Augmented aftercontractions in papillary from rats with cardiac hypertrophy LOIS JANE HELLER Department of Physiology, University of Minnesota, School of Medicine, Duluth, Minnesota 55812

HELLER, LOIS JANE. Augmented aftercontractions in papillary muscles from rats with cardiac hypertrophy. Am. J. Physiol. 237(6): H649-H654, 1979 or Am. J. Physiol.: Heart Circ. Physiol. 6(6): H649-H654,1979.-Paired-pulse stimulation induced larger aftercontractions in papillary muscles from spontaneously hypertensive rats (SHR) than from normotensive Wistar-Kyoto rats (WKY). To determine whether aftercontraction exaggeration is a general characteristic of hypertrophied cardiac muscle, three models were examined: SHRs, deoxycorticosterone acetate (DOCA)-treated rats, and aorta-constricted rats. Responses of papillary muscles from hypertrophied hearts tested under conditions conducive to aftercontraction generation were compared to papillary muscles from WKY or shamtreated controls, respectively. Field-stimulated papillary muscles mounted in an oxygenated temperature-controlled physiologic salt solution were exposed to calcium concentrations of 2.5 and 5.0 mM, and temperatures of 27°C and 17°C. Although testing conditions influenced the contractile responses to single stimuli, there was no difference in active tension, time to peak tension, or one-half relaxation time between the three experimental groups and their respective controls. Paired-pulse stimulation induced aftercontractions that were enhanced in highcalcium and low-temperature solutions. Under these conditions, papillary muscles from hypertrophied hearts developed larger aftercontractions than did their respective controls. spontaneously hypertensive rats; deoxycorticosterone acetate (DOCA) hypertension; aortic constriction; isometric myocardial contraction; paired-pulse stimulation

muscles

Duluth,

SHR and WKY strains. Another possibility, however, is that the subcellular condition(s) necessary for the generation of aftercontractions are more easily met in SHRs than in DOCA-hypertensive preparations. In this study, hypertrophied cardiac muscles were tested under conditions that were altered from previously used arbitrary levels of ion concentrations and temperature so as to produce an environment more conducive to the generation of aftercontractions: calcium concentration of the bathing medium was increased and the temperature decreased. Three experimental groups of rats with cardiac hypertrophy were examined: 1) spontaneously hypertensive rats, 2) rats made hypertensive by treatment with DOCA, and 3) rats with cardiac hypertrophy induced by a subdiaphragmatic aortic constriction. Isometric contractile properties of isolated papillary muscles from these three experimental groups were compared with appropriate normotensive controls. Under these testing conditions, preparations from all three experimental groups of rats with cardiac hypertrophy were found to produce larger aftercontractions than their respective controls. This suggests that the mechanisms responsible for producing aftercontraction in isolated heart muscle may be exaggerated whenever cardiac hypertrophy is present. METHODS

are small, slow contractile events that occur occasionally in preparations of isolated cardiac muscle. They closely follow a regular contraction and are most prominent in preparations that are either stimulated rapidly or exposed to paired pulses (3,4,6,9,11,X, 20). Isolated hypertrophied cardiac muscles from spontaneously hypertensive rats (SHR) have been shown to develop larger aftercontractions in response to pairedpulse stimulation than similar nonhypertrophied preparations from normotensive Wistar-Kyoto rats (WKY) (9). In a recent study examining isometric characteristics of hypertrophied cardiac muscle from rats made hypertensive by treatment with deoxycorticosterone acetate (DOCA), it was found that the incidence and amplitude of aftercontractions induced in these preparations were not different from those in normotensive controls (10). This suggested that the exaggerated aftercontractions in SHRs are not caused by the cardiac hypertrophy per se but rather represent genetic differences between the AFTERCONTRACTIONS

0363-6135/79/0000-0000$01.25

Copyright

0 1979 the American

Physiological

Animals. Three groups of rats with cardiac hypertrophy were compared to their respective controls. 1) Male spontaneously hypertensive rats (18) (16-20 wk old). These rats were bred and raised in the University of Minnesota, Duluth, facilities and were compared to identically treated age-matched male rats from their progenitor Wistar-Kyoto strain.

