Mid-term outcomes of concomitant Cox-Maze IV: Results from a multicenter prospective registry.

BACKGROUND: Benefits of concomitant atrial fibrillation (AF) surgical treatment are well established. Cardiac societies support treating AF during cardiac surgery with a class I recommendation. Despite these guidelines, adoption has been inconsistent. We report results of routine performance of concomitant Cox-Maze IV (CMIV) from participating centers using a standardized, prospective registry. METHODS: Nine surgeons at four cardiac surgery programs enrolled 807 patients undergoing concomitant CMIV surgery over 12 years. Lesions were created using bipolar radiofrequency clamps and cryoablation probes. Follow-up occurred at 3- and 6-months, then annually for 3 years. Freedom from AF was defined as no episode >30 s of atrial arrhythmia. RESULTS: Sixty-four percent of patients were male, mean age 69 years, mean left atrial size 4.6 cm, mean preoperative AF duration 4.0 years, mean EuroSCORE 6.4, and mean CHADS2 score 3.1. Thirty-day postoperative mortality and neurologic event rates were 3.3% and 1.3%, respectively. New pacemaker implant rate was 6.3%. Freedom from AF rates at 1- and 3-years stratified by preoperative AF type were: paroxysmal 94.6% and 87.5%, persistent 82.1% and 81.9%, and longstanding persistent 84.1% and 78.1%. At 3-year follow up, 84% of patients were off antiarrhythmic drugs and 74% of sinus rhythm patients were off oral anticoagulants. CONCLUSIONS: Routine CMIV is safe and effective. Acceptable outcomes can be achieved across multiple centers and multiple operators even in a moderate risk patient population undergoing more complex procedures. Surgeons and institutions should be encouraged by all cardiac societies to adopt the CMIV procedure to maximize patient benefit.

Heparin-induced thrombocytopenia presenting as splenic hemorrhage following cardiac surgery: a case report.

BACKGROUND: Heparin-induced thrombocytopenia with thrombosis (HITT) is a paradoxical prothrombotic complication of anticoagulant therapy. As many as 3% of patients undergoing cardiac surgery develop clinical HIT presenting as thrombocytopenia with or without thrombosis within 5-10 days of heparin exposure. Thrombotic complications associated with HIT carry a mortality rate of 5-10%. CASE PRESENTATION: We report a case of atraumatic splenic hemorrhage due to splenic vein thrombosis as the main indicator of HIT following cardiac surgery in a 62-year-old woman. She presented to the emergency department on day nine following coronary artery bypass graft surgery with acute weakness, dizziness, and malaise. Her evaluation in the emergency department found anemia and thrombocytopenia. A coagulation profile revealed a markedly elevated d-dimer. She underwent a computed tomography scan of the chest, abdomen and pelvis for suspected bleed and was found to have splenic vein thrombosis, right atrial filling defects consistent with atrial thrombus and mild to moderate hemoperitoneum. Surgical consultation was obtained due to splenic hemorrhage. Hematology was consulted on post-operative day 10, however, she unfortunately developed left sided weakness concerning for stroke. A magnetic resonance imaging scan of the brain demonstrated infarct involving distribution of the right anterior cerebral artery. A transesophageal echocardiogram demonstrated a large immobile thrombus within the right atrium with a second, mobile thrombus arising from the left tricuspid valve annulus. Due to a 4Ts score of 7 and markedly positive platelet factor 4 (PF4) IgG antibody a serotonin release assay was not performed given the high probability of HIT. She was cautiously treated with bivalirudin and was transitioned to warfarin anticoagulation. In the following days her platelet count recovered and 3 months later a transthoracic echocardiogram revealed solution of the intracardiac thrombi. CONCLUSIONS: Atraumatic splenic hemorrhage is an unusual presentation of HIT that is reminiscent of the rare bilateral adrenal hemorrhage due to adrenal necrosis that also occurs in HIT. Alternative anticoagulation is the mainstay of therapy for HIT despite hemorrhage, given the underlying acquired hypercoagulability. Despite similarities of the presentation between splenic hemorrhage and bilateral adrenal hemorrhage, splenic hemorrhage is rarely described in the literature. HIT should be considered in patients presenting with thrombocytopenia following cardiac surgery.

