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The effect of temperature on canine papillary muscle.

Measurements of the total duration, tA, of the action potential for canine papillary muscle in the temperature range 25-45 degrees C are shown to follow the law ta = tau exp (Q/kBT), with tau and the activation energy Q independent of temperature, T, and kB equal to Boltzmann's constant. The value obtained for Q = 0.65 +/- 0.10 eV. Results are also presented for the temperature dependence of points V(x) on the action potential curve, where x is the percentage of repolarisation within the range 30% less than x less than 100%.

Action Potentials↗

[Electrophysiologic effects of sophocarpine on papillary muscle in guinea pig].

Sophocarpine prolonged the action potential duration of guinea pig papillary muscle in a dose-dependent manner. After the preparations were exposed to sophocarpine 50 mumol/L for 30 min, APD50 and APD90 were prolonged from 189 +/- 21 and 216 +/- 24 ms to 205 +/- 27 and 241 +/- 25 ms (P less than 0.01). Simultaneously, ERP was prolonged from 202 +/- 14 to 211 +/- 16 ms, although the ERP/APD90 ratio was not changed. Sophocarpine had no significant effects on other AP parameters. Propranolol did not block sophocarpine effects.

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[Effects of cyproheptadine on the electrophysiological characteristics of the sinus node, ventricular myocytes and papillary muscles of the guinea pig heart].

Cyproheptadine is an antagonist of S1 serotoninergic and H1 histaminergic receptors, with a well known cardiovascular activity, mainly vasodilation and a negative chronotropic effect. It has been suggested that cyproheptadine as other antiserotoninergic drugs act by blocking the calcium channel. In order to explore this possibility the actions of this drug were studied in several cardiac preparations: sinus node, isolated ventricular myocytes and papillary muscle from guinea-pig's heart. The experiments were performed using the conventional recording techniques of intracellular electrical activity and isometric tension. Doses from 0.25 microM to 1.0 microM were studied. The main findings were: in sinus node: a) inhibition of automatic activity, b) a decrease in the upstroke, c) a decrease in the plateau level, and d) a shortening of the action potential. In isolated ventricular myocytes: a) a decrease in the rate of depolarization, b) a decrease in the plateau level and c) a shortening of the action potential. In the papillary muscle: a) a decrease in tension and b) a shortening of the action potential. All the effects observed were dose dependent an agree with a blockade of the calcium channel.

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[A case of infective endocarditis with subtotal rupture of the posterior papillary muscle].

We recently experienced a case of infective endocarditis with multiple embolic complications. The patient was a 21-year-old male who was admitted to our hospital with high fever and dyspnea. Echocardiography showed vegetation on the aortic valve, severe aortic regurgitation and mild mitral regurgitation. Abdominal echography revealed large splenic infarction. First we performed aortic valve replacement and splenectomy. But infective endocarditis developed after surgery, and echocardiography revealed severe mitral regurgitation, which has been a change for the worse. After treatment with antibiotics, mitral valve replacement (the second surgery) was performed. Intraoperative findings were confirmative of subtotal rupture of the posterior papillary muscle. Histological examination of the subtotal ruptured muscle revealed presence of coagulation necrosis. The patient is healthy without recurrence of infective endocarditis after the second surgery. It is exceedingly rare to experience a case of surgically treated subtotal papillary muscle rupture due to infective endocarditis.

Adult↗

Effects of hexoestrol on the contractility of the isolated, blood-perfused canine papillary muscle and of the guinea-pig ileum.

The effects of hexoestrol were studied on the blood flow and the tension development of the isolated, blood-perfused papillary muscle of the dog, as well as on the contractions of the guinea-pig ileum induced by acetylcholine, histamine or BaCl2. Hexoestrol caused an increase in coronary blood flow and a negative inotropic effect in a dose-dependent manner. High doses of hexoestrol produced a loss of contractility of the papillary muscle without significant alterations of the amplitude and shape of the electrical activity recorded extracellularly. Hexoestrol had a strong non-selective relaxant effect on the guinea-pig ileum and was 10-20 times more potent than papaverine in antagonizing contractions induced by the 3 agonists. These results indicate that hexoestrol probably acts by blocking certain steps in the process by which extracellular and/or superficially bound Ca ions move to the contractile machinery in cardiac and in smooth muscle cells. Thus, it may bear some resemblance to the so-called calcium antagonists.

