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Rupture of ventricular septum or papillary muscle complicating myocardial infarction.

Ninety-eight specimens with rupture of some portion of the left ventricle complicating acute myocardial infarction from atherosclerotic coronary disease were studied. In 90, a single structure (so-called isolated rupture) had ruptured as follows: free wall of left ventricle, 52 cases; ventricular septum, 18 cases; a papillary muscle, 20 cases. In eight cases, two structures had ruptured, the most common combination being rupture of ventricular septum and left ventricular wal. Inferolateral location of underlying infarction was the common situation in ruptured papillary muscle, while anteroseptal myocardial infarction was more common in rupture of the ventricular septum. Transmural infarction underlay each case of ruptured ventricular septum, while in ruptured papillary muscle 11 of 20 cases showed subendocardial infarction. There was no association between the type of papillary muscle rupture and the type of infarct. Clinically, collapse of the circulation was common in cases of ruptured ventricular septum and ruptured papillary muscle. Death within one week after rupture was usual when the papillary muscle was involved totally or when the ventricular septum was involved. With partial rupture of a papillary muscle, longer survival (months) was observed in two of ten cases.

Aged

A clinicopathological study on the papillary muscle dysfunction.

A total of 11 cases of papillary muscle dysfunction (PMD) was found among 600 consecutive autopsy (1.8%). There were 5 men and 6 women, with their ages ranging from 64 to 92 years. Auscultation and phonocardiograms revealed holosystolic murmurs in 9 cases and early systolic murmurs in 2. There were accentuated 1st sound in 8 cases, 3rd sound in 7, and 4th sound in 5. PMD was classified into 3 types according to the clinical course and pathologic examinations. In type A (6 cases), myocardial infarction (MI) preceded the occurence of mitral regurgitation (MR) by 3 or 4 years, with pathological verification of old MI. In type B (1 case), MR developed during acute MI. In type C (4 cases), pathological examinations disclosed various degrees of myocardial fibrosis, in which clinical diagnosis was MR of unknown etiology. In a total of 113 cases of MI, 36 cases (32%) showed papillary muscle infarction (PMI), which occurred with significantly high incidence in (1) male, (2) large MI, and (3) subendocardial or lateral MI. Among 36 cases of PMI, 9 cases developed PMD, which showed high incidence in inferior MI and in female. Various other factors concerning PMD and PMI were examined, and it was pointed out that not only PMI but also severe lesions in corresponding ventricular wall were necessary for the development of PMD.

Aged

[Mechanical activity of the papillary muscles of the rat heart under high altitude conditions].

Mechanical activity of isolated papillary muscles in the left ventricle of rats was studied during permanent high altitude adaptation. The main computer parameters were: maximal developing tension, force of contraction, and capacity of papillary muscles at different periods of mountain adaptation (3, 15, 30 and 45 days). On the 15th day of mountain exposure, a statistically significant increase of maximal developing tension and papillary muscles activity was observed, which remained until the 45th day. Capacity was considerably increased on the 30th--45th day of adaptation. The data suggest positive effect of high altitude hypoxia on inotropic function of intact myocardium.

Actomyosin

Effects of 2-nicotinamidoethyl nitrate (SG-75) on dog coronary artery and cat papillary muscle.

Effects of 2-nicotinamidoethyl nitrate (SG-75) on isolated dog coronary artery and cat papillary muscle were investigated. SG-75 dose-dependently relaxed the isolated coronary arterial strips contracted with potassium. Large doses of SG-75 depressed contraction of papillary muscle driven with electrical stimulation and inhibited enhancement of contraction of papillary muscle induced by calcium and isoproterenol. From these results it is suggested that SG-75 may have a weak Ca++-antagonistic action.

Animals

Frequency-dependence of the positive inotropic effect of methoxamine and naphazoline mediated by alpha-Adrenoceptors in the isolated rabbit papillary muscle.

