Contractile function and myofibrillar ATPase activity in the exercise-trained dog heart.

Contractile function and myofibrillar ATPase activity in the exercise-trained dog heart RUSSELL T. DOWELL, H. LOWELL STONE, LOUIS A. SORDAHL, AND G. K. ASIMAKIS Department of Physiulugy and Biophysics, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73190; and Divisiun of Biochemistry, University of Texas Medical Branch, Galveston, Texas 77550

DOWELL, RUSSELL T., H. LOWELL STONE, LOUIS A. SORDAHL, AND G. K. ASXMAKIS. Contractile function and myofibriLlar ATPase activity in the exercise-trained dog heart. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 43(6): 977-982, 1977. - Myocardial contractility and the enzymatic (ATPase) activity of cardiac contractile proteins were examined after exercise training using the chronically instrumented, unanesthetized dog as an experimental model. Before training, heart rate and the maximum rate of left ventricular pressure development (max dP/&> were measured at rest and during submaximal exercise. Animals were then subjected to an 8- to 10-wk treadmill running program. Training was verified by the establishment of a lo- to ZO-beat/min reduction in heart rate during submaximal exercise. After training max dP/dt was within normal limits at rest, but significantly elevated during submaximal exercise. When max dP/dt was plotted as a function of heart rate, either with the animal standing quietly on the treadmill or during submaximal exercise, a marked elevation in max dP/& at any given heart rate was observed following training. Myofibrillar protein yield and ATPase activity values were nearly identical in left ventricles from exercise-trained and sedentary control dogs. Although exercise training by treadmill running improved contractile function in the unanesthetized dog myocardium, this response does not appear to involve alterations in myofibrillar ATPase activity.

21, 28) would seem to represent a cellular mechanism

to account for the improvement in heart contractile function. However, the relationship between contractile protein ATPase activity and contractile function in the exercise-trained heart remains unclear due to the fact that significant elevations in heart weight and/or heartto-body weight ratio accompanied elevated ATPase activity in some groups of rats which had been subjected to swimming exercise (2, 28). In contrast, rats trained by treadmill running maintain normal heart mass (7, 8) and have no alteration in contractile protein ATPase activity (1). Animal model constraints have also limited the determination of myocardial contractile function in the intact, unanesthetized animal. Therefore, the present studies were conducted using the chronically instrumented, unanesthetized dog as an experimental model for exercise training. The relationship between myocardial contractile function and the enzymatic properties of myocardial contractile proteins was evaluated atier training. METHODS

Animal Selection and Experimental chronically instrumented animal; treadmill running; heart rate; maximum rate of left ventricular pressure development; myofibrillar salt sensitivity

EPIDEMIOLOGICAL (IO) and experimental (20) studies involving human subjects have illustrated the beneficial effects of repetitive exercise on the cardiovascular system. In experimental animals, where a direct evaluation of heart function can be obtained, exercise training has been shown to enhance normal, resting myocardial performance (5) and/or to impart an improved ability to maintain myocardial performance when stressful conditions are encountered (3, 7, 17, 21, 22) More specifically, enhanced cardiac contractile function has been noted in exercise-trained animals (3, 7). Since skeletal muscle contractile function is related to the enzymatic (ATPase) activity of contractile proteins (4) and evidence is accumulating which suggests a similar relationship in cardiac muscle (6, 19, 23, 31), the reported exercise-induced increase in cardiac contractile protein adenosine triphosphatase (ATPase) activity (2,

Groups

Adult, mongrel dogs of both sexes were used in these experiments. All animals were free of heartworms and those willing to run on a motor-driven treadmill were selected for exercise training. Two separate exercise training groups were used. Six dogs were surgically instrumented for contractile function studies as described below. Eight additional exercise-trained animals were utilized for contractile protein studies. Previous work (25) and preliminary experiments indicated that cardiac instrumentation had no significant effect on either the development of an exercise training response or the biochemical measurements made in the present studies. Therefore, some of the animals comprising the exercise-trained group for contractile protein studies were not instrumented and uninstrumented, sedentary animals (n = 10) that were allowed only normal cage activity served as controls. Contractile Function Studies Animal preparation and hemudynamic measurements, Animals were anesthetized and surgically in-

Downloaded from www.physiology.org/journal/jappl by ${individualUser.givenNames} ${individualUser.surname} (130.070.008.131) on November 7, 2018. Copyright © 1977 American Physiological Society. All rights reserved.

