Nasir Z. Sulemanjee

Monocyte Chemoattractant Protein 1-Induced Monocyte Infiltration Produces Angiogenesis but Not Arteriogenesis in Chronically Infarcted Myocardium

Background: Monocyte chemoattractant protein 1 (MCP-1) stimulates the invasion of monocytes into ischemic tissue with concomitant adhesion to endothelial cells. Monocyte stimulation has been shown to be involved in the induction of arteriogenesis, which is the development of functional arterioles resulting in improvement of perfusion. However, angiogenesis (newly developed capillaries contribute to improved tissue perfusion) in several models has not resulted in any improvement in blood flow. Objective: The effects of MCP-1 on potential angiogenesis and arteriogenesis as well as changes in left ventricular function were tested in a chronic infarct model in rat hearts. Methods: Anesthetized rats were subjected to open-chest ligation of the left coronary artery with subsequent myocardial infarction. After 6 weeks, animals were randomized to receive either MCP-1 (3 µL in 0.15 mL NaCl, group 1, n = 9) or saline (0.15 mL, group 2, n = 9), which was injected into the myocardium at the border zones of the infarcts. For assessment of left ventricular dimensions and global cardiac function, transthoracic two-dimensional echocardiography was performed at baseline, 6 weeks after myocardial infarction, and 4 weeks after MCP-1 or saline injection, by use of a 12-MHz pediatric transducer. For light microscopic analysis, myocardial tissue was stained with Elastica-van-Giesson and von Willebrand factor for blood vessels and endothelial cells, respectively. In a subset of animals, hearts were excised 24 hours after MCP-1 administration (n = 4) or saline administration (n = 4) for assessment of monocyte infiltration by immunohistologic staining of the CD31 antigen. Results: Left ventricular dimensions and ejection fraction changed after coronary occlusion (from 60.4% ± 2.85% to 24.8% ± 5.01% ejection fraction in group 1, and from 58.4% ±2.06% to 26.3% ± 4.3% ejection fraction in group 2 at 6 weeks, P < .005) without any further change 4 weeks after treatment (ejection fraction in group 1, 26.3% ± 2.7%, ejection fraction in group 2, 25.0% ± 5.18%). The MCP-1 group resulted in 390.6 ± 10.36 endothelial cells compared with 285.2 ± 13.56 in group 2 (P < .005) at the injection site. Monocyte infiltration was observed at the MCP-1 injection site with an increase in capillary growth (angiogenesis). However, there was no difference in the number of arteriolar structures between animals treated with MCP-1 and saline animals (group 1, 19.0 ± 1.52 vs group 2,16.4 ± 0.68, P > .05). Conclusion: A single intramyocardial injection of MCP-1 into the infarct border zone resulted in neo-angiogenesis and monocyte infiltration but not arteriogenesis in the rat heart. There was no functional change of chronically infarcted myocardium in the present model.

Administration of vascular endothelial growth factor adjunctive to fetal cardiomyocyte transplantation and improvement of cardiac function in the rat model.