Acetylcholine↗

Tension-independent heat in rabbit papillary muscle.

1. Heat and force were measured from isometrically contracting (0.2 Hz) rabbit papillary muscles at 21 degrees C during a single contraction-relaxation cycle using antimony-bismuth thermopiles and a capacitance force transducer. 2. Tension-independent heat (TIH) associated with excitation-contraction coupling was isolated from the initial heat by eliminating tension and tension-dependent heat with a Krebs-Ringer solution containing 2,3-butanedione monoxime (BDM) and mannitol. 3. A strategy for testing the validity of this new method for measuring TIH in heart muscle is described and the test confirms that the BDM-hypertonic solution partitioning method properly estimates the magnitude of the TIH component of initial heat. 4. TIH at the time of complete mechanical relaxation is 1.00 +/- 0.17 mJ/g wet weight and the data suggest that calcium cycling is complete by this time. Conversion of TIH to calcium cycled, assuming that 87% of TIH is due to calcium pumping by the sarcoplasmic reticulum, indicates that approximately 52 nmol calcium/g wet weight are required to support a single cycle of mechanical activity (0.2 Hz, 21 degrees C). 5. The length and frequency dependence of excitation-contraction coupling were demonstrated. TIH is reduced by shortening muscle length and by increasing the interval between stimuli. These steady-state data suggest that only a portion (approximately 40%) of TIH is directly related to activation of the contractile apparatus. 6. TIH in the first twitch following a 45 min rest period is significantly reduced by approximately 30%. 7. With subsequent twitches in the positive treppe following the rest period, TIH does not increase as steeply as expected suggesting that tension rise in twitches 1-10 may be modulated by competitive binding of calcium rather than increased calcium delivery.

Animals↗

Dynamic calcium requirements for activation of rabbit papillary muscle calculated from tension-independent heat.

The heat generated by right ventricular papillary muscles of rabbits was measured after adenosine triphosphate (ATP) splitting by the contractile proteins was chemically inhibited. This tension-independent heat (TIH) (1 mJ/g wet weight) was used to calculate the total calcium (Ca) cycled in a muscle twitch by assuming that 87% of TIH was due to Ca2+ transport by the sarcoplasmic reticulum with a coupling ratio of 2 Ca2+/ATP split; the enthalpy of creatine phosphate hydrolysis buffering ATP was taken as -34 KJ/mol. The estimated Ca turnover per muscle twitch at 21 degrees C, 0.2 Hz pacing rate, and 2.5 mM Ca in the Krebs solution was approximately equal to 50 nmol/g wet weight. There was a tight positive correlation between TIH and mechanical activation during steady-state measurements but no correlation during the sharp increase in mechanical activation (treppe) when stimulation was resumed after a rest period. It is suggested that while total Ca cycling remains unchanged during the initial period of tension treppe, the free Ca2+ transient and mechanical activation increase sharply due to resaturation of high affinity Ca2+ buffers, other than troponin C, depleted of Ca2+ during the rest period.

Actin Cytoskeleton↗

Leukotriene D4 increases both the force of contraction and polyphosphoinositide formation in guinea-pig papillary muscle.

Leukotriene D4 (LTD4) increased the force of contraction in guinea-pig papillary muscle. A rapid (less than 1 min), transient (less than 5 min) response to LTD4 (1 microM) reached 19.3 +/- 5.4% of isoproterenol maximum. A single exposure to LTD4 resulted in complete and homologous desensitization which was not influenced by indomethacin. LTD4 (0.1-3.0 microM) increased total inositol phosphates released from [3H]inositol-labeled tissue. ICI 198,615, a selective LT receptor antagonist, blocked both the increase in force of contraction and the increase in inositol phosphates by LTD4, but had no effect on the inotropic response to isoproterenol. These data support the existence of specific functional LTD4 receptors in myocardial tissue of guinea-pigs.

