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Biomedical subjects

William K Vaughn

Publications and source records attributed to William K Vaughn.

At least 19 recordsLinked to original sources

Spectrum of aortic operations in 300 patients with confirmed or suspected Marfan syndrome.

BACKGROUND: Cardiovascular disease is the main cause of morbidity and mortality in patients with Marfan syndrome. Many patients with presumed Marfan syndrome do not meet current diagnostic criteria. This study reviews the surgical aspects of aortic disease in 300 patients referred with the diagnosis of Marfan syndrome. METHODS: During a 16-year period, 300 patients with presumed Marfan syndrome underwent 398 operations on the aorta and branch arteries, including 125 aortic root operations, 59 aortic arch repairs, 31 descending thoracic aortic repairs, and 178 thoracoabdominal aortic repairs. Based on medical record review, patients were classified as confirmed Marfan syndrome if documented features satisfied current diagnostic criteria; patients not meeting these criteria were classified as suspected Marfan syndrome. RESULTS: There were 17 operative deaths (4.3%) after the 398 operations. Survival after the initial referral operation was 96.2% +/- 1.5% at 1 year, 82.7% +/- 2.4% at 5 years, and 74.6% +/- 3.1% at 10 years. Presentations, operative details, and outcomes were remarkably similar in the 137 patients (45.7%) with confirmed Marfan syndrome and the 163 patients (54.3%) with suspected Marfan syndrome. Freedom from repair failure, however, was significantly better in patients with confirmed Marfan syndrome (90.3% +/- 2.3% at 10 years) than in those with suspected Marfan syndrome (82.0% +/- 3.1% at 10 years; p = 0.001). CONCLUSIONS: Operative treatment of the full spectrum of aortic disease in Marfan patients enables excellent long-term survival. Similarities in surgical aspects of aortic disease suggest that patients with features of Marfan syndrome who do not meet diagnostic criteria should be managed in the same manner as patients with confirmed Marfan syndrome.

Adolescent↗

Obesity in diabetic patients undergoing coronary artery bypass graft surgery is associated with increased postoperative morbidity.

BACKGROUND: Despite the fact that obesity is a known risk factor for cardiovascular disease, many studies have failed to demonstrate that obesity is independently associated with an increased risk of cardiovascular morbidity and mortality in nondiabetic patients undergoing coronary artery bypass graft surgery. The authors investigated the influence of obesity on adverse postoperative outcomes in diabetic and nondiabetic patients after primary coronary artery bypass surgery. METHODS: A retrospective cohort study of patients undergoing primary coronary artery bypass surgery (n = 9,862) between January 1995 and December 2004 at the Texas Heart Institute was performed. Diabetic (n = 3,374) and nondiabetic patients (n = 6,488) were classified into five groups, according to their body mass index: normal weight (n = 2,148), overweight (n = 4,257), mild obesity (n = 2,298), moderate obesity (n = 785), or morbid obesity (n = 338). Multivariate, stepwise logistic regression was performed controlling for patient demographics, medical history, and preoperative medications to determine whether obesity was independently associated with an increased risk of adverse postoperative outcomes. RESULTS: Obesity in nondiabetic patients was not independently associated with an increased risk of adverse postoperative outcomes. In contrast, obesity in diabetic patients was independently associated with a significantly increased risk of postoperative respiratory failure (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.41-3.61; P < 0.001), ventricular tachycardia (OR, 2.27; 95% CI, 1.18-4.35; P < 0.02), atrial fibrillation (OR, 1.56; 95% CI, 1.03-2.38; P < 0.04), atrial flutter (OR, 2.38; 95% CI, 1.29-4.40; P < 0.01), renal insufficiency (OR, 1.66; 95% CI, 1.10-3.41; P < 0.03), and leg wound infection (OR, 5.34; 95% CI, 2.27-12.54; P < 0.001). Obesity in diabetic patients was not independently associated with an increased risk of mortality, stroke, myocardial infarction, sepsis, or sternal wound infection. CONCLUSION: Obesity in diabetic patients is an independent predictor of worsened postoperative outcomes after primary coronary artery bypass graft surgery.

Adult↗

Temperature during cardiopulmonary bypass: the discrepancies between monitored sites.