978

strumented as previously described (25) to obtain cardiovascular measurements. Instrumentation included a solid-state pressure transducer (Konigsberg Instruments, model P-17) which was placed in the left ventricular chamber via a stab wound in the apical region. After a 4-wk surgical recovery period, instrumented animals were familiarized with the treadmill so that initial hemodynamic measurements and submaximal exercise testing could be conducted. With the animal standing quietly on the treadmill, left ventricular pressure measurements were recorded using a Beckman dynograph and Ampex FR-1300 tape recorder. Heart rate was obtained from the recorded electrocardiogram. The maximum rate of left ventricular pressure development (max dP/&) was subsequently determined from the magnetic tape record using a digital computer. This measurement was utilized as an index of myocardial contractile function. After initial hemodynamic measurements were completed, a submaximal exercise test was conducted. The submaximal test began with a 3-min warm-up run at 4.8 km/h, 0% treadmill incline. Treadmill speed was then increased to 6.4 km/h and maintained constant throughout the exercise test. The treadmill incline was increased from 0% to 20% in 4% increments at 3-min intervals. Heart rate and max dP/ dt measurements were taken during the last minute of each exercise test stage. Exercise training program. The exercise training program described by Tipton et al. (26) was initiated after control studies had been completed. Animals were exercised daily 5 days/wk. During the 1st wk, the duration of each training session was 35 min. Running time and intensity were progressively increased until animals were running 75 minlexercise session during the 8th wk of the training program, The submaximal exercise test described above was administered at the end of the 4th wk and every 2 wk thereafter until a lQto 2@beat/min reduction in heart rate was observed at any given level in the submaximal exercise test. If this criterion was not achieved at the end of the 8th wk of training, then the 8-wk exercise level was maintained until a trained state was achieved. All exercised animals in this study achieved the criterion for training within 10 wk of exercise. At the termination of the contractile function studies, animals were anesthetized, and the heart was excised. The left ventricle plus interventricular septum was dissected and weighed, but heart biochemical analyses were not performed. Contractile Protein Studies Animal selection and treatment. Animals for exercise training were selected and treated as described above with the exception that some animals were not. surgically instrumented. However, heart rate was available from electrocardiographic recordings in all animals and was utilized in conjunction with submaximal exercise testing to determine the efficacy of the training program. Tissue preparation and assay procedures, Control and exercise-trained animals were anesthetized with pentobarbital sodium (30 mglkg, iv) and placed on positive-press ure respi ration with 100% oxygen deliv-

DOWELL,

STONE,

SORDAHL,

AND

ASIMAKIS

ered through an endotracheal tube. The heart was exposed through an incision in the fourth intercostal space and excised. Left ventricular tissue samples were obtained from the free wall of the ventricle, weighed, and frozen, The remaining left ventricle plus int,erventricular septum was dissected and weighed. Myofibrils were prepared from the left ventricular free wall tissue samples using the method previously described (6) which includes detergent treatment to solubilize and remove contaminating membranes. Purified myofibrils were resuspended in 50 mM tris (hydroxymethyl)aminomethane (Tris) buffer, pH 7.4, which contained 150 mM KCl. Protein concentration was measured by the biuret reaction (II) and subsequently adjusted to 6 mg/ ml with Tris-KC1 buffer. Myofibrillar ATPase activity was measured in a reaction mixture containing 1 mM MgS04, 0.1 mM CaCl,, 1 mM Na,ATP, 20 mM Tris, pH 7.4, and 1.2 mg myofibrillar protein in a final volume of 4.0 ml. Sodium azide (2 mM final concentration) was routinely added to inhibit possible contaminating mitochondrial ATPase activity. The reaction was initiated by substrate (ATP) addition. After 2 min incubation at 3O”C, the reaction was stopped with 1 ml of 10% (wt/vol) trichloroacetic acid. Precipitated protein was removed by centrifugation and the supernatant was assayed for inorganic phosphate (Pi) by the method of Rockstein and Herron (IS). Enzyme activity is expressed as pmol PJmg myofibrillar protein per min. Since structurally different forms of contractile proteins exhibit differences in their enzymatic sensitivity to salt (30), ATPase activity was determined in myofibrils from selected control and uninstrumented exercise-trained hearts as outlined above with the exception that increased concentrations of KC1 were present in the assay mixture. Enzyme activity was measured at 7.5 (control), 50, 100, and 200 mM final KC1 concentrations. The relative decrease in ATPase activity was plotted versus KC1 concentration to evaluate possible structural alterations in myocardial contractile proteins resulting from exercise training. Statistical Analyses Control and submaximal exercise test hemodynamic data were obtained from the magnetic tape recording using a PDP U/10 computer. Data were taken throughout a single cardiac cycle at 5-ms intervals and five consecutive beats were averaged under each condition analyzed. Since each exercise-trained animal served as its own control for contractile function studies, hemodynamic data were statistically evaluated using the Student paired t-test. Contractile protein data from exercise-trained animals were compared to control animals by the Student unpaired t-test. A P value of 0.05 or less was considered statistically significant. RESULTS

