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The Revivent TC System (BioVentrix Inc, San Ramon, CA) enables a less invasive approach for left ventricular reshaping and scar exclusion in selected patients with ischemic cardiomyopathy. Although the system is designed to improve quality of life and to promote reverse remodeling, patients can still progress to end-stage heart failure requiring advanced therapies. This report describes a case of left ventricular assist device surgery in a patient 16 months after Revivent System implantation. The planning process and surgical technique proved to be complex. This case report can help provide guidance to advanced heart failure teams who encounter patients with the Revivent System who require left ventricular assist device support.

Background Most studies of patients with isolated proximal left anterior descending (PLAD) coronary artery disease do not include all 3 procedural options: percutaneous coronary intervention (PCI), conventional coronary artery bypass graft (CABG) surgery, or minimally invasive CABG. Methods New York’s cardiac registries were used to identify patients who underwent revascularization for isolated PLAD disease between January 1, 2010, and November 30, 2016, in New York State. After exclusions, 14,327 patients, of whom 13,115 received PCI, 1001 of whom underwent CABG surgery, and 211 of whom underwent minimally invasive CABG were monitored through the end of 2017 to compare outcomes. Registry data were matched to vital statistics data to obtain deaths occurring after discharge and matched to claims data to obtain subsequent admissions for myocardial infarction and stroke. Results There were no significant differences in mortality or in mortality/myocardial infarction/stroke after 7 years (with median follow-up times in excess of 4 years) among the 3 procedures after adjusting for differences in patient risk factors. However, conventional CABG surgery was associated with a lower subsequent revascularization rate than PCI (adjusted hazard ratio, 0.45; 95% confidence interval, 0.35-0.58) and minimally invasive CABG surgery (adjusted hazard ratio, 0.46; 95% confidence interval, 0.32-0.66). Conclusions Among patients with isolated PLAD disease undergoing any of 3 revascularization options (PCI, conventional CABG surgery, or minimally invasive CABG surgery), conventional CABG surgery was associated with lower subsequent revascularization rates, but there were no differences in mortality or mortality/myocardial infarction/stroke rates.

Whether to repair nonsevere tricuspid regurgitation (TR) during surgery for ischemic mitral valve regurgitation (IMR) remains uncertain.The goal of this study was to investigate the incidence, predictors, and clinical significance of TR progression and presence of ≥moderate TR after IMR surgery.Patients (n = 492) with untreated nonsevere TR within 2 prospectively randomized IMR trials were included. Key outcomes were TR progression (either progression by ≥2 grades, surgery for TR, or severe TR at 2 years) and presence of ≥moderate TR at 2 years.Patients' mean age was 66 ± 10 years (67% male), and TR distribution was 60% ≤trace, 31% mild, and 9% moderate. Among 2-year survivors, TR progression occurred in 20 (6%) of 325 patients. Baseline tricuspid annular diameter (TAD) was not predictive of TR progression. At 2 years, 37 (11%) of 323 patients had ≥moderate TR. Baseline TR grade, indexed TAD, and surgical ablation for atrial fibrillation were independent predictors of ≥moderate TR. However, TAD alone had poor discrimination (area under the curve, ≤0.65). Presence of ≥moderate TR at 2 years was higher in patients with MR recurrence (20% vs. 9%; p = 0.02) and a permanent pacemaker/defibrillator (19% vs. 9%; p = 0.01). Clinical event rates (composite of ≥1 New York Heart Association functional class increase, heart failure hospitalization, mitral valve surgery, and stroke) were higher in patients with TR progression (55% vs. 23%; p = 0.003) and ≥moderate TR at 2 years (38% vs. 22%; p = 0.04).After IMR surgery, progression of unrepaired nonsevere TR is uncommon. Baseline TAD is not predictive of TR progression and is poorly discriminative of ≥moderate TR at 2 years. TR progression and presence of ≥moderate TR are associated with clinical events. (Comparing the Effectiveness of a Mitral Valve Repair Procedure in Combination With Coronary Artery Bypass Grafting [CABG] Versus CABG Alone in People With Moderate Ischemic Mitral Regurgitation, NCT00806988; Comparing the Effectiveness of Repairing Versus Replacing the Heart's Mitral Valve in People With Severe Chronic Ischemic Mitral Regurgitation, NCT00807040).

Background Operative mortality (in-hospital during the index admission or within 30 days of the procedure after discharge) is commonly used as a quality of care measure for public reporting of cardiac surgery outcomes, but the ability to capture out-of-hospital deaths accurately remains undetermined. The objective of the study was to estimate the impact of incomplete reporting of out-of-hospital deaths on hospital risk-adjusted mortality and outlier status. Methods New York State’s 2014 to 2016 cardiac registry data were used to compare the capture of 30-day postprocedure deaths after discharge with and without the use of national and state-level vital statistics data for all 54,442 patients undergoing isolated coronary artery bypass graft, cardiac valve surgery, or both. Hospital risk-adjusted operative mortality rates and mortality outliers were compared based on statistical models that were developed with and without the use of vital statistics data. Results Thirty-day deaths postprocedure after discharge ranged from 10% to 39% of all operative deaths among cardiac surgical procedures. More than 30% of these deaths were missing without vital statistics confirmation for 7 of the 10 cardiac procedures examined, and more than 40% were missing for 5 of the procedures examined. When vital statistics data were used to confirm 30-day postprocedure deaths after discharge, an additional high outlier for valve surgery was identified. Conclusions Operative mortality after cardiac surgery is often underreported owing to a considerable percentage of out-of-hospital cardiac surgery deaths that are missed by reporting centers. This can adversely affect the assessment of hospital risk-adjusted mortality in public reports.

Background Despite recent guideline statements, there is still wide practice variation in the use of multiple arterial grafts (MAGs) versus single arterial grafts (SAGs) for patients with multivessel disease undergoing coronary artery bypass graft surgery. This may be related to differences in findings between observational and randomized controlled studies. Objectives This study sought to compare intermediate-term MAG and SAG outcomes with enhanced matching to reduce selection bias. Methods New York’s cardiac registry identified 63,402 multivessel disease patients undergoing coronary artery bypass graft surgery between January 1, 2005, and December 31, 2014, to compare outcomes (median follow-up 6.5 years) for patients receiving SAGs and MAGs. SAG and MAG patients were propensity matched using 38 baseline characteristics to reduce selection bias. The primary endpoint was mortality, and secondary endpoints included repeat revascularization and a composite endpoint of mortality, acute myocardial infarction, and stroke. Results Before matching, 20% of procedures employed MAG. At 1 year, there was no mortality difference between matched MAG and SAG patients (2.4% vs. 2.2%, adjusted hazard ratio [AHR]: 1.11; 95% confidence interval [CI]: 0.93 to 1.32). At 7 years, MAG patients had lower mortality (12.7% vs. 14.3%, AHR: 0.86; 95% CI: 0.79 to 0.93), a lower composite outcome (20.2% vs. 22.8%, AHR: 0.88; 95% CI: 0.83 to 0.93), and a lower repeat revascularization rate (11.7% vs. 14.6%, AHR: 0.80; 95% CI: 0.74 to 0.87). At 7 years, the subgroups for which MAG did not have a lower mortality rate included patients with off-pump surgery, 2-vessel disease with right coronary artery disease, recent acute myocardial infarction, renal dysfunction, and patient ≥70 years of age. Conclusions Mortality and the composite outcome were similar between MAG and SAG patients at 1 year, but lower for MAG after 7 years. Patients of higher volume MAG surgeons experienced lower MAG mortality.

