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A relatively dense concentration of lymphatics in the region of the papillary muscles of the canine left ventricle has been described. It is suggested that these channels may play a role in the development of pathologic changes affecting the mitral valve apparatus which could subsequently cause valve dysfunction.
OBJECTIVE: The combination of mexiletine and amiodarone has proved useful in the control of serious ventricular arrhythmias, but the electrophysiological basis for their effectiveness in combination is unknown. The objective of this study was to compare the effects of mexiletine on action potential parameters of papillary muscles taken from guinea pigs chronically treated with amiodarone, with tissue taken from a control group. DESIGN: The effects of 12.5 to 200 microM mexiletine on action potential parameters of papillary muscles taken from guinea pigs chronically treated with amiodarone were compared with tissue taken from a control group, at frequencies of 1.0, 1.5 and 3.0 Hz, using standard microelectrode techniques. Onset of use-dependent block was assessed by 30 beat trains, and recovery from block by extrastimuli at diastolic intervals ranging from 200 to 5000 ms at both 1.5 and 3.0 Hz. ANIMALS: Eighteen four-week-old guinea pigs were randomly divided into two groups. One group received amiodarone in a loading dose of 20 mg/kg/day by intraperitoneal injection for one week, followed by 10 mg/kg/day for 15 weeks. The control animals were given equivalent volumes of dextrose intraperitoneally for 16 weeks. MAIN RESULTS: Mexiletine depressed the maximum rate of depolarization of phase 0 of the action potential (Vmax) in a concentration- and use-dependent fashion. Whereas chronic amiodarone treatment did not alter steady-state Vmax values, the extent of tonic Vmax depression induced by mexiletine was decreased, while use-dependent depression was increased. Mexiletine combined with amiodarone increased effective refractory period prolongation from 306.7 +/- 27.2 to 348.8 +/- 37.2 ms, while action potential duration shortening of mexiletine was moderated from 134.0 +/- 19.8 to 151.0 +/- 8.3 ms (to 90% repolarization at 3 Hz in the presence of 200 microM mexiletine).
A 76-year-old woman presented to our institution with shortness of breath, weakness, and syncope. Evaluation revealed severe mitral regurgitation and cardiogenic shock secondary to a flail posterior mitral valve leaflet. An emergency cardiac catheterization did not demonstrate significant coronary artery disease. The patient was sent for an emergency mitral valve replacement. Intraoperatively, the posteromedial papillary muscle was found to be transected. Histological analysis, clinical presentation, and a review of the literature of isolated papillary muscle infarction are presented.
We evaluated the role of the inositol 1,4,5-triphosphate (IP(3)) receptor-mediated Ca(2+) release on the positive inotropic effects of alpha-adrenergic stimulation using a novel, potent, selective membrane-permeable blocker of IP(3) receptor, xestospongin C. Guinea-pig papillary muscle permeabilized with saponin exhibited spontaneous oscillatory contractions in solution buffered with pCa(2+) 6.5 by a low concentration of EGTA. The oscillatory activity was increased by adding 100 microM IP(3) and abolished by 1 microM ryanodine or 30 microM cyclopiazonic acid. Xestospongin C (3 microM) inhibited the IP(3)-induced increase in the oscillatory contractions without affecting basal oscillations. In intact papillary muscle, xestospongin C (3 microM) inhibited the positive inotropic effects of phenylephrine, resulting in a rightward and downward shift of the concentration-response curve for phenylephrine. On the contrary, xestospongin C did not affect the concentration-response curve for phenylephrine obtained in the presence of ryanodine (1 microM). On the other hand, xestospongin C affected neither basal contractions nor the positive inotropic effects of a high extracellular Ca(2+) concentration (3.2 mM) or that of isoprenaline (1 and 10 nM). These results suggest that the IP(3)-mediated increase in Ca(2+) release is involved in the positive inotropic effects of alpha-adrenergic stimulation in the guinea-pig cardiac muscle.
