oligomycins and Heart-Failure

After inducing haemodynamic cardiac overload in rabbits, the authors studied in several stages (1-14 months) the calcium transport activity of the mitochondrial and sarcoplasmic myocardial fractions using labelled 45CaCl2. A coincidence was found between changes in myocardial contractility and changes in calcium transport activity of intracellular organelles. A possible important role of mitochondria in this adaptive process was also documented. Since the calcium transport capacity of the sarcoplasmic reticulum progressively decreases (with the exception of the earliest stages following overload induction), it seems that increased myocardial contractility ensures enhanced Ca transport activity of the mitochondria. Myocardial contractility drops only at the time when the Ca transport activity of the mitochondria decreases. Since these changes occur already at the time of regression of myocardial hypertrophy, which precedes heart failure, it can be assumed that they are causally connected with the reduced contractility of a failing heart.

Topics: Animals; Antimycin A; Calcium; Calcium-Transporting ATPases; Cardiomegaly; Chemical Fractionation; Heart Failure; Intracellular Membranes; Mitochondria, Heart; Myocardium; Oligomycins; Rabbits; Rotenone; Sarcoplasmic Reticulum

Topics: Adenosine Triphosphatases; Animals; Azides; Blood Pressure; Depression, Chemical; Dinitrophenols; Heart; Heart Failure; Heart Ventricles; Hypertrophy; Magnesium; Male; Myocardium; Oligomycins; Organ Size; Ouabain; Potassium; Rabbits; Sodium; Stimulation, Chemical

The ability of heavy microsomes and mitochondria, isolated from the control and failing hearts of genetically dystrophic hamsters (BIO 14.6 strain), to accumulate calcium was examined. The rate and extent of energy-linked calcium binding (in the absence of oxalate) by the heavy microsomes of the failing heart were markedly depressed. The calcium uptake (in the presence of 5 mM oxalate) by the heavy microsomes of the failing heart was similar to that of the control heart. On the other hand, both the rate and extent of energy-linked calcium binding (in the absence of Pi and succinate) and calcium uptake (in the presence of 4 mM Pi and 5 mM succinate) by mitochondria were greatly reduced in the failing heart in comparison to the control. No difference in the total adenosine triphosphatase activities (Ca(++)-Mg(++) stimulated) of heavy microsomes or mitochondria was observed between the control and failing hearts. These results indicate an abnormality of subcellular membranes of the failing heart to bind calcium and support the growing conviction concerning the defective "calcium pump" as a molecular abnormality associated with a moderate degree of congestive heart failure.

Topics: Adenosine Triphosphatases; Animals; Azides; Biological Transport, Active; Calcium; Cricetinae; Electron Transport Complex IV; Glucose-6-Phosphatase; Heart Failure; In Vitro Techniques; Microsomes; Mitochondria, Muscle; Muscular Dystrophies; Myocardium; Nucleotidases; Oligomycins

Topics: Adenosine Triphosphatases; Animals; Biological Transport, Active; Calcium; Depression, Chemical; Endoplasmic Reticulum; Heart Failure; In Vitro Techniques; Male; Microscopy, Electron; Mitochondria, Muscle; Myocardium; Oligomycins; Oxalates; Perfusion; Rats