Under the conditions of different stimulation frequencies the inotropic effects of the alpha-adrenoceptor stimulationg agents, methoxamine, naphazoling and oxymetazoline were studied on the isolated rabbit papillary muscle. 1. On the papillary muscle stimulated at 0.5 Hz methoxamine in concentrations from 10(-5)M caused a significant and dose-dependent positive inotropic effect. At 10(-3)M methoxamine decreased the developed tension. With increasing frequency of stimulation (0.5--1--1.5Hz), the positive inotropic effect became smaller, while the negative inotropic one was more pronounced. The time course of the disappearance of the negative inotropic effect of methoxamine by washout differed from that of the positive inotropic effect: the negative component disappeared within 30 min, whereas the positive one lasted for about 100 min. The positive inotropic effect of noradrenaline (10(-6)M), in contrast ot that of methoxamine, was not influenced by the frequency under the same conditions of stimulation. Also naphazoline (10(-5)M) caused a significant positive inotropic effect on the papillary muscle stimulated at 0.5 Hz, while oxymetazoline induced exclusively a negative inotropic effect. 2. The positive inotropic effect of metoxamine (10(-4)M) as well as of naphazoline (10(-5)M) evoked at a frequency of 0.5 Hz was abolished by phentolamine (10(-6)M). Methoxamine (10(-4)M) induced a significant negative inotropic effect in the presence of phentolamine. Phentolamine antagonized the positive inotropic effect of methoxamine in a non-competitive manner: the pD2-value was 7.76. 3. In the presence of methoxamine (10(-4)M) the developed tension in the lower range (0.05--1 Hz) of the frequency-force relationship was enhanced, while that in the higher range (greater that 1.5 Hz) was decreased. The enhancement was abolished by phentolamine (10(-6)M). 4. Papaverine (2x10(-5)M) did not affect the positive inotropic effect of methoxamine. 5. The present results show that methoxamine and naphazoline induced a positive inotropic effect via alpha-adrenoceptor in the ventricular myocardium of the rabbit. These effects were caused only at low, but not at high frequencies of stimulation.

Animals

An effective morphometric method for electron microscopic studies on papillary muscles.

Morphometry was performed on the left ventricular posterior papillary muscles of seven Wistar rats. The volume densities of myocardial cells, interstitial space, myocardial nuclei, sarcoplasm, mitochondria, myofibrils, ground substance and T tubules, and the surface densities of myocardial cells, mitochondrial membranes and T tubules, were calculated. Though only 1 ultrathin section per animal was evaluated the low standard errors of the means indicate that the method described here will be adequate in most experimental studies. Due to the anisotropy of the surfaces within myocardial cells, the papillary muscles were cut at an angle of 32.4 degrees to their longitudinal axis. This angle is derived from an equation published by Whitehouse (1974). The procedure to correct the loss of cristal membrane images from oblique sectioning is discussed.

Animals

No evidence for involvement of dopaminergic receptors in the positive inotropic action of dopamine on the isolated rabbit papillary muscle.

Experiments were carried out on the isolated rabbit papillary muscle driven at 0.5 Hz in order to further elucidate the mechanism of the positive inotropic effect evoked by dopamine. The dose-response curve for dopamine was not affected by the antagonists pimozide (10(-6) M), yohimbine (10(-5) M) pindolol (3 x 10(-8) M) and phentolamine (10(-6) M) when these agents were given separately. Only the simultaneous administration of yohimbine plus pindolol and phentolamine plus pindolol, respectively, shifted the entire curve to the right. This shift was not further influenced by pimozide. Dopamine (10(-4) M) increased the cyclic AMP content of the papillary muscle by about 50%; this increase was not affected by pimozide, but was markedly elevated by yohimbine and completely depressed by pindolol. From the present results it is concluded, that dopamine produces its positive inotropic effect through stimulation of myocardial alpha-as well as beta-adrenoceptors to about the same degree; stimulation of specific dopaminergic receptors, however, is not involved. The stimulation of beta-adrenoceptors is accompanied by an increase of the cyclic AMP level, while that of alpha-adrenoceptors is not.

Animals

Effects of prostaglandin E1 on the positive inotropic actions of noradrenaline, nerve stimulation and calcium in the isolated blood-perfused papillary muscle of the dog.

The effects of PGE1 on the dog heart were studied using the blood-perfused sinus node and papillary muscle preparations isolated separately from the same animal. PGE1 administered into the papillary muscle artery as bolus injections in doses of 1-1000 ng caused a dose-dependent increase of the developed tension and dT/dt of the papillary muscle. The effect was not inhibited by the beta-adrenoceptor blocking agent pindolol. PGE1 injected into the sinus node artery in doses of 3-300 ng did not change the rate of contraction of the sinus node preparation. PGE1 in the blood concentrations of 4.4 X 10(-9) to 1.7 X 10(-7) M enhanced the positive inotropic responses to noradrenalin and field stimulation as well as to calcium. The influence of PGE1 on the positive inotropic effect of perivascular nerve stimulation was not consistent: the action of perivascular nerve stimulation was enhanced by PGE1 in the majority of preparations but was reduced in one third of preparations. PGE1 in the same blood concentrations as used in the papillary muscle significantly depressed the positive chronotropic responses to noradrenaline and dopamine. The present results indicate that PGE1 induces multiple actions on the dog heart. Its predominant effect on the ventricular myocardium appears to be enhancement of the adrenergic stimuli probably via the facilitation of calcium movement through the myocardial cell membrane. In addition, PGE1 may decrease the sensitivity of beta-adrenoceptors to adrenergic stimuli in the sinus node.

