Free-breathing gradient recalled echo-based CMR in a swine heart failure model.

In swine models, there are well-established protocols for creating a closed-chest myocardial infarction (MI) as well as protocols for characterization of cardiac function with cardiac magnetic resonance (CMR). This methods manuscript outlines a novel technique in CMR data acquisition utilizing smart-signal gradient recalled echo (GRE)-based array sequences in a free-breathing swine heart failure model allowing for both high spatial and temporal resolution imaging. Nine male Yucatan mini swine weighing 48.7 ± 1.6 kg at 58.2 ± 3.1 weeks old underwent the outlined imaging protocol before and 1-month after undergoing closed chest left anterior descending coronary artery (LAD) occlusion/reperfusion. The left ventricular ejection fraction (LVEF) at baseline was 59.3 ± 2.4% and decreased to 48.1 ± 3.7% 1-month post MI (P = 0.029). The average end-diastolic volume (EDV) at baseline was 55.2 ± 1.7 ml and increased to 74.2 ± 4.2 ml at 1-month post MI (P = 0.001). The resulting images from this novel technique and post-imaging analysis are presented and discussed. In a Yucatan swine model of heart failure via closed chest left anterior descending coronary artery (LAD) occlusion/reperfusion, we found that CMR with GRE-based array sequences produced clinical-grade images with high spatial and temporal resolution in the free-breathing setting.

Epicardially Placed Bioengineered Cardiomyocyte Xenograft in Immune-Competent Rat Model of Heart Failure.

BACKGROUND: Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are under preclinical investigation as a cell-based therapy for heart failure post-myocardial infarction. In a previous study, tissue-engineered cardiac grafts were found to improve hosts' cardiac electrical and mechanical functions. However, the durability of effect, immune response, and in vitro properties of the tissue graft remained uncharacterized. This present study is aimed at confirming the graft therapeutic efficacy in an immune-competent chronic heart failure (CHF) model and providing evaluation of the in vitro properties of the tissue graft. METHODS: hiPSC-CMs and human dermal fibroblasts were cultured into a synthetic bioabsorbable scaffold. The engineered grafts underwent epicardial implantation in infarcted immune-competent male Sprague-Dawley rats. Plasma samples were collected throughout the study to quantify antibody titers. At the study endpoint, all cohorts underwent echocardiographic, hemodynamic, electrophysiologic, and histopathologic assessments. RESULTS: The epicardially placed tissue graft therapy improved (p < 0.05) in vivo and ex vivo cardiac function compared to the untreated CHF cohort. Total IgM and IgG increased for both the untreated and graft-treated CHF cohorts. An immune response to the grafts was detected after seven days in graft-treated CHF rats only. In vitro, engineered grafts exhibited responsiveness to beta-adrenergic receptor agonism/antagonism and SERCA inhibition and elicited complex molecular profiles. CONCLUSIONS: This hiPSC-CM-derived cardiac graft improved systolic and diastolic cardiac function in immune-competent CHF rats. The improvements were detectable at seven weeks post-graft implantation despite an antibody response beginning at week one and peaking at week three. This suggests that non-integrating cell-based therapy delivered by a bioengineered tissue graft for ischemic cardiomyopathy is a viable treatment option.

Human Induced Pluripotent Stem Cell-Derived Cardiomyocyte Patch in Rats With Heart Failure.

BACKGROUND: To treat chronic heart failure (CHF), we developed a robust, easy to handle bioabsorbable tissue-engineered patch embedded with human neonatal fibroblasts and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). This patch was implanted on the epicardial surface of the heart covering the previously infarcted tissue. METHODS: Sprague-Dawley rats (6-8 weeks old) underwent sham surgery (n = 12) or left coronary artery ligation (n = 45). CHF rats were randomized 3 weeks after ligation to CHF control with sham thoracotomy (n = 21), or a fibroblasts/hiPSC-CMs patch (n = 24) was implanted. All sham surgery rats also underwent a sham thoracotomy. At 3 weeks after randomization, hemodynamics, echocardiography, electrophysiologic, and cell survival studies were performed. RESULTS: Patch-treated rats had decreased (P < .05) left ventricular-end diastolic pressure and the time constant of left ventricular relaxation (Tau), increased anterior wall thickness in diastole, and improved echocardiography-derived indices of diastolic function (E/e' [ratio of early peak flow velocity to early peak LV velocity] and e'/a' [ratio of early to late peak left ventricular velocity]). All rats remained in normal sinus rhythm, with no dysrhythmias. Rats treated with the patch showed improved electrical activity. Transplanted hiPSC-CMs were present at 7 days but not detected at 21 days after implantation. The patch increased (P < .05) gene expression of vascular endothelial growth factor, angiopoietin 1, gap junction α-1 protein (connexin 43), ß-myosin heavy 7, and insulin growth factor-1 expression in the infarcted heart. CONCLUSIONS: Epicardial implantation of a fibroblasts/hiPSC-CMs patch electrically enhanced conduction, lowered left ventricular end-diastolic pressure, and improved diastolic function in rats with CHF. These changes were associated with increases in cytokine expression.

Surgical treatment for heart failure: cell-based therapy with engineered tissue.

This review will outline cell-based therapy for heart failure focusing on tissue engineering to deliver cells to the damaged heart. We will present an overview of the central approaches focusing on pluripotent stem cell-derived cells, mechanisms of action, autologous vs. allogeneic cell approaches, immunologic modulation, and safety considerations. We will outline the progress that has been made to-date and define the areas that still need to be investigated in order to advance the field.

Factors in the Selection and Management of Chest Tubes After Pulmonary Lobectomy: Results of a National Survey of Thoracic Surgeons.

BACKGROUND: This study determined patterns of chest tube (CT) selection and management after open lobectomy and minimally invasive lobectomy by thoracic surgeons. METHODS: Surveys were sent electronically to 5,175 thoracic surgeons, and 475 were completed. Responses, blinded so individuals could not be identified, were analyzed and compared according to surgeon characteristics (academic/private practice, years in practice, lobectomy volume, and geographic region). All indicated differences were statistically significant (p < 0.05 by χ(2) tests). RESULTS: CT selection: Most surgeons prefer rigid tubes, and the size most commonly used was 28F. Most place 2 CTs after open lobectomy and 1 CT after minimally invasive lobectomy. Academic surgeons are more likely than private surgeons to use 1 tube after open lobectomy, but both prefer 1 tube after minimally invasive lobectomy. Younger surgeons and high-volume surgeons are more likely to use 1 CT than senior surgeons and low-volume surgeons after both open lobectomy and minimally invasive lobectomy. CT management: Academic and younger surgeons remove the CT sooner after open lobectomy. Younger and high-volume surgeons remove the CT with greater drainage amounts. All groups remove CTs sooner after minimally invasive lobectomy than after open lobectomy. Approximately half of surgeons get a daily chest roentgenogram. Younger and low-volume surgeons are most likely to discharge patients with Heimlich valves, although overall use was in less than 5% (49 of 475) of respondents. Most surgeons believe clinical experience rather than training or the literature determined their CT strategy. CONCLUSIONS: This survey determined the difference in CT management among various groups of surgeons. Clinical experience was the most important factor in determining their CT strategy.