We performed studies in patients to determine whether temperature recordings from sites commonly monitored during hypothermic cardiopulmonary bypass adequately reflect cerebral temperature. In Study I (n = 12), temperatures monitored in the jugular bulb (JB) were compared with those recorded in the nasopharynx, esophagus, bladder, and rectum. In Study II (n = 30), temperature was also monitored in the arterial outlet of the membrane oxygenator. A calibrated recorder continuously and simultaneously recorded all temperatures. Study I found large temperature discrepancies between the JB and all other body sites during cooling and rewarming. There was considerable interindividual variability in the degree of discrepancy between the JB and other sites. Study II produced similar results but also showed that JB temperature reached equilibration with the temperature of blood entering the patient via the arterial outlet of the membrane oxygenator after cooling for 3.3 +/- 1.3 min and after rewarming for 16.5 +/- 5.5 min. Analysis of variance revealed that this arterial outlet site had the smallest average discrepancy of all temperature sites relative to the JB site (P < 0.001). In summary, temperatures measured in body sites over-estimated JB temperature during cooling and under-estimated it during rewarming, whereas arterial outlet blood temperature provided a good approximation.

Aged↗

Mesenchymal stem cells differentiate into an endothelial phenotype, enhance vascular density, and improve heart function in a canine chronic ischemia model.

BACKGROUND: Bone marrow-derived stem cells are under investigation as a treatment for ischemic heart disease. Mesenchymal stem cells (MSCs) have been used preferentially in the acute ischemia model; data in the chronic ischemia model are lacking. METHODS AND RESULTS: Twelve dogs underwent ameroid constrictor placement. Thirty days later, they received intramyocardial injections of either MSCs (100x10(6) MSCs/10 mL saline) (n=6) or saline only (10 mL) (controls) (n=6). All were euthanized at 60 days. Resting and stress 2D echocardiography was performed at 30 and 60 days after ameroid placement. White blood cell count (WBC), C-reactive protein (CRP), creatine kinase MB (CK-MB), and troponin I levels were measured. Histopathological and immunohistochemical analyses were performed. Mean left ventricular ejection fraction was similar in both groups at baseline but significantly higher in treated dogs at 60 days. WBC and CRP levels were similar over time in both groups. CK-MB and troponin I increased from baseline to 48 hours, eventually returning to baseline. There was a trend toward reduced fibrosis and greater vascular density in the treated group. MSCs colocalized with endothelial and smooth muscle cells but not with myocytes. CONCLUSIONS: In a canine chronic ischemia model, MSCs differentiated into smooth muscle cells and endothelial cells, resulting in increased vascularity and improved cardiac function.

Animals↗

Lung cancer after heart transplantation: a 17-year experience.

BACKGROUND: The effects of heart transplantation on lung cancer incidence in heart transplant recipients are unclear. METHODS: In an observational study, we retrospectively reviewed the charts of all patients undergoing heart transplantation at our institution from July 1982 to July 1999. Data on lung cancer incidence, risk factors, treatment, and outcome were collected. RESULTS: Five hundred seventy-two patients (mean age, 50 +/- 11 years; range, 18 to 73) were considered at risk for lung cancer. Of these, 324 (57%) had a more than 20 pack-year history of smoking before transplantation. Lung cancer developed in 2 patients 1 year or less after transplantation and in 8 patients more than 1 year after transplantation (incidence, 2.2 per 1,000 patients per year of follow-up). Non-small cell lung cancer was diagnosed in all cases. Median survival was 10.8 months (range, 2 to 37.5). Routine annual chest radiographs after transplantation enabled early diagnosis in 5 cases (stages Ia and IIa), which correlated with better mean survival (28.1 months [range, 19 to 37.5] versus 5.1 months [range, 2 to 10.8]; p = 0.0002). CONCLUSIONS: The incidence of lung cancer in our population of heart transplant recipients appears to be no higher than in nontransplant populations with similar risk factors (ie, smoking and age). Routine radiographic imaging of transplant recipients may allow earlier detection of lung cancer and thus offer a survival benefit.

Adolescent↗

Salvaging the failing Fontan: lateral tunnel versus extracardiac conduit.

