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Objective: Traditionally integrated coronary artery revascularization has been described as a 2-stage procedure. We evaluated the safety and feasibility of 1-stage, simultaneous, hybrid, robotically assisted coronary artery bypass grafting surgery and percutaneous coronary intervention., Methods: Fifty-eight patients underwent simultaneous, integrated coronary artery revascularization in an operating theater equipped with angiographic equipment. Forty-five patients were men. The mean age was 59 years. All internal thoracic arteries were harvested with robotic assistance. All anastomoses were manually constructed through a small anterior non-rib-spreading incision without cardiopulmonary bypass on the beating heart. Immediately after and within the same operative suite, both angiographic confirmation of graft patency and percutaneous coronary intervention were performed. In 52 patients therapeutic anticoagulation was achieved with the direct thrombin inhibitor bivalirudin., Results: There were no deaths or wound infections. There was 1 perioperative myocardial infarction. One patient had a stroke, and 3 patients required re-exploration for bleeding. The median lengths of intensive care and hospital stay were 1 and 4 days, respectively. All patients were alive and symptom free at follow-up (mean, 20.2 months; range, 1.1-40.8 months). Long-term angiographic follow-up in 54 patients showed 49 (91%) patent grafts (mean, 9.0 months; range, 4.3-40.8 months). There were 7 in-stent restenoses and 2 occluded stents., Conclusion: For multivessel coronary artery disease, simultaneous integrated coronary artery revascularization with bivalirudin is safe and feasible. This approach enables complete multivessel revascularization with decreased surgical trauma and postoperative morbidity. Further studies are necessary to better determine patient selection and long-term outcomes.

Objective: We previously applied non-risk-adjusted cumulative sum methods to analyze coronary bypass outcomes. The objective of this study was to assess the incremental advantage of risk-adjusted cumulative sum methods in this setting., Methods: Prospective data were collected in 793 consecutive patients who underwent coronary bypass grafting performed by a single surgeon during a period of 5 years. The composite occurrence of an "adverse outcome" included mortality or any of 10 major complications. An institutional logistic regression model for adverse outcome was developed by using 2608 contemporaneous patients undergoing coronary bypass. The predicted risk of adverse outcome in each of the surgeon's 793 patients was then calculated. A risk-adjusted cumulative sum curve was then generated after specifying control limits and odds ratio. This risk-adjusted curve was compared with the non-risk-adjusted cumulative sum curve, and the clinical significance of this difference was assessed., Results: The surgeon's adverse outcome rate was 96 of 793 (12.1%) versus 270 of 1815 (14.9%) for all the other institution's surgeons combined (P = .06). The non-risk-adjusted curve reached below the lower control limit, signifying excellent outcomes between cases 164 and 313, 323 and 407, and 667 and 793, but transgressed the upper limit between cases 461 and 478. The risk-adjusted cumulative sum curve never transgressed the upper control limit, signifying that cases preceding and including 461 to 478 were at an increased predicted risk. Furthermore, if the risk-adjusted cumulative sum curve was reset to zero whenever a control limit was reached, it still signaled a decrease in adverse outcome at 166, 653, and 782 cases., Conclusions: Risk-adjusted cumulative sum techniques provide incremental advantages over non-risk-adjusted methods by not signaling a decrement in performance when preoperative patient risk is high.

Background: Exogenous surfactant therapy of lung donors improves the preservation of normal canine grafts. The current study was designed to determine whether exogenous surfactant can mitigate the damage in lung grafts induced by mechanical ventilation before procurement., Methods and Results: Five donor dogs were subjected to 8 hours of mechanical ventilation (tidal volume 45 ml/kg). This produced a significant decrease in oxygen tension (p = 0.007) and significant increases in bronchoscopic lavage fluid neutrophil count (p = 0.05), protein concentration (p = 0.002), and the ratio of poorly functioning small surfactant aggregates to superiorly functioning large aggregates (p = 0.02). Five other animals given instilled bovine lipid extract surfactant and undergoing mechanical ventilation in the same manner demonstrated no significant change in oxygen tension values, lavage fluid protein concentration, or the ratio of small to large aggregates. All 10 lung grafts were then stored for 17 hours at 4 degrees C. Left lungs were transplanted and reperfused for 6 hours. After 6 hours of reperfusion the ratio of oxygen tension to inspired oxygen fraction was 307 +/- 63 mm Hg in lung grafts administered surfactant versus 73 +/- 14 mm Hg in untreated grafts (p = 0.007). Furthermore, peak inspired pressure was significantly (p < 0.05) lower in treated animals from 90 to 360 minutes of reperfusion. Analysis of lavage fluid of transplanted grafts after reperfusion revealed small to large aggregate ratios of 0.17 +/- 0.04 and 0.77 +/- 0.17 in treated versus untreated grafts, respectively (p = 0.009)., Conclusions: Instillation of surfactant before mechanical ventilation reduced protein leak, maintained a low surfactant small to large aggregate ratio, and prevented a decrease of oxygen tension in donor animals. After transplantation, surfactant-treated grafts had superior oxygen tension values and a higher proportion of superiorly functioning surfactant aggregate forms in the air space than untreated grafts. Exogenous surfactant therapy can protect lung grafts from ventilation-induced injury and may offer a promising means to expand the donor pool.