Animals↗

Post-natal developmental changes in the length-tension relationship of cat papillary muscles.

The length-tension relationship and the effect of paired electrical stimulation were studied in right ventricular papillary muscles obtained from cats. The animals were divided into three age groups: neonatal kittens, less than 24 hr of age; infant kittens, 16--18 days of age; and adult cats. 2. The muscles were electrically driven to contract isometrically using field stimulation at 10--20% above the threshold valus. 3. At Lmax the neonatal preparations produced significantly less developed (active) tension than did the adult preparations. The resting tension at Lmax was significantly greater in the neonatal preparations than in the adult ones. The infant group occupied an intermediate position between the two other groups. 4. The response to paired electrical stimulation was less in the neonatal group than in either the infants or the adults. 5. It is concluded that post-natal developmental changes occur in the contractile properties of the myocardium of the cat.

Age Factors↗

[Relation of mechanical noise in the rat papillary muscle to the level of its contraction].

The existence of mechanical noise (MN) has been demonstrated in isolated papillary muscles of rats at rest. The mean amplitude of the MN was about 1 mg, the mean frequency 1.5 Hz (t 22 degrees C). A good agreement was found between the MN amplitude and the contracture level of the muscle. However, during long contractures, the correlation between the noise and contracture magnitude was disturbed. There was no relationship between the MN amplitude and contracture magnitude during exposures inducing metabolic alterations (hypoxia, NaCN) and upsetting the work of the sarcoplasmic reticulum (caffeine). It is believed that the MN amplitude is in a good agreement with the contracture magnitude and, therefore, with the concentration of intracellular Ca2+, if the sarcoplasmic reticulum and contractile elements of the cells are intact.

Animals↗

Negative inotropic effect of etomidate in rabbit papillary muscle.

The effect of etomidate on the developed force of isometrically contracting rabbit papillary muscles in modified Krebs-Henseleit bicarbonate medium was evaluated under various stimulation conditions to gain insight into the mechanism underlying the negative inotropic effect of this anesthetic. Myocardial depressant effects of etomidate (2 and 4 mg/L) on steady-state contractions at low stimulation frequencies (0.1-0.5 Hz) were more pronounced than the effects on either steady-state contraction at high stimulation frequencies (1.0-2.0 Hz) or the effects on post-rest potentiated state contractions. Increases in the concentration of extracellular Ca2+ from an initial level of 2.5 mM to 3.4-4.0 mM reversed the effect of 2 mg/L of etomidate, whereas an increase to 4.6-5.0 mM was required to reverse the effect of 4 mg/L of etomidate. The dependence of post-rest potentiation on the duration of the preceding rest period was virtually unaffected by etomidate. These results suggest that etomidate inhibits the influx of extracellular Ca2+ but has little effect on the availability of intracellular Ca2+ required for the activation of myocardial contractile activity. Because the concentrations of etomidate required to produce negative inotropic responses in the present study are substantially greater than those likely to be achieved under clinical conditions, the present results also suggest that negative inotropism is unlikely in patients with normal hearts.

Animals↗

Block of inactivated sodium channels and of depolarization-induced automaticity in guinea pig papillary muscle by amiodarone.