BACKGROUND: Since Fontan revision has been demonstrated to provide hemodynamic and symptomatic improvement in select patients with failing Fontan circulations, we now believe it is important to determine if one type of revision (lateral tunnel [LT] or extracardiac conduit [ECC]) provides superior outcomes. METHODS: Thirty-five Fontan revisions were performed (Jun 1997 to Dec 2004): 19 ECC (54%) and 16 LT. Preoperative variables were similar: New York Heart Association (NYHA) IV (LT = 4 vs ECC = 2, p = not significant [NS]), preoperative arrhythmias (LT = 13 vs ECC = 16, p = NS) and systemic right ventricle (LT = 4 vs ECC = 2, p = NS). Twenty-eight patients (80%) underwent a modified maze procedure (LT = 12 vs ECC = 16, p = NS) and 29 (83%) had pacemaker placement (LT = 11 vs ECC = 18, p < 0.05). RESULTS: There were no hospital deaths and no arrhythmias at hospital discharge. There were no differences in mean duration of intubation (LT 0.6 vs ECC 0.9 days, p = NS), inotropic support (LT 1.5 vs ECC 2.1 days, p = NS), intensive care unit stay (LT 2.6 vs ECC 3.5 days, p = NS), hospital stay (LT 8.8 vs ECC 9.7 days, p = NS), or episodes of acute postoperative arrhythmias (LT = 2 vs ECC = 4, p = NS). On intermediate follow-up (29 +/- 22 months), the overall cohort had 94% survival, 97% of survivors in NYHA class I/II, 91% freedom from late arrhythmias requiring medication, and no patient required cardiac transplantation. Follow-up revealed no differences in NYHA I/II (LT = 14 vs ECC = 18, p = NS), mortality (LT = 2 vs ECC = 0, p = NS), or late arrhythmia (LT = 4 vs ECC = 4, p = NS). CONCLUSIONS: Both the LT and ECC revisions provide symptomatic benefit for a failing Fontan connection and have equivalent early and intermediate results including arrhythmia recurrence.

Adolescent↗

Factors predicting 10-year survival after heart transplantation.

BACKGROUND: We sought to identify factors predictive of long-term (>10-year) survival in heart transplant (HTx) recipients. METHODS: Four hundred fifteen adult patients underwent HTx at our institution between August 1982 and May 1997. The 158 patients who survived >10 years (Group A) and the 116 patients who died between 2 and 6 years (Group B) of HTx were compared in terms of gender, gender mismatch, ethnicity, age, height, weight, United Network for Organ Sharing status, type of induction therapy (OKT3 or anti-thymocyte globulin), infections (bacterial, viral, fungal and protozoal), cytomegalovirus (CMV) status, CMV mismatch, diabetes mellitus, hypertension and incidence of rejection episodes and transplant coronary artery disease within 2 years of HTx. RESULTS: Group A (135 men, 23 women; mean age 48 +/- 11 years) had significantly fewer post-HTx rejection episodes and viral, bacterial, fungal and total infections than did Group B (95 men, 21 women; mean age 49 +/- 12 years). Group A also had a significantly lower mean donor age, a lower incidence of pre-HTx diabetes, and a lower mean cholesterol level 1 year after HTx. In a multivariate analysis, fewer bacterial infections and rejection episodes after HTx, the absence of pre-HTx diabetes, and lower donor age were associated with longer survival. CONCLUSIONS: Pre-HTx diabetes, donor age and incidences of infection and rejection within 2 years of HTx predict long-term (>10-year) survival. Better control of infection and rejection during the first 2 years after HTx may improve survival.

Age Factors↗

Alterations in alpha adrenoreceptor density and localization after mechanical left ventricular unloading with the Jarvik flowmaker left ventricular assist device.

Cardiac alpha one adrenoreceptors (alpha(1)AR) are known to mediate positive inotropism in human ventricular myocardium. In the early stages of heart failure, ventricular contractility is maintained by adrenergic stimulation, rennin-angiotensin activation, and other neurohormonal and cytokine system responses. As the disease progresses, however, these compensatory mechanisms cease to provide benefit; ventricular dilation and fibrosis occur and cardiac function deteriorates. When ventricular contractility becomes severely depressed and is no longer responsive to inotropic support, insertion of a left ventricular assist device (LVAD) may allow the left ventricle to rest, remodel, and recover some contractile function. Our previous work has demonstrated that the myocardium has the capacity to repair itself during a period of unloading, after which some patients are able to resume a normal lifestyle and no longer need a cardiac transplant.