The negative inotropic effect of thiopental was examined on the canine papillary muscle. The slow-channel-mediated action potential was induced by 5mM of caffeine in high-K (27 mM) Tyrode solution. The drug reduced the slow action potential and the twitch tension, suggesting a reduction in the slow inward current.
During hibernation the body temperature may fall to only a few degrees above 0 degree C. The heart of the hedgehog continues to function whereas the hearts of nonhibernating mammals stop beating. The present study was performed to investigate and compare the mechanical responses to hypothermia in rabbits, rats, and hedgehogs. Isometric force was recorded from papillary muscles mounted in an organ bath and effects of hypothermia on the mechanical restitution curve were also compared. A reduction of bath temperature from 35 degrees C caused an increase in peak developed force. Maximum force was seen at 20 degrees C in the rabbit, 15 degrees C in the rat, and 10 degrees C in the hedgehog preparations. In all the species there was a similar prolongation of time to peak force and of time from peak to half-relaxation as temperature was lowered. An increase in resting force and after-contractions were recorded in the rabbit and rat muscles at temperatures below 15 and 10 degrees C, respectively. The rabbit and rat preparations became inexcitable at temperatures below 10 and 5 degrees C, respectively. The hedgehog papillary muscle, on the other hand, still contracted at 0 degree C and did not show increased resting force nor after-contractions. The results are consistent with the hypothesis that there is a calcium overload in cardiac cells from rabbit and rat at low temperatures but there is no calcium overload in the hedgehog muscle during hypothermia.
The present study investigates the effects of adriamycin on the electrophysiological properties of the myocardium as monitored by intracellular recordings of the cardiac action potential. ADR was administered to rats at a dose of 20 mg . kg-1 given as a single intravenous injection or in four daily doses of 5 mg . kg-1 each. Twenty-four hours following the last injection, papillary muscles were removed and intracellular recordings of the action potential were sampled from the tissue. In another set of experiments, papillary muscles were removed from non-injected, control animals and superfused in vitro with adriamycin at a concentration of 200 mumol . litre-1. Several parameters of the action potential were measured and compared with control values in both in vivo and in vitro experiments. In all studies, the major effect of adriamycin on the cardiac action potential was shown to be a prolongation of the duration at 20%, 50% and 98% repolarisation. Adriamycin did not appear to exert its effect by depression of cell metabolism, as superfusion with NaCN or dinitrophenol reduced the action potential duration. The upstroke velocity, which is proportional to the sodium conductance, was unaltered by ADR; it appears that ADR alters conductance of calcium and/or potassium across the myocardial membrane by an as yet unknown mechanism.
A total of 14 cases of papillary muscle dysfunction have been observed in Ehlers Danlos syndrome. Five patients had clinically identifiable syndrome of prolapsing mitral leaflets. This form of rare interesting cardiovascular abnormality in Ehlers Danlos syndrome is discussed. The relevant literature is reviewed.
To investigate whether cardiac dysfunction in prefailure cardiomyopathic (CM) hamster hearts is due to Ca2+ overload or alternatively to decreased availability of Ca2+ in the sarcoplasmic reticulum (SR), the Ca2+ channel agonist, BAY K 8644, was used to compare the effects of increased Ca2+ influx on function and subcellular Ca2+ distribution in papillary muscles from hearts of 110-day-old CM and normal hamsters. A band, mitochondrial, and junctional SR Ca2+ were measured by electron probe microanalysis in CM and normal papillary muscles, which were either untreated or pretreated with BAY K 8644. Muscles were then rapidly frozen during contraction or relaxation. The results showed decreased tension development and decreased inotropic response to BAY K 8644 in CM muscles versus normals. There was no elevation of mitochondrial or A-band Ca2+ in BAY K 8644-treated or untreated CM muscles frozen during contraction or relaxation compared with similarly treated normals. In muscles frozen during relaxation, junctional SR Ca2+ was lower in both untreated and BAY K 8644-treated CM muscles versus comparably treated normals. These results do not support the hypothesis of an increased sensitivity to Ca2+ in hypertrophied, prefailure CM hearts but do indicate that less Ca2+ is available in the SR for activation of contraction.
