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Studies indicate that learning surgical skills on low-fidelity models is equally beneficial to learning on high-fidelity models in terms of skills retention and transfer. However, it is unclear how low-fidelity simulation training impacts retention and transfer in novice learners, particularly on complex surgical tasks that incorporate multiple challenging skills. This study explores the capacity of complete novices to learn and transfer complex surgical skills from a low-fidelity model to a high-fidelity simulation after a delay.Task-naïve medical and nonmedical undergraduate students (n = 62) participated in a three-phase prospective double-arm randomized (2:1) experimental study. Participants completed two skills training sessions (end-to-side anastomosis) on a low-fidelity bench model. After a 4-week delay, participants completed the task again either using the low-fidelity model or a high-fidelity model (cadaver) and were assessed using a validated checklist.There was a significant time × fidelity group interaction (P = 0.004). Simple effects analysis indicated the high-fidelity group (MThese findings suggest that for novice populations, relying on low-fidelity simulation training as a source of teaching complex skills may not provide a reliable transfer to high-fidelity models and in turn clinical settings.

Visual Abstract, Highlights • Short leukocyte telomeres have been associated with adverse cardiovascular outcomes in population studies, but this relationship has not translated to patient care. The authors report a telomere length autologous referencing strategy that has the potential to mark biological aging and to identify high-risk individuals. • Among 163 patients who underwent cardiovascular surgery, telomeres in leukocytes and skeletal muscle displayed age-related shortening, whereas the telomere length in the cardiac right atrium was stable during 6 decades of life. • The magnitude of the telomere length gap between cardiac atrial tissue and leukocytes was associated with post-operative complications and length of stay in the intensive care unit. • This study provided proof of concept that a single-time, internally referenced assessment of leukocyte telomere shortening behavior could inform acute risks in patients with cardiovascular disease., Summary Leukocyte telomere shortening reflects stress burdens and has been associated with cardiac events. However, the patient-specific clinical value of telomere assessment remains unknown. Moreover, telomere shortening cannot be inferred from a single telomere length assessment. The authors investigated and developed a novel strategy for gauging leukocyte telomere shortening using autologous cardiac atrial referencing. Using multitissue assessments from 163 patients who underwent cardiovascular surgery, we determined that the cardiac atrium-leukocyte telomere length difference predicted post-operative complexity. This constituted the first evidence that a single-time assessment of telomere dynamics might be salient to acute cardiac care.

Hypertrophic pyloric stenosis (HPS) is a common neonatal condition treated with open or laparoscopic pyloromyotomy. 3D-printed organs offer realistic simulations to practice surgical techniques. The purpose of this study was to validate a 3D HPS stomach model and assess model reliability and surgical realism.Medical students, general surgery residents, and adult and pediatric general surgeons were recruited from a single center. Participants were videotaped three times performing a laparoscopic pyloromyotomy using box trainers and 3D-printed stomachs. Attempts were graded independently by three reviewers using GOALS and Task Specific Assessments (TSA). Participants were surveyed using the Index of Agreement of Assertions on Model Accuracy (IAAMA).Participants reported their experience levels as novice (22%), inexperienced (26%), intermediate (19%), and experienced (33%). Interrater reliability was similar for overall average GOALS and TSA scores. There was a significant improvement in GOALS (p0.0001) and TSA scores (p=0.03) between attempts and overall. Participants felt the model accurately simulated a laparoscopic pyloromyotomy (82%) and would be a useful tool for beginners (100%).A 3D-printed stomach model for simulated laparoscopic pyloromyotomy is a useful training tool for learners to improve laparoscopic skills. The GOALS and TSA provide reliable technical skills assessments.II.

Objective The aims of the study were to determine whether endoscopic harvesting of the radial artery (RA) reduces morbidity due to pain, infection, and disability with improvement in satisfaction and cosmesis compared to the conventional technique and (2) to compare the 6-month angiographic patency of the RA harvested conventionally and endoscopically. Methods In a prospective randomized study, 119 patients undergoing coronary artery bypass grafting using the RA were randomized to have RA harvested either conventionally (n = 59) or endoscopically (n = 60). Results Radial artery harvest time (open wound time) was significantly reduced in the endoscopic group (36.5 ± 9.4 vs 57.7 ± 9.4 minutes, P < 0.001). Only one patient developed wound infection (1.6%) in the endoscopic group compared with six patients (10.2%), P = 0.061, in the conventional group. Although this was not statistically significant, clinically this was relevant in terms of reduction in postoperative morbidity. Postoperative pain in the arm incision was significantly lower in the endoscopic group at postoperative day 2 ( P < 0.001) and at discharge ( P < 0.001) and similar to the conventional open group at 6 weeks’ follow-up ( P = 0.103). Overall patient satisfaction and cosmesis were significantly better in the endoscopic group at postoperative day 2 ( P < 0.001), at discharge ( P < 0.001), and at 6 weeks’ follow-up ( P < 0.001). There was no difference in the arm disability postoperatively ( P = 0.505) between the two groups. Six-month angiographic assessment of 23 patients (12 endoscopic and 11 open) revealed no difference in the patency rate (10/12 in endoscopic and 9/11 in open group). Conclusions Endoscopic RA harvesting reduced the incidence of postoperative wound infection and wound pain and improved patient satisfaction and cosmesis compared with conventional harvesting technique. There was no difference in the 6-month angiographic patency of the RA harvested conventionally and endoscopically.

Background Persistent incisional pain is common after cardiac surgery and is believed to be in part related to inflammation and poorly controlled acute pain. Methylprednisolone is a corticosteroid with substantial antiinflammatory and analgesic properties and is thus likely to ameliorate persistent surgical pain. Therefore, the authors tested the primary hypothesis that patients randomized to methylprednisolone have less persistent incisional pain than those given placebo. Methods One thousand forty-three patients having cardiopulmonary bypass for cardiac surgery via a median sternotomy were included in this substudy of Steroids in Cardiac Surgery (SIRS) trial. Patients were randomized to 500 mg intraoperative methylprednisolone or placebo. Incisional pain was assessed at 30 days and 6 months after surgery, and the potential risk factors were also evaluated. Results Methylprednisolone administration did not reduce pain at 30 days or persistent incisional pain at 6 months, which occurred in 78 of 520 patients (15.7%) in the methylprednisolone group and in 88 of 523 patients (17.8%) in the placebo group. The odds ratio for methylprednisolone was 0.93 (95% CI, 0.79 to 1.09, P = 0.37). Furthermore, there was no difference in worst pain and average pain in the last 24 h, pain interference with daily life, or use of pain medicine at 6 months. Younger age, female sex, and surgical infections were associated with the development of persistent incisional pain. Conclusions Intraoperative methylprednisolone administration does not reduce persistent incisional pain at 6 months in patients recovering from cardiac surgery.