Effects of red-cell storage duration on patients undergoing cardiac surgery.

BACKGROUND: Some observational studies have reported that transfusion of red-cell units that have been stored for more than 2 to 3 weeks is associated with serious, even fatal, adverse events. Patients undergoing cardiac surgery may be especially vulnerable to the adverse effects of transfusion. METHODS: We conducted a randomized trial at multiple sites from 2010 to 2014. Participants 12 years of age or older who were undergoing complex cardiac surgery and were likely to undergo transfusion of red cells were randomly assigned to receive leukocyte-reduced red cells stored for 10 days or less (shorter-term storage group) or for 21 days or more (longer-term storage group) for all intraoperative and postoperative transfusions. The primary outcome was the change in Multiple Organ Dysfunction Score (MODS; range, 0 to 24, with higher scores indicating more severe organ dysfunction) from the preoperative score to the highest composite score through day 7 or the time of death or discharge. RESULTS: The median storage time of red-cell units provided to the 1098 participants who received red-cell transfusion was 7 days in the shorter-term storage group and 28 days in the longer-term storage group. The mean change in MODS was an increase of 8.5 and 8.7 points, respectively (95% confidence interval for the difference, -0.6 to 0.3; P=0.44). The 7-day mortality was 2.8% in the shorter-term storage group and 2.0% in the longer-term storage group (P=0.43); 28-day mortality was 4.4% and 5.3%, respectively (P=0.57). Adverse events did not differ significantly between groups except that hyperbilirubinemia was more common in the longer-term storage group. CONCLUSIONS: The duration of red-cell storage was not associated with significant differences in the change in MODS. We did not find that the transfusion of red cells stored for 10 days or less was superior to the transfusion of red cells stored for 21 days or more among patients 12 years of age or older who were undergoing complex cardiac surgery. (Funded by the National Heart, Lung, and Blood Institute; RECESS ClinicalTrials.gov number, NCT00991341.).

The "free" right internal thoracic artery: a versatile and durable conduit.

BACKGROUND: Despite its potential advantages, the right internal thoracic artery (RITA) is used as a conduit in only 4% of coronary revascularizations. To broaden its application, we frequently use the RITA as a free graft. In this study, we review our experience with the RITA as an in situ and free graft. METHODS: We reviewed the perioperative outcomes and angiographic patency rates of 479 consecutive patients who underwent RITA grafting between January 1987 and December 2011. RESULTS: The RITA was harvested free (FRITA) in 380 patients (79%) and in situ in 99 (21%). The predominant target for the in situ RITA was the right coronary system (79%). The predominant targets for the FRITA were divided between the right (54%) and left coronary systems (46%). There was no perioperative mortality. Mean follow-up was 10 years. Perioperative complications included myocardial infarction (0.4%), sternal nonunions (0.4%), and reoperation for hemorrhage (0.6%). Coronary angiograms were performed in symptomatic patients (17%) after a median of seven years. FRITA patency rates at five, 10, and 15 years were 100%, 95%, and 95%, respectively, comparable to the left internal thoracic artery patency rates and superior to those of saphenous vein graft. Survival rates of FRITA patients at 10, 15, and 20 years were 92%, 89%, and 76%, respectively. CONCLUSION: The FRITA graft reaches all distal coronary vessels and is associated with excellent patency and survival rates. Its application in coronary revascularization vastly expands the benefits of internal thoracic artery grafting.

Underwater Soft Robotics: A Review of Bioinspiration in Design, Actuation, Modeling, and Control.

Nature and biological creatures are some of the main sources of inspiration for humans. Engineers have aspired to emulate these natural systems. As rigid systems become increasingly limited in their capabilities to perform complex tasks and adapt to their environment like living creatures, the need for soft systems has become more prominent due to the similar complex, compliant, and flexible characteristics they share with intelligent natural systems. This review provides an overview of the recent developments in the soft robotics field, with a focus on the underwater application frontier.

Design and control of soft biomimetic pangasius fish robot using fin ray effect and reinforcement learning.