2) Male Sprague-Dawley rats in which DOCA-hypertension was induced. Animals were unilaterally nephrectomized under sodium pentobarbital anesthesia (37 mg/ kg ip) and, following recovery, were given 1% NaCl to drink. Biweekly subcutaneous injections of 10 mg DOCA in sesame oil were given for 7 wk postsurgery. Shamoperated, sesame oil-injected, age-matched male Sprague-Dawley rats served as the control group. Rats were 16-18 wk old at time of death. 3) Male Sprague-Dawley Society

rats in which subdiaphragH649

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H650 matic aortic constrictions were produced. Animals were anesthetized with sodium pentobarbital, and the abdominal aorta between the diaphragm and the renal artery was exposed via a flank incision. A 19,gauge blunted needle was laid alongside the exposed segment of the aorta. A 3-O silk ligature was passed under both the aorta and the needle and tied securely, and then the needle was carefully withdrawn. This degree of constriction was tolerated by 75% of the animals, the remainder dying with a ruptured aortic aneurysm appearing above the constriction within the 1st wk after surgery. The surviving animals were killed 4-6 wk postsurgery. Sham-operated, age-matched male Sprague-Dawley rats served as the control group. All animals were 16-18 wk old at time of death.

Papillary muscle preparations. Details concerning the muscle preparation and the stimulating and recording systems have been previously. described (9, 10). On the day of the experiment, rats were anesthetized with sodium pentobarbital, and mean arterial pressure was determined by carotid artery cannulation. The heart was rapidly removed and placed in an oxygenated physiologic salt solution (27-32OC) containing (mM): NaCl 115, KC1 6.0, MgC12 1.2, CaC12 2.5, glucose 11.5, and Tris-Cl 35.0, at pH 7.4. The left ventricular posterior papillary muscle was removed and mounted in the muscle bath through which the above solution at 27 t 0.5OC was circulated. Suprathreshold field stimulation was produced through stainless steel plate electrodes positioned on either side of the muscle. Isometric force development was recorded along with stimulus artifacts that served as a timing reference on a Brush 440 recording system. Cardiac hypertrophy was assessed by determining the blotted wet ventricular weight-to-body weight ratio and comparing experimental groups with their respective controls. ’ ProtocoZ. Steady-state active tension development of papillary muscles stimulated at 0.2 Hz was reached after 30-60 min. At this time the length of the muscle at which tension development was maximal (LmaX)was determined by stretching the muscle in 0.5.mm increments. Active tension, time to peak tension development (TPT), and one-half relaxation times (%RT) were measured at L,,,. This’length was not changed during the remainder of the experiment. Responses to paired-pulse stimulation were determined by subjecting the muscle to a repetitive pattern of four single stimuli followed by four paired stimuli (0.2 Hz). The interval between the stimuli of the paired pulses was progressively increased from 100 to 1,000 ms in steps ranging from 25 m to 100 ms. The incidence of aftercontractions was noted and their amplitude measured from tracings obtained at high-sensitivity amplification. The amplitude was expressed in absolute values and as a percent of the amplitude of the response to the first stimulus of the pair. Twitch characteristics and responses to paired-pulse stimulation were obtained under four different testing conditions presented in the following order: I) normal solution at 27°C U) high Ca2’ (5.0 mM) solution at 27”C, 110 normal solution at 17*C, and IV) high W* solution at 17°C.