Body Weight and Heart Weight The genera 1 health status of the animals used in these studies was not visibly influenced by either


HEART

FUNCTION

AND

ATPASE

ACTIVITY

AFTER

chronic cardiovascular instrumentation or exercise training. Body weights ranged from 14 ti 30 kg prior to the initiation of the experiments, with an average value of 22 t 2 kg (mean -t- SE) for all exercise-trained animals studied (n = 14). Body weight was not significantly altered (21 k I kg) at the completion of the exercise program and was comparable to sedentary control values. Left ventricular (plus septum) weight was 73 * 4 and 85 t 8 g in sedentary control and exercise-trained (n = 14) animals, respectively. When normalized for individual differences in body weight, the lefi ventricle-tubody weight ratio was 4.40 t 0.11 and 4.51 k 0.20 in control and exercise-trained animals, respectively. No significant differences were detected in either of the above measurements. Contractile

Function

TABLE 1. Hemodynamic measurements standing quietly on treadmill before and after exercise training

Untrained Trained

132 123

-+ 8 k 9

240

1

220 -

t-hrt

Rate

mQ

(beatshin.)

!

Studies

In the animals utilized for contractile function studies, initial hemodynamic measurements were taken with the animals standing quietly on the treadmill. The results before and after training are given in Table 1. Heart rate was reduced by approximately 10 beats/ min after training, but this effect was not statistically significant. Left ventricular peak systulic and end-diastolic pressures were essentially unchanged under resting conditions. Maximal dP/& was increased by approximately 15% after training, but this increase did not achieve statistical significance. The heart rate responses during submaximal exercise testing are shown in Fig. 1. Prior to training, heart rate increased in a nearly linear fashion as a function of treadmill incline. It should be noted that many untrained animals were not able to exercise at a level greater than 6.4 km/h at a 16% incline. Therefore, the data for the animals in this group that achieved this level of exercise were not included. ARer training, a 15- to 30-beat/‘min average reduction in heart rate was observed at any given point during the submaximal exercise test. Although statistically nonsignificant (0.05 < P < 0.10) compared to untrained values by paired t analysis, the heart rate results demonstrate the efficacy of the treadmill running program in producing a cardiovascular training response. Maximal dP/& responses during submaximal exercise testing are shown in Fig. 2. As was the case with heart rate, max dP/& increased as a function of treadmill incline prior to training. Once a trained state had been achieved, however, the index of contractile function was consistently elevated at all stages of the

Heart Rate beatslmin

979

TRNNING

LVP, Tot-r

114 113

Values are mean 2 SE from peak systolic pressure; LVEDP pressure.

A 6 * 7

6 animals. = left

LVEDP, Torr

321 4+2

with animal

Max dPldt,

2,620 2,969

Tom/s

+ 450 XL 423

LVP = left ventricular ventricular end-diastolic

FIG. 1. Heart rate response during before and after exercise trailking. Mean same 6 animals indicated in Table 1.

s&maximal exercise test values showrm are from the

7

o- ---0 Trained

6

Max.

dP/dt

(mmHgAec.

x to31

5

4

I

I

I

0

4

8

Treadmill FIG, 2. Maximal dP/& response during before and after exercise training. Mean same 6 animals indicated in Table 1. untrained by paired E analysis.