Other investigators have claimed that norepinephrine does not evoke a significant alpha adrenergic inotropic effect in rabbit ventricular myocardium in contrast to some other mammalian species, indicating an important functional limitation of the cardiac alpha adrenoceptors. We therefore characterized the inotropic effects of norepinephrine in isometrically contracting rabbit papillary muscles. We studied both contraction and relaxation by measuring developed tension and its first and second derivatives. Both the influence of propranolol and prazosin on concentration-effect curves of norepinephrine and the qualitative characteristics of the responses revealed that norepinephrine evoked both alpha and beta adrenergic inotropic effects. The alpha adrenergic response to norepinephrine was qualitatively markedly different from the beta adrenergic effect and qualitatively similar to the alpha adrenergic effect of phenylephrine which was also characterized for comparison. Although the alpha adrenergic response to norepinephrine was marked, the beta adrenergic effect was the dominating one when norepinephrine was administered alone. Thus, the beta adrenergic effect had to be extensively blocked to reveal the prazosin-sensitive alpha-1 adrenergic response. It is concluded that also in rabbit papillary muscles, norepinephrine evokes inotropic effects through both alpha and beta adrenoceptors.
Equilibration and washout curves of inulin were determined in isolated rat papillary muscles. Inulin uptake did not reach a steady-state value even after a long equilibration time. The effects of contractile activity were investigated. Isometric contractions increased the rate of inulin uptake and washout. In isotonic conditions, a smaller increase in the uptake and washout was observed. These changes could be attributed to an actual increase of inulin distribution space and/or to an accelerated diffusion kinetics.
Na+/Ca2+ exchange is inhibited in both guinea pig cardiac membrane vesicles and papillary muscles in a concentration-dependent fashion by several analogs of the pyrazine diuretic amiloride. Structure/activity studies based on transport measurements in vesicles prepared from guinea pig left ventricle indicate that hydrophobic substitutions at the terminal nitrogen atom of the guanidinium moiety of amiloride improved the inhibitory potency almost 100-fold over that of the parent compound. 3',4'- Dichlorobenzamil ( DCB ) is one of the most active inhibitors (IC50 = 17 microM). In electrically stimulated papillary muscles isolated from guinea pig heart, 10-40 microM DCB decreases contractile force. At 100 microM inhibitor, diastolic tension is significantly increased. The positive inotropic responses to veratridine and ouabain are inhibited by 20 and 40 microM DCB . Since the responses to these interventions were a consequence of increased intracellular Na+ concentration, these data indicate that DCB is an inhibitor of Na+-dependent Ca2+ influx in the intact tissue. Interpretation of mechanical responses elicited by paired pulses suggests that 40 microM but not 100 microM DCB decreases release of Ca2+ from the sarcoplasmic reticulum. The mechanical data obtained with concentrations of DCB that inhibited Na+/Ca2+ exchange in vesicles suggest that a significant amount of Ca2+ can enter the cardiac cell via Na+/Ca2+ exchange under normal conditions and that this transport system may be an important source of Ca2+ supplying the sarcoplasmic reticulum in guinea pig heart. Moreover, these amiloride analogs function as potent inhibitors of the positive inotropic effect caused by increased intracellular Na+ concentration.
We report a case of anterolateral papillary muscle rupture in a 22-year-old man who had blunt chest trauma caused by a car accident. Transesophageal echocardiography revealed severe mitral regurgitation caused by the rupture. He successfully underwent emergency mitral valve replacement and was discharged 9 days after the surgical correction.
