Species differences in the positive inotropic response to DPI 201-106, a novel cardiotonic agent

1989 ◽  
Vol 67 (11) ◽  
pp. 1460-1463 ◽  
Author(s):  
Stephen J. Haleen ◽  
Robert P. Steffen ◽  
Ronald E. Weishaar
Keyword(s):  
Guinea Pig ◽  
Sodium Channel ◽  
Species Differences ◽  
Isolated Heart ◽  
Inotropic Response ◽  
Inotropic Effects ◽  
Isolated Hearts ◽  
Cardiotonic Agent ◽  
Rat Hearts ◽  
First Time

The positive inotropic activity of the novel cardiotonic DPI 201-106 was investigated in rat and guinea pig isolated hearts. For comparative purposes, the adenylate cyclase stimulant forskolin and the sodium channel agonist veratridine were also evaluated in both species. DPI 201-106 and veratridine produced greater inotropic effects in rat hearts than in guinea pig hearts, whereas forskolin produced comparable effects. In both species the inotropic response to DPI 201-106 and veratridine, but not forskolin, was reversed by the sodium channel antagonist tetrodotoxin. These results confirm that the positive inotropic effect of DPI 201-106 is due to stimulation of the sodium channel and demonstrate for the first time that species differences exist in the inotropic response to this novel cardiotonic drug.Key words: cardiac muscle, contractility, cardiotonic drug, sodium channel, isolated heart.

Reduced glutathione modulates the arachidonic acid induced coronary reactions

1984 ◽  
Vol 62 (10) ◽  
pp. 1261-1267 ◽  
Author(s):  
Jaime Talesnik ◽  
James N. Tsoporis
Keyword(s):  
Arachidonic Acid ◽  
Guinea Pig ◽  
Reduced Glutathione ◽  
Isolated Heart ◽  
Prostaglandin E ◽  
Guinea Pig Heart ◽  
Rat Hearts ◽  
Resistance Vessels ◽  
Vasodilator Action ◽  
Perfused Hearts

Coronary flow was recorded from spontaneously beating isolated perfused hearts of rats and guinea pigs. Arachidonic acid (AA), in single bolus doses, produced a fast short lasting coronary constriction followed by a slow developing but persisting vasodilation. These reactions (biphasic type) were characteristic of the guinea pig heart. In about 50% of the rat hearts the vasoconstrictor action predominated while the biphasic response was obtained in the rest of the experiments. Pretreatment of rats with aspirin prevented the responses to AA in the isolated heart. The administration of reduced glutathione (GSH) (about 1 mM to the rat or 0.5–0.75 mM to the guinea pig hearts) produced a marked development and (or) enhancement of the vasodilator action of AA. Repeated or single large doses of AA produced a change of pattern of responses from biphasic to constrictor type; the addition of GSH restored the vasodilator phase. Since GSH directs the endoperoxide metabolism towards the synthesis of prostaglandin E2 (PGE2), we postulate that the coronary dilatation of resistance vessels produced by AA would be due to a great extent to PGE2.

scholarly journals ANAPHYLAXIS IN THE ISOLATED HEART

1938 ◽  
Vol 67 (2) ◽  
pp. 169-180 ◽  
Author(s):  
Herbert B. Wilcox ◽  
E. Cowles Andrus
Keyword(s):  
Guinea Pig ◽  
Intact Animal ◽  
Isolated Heart ◽  
Horse Serum ◽  
Coronary Vessels ◽  
Cardiac Rate ◽  
Isolated Hearts ◽  
Flow Through ◽  
Perfused Hearts ◽  
Electrocardiographic Abnormalities

The isolated hearts of guinea pigs sensitized to horse serum have been shown to react characteristically upon exposure to small amounts of antigen. The cardiac rate is temporarily accelerated and transient alterations in amplitude of contraction are to be observed. Electrocardiographic abnormalities, previously recorded by remote leads during anaphylactic shock in the intact animal, have been recorded by direct leads from the isolated perfused hearts of sensitized animals during this reaction. An additional effect of anaphylaxis in the isolated heart of the guinea pig is reported: a striking reduction in the rate of flow through the coronary vessels. The anaphylactic reaction of the isolated heart of the guinea pig has been compared with the action of histamine upon the same preparation and the effect of atropine upon each has been observed. The implications of certain quantitative differences in the influence of atropine upon these reactions are discussed.