The electrophysiological effects of amiodarone were studied in guinea pig papillary muscle by means of the single sucrose gap voltage clamp technique. The first time derivative of the upstroke of the action potential was measured as an indicator of the sodium current. The preparations were not voltage clamped during the action potential upstroke. Acute effects of amiodarone (4.4 X 10(-5) M and 8.8 X 10(-5) M; six experiments each) and effects of chronic administration at a single dose level (nine experimental vs. eight control animals) were studied. Results were qualitatively the same for all experimental conditions, and concentration dependent in the acute studies. Amiodarone caused marked use-dependent depression of the first time derivative of the upstroke of the action potential during stimulus trains. For example, at normal resting potential, chronic amiodarone treatment reduced the first time derivative of the upstroke of the action potential of the 16th beat of trains of cycle length 300 msec to 70 +/- 15% (mean +/- SD) of the initial value. This blocking effect was accentuated at more depolarized holding potentials and reduced at hyperpolarized holding potentials. Reduction of the first time derivative of the upstroke of the action potential was found to depend upon sodium channel inactivation. For all experiments, the mean normalized first time derivative of the upstroke of the action potential following a 1-second clamp in the -20 to +20 mV range was 0.92 +/- 0.08 in the control condition and 0.66 +/- 0.20 in the presence of amiodarone (less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

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A cryoclamp for the rapid cryofixation of the isolated blood-perfused rabbit cardiac papillary muscle preparation at predefined times during the contraction cycle.

There is increasing evidence that the distribution of monovalent cations in cardiac cells may be non-uniform, particularly in the region immediately beneath the sarcolemma, and we have proposed that a build-up of sodium in this region could be an important factor in the development of ischaemia-reperfusion injury. Electron probe X-ray microanalysis is ideal for the study of such changes in distribution but the application of the technique to this problem imposes severe requirements on the specimen and on the method for cryofixation. The specimen must be perfused through its vasculature so that it can be made truly ischaemic and be successfully reperfused. It is necessary to be able to cryofix the specimen without disturbance of its blood supply, electrical stimulation or temperature. It is also important to know the time in the contraction cycle when cryofixation occurs. Here we describe the design of an automated cryofixation device which can be used to cryofix a blood perfused papillary muscle preparation at predetermined time points in the contraction cycle. Preliminary data obtained from the analysis of rabbit papillary muscles subjected to varying periods of ischaemia are included as an example of the use of the cryoclamp.

Animals↗

Age-related differences in excitation-contraction coupling in rat papillary muscle.

To investigate the possible role of an alteration in excitation-contraction coupling during development, aging and senescence we compared simultaneously recorded mechanical and electrical activity of left ventricular papillary muscles from 3, 6, 12, and 24-month-old male rats. In addition, the effects of calcium and verapamil on excitation-contraction coupling were evaluated. We recorded transmembrane action potentials during both isometric and isotonic contractions. At al external bath calcium = 2.4 mM, action potential duration at 75% complete repolarization (APD75) was significantly prolonged as a function of age (3 mo = 28.2 +/- 2.7; 6 mo = 29.5 +/- 2.6; 12 mo = 49.5 +/- 5.6; 24 mo = 121 +/- 8.5 msec) while peak developed tension (DT) was not significantly altered (3 mo = 5.13 +/- 0.53; 6 mo = 4.75 +/- 0.53; 12 mo = 7.26 +/- 0.51; 24 mo = 6.01 +/- 0.67 g/mm2). The correlation coefficient (r value) for APD75 and DT was strong for 3-month-old animals (4 = 0.99) but weakened as a function of age (6 mo = 0.93; 12 mo = 0.81; 24 mo = 0.57). Similar results were observed when APD75 was correlated with time-to-peak tension (TPT) (3 mo = 0.95; 6 mo = 0.98; 12 mo = 0.85; 24 mo = 0.68), time-to-one-half relaxation (T1/2R) 3 mo = 0.91; 6 mo = 0.97; 12 mo = 0.85; 24 mo = 0.81) and time to peak shortening (TPS) (3 mo = 0.89; 6 mo = 0.81; 12 mo = 0.82; 24 mo = 0.51). Correlations between action potential duration and contractile parameters became weak in all age groups upon the addition of verapamil (V). The correlation between APD75 and DT for 3-month-old animals decreased by 34% upon the addition of V while a 70% decrease was seen in 24-month-old animals. Similar results were seen when APD75 was correlated with TPT, T1/2R and TPS when V was added to the perfusate. Our results indicate that excitation-contraction coupling, as evidence by alterations in not only the contractile apparatus but also in the surface membrane, may be altered in ventricular muscle as in function of age.

