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Depressed myocardial contractility with paradoxically increased oxygen consumption has been demonstrated in previous studies of pressure overload hypertrophy. To determine whether altered mitochondrial respiration participates in the abnormal energetics of this muscle, right ventricular hypertrophy (RVH) was produced in 12 cats by pulmonary artery banding. A polarographic muscle bath was used to study eight control and eight RVH papillary muscles, and the respiration of mitochondria isolated from these right ventricles was characterized. RVH muscles demonstrated depressed force-velocity and length-tension curves. The myocardial oxygen consumption per gram of peak active tension was increased from 0.65 ± 0.05 nliters/mg beat -1 (control) to 1.10±0.07 nliters/mg beat -1 (RVH) ( P <0.001). Abnormal mitochondrial respiration was shown by an increase in the rate of state 4 oxygen consumption from 12.5±0.8 natoms/mg min -1 (control) to 19.9±0.8 natoms/mg min -1 (RVH) ( P < 0.001). The altered oxygen cost of active isometric tension in the RVH muscles was linearly correlated with the altered rate of mitochondrial state 4 oxygen consumption ( r = 0.91). Ruthenium red, a compound that blocks mitochondrial calcium uptake, reduced the rate of RVH state 4 oxygen consumption to the control level. The present study suggests a mechanism for the abnormal myocardial oxygen consumption in pressure overload hypertrophy and relates it to nonphosphorylating mitochondrial respiration linked to calcium transport.

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Depressed contractility with a paradoxically increased myocardial oxygen consumption has been associated with pressure-overload hypertrophy. The present experiments investigated myocardial hypertrophy induced by volume overload. Right ventricular volume overload was produced in 19 cats by surgically creating atrial septal defects (ASD); these cats were compared with 10 sham-operated control cats. The ASD cats showed an increase in the ratio of pulmonary blood flow to systemic blood flow from 1.04 ± 0.01 ( SE ) (control) to 3.30 ± 0.28 (ASD) ( P < 0.001). Hypertrophy was evidenced by a ratio of right ventricular weight to body weight of 0.59 ± 0.03 g/kg for control cats and 0.97 ± 0.03 for ASD cats ( P < 0.001). A polarographic muscle bath was used to study papillary muscles from 8 control and 8 ASD cats. ASD muscles demonstrated normal force-velocity curves, with maximal measured preload velocities of 1.32 ± 0.05 muscle lengths/sec: control velocities were 1.33 ± 0.05 muscle lengths/sec ( P > 0.9). The myocardial oxygen consumption of isotonic contractions was normal for ASD muscles. The length-tension curves were comparable, with developed tensions at Lmax of 6.20 ± 0.31 g/mm 2 for ASD muscles and 6.34 ± 0.23 g/mm 2 for control muscles ( P > 0.7). Myocardial oxygen consumption pergram of tension development at Lmax was 0.66 ± 0.06 µliters/mg beat -1 x 10 -3 in the ASD muscles and 0.65 ± 0.05 µliters/mg beat -1 x 10 -3 in the control muscles ( P > 0.8). The mitochondrial oxidative indexes from control and hypertrophied right ventricles were similar, with respiratory control indexes of 14.3 ± 0.8 for ASD hearts and 12.8 ± 1.6 for control hearts ( P > 0.1). These data demonstrate that contractility and energetics are normal in volume-overload hypertrophy, although these same factors are abnormal in pressure-overload hypertrophy. Thus, hypertrophy alone is not a common denominator for abnormal myocardial function and energetics.

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A polarographic method was used to determine the effects of acetylstrophanthidin on myocardial oxygen consumption (MVO 2 ) of 19 cat papillary muscles contracting under both afterloaded and isometric conditions. Under afterloaded conditions, acetylstrophanthidin shifted the force-velocity relation to the right and produced increments in both the extent and velocity of shortening at constant levels of developed force. These changes in myocardial mechanical behavior after strophanthidin were always associated with an increased MVO. Since both the extent and velocity of shortening increased following augmentation of the contractile state with glycoside, consideration of the individual effect of these variables in myocardial mechanical behavior on MVO was precluded. Therefore, experiments were performed on isometrically contracting muscle to evaluate the effect of changes in the velocity of contraction on MVO;> independent of changes in contractile element shortening. Comparison of the MVO 2 of isometric contractions at equal levels of developed tension (and thus equivalent amounts of internal contractile element shortening) was accomplished by decreasing initial muscle length after augmentation of the contractile state by acetylstrophanthidin. Under these conditions, augmentation of the contractile state, characterized by an increase in the velocity of contraction, was associated with an increased MVO. Thus it is concluded that the effect of acetylstrophanthidin is to increase MVO 2 at a constant load and that this augmentation of MVO 2 can be related to the change in contractile state of the muscle. INFLOW DtAJH CENTRAL TUBULAR MUSCLE CHAMBER STIM, FIGURE 1 Schematic illustration of the experimental apparatus. B = electrode controls for position and polarizing voltage; C == condenser column; E = electrode; M = lever stop; L = lever; R = pressure regulator.

SUMMARYThis study sought to determine whether the electrolyte content of peripheral arteries is altered in experimental congestive heart failure (CHF) XLI, February 1970 study the ionic composition of certain arterial segments of animals with experimentally induced chronic congestive heart failure. Methods Seventeen mongrel dogs weighing 26.1 to 46 pounds were studied. Congestive heart failure was induced in six animals by rapid ventricular stimulation by means of an implanted pacemaker at a fixed rate of 280 beats per minute over a period of 11 to 29 days.2 After chronic pacing, these animals all had ascites, pleural effusions, peripheral edema, and ventricular diastolic gallops on auscultation. In the 11 animals which comprise the control group ventricular stimulation was stopped prior to the production of congestive heart failure or pacing was not carried out prior to the time of study; none had evidence of fluid accumulation. Both groups of animals were fed the same standard diet. The cardiocirculatory dynamics in both the animals with heart failure and the control group were studied in the intact animal under light sedation. The animals were sedated with morphine, 3 mg/kg, promazine, 1.5 mg/kg, and promethazine, 1.5 mg/kg, by intramuscular injection.

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