Background Complete handover of anesthesia care to a second anesthesiologist has been demonstrated to be associated with worse short-term adverse outcomes among cardiac surgery patients, but little information from multi-institutional studies is available. Methods New York's cardiac surgery registry was used to identify patients who underwent cardiac surgery in New York between 2010 and 2016 with and without complete handovers of anesthesia care. A retrospective observational study with inverse probability treatment weighting (IPTW) based on the propensity score was used to adjust for differences in preoperative patient characteristics while comparing differences in the primary outcome (in-hospital/30 day mortality), major complications in the index admission or within 30 days of the index surgery, readmissions within 30 days, and length of stay. Results A total of 8.5% of the 103,102 cardiac surgery procedures involved complete handovers. After adjustment, there was a difference between patients with and without handovers in the primary outcome (2.86% vs 2.48%, adjusted risk ratio [ARR] = 1.15 [1.01-1.31]). There was no difference in readmissions within 30 days (13.7% vs 14.4%, ARR = 0.95 [0.90-1.00]), and the differences in complications and length of stay were not clinically meaningful (adjusted differences of Conclusions Cardiac surgery patients in New York who had complete anesthesia handovers experienced higher short-term mortality rates, but there were no meaningful differences in other outcomes. Unnecessary handovers should be carefully monitored.

Background: Hybrid coronary revascularization (HCR) treats multivessel coronary artery disease by combining a minimally invasive surgical approach to the left anterior descending artery with percutaneous coronary intervention for non–left anterior descending diseased coronary arteries. The objective of this study is to compare HCR and conventional coronary artery bypass graft (CABG) surgery medium-term outcomes. Methods: Data from multivessel disease patients in New York’s cardiac surgery and percutaneous coronary intervention registries in 2010 to 2016 were used to compare mortality and repeat revascularization rates for HCR and conventional CABG after using propensity matching to reduce selection bias. Results: There was a total of 303 HCR (0.80%) patients and 37 556 conventional CABG patients after exclusions. After propensity matching, the respective median follow-up times were 3.72 years and 3.76 years. There was no difference between HCR and conventional CABG in survival at 6 years (80.9% versus 85.8%%, adjusted hazard ratio, 1.44 [0.90–2.31]), but HCR had higher mortality excluding deaths during the first year (adjusted hazard ratio, 1.88 [1.10–3.23]). Conventional CABG patients were more likely to be free from repeat revascularization at 6 years than HCR patients (88.2% versus 76.6%; hazard ratio, 2.22 [1.44–3.42]). Conclusions: HCR is rarely performed for patients with multivessel coronary artery disease. HCR and conventional CABG had no different 6-year mortality rates, but HCR had higher mortality after 1 year and higher rates of subsequent revascularization that were caused by both the need for repeat revascularization in the left anterior descending artery where minimally invasive CABG was performed, and in the coronary arteries where percutaneous coronary intervention was performed. Graphic Abstract: A graphic abstract is available for this article.

The Revivent TC™ Transcatheter Ventricular Enhancement System (BioVentrix Inc.) is intended for use in heart failure with cardiac dysfunction a previous myocardial infarction. The resultant increased left ventricular systolic volume and discrete, contiguous, noncontractile (akinetic and/or dyskinetic) scar located in the anteroseptal, apical (may extend laterally) region of the left ventricle (LV) lends itself to Revivent. The procedure, called Less Invasive Ventricular Enhancement, consists of the implantation of a series of microanchors pairs to exclude the scarred myocardium, to reduce and reshape the LV. We present the procedure step-by-step, as team coordination between the cardiac surgeon and the interventional cardiologist is essential to ensure good procedural outcomes. This is a novel and new technique to address heart failure secondary to myocardial infarction.

To determine the frequency and risk factors for non-home discharge (NHD) and its association with clinical outcomes and quality of life (QOL) at 1 year following cardiac surgery in patients with ischemic mitral regurgitation (IMR).Discharge disposition was evaluated in 552 patients enrolled in trials of severe or moderate IMR. Patient and in-hospital factors associated with NHD were identified using logistic regression. Subsequently, association of NHD with 1-year mortality, serious adverse events (SAEs), and QOL was assessed.NHD was observed in 30% (154/522) with 25% (n = 71/289) in moderate and 36% (n = 83/233) in patients with severe IMR (unadjusted P = .006), a difference not significant after including age (5-year change: adjusted odds ratio [adjOR], 1.52; 95% confidence interval [CI], 1.35-1.72; P .001), diabetes (adjOR, 1.94; 95% CI, 1.27-2.94; P = .002), and previous heart failure (adjOR, 1.64; 95% CI, 1.06-2.52; P = .03). Odds of NHD were increased for patients with postoperative SAEs (adjOR, 1.85; 95% CI, 1.19-2.86; P = .01) but not based on type of cardiac surgery. Greater rates of death and SAEs were observed in NHD patients at 1 year: adjusted hazard ratio, 4.29 (95% CI, 2.14-8.59; P .001) and adjusted rate ratio, 1.45 (95% CI, 1.03-2.02; P = .03), respectively. QOL did not differ significantly between groups.NHD is common following surgery for IMR, influenced by older age, diabetes, previous heart failure, and postoperative SAEs. These patients may be at greater risk of death and subsequent SAEs after discharge. Discussion of NHD with patients may have important implications for decision-making and guiding expectations following cardiac surgery.