L. J. HELLER

At the end of each experiment, the muscle wa .s removed from the bath and weighed. Cross-sectional area was estimated by dividing the muscle weight by L,,,. This requires the assumptions that the muscle has a constant cross-sectional area throughout its length and a tissue density of 1.0 mg/mm3. Data analysis. All tension data were normalized for cross-sectional area and are reported as means t SE. The unpaired Student t test was applied to make statistical comparisons between data obtained under constant testing conditions from experimental and control groups. RESULTS

General information about the animals used in the study is summarized in Table 1. Mean arterial pressure was higher in the SHR and DOCA-treated animals than in their respective controls. Although this difference was not apparent between the aorta-constricted preparations and . their controls, all three experimental groups developed significant cardiac hypertrophy as assessed by comparison of heart weight/body weight ratios with their respective controls. Resting tension of the hypertrophied papillary muscles determined at L max under testing condition I was not found to be significantly different from that of their respective controls (in g/mm2, SHR 1.63 t 0.13 vs. WKY 1.48 t 0.21; DOCA treated 1.81 t 0.12 vs. DOCA sham 1.60 t 0.10; aorta constricted 1.93 t 0.24 vs. sham constricted 1.74 t 0.18). Change to high [Ca”‘] solution did not alter resting tension. However, changing from 27OC to 17OC (from testing condition II to testing condition III) increased the resting tension in all preparations, with no significant differences between the hypertrophied preparations and their respective nonhypertrophied controls (in g/mm2, SHR 1.90 t 0.26 vs. WKY 1.78 t 0.24; DOCA treated 2.50 t 0.14 vs. DOCA sham 2.38 t 0.19; TABLE

1. Animals

used in the study

n

Body w g

Heart wt, g

Heart WV Body wt, mgk

Papillary Muscle Crosssectional Area, mm2

Mean Arterial Pressure, mmHg

SHR

6

204 k20 *

0.74 t 0.06

3.67 t 0.17

0.63 t 0.05

146 -+ 5

t

WKY

6

295 t33

0.81 t 0.07

2.82 t 0.13

t 1.01 t 0.11

loo k7

DOCAtreated

12

394 t 14

1.11 Ifr 0.05

0.90 to.07

179 t 6

DOCA sham

12

408 t 11

0.86 t 0.03

2.82 t 0.08 t 2.11 t 0.05

0.75 k 0.06

125 t 7

372 k25

1.21 t 0.03

3.45 t 0.32

1.13 t 0.12

168 t8

416

t 1.03 5 0.03

t 2.48 * 0.03

0.93 5

153 5 5

t

Aortaconstricted

9

10

99 * P < 0.05.

t

t

0.09

'

t P < 0.01.

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AFTERCONTRACTIONS

IN

HYPERTROPHIED

CARDIAC

H651

MUSCLE

aorta constricted 2.46 t 0.20 vs. sham constricted 2.29 t 0.18). Papillary muscle active tension development in each of the groups under the four testing conditions is shown in Fig. 1. Comparison between each experimental group and its respective control under each testing condition revealed no difference in the ability of the muscles to develop tension in response to single stimuli. The general decline in developed tension within each group as the testing conditions were changed reflects in part a timedependent deterioration of the preparations because the test conditions were always applied in the same sequence and each experiment took about 4 h. Papillary muscles from SHRs perfused by the initial solution alone (testing condition I) for an equivalent period of time showed a 15-20s loss in active tension developed (n = 4). Information about possible differences in time-dependent regression of active tension development capabilities of these groups under constant testing conditions is not available from these experiments because testing conditions were varied during the time period and were not returned to the initial testing condition. However, differences between group means of active tension of hypertrophied preparations and their respective controls did not appear as the experiment progressed and therefore indicates that the time-dependent factors accompanying the experimental protocol and affecting the hypertrophied preparations were not different from those affecting the respective nonhypertrophied controls. There was a difference in active tension development under any given testing condition between the control animals used for the DOCA experiments and the aorta constriction experiments. This difference was most ap-