Incline

1

I

t6

t2

I

20

(“/ok

submaximal values shown *P < 0.05

exercise test are from the compared tu

submaximal exercise test and was significantly increased at treadmill inclines of 4% or greater. To further illustrate the contractile function response to exercise training, left ventricular max dP/& is plotted as a function of heart rate before and afier training in Fig. 3. At any given heart rate, either with the animal standing quietly on the treadmill or during submaximal exercise, exercise-trained animals have an elevated max dP/& when compared to that observed prior to exercise training. Contractile

Protein

Studies

Although complete contractile function data were not available from animals comprising the exercise-trained group in this series of experiments, heart rate was obtained from electrocardiographic recordings. On the


980

DOWELL, 7

STONE,

SORDAHL,

AND

ASIMAKIS

P I P

6 *-a o----o

Untrained Trained /

/

0

0-0

Sedentary Control Exercise-Trained

!

0’

//’ d

5

Max. dP/dt (mml-lgkec.

60 ATPase

Activity

(% Control )

x 103) 4

40

3 20

2 h0 /,

Heart 3. Maximal and after exercise standing quietly testing is plotted same conditions. cated in Table 1. FIG.

200 1

150 1

Rote

250 I

dP/dt response as a function training. Average maximal on the treadmill and during as a function of the average Values shown are from the

Sedentary control (10) Exercise-trained (8)

46 4 3 47 1 3

ATPase

Activity, pmol per min

0.199 0.194

50 mM

of heart rate before dP/& with the animal submaximal exercise heart rate under the same 6 animals indi-

TABLE 2. Left ventricular myofibril yield and ATPase activity of sedentary control and exercise-trained animals Myofibrillar Protein, mglg

7.5

(beats/min.)

P,/mg

-t- 0.012 * 0.012

Values are mean k SE. Number of animals in each group are given in parentheses. Enzyme activity was measured under optimum (control) conditions as described in METHODS.

basis of heart rate responses during submaximal exercise testing, all animals in this exercise group met the criterion for training. The contractile protein results are given in Table 2. Myofibrillar protein yield was not significantly different in left ventricular tissue obtained from control and exercise-trained animals. When assayed under optimum conditions, nearly identical myofibrillar ATPase activity was detected in both groups of animals. Furthermore, no marked contractile protein structural alterations were apparent in myofibrils from selected exercise-trained animals as indicated by enzymatic salt sensitivity (Fig. 4).

A slower heart rate at comparable workloads is considered to be a characteristic cardiovascular training response (26). After B-10 wk of treadmill running, the slower resting heart rate and 15 to 30-beatlmin average reduction in heart rate at any given work intensity indicate the establishment of a trained state in the

100 Final

200 [KU]

4. Enzymatic (ATPase) salt sensitivity of left ventricular myofibrils from sedentary control and exercise-trained animals. Mean values from 5 sedentary control and 2 exercise-trained animals are shown. Bars through sedentary control values represent 1 standard error of the mean. Enzyme activity measured under optimum (7.5 mM final KCl) conditions was considered control (100%) activity for each determination. FIG+

exercised animals utilized in the present studies. Enhanced skeletal muscle respiratory capacity represents another characteristic index of exercise training (13). Previous studies in our laboratory (24) have shown increases in skeletal muscle mitochondrial oxygen consumption and cytochrome oxidase specific activity in dogs which have completed the treadmill running program described. In contrast, dog heart mitochondrial respiratory activity is unchanged affer training (24) and these results are in accord with training studies conducted in other animal models (15, 16). Although repetitive treadmill running was effective in producing a training response in dogs, significant left ventricular hypertrophy was not present in exercise-trained animals. In the present studies, myocardial contractile function was determined in unanesthetized animals via left ventricular pressure measurements obtained with an implanted, high-fidelity pressure transducer. Therefore, potential uncertainties regarding a) the influence of anesthetic agents on heart function and b) the frequency response characteristics of the pressure measuring system were avoided. The maximum rate of pressure development (max dP/&) was utilized as an index of left ventricular contractile function. We recognize that max dP/& may be influenced by heart rate (27) as well as myocardial loading conditions (12, 14). Since heart rate was reduced due to exercise training under all conditions studied, the “treppe” phenomenon (9) cannot account for the observed increases in max dP/dt. Myocardial preload and afterload were unchanged under resting conditions after training as indi-