Supply-to-demand ratio for oxygen determines formation of adenosine by the heart

1986 ◽  
Vol 250 (2) ◽  
pp. H173-H180 ◽  
Author(s):  
H. Bardenheuer ◽  
J. Schrader
Keyword(s):  
Coronary Arteries ◽  
Rank Order ◽  
Isolated Heart ◽  
Basic Mechanism ◽  
Cardiac Metabolism ◽  
Feedback Signal ◽  
Inotropic Effects ◽  
Cardiotonic Agent ◽  
Heart Preparation ◽  
O2 Supply

To investigate the basic mechanism for formation of adenosine, cardiac work was increased using an isolated guinea pig working heart preparation. Cardiac metabolism was stimulated by intracoronary infusion of isoproterenol, norepinephrine (NE), ouabain, and the cardiotonic agent 1H-imidazo[4,5-b]pyridine, 2-[2-methoxy-4-(methylsulfinyl)-phenyl] (AR-L 115), and the release of adenosine into the effluent was determined. Besides their inotropic effects on myocardial tissue, these substances affect differently the tone of coronary arteries. Thus they influence the supply-to-demand ratio for O2 and the tissue cyclic AMP content differently. When myocardial O2 consumption was increased to the same extent, the changes in coronary flow induced followed the order of AR-L 115 greater than isoproterenol greater than NE greater than ouabain. Conversely, the rank order of potency causing adenosine and inosine release was NE greater than ouabain greater than isoproterenol greater than AR-L 115. When NE-induced vasoconstriction was abolished by prazosin, the release of adenosine and inosine was significantly diminished. Enhancement of O2 supply by overperfusion of the coronary arteries in isoproterenol-stimulated hearts was associated with a significant reduction of nucleoside release into the effluent. Our findings suggest that the major stimulus for myocardial adenosine formation is an imbalance between O2 delivery and O2 demand and not the metabolic rate as such. In the isolated heart, adenosine is formed as a feedback signal and can compete with NE- and ouabain-induced vasoconstriction.

Effects of peptide leukotrienes on cardiac dynamics in rat, cat, and guinea pig hearts

1985 ◽  
Vol 249 (3) ◽  
pp. H477-H484 ◽  
Author(s):  
D. M. Roth ◽  
D. J. Lefer ◽  
C. E. Hock ◽  
A. M. Lefer
Keyword(s):  
Guinea Pig ◽  
Coronary Perfusion Pressure ◽  
Contractile Force ◽  
Coronary Perfusion ◽  
Papillary Muscles ◽  
Inotropic Effects ◽  
Isolated Hearts ◽  
Cardiac Contractile ◽  
Myocardial Contractile Force ◽  
Leukotriene Antagonist

The purpose of the present investigation was to examine potential inotropic effects of leukotrienes C4 (LTC4) and D4 (LTD4) in relation to their potent coronary constricting effects. The experiments were carried out in isolated Langendorff perfused hearts and isolated electrically driven isometrically contracting papillary muscle preparations. Tissues from cat, rat, and guinea pig were used in the study. Both LTC4 and LTD4 at 50 ng/ml had no effect on papillary muscles isolated from the rat, guinea pig, or cat. These papillary muscles responded to known negative inotropic agents including pentobarbital sodium and methanol. In isolated hearts perfused under constant flow, both LTC4 and LTD4 at 50 ng/ml increased coronary perfusion pressure and decreased contractile force of the heart in all three species. In hearts perfused under constant pressure perfusion, both LTC4 and LTD4 decreased coronary flow with concomitant decreases in contractile force. The leukotriene antagonist, FPL 55712, blocked both the coronary constrictor and the cardiodepressant effects of both leukotrienes. Pentobarbital (100 micrograms/ml) significantly decreased cardiac contractile force without inducing coronary vasoconstriction. These findings demonstrate that LTC4 and LTD4 do not possess direct negative inotropic activity in cardiac muscles of these three species. However, LTC4 and LTD4 are potent coronary constrictors that can secondarily decrease myocardial contractile force via their coronary constrictor action.