Soft robots provide a pathway to accurately mimic biological creatures and be integrated into their environment with minimal invasion or disruption to their ecosystem. These robots made from soft deforming materials possess structural properties and behaviors similar to the bodies and organs of living creatures. However, they are difficult to develop in terms of integrated actuation and sensing, accurate modeling, and precise control. This article presents a soft-rigid hybrid robotic fish inspired by the Pangasius fish. The robot employs a flexible fin ray tail structure driven by a servo motor, to act as the soft body of the robot and provide the undulatory motion to the caudal fin of the fish. To address the modeling and control challenges, reinforcement learning (RL) is proposed as a model-free control strategy for the robot fish to swim and reach a specified target goal. By training and investigating the RL through experiments on real hardware, we illustrate the capability of the fish to learn and achieve the required task.

Modeling of Soft Pneumatic Actuators with Different Orientation Angles Using Echo State Networks for Irregular Time Series Data.

Modeling of soft robotics systems proves to be an extremely difficult task, due to the large deformation of the soft materials used to make such robots. Reliable and accurate models are necessary for the control task of these soft robots. In this paper, a data-driven approach using machine learning is presented to model the kinematics of Soft Pneumatic Actuators (SPAs). An Echo State Network (ESN) architecture is used to predict the SPA's tip position in 3 axes. Initially, data from actual 3D printed SPAs is obtained to build a training dataset for the network. Irregular-intervals pressure inputs are used to drive the SPA in different actuation sequences. The network is then iteratively trained and optimized. The demonstrated method is shown to successfully model the complex non-linear behavior of the SPA, using only the control input without any feedback sensory data as additional input to the network. In addition, the ability of the network to estimate the kinematics of SPAs with different orientation angles θ is achieved. The ESN is compared to a Long Short-Term Memory (LSTM) network that is trained on the interpolated experimental data. Both networks are then tested on Finite Element Analysis (FEA) data for other θ angle SPAs not included in the training data. This methodology could offer a general approach to modeling SPAs with varying design parameters.

A Reproducible and Effective Technique for Coronary Sinus Injury Repair.

Objective: Coronary sinus injury related to the use of a retrograde cardioplegia catheter is a rare but potentially life-threatening complication with mortality reported as high as 20%. We present a series of iatrogenic coronary sinus injuries as well as an effective method of repair without any ensuing mortality. Methods: There were 3,004 cases that utilized retrograde cardioplegia at our institution from 2007 to 2018. Of these, 15 patients suffered a coronary sinus injury, an incidence of 0.49%. A pericardial roof repair was performed in 14 cases in which autologous pericardium was sutured circumferentially to normal epicardium around the injury with purified bovine serum albumin and glutaraldehyde injected into the newly created space as a sealant. Incidence of perioperative morbidity and mortality, operative time, and length of stay were collected. Results: In our series, there were no intraoperative or perioperative mortalities. Procedure types included coronary artery bypass grafting (CABG), valve replacement and repair, or combined CABG and valve procedures. Median (interquartile range) cross-clamp time was 100 (88 to 131) minutes, cardiopulmonary bypass duration was 133 (114 to 176) minutes, and length of stay was 6 (4 to 8) days. None of the patients returned to the operating room for hemorrhage, and there were no complications associated with the repair of a coronary sinus injury when using the pericardial roof technique. Conclusions: Coronary sinus injuries can result in difficult to manage perioperative bleeding and potentially lethal consequences from cardiac manipulation. Our series supports the pericardial roof technique as an effective solution to a challenging intraoperative complication.

COVID-19 Respiratory Failure: Targeting Inflammation on VV-ECMO Support.

The outbreak of novel coronavirus (SARS-CoV-2) that causes the respiratory illness COVID-19 has led to unprecedented efforts at containment due to its rapid community spread, associated mortality, and lack of immunization and treatment. We herein detail a case of a young patient who suffered life-threatening disease and multiorgan failure. His clinical course involved rapid and profound respiratory decompensation such that he required support with venovenous extracorporeal membrane oxygenation (VV-ECMO). He also demonstrated hyperinflammation (C-reactive protein peak 444.6 mg/L) with severe cytokine elevation (Interleukin-6 peak > 3000 pg/ml). Through treatment targeting hyperinflammation, he recovered from critical COVID-19 respiratory failure and required only 160 hours of VV-ECMO support. He was extubated 4 days after decannulation, had progressive renal recovery, and was discharged to home on hospital day 24. Of note, repeat SARS-CoV-2 test was negative 21 days after his first positive test. We present one of the first successful cases of VV-ECMO support to recovery of COVID-19 respiratory failure in North America.