Animals

Acute and subacute effects of doxorubicin on postextrasystolic potentiation in guinea pig papillary muscles.

To investigate the effects of doxorubicin on postextrasystolic potentiation (PESP), isolated guinea pig papillary muscles were field-stimulated and the resulting isometric force was recorded. Postextrasystolic contraction was evoked following trains of 37 regular stimulations. The effects of acute doses of doxorubicin (0.2 mM) on regular contractions and postextrasystolic contractions were examined for 2 hr. The effects of subacute doses of doxorubicin (total dose 5 mg/kg intraperitoneally) on the relationship between %PESP (postextrasystolic/regular contraction) and both the extra-stimulus coupling interval and the postextrasystolic interval were examined. Acute administration of doxorubicin decreased the amplitude of postextrasystolic contractions more than that of regular contractions. Thus, %PESP in the doxorubicin-treated group decreased significantly over time. There was no similar decrease in the control papillary muscles. Both the extra-stimulus coupling interval and the postextrasystolic interval had less of an effect on %PESP in doxorubicin-treated animals than in control animals. Since PESP depends upon sarcoplasmic reticulum activity, our results indicate that acute and subacute exposure to doxorubicin impairs the activity of the sarcoplasmic reticulum of guinea pig papillary muscles.

Animals

Augmented aftercontractions in papillary muscles from rats with cardiac hypertrophy.

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 pipillary muscles from hypertrophied hearts tested under conditions conducive to aftercontraction generation were compared to pipillary muscles from WKY or sham-treated 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 degrees C and 17 degrees 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 high-calcium and low-temperature solutions. Under these conditions, papillary muscles from hypertrophied hearts developed larger aftercontractions than did their respective controls.

Animals

The pathogenesis of papillary muscle rupture complicating myocardial infarction: hemorrhage accompanying contraction band necrosis.

Although frank rupture of the papillary muscle complicating myocardial infarction is gaining widespread interest as its incidence continues to rise, the mechanism of rupture remains unclear. Of all patients who died with myocardial infarction and who came to autopsy at this institution over the past 21 years, 13 were found to have papillary muscle rupture. Twelve of these 13 had severe contraction band necrosis with interstitial hemorrhage in the areas surrounding the site of rupture. The hemorrhages infiltrated the interstitium and appeared to have dissected both longitudinally and transversely through the myocardium. In contrast, those patients with papillary muscle infarction without rupture were found to have coagulation necrosis. These findings suggest that the interstitial hemorrhages occurring with contraction band necrosis may act as dissecting masses of blood, thereby causing the rupture.

Adult

[False aneurysm associated with mitral insufficiency due to rupture of the heart at the point of insertion of the anterior papillary muscle. A successfully operated case].

Although rupture of a mitral papillary muscle during myocardial infarction is well known, and post-infarction transmural ruptures causing false aneurysms occasionally reported, the association of rupture of the anterior papillary muscle and a underlying transmural parietal rupture giving rise to a false aneurysm is quite exceptional, and, to the best of our knowledge, has not previously been reported. Despite the serious nature of the disease, surgical cure of the aneurysm with mitral valve replacement was successful, due to the limitation of the anatomical disruption by early pericardial symphysis.

Aneurysm

Different patterns of protein kinase C redistribution mediated by alpha 1-adrenoceptor stimulation and phorbol ester in rat isolated left ventricular papillary muscle.

1. In rat left ventricular papillary muscle, phenylephrine, an alpha 1-adrenoceptor agonist, had a staurosporine-sensitive positive inotropic effect and increased the particulate-associated protein kinase C (PKC) activity without significant changes in total PKC activity or in cytosolic Ca2+/phospholipid-independent kinase (PKI) activity. 2. A PKC stimulant, phorbol 12,13-dibutyrate (PDBu), decreased contractility and slightly increased PKC activity in the particulate fractions, with a marked decrease and increase in total PKC and PKI activities, respectively. 3. The PDBu-induced negative inotropic response was attenuated by two protease inhibitors, leupeptine and a microbial peptide isolated from Aspergillus japonicus (E-64), which are known to inhibit the conversion of particulate-associated PKC to PKI. 4. Such differences in the patterns of PKC redistribution, i.e. marked increases in particulate PKC and cytosolic PKI activities caused by phenylephrine and PDBu, respectively, may account for the opposite inotropic effects of PKC stimulation by an alpha 1-agonist and a phorbol ester.