Transient inotropic effects of low extracellular sodium in perfused rat heart

1990 ◽  
Vol 259 (3) ◽  
pp. H712-H719 ◽  
Author(s):  
F. Kolar ◽  
W. C. Cole ◽  
B. Ostadal ◽  
N. S. Dhalla
Keyword(s):  
Rat Heart ◽  
Positive Inotropic Effect ◽  
Minor Role ◽  
Inotropic Response ◽  
Inotropic Effects ◽  
Low Concentrations ◽  
Rat Hearts ◽  
Rapid Loading ◽  
Perfused Rat Hearts ◽  
Extracellular Sodium

The inotropic effects of low concentrations of extracellular Na+ (35-110 mM) were studied using Langendorff-perfused rat hearts. Low Na+ induced an initial positive inotropic response proportional to the decrease of transsarcolemmal Na+ gradient. At 35 mM Na+, this effect was followed by a secondary fall in contractility and rise of resting force (RF) and then by a delayed positive inotropic effect and recovery of RF. The magnitude of these low Na(+)-induced transient changes was dependent on the extracellular Ca2+ concentration and was altered by amiloride (6 x 10(-4) and 2.5 x 10(-3) M), ouabain (5 x 10(-5) and 5 x 10(-4) M), ryanodine (2 x 10(-8), 1 x 10(-7) and 1 x 10(-6) M), and sodium azide (1 x 10(-3) and 5 x 10(-3) M) but not by verapamil (2 x 10(-8) and 1 x 10(-7) M) or vanadate (4 x 10(-6) M). The data indicate the initial positive inotropic response of the rat heart to low Na+ may be due to rapid loading of myocytes with Ca2+ through the Na(+)-Ca2+ exchange mechanism. The secondary depression of contractility and the rise of RF appear to be the consequence of the short-lived intracellular Ca2+ overload. Furthermore, the recovery of contractions and the delayed positive inotropic response may be the result of the intracellular redistribution of excessive Ca2+ into the sarcoplasmic reticulum with mitochondria and increased transsarcolemmal Ca2+ efflux apparently playing a more minor role.

scholarly journals The positive inotropic effects of OPC-18790, a new cardiotonic agent, in guinea-pig papillary muscles

1992 ◽  
Vol 58 ◽  
pp. 271
Author(s):  
Michio Yajima ◽  
Yoshihiro Hotta ◽  
Pao Chi Isao ◽  
Hiroaki Ando ◽  
Hirohiko Nomura ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Papillary Muscles ◽  
Inotropic Effects ◽  
Cardiotonic Agent ◽  
Positive Inotropic Effects

Identification of a PKCε-dependent regulation of myocardial contraction by epicatechin-3-gallate

2008 ◽  
Vol 294 (1) ◽  
pp. H345-H353 ◽  
Author(s):  
Daxiang Li ◽  
Changjun Yang ◽  
Ying Chen ◽  
Jiang Tian ◽  
Lijun Liu ◽  
...  
Keyword(s):  
Cultured Cells ◽  
Myocardial Contraction ◽  
Tea Catechins ◽  
Inotropic Effects ◽  
Isolated Hearts ◽  
Rat Hearts ◽  
Adult Cardiac Myocytes ◽  
Positive Inotropic Effects ◽  
Intracellular Ca ◽  
Dependent Signaling Pathway

In this study, the effects of tea catechins and tea theaflavins on myocardial contraction were examined in isolated rat hearts using a Langendorff-perfusion system. We found that both tea catechins and theaflavins had positive inotropic effects on the myocardium. Of the tested chemicals, epicatechin-3-gallate (ECG) and theaflavin-3,3′-digallate (TF4) appear to be the most effective tea catechin and theaflavin, respectively. Further studies of ECG-induced positive inotropy revealed the following insights. First, unlike digitalis drugs, ECG had no effect on intracellular Ca2+ level in cultured adult cardiac myocytes. Second, it activated PKCε, but not PKCα, in the isolated hearts as well as in cultured cells. Neither a phospholipase C (PLC) inhibitor ( U73122) nor the antioxidant N-acetyl cysteine (NAC) affected the ECG-induced activation of PKCε. Third, inhibition of PKCε by either chelerythrine chloride (CHE) or PKCε translocation inhibitor peptide (TIP) caused a partial reduction of ECG-induced increases in myocardial contraction. Moreover, NAC was also effective in reducing the effects of ECG on myocardial contraction. Finally, pretreatment of the heart with both CHE and NAC completely abolished ECG-induced inotropic effects on the heart. Together, these findings indicate that ECG can regulate myocardial contractility via a novel PKCε-dependent signaling pathway.