Role and possible mechanisms of clenbuterol in enhancing reverse remodelling during mechanical unloading in murine heart failure.

AIMS: Combined left ventricular assist device (LVAD) and pharmacological therapy has been proposed to favour myocardial recovery in patients with end-stage heart failure (HF). Clenbuterol (Clen), a beta(2)-adrenoceptor (beta(2)-AR) agonist, has been used as a part of this strategy. In this study, we investigated the direct effects of clenbuterol on unloaded myocardium in HF. METHODS AND RESULTS: Left coronary artery ligation or sham operation was performed in male Lewis rats. After 4-6 weeks, heterotopic abdominal transplantation of the failing hearts into normal recipients was performed to induce LV unloading (UN). Recipient rats were treated with saline (Sal) or clenbuterol (2 mg/kg/day) via osmotic minipumps (HF + UN + Sal or HF + UN + Clen) for 7 days. Non-transplanted HF animals were treated with Sal (Sham + Sal, HF + Sal) or clenbuterol (HF + Clen). LV myocytes were isolated and studied using optical, fluorescence, and electrophysiological techniques. Clenbuterol treatment improved in vivo LV function measured with echocardiography (LVEF (%): HF 35.9 +/- 2 [16], HF + Clen 52.1 +/- 1.4 [16]; P < 0.001; mean +/- SEM [n]). In combination with unloading, clenbuterol increased sarcomere shortening (amplitude (microm): HF + UN + Clen 0.1 +/- 0.01 [50], HF + UN + Sal 0.07 +/- 0.01 [38]; P < 0.001) by normalizing the depressed myofilament sensitivity to Ca(2+) (slope of the linear relationship between Ca(2+) transient and sarcomere shortening hysteresis loop during relaxation (microm/ratio unit): HF + UN + Clen 2.13 +/- 0.2 [52], HF + UN + Sal 1.42 +/- 0.13 [38]; P < 0.05). CONCLUSION: Clenbuterol treatment of failing rat hearts, alone or in combination with mechanical unloading, improves LV function at the whole-heart and cellular levels by affecting cell morphology, excitation-contraction coupling, and myofilament sensitivity to calcium. This study supports the use of this drug in the strategy to enhance recovery in HF patients treated with LVADs and also begins to elucidate some of the possible cellular mechanisms responsible for the improvement in LV function.

The role of computed tomography angiography in patients undergoing evaluation for minimally invasive cardiac surgery: an early program experience.

OBJECTIVE: An increasing number of patients are undergoing surgical procedures using minimally invasive cardiac surgery (MICS). These techniques use conventional or retrograde arterial perfusion with direct aortic cross-clamping or endoballoon occlusion. Precise knowledge of the arterial tree is required to avoid complications and to plan for the operation. We examined the role of computed tomography angiography (CTA) in evaluating patients for MICS. METHODS: We reviewed all consecutive candidates undergoing CTA during preoperative evaluation for MICS aortic, mitral, tricuspid, Maze, atrial septal defect, or myxoma procedures between February 2008 and May 2010. The CTA findings of patients excluded from MICS were compared against those successfully undergoing MICS. RESULTS: One hundred eleven MICS candidates underwent preoperative CTA. Thirty-five (32%) had single or multiple CTA findings precluding MICS and underwent sternotomy. Seventy-six (68%) had favorable CTA findings and underwent MICS. The MICS group had a mean age of 62 years, with 29 women (39%); the non-MICS group had a mean age of 68 years, with 17 women (48%). Of the patients excluded from MICS, two (6%) had diminished or absent lower extremity pulses. All MICS patients (except for aortic) had successful use of the endoballoon. There were no perfusion or peripheral vascular complications. There was one stroke, one lymphocele, and one death (chronic obstructive pulmonary disease exacerbation). CONCLUSIONS: Computed tomography angiography is of fundamental importance in evaluating patients for MICS. It can identify calcified regions that make for threatening catheter passage with subsequent retrograde arterial perfusion. Abnormalities of the arterial tree are identified. The use of CTA-guided patient selection can thus avoid major perioperative complications.

Resident Perception of Technical Skills Education and Preparation for Independent Practice.