Adrenergic alpha-Agonists

Effects of extracellular calcium and sodium on depolarization-induced automaticity in guinea pig papillary muscle.

Regenerative discharge of action potentials is induced in mammalian papillary muscles by passage of small depolarizing currents. In this paper, the effects of various extracellular calcium and sodium concentrations and of tetrodotoxin on this phenomenon were studied in guinea pig papillary muscles in a sucrose gap chamber. Phase 4 diastolic depolarization was found to be associated with an increase in membrane resistance. The slope of phase 4 depolarization was decreased by reductions in extracellular calcium or sodium concentration. The range of maximum diastolic potentials and the thresholds from which regenerative potentials arose were reduced, especially at the positive limit of potentials, by a reduction in either ion. It was concluded that both calcium and sodium influence diastolic depolarization and participate in the regenerative action potentials of depolarization-induced ventricular automaticity.

Action Potentials

Transient force responses in blood-perfused papillary muscle after step changes in load.

In in situ canine papillary muscles, we studied transient responses in peak isometric force at control length, after contraction was suddenly switched from isotonic contractions at various forces and isometric contractions at different lengths. Peak isometric force rapidly decreased after isotonic contractions at relatively low forces and isometric contractions at shorter lengths. In contrast, peak isometric force rapidly increased after isotonic contractions at relatively high forces and isometric contractions at longer lengths. There was no transient response when the preceding isotonic force was about half of the present peak isometric force. Magnitude and direction of the transient force response depended on magnitude and direction of the change in the mean muscle force level produced by the sudden switch of loading conditions. Transient force responses were accompanied by simultaneous changes in time to peak isometric force in the same direction. We proposed that, in the blood-perfused papillary muscle, a sudden change in the mean muscle force causes an abrupt change in coronary flow supply-demand relation which in turn causes a transient change in contractile force.

Animals

The effects of batrachotoxin on cat papillary muscle.

The effects of batrachotoxin (BTX) upon the contraction and transmembrane potential of cat right ventricular papillary muscles were studied in vitro at 37 degrees C. BTX (2.0 x 10(-9) M) increased isometric contractile force by about 50% from control force, decreased the potential difference across the cell membrane to approximate -50 mV and produced spontaneous contractions of the papillary muscles. Each BTX-induced spontaneous contraction was accompanied by a spontaneous action potential which was generated when an oscillation in membrane potential reached threshold level. Spontaneous activity ovvurred only in muscles which were previously stimulated electrically. The positive inotropic effect of BTX was accompanied by an increase in the rate of force development. Papillary muscles from cats pretreated with reserpine did not differ from normal muscles in their responses to BTX treatment. Tetrodotoxin (2.0 x 10(-7) M) antagonized the effects of BTX, a finding which suggests that the actions of BTX are mediated by a selective increase in membrane permeability to sodium ions. The resultant BTX-elicited increase in the intracellular sodium ion concentration may increase the force of contraction through an augmentation of calcium influx via the sodium-calcium exchange system.

Action Potentials

Effect of hypoxia on mechanical properties of hyperthyroid cat papillary muscle.

It has been previously established that hyperthyroid myocardium exhibits increased performance under well-oxygenated conditions. To date, it is not known whether hyperthyroid cardiac muscle can maintain this increased performance during hypoxia. The responses of isolated right ventricular papillary muscles from hyperthyroid and euthyroid kittens to hypoxia were compared under isometric conditions at 31 degrees C. Under well-oxygenated conditions, the hyperthyroid cardiac muscle exhibited both an increased contractility and an accelerated rate of relaxation. A similar degree of acute hypoxic stress for 15 min resulted in a greater decrease in contractility in the hyperthyroid compared with the euthyroid papillary muscle as indicated by a greater fall in both peak tension development (2.2 +/- 0.25 from 4.2 +/- 0.2 vs. 0.9 +/- 0.15 from 3.2 +/- 0.4 g/mm2, P less than 0.01) and +dT/dt (12.9 +/- 2.3 from 25 +/- 3 vs. 4.0 +/- 0.6 from 14 +/- 1 g-s-1-mm-2, P less than 0.01). In addition, compared with the euthyroid data, hypoxia resulted in impaired myocardial relaxation in the hyperthyroid cardiac muscle. Thus, the hyperthyroid compared with the euthyroid papillary muscle exhibits both a greater decrease in contractility and an impairment of myocardial relaxation during hypoxia, indicating a greater susceptibility to a given hypoxic stress.

Animals