Aged↗

Is bridging to transplantation with a left ventricular assist device a risk factor for transplant coronary artery disease?

BACKGROUND: Left ventricular assist device (LVAD) support is associated with coagulopathy, bleeding, increased blood transfusion, and increased anti-HLA antibody production. Increased anti-HLA antibody production is associated with early transplant rejection, transplant coronary artery disease (CAD), and decreased post-transplant survival rates. We asked whether bridging to transplantation with an LVAD increases the risk of transplant CAD. METHODS: We reviewed data for all adults (>18 years old) who underwent heart transplantation at our institution between 1988 and 2000. After exclusion of transplant recipients who survived <3 years, we divided the remaining cohort into 2 groups: those bridged to transplantation with LVADs (mean duration of support, 149 +/- 107 days, n = 29) and those in United Network for Organ Sharing Status 1 bridged to transplantation without LVADs (controls, n = 86). We compared groups in terms of disease cause, age, sex, donor age, panel-reactive antibody testing, crossmatching, pre- and post-transplant cholesterol concentrations, diagnosis of diabetes mellitus or treated hypertension, infections, calcium channel blocker use, transplant rejection, ischemic time, cytomegalovirus infection, pre-transplant transfusion, and incidence of transplant CAD (defined as any coronary lesion identified by coronary angiography). We considered p < 0.05 to be significant. RESULTS: The bridged and control groups were similar in all respects except mean ischemic time (217 +/- 58 minutes vs 179 +/- 67 minutes, p = 0.007), post-transplant cholesterol concentration (212 +/- 55 mg/dl vs 171 +/- 66 mg/dl, p = 0.007), and pre-transplant transfusion incidence (100% vs 22%, p < 0.001). The incidence of transplant CAD was similar in both groups during a 3-year follow-up period (28% vs 17%, p = 0.238) and during total follow-up (34% vs 35%, p = 0.969). Multivariate logistic regression analysis identified cholesterol concentration at 1 year after transplantation as a significant predictor of CAD at 3 years after heart transplantation (p = 0.0029, odds ratio = 0.984). CONCLUSIONS: Bridging to transplantation with an LVAD does not increase the risk of transplant CAD. Nevertheless, aggressive prophylactic therapy to minimize potential risk factors for transplant CAD, such as increased cholesterol concentration, is warranted in all transplant recipients.

Adult↗

Perturbations in laboratory values after coronary artery bypass graft surgery with cardiopulmonary bypass.

OBJECTIVE: The purpose of this study was to describe the sequential changes in commonly obtained laboratory values after coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). METHODS: The authors examined laboratory data from 375 patients who underwent uncomplicated CABG with CPB in a multicenter clinical trial of a medication for postoperative pain. Data were obtained preoperatively, at the time of postoperative extubation, and at 4 subsequent intervals ending 14 days after extubation. Data obtained before study drug administration are reported for all patients; thereafter, only data from placebo patients without perioperative complications (n=123) are reported. RESULTS: Mean postoperative coagulation values remained within their reference ranges at the time of extubation. However, platelet counts increased to a peak value well above the reference range by the end of the study. Postoperative white blood cell counts rose above the reference range, mainly because of increased neutrophils. Serum chemistries were also altered; most patients showed a persistent postoperative hyperglycemia. Creatine kinase levels rose to nearly 4 times the upper limit of the reference range in the early postoperative period. Lactate dehydrogenase, serum aspartate aminotransferase, and alanine aminotransferase levels also increased above the reference range. Total protein and albumin values were below the reference range throughout the postoperative period. CONCLUSIONS: Laboratory values for hematology, blood coagulation, and serum chemistry change substantially after uncomplicated CABG with CPB. Recognition of these changes will facilitate the conduct of clinical research and may prevent inappropriate treatment based on abnormal laboratory findings that have no clinical significance.

Blood Coagulation Tests↗

Statins are associated with a reduced incidence of perioperative mortality after coronary artery bypass graft surgery.