Background: The functional impact of cellular transplantation and the potential role of the addition of angiogenic factors for survival of engrafts remain controversial. Methods: Vascular endothelial growth factor (VEGF) (25 ng/mL) was added to cultured fetal cardiomyocytes labeled with bromodeoxyuridine (BrDU), which was injected into the border zones of myocardial infarction 4 weeks after coronary occlusion in rat hearts. Group 1 (n = 12) received cells plus VEGF protein (100 ng), group 2 (n = 12) received cells without VEGF, group 3 (n = 10) received VEGF without cells, and group 4 (n = 12) received pure culture medium. Cardiac function was then assessed by transthoracic two-dimensional echocardiography and Langendorff perfusion system. In situ hybridization for Y chromosomes of transplanted cells, detection of BrDU-labeled cells, and platelet/endothelial cell adhesion molecule-1 (PECAM-1) staining for endothelial cells was performed. Results: Echocardiography revealed smaller end-diastolic left ventricular dimensions in transplanted hearts in group 1 (0.83 ± 0.13 cm 4 weeks after coronary occlusion before transplantation and 0.69 ± 0.14 cm 2 months after transplantation, P < .05) and in group 2 (0.88 ± 0.09 cm after coronary occlusion before transplantation and 0.76 ± 0.08 cm 2 months after transplant), and increases in fractional shortening (34.2% ± 8.53% before transplant and 45.3% ± 10.9% after [P < .05] in group 1; 26.9% ± 6.02% before transplant and 37.15% ± 8.08% after [P < .005] in group 2), whereas groups 3 and 4 showed a decrease in fractional shortening. Transplanted hearts developed higher pressures at rest (group 1, 96.8 ± 20.8 mm Hg; group 2, 98.6 ± 21.9 mm Hg) compared with controls (group 4, 70.9 ± 25 mm Hg) (P < .05) and during inotropic stimulation (group 1, 111 ± 19.5 mm Hg and group 2, 113.3 ± 32.6 vs group 4, 80.7 ± 31.6 mm Hg, P < .05). Histologic analysis demonstrated the presence of transplanted cells in border zones of infarcted host myocardium with neovascularization in all transplanted hearts. Conclusion: Transplantation of fetal cardiomyocytes results in improvement of left ventricular function. The addition of VEGF does not contribute to further improvement of left ventricular function and angiogenesis in the present model.

Sexual function after left ventricular assist device.

To the Editor: Impaired sexual function is common in patients with heart failure ([1][1]) and following cardiac transplant. Left ventricular assist devices (LVADs) improve survival, functional capacity, and quality of life for end-stage heart failure, but data regarding their impact on sexual

The first year post-heart transplantation: use of immunosuppressive drugs and early complications.

A large number of heart transplants are performed annually in different transplant centers in the United States. This is partly because of the improved survival of patients who undergo cardiac transplantation, thus making it a more viable option in the management of end-stage heart failure. The survival benefit after heart transplantation is a result of newer immunosuppressive drug regimens and a better understanding of their effects and interactions. Several studies, mostly involving a small number of patients, describe use and comparison of the many distinct immunosuppressive drugs available to date. Interestingly, many transplant centers perform in-house typical induction treatment regimens because of their own experience and intra-institutional preference. This review summarizes current practices of immunosuppressive drug therapy in the first year post–heart transplant based on the available clinical evidence and discusses future options of heart transplant immunosuppressive drug therapies.

Association between sleep disordered breathing and life threatening ventricular arrhythmia among left ventricular assist device patients

The association between sleep disordered breathing (SDB) and ventricular arrhythmias (VA) is well established. Limited data is available on the severity of SDB and VA among patients with continuous flow left ventricular assist device (CF-LVAD). Among 230 patients who received CF-LVAD between Jan

Does Left Ventricular Assist Device Implantation Affect Driving Patterns in Patients With End-Stage Heart Failure?

Background In 2012, the Canadian Society of Cardiology indicated that patients supported with left ventricular assist device (LVAD) may drive a private vehicle 2 months after implantation, provided they are deemed clinically stable. Objective evidence supporting this recommendation is limited. We sought to compare data regarding driving habits in our patients following LVAD implantation. Citation: Pinniti M.et al. (2017) “Does Left Ventricular Assist Device Implantation Affect Driving Patterns in Patients With EndStage Heart Failure?” The VAD Journal, 3. doi: https://doi.org/10.13023/VAD.2017. 05 Editor-in-Chief: Maya Guglin, University of Kentucky Received: February 15, 2016 Accepted: March 16, 2017 Published: March 16, 2017

Favorable Outcomes of LVAD as Bridge to Simultaneous Heart-Kidney Transplantation

Chronic kidney disease (CKD) is an established risk factor for incident cardiovascular disease and progression of heart failure disease state, and is associated with decreased survival after left ventricular assist device (LVAD) therapy or heart transplantation (HT). Combined heart-kidney transplantation (HKT) compared with isolated HT recently has been shown to have survival advantage among patients whose estimated glomerular filtration rate is less than 37 ml/min/m2. Data on LVAD to HKT are limited.

Can gene-expression profiling score help explain the adverse clinical outcomes seen in gender-mismatched heart transplants?

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