Objectives Microembolic signals (MES) on transcranial Doppler (TCD) predict stroke and cognitive decline. Plasma levels of total homocysteine (tHcy), a prothrombotic factor, are higher in patients with microemboli in carotid stenosis and in patients with paradoxical embolism. In this study we assessed the association between the level of tHcy and the number of MES in patients with mechanical heart valves (MHVs). Methods TCD monitoring was performed to detect MES before and after breathing 100% oxygen and repeated every 2–4 weeks up to six times. Results Twenty-five patients with MHVs (mean age: 63.60±10.15 years) participated in this study; 15 were men (66.47±7.25 years) and 10 were women (59.30±12.60 years). In total, there were 126 study visits. In multiple regression, higher tHcy was associated with more MES in both preoxygenation (OR 1.34 (95% CI 1.07 to 1.68, P=0.009)) and postoxygenation (OR 1.40 (95% CI 1.07 to 1.83, P=0.01)) phases. Current smoking and the length of time between the operation and monitoring also correlated with a higher number of MES before and after breathing oxygen, particularly in women. Conclusions Higher tHcy and smoking were associated with a higher MES count in both preoxygenation and postoxygenation phases. Because smoking can be stopped and hyperhomocysteinaemia is treatable, these are clinically important findings.

Background Although often short-lived and self-limiting, postoperative atrial fibrillation (POAF) is a well-recognized postoperative complication of cardiac surgery and is associated with a 2-fold increase in cardiovascular mortality and morbidity. Objective Our aim was to determine whether intraoperative bilateral pulmonary vein radiofrequency ablation decreases the incidence of POAF in patients undergoing coronary artery bypass grafting (CABG). Methods A total of 175 patients undergoing CABG was prospectively randomized to undergo adjuvant bilateral radiofrequency pulmonary vein ablation in addition to CABG (group A; n=89) or CABG alone (group B; n=86). Intraoperative pulmonary vein isolation was confirmed by the inability to pace the heart via the pulmonary veins after ablation. All patients received postoperative β-blocker. Results There was no difference in the incidence of POAF in the treatment group who underwent adjuvant pulmonary vein ablation (group A; 37.1%) compared with the control group who did not (group B; 36.1%) ( P = .887). There were no differences in postoperative inotropic support, antiarrhythmic drug use, need for oral anticoagulation, and complication rates. The mean length of postoperative hospital stay was 8.2 ± 6.5 days in the ablation group and 6.7 ± 4.6 days in the control group ( P Conclusion Adjuvant pulmonary vein isolation does not decrease the incidence of POAF or its clinical impact but increases the mean length of stay in the hospital. The mechanism of POAF does not appear to depend on the pulmonary veins.

Objective From 2005 to 2007, 119 patients were enrolled in a prospective randomized controlled trial comparing open and endoscopically harvested radial arteries for coronary artery bypass grafting. The objective of the current study was to compare graft patency between intervention groups at more than 5 years from the initial trial. We hypothesized that endoscopically harvested radial arteries would show equivalent patency to those conventionally harvested. Methods At 5 years or greater from their operation, all consenting patients underwent a single-day anatomic and functional cardiac assessment with coronary computed tomography angiography and sestamibi myocardial perfusion scanning. Medical Outcomes Study 36-Item Short-Form Health Surveys and Seattle Angina Questionnaires were completed to assess the overall quality of life. All patients had received calcium channel blocker therapy for at least 6 months postoperatively. Results The mean (SD) duration of follow-up was 79.2 (8.6) months for all patients. One death occurred within 30 days of coronary artery bypass grafting in each treatment group, and eight additional noncardiac deaths occurred during the study time frame. Of 119 patients, 66 consented to follow-up. Thirty-two had open radial artery harvest, and 34 had endoscopic radial artery harvest. At more than 5 years, there were 28 patent conventionally harvested radial arteries (87.5%) and 31 patent endoscopically harvested radial arteries (91.2%) ( P = 0.705). Measured quality of life was comparable between groups. Conclusions Endoscopic radial artery harvest is safe and effective when compared with open radial artery harvest, with excellent graft patency demonstrated at more than 5 years. Patency results are noninferior in endoscopic radial artery harvest.

Current guideline-based recommendations for oral dual-antiplatelet therapy in an acute coronary syndrome (ACS) include the use of newer adenosine diphosphate receptor inhibitor (ADPri) regimens and agents. The Canadian ACS Reflective Program is a multicenter observational quality-enhancement project that compared the use of ADPri therapy in 2 phases (November 2011-March 2013 and April 2013-November 2013) and also compared ADPri use with previous national data from the Canadian Global Registry of Acute Coronary Events (2000-2008). Of 3099 patients with ACS, 30.6% had ST-segment elevation myocardial infarction (STEMI), 52.3% had non-STEMI, and 17% had unstable angina. There was high use of dual-antiplatelet therapy for ≤ 24 hours, with important increases noted when compared with previous national experience (P for trend, < 0.0001). Clopidogrel was the most commonly used ADPri (82.2%), with lower use of the newer agents ticagrelor (9.0%) and prasugrel (3.1%). Ticagrelor and prasugrel use was most frequent in patients with STEMI undergoing percutaneous coronary intervention PCI (34.3%). There was relatively lower use of ADPri therapy at discharge; it was given mainly to patients who did not undergo PCI (68.2%) and to those with non-ST-elevation ACS (82%). When comparing the 2 consecutive phases of data collection in the ACS Reflective, there was an approximate 3- and 2-fold increase in the early and discharge use of the newer ADPri agents, respectively. In conclusion, there has been a temporal increase in ADPri use compared with previous national experience and an increased uptake of newer ADPri agents. Additional work is needed to identify and address barriers limiting optimal implementation of these newer guideline-recommended agents into routine Canadian practice.

Acute ischemic stroke secondary to vessel occlusion from an aneurismal dissection is an uncommon presentation. Disseminated intravascular coagulation (DIC) can present as a consequence of aortic dissection, although this is also rare. In some cases, the laboratory diagnosis of DIC uncovers a vascular abnormality or bleeding diathesis. This article describes a patient presenting with three sequential complications of a dissecting thoracic aortic aneurysm: ischemic stroke, upper gastrointestinal bleeding, and consumptive coagulopathy.