BACKGROUND: Statin therapy in nonsurgical patient populations is associated with a significant reduction in adverse cardiovascular events, including death, myocardial infarction (MI), and stroke. Recently, statin therapy was shown to be associated with a reduced incidence of postoperative mortality in patients undergoing major noncardiac vascular surgery. We investigated the influence of preoperative statin therapy on adverse outcomes after primary coronary artery bypass graft (CABG) surgery. METHODS AND RESULTS: A retrospective cohort study of patients undergoing primary CABG surgery with cardiopulmonary bypass (CPB) (n=1663) between January 1, 2000 and December 31, 2001 at the Texas Heart Institute was performed. Patients were classified into 2 groups: patients receiving preoperative statin therapy (n=943) and patients not receiving preoperative antihyperlipidemic therapy (n=720). To determine if preoperative statin therapy was independently associated with a reduction in the risk of adverse postoperative outcomes, multivariate stepwise logistic regression was performed controlling for patient demographics, medical history, and preoperative medications. Multivariate logistic regression analysis demonstrated that preoperative statin therapy was independently associated with a significant reduction ( approximately 50%) in the risk of 30-day all-cause mortality (3.75% versus 1.80%; P<0.05). The adjusted odds ratio for early mortality in patients receiving preoperative statin therapy compared with patients not receiving antihyperlipidemic agents was 0.53 (95% CI, 0.28 to 0.99). Statin therapy was not independently associated with a reduced risk of postoperative MI, cardiac arrhythmias, stroke, or renal dysfunction. In an attempt to further control for selection bias related to the choice of therapy, multivariate analysis of a propensity-matched cohort of 1362 patients revealed that preoperative statin therapy was independently associated with a significant reduction in the composite endpoint of 30-day all-cause mortality and stroke (7.1% versus 4.6%; P<0.05). CONCLUSIONS: Preoperative statin therapy may reduce the risk of early mortality after primary CABG surgery with CPB.

Aged↗

Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy.

BACKGROUND: We recently reported the safety and feasibility of autologous bone marrow mononuclear cell (ABMMNC) injection into areas of ischemic myocardium in patients with end-stage ischemic cardiomyopathy. The present study evaluated the safety and efficacy of this therapy at 6- and 12-month follow-up. METHODS AND RESULTS: Twenty patients with 6- and 12-month follow-up (11 treated subjects; 9 controls) were enrolled in this prospective, nonrandomized, open-label study. Complete clinical and laboratory evaluations as well as exercise stress (ramp treadmill), 2-dimensional Doppler echocardiography, single-photon emission computed tomography (SPECT) perfusion scanning, and 24-hour Holter monitoring were performed at baseline and follow-up. Transendocardial delivery of ABMMNCs was performed with the aid of electromechanical mapping to identify viable myocardium. Each patient received 15 ABMMNC injections of 0.2 mL each. At 6 and 12 months, total reversible defect, as measured by SPECT perfusion scanning, was significantly reduced in the treatment group as compared with the control group. At 12 months, exercise capacity was significantly improved in the treatment group. This improvement correlated well with monocyte, B-cell, hematopoietic progenitor cell, and early hemapoietic progenitor cell phenotypes. CONCLUSIONS: The 6- and 12-month follow-up data in this study suggest that transendocardial injection of ABMMNCs in patients with end-stage ischemic heart disease may produce a durable therapeutic effect and improve myocardial perfusion and exercise capacity.

Aged↗

Cyclooxygenase-2 inhibitor treatment improves left ventricular function and mortality in a murine model of doxorubicin-induced heart failure.