parent when the preparations were tested at 17°C as assessed by applying Student’s unpaired t test to data obtained from those two control groups (P < 0.05). Although the time to peak tension and the half relaxation times varied with the testing conditions, there was no detectable difference between the experimental groups and their controls when compared under identical conditions. Typical responses of an isolated papillary muscle from a DOCA-treated rat to paired-pulse stimulation are shown in Fig. 2. This stimulus pattern generally induced aftercontractions, the amplitude of which tended to increase when either the calcium concentration was elevated or the temperature was lowered. Neither the incidence nor the relative amplitude of aftercontractions was altered in the preparations that remained in the initial testing condition (r) for 4 h. As can be seen in Fig. 2, lowering the temperature from 27°C to 17°C greatly slowed the responses to the paired stimuli. In addition, resting tension tended to increase slightly and stabilized at a new steady state. The interval between pulses (5 s) was long enough to allow the resting tension between beats to return to the base line, even when aftercontractions were present. The pairing intervals associated with maximal aftercontraction development at 27” C ranged from 250 to 350 ms and at 17°C ranged from 500 to 600 ms. As shown in Fig. 3, the absolute amplitude of the aftercontractions elicited from preparations with cardiac hypertrophy were generally greater than that from their respective controls. Under testing condition I, this difference was significant only for SHRs and WKYs but became more apparent in the other models of hypertro-

l 6.0

SHR

a

Doca

m

Aorta-constricted

-t reated

0

Controls

T

TA I

f

T

IV 2.5 mM Ca++ 27°C

5.0 mM Ca* 27°C

TESTING FIG.

each

1. Active

experimental

tension group.

development by isolated papillary Data represent means t SE.

muscles

2.5 mM Ca* 17°C

5.0 mM Ca* 17°C

CONDITIONS

under

testing

conditions

described

in the text.

Controls

are specific

for

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H652

L. J. HELLER

TESTING

CONDITION 4.00

I

1

I 2.5mM Ca* 2VC

n

3 1 .O second

f

n

5.0mMII 27k

C8 *IV

Ill 2SmM Ca* 17.C

1

FIG. 2. Tension development (upper truce) of a papillary response to paired-pulse stimulation (lower trace) under the conditions described in the text. Muscle was isolated from treated rat with mean arterial pressure of 195 mmHg and body wt of 3.25 mg/g. All records were obtained at identical time calibrations as shown in the upper right corner. Arrows aftercontractions.

muscle in 4 testing a DOCAheart wt/ force and identify

phy and their controls when the Ca2’ concentration was raised (condition II) and the temperature was lowered (conditions III and IV). Because the absolute amplitude of the aftercontraction may be in part dependent on the absolute amplitude of the preceding twitch, the relative amplitude of the aftercontractions (expressed as a percent of the amplitude of the response to the first stimulus of the pair) obtained under the different testing conditions was also examined. These data are shown in Fig. 4. The relative amplitude of the aftercontractions from the hypertrophied preparations tended to be greater than that from the respective controls. Lowering the temperature and raising the Ca2’ concentration tended to exaggerate this difference in all three models of cardiac hypertrophy. DISCUSSION

The results of this study indicate that in these three rat models of cardiac hypertrophy, certain contractile processes of the isolated muscle preparations are different from the normal nonhypertrophied controls. Specifically, when testing conditions are conducive to development of papillary muscle aftercontractions, all hypertrophied preparations develop larger aftercontractions than do their controls. The hypertrophy present in each of the experimental groups was apparently not severe enough to cause a measurable change from its control in the response to a single stimulus. Decreases in active tension development and prolongation of contraction time are characteristic of hypertrophied papillary muscles exposed to severe pressure overload (1, 2, 22). The difference in active tension between the control