AIMS Surgical ventricular reconstruction to remodel, reshape, and reduce ventricular volume is an effective therapy in selected patients with chronic heart failure (HF) of ischaemic aetiology. The BioVentrix Revivent TC System offers efficacy comparable to conventional surgical ventricular reconstruction and is less invasive utilizing micro-anchor pairs to exclude scarred myocardium on the beating heart. Here, we present 12-months follow-up data of an international multicenter study. METHODS AND RESULTS Patients were considered eligible for the procedure when they presented with symptomatic HF [New York Heart Association (NYHA) class ≥II], left ventricular (LV) dilatation and dysfunction caused by myocardial infarction, and akinetic and/or dyskinetic transmural scarred myocardium located in the anteroseptal, anterolateral, and/or apical regions. A total of 89 patients were enrolled and 86 patients were successfully treated (97%). At 12 months, a significant improvement in LV ejection fraction (29 ± 8% vs. 34 ± 9%, P

Objective The Cardiothoracic Surgical Trials Network reported that left ventricular reverse remodeling at 2 years did not differ between patients with moderate ischemic mitral regurgitation randomized to coronary artery bypass grafting plus mitral valve repair (n = 150) or coronary artery bypass grafting alone (n = 151). To address health resource use implications, we compared costs and quality-adjusted survival. Methods We used individual patient data from the Cardiothoracic Surgical Trials Network trial on survival, hospitalizations, quality of life, and US hospitalization costs to estimate cumulative costs and quality-adjusted life years. A microsimulation model was developed to extrapolate to 10 years. Bootstrap and deterministic sensitivity analyses were performed to address uncertainty. Results In-hospital costs were $59,745 for coronary artery bypass grafting plus mitral valve repair versus $51,326 for coronary artery bypass grafting alone (difference $8419; 95% uncertainty interval, 2259-18,757). Two-year costs were $81,263 versus $67,341 (difference 13,922 [2370 to 28,888]), and quality-adjusted life years were 1.35 versus 1.30 (difference 0.05; −0.04 to 0.14), resulting in an incremental cost-effectiveness ratio of $308,343/quality-adjusted life year for coronary artery bypass grafting plus mitral valve repair. At 10 years, its costs remained higher ($107,733 vs $88,583, difference 19,150 [−3866 to 56,826]) and quality-adjusted life years showed no difference (−0.92 to 0.87), with 5.08 versus 5.08. The likelihood that coronary artery bypass grafting plus mitral valve repair would be considered cost-effective at 10 years based on a cost-effectiveness threshold of $100K/quality-adjusted life year did not exceed 37%. Only when this procedure reduces the death rate by a relative 5% will the incremental cost-effectiveness ratio fall below $100K/quality-adjusted life year. Conclusions: The addition of mitral valve repair to coronary artery bypass grafting for patients with moderate ischemic mitral regurgitation is unlikely to be cost-effective. Only if late mortality benefits can be demonstrated will it meet commonly used cost-effectiveness criteria.

Background The incidence of permanent pacemaker (PPM) implantation is higher following mitral valve surgery (MVS) with ablation for atrial fibrillation (AF) compared with MVS alone. Objectives This study identified risk factors and outcomes associated with PPM implantation in a randomized trial that evaluated ablation for AF in patients who underwent MVS. Methods A total of 243 patients with AF and without previous PPM placement were randomly assigned to MVS alone (n = 117) or MVS + ablation (n = 126). Patients in the ablation group were further randomized to pulmonary vein isolation (PVI) (n = 62) or the biatrial maze procedure (n = 64). Using competing risk models, this study examined the association among PPM and baseline and operative risk factors, and the effect of PPM on time to discharge, readmissions, and 1-year mortality. Results Thirty-five patients received a PPM within the first year (14.4%), 29 (83%) underwent implantation during the index hospitalization. The frequency of PPM implantation was 7.7% in patients randomized to MVS alone, 16.1% in MVS + PVI, and 25% in MVS + biatrial maze. The indications for PPM were similar among patients who underwent MVS with and without ablation. Ablation, multivalve surgery, and New York Heart Association functional (NYHA) functional class III/IV were independent risk factors for PPM implantation. Length of stay post-surgery was longer in patients who received PPMs, but it was not significant when adjusted for randomization assignment (MVS vs. ablation) and age (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.61 to 1.08; p = 0.14). PPM implantation did not increase 30-day readmission rate (HR: 1.43; 95% CI: 0.50 to 4.05; p = 0.50). The need for PPM was associated with a higher risk of 1-year mortality (HR: 3.21; 95% CI: 1.01 to 10.17; p = 0.05) after adjustment for randomization assignment, age, and NYHA functional class. Conclusions AF ablation, multivalve surgery, and NYHA functional class III/IV were associated with an increased risk for permanent pacing. PPM implantation following MVS was associated with a significant increase in 1-year mortality. (Surgical Ablation Versus No Surgical Ablation for Patients With Atrial Fibrillation Undergoing Mitral Valve Surgery; NCT00903370)

Background Surgical ventricular reconstruction to remodel, reshape and reduce ventricular volume is an effective therapy in selected patients with ischemic heart failure (IHF). The BioVentrix Revivent System offers comparable efficacy to conventional surgical ventricular reconstruction aiming to exclude nonfunctioning myocardium, reshape ventricular size and reduce ventricular volume in selected patients with IHF, but is a less-invasive procedure on the beating heart. With this study we aimed to assess its functional effectiveness. Methods Patient were considered eligible for the procedure when they presented with symptomatic (at least NYHA II) left ventricular (LV) dilatation and dysfunction, caused by myocardial infarction (MI) that occurred at least 90 days prior to study enrollment, and with akinetic and/or dyskinetic scarred myocardium of at least 50% transmurality located in the antero-septal, anterolateral, and/or apical regions. The BioVentrix Revivent System consists of polyester-covered titanium anchor pairs that are drawn together to exclude scarred areas of the LV free wall. The anchors were implanted via sternotomy or, alternatively, through a combined mini-thoracotomy and transcatheter procedure. Results Eighty-nine patients were enrolled. At 2 years, a significant improvement in LVEF(30 ± 8% vs 34 ± 9%, p Conclusions Less invasive reconstruction with the BioVentrix Revivent system in patients with symptomatic IHF results in significant and sustained improvement of LV function, reduction in LV volumes with reduction of heart failure symptoms and improved quality of life at mid-term follow-up.

Objectives The purpose of this study was to investigate changes in the use of transcatheter aortic valve replacement (TAVR) relative to surgical aortic valve replacement (SAVR) and to examine relative 1-year TAVR and SAVR outcomes in 2011 to 2012 in a population-based setting. Background TAVR has become a popular option for patients with severe aortic stenosis, particularly for higher-risk patients. Methods New York’s Cardiac Surgery Reporting System was used to identify TAVR and SAVR volumes and to propensity match TAVR and SAVR patients using numerous patient risk factors contained in the registry to compare 1-year mortality rates. Mortality rates were also compared for different levels of patient risk. Results The total number of aortic valve replacement patients increased from 2,291 in 2011 to 2,899 in 2012, an increase of 27%. The volume of SAVR patients increased by 7.1% from 1,994 to 2,135 and the volume of TAVR patients increased 157% from 297 to 764. The percentage of SAVR patients that were at higher risk (≥3% New York State [NYS] score, equivalent to a Society of Thoracic Surgeons score of about 8%) decreased from 27% to 23%, and the percentage of TAVR patients that were at higher risk decreased from 83% to 76%. There was no significant difference in 1-year mortality between TAVR and SAVR patients (15.6% vs. 13.1%; hazard ratio [HR]: 1.30 [95% confidence interval (CI): 0.89 to 1.92]). There were no differences among patients with NYS score Conclusions TAVR has assumed a much larger share of all aortic valve replacements for severe aortic stenosis, and the average level of pre-procedural risk has decreased substantially. There are no differences between 1-year mortality rates for TAVR and SAVR patients.

