functional protection 2) Ca(2+)-induced functional protection is PKC regulated via the translocation of specific isoforms, and 3) Ca(2+)-induced cardioadaptation to IR injury may have important therapeutic implications prior to planned ischemic events such as cardiac allograft preservation and cardiac bypass surgery.

Stress-induced cardioadaptation reveals a code linking hormone receptors and spatial redistribution of PKC isoforms.

Extracellular agents, including growth factors, cytokines and hormones, transmit their information into cells utilizing a balanced mosaic of intracellular phosphatases and kinases. How do these agonists select the correct substrates and modify them in order to produce defined physiological responses? Our studies have centered on the mechanisms of stress-induced cardioprotection (preconditioning) against postischemic dysfunction. In several species, the ischemia-reperfusion resistant phenotype appears to be induced by metabotropic-receptor pathways linked to PKC. Our results on the isolated rat heart show that each protective stimulus involves a characteristic mosaic of PKC isoforms, translocating into distinct cellular compartments. The distinct receptor-stimulated PKC isoform profile engaged by each extracellular metabotropic agent could allow the heart several overlapping modes of phenotypic adaptation to ischemia.

Norepinephrine-induced sustained myocardial adaptation to ischemia is dependent on alpha 1-adrenoceptors and protein synthesis.

The authors have shown that stimulation of cardiac alpha 1-adrenoceptors confers immediate cardioprotection in the isolated rat heart against post-ischemic dysfunction, and have recently demonstrated that in vivo treatment of rats with norepinephrine (NE) induces cardiac heat shock protein 72 and myocardial adaptation to ischemia 24 h after treatment. To characterize the delayed myocardial adaptive response induced by NE further, the present study examined its time course and effects of adrenoceptor antagonism and protein synthesis inhibition on this adaptive response during optimal myocardial protection. Rats were treated with NE (3.1 mumol/kg, i.p.) or normal saline (0.4 ml, i.p.), and hearts isolated at 2, 4, 24, 72 and 168 h after injection. Isolated hearts were subjected to 25 min of normothermic global ischemia and 40 min of reperfusion by the Langendorff technique, and left ventricular developed pressure (LVDP) was assessed. There was no difference in baseline LVDP among groups. Post-ischemic LVDP recovered to 44.7 +/- 2.1 mmHg in pooled saline control. LVDP was significantly improved in hearts isolated at 4, 24 and 72 h after injection of NE (66.3 +/- 3.8, 68.6 +/- 2.7 and 72.6 +/- 8.3 mmHg, respectively, P < 0.05 v control) but not in hearts isolated at 2 or 168 h. Effects of antecedent adrenoceptor antagonism and protein synthesis inhibition were examined in hearts isolated at 72 h after NE treatment. Prazosin pretreatment (2.4 mumol/kg, i.p.) abolished the delayed myocardial adaptive response induced by NE at 72 h (post-ischemic LVDP 48.3 +/- 6.1 mmHg, P > 0.05 v control) while propranolol pretreatment (3.4 mumol/kg, i.p.) had no effect (post-ischemic LVDP 67.3 +/- 3.7 mmHg, P < 0.05 v control). Cycloheximide pretreatment (3.6 mumol/kg, i.p.) also abolished the beneficial effect of NE at 72 h (post-ischemic LVDP 50.2 +/- 6.0 mmHg, P > 0.05 v control). In conclusion, administration of NE to rats can induce delayed and sustained cardioprotection against post-ischemic myocardial dysfunction. NE-induced myocardial adaptation to ischemia at 72 h is mediated by alpha 1-adrenoceptors and appears to require protein synthesis.

Clinical and radiographic outcome of a cementless, titanium, plasma spray-coated total hip arthroplasty femoral component. Justification for continuance of use.

Between 1984 and 1986, 177 nonconsecutive, primary total hip arthroplasties were performed in 150 patients using the Mallory-Head Porous femoral component (Biomet, Warsaw, IN) inserted without cement. Average time to follow-up evaluation for the entire population (including all early revisions) was 76 months (6.3 years). There were 10 revisions (6%) with an average time to revision of 50 months (4.2 years). Two revisions were for component undersizing; three revisions were for aseptic loosening; four revisions were for acetabular component failure and one revision was due to a femoral fracture secondary to trauma. At the most recent follow-up visit, the average Harris hip score for all hips increased from 41.5 before surgery to 86.8 (P < .001). Radiographic assessments yielded an average Engh fixation score of 20.7. The Kaplan-Meier survival estimate for the average time to follow-up evaluation was 0.98. Based on our patient selection criteria and excellent intermediate clinical and radiographic results, the initial design strategies of the Mallory-Head Porous femoral prosthesis have been confirmed.