animals used for the DOCA experiments and the aorta constriction experiments are unexpected because these controls are of the same rat strain. The sham-treated rats for the aorta constriction experiments also had an unexplainably higher mean arterial pressure and thicker papillary muscles than did the controls for the DOCAtreated experiments. It is possible that the sham operation (isolation of the abdominal aorta segment) produced an alteration in cardiac work load which, although not inducing as much cardiac hypertrophy as the actual aorta constriction, was somewhat greater than that produced by the preparation of the controls for the DOCA-treated group. An untreated control group was not included in these experiments. The cellular or subcellular basis for the production of aftercontractions is not understood. They have been identified primarily in isolated cardiac muscle preparations and are exaggerated by high [Ca”‘] and low temperatures, as has been shown in this study and others (3, 4, 15,20,21). They are commonly elicited by paired-pulse or high-frequency stimulation and under certain conditions may repeat themselves, suggestive of a damped oscillatory process (11, 15, 19). Contractile responses of rat myocardium have been shown to be less sensitive to changes in external calcium ion concentration than other species. Tension development is not decreased until [Cal, is quite low (less than 1.0 mM) (8). The present study also supports this general conclusion in that increasing [Cal, from 2.5 to 5.0 mM at either 27*C or 17*C did not produce dramatic changes in active tension. However the amplitude of the aftercontractions did tend to increase somewhat when [Cal, was elevated, suggesting that a change in the absolute amount of calcium does play a role in aftercontraction generation. Changes in temperature, however, produced a much more dramatic change in the amplitude of the aftercontractions, further suggesting that slowing of some critical reaction rate (i.e., calcium sequestration) may be an important factor for development of aftercontractions. Small, slow subthreshold depolarizations of cardiac muscle-cell membranes are associated with aftercontractions (4, 6, 12). Ferrier et al. (5, 7) reported that acetylstrophanthidin produced small oscillatory transient depolarizations in canine myocardial tissue following cessation of a train of rapidly applied stimuli. If these small depolarizations reach threshold they produce repetitive firing in the nonstimulated, usually quiescent, preparation, thus suggesting a mechanism for the development of arrhythmias commonly associated with digitalis intoxication (7). Recent experiments in this lab have confirmed this association of transient depolarizations with aftercontractions in the SHR preparations (12). Whether the transient depolarizations of the membrane actually trigger the aftercontractions or are a result of some intracellular alteration has not been determined. Kass and co-workers (13, 14) have shown that the transient depolarizations and aftercontractions associated with strophanthidin treatment are most likely due to internal cyclical change in calcium concentration. Catecholamines also have been reported to potentiate aftercontractions (21). Indeed, it is possible that the aftercontractions seen in these field-stimulated preparations may reflect release of norepinephrine from adre-

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AFTERCONTRACTIONS

ii

IN

HYPERTROPHIED

1.0

CARDIAC

n

SHR

m

Doca-treated

El2%

Aorta-

0

Controls

H653

MUSCLE

constricted

0 5 0

2 t

0.8

E 0 K

: 0.6 k-LLNE OE \ 0” z 0.4 2 3 %

0.2

I 2SmM 27°C

Ca*

5.0

II

Ill

mM 27”

Ca*

TESTING 3. Absolute muscles responding 4 testing conditions from high-sensitivity FIG.

Doca-t

Ca* c

5.OmM 17OC

Ca*

CONDITIONS

amplitude of aftercontractions of isolated papillary to paired-pulse stimulation determined under the described in the text. The amplitude was measured tracings and corrected for differences in muscle

cross-sectional area. Data represent means t SE. *P c 0.05 or **P < 0.01 indicates a significant difference between experimental group and its control under the designated testing conditions.

reated

v. El

Aorta-constricted

0

Controls

l .*.

2SmM 17”

c

I

II

I 2.5mM 27%

Ce

5.OmM 27.C

Ill Cd+

2SmM 17’C

IV Cd+

5.OmM Ca* 17O c

TESTING CONDITIONS represent means k SE. *P < 0.05 or **P -C 0.001 indicates a significant 4. Relative amplitude of aftercontractions of isolated papillary muscles responding to paired-pulse stimulation determined under the difference between experimental group and its control under the des4 testing conditions described in the text. The amplitude is expressed ignated testing condition. as percent of the initial response to the first stimulus of the pair. Data FIG.