Objective: An international series of pulmonary retransplantation was updated to determine the factors associated with pulmonary function, bronchiolitis obliterans syndrome stage, and survival after operation., Methods: One hundred sixty patients underwent retransplantation in 35 centers from 1985 to 1995. Logistic regression methods were used to determine variables associated with 3-month and 2-year survival after retransplantation. Values of forced expiratory volume in 1 second were contrasted between groups by unpaired, two-tailed t tests., Results: The median follow-up in surviving recipients was 780 days. Actuarial survival was 45% +/- 4%, 41% +/- 4%, and 33% +/- 4% at 1, 2, and 3 years, respectively. On multivariable analysis, the only predictor of 3-month survival was preoperative ambulatory status (p = 0.005), whereas center experience with at least five pulmonary retransplantations was the sole predictor of 2-year survival (p = 0.04). The prevalence of stage 3 (severe) bronchiolitis obliterans syndrome was 12% at 1 year, 15% at 2 years, and 33% at 3 years after retransplantation. Retransplant recipients with stage 3 bronchiolitis obliterans syndrome at 1 year had a significantly worse actuarial survival than those with stages 0 to 2 (p < 0.01). By 3 years after retransplantation, the forced expiratory volume in 1 second was significantly lower in patients who underwent reoperation because of obliterative bronchiolitis than in patients who underwent retransplantation because of acute graft failure or an airway complication (p = 0.02). Only 31% of patients who underwent retransplantation because of obliterative bronchiolitis were free of bronchiolitis obliterans syndrome at 3 years versus 83% of patients who underwent retransplantation because of other indications (p = 0.02)., Conclusions: Preoperative ambulatory status predicts early survival and center volume predicts intermediate-term outcome after retransplantation. Improved management strategies are necessary to prevent the development of progressive graft dysfunction after retransplantation for obliterative bronchiolitis.

An international series of pulmonary retransplantation was updated to identify the predictors of outcome and the prevalence and recurrence rate of obliterative bronchiolitis after operation. The study cohort included 139 patients who underwent retransplantation in 34 institutions in North America and Europe between 1985 and 1994. Eighty patients underwent retransplantation because of obliterative bronchiolitis, 34 because of acute graft failure, 13 because of intractable airway complications, 8 because of acute rejection, and 4 because of other indications. Survivors were followed up for a median of 630 days, with 48 patients alive at 1 year, 30 at 2 years, and 16 at 3 years after retransplantation. Actuarial survival was 65% +/- 4% at 1 month, 54% +/- 4% at 3 months, 45% +/- 4% at 1 year, 38% +/- 5% at 2 years, and 36% +/- 5% at 3 years; nonetheless, of 90-day postoperative survivors, 65% +/- 6% were alive 3 years after retransplantation. Life-table and univariate Cox analysis revealed that more recent year of retransplantation (p = 0.009), identical match of ABO blood group (p = 0.01), absence of a donor-recipient cytomegalovirus mismatch (p = 0.04), and being ambulatory immediately before retransplantation (p = 0.04) were associated with survival. By multivariate Cox analysis, being ambulatory before retransplantation was the most significant predictor of survival (p = 0.008), followed by reoperation in Europe (p = 0.044). Complete pulmonary function tests were done yearly in every survivor of retransplantation and bronchiolitis obliterans syndrome stages were assigned. Eleven percent of patients were in stage 3 at 1 year, 20% at 2 years, and 25% at 3 years after retransplantation. Values of forced expiratory volume in 1 second decreased from 1.89 +/- 0.13 L early after retransplantation to 1.80 +/- 0.15 L at 1 year and 1.54 +/- 0.16 L at 2 years (p = 0.006, year 2 versus baseline postoperative value). Most of this decrease occurred in patients who underwent retransplantation because of obliterative bronchiolitis, whereas the pulmonary function of patients who underwent retransplantation because of other conditions did not significantly change. We conclude that survival after pulmonary retransplantation is improving. Optimal results can be obtained in patients who are ambulatory before retransplantation. Compared with recent data after primary lung transplantation, bronchiolitis obliterans syndrome does not appear to recur in an accelerated manner after retransplantation. As long as early mortality as a result of infection can be minimized, pulmonary retransplantation appears to offer a reasonable option in highly selected patients.