Effects of inotropic agents on isolated guinea pig heart under conditions that modify calcium pools involved in contractile activation

1986 ◽  
Vol 64 (7) ◽  
pp. 947-953 ◽  
Author(s):  
Kyosuke Temma ◽  
Tai Akera ◽  
Yuk-Chow Ng
Keyword(s):  
Guinea Pig ◽  
Heart Muscle ◽  
Isolated Heart ◽  
Bay K 8644 ◽  
Inotropic Effect ◽  
Common Mechanism ◽  
Primary Role ◽  
Guinea Pig Heart ◽  
Inotropic Effects ◽  
Contractile Activation

Positive inotropic effects of strophanthidin were compared with those of isoproterenol, BAY K 8644, grayanotoxin, veratridine, and monensin in electrically stimulated left atrial muscle preparations of guinea pig heart under conditions in which the calcium pool, playing a primary role in contractile activation, was altered. In concentrations that caused similar degrees of increase in developed tension under 1 Hz stimulation, grayanotoxin and strophanthidin caused a relatively large increase in potentiated postrest contraction compared with that caused by isoproterenol, whereas the effect of BAY K 8644 on the postrest contraction was the smallest. The effect of high concentrations of grayanotoxin or strophanthidin, however, resembled that of isoproterenol. The sensitivity of the isolated heart muscle to these agents was compared under conditions in which utilization of various calcium pools contributing to contractile activation was suppressed. Mn2+, which reduces contribution of very superficial Ca2+, reduced sensitivity of heart muscle to the positive inotropic effect of isoproterenol and enhanced the inotropic effect of monensin or veratridine. Verapamil, nifedipine, diltiazem, or ryanodine did not have marked effects on the positive inotropic action of Ca2+, monensin, veratridine, or strophanthidin. These results suggest that the positive inotropic actions of veratridine, grayanotoxin, and strophanthidin share a common mechanism and that low concentrations of strophanthidin may increase loading of Ca2+ pool, which plays an important role in potentiated postrest contraction.

Effects of thyroid state on respiration of perfused rat and guinea pig hearts

1987 ◽  
Vol 253 (3) ◽  
pp. H519-H523 ◽  
Author(s):  
L. C. Read ◽  
P. G. Wallace ◽  
M. N. Berry
Keyword(s):  
Oxygen Consumption ◽  
Guinea Pig ◽  
Thyroid Hormones ◽  
Isolated Heart ◽  
Basal Respiration ◽  
Perfused Heart ◽  
Guinea Pig Heart ◽  
Thyroid State ◽  
Contraction Frequency ◽  
Rat Hearts

The effects of thyroid state on the respiration of the isolated heart were investigated using retrograde perfused rat and guinea pig hearts. In both species, hypothyroidism caused a marked depression in circulating thyroid hormone concentrations and in the respiration of the isolated, retrograde perfused heart. The effects on myocardial respiration could be attributed to changes in the contraction frequency and in the oxygen consumption per beat, with little contribution from basal respiration. Treatment of animals with thyroxine elevated plasma thyroid hormones to a similar extent in rats and guinea pigs. In the latter, thyroxine treatment was associated with substantial increases in the contraction frequency and the oxygen consumption per beat of the isolated heart. In contrast, only small changes were apparent in the retrograde perfused rat heart, observations that were confirmed in rat hearts perfused at near physiological work loads. It was concluded that rat hearts isolated from normal animals function at near maximal thyroid state, in contrast to the guinea pig heart, which requires higher circulating concentrations of thyroid hormones to attain maximal responses.

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