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Biomedical subjects

Edmund H Sonnenblick

Publications and source records attributed to Edmund H Sonnenblick.

8 recordsLinked to original sources
PubMed2006

Cause of death: suicide.

In the last decade, apoptosis has gained recognition as an important event determining the structure and function of the myocardium. The purpose of this review is to provide insights into the mechanisms controlling programmed cell death of myocytes. In this regard, the role of the local renin-angiotensin system and oxidative stress is emphasized. Moreover, the effect of cell death on ventricular remodeling and performance is analyzed. The impact of the identification of apoptosis in the heart on the current view of myocardium as a dynamic organ is discussed.

Animals↗
PubMed2005

Nuclear targeting of Akt enhances ventricular function and myocyte contractility.

Cytoplasmic overexpression of Akt in the heart results in a myopathy characterized by organ and myocyte hypertrophy. Conversely, nuclear-targeted Akt does not lead to cardiac hypertrophy, but the cellular basis of this distinct heart phenotype remains to be determined. Similarly, whether nuclear-targeted Akt affects ventricular performance and mechanics, calcium metabolism, and electrical properties of myocytes is unknown. Moreover, whether the expression and state of phosphorylation of regulatory proteins implicated in calcium cycling and myocyte contractility are altered in nuclear-targeted Akt has not been established. We report that nuclear overexpression of Akt does not modify cardiac size and shape but results in an increased number of cardiomyocytes, which are smaller in volume. Additionally, the heart possesses enhanced systolic and diastolic function, which is paralleled by increased myocyte performance. Myocyte shortening and velocity of shortening and relengthening are increased in transgenic mice and are coupled with a more efficient reuptake of calcium by the sarcoplasmic reticulum (SR). This process increases calcium loading of the SR during relengthening. The enhanced SR function appears to be mediated by an increase in SR Ca2+-ATPase2a activity sustained by a higher degree of phosphorylation of phospholamban. This posttranslational modification was associated with an increase in phospho-protein kinase A and a decrease in protein phosphatase-1. Together, these observations provide a plausible biochemical mechanism for the potentiation of myocyte and ventricular function in Akt transgenic mice. Therefore, nuclear-targeted Akt in myocytes may have important implications for the diseased heart.

Actin Cytoskeleton↗
PubMed2005

Myocardial aging--a stem cell problem.

This review questions the old paradigm that describes the heart as a post-mitotic organ and introduces the notion of the heart as a self-renewing organ regulated by a compartment of multipotent cardiac stem cells (CSCs) capable of regenerating myocytes and coronary vessels throughout life. Because of this dramatic change in cardiac biology, the objective is to provide an alternative perspective of the aging process of the heart and stimulate research in an area that pertains to all of us without exception. The recent explosion of the field of stem cell biology, with the recognition that the possibility exists for extrinsic and intrinsic regeneration of myocytes and coronary vessels, necessitates reevaluation of cardiac homeostasis and myocardial aging. From birth to senescence, the mammalian heart is composed of non-dividing and dividing cells. Loss of telomeric DNA is minimal in fetal and neonatal myocardium but rather significant in the senescent heart. Aging affects the growth and differentiation potential of CSCs interfering not only with their ability to sustain physiological cell turnover but also with their capacity to adapt to increases in pressure and volume loads. The recognition of factors enhancing the activation of the CSC pool, their mobilization, and translocation, however, suggests that the detrimental effects of aging on the heart might be prevented or reversed by local stimulation of CSCs or the intramyocardial delivery of CSCs following their expansion and rejuvenation in vitro. CSC therapy may become, perhaps, a novel strategy for the devastating problem of heart failure in the old population.

Aging↗
PubMed2005

Dissociation between improvement in left ventricular performance and functional class in patients with chronic heart failure.