Pulmonary vasomotor dysfunction is produced with chronically high pulmonary blood flow.

This study examined the hypothesis that chronic high pulmonary blood flow produces dysfunction of the mechanisms of pulmonary vasorelaxation. A 3:1 left-to-right shunt was created in dogs by bilateral femoral artery-femoral vein shunts with use of 6 mm polytetrafluoroethylene grafts. Isolated pulmonary artery rings were studied at the following times: 3 days (n = 2), 2 weeks (n = 4), and 5 months (n = 6). Control animals had no shunt. The following mechanisms of pulmonary vasorelaxation were studied in isolated pulmonary artery rings (4 rings from each dog): (1) endothelium-dependent cyclic guanosine monophosphate-mediated relaxation (response to acetylcholine), (2) endothelium-independent cyclic guanosine monophosphate-mediated relaxation (response to sodium nitroprusside), and (3) beta-adrenergic cyclic adenosine monophosphate-mediated relaxation (response to isoproterenol). Statistical analysis was done by analysis of variance. This model of high pulmonary flow did not produce an increase in pulmonary arterial pressure or transpulmonary gradient. However, chronic high pulmonary flow produced progressive dysfunction of all three of these mechanisms of pulmonary vasorelaxation. By 5 months of high pulmonary flow, acetylcholine produced only 36% +/- 6% relaxation versus 95% +/- 5% in control animals (p < 0.05). Likewise, sodium nitroprusside produced only 69% +/- 6% relaxation versus 100% in control animals (p < 0.05). Finally, isoproterenol produced only 55% +/- 5% relaxation versus 94% +/- 6% in control animals (p < 0.05). We conclude that dysfunction of the mechanisms of pulmonary vasorelaxation may contribute to exaggerated perioperative pulmonary vasoconstriction in the setting of chronic high pulmonary blood flow.

Failure of intraoperatively customized non-porous femoral components inserted without cement in total hip arthroplasty.

Seventy-four primary total hip arthroplasties were performed in sixty-eight patients between August 1990 and September 1991. Clinical assessments were made with use of the Harris hip score and, specifically, the pain component of that score. The preoperative radiographs were digitally quantified for calculation of the so-called canal-to-calcar ratio and the so-called cortical index. The postoperative radiographs were evaluated for the percentage of the cross-sectional area of the femoral canal that was occupied by the prosthesis; subsidence of the prosthesis; and adaptive osseous changes, including hypertrophic cortical remodeling, osteolysis, formation of sclerotic radiolucent lines around the prosthesis, and formation of a pedestal at the tip of the prosthesis. The indication for the arthroplasty was osteoarthrosis in fifty hips (68 per cent), avascular necrosis in fourteen (19 per cent), congenital dysplasia in six (8 per cent), and another diagnosis in four (5 per cent). The average duration of follow-up was thirty-one months (range, eleven to forty-six months). The average Harris hip score (and standard deviation) was 75 +/- 16.8 points (range, 29 to 100 points), and the average score for the pain component was 37 +/- 7.5 points (range, 0 to 44 points). The average canal-to-calcar ratio of the hips was 0.44 (range, 0.32 to 0.74), and the average cortical index was 0.54 (range, 0.33 to 0.66). The average subsidence of the component was 0.6 centimeter (range, 0.0 to 2.3 centimeters). The average fill of the canal was 100 per cent proximally, 97 per cent at the middle of the stem, and 92 per cent distally as measured on the anteroposterior radiographs made immediately postoperatively and 100, 95, and 90 per cent, respectively, as measured on the lateral radiographs. A failure occurred in twenty-one hips (28 per cent) in twenty-one patients, with an average time to failure of 21 +/- 13 months (range, one to forty-four months). The Kaplan-Meier survival estimate (and standard error) for this population was 0.45 +/- 0.11 (confidence interval, 0.67 to 0.23) at forty-four months. The average subsidence of the components that failed was 0.7 centimeter (range, 0.1 to 2.3 centimeters). There was no significant relationship between failure of the component and the age or sex of the patient, the diagnosis, or the side of the operation. Postoperative severity of pain (p = 0.09) or subsidence (p = 0.08) alone did not reach significance for predicting outcome. The Harris hip score alone (p = 0.05), the Harris hip score in combination with subsidence of the femoral component (p = 0.01), and the pain component of the Harris hip score in combination with subsidence of the femoral component (p = 0.01) were all significant for predicting outcome. No other measured radiographic variable was predictive of failure. Despite optimization of the fit of the component within the femoral canal and the percentage of the cross-sectional area of the femoral canal occupied by the component, the clinical results indicated a high rate of failure. Thus, these criteria are not the only requisites for stabilization of these femoral components without cement. On the basis of these data, we have discontinued the use of these intraoperatively customized, non-porous, smooth femoral prosthesis.