Cardiac retransplantation remains the most viable option for patients with allograft heart failure; however, careful patient selection is paramount considering limited allograft resources. We analyzed clinical outcomes following retransplantation in an academic, tertiary care institution.Between 1981 and 2011, 593 heart transplantations, including 22 retransplantations were performed at our institution. We analyzed the preoperative demographic characteristics, cause of allograft loss, short- and long-term surgical outcomes and cause of death among patients who had cardiac retransplantations.Twenty-two patients underwent retransplantation: 10 for graft vascular disease, 7 for acute rejection and 5 for primary graft failure. Mean age at retransplantation was 43 (standard deviation [SD] 15) years; 6 patients were women. Thirteen patients were critically ill preoperatively, requiring inotropes and/or mechanical support. The median interval between primary and retransplantation was 2.2 (range 0-16) years. Thirty-day mortality was 31.8%, and conditional (30 d) 1-, 5- and 10-year survival after retransplantation were 93%, 79% and 59%, respectively. A diagnosis of allograft vasculopathy (p = 0.008) and an interval between primary and retransplantation greater than 1 year (p = 0.016) had a significantly favourable impact on 30-day mortality. The median and mean survival after retransplantation were 3.3 and 5 (SD 6, range 0-18) years, respectively; graft vascular disease and multiorgan failure were the most common causes of death.Long-term outcomes for primary and retransplantation are similar if patients survive the 30-day postoperative period. Retransplantation within 1 year of the primary transplantation resulted in a high perioperative mortality and thus may be a contraindication to retransplantation.

Introduction: Ascertaining the biological age of patients with advanced vascular disease could advance risk assessment and management. The extent to which telomeres shorten in leukocytes could be a marker of biological age because it reflects the accumulation of replication stresses imposed on leukocyte progenitors. However, because of wide, genetic variability in leukocyte telomere length (TL), a single leukocyte TL measurement does not reliably indicate telomere shortening. Hypothesis: We hypothesized that the difference in length of telomeres in “non-replicating” muscle-rich tissue and that of circulating leukocytes provides a patient-specific index of telomere shortening in patients with advanced vascular disease. Methods: TL in leukocytes, skeletal muscle, and right atrial cardiac muscle were measured from 134 patients undergoing coronary or thoracic aortic surgery, using quantitative polymerase chain reaction. Relationships between leukocyte TL or the muscle-leukocyte TL difference (ΔTL) and early post-operative outcomes were tested using Cox proportional hazard and binary logistic regression analyses. Results: Telomeres in cardiac muscle and skeletal muscle were significantly longer than those in leukocytes (p Conclusions: Right atrium-leukocyte ΔTL provides an index of telomere shortening and may inform outcomes in patients with advanced vascular disease. This two-component telomere measurement may reflect the biological age of individuals with chronic vascular disease.

Management of cardiac surgery health human resources (HHR) has been challenging, with recent graduates struggling to secure employment and a shortage of cardiac surgeons predicted as early as 2020. The length of cardiac surgery training prevents HHR supply from adapting in a timely fashion to changes in demand, resulting in a critical need for active workforce management. This study details the results of the 2015 Canadian Society of Cardiac Surgeons (CSCS) workforce survey undertaken as part of the CSCS strategy for active workforce management. The 38-question survey was administered electronically to all 96 trainees identified as being registered in a Canadian cardiac surgery residency program for the 2015-2016 academic year. Eighty-four of 96 (88%) trainees responded. The majority of participants were satisfied with their training experience. However, 29% stated that their clinical and operative exposure needed improvement, and 57% of graduating trainees did not believe that they would be competent to practice independently at the conclusion of their training. Although 51% of participants believe the job market is improving, 94% of senior trainees found it competitive or extremely difficult to secure an attending staff position. Participants highlighted a need for improved career counselling and formal mentorship. Although the job market is perceived to be improving, a mismatch in the cardiac surgery workforce supply and demand remains because current trainees continue to experience difficulty securing employment after the completion of residency training. Trainees have identified improved career counselling and mentorship as potential strategies to aid graduates in securing employment.

Background Randomized trials have established the efficacy of clopidogrel in acute coronary syndromes (ACS). The benefit of clopidogrel has also been observed in the subgroup of ACS patients who subsequently undergo coronary artery bypass surgery (CABG); however, this therapy is discontinued preoperatively and the frequency with which clopidogrel is restarted post-CABG is unknown. Methods We examined the pattern of clopidogrel use in the Canadian Global Registry of Acute Coronary Events (GRACE), GRACE2, and CANRACE (2003-2008) post-CABG ACS patients. We stratified the patients according to whether they underwent CABG during their index hospitalization for ACS and whether they were prescribed clopidogrel at discharge. Results Among those patients in whom clopidogrel status at discharge was known, 5904 (60%) of 9841 were discharged from hospital on clopidogrel. Use of clopidogrel at discharge was observed in 2222 (40.8%) of 5443 patients who were medically managed (ie, did not undergo percutaneous coronary intervention [PCI] or CABG) and in 3585 (90.1%) of 3980 patients who underwent in-hospital PCI. Overall, 455 (3.3%) of 13,776 patients underwent CABG during the index hospitalization; 255 (56%) patients were started on clopidogrel during the first 24 hours, and 66 of these patients (25.9%) were discharged on clopidogrel. In contrast, 5681 (61.3%) of the 9262 patients who did not undergo in-hospital CABG were discharged on clopidogrel. Conclusions Although current guidelines recommend the use of clopidogrel post-CABG in patients with ACS, our observations suggest that only 1 in 4 or 5 Canadian patients are discharged on this therapy.

Cerebral deoxygenation is associated with various adverse systemic outcomes. We hypothesized, by using the brain as an index organ, that interventions to improve cerebral oxygenation would have systemic benefits in cardiac surgical patients.Two-hundred coronary artery bypass patients were randomized to either intraoperative cerebral regional oxygen saturation (rSO2) monitoring with active display and treatment intervention protocol (intervention, n = 100), or underwent blinded rSO2 monitoring (control, n = 100). Predefined clinical outcomes were assessed by a blinded observer.Significantly more patients in the control group demonstrated prolonged cerebral desaturation (P = 0.014) and longer duration in the intensive care unit (P = 0.029) versus intervention patients. There was no difference in overall incidence of adverse complications, but significantly more control patients had major organ morbidity or mortality (death, ventilation48 h, stroke, myocardial infarction, return for re-exploration) versus intervention group patients (P = 0.048). Patients experiencing major organ morbidity or mortality had lower baseline and mean rSO2, more cerebral desaturations and longer lengths of stay in the intensive care unit and postoperative hospitalization, than patients without such complications. There was a significant (r(2) = 0.29) inverse correlation between intraoperative rSO2 and duration of postoperative hospitalization in patients requiringor =10 days postoperative length of stay.Monitoring cerebral rSO2 in coronary artery bypass patients avoids profound cerebral desaturation and is associated with significantly fewer incidences of major organ dysfunction.