Resting left ventricular ejection fraction (LVEF) and functional capacity do not correlate in chronic heart failure patients treated with digitalis, diuretics, and angiotensin-converting enzyme inhibitors. We sought to determine whether substantial improvement in LVEF, as may occur during long-term beta-blockade or after coronary artery bypass graft (CABG) surgery, leads consistently to improvement in functional class. Doppler echocardiogram and assessment of functional class were obtained at baseline and 12 months after initiation of beta-blockade (87 patients) or CABG surgery (51 patients). At 12 months the effects of beta-blockade were variable: LVEF increased greatly by >or=11% (median value) in 45 patients (52%) and by <11% in 19 (22%), but it decreased or remained unchanged in 23 patients (26%). In contrast, functional class was unchanged or worsened in 59 patients (68%) and improved in only 28 (32%). Similarly, surgery had variable effects on LVEF. LVEF increased by >or=12% (median) in 28 patients (55%) and by <12% in 14 (27%), whereas it decreased or remained unchanged in 9 patients (18%). Functional class was unchanged or worsened in 41 patients (80%) and improved in only 10 (20%). Changes in functional class and LVEF were unrelated for both interventions. Both beta-blockade and CABG surgery improve LVEF in the majority of patients. However, significant improvement in LVEF does not enhance functional capacity consistently in chronic heart failure.

Adrenergic beta-Antagonists↗
PubMed2004

Mortality in patients after a recent myocardial infarction: a randomized, placebo-controlled trial of azimilide using heart rate variability for risk stratification.

BACKGROUND: Depressed left ventricular function (LVF) and low heart rate variability (HRV) identify patients at risk of increased mortality after myocardial infarction (MI). Azimilide, a novel class III antiarrhythmic drug, was investigated for its effects on mortality in patients with depressed LVF after recent MI and in a subpopulation of patients with low HRV. METHODS AND RESULTS: A total of 3717 post-MI patients with depressed LVF were enrolled in this randomized, placebo-controlled, double-blind study of azimilide 100 mg on all-cause mortality. Placebo patients with low HRV had a significantly higher 1-year mortality than those with high HRV (>20 U; 15% versus 9.5%, P<0.0005) despite nearly identical ejection fractions. No significant differences were observed between the 100-mg azimilide and placebo groups for all-cause mortality in either the "at-risk" patients identified by depressed LVF (12% versus 12%) or the subpopulation of "high-risk" patients identified by low HRV (14% versus 15%) or for total cardiac or arrhythmic mortality. Significantly fewer patients receiving azimilide developed atrial fibrillation than did patients receiving placebo (0.5% versus 1.2%, P<0.04). The incidences of torsade de pointes and severe neutropenia (absolute neutrophil count < or =500 cells/microL) were slightly higher in the azimilide group than in the placebo group (0.3% versus 0.1% for torsade de pointes and 0.9% versus 0.2% for severe neutropenia). CONCLUSIONS: Azimilide did not improve or worsen the mortality of patients after MI. Low HRV independently identified a subpopulation at high risk of mortality.

Aged↗
PubMed2003

Evolving rationale for angiotensin-converting enzyme inhibition in chronic heart failure.

The rationale behind the use of angiotensin-converting enzyme (ACE) inhibitors has evolved considerably since their approval for the treatment of hypertension. The initial rationale behind their use for the treatment of chronic heart failure was to duplicate with one agent the hemodynamic effects produced by the hydralazine-isosorbide dinitrate combination, i.e., increasing cardiac output while reducing ventricular filling pressures. The observation that the acute hemodynamic effects of ACE inhibitors did not predict long-term clinical benefits led to the search for mechanisms other than hemodynamic improvement. Attenuation or even reversal of left ventricular dilatation after myocardial infarction, which was first reported with ACE inhibition in an experimental model of myocardial infarction and subsequently in patients with recent myocardial infarction, provided a new rationale for the use of these inhibitors for chronic heart failure. However, this apparent prevention of left ventricular dilatation by ACE inhibitors is less apparent in patients with congestive heart failure due to left ventricular systolic dysfunction (decreased ejection fraction) than in patients with recent myocardial infarction. Furthermore, the unexpected finding that long-term ACE inhibition decreases the incidence of recurrent myocardial infarction in patients with coronary artery disease and an already reduced systolic function, suggested the hypothesis that vascular protection may provide most of the clinical benefits of ACE inhibitors. This hypothesis was successfully tested by demonstrating a lower incidence of cardiovascular events in high-risk vascular patients randomized to long-term ACE inhibition with ramipril. Accordingly, the current rationale behind the use of ACE inhibitors in patients with chronic heart failure is largely that of vascular protection.

Angiotensin-Converting Enzyme Inhibitors↗