BACKGROUND: Surgical skills are traditionally taught and practiced in the operating room. However, changes in health care policy and outcome-based evaluation have decreased trainee operative autonomy. We examined cardiothoracic residents' perceptions of operative experience and the role of simulation. METHODS: The In-Training Examination (ITE) is taken each year by all residents. Completion of a 30-question preexamination survey is mandatory, ensuring a 100% response rate. Survey data related to operative experience, career preparedness, and surgical simulation were analyzed. Opinion questions were asked on a 5-point Likert scale. Respondents were grouped into three cohorts by training paradigm (2-year versus 3-year traditional programs and 6-year integrated programs). RESULTS: In all, 314 respondents (122 2-year, 96 3-year, and 96 6-year integrated) completed the survey. Of the three groups, residents in 3-year programs had the highest levels of satisfaction. Advanced training was most common among residents in 6-year integrated programs (66%, versus 49% for 2-year and 26% for 3-year programs; p = 0.63). Desire to specialize drove further training (97%), with 2% stating further training was needed owing to inadequacy and 1% owing to a poor job market. In all assessed categories, the majority of residents believed that simulation did not completely replicate the educational value of an operative case. CONCLUSIONS: Cardiothoracic residents largely feel well prepared for the transition to practice under the current educational paradigm. Although many residents seek advanced training, it seems driven by the desire for specialization. Residents view simulation as an adjunct to traditional intraoperative education, but not as a viable replacement. Further study is necessary to better understand how best to integrate simulation with operative experience.

Resident Perceptions of 2-Year Versus 3-Year Cardiothoracic Training Programs.

BACKGROUND: Resident perceptions of 2-year (2Y) vs 3-year (3Y) programs have never been characterized. The objective was to use the mandatory Thoracic Surgery Residents Association and Thoracic Surgery Directors Association In-Training Examination survey to compare perceptions of residents graduating from 2Y vs 3Y cardiothoracic programs. METHODS: Each year Accreditation Council for Graduate Medical Education cardiothoracic residents are required to take a 30-question survey designed by the Thoracic Surgery Residents Association and the Thoracic Surgery Directors Association accompanying the In-Training Examination with a 100% response rate. The 2013 and 2014 survey responses of residents graduating from 2Y vs 3Y training programs were compared. The Wilcoxon signed rank test was used to analyze ordinal and interval data. RESULTS: Graduating residents completed 167 surveys, including 96 from 2Y (56%) and 71 from 3Y (43%) programs. There was no difference in the perception of being prepared for the American Board of Thoracic Surgery examinations or amount of debt between 2Y and 3Y respondents. There was no difference in intended academic vs private practice. Graduating 3Y residents felt more prepared to meet case requirements and better trained, were more likely to pass their written American Board of Thoracic Surgery examinations, and were less likely to pursue additional training beyond their cardiothoracic residency. CONCLUSIONS: There was no difference in field of interest, practice type, and amount of debt between graduating 2Y vs 3Y residents. Respondents from 2Y programs expressed more difficulty in meeting case requirements, whereas residents from 3Y programs felt more prepared for independent practice and had higher American Board of Thoracic Surgery written pass rates.

Novel valved graft modification of Cabrol fistula for bleeding after aortic root surgery.

The Cabrol fistula, which shunts blood from the perigraft space to the right atrium in cases of refractory bleeding after ascending aortic replacement, is a useful technique. A drawback is the potential for troublesome venous back-bleeding into the perigraft space. We describe a modification using a valved Contegra graft, which obligates unidirectional flow and eliminates venous back-bleeding. This renders the Cabrol fistula an even more useful technique.

Pseudoprolapse of the anterior leaflet in chronic ischemic mitral regurgitation: identification and repair.