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H654 nergic nerve endings within the muscle. If the preparations from hypertrophied hearts in this study either contai .n more catecholamine or are more sensi t&e to its effect, exaggerated aftercontractions might be expected. Earlier studies have shown that catecholamine metabolism in heart muscle from rats with DOC A hypertension (16) and spontaneou .s hypertension (17) and cats with cardiac hypertrophy in .duced by pulmonic banding (22) is different from that in norm0 ltensive untreated controls. However, catecholamine metabolism in these different models of cardiac hypertrophy apparently differ from each other. DOCA hypertension is associated with a storage defect and decreased total endogenous norepinephrine content (16). It was suggested that these defects might permit increased amounts of physiologically active catecholamine to be available to the receptor. In hypertrophied cat cardiac muscle, endogenous norepinephrine stores were also depleted, but these preparations demonstrated an augmented sensitivity to exogenous l norepinephrine reminiscent of denervation sensitivity (22). On the other hand, the spontaneous hypertension of the -SHR is associated with normal endogenous norepinephrine content but a decrease in the rate of release of norepinephrine, which suggests a decrease in the amount of catecholamine available to the receptor (17). Thus, a definitive role for the participation of catecholamine in the production of aftercontractions in these hypertrophied muscles cannot yet be assigned. Whether or not the observation that aftercontractions are exaggerated in isolate d cardia .c muscle preparations of these three models of cardiac hypertrophy has any

L. J. HELLER

significance in terms of altered functional capacity of the heart in vivo has not been determined. However, their presence does raise additional questions. Since both cardiac hypertrophy and cardiac glycoside treatment are associated with aftercontractions and transient depolarizations (5, 7, 12, 13, 14), are hypertrophied hearts more sensitive to arrhythmias associated with digitalis intoxication? Is there an active component within the diastolic period of the cardiac cycle (4, 23) that might alter the diastolic stiffness of hypertrophied hearts? Since superimposition of action potential-driven twitches on different phases of the aftercontractions results in an alteration in the magnitude of the response (3, 6, 19), will forcefrequency relationships be altered in the intact hypertrophied heart? In summary, isolated papillary muscle preparations from three rat models of cardiac hypertrophy tended to develop larger aftercontractions in response to pairedpulse stimulation than did their respective nonhypertrophied controls. This difference was exaggerated under testing conditions that were conducive to aftercontraction generation. The mechanism(s) responsible for their generation and the significance of their existence is not yet known. The author thanks Kevin Costley and William Fox for their technical assistance. The project was supported by grants from the American Heart Association, Minnesota Affiliate, and the Minnesota Medical Foundation. Received

6 November

1978; accepted

in final form

25 July

1979.