We present a case of a 48-year-old female patient successfully bridged to recovery with the Impella 5.0 microaxial pump (Abiomed, Danvers, MA USA) after presenting with cardiogenic shock secondary to acute fulminant viral myocarditis. After 1 week of flu-like symptoms, the patient presented to her community emergency department with chest pain and hypotension. A diagnosis of inferior ST elevation myocardial infarction was made; subsequent angiography demonstrated normal coronary arteries and a left ventricular ejection fraction of 10%. A provisional diagnosis of viral myocarditis was made. As her condition deteriorated further, she underwent insertion of an Impella 5.0 after failure of supportive medical therapy. Myocardial recovery occurred, and the Impella was removed after 1 week. After a prolonged cardiac intensive care unit stay requiring temporary hemodialysis, the patient recovered sufficiently to tolerate device explant, transfer to the recovery ward, and ultimate discharge home. This case report highlights the benefit of mechanical circulatory support in a patient with cardiogenic shock from viral myocarditis as well as some of the complications that can occur in this critically ill subset of patients.

Background Off-pump coronary artery bypass (OPCAB) surgery has been successfully used in diverse patient populations and has been postulated to be safer than conventional coronary artery bypass (CCAB) surgery in some high-risk patients, including the elderly. Objective To compare the safety of OPCAB surgery versus CCAB surgery in the octogenarian population of two large southwestern Ontario cardiac surgical units. Results Two hundred thirty-six consecutive octogenarians underwent primary isolated coronary artery bypass sugery from November 2000 to March 2005. Patients undergoing OPCAB surgery tended to have higher Parsonnet scores, while patients undergoing CCAB surgery had a greater number of emergent operations. The Canadian Cardiovascular Network predicted that mortality risk was similar in both groups. In-hospital mortality was similar between groups, as was postoperative myocardial infarction and new onset of renal dysfunction. However, in the OPCAB group, there was a decreased incidence of postoperative neurological dysfunction (2.3% in the OPCAB group versus 10.5% in the CCAB group, P=0.01), in particular cerebrovascular accidents (1.5% in the OPCAB group versus 7.6% in the CCAB group, P=0.05), and a decreased incidence of prolonged intubation (5.3% in the OPCAB group versus 13.3% in the CCAB group, P=0.04). Multivariable analysis found that cardiopulmonary bypass had no significant impact on mortality or length of stay. Conclusions In octogenarian patients, OPCAB surgery is as safe as CCAB surgery in terms of mortality and major morbidity. Furthermore, a significant reduction in neurological dysfunction and prolonged intubation was seen in the OPCAB group compared with the CCAB group.

Clopidogrel (Plavix) is a potent inhibitor of platelet aggregation used concomitantly with percutaneous coronary interventions and in patients with acute coronary syndromes. Its favorable effects on preventing thrombus formation may have deleterious effects on hemostasis in patients undergoing coronary surgery.Data were collected prospectively on 312 consecutive urgent or emergent coronary artery bypass patients from July 1999 through April 2001 at a tertiary care center. Patients were stratified into three groups: clopidogrel within 4 days of operation (n = 41), clopidogrel continued until 5 to 8 days before operation (n = 39), and clopidogrel discontinued more than 8 days before operation or were never taking clopidogrel (n = 232).Preoperative and intraoperative characteristics were similar among all groups. Mediastinal and pericardial chest tube losses in the first 24 hours were 1,044 +/- 750 mL in the clopidogrel within 4 days group, 528 +/- 250 mL in the clopidogrel 5 to 8 days group, and 573 +/- 329 mL in the clopidogrel more than 8 days group (p0.01). The mean total blood product transfusions were 12.2 +/- 15.4 U, 1.2 +/- 2.0 U, and 2.6 +/- 5.7 U, respectively (p0.001). Reoperation for bleeding was noted in 14.6%, 2.6%, and 1.7%, respectively (p = 0.002). The median hospital lengths of stay for the three groups were 9 days, 7 days, and 7 days, respectively (p = 0.018). There were no statistically significant differences in mortality rate, myocardial infarction, stroke, mediastinitis, or postoperative renal failure among the groups. Multivariable analysis revealed that clopidogrel within 0 to 4 days of operation was an independent predictor of transfusion requirements (OR 4.22, 95% confidence interval [CI] 2.07, 9.34, p = 0.001), intensive care unit (ICU) length of stay (OR 3.14, 95% CI 1.40, 7.04, p = 0.006), and total hospital length of stay (coefficient 7.65, se 2.41, p = 0.002).Clopidogrel within 4 days of coronary bypass surgery is associated with increased blood losses and reoperation for bleeding and, according to multivariable models, is an independent risk factor for increased transfusion requirements and prolonged ICU and hospital length of stay.

Although current artificial heart valves are life sustaining medical devices, improvements are still necessary to address deficiencies. Bioprosthetic valves have a compromised fatigue life, while mechanical valves have better durability but are prone to thromboembolic complications. A novel, one-piece, tricuspid valve, consisting of leaflets, stent and sewing ring, made entirely from the hydrogel, polyvinyl alcohol cryogel (PVA-C), has been developed and demonstrated. This valve has three thin leaflets attached to a cylindrical stent. In order to approximate the complex shape of the surface of the natural heart valve leaflets, two different geometries have been proposed: revolution about an axis of a hyperboloid shape and revolution about an axis of an arc subtending (joining) two straight lines. The parameters of both geometries were examined based on a compromise between avoiding sharp curvature of leaflets and minimization of the central opening of the valve when closed. The revolution of an arc subtending two straight lines was selected as the preferred geometry since it has the benefit of a smaller central opening when the value of the maximum curvature for the leaflets is the same for each valve geometry. A cavity mold has been designed and constructed to form the PVA-C heart valve. The three leaflets were formed and integrated into the stent and sewing ring in a single process. Prototype heart valves were manufactured in the mold from a solution of PVA and water, by controlled freezing and thawing cycles.

Background Pulmonary function testing is an integral part of evaluating patients who are being considered for cardiac transplantation. The accurate measurement of diffusing capacity (D lco ) and alveolar volume (VA) is dependent on a 10-s breath-holding maneuver that may be difficult for patients with congestive heart failure to perform. The intrabreath (IB) technique is not dependent on a breath-holding maneuver and may provide more accurate pulmonary function testing results in chronically debilitated patients. Methods Seventy-five patients performed maneuvers with IB and single-breath (SB) techniques during evaluation for heart transplantation and at 3 and 12 months following transplantation. The D lco , VA, and total lung capacity (TLC) were compared using Pearson correlation coefficients, a Student t test, and intercorrelation coefficients. Results The D lco and VA, when determined with the IB technique, had excellent correlations to the SB technique over all ranges of D lco values. VA values that were determined by the IB technique were greater than those determined by the SB technique and more closely approximated the TLC values. The satisfactory correlation between the two techniques was maintained when D lco was corrected for VA. However, due to the lower values for VA as determined by the SB method, the corrected measurements were consistently higher for the SB technique. Conclusion Pulmonary function can be measured accurately in a population of patients with long-standing congestive heart failure, both before and after cardiac transplantation, using the IB technique. Furthermore, the IB technique may provide a more accurate measurement of VA.