Previous work in our laboratory has documented alterations in surfactant composition and function after prolonged lung graft storage and transplantation in dogs (Am Rev Respir Dis 1993;148:208-15). To determine whether exogenous surfactant therapy was beneficial, we pretreated 13 canine double lung blocks with prostacyclin, flushed them with 4 degrees C modified Euro-Collins solution, and stored them at 4 degrees C for 37 to 38 hours. After left lung transplantation and immediately before reperfusion, eight dogs were administered 50 mg of bovine lung lipid extract surfactant per kilogram (50 mg/ml) directly into the left main bronchus and five served as nontreated control animals. Blood gases, peak inspired pressures, and individual pulmonary artery blood flows were measured every 30 minutes during 6 hours of reperfusion. The native right and transplanted left lungs were then lavaged and surfactant large and small aggregates and protein yields were analyzed. All nontreated animals had physiologic evidence of severe ischemia-reperfusion lung injury during reperfusion. Three of eight dogs treated with bovine lung lipid extract surfactant had near normal lung function at 6 hours of reperfusion, as reflected by maintenance of an oxygen tension/inspired oxygen fraction ratio of more than 400 mm Hg and a normal carbon dioxide tension. Five of eight dogs did not respond to surfactant therapy and had decreases in gas exchange identical to those of the control animals. Blood flow through the left pulmonary artery was maintained in the three animals that responded to exogenous surfactant, whereas flow significantly decreased to the left lung in all other animals, reflecting the patterns of gas exchange. In addition, the ratio of poorly functioning small surfactant aggregates to the well-functioning large aggregates isolated from lung lavage after 6 hours of reperfusion was decreased in surfactant-treated animals, especially in those exhibiting a beneficial physiologic response to surfactant therapy. We conclude that therapy with bovine lung lipid extract surfactant can result in excellent preservation of lung grafts after prolonged storage and transplantation, but that the results are not consistent. Further investigations are required to determine the factors responsible for the differential response to surfactant therapy.

An international series of pulmonary retransplantation was updated to identify the predictors of survival in the intermediate-term after reoperation for obliterative bronchiolitis. The study cohort included 32 patients with end-stage obliterative bronchiolitis who underwent retransplantation in 15 North American and European centers between 1988 and 1992. Five types of retransplantation procedures were done, including repeat ipsilateral single lung transplantation (7 patients), repeat contralateral single lung transplantation (8 patients), repeat double lung transplantation (3 patients), double lung transplantation after a previous single lung transplantation (3 patients), and single lung transplantation after a previous double lung or heart-lung transplantation (11 patients). The mean interval between transplants was 564 +/- 51 days (range 187 to 1589 days). Postoperative follow-up was 100% complete and the average follow-up in surviving patients was 678 +/- 63 days. Actuarial survival was 72%, 53%, 50%, 41%, and 33% at 1, 3, 6, 12, and 24 months, respectively. Survival did not differ according to the age, preoperative diagnosis, ambulatory or ventilator status, or cytomegalovirus serologic status of the recipient before reoperation. Life-table and Cox proportional hazards analysis identified the type of retransplantation procedure and the year of reoperation as significant (p < 0.05) predictors of postoperative survival. Actuarial survival was significantly better in patients without an old, retained contralateral graft after retransplantation and in patients who underwent reoperation between 1990 and 1992, as opposed to between 1988 and 1989. Infection was the most common cause of death at all time intervals after retransplantation, although all deaths beyond 2 years resulted from obliterative bronchiolitis of the second graft. Most surviving patients are in a satisfactory clinical condition, with a mean forced expired volume in 1 second of 59% +/- 13% of predicted (repeat double lung transplant recipients) or 41% +/- 6% of predicted (repeat single lung transplant recipients). We conclude that pulmonary retransplantation for obliterative bronchiolitis is associated with significantly worse survival than after primary lung transplantation. The absence of an old contralateral graft after retransplantation and reoperation after 1989 are important predictors of survival. Additional data and follow-up are required to determine the merit of pulmonary retransplantation for obliterative bronchiolitis.

