cytochrome-c-t and Cardiac-Output--Low

Apoptosis or programmed cell death is an evolutionarily conserved process of cell death, wherein cells die without provoking significant inflammatory response. There is convincing evidence that apoptosis contributes to the progression of heart failure. Apoptosis occurs through a cascade of subcellular events including cytochrome c release into the cytoplasm and activation of proteolytic caspases. Activated caspases lead to fragmentation of cytoplasmic proteins, including contractile apparatus, to a variable extent. It is proposed that the release of cytochrome c from mitochondria and contractile protein loss in living heart muscle cells contributes to systolic dysfunction. Interestingly, despite extensive changes in the cytoplasm, nuclear damage, which is the final event in apoptosis, is rather infrequent in the failing heart. Since the nucleus remains unaffected and the genetic blueprint intact in cells with interrupted apoptosis, these heart muscle cells might be amenable to cytoplasmic reconstitution. This process of 'apoptosis interruptus' could allow development of novel strategies to reverse or attenuate heart failure.

Topics: Animals; Apoptosis; Cardiac Output, Low; Caspases; Cytochromes c; Energy Metabolism; Enzyme Activation; Humans; Mitochondria, Heart; Myocardial Contraction; Myocardium; Protease Inhibitors; Ventricular Remodeling

Composite preparation refracterin administered in a dose of 300 mg/day for 3 days in addition to routine therapy significantly improved the results of treatment of severe cardiac insufficiency of ischemic genesis compared to placebo. Improvement of clinical status of patients is determined by positive dynamics of systolic and diastolic functions of the left ventricle.

Topics: Acetyldigoxins; Aged; Cardiac Output, Low; Cardiotonic Agents; Chronic Disease; Coronary Disease; Cytochromes c; Drug Combinations; Echocardiography; Female; Humans; Inosine; Male; Middle Aged; NAD; Oxyfedrine; Systole; Treatment Outcome; Ventricular Function, Left

Changes in oxidative stress and apoptotic process were studied during the progression of a compensated hypertrophy to a decompensated heart failure in guinea pigs. Banding of the ascending aorta resulted in heart hypertrophy. At 10 wk, ventricle-to-body weight ratio and thickness of the interventricular septum as well as the left ventricular wall were increased significantly. Although fractional shortening and ejection fraction were decreased, there were no signs of heart failure. Furthermore, there was no increase in wet-to-dry weight ratios for the lungs and liver at this stage. However, at 20 wk, heart failure was characterized by a significant depression in heart function as indicated by a decrease in fractional shortening, and ejection fraction and a lesser increase in wall thickness from diastole to systole. Animals also showed clinical signs of heart failure, and the wet-to-dry weight ratios of the lungs and liver were significantly higher. Cardiomyocyte oxidative stress was significantly higher in the 20-wk aortic-banded group. The ratio of Bax to Bcl-xl showed an increase at 10 wk, and there was a further increase at 20 wk. Mitochondrial membrane potential in the aortic-banded animals was significantly decreased at 10 and 20 wk. Cytochrome c levels were higher in the cytosol compared with the mitochondria, leading to a considerable increase in the expression of p17 subunit of caspase-3. At 20 wk, both early and late stages of apoptosis were observed in isolated cardiomyocytes. It is suggested that an increase in oxidative stress initiates mitochondrial death pathway during the hypertrophic stage, leading to apoptosis and heart failure at a later stage.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Cardiac Output, Low; Caspase 3; Cytochromes c; Disease Models, Animal; Disease Progression; Guinea Pigs; Heart; Hypertrophy, Left Ventricular; Male; Membrane Potential, Mitochondrial; Myocardium; Myocytes, Cardiac; Oxidative Stress

Topics: Animals; Apoptosis; Aurintricarboxylic Acid; Cardiac Output, Low; Caspase 3; Cytochromes c; Guinea Pigs; Hypertrophy, Left Ventricular; Membrane Potential, Mitochondrial; Mitochondrial Proteins; Myocardium; Oxidative Stress

Muscle atrophy is a determinant of exercise capacity in heart failure (CHF). Myocyte apoptosis, triggered by tumor necrosis factor-alpha (TNF-alpha) or its second messenger sphingosine (SPH), is one of the causes of atrophy. Growth hormone (GH) improves hemodynamic and cardiac trophism in several experimental models of CHF, but its effect on skeletal muscle in CHF is not yet clear. We tested the hypothesis that GH can prevent skeletal muscle apoptosis in rats with CHF. CHF was induced by injecting monocrotaline. After 2 wk, 2 groups of rats were treated with GH (0.2 mg.kg(-1).day(-1) and 1.0 mg.kg(-1).day(-1)) subcutaneously. A third group of controls had saline. After 2 additional weeks, rats were killed. Tibialis anterior cross-sectional area, myosin heavy chain (MHC) composition, and a study on myocyte apoptosis and serum levels of TNF-alpha and SPH were carried out. The number of apoptotic nuclei, muscle atrophy, and serum levels of TNF-alpha and SPH were decreased with GH at high but not at low doses compared with CHF rats. Bcl-2 was increased, whereas activated caspases and bax were decreased. The MHC pattern in GH-treated animals was similar to that of controls. Monocrotaline slowed down both contraction and relaxation but did not affect specific tetanic force, whereas absolute force was decreased. GH treatment restored contraction and relaxation to control values and brought muscle mass and absolute twitch and tetanic tension to normal levels. These findings may provide an insight into the therapeutic strategy of GH given to patients with CHF to improve exercise capacity.

Topics: Angiotensin II; Animals; Apoptosis; Body Weight; Cardiac Output, Low; Caspases; Cytochromes c; Human Growth Hormone; In Situ Nick-End Labeling; Insulin-Like Growth Factor I; Isometric Contraction; Male; Monocrotaline; Muscle, Skeletal; Muscular Atrophy; Myosin Heavy Chains; Physical Endurance; Rats; Rats, Sprague-Dawley; Sphingosine; Tumor Necrosis Factor-alpha