HEART

FUNCTION

AND

ATPASE

ACTIVITY

AFTER

981

TRAINING

cated by left ventricular end-diastolic pressure and left ventricular peak systolic pressure measurements, respectively. A more extensive hemodynamic study involving exercise-trained dogs (25) found no alterations in preload and afterload during submaximal exercise testing. Therefore, enhanced max dP/dt in trained animals during submaximal exercise indicates an improvement in left ventricular contractile function. This conclusion is in agreement with studies in rats (3, 7) where previous exposure to treadmill running favorably influenced contractile performance when the heart was subjected to stressful conditions. It should also be noted that heart weight (7) and resting heart function (3, 7) were maintained within normal limits in the above studies. The divergent contractile function responses seen before and after training suggest that repetitive exercise exerts some influence at the level of the contractile proteins. Autonomic (sympathetic) nervous system activation could produce a positive inotropic effect. However, chronotropic responses are clearly attenuated in trained animals and any neurally mediated mechanism would require a dissociation of normal autonomic nervous system function to allow positive inotropy without comparable chronotropic effects. Increased enzymatic (ATPase) activity of myocardial contractile proteins has been observed in rats subjected to swimming exercise (2, 21, 28). Such a response could improve contractile function. However, cardiac actomyosin ATPase activity was unchanged in rats trained by treadmill running (1) and myofibrillar enzymatic activity was unaltered in the present treadmill exercise experiments. In a recent study by Williams and Potter (29), cardiac hypertrophy was not present in cats that were trained by treadmill running and isolated papillary muscles from exercise-trained animals exhibited normal mechanical performance. The authors concluded that “the intrinsic contractile state of the myocardium

is unaffected by exercise sufficient to produce a cardioincreased cardiac vascular training effect .” Therefore, contractile protein enzymatic activity, which implies alterations in the intrinsic contractile state of the myocardium, appears to be a function of swimming exercise rather than a generalized exercise-training response. It is clear from our results that repetitive treadmill exercise exerts a significant effect on myocardial contractile performance without producing detectable alterations in the enzymatic properties of cardiac contractile proteins. Because our experiments were conducted in the intact animal, the autonomic nervous system and/or humoral factors may play a role in this cardiovascular adaptation. Nevertheless, some intracellular mechanism must ultimately contribute to the improved functional capacity of the exercise-trained heart. Both mitochondria and sarcoplasmic reticulum are capable of regulating myocardial intracellular calcium levels which, in turn, may influence contractile function. We have previously noted changes in mitochondrial and sarcoplasmic reticulum calcium transport kinetics in isolated subcellular preparations from exercise-trained dog hearts (24). The factor(s) contributing to these subcellular changes and their potential physiological role in regulating myocardial contractile function have not been established. However, changes in subcellular calcium transport properties would offer an attractive, but speculative, mechanism which could achieve improved contractile performance in the exercise-trained heart without any alteration in the enzymatic properties of cardiac contractile proteins. The expert technical assistance of Ms. Judith Haithcoat is gratefully acknowledged. This work was supported in part by the National Institutes of Health Grants HL-16352, HL-18839, and HL-14828 and a grant from the American Heart Association. Received

for publication

19 January

1977.