OBJECTIVE: To analyze patient risk factors and processes of care associated with secondary surgical site infection (SSI) after coronary artery bypass grafting (CABG). METHODS: Data were collected prospectively between February and October 2010 for consenting adult patients undergoing CABG with saphenous vein graft (SVG) conduits. Patients who developed a deep or superficial SSI of the leg or groin within 65 days of CABG were compared to those who did not develop a secondary SSI. RESULTS: Among 2,174 patients identified, 65 (3.0%) developed a secondary SSI. Median time to diagnosis was 16 days (interquartile range [IQR]: 11 - 29) with the majority (86%) diagnosed after discharge. Gram-positive bacteria were most common. Readmission was more common in patients with a secondary SSI (34% vs 17%, p < 0.01). After adjustment, an open SVG harvest approach was associated with an increased risk of secondary SSI (adjusted hazard ratio [HR]: 2.12, 95% confidence interval [CI]: 1.28, 3.48). Increased body mass index (BMI) (adjusted HR: 1.08, 95% CI: 1.04, 1.12) and packed red blood cell (PRBC) transfusions (adjusted HR: 1.13, 95% CI: 1.05, 1.22) were associated with a higher risk of secondary SSI. Antibiotic type, antibiotic duration, and post-operative hyperglycemia were not associated with risk of secondary SSI. CONCLUSIONS: Secondary SSI following CABG continues to be an important source of morbidity. This serious complication often occurs after discharge and is associated with open SVG harvesting, larger BMI, and blood transfusions. Patients with a secondary SSI have longer lengths of stay and are readmitted more frequently.

OBJECTIVES: Surgical ventricular reconstruction has been used to treat ischaemic cardiomyopathy with large akinetic or dyskinetic areas. However, application of this approach requires a sternotomy, cardiopulmonary bypass and a left ventriculotomy. This study assessed the feasibility and efficacy of minimally invasive, off-pump, epicardial catheter-based ventricular reconstruction (ECVR) in an anteroapical aneurysm ovine model. METHODS: Left ventricular (LV) anteroapical myocardial infarction was induced percutaneously by coil embolization of the left anterior descending coronary artery. Eight weeks after infarction, via mini left thoracotomy and without cardiopulmonary bypass, ECVR was performed in six sheep. The scar was excluded by placing anchor pairs on the LV epicardial anterior wall and the right ventricular side of the interventricular septum under fluoroscopic guidance. LV performance was evaluated before, immediately after device implantation and after 6 weeks by echocardiography. Terminal histopathology was performed. RESULTS: ECVR was completed expeditiously in all animals without complications. Parameters obtained 6 weeks after device implantation were compared with baseline (pre-device). End-systolic volume was decreased by 38% (25.6 ± 6.1 ml vs baseline 41.2 ± 7.2 ml, P= 0.02) with preservation of stroke volume. Ejection fraction was significantly increased by 13% (48.5 ± 7% vs baseline 35.8 ± 7%, P= 0.02). The circumferential strain in the anterior septum (−7.67 ± 5.12% vs baseline −0.96 ± 2.22%, P= 0.03) and anterior wall (−9.01 ± 3.51% vs baseline −4.15 ± 1.36%, P= 0.01) were significantly improved. The longitudinal strain in apex was reversed (−3.08 ± 1.53% vs baseline 3.09 ± 3.39%, P= 0.01). Histopathology showed full endocardial healing over the anchors with appreciable reduction of the chronic infarct in the LV. CONCLUSIONS: ECVR without cardiopulmonary bypass is a less invasive alternative to current standard therapies, reverses LV remodelling and improves cardiac performance in an ovine model of anteroapical aneurysm.

Few studies have examined differences in long-term mortality between coronary artery bypass graft surgery and stenting with drug-eluting stents (DES) for multivessel disease without left main coronary artery stenosis. This study compares the risks of long-term mortality between these 2 procedures during a follow-up of up to 5 years.Patients who underwent isolated bypass surgery (n=13,212) and stenting with DES (n=20,161) between October 2003 and December 2005 in New York State were followed for their vital status through 2008. To control for treatment selection bias, bypass and stenting patients were matched on age, number of diseased coronary vessels, presence of proximal or nonproximal left anterior descending (LAD) artery disease, and propensity of undergoing bypass surgery. Five-year survival rates for the 2 procedures were compared and hazard ratios for death of bypass surgery compared with stenting were obtained.The respective 5-year survival rates in the 8,121 pairs of matched bypass and stenting patients were 80.4% and 73.6% (p0.001), and the risk of death after bypass surgery was 29% lower than for stenting (hazard ratio = 0.71, 95% confidence interval: 0.67 to 0.77, p0.001). Significantly lower risks of death for bypass surgery were observed in patients with LAD artery disease but not in patients without LAD artery disease. Significantly lower risks of death for bypass surgery were also found in all patient subgroups defined by the presence of selected baseline risk factors.Bypass surgery is associated with lower risk of death than stenting with DES for multivessel disease without left main stenosis.

The management of patients with ischemic cardiomyopathy involves evaluation of the relative benefits of revascularization versus medical management, or the referral for advanced heart failure therapies. While the decision to proceed with revascularization may be straight-forward in patients with severe angina or important stenosis of the left main coronary artery, many patients have less clear indications for revascularization and require additional evaluation. Viability testing, assessment of hemodynamics or evaluation of mechanical dyssynchrony can provide information that may help define the relative risks of revascularization and medical management. Even in the situation where the operative risk is elevated, it may still be less than the risk of non-operative therapy. When faced with a patient with very high operative risk, one should consider alternative approaches such as cardiac transplantation or the use of long-term ventricular assist devices.