Background: Patients with heart disease are frequently maintained on a regimen of aspirin because of its ability to decrease thrombotic complications and reduce the prevalence of unstable angina and myocardial infarction. Aspirin-induced platelet acetylation also increases bleeding caused by impairment of platelet function during cardiac surgery., Methods: Between October 1990 and November 1991 this double-blind, randomized, placebo-controlled, parallel group interventional study examined the efficacy of high-dose aprotinin administration (up to 7 million KIU) to decrease blood loss and transfusion requirements in patients receiving aspirin within 48 hours of undergoing coronary bypass or valvular heart operations. Primary outcome measures in this study were total volume of blood loss (intraoperative blood loss plus postoperative chest tube drainage) and volume of transfusion during hospitalization., Results: Patients treated with aprotinin (n = 29) had significantly lower total blood loss (1409 +/- 232 ml versus 2765 +/- 248 ml; p = 0.0002), intraoperative blood loss (503 +/- 53 ml versus 1055 +/- 199 ml; p = 0.0001), postoperative blood loss (906 +/- 204 ml versus 1710 +/- 202 ml; p = 0.0074), and prevalence of transfusion (59% versus 88% of patients; p = 0.016) than the placebo group (n = 25). The prevalence of complications including myocardial infarction was similar in the two groups., Conclusions: High-dose aprotinin significantly reduces blood loss and red blood cell transfusions in patients receiving aspirin who undergo cardiac operations.

The results of heart-lung transplantation are improving with increasing experience in postoperative management, but obliterative bronchiolitis may still develop late postoperatively. We have performed 19 heart-lung transplants, with 1-month, 1-year, and 2-year actuarial survival rates of 95% +/- 5%, 84% +/- 8%, and 69% +/- 16%, respectively. Three early recipients died of bronchiolitis, and four patients who were operated on more than 2 years ago are currently being followed up with bronchiolitis. Since August 1988, 13 surviving recipients have undergone serial postoperative bronchoscopies and transbronchial biopsies with topical analgesia. Diffuse bronchomalacia, involving the main bronchi down to the fifth-order bronchi bilaterally, has developed in four patients with bronchiolitis 9 +/- 2 months after the diagnosis of bronchiolitis was confirmed. Pulmonary function tests have revealed a lower ratio of forced expiratory volume in 1 second to forced vital capacity, lower specific airway conductance, and higher airway resistance in heart-lung recipients with bronchomalacia than in patients with bronchiolitis alone. We conclude that diffuse bronchomalacia occurs frequently in heart-lung transplant recipients who have obliterative bronchiolitis. Bronchomalacia worsens the functional airflow obstruction caused by bronchiolitis and may play an important role clinically in the declining respiratory status of heart-lung transplant recipients.

Hemodynamic changes have been documented during protamine infusion into heparinized but not unheparinized pigs and suggest that a protamine-heparin interaction might be responsible. This hypothesis was tested in four groups of pigs by varying the dosage and order of administration of these two drugs: Group I (n = 9) received heparin (3 mg/kg) followed by protamine (3 mg/kg); Group II (n = 9) received protamine (3 mg/kg) followed by heparin (3 mg/kg); Group III (n = 9) received protamine (25 mg/kg) followed by heparin (3 mg/kg); and Group IV (n = 16) received protamine-heparin complex (protamine 3 mg/kg and heparin 3 mg/kg mixed immediately prior to injection). Systemic and pulmonary arterial pressures, systemic and pulmonary vascular resistances, left ventricular end-diastolic pressure, central venous pressure, cardiac output, and heart rate were measured before and at 1.0, 2.5, 5.0, and 15 minutes after protamine, heparin, or protamine-heparin complex infusions. Immediately following protamine infusion, Group I pigs exhibited transiently but significantly increased pulmonary artery pressure, pulmonary vascular resistance, systemic vascular resistance, and central venous pressure and decreased cardiac output with (Group Ib, n = 5) or without (Group Ia, n = 4) systemic hypotension. The fact that no hemodynamic changes occurred in Group II confirms that infusion of clinical doses of protamine produces no hemodynamic changes in unheparinized pigs. Protamine alone in high doses (Group III) produced hemodynamic changes similar to clinical-dose protamine reversal of heparin (Group I). This effect suggests that the presence of heparin in the circulation lowers the threshold for protamine-mediated hemodynamic responses. Infusion of heparin (3 mg/kg) into pigs 15 minutes after treatment with high (25 mg/kg) (Group III) but not clinical (3 mg/kg) (Group II) doses of protamine produced hemodynamic effects similar to clinical-dose protamine reversal of heparin (Group I), suggesting that a protamine-heparin interaction may be responsible. These results also suggest a rapid inactivation in vivo of clinical doses (3 mg/kg) (Group II) of infused protamine. Protamine-heparin complex formed in vitro (Group IV) also produced hemodynamic changes similar to clinical-dose protamine reversal of heparin (Group I), suggesting that formation of this complex in vivo may be the protamine-heparin interaction responsible. Protamine-heparin complex may well be a useful tool in further elucidating the full effects of protamine reversal of heparin.