BACKGROUND: Progression of heart failure after initial myocardial injury is mediated in part by various redundant inflammatory mediators, including the widely expressed cyclooxygenase-2 (COX-2). Because COX-2 inhibitors are useful in treating many inflammation-mediated diseases, we asked whether COX-2 inhibition can attenuate heart failure progression. METHODS AND RESULTS: Heart failure was experimentally induced in 100 mice by administration of doxorubicin (4 mg. kg(-1). wk(-1) for 6 weeks). Beginning at day 42, mice were fed daily with either COX-2 inhibitor-containing mice chow (n=50) or plain mice chow (controls; n=50). Left ventricular ejection fraction was evaluated as a measure of heart failure by a novel method of transthoracic echocardiography (with intravascular ultrasound catheters) at baseline and on days 42, 56, and 70. From baseline to study termination, left ventricular ejection fraction in COX-2 inhibitor-treated mice decreased significantly less than in control mice (9% versus 29%, P<0.01). Mortality was significantly lower for COX-2 inhibitor-treated mice than for control mice (18% versus 38%, P<0.01). These results were confirmed in a revalidation study in COX-2 inhibitor-treated mice (n=25) and controls (n=25). That study revealed that the hearts from control mice weighed roughly the same as hearts from COX-2 inhibitor-treated mice but showed more extensive signs of cardiomyopathy (as determined by pathological analysis by an independent, blinded observer) and higher levels of COX-2 proteins (as determined by immunoblotting [6442+/-1635 versus 4300+/-2408 arbitrary units, P<0.022]). CONCLUSIONS: COX-2 inhibitors can attenuate the progression of heart failure in a murine model of doxorubicin-induced heart failure.

Animals↗

Clopidogrel and bleeding in patients undergoing elective coronary artery bypass grafting.

OBJECTIVE: In an effort to minimize transfusions in patients undergoing elective coronary artery bypass grafting operations after recent clopidogrel exposure, we studied laboratory tests predictive of platelet dysfunction and used a strict algorithm-driven treatment of bleeding. METHODS: Forty-five patients receiving clopidogrel within 6 days of the operation and 45 control subjects were studied. Prothrombin time, activated partial thromboplastin time, platelet count, and platelet function test results were measured before heparinization, after protamine administration, and then every 2 hours. No transfusions were administered unless a patient met both laboratory and clinical criteria. RESULTS: Algorithm-driven treatment of bleeding significantly reduced the mean units of all blood components transfused by about one third, as shown by comparison with current control and historical data. Compared with current control subjects, clopidogrel recipients required significantly more transfusions of platelets (9.0 +/- 1.7 vs 1.2 +/- 0.5 U; P <.0001) and packed red blood cells (4.3 +/- 0.6 vs 2.3 +/- 0.5 U; P =.01) and required longer periods of controlled ventilation (12.4 +/- 1.3 vs 8.6 +/- 0.8 hours; P =.02). Preoperative platelet dysfunction before heparin administration for cardiopulmonary bypass, as measured by using adenosine diphosphate aggregometry (response <40%), predicted all but 1 case of severe coagulopathy requiring multiple transfusions (16.6 +/- 2.8 U of platelets and 5.8 +/- 1.0 U of packed red blood cells). CONCLUSIONS: A strict transfusion algorithm can reduce the transfusion requirement for all blood components. Preheparin testing of platelet function with adenosine diphosphate aggregometry can identify patients at highest risk for perioperative bleeding and transfusions and might further reduce the perioperative transfusion requirement.

Algorithms↗

Current expectations for newborns undergoing the arterial switch operation.

BACKGROUND: The arterial switch operation (ASO) represents a remarkable success story in the surgical treatment of cyanotic congenital heart disease. This study is designed to assess recent outcomes after the ASO in babies presenting with transposition of the great arteries (TGA) and Taussig-Bing anomaly (TBA). METHODS: One hundred twenty-five consecutive neonatal and infant ASOs were performed by 2 surgeons at Texas Children's Hospital between July 1, 1995 and October 1, 2003. Patients with TGA and TBA were offered ASO irrespective of patient size and associated cardiac malformations. Primary cardiac diagnoses included TGA with intact ventricular septum (TGA/IVS, n = 79, 63%), TGA with ventricular septal defect (TGA/VSD, n = 37, 30%), and Taussig Bing Anomaly (TBA, n = 9, 7%). RESULTS: With complete follow-up, we observed a 30-day mortality rate of 1.6% (n = 2) with 2 late deaths (1.6%), for an overall actuarial survival rate of 96.3% at 7 years. Although there was a significant incidence of complex coronary ostial origin and branching including single coronary (n = 8, 6.4%) and intramural coronary artery (n = 8, 6.4%), this was not associated with increased operative risk. All patients are fully saturated and NYHA functional class I at latest clinic visit (0.3 to 88.4 months postoperatively). There have been no late coronary events. Of 121 survivors, 7 patients (5.8%) have required cardiovascular reoperation at an average of 15.3 +/-11.7 months postoperatively (range, 3.6 to 30.6 months) for an actuarial freedom from reoperation of 90% at 7 years. CONCLUSIONS: Using current methodologies, the ASO can be performed safely and with a low incidence of need for reoperation on intermediate follow-up. Recent experience indicates operative survival rates approaching 100%.