The elastic modulus of bioengineered materials has a strong influence on the phenotype of many cells including cardiomyocytes. On polyacrylamide (PAA) gels that are laminated with ligands for integrins, cardiac myocytes develop well organized sarcomeres only when cultured on substrates with elastic moduli in the range of 10 kPa to 30 kPa, near those of the healthy tissue. On stiffer substrates (>60 kPa) approximating the damaged heart, myocytes form stress fiber-like filament bundles but lack organized sarcomeres or an elongated shape. On soft (

Multiple ablation technologies are used to treat atrial fibrillation during cardiac operations. All such ablation technologies use locally induced temperature extremes (>50°C or −20°C) to kill tissue and create a lesion pattern in the atria which blocks activation pathways that initiate and sustain atrial fibrillation. The technologies used to heat tissue have included radiofrequency (RF), microwave, high-intensity focused ultrasound, and infrared laser. RF accounts for more than 95% of the heating-based ablation technology used by cardiac surgeons. Energy delivery with RF is easier to control than with some other technologies, the heating produced by the energy source is well understood, and manufacturing costs are not excessive. Whichever heating technology is used, control of energy delivery is required to ensure both safe and effective heating of the targeted tissue. All targeted tissue needs to be heated above 50°C to achieve cell death. However, the targeted tissue should not be heated above 100°C, as this can cause perforation due to a steam pop. In addition, adjacent noncardiac tissues must not be damaged during the ablation procedure. The best method to achieve this control uses direct measurement of tissue temperature, because the tissue temperature defines both the safe and effective limits for the ablative process.

The objective of the present study was to determine if a new procoagulant molecule, carbon monoxide releasing molecule (tricarbonyldichlororuthenium (II) dimer; CORM-2) would improve coagulation following cardiopulmonary bypass (CPB). Plasma was obtained from patients undergoing elective cardiac surgery requiring CPB. Whole blood was collected and anticoagulated with sodium citrate after induction of anesthesia and again after CPB and heparin neutralization with protamine. Blood samples were centrifuged for 15 min, with plasma collected and stored at -80°C prior to analysis. Samples were subsequently exposed to 0 or 100 μmol/l CORM-2, with coagulation activated with tissue factor. Data were collected with thrombelastography until clot strength stabilized. Patients underwent CPB for 133 ± 61 min (mean ± SD). The velocity of thrombus formation was significantly decreased (52%) by CPB, as was clot strength (53%). Addition of CORM-2 to plasma samples obtained after CPB significantly increased the velocity of clot formation (75%) and strength (52%) compared to matched unexposed samples. The lesion of plasmatic coagulation associated with CPB was significantly improved in vitro by addition of CORM-2. If preclinical assessments of efficacy and safety of CORM-2 are favorable, future clinical trials involving CORM-2 or other CORMs as a hemostatic intervention in the setting of CPB are justified.

Objective To use novel statistical methods for analyzing the effect of lesion set on (long-standing) persistent atrial fibrillation (AF) in the Cardiothoracic Surgical Trials Network trial of surgical ablation during mitral valve surgery (MVS). Methods Two hundred sixty such patients were randomized to MVS + surgical ablation or MVS alone. Ablation was randomized between pulmonary vein isolation and biatrial maze. During 12 months postsurgery, 228 patients (88%) submitted 7949 transtelephonic monitoring (TTM) recordings, analyzed for AF, atrial flutter (AFL), or atrial tachycardia (AT). As previously reported, more ablation than MVS-alone patients were free of AF or AF/AFL at 6 and 12 months (63% vs 29%; P Results Estimated freedom from AF/AFL/AT on any transmission trended higher after biatrial maze than pulmonary vein isolation (odds ratio, 2.31; 95% confidence interval, 0.95-5.65; P = .07) 3 to 12 months postsurgery; estimated AF/AFL/AT load (ie, proportion of TTM strips recording AF/AFL/AT) was similar (odds ratio, 0.90; 95% confidence interval, 0.57-1.43; P = .6). Within 12 months, estimated prevalence of AF/AFL/AT by TTM was 58% after MVS alone, and 36% versus 23% after pulmonary vein isolation versus biatrial maze (P Conclusions Statistical modeling using TTM recordings after MVS in patients with (long-standing) persistent AF suggests that a biatrial maze is associated with lower AF/AFL/AT prevalence, but not a lower load, compared with pulmonary vein isolation. The discrepancy between AF/AFL/AT prevalence assessed at 2 time points by Holter monitoring versus weekly TTM suggests the need for a confirmatory trial, reassessment of definitions for failure after ablation, and validation of statistical methods for assessing atrial rhythms longitudinally.

Most mediastinal masses seen on thoracic imaging are of solid tumor origin. As such, vascular lesions of the mediastinum can be mistaken for, or misinterpreted as, one of these more common mediastinal masses. This article stresses the importance of considering vascular entities in the differential diagnosis of mediastinal masses.

Background In patients with multivessel coronary artery disease, performing multiple internal mammary artery (MIMA) grafts to two coronary systems during coronary artery bypass grafting (CABG) improves clinical outcome. Few databases have decades of follow-up, however, and the optimal configuration is still in question. The purpose of this study was to assess 20-year clinical benefits of MIMA grafting and to evaluate the possible effects of two different MIMA configurations. Methods From 1984 to 1986, 867 patients with multivessel coronary disease underwent CABG. Single (SIMA) IMA grafts were used in 490 and multiple (MIMA) IMA grafts in 377, along with concomitant saphenous veins. Generally, MIMAs were placed to the two largest coronary systems. Among baseline characteristics, only smoking, diabetes, and hypertension were significantly higher for MIMA versus SIMA. Multivariable Cox model analysis was used to assess outcome differences between groups. Results During a median follow-up of 20 years, the composite of mortality, myocardial infarction, percutaneous coronary intervention, and redo CABG was significantly reduced after MIMA versus SIMA (p = 0.013). Event-free survival was extended by almost 1 year (p = 0.018), and redo CABG was reduced by 59% (p = 0.005). A comparison within the MIMA group was made between 235 patients receiving IMA grafts to left anterior descending/left circumflex territories versus 122 with grafts to left anterior descending/right coronary artery systems. No significant difference in composite outcome was observed between these configurations (p = 0.88). Conclusions These data confirm the clinical benefits of MIMA grafting in multivessel coronary disease to 20 years of follow-up. As long as MIMAs are placed to the two largest coronary systems, no significant differences in long-term results are evident between left anterior descending/left circumflex and left anterior descending/right coronary artery configurations.