The myocardial protective effects of crystalloid, blood, and Fluosol-DA-20% cardioplegia were compared by subjecting hypertrophied pig hearts to 3 hours of hypothermic (10 degrees to 15 degrees C), hyperkalemic (20 mEq/L) cardioplegic arrest and 1 hour of normothermic reperfusion. Left ventricular hypertrophy was created in piglets by banding of the ascending aorta, with increase of the left ventricular weight-body weight ratio from 3.01 +/- 0.2 gm/kg (control adult pigs) to 5.50 +/- 0.2 gm/kg (p less than 0.001). An in vivo isolated heart preparation was established in 39 grown banded pigs, which were divided into three groups to receive aerated crystalloid (oxygen tension 141 +/- 4 mm Hg), oxygenated blood (oxygen tension 584 +/- 41 mm Hg), or oxygenated Fluosol-DA-20% (oxygen tension 586 +/- 25 mm Hg) cardioplegic solutions. The use of crystalloid cardioplegia was associated with the following: a low cardioplegia-coronary sinus oxygen content difference (0.6 +/- 0.1 vol%), progressive depletion of myocardial creatine phosphate and adenosine triphosphate during cardioplegic arrest, minimal recovery of developed pressure (16% +/- 8%) and its first derivative (12% +/- 7%), and marked structural deterioration during reperfusion. Enhanced oxygen uptake during cardioplegic infusions was observed with blood cardioplegia (5.0 +/- 0.3 vol%), along with excellent preservation of high-energy phosphate stores and significantly improved postischemic left ventricular performance (developed pressure, 54% +/- 4%; first derivative of left ventricular pressure, 50% +/- 5%). The best results were obtained with Fluosol-DA-20% cardioplegia. This produced a high cardioplegia-coronary sinus oxygen content difference (5.8 +/- 0.1 vol%), effectively sustained myocardial creatine phosphate and adenosine triphosphate concentrations during the extended interval of arrest, and ensured the greatest hemodynamic recovery (developed pressure, 81% +/- 6%, first derivative of left ventricular pressure, 80% +/- 10%) and the least adverse morphologic alterations during reperfusion. It is concluded that oxygenated Fluosol-DA-20% cardioplegia is superior to oxygenated blood and especially aerated crystalloid cardioplegia in protecting the hypertrophied pig myocardium during prolonged aortic clamping.

Right atrial electrical activity and myocardial temperatures of all four chambers were monitored during a 1 hour period of cardioplegic arrest in 20 pigs subjected to different methods of venous cannulation and cardiac cooling. Myocardial protection was provided by systemic hypothermia (28 degrees C) and intermittent intra-aortic administration of cold (4 degrees C) hyperkalemic (20 mEq/L) crystalloid cardioplegia. The use of a single right atrial cannula for venous drainage was associated with sustained atrial activity (50 +/- 5.5 minutes) during cardioplegic arrest and the warmest right atrial (27 degrees +/- 0.2 degrees C) and right ventricular (20.5 degrees +/- 0.4 degrees C) temperatures. Separate caval cannulation with snaring and right atrial venting decreased right atrial and ventricular temperatures marginally (25.3 degrees +/- 0.5 degrees C and 19.1 degrees +/- 0.4 degrees C, respectively, p less than 0.05) but did not significantly alter the duration of atrial electrical activity (42.2 +/- 2.5 minutes, p greater than 0.05). Addition of an extracavitary right atrial drip of cold (4 degrees C) saline, 750 ml for the 1 hour aortic clamping period, reduced right atrial temperature (22.8 degrees +/- 0.4 degrees C) and activity (24.8 +/- 6.3 minutes) to a significant extent. Intracavitary irrigation of the right atrium with cold saline, in the presence of snared double caval cannulas, decreased right atrial and ventricular temperatures most dramatically (17.0 degrees +/- 0.5 degrees C and 17.5 degrees +/- 0.3 degrees C, respectively, p less than 0.05), reduced the duration of atrial electrical activity by 84% (to 8 +/- 3.9 minutes, p less than 0.01), and diminished the total number of atrial contractions per hour of aortic clamping by 88%. It is concluded that intracavitary right atrial cooling with separate snared caval cannulation is the most effective method of ensuring atrial inactivity and prolonged right heart hypothermia during cardioplegic arrest.