Action Potentials↗

Inhibition by multivalent cations of contraction induced by Chinese cobra venom cardiotoxin in guinea pig papillary muscle.

The effects of cardiotoxin (CTX), purified from the venom of Chinese Cobra (Naja naja atra) by a three-step chromatography, on the contractile responses of isolated guinea pig papillary muscle preparation and its antagonism by lanthanum ion (La3+) and divalent cations were examined. CTX induced tonic contraction following a transient augmentation of electrically evoked rhythmic contractions, which is similar to that seen in perfused heart preparation. Multivalent cations, La3+, Ca2+, Mn2+ and Mg2+, concentration-dependently blocked CTX-induced contraction. In Ca(2+)-free medium, CTX did not induce contraction and CTX-induced contraction was not modified in Na(+)-free medium. Nifedipine (1 mumol/L), effectively blocked KCl-induced contracture, but only partially inhibited CTX-induced contraction; thus suggesting that Ca2+ influx induced by CTX utilizes channels other than L-type Ca2+ channels. These cations may compete with CTX for the negatively charged membrane binding site which is responsible for the modulation of Ca2+ movement.

Animals↗

Effects of hypoxia and reoxygenation on steady-state and potentiated contractions in papillary muscle of guinea pigs.

We studied the effects of hypoxia and reoxygenation on steady-state contractions and potentiated contractions of papillary muscles of guinea pigs. Isometric tension was measured while 120 min periods of hypoxia and reoxygenation were repeated twice. Reoxygenation after the first period of hypoxia induced a gradual recovery in steady-state contractions and a rapid recovery in potentiated contractions from the first hypoxia-induced contractile depression. After the second period of hypoxia, steady-state and potentiated contractions decreased progressively. During the second period of reoxygenation, the recovery of steady-state and potentiated contractions was very poor and the marked elevation of diastolic tension did not decrease. There were no good correlations between hypoxic depression just before reoxygenation and the recovery of both potentiated contraction and steady-state contraction at 120 min of reoxygenation. The recovery from the hypoxia-induced depression was poor in the preparations with marked elevation in diastolic tension. From these findings, we conclude that hypoxia-induced depression is progressively worsened by an additional episode of hypoxia and that diastolic tension is one of the determinants of the low contractile level achieved by steady-state and potentiated contractions in the severely hypoxic state. The degree of hypoxia-induced depression does not determine redevelopment of force with reoxygenation.

Animals↗

Effects of strontium ions on contraction and action potential in rabbit papillary muscles. A comparison with effects of tetraethylammonium ions.

The effects of Sr2+ on contraction and action potential were studied in rabbit papillary muscles and compared with effects of tetraethylammonium (TEA+). The membrane potential was measured with KCl-filled microelectrodes and the contraction was simultaneously recorded using a mechanoelectrical transducer. A partial (90%) substitution of extracellular Ca2+ (Ca2+e) by Sr2+ produced stimulation frequency-dependent prolongation of the action potential (AP) with a dominant phase "plateau" as well as prolongation of the contraction. At low frequencies where the AP prolongation was well pronounced, the contraction became biphasic. The effect of Sr2+ on both AP and contraction was blocked by nifedipine (10 mumol/l) or by increasing Ca2+e. Ryanodine suppressed the early contraction component only. AP was prolonged to a similar extent and in the same frequency-dependent manner by TEA+ (20 mmol/l). Despite similar AP configuration, no biphasic contraction developed in the presence of TEA+. High Ca2+e (10 mmol/l) or low Na+e (70 mmol/l) suppressed the TEA+ effect on AP. The data indicate that the two components of the biphasic contraction are of different origin; the early one is activated by activator cation released from the sarcoplasmic reticulum while the late one results from the Sr2+ entry across the sarcolemma via L-type Ca2+ channels.

Action Potentials↗