Background and Aim: We have shown that cumulative sum (CUSUM) failure analysis may be more sensitive than standard statistical methods in detecting a cluster of adverse patient outcomes after cardiac surgical procedures. We therefore applied CUSUM, as well as standard statistical techniques, to analyze a surgeon's experience with off-pump coronary artery bypass grafting (OPCAB) and on-pump procedures to determine whether the two techniques have similar or different outcomes. Methods: In 320 patients undergoing nonemergent, first time coronary artery bypass grafting, preoperative patient characteristics, rates of mortality and major complications, and ICU and hospital lengths of stay were compared between the on-pump and OPCAB cohorts using Fisher's exact tests and Wilcoxon two sample tests. Predicted mortality and length of stay were determined using previously validated models of the Cardiac Care Network of Ontario. Observed versus expected ratios of both variables were calculated for the two types of procedures. Furthermore, CUSUM curves were constructed for the on-pump and OPCAB cohorts. A multivariable analysis of the predictors of hospital length of stay was also performed to determine whether the type of coronary artery bypass procedure had an independent impact on this variable. Results: The predicted mortality risk and predicted hospital length of stay were almost identical in the 208 on-pump patients ( 2.2 ± 3.9% ; 8.2 ± 2.5 days) and the 112 OPCAB patients ( 2.0 ± 2.2% ; 7.8 ± 2.1 days). The incidence of hospital mortality and postoperative stroke were 2.9% and 2.4% in on-pump patients versus zero in OPCAB patients (p= 0.09 and 0.17, respectively). Mechanical ventilation for greater than 48 hours was significantly less common in OPCAB (1.8%) than in on-pump patients (7.7%, p= 0.04). The rate of 10 major complications was 14.9% in on-pump versus 8.0% in OPCAB patients (p= 0.08). OPCAB patients experienced a hospital length of stay that was a median of 1.0 day shorter than on-pump patients (p= 0.01). The observed versus expected ratio for length of stay was 0.78 in OPCAB patients versus 0.95 in on-pump patients. On CUSUM analysis, the failure curve in OPCAB patients was negative and was flatter than that of on-pump patients throughout the duration of the study. Furthermore, OPCAB was an independent predictor of a reduced hospital length of stay on multivariable analysis. Conclusions: OPCAB was associated with better outcomes than on-pump coronary artery bypass despite a similar predicted risk. This robust finding was documented on sensitive CUSUM analysis, using standard statistical techniques and on a multivariable analysis of the independent predictors of hospital length of stay.(J Card Surg 2002;17:520-528)

Introduction Steroids In caRdiac Surgery trial (SIRS) is a large international randomised controlled trial of methylprednisolone or placebo in patients undergoing cardiac surgery with the use of a cardiopulmonary bypass pump. At the time of surgery, compared with placebo, methylprednisolone divided into two intravenous doses of 250 mg each may reduce the risk of postoperative acute kidney injury (AKI). Methods and analysis With respect to the study schedule, over 7000 substudy eligible patients from 81 centres in 18 countries were randomised in December 2013. The authors will use a logistic regression to estimate the adjusted OR of methylprednisolone versus placebo on the primary outcome of AKI in the 14 days following surgery (a postoperative increase in serum creatinine of ≥50%, or ≥26.5 μmol/L, from the preoperative value). The stage of AKI will also be considered, as will the outcome of AKI in those with and without preoperative chronic kidney disease. After receipt of grant funding, the authors began to record additional perioperative serum creatinine measurements in consecutive patients enrolled at substudy participating centres, and patients were invited to enroll in a 6-month serum creatinine collection. In these trial subpopulations, the authors will consider the outcome of AKI defined in alternate ways, and the outcome of a 6-month change in kidney function from the preoperative value. Ethics and dissemination The authors were competitively awarded a grant from the Canadian Institutes of Health Research for this SIRS AKI substudy. Ethics approval was obtained for additional serum creatinine recordings in consecutive patients enrolled at participating centres. The additional kidney data collection first began for patients enrolled after 1 March 2012. In patients who provided consent, the last 6-month kidney outcome data will be collected in 2014. The results will be reported no later than 2015. Clinical Trial Registration Number NCT00427388.

Background Steroids may improve outcomes in high-risk patients undergoing cardiac surgery with the use of cardiopulmonary bypass (CBP). There is a need\ for a large randomized controlled trial to clarify the effect of steroids in such patients. Methods We plan to randomize 7,500 patients with elevated European System for Cardiac Operative Risk Evaluation who are undergoing cardiac surgery with the use of CBP to methylprednisolone or placebo. The first coprimary outcome is 30-day all-cause mortality, and the most second coprimary outcome is a composite of death, MI, stroke, renal failure, or respiratory failure within 30 days. Other outcomes include a composite of MI or mortality at 30 days, new onset atrial fibrillation, bleeding and transfusion requirements, length of intensive care unit stay and hospital stay, infection, stroke, wound complications, gastrointestinal complications, delirium, postoperative insulin use and peak blood glucose, and all-cause mortality at 6 months. Results As of October 22, 2013, 7,034 patients have been recruited into SIRS in 82 centers from 18 countries. Patient's mean age is 67.3 years, and 60.4% are male. The average European System for Cardiac Operative Risk Evaluation is 7.0 with 22.1% having an isolated coronary artery bypass graft procedure, and 66.1% having a valve procedure. Conclusions SIRS will lead to a better understanding of the safety and efficacy of prophylactic steroids for cardiac surgery requiring CBP.