REFERENCES 1. ALPERT, N. R., B. B. HAMRELL, AND W. HALPERN. Mechanical and biochemical correlates of cardiac hypertrophy. Circ. Res. 34-35, SuppZ. 2: 71-82, 1974. 2. BING, 0. H. L., S. MATSUSHITA, B. L. FANBURG, AND H. J. LEVINE. Mechanical properties of rat cardiac muscle during experimental hypertrophy. Circ. Res. 28: 234-245, 1971. 3. BRAVEN~, P., J. SUMBERA, AND V. KRUTA. Aftercontractions and restitution of contractility in the isolated guinea-pig auricles. Arch. Intern. Physiol. Biochem. 74: 169-178, 1966. 4. FEIGL, E. 0. Effects of stimulation frequency on myocardial extensibility. Circ. Res. 20: 447-458, 1967. 5. FERRIER, G. R. The effects of tension of acetylstrophanthidininduced transient depolarizations and aftercontractions in canine myocardial and Purkinje tissue. Circ. Res. 38: 156-162, 1976. 6. FERRIER, G. R. Relationship between acetylstrophanthidin-induced aftercontractions and the strength of contraction of canine ventricular myocardium. Circ. Res. 41: 622-629, 1977. 7. FERRIER, G. R., J. H. SAUNDERS, AND C. MENDEZ. A cellular mechanism for the generation of ventricular arrhythmias by acetylstrophanthidin. Circ. Res. 32: 600-609, 1973. 8. FORESTER, G. V., AND G. W. MAINWOOD. Interval dependent inotropic effects in the rat myocardium and the effect of calcium. Pfluegers Arch. 352: 189-196, 1974. 9. HELLER, L. J. Mechanical properties of cardiac muscle from spontaneously hypertensive rats: accentuated aftercontractions. Proc. Sot. Exp. BioZ. Med. 154: 479-482, 1977. 10. HELLER, L. J. Cardiac muscle mechanics from DOCAand aging spontaneously hypertensive rats. Am. J, Physiol. 235: H82-H86, 1978 or Am. J. Physiol.: Heart Circ. Physiol. 4: H82-H86, 1978. 11. HELLER, L. J., AND J. M. BECK. Characteristics of aftercontractions and oscillations in cardiac muscle of spontaneously hypertensive rats (Abstract). Federation Proc. 35: 288, 1976. 12. HELLER, L. J., E. K. STAUFFER, AND W. D. Fox. Electrical and mechanical properties of cardiac muscle from spontaneously hy-

pertensive rats (Abstract). ti’ederation Proc. 37: 349, 1978. 13. KASS, R. S., W. J. LEDERER, R. W. TSIEN, AND R. WEINGART. Role of calcium ions in transient inward currents and aftercontractions induced by strophanthidin in cardiac Purkinje fibers. J. Physiol. London 281: 187-208, 1978. 14. KASS, R. S., R. W. TSIEN, AND R. WEINGART. Ionic basis of transient inward current induced by strophanthidin in cardiac Purkinje fibers. J. Physiol. London 281: 209-226, 1978. 15. KATZUNG, B. Diastolic oscillation in muscle tension and length. J. cell. Comp. PhysioZ. 64: 103-114, 1964. 16. KRAKOFF, L. R., J. DE CHAMPLAIN, AND J. AXELROD. Abnormal storage of norepinephrine in experimental hypertension in the rat. Circ. Res. 31: 583-591, 1967. 17. LOUIS, W. J., S. SPECTOR, R. TABEI, AND A. SJOERDSMA. Synthesis and turnover of norepinephrine in the heart of the spontaneously hypertensive rat. Circ. Res. 34: 85-91, 1969. 18. OKAMOTA, K., AND K. AOKI. Development of a strain of spontaneously hypertensive rats. Jpn Circ. J. 27: 282-293, 1963. 19. POSNER, C. J., AND D. A. BERMAN. Mathematical analyses of oscillatory and non-oscillatory recovery of contractility after a rested-state contraction and its modification by calcium. Circ. Res. 25: 725-733, 1969. 20. REITER, M. Die Entstchung von “Nachkontraktionen” im Herzmuskel unter Einwirkung von Calcium und Digitalis-glykosiden in Abhangigkeit von der Reizfrequenz. Naunyn-Schmiedebergs Arch. Exp. PathoZ. PharmakoZ. 242: 497-507, 1962. 21. REITER, M. Drugs and heart muscle. Am. Rev. PharmacoZ. 12: lll124, 1972. 22. SPANN, J. F., R. A. BUCCINO, E. H. SONNENBLICK, AND E. BRAUNWALD. Contractile state of cardiac muscle obtained from cats with experimentally produced ventricular hypertrophy and heart failure. Circ. Res. 21: 341-354, 1967. 23. WEZLER, K. The tonic autoregulation of the heart. Nova Acta Leopold., Neue FoZge (221) 38: 10-47, 1973.

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Augmented aftercontractions in papillary muscles from rats with cardiac hypertrophy.

Augmented aftercontractions in papillary from rats with cardiac hypertrophy LOIS JANE HELLER Department of Physiology, University of Minnesota, School...
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