The effects of a frequently used sclerosing agent (Sotravarix 6%, main constituent polidocanol 60 mg/ml = 0.1 mol/l) on the electrical activity of the isolated perfused guinea pig heart and on transmembrane potential of isolated papillary muscle and sinus node were studied. Application of the sclerosing agent in a dilution of 1:40,000 (corresponding to polidocanol 2.6 x 10(-6) mol/l) caused a significant decrease in frequency (-27%) and (at constant frequency) a significant delay of the atrioventricular as well as of the intraventricular conduction (+105% or + 210%, resp. n = 4). These effects were only slightly reversible in a 30 min wash-out period. In the isolated papillary muscle, the sclerosing agent (dilution 1:10,000; polidocanol 1 x 10(-5) mol/l) decreased the maximum rate of rise of the action potential and shortened its duration, both by about 10%. In the isolated sinus node the same dilution decreased the spontaneous rate by about 8% mainly by reducing the diastolic depolarization rate (-18%). The effects of the sclerosing agent are attributable to the influence of polidocanol and consist in a blockade of the fast sodium channels (local anesthesia) and in additional inhibitory effects on calcium and/or potassium conductance.
In experiments on isolated guinea pig papillary muscles the effects of verapamil (5 mg/L) and caffeine (1 g/L) on the two-component contraction were investigated. The muscles were continuously superfused with normal Tyrode's solution containing 2 mg of noradrenaline/L at 20--22 degrees C. The first derivative of contractile response and transmembrane action potential were simultaneously recorded. Verapamil suppressed the amplitude of the second component and had no influence on the first component of contraction. Caffeine eliminated the first component and increased the second component of contraction. It was suggested that in the activation of two-component contraction calcium ions from two different pools take part: (1) those released from sarcoplasmic reticulum, and (2) those that crossed a cell membrane during the plateau of the action potential.
In ferret and guinea pig papillary muscles enprofylline (10 microM-10 mM) and theophylline (0.1-2 mM) alone or in combination with terbutaline (0.05 microM-0.1 microM) decreased the action potential duration and increased the plateau height, increased the peak force of contraction and facilitated the depolarization-induced automaticity. In voltage clamp, the xanthines alone or in combination with terbutaline increased second inward currents, ICa,f and ICa,2, but had relatively less effect on the time-dependent outward current. No qualitative differences between enprofylline and theophylline could be detected but the former was about 5 times more potent in increasing ICa,f. In clinically relevant concentrations, enprofylline and theophylline alone, or in combination with terbutaline caused a small (2-5%) shortening of the action potential.
The effects of 4-aminopyridine (4-AP) were studied on isolated papillary muscles from the heart of reserpinized rabbits (at 37 degrees C). The preparations were paced to contract at 0.67 Hz under isometric conditions and the muscle length was adjusted to 95% of the length for optimum force production. Simultaneous recordings of isometric force and membrane potentials were performed. 4-AP (50 microM) increased peak force by approximately 20% of the control and prolonged the action potential by 20%. Higher concentrations of 4-AP (800 microM) resulted in further increments of force and action potential duration (60 and 70% of controls, respectively). Prolongation of the action potential and potentiation of the isometric force was still present one hour after withdrawal of the drug from the perfusate. The results are consistent with the view that 4-AP prolongs the action potential by inhibiting the late repolarizing potassium current. It is suggested that the calcium uptake by the ventricular cell during the prolonged action potential is increased and that this leads to the positive inotropic effect.
BACKGROUND: The papillary muscles (PMs) play an important role in normal cardiac function, helping to prevent leakage through the AV valves during systole. The nature of their attachment to the heart wall can affect the understanding of their function. This attachment is conventionally portrayed as a direct connection of their bases to the solid portion of the heart wall. X-ray multidetector CT provides a new, noninvasive way to investigate this connection in vivo. METHODS AND RESULTS: With the use of x-ray multidetector CT with interactive 3D reconstruction, the bases of the PMs are seen to attach to the trabeculae carneae lining the ventricular wall rather than directly to the solid portion of the wall, as has been conventionally believed. This is true for both the left and right ventricular PMs. CONCLUSIONS: This new picture of the geometry of the attachment of the PMs to the heart wall may have important implications for the understanding of their function, including the nature of the transmission of the forces between the PMs and the heart wall.