Background and Objective: Human leukocyte antigen (HLA) compatibility has been shown to improve the outcome of renal and cardiac transplantation. However, its impact on outcome following lung transplantation is not clear, with several single-center studies reporting inconsistent results. We studied the influence of HLA matching on survival and the development of rejection and obliterative bronchiolitis after lung transplantation, using data from the United Network for Organ Sharing/International Society for Heart and Lung Transplantation registry. Methods The study population included adult patients who received cadaveric lung transplants between October 1987 and June 1997 for whom HLA data were available. Two cohorts were examined, depending on the era of transplantation: (1) October 1987 to June 1997 ( n = 3,549): Differences in actuarial survival as stratified by either the total number of HLA mismatches or the number of mismatches at each HLA locus were determined using a log-rank test. Multivariate logistic regression models were developed to determine independent predictors of survival at 1, 3, and 5 years following lung transplantation. (2) April 1994 to June 1997 ( n = 1,796): The association of HLA mismatching with acute rejection and obliterative bronchiolitis was determined using a chi-squared analysis. Results Only 164 patients (4.6%) received lung grafts with 2 or fewer HLA mismatches. Univariate analyses demonstrated a significant difference in post-transplant survival by mismatch level, with the total number of HLA mismatches ( p = 0.0008) and mismatching at the HLA-A locus ( p = 0.002) associated with worse survival. Multivariate logistic regression demonstrated that the number of mismatches at the HLA-A and HLA-DR loci predicted 1-year mortality (incremental odds ratios 1.18, p = 0.01, and 1.15, p = 0.03, respectively). The total number of HLA mismatches predicted 3- and 5-year mortality (incremental odds ratios 1.13 at 3 years, p = 0.0004, and 1.14 at 5 years, p = 0.0002). However, other covariates such as repeat transplantation, transplantation for congenital heart disease, advanced recipient age, and an early era of transplantation were stronger predictors of mortality. We found no significant association between HLA mismatching and the development of obliterative bronchiolitis, although there was an association between mismatching at the HLA-A locus and acute rejection episodes requiring hospital admission ( p = 0.008). We also found no association between mismatching at the HLA-B locus and rejection episodes requiring either hospitalization or the alteration of anti-rejection medications ( p = 0.034). Conclusion Although the number of HLA mismatches at the HLA-A and HLA-DR loci predicted 1-year mortality and the total number of mismatches predicted 3- and 5-year mortality following lung transplantation, the effect of each covariate was small in this multicenter study of 3,549 patients. Further close follow-up of registry patients is necessary to determine the effect of HLA matching on long-term survival and freedom from obliterative bronchiolitis and rejection following lung transplantation. A prospective study of HLA matching for lung transplantation should not yet be considered in view of the small number of grafts with 2 or fewer mismatches and the modest effect of HLA matching on outcome.

Objective To compare measurements obtained by transesophageal echocardiography (TEE) and epicardial echocardiography (EE) for evaluation of the tricuspid valve (TV) and pulmonary valve (PV). Design Prospective observational. Setting University hospital. Participants Patients undergoing elective coronary artery bypass grafting with or without aortic valve replacement. Interventions After routine intraoperative TEE, EE was performed to compare measurements obtained by the 2 methods. Measurements and main results After institutional review board approval, 25 patients >18 years old were recruited. Biases with EE versus TEE for E and A waves were 11.9 cm/second (95% confidence interval [CI], 48.2 to −24.4) and 6.8 cm/second (95% CI, 28 to −15), respectively, and for E/A ratio was 0.08 (95% CI, 1.2 to −1). Pulmonary velocity bias was 57.94 cm/second (95% CI, 192.9 to −76.98), with higher values using EE. Bias for pulmonary trunk diameter was −0.31 cm (95% CI, 1.5 to −2.1). For quality of images, means were 2.4 (standard deviation [SD], 1.0) for EE and 2.3 (SD, 0.57) with TEE for TV and 2.4 (SD, 1.0) with EE and 2.5 (SD, 1.0) with TEE for PV. For the number of leaflets visualized, means were 2.2 (SD, 1.0) with EE and 2.5 (SD, 0.5) with TEE for TV and 2.5 (SD, 0.5) for EE and 1.3 (SD, 1.1) with TEE for PV. Conclusions There was good agreement for Doppler measurements across TVs; however, measurements across PVs were significantly higher with EE versus TEE. TV Doppler measurements were difficult to acquire even for surgeons experienced in epiaortic scanning.

Exposure to cardiopulmonary bypass (CPB) is associated with postoperative coagulopathy and hemorrhage. Recent literature indicates that heparin rebound occurs almost universally following cardiac surgery. We conducted this pilot study to evaluate if the presence of residual circulating heparin following cardiac surgery can be diagnosed by elevation of activated partial thromboplastin time (APTT).After obtaining Research Ethics Board approval, blood samples from 30 patients receiving heparin for CPB were evaluated at the time of intensive care unit admission and 2, 4, and 6 hr thereafter. Activated clotting time, whole blood heparin concentration (Hepcon HMS Plus, Medtronic), anti-Xa levels, and APTT were measured at each time point. Samples with prolonged APTT were subjected to mechanistic studies with heparin adsorption and 1:1 mixing.Anti-Xa was elevated in 52 of the 120 blood samples (0.08 +/- 0.08 U . mL(-1), mean +/- SD). APTT was elevated in 49 (40.8%) samples with an average of 51.4 +/- 31.9 sec. At all time points, the APTT correlated poorly with anti-Xa levels with correlation coefficients ranging from -0.26 to -0.05. Mean APTT was modestly, but not significantly, associated with total dose of protamine with r = 0.34 (CI: -0.03, 0.62). After 1:1 mixing studies, APTT returned to normal in most (82%) samples tested.Circulating residual heparin is commonly presented following cardiac surgery and does not correlate with APTT. Considering that mixing studies normalize APTT in most samples, elevated APTT following CPB may reflect deficiency of coagulation factors or presence of a coagulation inhibitor such as protamine. Further studies are required to confirm this observation.

Objective The purpose of this study was to compare transvalvular flow velocities obtained by transesophageal echocardiography and epicardial echocardiography (EE) during aortic valve replacement (AVR). Design Prospective observational study. Setting University hospital. Participants Patients undergoing AVR for aortic stenosis. Interventions After institutional review board approval, 17 patients undergoing AVR consented. Deep transgastric (deep TG LAX) and transgastric long-axis (TG LAX) views and epicardial aortic valve long-axis views (S8 probe) were obtained on a SONOS 5500 (Phillips Medical Systems, Bothell, WA) before and after AVR. Transvalvular flow velocity and velocity time integral (VTI) were recorded via each technique. Measurements were made offline by 2 independent reviewers. Agreement between measurements made by different views was evaluated by using Bland-Altman analysis. Measurements and Main Results The epicardial probe was well tolerated. Quality images were obtained in all patients with TEE and 30 of 34 studies via epicardial scanning. The mean bias for peak velocities derived through EE and deep TG LAX was 96.3 cm/s (95% confidence interval [CI], 51.1-141.4) before AVR and 58 cm/s (95% CI, 32.4-83.7) after AVR. The mean bias for peak velocities between EE and TG LAX was 70 cm/s (95% CI, 31.1-108.9) before and 84.7 cm/s (95% CI, 55.6-113.7) after AVR. Similar results were obtained for VTI. Conclusions Peak transaortic valve velocities and VTI measured with epicardial echocardiography are higher in comparison to measurements via TEE in patients undergoing AVR. The precise role of epicardial echocardiography in the comprehensive echocardiographic examination of patients undergoing aortic valve replacement needs further evaluation.