Enhancing peer review with communication skill building.

The purpose of this pilot was to improve the peer review process by enhancing the communication skills of staff nurses. Communication skill building was taught to staff members with practice time allotted. The paradigm shift occurred in teaching staff that communication is a learned skill built through practice and not solely a cognitive skill. The results of this pilot demonstrated improved verbal communication, increased comfort with peer review, improved ability to separate performance from individual style differences, and increased accuracy with which staff rate themselves on self evaluations. An indirect benefit has been improved teamwork from increased support among the staff.

Role of bradykinin in cardiac functional protection after global ischemia-reperfusion in rat heart.

We have reported that cardiac preconditioning against ischemia-reperfusion (IR) can be induced by transient ischemia (TI) and alpha 1-adrenoreceptor stimulation, both mediated by protein kinase C (PKC) (Mitchell, M., X. Meng, C. Parker, E. Brew, A. Harken, and A. Banerjee. Circ. Res. 76: 73-81, 1995). Our study objective was to explore the mechanism of endogenous preconditioning and address the role of PKC activation in bradykinin-mediated cardiac functional protection. Isolated rat heart was used to assess the effects of exogenous bradykinin, TI, selective B2-receptor blocker, and PKC antagonism on cardiac functional recovery after a global IR injury. Final recovery of developed pressure was improved in hearts treated with bradykinin and TI compared with controls. Bradykinin- and TI-mediated preconditioning was eliminated with coinfusion of the B2-receptor antagonist. Further evaluation of bradykinin-mediated preconditioning revealed that PKC blockade also eliminated functional protection. Immunofluorescent stains of bradykinin-treated hearts demonstrated translocation and activation of specific PKC isoforms in the preconditioned heart. We conclude that TI-mediated preconditioning involves intrinsic cardiac bradykinin receptor stimulation. Bradykinin, through the B2 receptor, initiates a series of intracellular events culminating in the activation of PKC.

Lung transplantation with cardiopulmonary bypass exaggerates pulmonary vasomotor dysfunction in the transplanted lung.

Pulmonary vascular resistance is significantly increased in the transplanted lung. If cardiopulmonary bypass is required, the transplanted lung is reperfused with activated blood elements, which might exacerbate the reperfusion injury. The purpose of this study was to examine the influence of cardiopulmonary bypass on the following mechanisms of pulmonary vasomotor control in a dog model of autologous lung transplantation: (1) endothelium-dependent cyclic guanosine monophosphate-mediated relaxation (response to acetylcholine), (2) endothelium-independent cyclic guanosine monophosphate-mediated relaxation (response to nitroprusside), and (3) beta-adrenergic cyclic adenosine monophosphate-mediated relaxation (response to isoproterenol). Autologous right lung transplants were performed with (n = 4 dogs) and without (n = 5 dogs) bypass. Lungs were stored in cold saline solution (4 degrees C, 3 hours) before reimplantation. Pulmonary vasomotor control mechanisms were studied in isolated pulmonary arterial rings immediately after harvest and 1 hour after reimplantation. Ten rings were studied in each group at each time. Statistical analysis was by analysis of variance. Without bypass, endothelium-dependent cyclic guanosine monophosphate-mediated relaxation and beta-adrenergic cyclic adenosine monophosphate-mediated relaxation were significantly impaired, although endothelium-independent cyclic guanosine monophosphate-mediated relaxation was not. Use of bypass produced significantly greater impairment of both endothelium-dependent cyclic guanosine monophosphate-mediated relaxation and beta-adrenergic cyclic adenosine monophosphate-mediated relaxation. In addition, use of bypass produced significant dysfunction of endothelium-independent cyclic guanosine monophosphate-mediated relaxation as well. We conclude that using cardiopulmonary bypass to perform lung transplantation greatly exaggerates pulmonary vasomotor dysfunction in the transplanted lung. This dysfunction may contribute to significantly higher pulmonary vascular resistance in the transplanted lung if cardiopulmonary bypass is used.