REFERENCES 1. BALDWIN, K. M., W. W. WINDER, AND J. 0. HOLLOSZY. Adaptation of actomyosin ATPase in different types of muscle to endurance exercise. Am. J. Physid. 229: 422-426, 1975. 2. BHAN, A. K., AND J. SCWEUER. Effects of physical training on cardiac actomyosin adenosine triphosphatase activity. Am. J. Physiol. 223: 1486-1490, 1972. 3. CAREY, R. A., C. M. TIPTON, AND D.. R. LUND. Influence of training on myocardial responses of rats subjected to conditions of ischaemia and hypoxia. Cardiovascular Res. 3: 359-367, 1976. 4. CLOSE, R, I. Dynamic properties of mammalian skeletal muscles. Physiol. Rev. 52: 129-197, 1972. 5. CREWS, J*, AND E. E, ALDINGER. Effect of chronic exercise on myocardial function. Am. Heart J. 74: 536-542, 1967. 6. DOWELL, R. T. Myocardial contractile function and myofibrillar ATPase activity in chemically sympathectomized rats. Circulation Res. 39: 683-689, 1976. 7. DOWELL, R. T., A. F. CUTILLETTA, M. A. RUDNIK, AND P. C. SODT. Heart functional responses to pressure overload in exercised and sedentary rats. Am. J. Physiol. 230: 199-204, 1976. 8. DOWELL, R. T., C. M. TIPTON, AND R. J. TOMANEK. Cardiac enlargement mechanisms with exercise training and pressure overload. J. Mol. CeZZuZar Cardi&. 8: 407-418, 1976. 9. FOLKOW, B., AND E. NEIL. Circulation. New York: Oxford, 1971, p, 178-179. 10. Fox, S. M. III, AND J. S. SKINNER. Physical activity and cardiovascular health. Am. J. Cardiol. 14: 731-746, 1964.

11. GORNALL, A. G., C. J. BARDAWILL, AND M. M. DAVID. Determination of serum proteins by means of the biuret reaction. 9. &ok Chem. 177: 751-766, 1949. 12. GROSSMAN, W., F. HAYNES, J. A. PARASKOS, S. SALTZ, J. E, DALEN, AND L. DEXTER. Alterations in preload and myocardial mechanics in the dog and in man. Circulation Res. 31: 83-94, 1972. 13. HOLLOSZY, J. O., AND F. W. BOOTH. Biochemical adaptations to endurance exercise in muscle. Ann. Rev. Physiol. 38: 273-291, 1976. 14. MASON, D. T., J. F. SPANN, JR., AND R. ZELIAS. Quantification of the contractile state of the intact human heart. Am. J. Cardiol. 26: 248-257, 1970. 15. OSCAI, L. B., P. A. MOLE, B. BREI, AND J. 0. HOLLOSZY. Cardiac growth and respiratory enzyme levels in male rats subjected to a running program. Am. J. Physiok. 220: 1238-1241, 1971. 16. OSCAI, L. B., P. A. MOLE, AND J. 0. HOLLOSZY. Effects of exercise on cardiac weight and mitochondria in male and female rats. Am. J. PhysioZ. 220: 1944-1948, 1971, 17. PENPARGKUL, S., AND J. SCHEUER. The effect of physical training upon the mechanical and metabolic properties of the rat heart. J. Ch. Invest. 49: 1859-1868, 1970, 18. ROCKSTEIN, M., AND P. W. HERRON. Calorimetric determination of inorganic phosphate in microgram quantities. AnaL Chem. 23: 1500, 1951. 19. ROVETTO, M. J., A. C. HJALMARSON, H. E. MORGAN, M. J.


982

20.

21.

22.

23,

24.

25.

BARRETT, AND R. A. GOLDSTEIN, Hormonal control of cardiac myosin adenosine triphosphatase in the rat. Circulation Res. 31: 397-409, 1972. SALTIN,~.,G.B~M~VIST,~, H. MITCHELLJL LJOHNSONJR., K. WILDBNTHAL, AND C. B. CHAPMAN. Response to exercise after bed rest and training. Circulation. 38, Suppl. 7: l-78, 1968. SCHEUER, J., S. PENBABGKUL, AND A. K. BHAN, Experimental observations on the effect of physical training upon intrinsic cardiac physiology and biochemistry. Am. J, Cardiol. 33: 744751, X974. SCHEUER, J., AND S, W, STEZOSKI. Effect of physical training on the mechanical and metabolic response of the rat heart to hypoxia. Circulution Res. 30: 418-429, 1972. SHIVERICK,K.T.,B.B.HAMRELL,AND N.R.ALPERT. Structural and functional properties of myosin associated with the compensatory cardiac hypertrophy in the rabbit. J. Mol. CelZular Casdiol. 8: 837-851, 1976. SORDAHL, L. A., G. IL ASIMAKIS, R. T. DOWELL, AND H. L. STONE. Functions of selected biochemical systems from the exercise-trained dog heart. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 42: 426-431, 1977. STONE, H. L. Cardiac function and exercise training in conscious

DOWELL,

26.