OBJECTIVE: Recurrence rates as high as 30% have been observed 6 months after treatment of chronic ischemic mitral regurgitation (CIMR) with isolated annuloplasty. We postulated that the high early recurrence rates resulted from the presence of untreated pseudoprolapse of the anterior leaflet. METHODS: We conducted a retrospective study of all mitral valve repairs for CIMR performed by a single surgeon (S.W.H.) from 1995 to 2011. After annuloplasty, Gore-Tex neochordae were added if the high-pressure saline test indicated the presence of pseudoprolapse of the anterior leaflet. RESULTS: A total of 47 patients underwent mitral valve repair for CIMR. Of the 47 patients, 24 (51%) were found to have pseudoprolapse requiring the addition of neochordae. For all patients, the average age was 65.1 years, and 65.2% were men. Fourteen (30%) had had a preoperative intra-aortic balloon pump placed by cardiologists. Fourteen (30%) had severe pulmonary hypertension. Concomitant coronary artery bypass grafting was performed in 40 patients, with an average of 2.2 grafts; 7 had previously undergone coronary artery bypass grafting. Mitral Carpentier-Edwards physio annuloplasty rings were used in all patients with a mean size of 29 mm. One patient died postoperatively. Follow-up data were available for all 47 patients at an average of 4.9 years. The 5-year survival rate was 82.5%. The mean pre- and postoperative New York Heart Association class, ejection fraction, and mitral regurgitation grade were 3 and 1.52 (P < .0001), 34% and 41% (P = .0006), and 3.51 and 1.08 (P < .0001), respectively. Two patients developed greater than moderate mitral regurgitation. CONCLUSIONS: Effective repair of CIMR should include surgical techniques to correct pseudoprolapse of the anterior leaflet, when present. The selective addition of Gore-Tex neochordae to an undersized annuloplasty nearly eliminates recurrent regurgitation after mitral valve repair for CIMR.

Safety and utility of mediastinoscopy in non-small cell lung cancer in a complex mediastinum.

BACKGROUND: Adequate mediastinal staging is crucial in patients with locally advanced non-small cell lung cancer. Mediastinoscopy is often omitted after induction therapy or prior mediastinoscopy because of concerns for potential morbidity, safety and unknown utility. We sought to determine the safety and utility of restaging mediastinoscopy before surgical resection. METHODS: A retrospective review was made of non-small cell lung cancer patients who underwent mediastinoscopy with a complex mediastinum, defined as any or all of the following: previous mediastinoscopy or induction chemotherapy or mediastinal radiation. RESULTS: Seventy-five patients underwent mediastinoscopy including 15 redo mediastinoscopies. In the non-redo group, 9 patients received induction chemotherapy, 16 received induction chemoradiotherapy (<46 Gy), 29 received definitive chemoradiotherapy (>50 Gy), and 6 received radiation alone. Two were aborted owing to fibrosis. Stations 4L, 4R, and 7 were accessed in 84% of patients, with confirmed nodal tissue in 88%. There was 1 azygos vein injury that required urgent thoracotomy and 2 recurrent nerve injuries. Resection ensued in 63 patients: 53 with negative mediastinoscopy, 8 with microscopic nodal metastases, and the 2 aborted cases. In patients with negative mediastinoscopy, 5 had N2 disease at thoracotomy: 3 in stations 4 and 7 and 2 in nodal stations inaccessible by mediastinoscopy. The sensitivity was 71%, specificity was 100%, and negative predictive value was 91%. CONCLUSIONS: In experienced hands, mediastinoscopy in a complex mediastinum is safe. Preclusive mediastinal fibrosis is rare. Expected lymph node stations can be accessed, and the results strongly correlate with postresection pathology. Mediastinoscopy is valuable to evaluate the nodal response to therapy in the setting of combined modality therapy.

Comparison of open and minimally invasive thymectomies at a single institution.

BACKGROUND: Most thymectomies are performed via sternotomy. Minimally invasive thymectomy (MIT) has been described but its potential benefits and drawbacks remain unclear. METHODS: A retrospective chart review comparing thymectomies performed via sternotomy to MIT at a single institution between 2005 and 2009. RESULTS: Eight patients underwent MIT and 8 patients underwent sternotomy in the management of myasthenia gravis, thymic hyperplasia, or small thymic tumors. There was 1 perioperative death unrelated to the surgical procedure and no morbidity. The surgical time, estimated blood loss, and chest tube output was similar in both groups. The average hospital stay for MIT was 2.4 days compared with 4.3 days for sternotomy. One MIT patient remained on narcotic pain medication 2 weeks after surgery compared with 6 in the open group. CONCLUSIONS: MIT can be performed with similar morbidity and efficacy as transsternal thymectomy. Patients require fewer narcotics and can be discharged earlier.