Background— Several studies have compared short-term and medium-term mortality rates for patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR), but no studies have compared short-term readmission rates for the 2 procedures. Methods and Results— New York’s Cardiac Surgery Reporting System was used to propensity match 617 TAVI and 1981 SAVR patients using numerous patient risk factors contained in the registry. The 389 propensity-matched pairs were then used to analyze differences in readmission rates between the 2 groups. TAVI and SAVR readmission rates were also compared for patients with a history of congestive heart failure and for patients aged ≥80. Also, reasons for readmission for TAVI and SAVR patients were examined and compared. Readmission rates were not statistically different for all propensity-matched TAVI and SAVR patients (respective rates, 18.8% and 19.3%; P =0.86). After further adjustment using a logistic regression model, there was still no significant difference (adjusted odds ratio, 0.97; 95% confidence interval [0.68–1.39]). For patients aged ≥80, the 30-day readmission rates were 19.9% and 22.0% ( P =0.59), and when further adjusted using the logistic regression model, adjusted odds ratio=0.89 (0.55–1.45). For patients with a history of congestive heart failure, the respective rates were 22.8% and 20.4% ( P =0.56), and with further adjustment, adjusted odds ratio became 1.15 (0.72–1.82). Conclusions— There are no statistically significant differences between TAVI and SAVR patients in short-term readmission rates.

Background During tricuspid valve replacement in a patient with previous mitral valve surgery, we made an incidental observation that the right atrium can be opened without caval snaring and without air entering the venous reservoir. We tested this hypothesis on an animal model. Methods Two patients underwent right atrial surgery using percutaneous cannulation, and no air was entrained without caval snaring. This principle was tested in an animal model using 2 pigs weighing 80 kg each. Percutaneous cannulae were placed under epicardial echo guidance with their tips 4 cm from the right atrium. A “collapsible bag with air drainage system” was introduced into the venous return system to quantify air return from the superior vena cava (SVC) and inferior vena cava (IVC). Two types of percutaneous cannulae with (Cardiovations Quick Draw) and without (Biomedicus) proximal side holes were tested. Results In the animal model using Biomedicus cannulae, upon opening the right atrium, air was entrained from the SVC cannula at 60 mL/minute with no air in the IVC. There was no difference in the amount of air between the two cannulae. Pressures measured were 5 cm of water in the IVC and −20 cm water in the SVC. Epicardial ultrasound demonstrated complete collapse of both vena cavae. Partial clamping of the SVC cannula reduced the amount of air to 60 cc/min, and placing a small straight clamp at the SVC atrial junction eliminated the air. No air was noted in IVC cannula. Conclusions Inferior vena caval drainage by percutaneous cannula does not entrain air with either type of cannula and without snaring (both in clinical cases and animal model). This might be explained by the presence of a competent Eustachian valve. However, the SVC is not immune to air. Minimal air (approximately 60 mL/minute) could be managed by partial clamping or completely be avoided by placing a small straight clamp without snaring.

For the past thirty years cardiac surgeons have had a unique opportunity to study the consequences of myocardial ischemia and reperfusion. With the advent of an ability to intervene in acute myocardial syndromes, cardiologists have vigorously joined that effort as have fundamental scientists. Exogenous myocardial protective strategies have emerged as have novel strategies that take advantage of endogenous mechanisms of myocardial protection. As a consequence of improved myocardial protection, operative mortality and morbidity, in particular the low output syndrome, have diminished. However, despite important increases in the knowledge base referable to myocardial ischemia and reperfusion, major advances in myocardial protection have slowed in the past several years. This article explores potential untapped options for augmenting myocardial protection and focuses on the potential adverse interactions between cardiopulmonary bypass and myocardial protection as a prime target for future investigations leading to improved myocardial management during heart operations. Perfusion (2003) 18, 139i/143. It has been about 30 years since myocardial protection was identified as an important area for study by cardiac surgeons. I have had the opportunity to poll several audiences within the past few years regarding the management of two illustrative cases. One of these cases is a patient with complex coronary artery disease and the second is that of a patient with combined coronary and valvular heart disease. In each instance, I provided several options for the use of cardioplegia. These included the temperature and composition of the cardioplegia, the mode (antegrade and/or retrograde) delivery, the frequency of administration and the use of terminal warm cardioplegia. The point of most common agreement was that cardioplegia should be used and generally surgeons employ blood cardioplegia. Very few surgeons responded that they use complex buffering, metabolic fortification or normothermia. Most surgeons employ a selective use of retrograde cardioplegia and administer cardioplegia every 15 i/30 minutes. Remarkably, there was a great disparity among respondents if you consider the total cardioplegic strategy. I remain impressed at this fact, which may reflect the disagreement over the efficacy of the many advantages that complex cardioplegia compositions offer, a general satisfaction with the techniques individually employed or a dissociation between practical application and the science of myocardial protection. Surveys are useful to determine how effectively a body of evidence that may be derived from the literature is applied to daily practice. In this instance, the results are slightly surprising to the extent that one might have predicted a greater degree of uniformity of responses after 30 years of investigation in this field. Some of the reasons for these disparities are explored in this paper. When considering protection for the heart during cardiac operations, it is useful to consider the interaction between four elements common to most procedures. These are ischemia, reperfusion, cardiopulmonary bypass (CPB) and the operation performed. Each of these components of the surgery has the potential to induce injury. In any instance of injury, the inciting factor may be primarily the consequence of any one of these four causes, but the other three will always intensify the extent of injury. In recent years, the evolution of off-pump techniques for coronary bypass grafting has elimi

Background Several randomized controlled trials and observational studies have compared outcomes for coronary artery bypass graft (CABG) surgery and drug-eluting stents (DES), but these studies have not thoroughly investigated the relative difference in outcomes by sex. We aimed to compare 3-year outcomes (mortality, mortality/myocardial infarction/stroke, and repeat revascularization) for CABG surgery and percutaneous coronary interventions with DES by sex. Methods A total of 4,532 women (2,266 pairs of CABG and DES patients) and 11,768 men (5,884 pairs) were propensity matched separately using multiple patient risk factors and were compared with respect to 3-year outcomes. Results Both women and men receiving DES had significantly higher mortality rates (adjusted hazard ratio, 1.28; 95% confidence interval, 1.06 to 1.54 and adjusted hazard ratio, 1.22; 95% confidence interval, 1.06 to 1.41, respectively) and myocardial infarction/mortality/stroke rates (adjusted hazard ratio, 1.40; 95% confidence interval, 1.19 to 1.64 and adjusted hazard ratio, 1.36; 95% confidence interval, 1.20 to 1.54, respectively) with DES. The advantage for CABG surgery was also present for several preselected patient subgroups. Men had consistently lower adverse outcome rates than women for both procedures. For example, the mortality rates for CABG and DES for men were 8.0% and 9.1%, compared with respective rates of 11.8% and 13.7% for women. Conclusions For women, the advantage of CABG surgery over DES is very similar to what was found for men, and this advantage persisted for patients with and without high-risk characteristics.

