Injection of Human Bone Marrow and Mononuclear Cell Extract into Infarcted Mouse Hearts Results in Functional Improvement

Background: We have previously shown that mouse whole bone marrow cell (BMC) extract results in improvement of cardiac function and decreases scar size in a mouse model of myocardial infarction (MI), in the absence of intact cells. It is not clear if thes

Assessment of acute myocardial infarction: current status and recommendations from the North American society for cardiovascular imaging and the European society of cardiac radiology

There are a number of imaging tests that are used in the setting of acute myocardial infarction and acute coronary syndrome. Each has their strengths and limitations. Experts from the European Society of Cardiac Radiology and the North American Society for Cardiovascular Imaging together with other prominent imagers reviewed the literature. It is clear that there is a definite role for imaging in these patients. While comparative accuracy, convenience and cost have largely guided test decisions in the past, the introduction of newer tests is being held to a higher standard which compares patient outcomes. Multicenter randomized comparative effectiveness trials with outcome measures are required

Mesenchymal stem cells for cardiac regenerative therapy

Until recently, the concept of treating the injured or failing heart by generating new functional myocardium was considered physiologically impossible. Major scientific strides in the past few years have challenged the concept that the heart is a post-mitotic organ, leading to the hypothesis that cardiac regeneration could be therapeutically achieved. Bone marrow-derived adult stem cells were among the first cell populations that were used to test this hypothesis. Animal studies and early clinical experience support the concept that therapeutically delivered mesenchymal stem cells (MSCs) safely improve heart function after an acute myocardial infarction (MI). MSCs produce a variety of cardio-protective signalling molecules, and have the ability to differentiate into both myocyte and vascular lineages. Additionally, MSCs are attractive as a cellular vehicle for gene delivery, cell transplantation or for tissue engineering because they offer several practical advantages. They can be obtained in relatively large numbers through standard clinical procedures, and they are easily expanded in culture. The multi-lineage potential of MSC, in combination with their immunoprivileged status, make MSCs a promising source for cell therapy in cardiac diseases. Here we provide an overview of biological characteristics of MSCs, experimental animal studies and early clinical trials with MSCs. In addition, we discuss the routes of cell delivery, cell tracking experiments and current knowledge of the mechanistic underpinnings of their action

Door-to-unload: left ventricular unloading before reperfusion in ST-elevation myocardial infarction

ST-elevation myocardial infarction treatment in the modern era has focused on minimizing time of ischemia by reducing door-to-balloon time to limit infarct size and improve survival. Although there have been significant improvements in minimizing time to coronary reperfusion, the incidence of heart failure following a myocardial infarction has remained high. Preclinical studies have shown that unloading the left ventricle for 30 min prior to coronary reperfusion can reduce infarct size and promote myocardial recovery. The DTU-STEMI randomized prospective trial will test the hypothesis that left ventricular unloading for at least 30 min prior to coronary reperfusion will improve infarct size and heart failure-related events as compared with the current standard of care

Deficiency of neuronal nitric oxide synthase increases mortality and cardiac remodeling after myocardial infarction - Role of nitroso-redox equilibrium

Background - Neuronal nitric oxide synthase ( NOS1) plays key cardiac physiological roles, regulating excitation-contraction coupling and exerting an antioxidant effect that maintains tissue NO- redox equilibrium. After myocardial infarction ( MI), NOS1 translocates from the sarcoplasmic reticulum to the cell membrane, where it inhibits beta- adrenergic contractility, an effect previously predicted to have adverse consequences. Counter to this idea, we tested the hypothesis that NOS1 has a protective effect after MI.Methods and Results - We studied mortality, cardiac remodeling, and upregulation of oxidative stress pathways after MI in NOS1- deficient ( NOS1 -/ -) and wild- type C57BL6 ( WT) mice. Compared with WT, NOS1 -/ - mice had greater mortality ( hazard ratio, 2.06; P = 0.036), worse left ventricular ( LV) fractional shortening ( 19.7 +/- 1.5% versus 27.2 +/- 1.5%, P < 0.05), higher LV diastolic diameter ( 5.5 +/- 0.2 versus 4.9 +/- 0.1 mm, P < 0.05), greater residual cellular width ( 14.9 +/- 0.5 versus 12.8 +/- 0.5 mu m, P < 0.01), and equivalent beta- adrenergic hyporesponsiveness despite similar MI size. Superoxide production increased after MI in both NOS1 -/ - and WT animals, although NO increased only in WT. NADPH oxidase ( P < 0.05) activity increased transiently in both groups after MI, but NOS1 -/ - mice had persistent basal and post- MI elevations in xanthine oxidoreductase activity.Conclusions - Together these findings support a protective role for intact NOS1 activity in the heart after MI, despite a potential contribution to LV dysfunction through beta- adrenergic hyporesponsiveness. NOS1 deficiency contributes to an imbalance between oxidative stress and tissue NO signaling, providing a plausible mechanism for adverse consequences of NOS1 deficiency in states of myocardial injury.Johns Hopkins Med Inst, Div Cardiol, Baltimore, MD 21205 USAJohns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USAUniversidade Federal de São Paulo, UNIFESP, São Paulo, BrazilJohns Hopkins Med Inst, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21205 USAUniversidade Federal de São Paulo, UNIFESP, São Paulo, BrazilWeb of Scienc

Autologous mesenchymal stem cells produce reverse remodelling in chronic ischaemic cardiomyopathy

Aims The ability of mesenchymal stem cells (MSCs) to heal the chronically injured heart remains controversial. Here we tested the hypothesis that autologous MSCs can be safely injected into a chronic myocardial infarct scar, reduce its size, and improve ventricular function. Methods and results Female adult Göttingen swine (n = 15) underwent left anterior descending coronary artery balloon occlusion to create reproducible ischaemia-reperfusion infarctions. Bone-marrow-derived MSCs were isolated and expanded from each animal. Twelve weeks post-myocardial infarction (MI), animals were randomized to receive surgical injection of either phosphate buffered saline (placebo, n = 6), 20 million (low dose, n = 3), or 200 million (high dose, n = 6) autologous MSCs in the infarct and border zone. Injections were administered to the beating heart via left anterior thoracotomy. Serial cardiac magnetic resonance imaging was performed to evaluate infarct size, myocardial blood flow (MBF), and left ventricular (LV) function. There was no difference in mortality, post-injection arrhythmias, cardiac enzyme release, or systemic inflammatory markers between groups. Whereas MI size remained constant in placebo and exhibited a trend towards reduction in low dose, high-dose MSC therapy reduced infarct size from 18.2 ± 0.9 to 14.4 ± 1.0% (P = 0.02) of LV mass. In addition, both low and high-dose treatments increased regional contractility and MBF in both infarct and border zones. Ectopic tissue formation was not observed with MSCs. Conclusion Together these data demonstrate that autologous MSCs can be safely delivered in an adult heart failure model, producing substantial structural and functional reverse remodelling. These findings demonstrate the safety and efficacy of autologous MSC therapy and support clinical trials of MSC therapy in patients with chronic ischaemic cardiomyopathy