27.

28.

29.

30.

31,

STONE,

SORDAHL,

AND

ASIMAKIS

dogs. J, Appl. Physiol.: Respirat. Environ. Exercise Physiol. 42: 824-832, 1977. TXPTON, C. M., R. A. CAREY, W. C. EASTIN, AND H. H. ERICKSON. A submaximal test for dogs: evaluation of effects of training, detraining, and cage environment. J. Appl. Physiol. 37: 271275, 1974. WALLACE, A. G., N. S. SKINNER, JR,, AND J. H. MITCHELL, Hemodynamic determinants of the maximal rate of rise of left ventricular pressure. Am. J, Physiol. 205: 30-36, 1963. WILKERSON, J. E., AND E. EVONUK. Changes in cardiac and skeletal muscle myosin ATPase activities after exercise. J. Appl. Physiol. 30: 328-330, 1971. WILLIAMS, 6. F., JR., AND R. D, POTTER. Effect of exercise conditioning on the intrinsic contractile state of cat myocardium. Circulation Res. 39: 425-428, 1976. YAZAKI, Y., AND M. S. RABEN. Cardiac myosin adenosinetriphosphatase of rat and mouse. Distinctive enzymatic properties compared with rabbit and dog cardiac myosin. Circulation Res. 35: 15-23, 1974. YAZAKX, Y ., AND M. S. RABEN. Effect of the thyroid state on the enzymatic characteristics of cardiac myosin. Circulation Res. 36: 208-215, 1975.


Myofibrillar ATPase activity in rat heart after chronic propranolol administration.

Myocardial contractile function and myofibrillar adenosine triphosphatase activity in chemically sympathectomized rats.

Neuronostatin attenuates myocardial contractile function through inhibition of sarcoplasmic reticulum Ca2+-ATPase in murine heart.

Ultrastructural localization of ATPase activity in the dog area postrema.

Developmental difference in the stimulation of cardiac myofibrillar Mg2(+)-ATPase activity by calmidazolium.

The effects of ATP, inorganic phosphate, protons, and lactate on isolated myofibrillar ATPase activity.

Tellurite effect on ATPase activity of contractile membrane protein.

Cardiac contractile proteins. Adenosine triphosphatase activity and physiological function.

Myocardial contractile protein ATPase activities in adrenalectomized and thyroidectomized rats.

Effects of acute and chronic ethanol on cardiac contractile protein ATPase activity of Syrian hamsters.

Molecule specific effects of PKA-mediated phosphorylation on rat isolated heart and cardiac myofibrillar function.

Myofibrillar bound cyclic nucleotide phosphodiesterase in heart and skeletal muscle.

Pathomechanisms in heart failure: the contractile connection.

Dog Footprint in the Heart.

Ca(2+)-activated myofibrillar ATPase: transient kinetics and the titration of its active sites.

Effects of atrial natriuretic peptide on myocardial contractile and diastolic function in patients with heart failure.

Oncometabolite d-2-hydroxyglutarate impairs α-ketoglutarate dehydrogenase and contractile function in rodent heart.

Sinus nodal function in the intact dog heart evaluated by premature atrial stimulation and atrial pacing.

Studies on the distribution of cholinesterases: activity in the human and dog heart.

L-sorbose does not cause hemolysis in dog erythrocytes with inherited high Na, K-ATPase activity.

The effects of Bay K 8644 on diastolic function in the dog heart.

Paradoxical dynamic interaction of heart period and vagal activity on atrioventricular conduction in the dog.

Fiber differentiation of the human laryngeal muscles using the inhibition reactivation myofibrillar ATPase technique.

Effect of intravenous C-terminal octapeptide of cholecystokinin and intraduodenal ricinoleic acid on contractile activity of the dog intestine.