Cardiovascular disease is one of the leading causes of death in the United States and also a major disease nationwide. Over 700,000 coronary artery bypass graft (CABG) procedures are performed annually all around the world, of which 350,000 are performed in the United States. The use of mechanical stabilizers to isolate and immobilize the surface region of the heart is not without its limitations such as hemodynamic deterioration, and arrythmia induction requiring inotropic support. Consequently, the use of mechanical stabilizers leads to a poor immobilization of the surgical field in spite of significant forces of traction and retraction used with these devices. The primary goal of this research is to develop effective haptic (sense of touch) and visual servoing methods with the long-term goal of eliminating the need for mechanical stabilizers and extracorporeal support for CABG procedures. We present in this paper the results from our initial work in the area of tracking a deformable membrane using vision and providing haptic feedback to the user, based on the visual information through the vision hardware and the material properties of the membrane. In our first experiment, we track the deformation of a rubber membrane in real-time through stereovision while providing haptic feedback to the user interacting with the reconstructed membrane through the PHANToM haptic device. In the second experiment, we verify the ability of our vision system to track a point on a surface undergoing a complex 3D motion.

Background . Mechanical circulatory assist industries have developed ventricular assist devices (VAD) for short-, intermediate-, and long-term use. The purpose of this report is to describe the progress made with the ABIOMED Biventricular System (BVS) 5000 (ABIOMED, Inc, Danvers, MA) short-term VAD. Methods . From June 1994 through August 2000, all cardiogenic shock patients who required short-term mechanical assist were supported with the ABIOMED BVS 5000. Insertion criteria included any condition that may potentially result in cardiac recovery. A formal algorithm for timing of insertion was established to standardize implantation criteria. Results . A total of 45 patients were supported at Hahnemann University Hospital, Philadelphia, PA. There were 26 male and 19 female patients, with a mean age of 57.9 years (range 33 to 80 years). Devices were inserted for postcardiotomy shock in 36 patients (80%) and precardiotomy shock in 9 patients (20%). The average duration of support was 8.3 days (range 1 to 31 days). Overall, there were 22 (49%) patients weaned from support and 14 (31%) discharged from the hospital. For patients in whom the device was implanted in accordance with an established protocol (group A), the wean and discharge rates were 60% and 43%, respectively. The most common morbidities included bleeding and adverse neurologic events. Conclusions . The ABIOMED BVS 5000 VAD continues to be a valuable form of short-term mechanical assist for acute cardiogenic shock. The formation of a uniform VAD insertion algorithm has helped to standardize protocols in management.

Objective: The first months after orthotopic heart transplantation are associated with the highest risk of acute allograft rejection. This study explores the utility and reliability of linear and novel nonlinear metrics of heart rate variability as predictors of graft rejection. The underlying hypothesis is that the transplanted heart, in response to inflammatory mediators, alters the dynamic properties of its rhythm-generating system. Methods: In a cross-sectional study of 45 patients who had undergone heart transplantation, spanning a period of 4 months after the operation, heart rate variability was examined by time- and frequency-domain analysis. The nonlinear features of heart rate variability were studied by computing a pointwise correlation dimension of R-R interval time series. The results of heart rate variability analysis were compared with those of endomyocardial surveillance biopsy studies using the International Society for Heart and Lung Transplantation scoring system. Results: Duration of heart transplantation itself exhibited a significant (P < .05) association with the onset of rejection. Specific predictors of acute rejection based on heart rate variability were identified, including shortening of the R-R interval (from 700 ± 68 to 648 ± 72 ms), an increase in the ratio of low-frequency (0.04-0.15 Hz) to high-frequency (0.15-0.40 Hz) spectral power (from 0.3 ± 0.2 to 0.6 ± 0.4), and a decrease in pointwise correlation dimension values (from 1.7 ± 0.7 to 0.9 ± 0.3 units). Multivariable logistic regression analysis (R 2 = 0.4) revealed that the only significant independent risk predictors were pointwise correlation dimension (odds ratio, 2.2 per 0.1 unit) and duration of heart transplantation (odds ratio, 1.7 per week). Conclusion: Nonlinear measures of heart rate variability provide noninvasive means for identifying patients undergoing cardiac transplantation with acute rejection, thereby enabling the assessment of the time-dependent adaptive response of the donor heart to its host. (J Thorac Cardiovasc Surg 2000;120:737-45)

Vascular rings are congenital lesions that cause tracheobronchial and esophageal symptoms as a result of compression of these structures. The majority of cases are recognized in infancy, childhood, and occasionally adolescence. Rarely, vascular rings first present in adulthood. The authors present the case of a vascular ring in an elderly woman who complained of dysphagia.

Alpha-adrenergic stimulation induces protection in reperfused ischemic (I/R) myocardium 24 hours later. We tested the hypothesis that phenylephrine improves dysfunction after global I/R by limiting cell death not stunning.Rabbits were pretreated with either phenylephrine or vehicle. Twenty-four hours later, isolated hearts underwent either 45 (infarction protocol) or 20 minutes (stunning protocol) of global ischemia before 2 hours of reperfusion (n = 6 per group). Cell death was determined by triphenyl tetrazolium chloride staining (infarction) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) (apoptosis).Compared with vehicle, phenylephrine pretreatment improved post-I/R-developed pressures in hearts after infarction (53.2 +/- 4.0 vs 35.8 +/- 4.1 mm Hg, p = 0.01) but not stunning protocol (64.3 +/- 8.9 vs 57.7 +/- 6.2 mm Hg, p = NS). The improved developed pressure was due to better diastolic recovery. Systolic pressures were similar between groups. Phenylephrine markedly decreased infarction (9.0 +/- 1.9% vs 40.8 +/- 1.8% for vehicle, p0.001) and TUNEL-positive staining. Stunned hearts of either group had less than 3% infarction and no apoptosis.Phenylephrine pretreatment 24 hours before global I/R improves function by limiting infarction but not stunning.

The incidence of coronary artery disease in identical twins is unknown. The knowledge of ischemic heart disease in this patient population is represented by case reports. There is considerable controversy regarding the environmental and genetic factors that play a role in the pathogenesis of this disorder. The natural history of coronary artery disease in an asymptomatic twin with a symptomatic counterpart is unclear. We present a case report and literature review of coronary artery disease in identical twins. On the basis of our patient and the information of other patients, asymptomatic twins of symptomatic counterparts require aggressive assessment and management for occult coronary artery disease.