Cardiac Surgical Procedures↗

Anesthetic induction with ketamine inhibits platelet activation before, during, and after cardiopulmonary bypass in baboons.

The objective of this study was to investigate the effects of antifactor D monoclonal antibody (Mab) 166-32 on platelet activation during and after hypothermic cardiopulmonary bypass (CPB) in baboons. Fourteen baboons (mean weight, 15 kg) underwent hypothermic CPB. Seven of them were treated with a single injection of antifactor D Mab 166-32 (5 mg/kg) and the other seven animals were given saline as control. Each baboon was sedated with an intramuscular injection of 10 mg/kg of ketamine hydrochloride. A 20-gauge angiocatheter was placed in the cephalic vein, and 5 mg of diazepam was administered intravenously. Anesthesia was maintained with 0.80% to 2.25% isoflurane, 100% O2, and an inspiratory tidal volume of 13 mL/kg at a rate of 13 breaths per minute throughout the surgical procedure except during CPB. Pancuronium bromide, 0.1 mg/kg, was administered to achieve adequate muscle paralysis. Blood samples were collected before CPB, during CPB, and 1, 2, 3, and 6 h after CPB. Assays were performed to measure platelet activation [CD62P (P-selectin)] using immunofluorocytometric methods. There were no significant differences on CD62P expression of platelets between control and antibody groups before CPB (105 +/- 12% vs. 99 +/- 8%, P=NS), during normothermic CPB (62 +/- 6% vs. 63 +/- 19%, P=NS), during hypothermic CPB (55 +/- 8% vs. 54 +/- 13%, P=NS), and 1, 3, or 6 h after CPB (74 +/- 20% vs. 81 +/- 11%, P=NS). Anesthetic induction with ketamine caused significant reduction in the platelet activation in both groups. Ketamine did not affect complement, neutrophil, and monocyte activation or cytokine production. Further studies on the mechanisms of platelet inhibition by ketamine are warranted.

Analysis of Variance↗

Catheter-based transendocardial delivery of autologous bone-marrow-derived mononuclear cells in patients listed for heart transplantation.

Growing evidence suggests that transplantation of autologous bone-marrow mononuclear cells (ABMMNCs) can improve the perfusion and contractile function of ischemic myocardium. This procedure could potentially benefit transplant candidates awaiting a donor heart. To study the safety and feasibility of ABMMNC injection, we performed a prospective, nonrandomized, open-label study in 5 heart transplant candidates with severe ischemic heart failure. Each patient underwent baseline single-photon emission computed tomography, a ramp treadmill protocol, 2-dimensional echocardiography, 24-hour Holter monitoring, and signal-averaged electrocardiography, which were repeated at 2 and 6 months. Transendocardial delivery of ABMMNCs was done with the aid of electromechanical mapping to identify viable myocardium. Each patient received 15 ABMMNC injections of 0.2 cc each. There were no deaths, significant arrhythmias, or other major complications. The ABMMNC injection reduced the amount of ischemic myocardium (not statistically significant). More important, exercise test results improved significantly. Myocardial volume oxygen consumption increased from 10.6 +/- 3 mL/kg/min (baseline) to 16.3 +/- 7 mL/kg/min (2 months) and 23 +/- 7 mL/kg/min (6 months) (P = 0.0091). In 4 of the 5 cases, this was such an improvement that the patients were no longer eligible for cardiac transplantation. In addition, metabolic equivalents improved from 3.03 +/- 0.66 (baseline) to 4.65 +/- 1.99 (2 months) and 6.5 +/- 2.0 (6 months) (P = 0.0092). In conclusion, ABMMNC injections were performed safely and resulted in improved exercise capacity. This technique may hold promise as an alternative to medical management in patients with severe ischemic heart failure who are ineligible for conventional revascularization.

Bone Marrow Transplantation↗