Background There is a relative dearth of information on how the resident's level of training affects patient outcomes in cardiac surgery. We designed this study to determine if there were any significant differences in patient demographics and clinical outcomes of coronary artery bypass procedures (CABG) performed by residents of PGY 4/lower, residents of PGY 5/6, fellows, or consultants. Methods Standardized preoperative, intraoperative, and postoperative variables were prospectively collected and analyzed on 2906 isolated CABG procedures, performed between July 1999 and March 2006 with the primary surgeon prospectively classified as PGY4/lower, PGY5/6, fellow, and consultant. Results The number of cases performed by residents of PGY4/lower, PGY5/6, fellows and consultants were 179, 263, 301, and 2163, respectively. Preoperative demographics and comorbidities were similar except PGY4/lower group had more diabetics and consultant group had more patients requiring IABP. More non-LIMA arterial conduits were used in the consultant and fellow groups. However, there were neither significant differences in the mean number of grafts nor in the composite postoperative morbidity, median ICU, and hospital lengths of stay. Observed in-hospital mortality was 2.2%, 1.5%, 1.7%, and 2.7% (p = 0.49), respectively. Conclusions Preoperative patient demographics and operative data were similar in all groups except that patients requiring IABP preoperatively were more likely operated on by consultants and arterial revascularization was performed more commonly by consultants and fellows. Postoperative mortality and morbidity rates were similar among all groups, thus demonstrating that with appropriate supervision, trainees of all levels can safely be taught CABG.

Background: Arterial bifurcations are commonly the sites of developing atherosclerotic plaque that lead to arterial occlusions and plaque rupture (myocardial infarctions and strokes). Laser induced fluorescence (LIF) spectroscopy provides an effective nondestructive method supplying spectral information on extracellular matrix (ECM) protein composition, specifically collagen and elastin. Purpose: To investigate regional differences in the ECM proteins -- collagen I, III and elastin in unstable plaque by analyzing data from laser-induced fluorescence spectroscopy of human carotid endarterectomy specimens. Methods: Gels of ECM protein extracts (elastin, collagen types I & III) were measured as reference spectra and internal thoracic artery segments (extra tissue from bypass surgery) were used as tissue controls. Arterial segments and the endarterectomy specimens (n=21) were cut into 5mm cross-sectional rings. Ten fluorescence spectra per sampling area were then recorded at 5 sites per ring with argon laser excitation (357nm) with a penetration depth of 200 μm. Spectra were normalized to maximum intensity and analyzed using multiple regression analysis. Tissue rings were fixed in formalin (within 3 hours of surgery), sectioned and stained with H&E or Movat's Pentachrome for histological analysis. Spectroscopy data were correlated with immunohistology (staining for elastin, collagen types I, III and IV). Results: Quantitative fluorescence for the thoracic arteries revealed a dominant elastin component on the luminal side -- confirmed with immunohistology and known artery structure. Carotid endarterectomy specimens by comparison had a significant decrease in elastin signature and increased collagen type I and III. Arterial spectra were markedly different between the thoracic and carotid specimens. There was also a significant elevation (p

Laser extraction of device leads offers an attractive alternative to countertraction and electrosurgical dissection sheath, potentially increasing efficacy and reducing complications. Wider adoption of this technology depends on relative ease of use. We report the experience of a new center to define the "learning curve." We performed 76 laser lead extractions in 75 patients (age 63 +/- 17 years, 59 male) from July 2001 to January 2004. Two experienced device implanters who were novice extractors underwent a 2-day site visit to a high volume extraction center for training. Lead extractions were performed in the operating room with immediate surgical backup. The indication for extraction was infection in 39 (systemic in 15), erosion or pain in 11, and lead related or debulking in 25. Complete removal was achieved in 139 of 145 leads (14 ICD, 131 pacemaker). Partial removal (

Background Serial measurements of pulmonary function to indicate decreasing respiratory muscle strength in patients with amyotrophic lateral sclerosis (ALS) is well documented. Quantitative outcome measures include declining FVC, FEV1, maximal inspired pressure, maximal expired pressure, and maximal voluntary ventilation. Increasing peak expiratory flow time (PEFT) may represent a further sensitive measure of declining respiratory muscle strength in ALS. Methods Fifty-five patients with ALS performed flow-volume loops serially after presentation. The percentage change from baseline values for FVC, peak expiratory flow (PEFR), and PEFT were compared using Spearman correlation coefficients. The prolongation of PEFT with serial tests was analyzed using a Kruskal-Wallis with a Dunn multiple comparison test. Bulbar-onset and limb-onset PEFT was compared using the Mann-Whitney test. Results PEFT was significantly increased from baseline values at all follow-up tests. However, PEFTs measured at the third, fourth, fifth, and sixth visits, although higher, were not significantly different. Significant negative correlations existed between the increase in PEFT and the decrease in PEFR and FVC. Significant positive correlations existed between the increase in PEFT and days from diagnosis and the decrease in PEFR and decrease in FVC. Conclusion PEFT increases significantly and linearly with time in patients with ALS and may begin to plateau with bulbar symptoms. PEFT increases at a faster rate than the rate of decline in both FVC and PEFR. PEFT is a quantitative measure of decreasing pulmonary function in ALS that is easily measured.

We have demonstrated that in vitro fluorescence spectroscopic analysis of diseased carotid arteries can identify clinically relevant compositional changes in connective tissue (collagen type I, III, IV and elastin) associated with plaque remodeling and instability.

We report the case of a previously healthy 32-year-old man who was seen with flulike symptoms, dyspnea, and chest pain. The diagnosis was pyopneumopericardium, and pericardial tap revealed 1.3 L of purulent material. Computed tomography of the chest demonstrated a calcified mass inferior to the carina. Urgent exploration through a right thoracotomy revealed that the mass was adherent to the esophagus and pericardium. The subcarinal mass was resected. Pathological study demonstrated granulomatous lymph nodes, which were likely due to histoplasmosis. This is among the first reports of granulomatous erosion into the pericardium causing pyopneumopericardium. The patient made a good recovery, and his case demonstrates the importance of early imaging and mediastinal exploration for pyopneumopericardium.