Adult progenitor cell transplantation influences contractile performance and calcium handling of recipient cardiomyocytes.

Adult progenitor cell transplantation has been proposed for the treatment of heart failure, but the mechanisms effecting functional improvements remain unknown. The aim of this study was to test the hypothesis that, in failing hearts treated with cell transplantation, the mechanical properties and excitation-contraction coupling of recipient cardiomyocytes are altered. Adult rats underwent coronary artery ligation, leading to myocardial infarction and chronic heart failure. After 3 wk, they received intramyocardial injections of either 10(7) green fluorescence protein (GFP)-positive bone marrow mononuclear cells or 5 x 10(6) GFP-positive skeletal myoblasts. Four weeks after injection, both cell types increased ejection fraction and reduced cardiomyocyte size. The contractility of isolated GFP-negative cardiomyocytes was monitored by sarcomere shortening assessment, Ca(2+) handling by indo-1 and fluo-4 fluorescence, and electrophysiology by patch-clamping techniques. Injection of either bone marrow cells or skeletal myoblasts normalized the impaired contractile performance and the prolonged time to peak of the Ca(2+) transient observed in failing cardiomyocytes. The smaller and slower L-type Ca(2+) current observed in heart failure normalized after skeletal myoblast, but not bone marrow cell, transplantation. Measurement of Ca(2+) sparks suggested a normalization of sarcoplasmic reticulum Ca(2+) leak after skeletal myoblast transplantation. The increased Ca(2+) wave frequency observed in failing myocytes was reduced by either bone marrow cells or skeletal myoblasts. In conclusion, the morphology, contractile performance, and excitation-contraction coupling of individual recipient cardiomyocytes are altered in failing hearts treated with adult progenitor cell transplantation.

Prolonged mechanical unloading reduces myofilament sensitivity to calcium and sarcoplasmic reticulum calcium uptake leading to contractile dysfunction.

BACKGROUND: Prolonged unloading using left ventricular (LV) assist devices (LVADs) leads to unloading-induced atrophy with altered cardiomyocyte contractility. The causes for this time-dependent deterioration of myocardial function are unclear. Our aim was to determine the effects of prolonged mechanical unloading on cardiomyocyte function and, more specifically, on Ca(2+) cycling and myofilament sensitivity to Ca(2+). METHODS: LV unloading was induced by heterotopic abdominal transplantation (UN) in rats for 5 weeks. Recipient hearts were used as controls (REC). LV myocytes were isolated and cardiomyocyte area measured by planimetry, sarcomere length measured by Fourier analysis of digitized cardiomyocyte images, and cytoplasmic [Ca(2+)] monitored using Indo-1. Myofilament sensitivity to Ca(2+) was assessed as the slope of the linear relationship between Indo-1 ratio and sarcomere shortening during relaxation. RESULTS: UN cardiomyocyte area was smaller compared with REC (mean +/- SEM: UN 2,503 +/- 78 microm(2) [n = 132], REC 3,856 +/- 89 microm(2) [n = 116]; p < 0.001). UN cardiomyocytes had a smaller sarcomere shortening amplitude (UN 0.08 +/- 0.01 microm [n = 37], REC 0.11 +/- 0.01 microm [n = 38]; p < 0.01), despite normal Ca(2+) transient amplitude (UN 0.13 +/- 0.01 Indo-1 ratio units [n = 37], REC 0.11 +/- 0.01 Indo-1 ratio units [n = 38]; p = non-significant). Myofilament sensitivity to Ca(2+) was reduced in UN (UN 2.0 +/- 1.2 microm/ratio unit [n = 20], REC 3.7 +/- 0.4 microm/ratio unit [n = 22]; p < 0.01). Sarcoplasmic reticulum (SR) Ca(2+) uptake (assessed by 20 mmol/liter caffeine) was also reduced in UN (UN 84.3 +/- 0.79% relative contribution [n = 22], REC 89.8 +/- 0.67% relative contribution [n = 24]; p < 0.001). CONCLUSIONS: Prolonged myocardial unloading causes depressed contractility due to reduced SR Ca(2+) uptake and myofilament sensitivity to Ca(2+). These effects may be relevant with regard to myocardial performance after prolonged LVAD support.