Objective: Previous studies have demonstrated that α1-adrenoceptor activation increases myocardial resistance to ischemic injury 24 hours later. Here we tested the hypothesis that delayed protection is associated with limited infarction and involves altered expression of pro-apoptotic and/or anti-apoptotic proteins. Methods : Rabbits were treated with phenylephrine or an equivalent volume of vehicle (n = 6 per group). Twenty-four hours after pretreatment, isolated hearts were perfused with a bovine erythrocyte suspension in modified Krebs solution, subjected to 45 minutes of global ischemia (37°C), and reperfused for 120 minutes. Infarct size was determined by triphenyltetrazolium chloride staining. Apoptosis was quantified by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Left ventricular tissue from separate groups of animals (n = 5 per group), 24 hours after pretreatment with phenylephrine or vehicle but without ischemia and reperfusion, was analyzed by Western blotting for content of the anti-apoptotic protein, bcl x , and pro-apoptotic protein, bax. Results : Isolated hearts after phenylephrine pretreatment had increased end-reperfusion developed pressures (56.8 ± 4.9 vs 36.2 ± 3.9 mm Hg for vehicle, P = .008) and decreased elevated end-diastolic pressures (26.7 ± 4.5 vs 42.3 ± 5.0 mm Hg for vehicle, P = .04). Phenylephrine pretreatment abrogated infarction (9.9 ± 2.4% vs 42.6 ± 6.3% for vehicle, P = .002) and reduced the number of apoptotic nuclei (24 ± 4.8 vs 51 ± 4.6 for vehicle, P = .038). Analysis by Western blotting showed that the ratio of bcl x to bax protein increased in phenylephrine-pretreated hearts (2.65 ± 0.5 vs 1.0 ± 0.1 for vehicle, P = .008). Conclusion : Delayed myocardial protection to infarction mediated by α1-adrenoceptor activation involves an increased bcl x /bax ratio, thereby limiting apoptotic cell death. (J Thorac Cardiovasc Surg 1999;117:980-6)

Ultrastructural studies of stunned myocardium have shown disorganization and loss of extracellular collagen and increased collagenase activity early after ischemia and reperfusion. The interplay between matrix metalloproteinase 1 (MMP-1) and tissue inhibitor of metalloproteinase 1 (TIMP-1) regulates the turnover of cardiac extracellular matrix fibrillar collagens. However, the gene expression of MMP-1 and TIMP-1 in stunned myocardium is not known. Here, we determined whether altered expression of MMP-1 and TIMP-1 occurs in globally stunned hearts. An isolated nonworking rabbit heart preparation, perfused with a bovine erythrocyte suspension in modified Krebs solution, was used. Two groups were studied: the stunned group was subjected to 20 min of normothermic global ischemia followed by 120 min of normal reperfusion (n = 8), and the control group underwent 140 min of uninterrupted perfusion (n = 7). The developed pressures at the end of reperfusion for ischemic and control hearts were 67.0 +/- 2.73 and 83.1 +/- 1.52 mm Hg (P < 0. 006) respectively. Ribonuclease protection assays of total left ventricular RNA using riboprobes for MMP-1, TIMP-1, and 18S rRNA were performed. A significant decrease (twofold, P < 0.03) in TIMP-1 gene expression was found in the stunned hearts, while MMP-1 mRNA expression was unchanged. Thus, in early stunning, the decrease in TIMP-1 expression could tip the balance favoring enhanced metalloproteinase activity, promoting collagen turnover, and initiating extracellular matrix remodeling. This may contribute to delayed recovery from myocardial stunning.

Previously, we have demonstrated the role of nucleoside transport and purine release in post-ischemic reperfusion injury (myocardial stunning) in several canine models of ischemia. Since rabbits are deficient of xanthine oxidase, it is not known whether selective blockade of purine release is beneficial in a rabbit model of coronary artery occlusion and reperfusion (stunning). Therefore, we determined the hemodynamic and metabolic correlates in response to myocardial stunning in the presence or absence of selective nucleoside transport blocker (p-nitrobenzylthioinosine, NBMPR) and adenosine deaminase inhibitor (erythro-9-(2-hydroxy-3-nonyl)adenine, EHNA). Sixty adult anaesthetized rabbits were surgically prepared for hemodynamic measurements. After stabilization period, the left anterior descending coronary artery was occluded for 15 min and reperfused for 30 min. Transmural myocardial biopsies were obtained from the ischemic LAD area and from the non-ischemic posterior (circumflex, CFX) segment of the myocardium. Rabbits (n = 60) were randomly assigned to either the control or the EHNA/NBMPR-treated group (n = 30 each). Each group was further divided to either functional or metabolic groups (n = 15 each subgroup). Each animal received intravenously 30 ml of either a vehicle solution or 100 M EHNA and 25 M NBMPR 10 min before ischemia. Although administration of EHNA/NBMPR did not affect the heart rate, it did cause mild hypotension (about 20-30%). Fifteen minutes of LAD occlusion resulted in significant ATP depletion and concomitant accumulation of nucleosides in both groups (p < 0.05 vs. baseline and non-ischemic CFX segment). AMP was higher in the LAD compared to the CFX segment. Significant accumulation of adenosine was observed in the treated group compared to the control group. It is concluded that EHNA/NBMPR induced site specific entrapment of adenosine of nucleoside transport in the rabbit heart, in vivo.

Chronic low frequency stimulation of predominantly fast-twitch skeletal muscles decrease the levels of SERCA1 (fast-twitch sarco(endo)plasmic reticulum Ca2+-ATPase) mRNA, and increase the levels of SERCA2 (slow-twitch sarco(endo)plasmic reticulum Ca2+-ATPase) and phospholamban mRNAs. To assess the role of transcription in these changes in mRNA levels, nuclei were isolated from chronically stimulated canine latissimus dorsi muscles and transcription rates were estimated by nuclear run-on assays. Decreases in the rates of SERCA1 gene transcription matched the fall in its mRNA level and increases in the rates of SERCA2 and phospholamban gene transcription matched the increases in their mRNAs.

The canine latissimus dorsi was stimulated at 1 Hz via the thoracodorsal nerve for 70 days. Seven days of muscle stimulation caused muscle mass, fibre cross-sectional areas, and tetanic tensions to decrease. Fourteen days of stimulation produced marked decreasesin Ca2+-uptake rates in a membrane fraction containing sarcoplasmic reticulum. At this time there was a decline infusion frequency, but no statistically significant changes in time-to-peak tension, total contraction times, or half-relaxation times. With 42 days of stimulation a switch from the fast-twitch to the slow-twitch phenotype was indicated by elevations in the levels of expression of the slow-twitch isoform of sarco(endo)plasmic reticulum Ca2+-ATPase and myosin heavy chain-I, and increases in half-relaxation times, total contraction times and time-to-peak tensions. Decreases in muscle shortening velocity correlated negatively with increases in myosin heavy chain-I levels. Up-regulation of the slow-twitch isoform of sarco(endo)plasmic reticulum Ca2+-ATPase protein positively correlated with increases in half-relaxation times. The changes in the slow-twitch isoform of sarco(endo)plasmic reticulum Ca2+-ATPase and myosin heavy chain-I levels indicated coordinate expression of these two proteins in chronically stimulated muscles