Several studies have reported the incidence, morbidity, and mortality of general surgical conditions (GSCs) in orthotopic heart transplant (OHT) patients. The following is the largest reported series of such patients and the first study with sufficient patient numbers to formally evaluate peritransplant variables as risk factors for GSC development.A GSC was defined as a condition for which a general surgeon had been consulted or as a general surgical condition recognized at the time of autopsy. The records of 453 consecutive patients who underwent OHT between 1981 and 1999 were reviewed to identify patients who developed a GSC. Kaplan-Meier actuarial analysis on this cohort, and univariate and multivariate logistic regression models applied to a subpopulation of 324 consecutive OHT patients between 1987 and 1997 were used to determine factors associated with and predictive of GSC after OHT.Of 453 OHT patients, 371 (81.9%) were men, and the average age was 44.5 +/- 15 (standard deviation) years. Median followup was 2,086 days (range 1 to 6,642 days). Ninety-three patients (20.5%) developed 111 GSCs. Of these, 78 were men, and the average age was 49.9+/-10.2 years. There were 83 general surgical interventions. Actuarial analyses revealed that age greater than 50 years, pretransplant diagnosis of ischemic (PTDxI) versus nonischemic heart disease, and previous general surgical history were factors associated (p0.05) with a higher GSC incidence. Gender, more urgent transplant priority status, cardiopulmonary bypass time, total graft ischemic time, and intensive care unit length of stay were not associated with GSC. Factors associated with GSC on univariate analysis, with odds ratios (ORs) and 95% confidence intervals (CIs) included: age analyzed as a continuous variable (OR 1.04 per year; CI 1.01, 1.06 per year; p = 0.0021), PTDxI (OR 2.40; CI 1.39, 4.15; p = 0.0016), and pretransplant general surgical history (OR 3.35; CI 1.65, 6.82; p = 0.0008). Multivariate analysis revealed that only pretransplant general surgical history (OR 3.27; CI 1.58, 6.76; p = 0.0004) and PTDxI (OR 2.37; CI 1.35, 4.16; p = 0.0023) were associated with subsequent development of GSC.A pretransplant diagnosis of ischemic heart disease and previous history of a general surgical procedure are two independent risk factors that predispose OHT patients to development of GSC. Because GSC may arise insidiously in immunosuppressed patients, identification of OHT patients at higher risk for GSC will permit timely intervention decisions, decreasing morbidity and mortality in this challenging group of patients.

Objective To determine the effect of consultant surgeon sleep hours on patient outcomes in cardiac surgery. Design Prospective observational cohort study. Subjects Between January 2004 and December 2009, we prospectively collected sleep hours of 6 consultant surgeons, ranging in age from 32 to 55 years, working in a tertiary care academic institution. The prospective study cohort included all patients undergoing coronary artery bypass, valve, combined valve–coronary artery bypass, and aortic surgery. The predicted risk of death and/or any of 10 major complications was calculated using our institutional multivariable model, which was then compared with observed values. Additional prespecified analyses examined the interaction between surgeon age, sleep hours, and postoperative outcomes. This study had more than 90% power to detect a 4% (clinically important) difference in overall complication rates among groups. Main Outcome Measures Complication and mortality rates in operations performed by surgeons with 0 to 3, 3 to 6, or more than 6 hours' sleep the evening prior to surgery. Results Of 4047 consecutive surgical procedures, 83 were performed by a consultant with 0 to 3 hours, 1595 with 3 to 6 hours, and 2369 with more than 6 hours of sleep. Rates of mortality (3 [3.6%], 44 [2.8%], and 80 [3.4%], respectively; P = .53) were similar in the 3 groups, as were the observed vs expected ratios of major complications (1.20, 0.95, and 1.07, respectively; P = .25). There was no significant interaction between surgeon age, hours of sleep, and occurrence of death or any of 10 major complications (P = .09). Conclusion This well-powered prospective study showed no evidence that consultant surgeon sleep hours had an effect on postoperative outcomes.

The purpose of these experiments was to study the pharmacological response of quinidine induced early afterdepolarisations to gain insights into underlying ionic mechanisms. Quinidine (8.5 microM) induced stable early afterdepolarisations at low activation frequencies in 80% of canine cardiac Purkinje fibres superfused with a modified Tyrode's solution. Early afterdepolarisations arose from a secondary plateau in the voltage range of -30 to -60 mV. Calcium channel blockers (verapamil, 1 microM, in 3/6 preparations; verapamil, 10 microM in 6/6 preparations; nifedipine, 0.1 microM in 5/5 preparations) completely eliminated early afterdepolarisations, despite continued quinidine superfusion, without altering the underlying action potential. Isoprenaline (0.2-1 microM) restored them in 75% of these preparations during continued calcium blocker superfusion. Tetrodotoxin (5/5 preparations) eliminated early afterdepolarisations by abbreviating action potentials and reducing or eliminating the quinidine induced secondary plateau. While low concentrations of isoprenaline favoured the occurrence of early afterdepolarisations, larger concentrations eliminated them by enhancing spontaneous automaticity. These experiments suggest that voltage dependent and/or receptor regulated slow inward current plays an important role in quinidine induced early afterdepolarisations. Beta receptor stimulation can enhance or suppress early afterdepolarisations, depending on whether effects on slow inward current (tending to favour them) or on automaticity (suppressing them) predominate.

The purpose of these experiments was to determine the frequency dependence of the effects of amiodarone and its active desethyl metabolite on slow-channel tissues. Intravenous amiodarone and desethylamiodarone (10 or 25 mg/kg) increased atrioventricular conduction time (AVCT) and refractory period (AVERP) in open-chest, chloralose-anesthetized dogs. Drug effects on AVCT and AVERP were greatly augmented by increasing atrial stimulation frequency. The frequency dependence of drug effects was quantified by studying the response of atrioventricular (AV) conduction to changes in coupling interval. Under control conditions, premature atrial stimulation increased AVCT with a time constant of 70 msec. In the presence of amiodarone and desethylamiodarone, a biexponential relationship between AVCT and coupling interval was observed. One component had a time constant similar to control, and a slower component with a time constant of about 1 sec appeared. Slow-channel action potentials produced in canine cardiac false tendons by elevated potassium (25 mM) and isoproterenol in vitro showed interval-dependent changes in Vmax with a time constant averaging 74 msec in the absence of amiodarone. In the presence of amiodarone, a slower recovery phase of Vmax with a time constant averaging 0.94 sec was observed. These results indicate that amiodarone and its metabolite produce heart rate-dependent changes in AV nodal function in vivo and suggest use-dependent calcium-channel blockade as a mechanism of this action. Amiodarone's rate-related effects on slow-channel properties should produce selective depression of supraventricular tachyarrhythmias involving rapid activation of the AV node.