Pyruvate potentiates inotropic effects of isoproterenol and Ca2+ in rabbit cardiac muscle preparations

Catecholamines and elevated extracellular Ca2+concentration ([Ca2+]o) augment contractile force by increased Ca2+ influx and subsequent increased sarcoplasmic reticulum (SR) Ca2+ release. We tested the hypothesis that pyruvate potentiates Ca2+ release and inotropic response to isoproterenol and elevated [Ca2+]o, since this might be of potential importance in a clinical setting to circumvent deleterious effects on energy demand during application of catecholamines. Therefore, we investigated isometrically contracting myocardial preparations from rabbit hearts at 37°C, pH 7.4, and a stimulation frequency of 1 Hz. At a [Ca2+]o of 1.25 mM, pyruvate (10 mM) alone increased developed force (Fdev) from 1.89 ± 0.42 to 3.62 ± 0.62 (SE) mN/mm2 ( n = 8, P < 0.05) and isoproterenol (10−6 M) alone increased Fdev from 2.06 ± 0.55 to 25.11 ± 2.1 mN/mm2 ( P < 0.05), whereas the combination of isoproterenol and pyruvate increased Fdevoverproportionally from 1.89 ± 0.42 to 33.31 ± 3.18 mN/mm2 ( P < 0.05). In a separate series of experiments, we assessed SR Ca2+ content by means of rapid cooling contractures and observed that, despite no further increase in Fdev by increasing [Ca2+]o from 8 to 16 mM, 10 mM pyruvate could still increase Fdev from 26.4 ± 6.8 to 29.7 ± 7.1 mN/mm2( P < 0.05, n = 9) as well as the Ca2+ load of the SR. The results show that the positive inotropic effects of pyruvate potentiate the inotropic effects of isoproterenol or Ca2+, because in the presence of pyruvate, Ca2+ and isoproterenol induced larger increases in inotropy than can be calculated by mere addition of the individual effects.

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Contractile effects of cardiac neuropeptides in isolated canine atrial and ventricular muscles

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1989.257.4.h1082 ◽

1989 ◽

Vol 257 (4) ◽

pp. H1082-H1087 ◽

Cited By ~ 1

Author(s):

D. F. Rigel ◽

I. L. Grupp ◽

A. Balasubramaniam ◽

G. Grupp

Keyword(s):

Isometric Force ◽

Contractile Force ◽

Adrenergic Blockade ◽

Canine Heart ◽

Inotropic Action ◽

Inotropic Effects ◽

Calcitonin Gene ◽

Positive Inotropic Effects ◽

The Right ◽

Ventricular Trabeculae

Contractile effects of the cardiac neuropeptides vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), and neurotensin (NT) were compared with those of l-isoproterenol (ISO) in isolated canine atrial and ventricular trabeculae muscles stimulated to contract at 1 Hz. In ventricular muscles, ISO, VIP, and PHI augmented developed isometric force by approximately 100%. VIP and PHI were three times and 1/10, respectively, as potent as ISO. VIP also exhibited positive inotropic effects in atrial trabeculae. The contractile responses to VIP were unchanged after beta-adrenergic blockade with nadolol at a concentration (10 microM) that shifted the ISO dose-response curve two to three orders of magnitude to the right. In atrial and ventricular trabeculae, NPY (1 microM) attenuated contractile force by 36 +/- 8 and 30 +/- 4%, respectively. Each peptide also caused comparable increases or decreases in the rate of development of force and the rate of relaxation. CGRP and NT caused no significant changes in developed force in either atrial or ventricular muscles in concentrations up to 1 microM. Our results indicate a potential positive inotropic action of endogenous VIP and PHI and a cardiodepressant effect of endogenous NPY in the canine heart.

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Ontogeny of positive inotropic responses to sympathomimetic agents and of myocardial adrenoceptors in rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y94-053 ◽

1994 ◽

Vol 72 (4) ◽

pp. 361-367 ◽

Cited By ~ 8

Author(s):

Arjumand Inayatulla ◽

Ding-You Li ◽

Sylvain Chemtob ◽

Daya R. Varma

Keyword(s):

Contractile Force ◽

Inotropic Response ◽

Chemical Sympathectomy ◽

Adult Rats ◽

Maximal Increase ◽

Inotropic Effects ◽

Mediated Effects ◽

Adrenoceptor Agonist ◽

6 Hydroxydopamine ◽

Inotropic Responses

Positive inotropic efficacies (maximal increase in contractile force) and potencies of the α-adrenoceptor agonist methoxamine and β-adrenoceptor agonist isoprenaline were determined on electrically driven (1 Hz) ventricular strips from rats aged 0.5, 1, 2, 3, 6, and 10 (adult) weeks. The inotropic response to methoxamine significantly decreased after 2 weeks of age. The inotropic potency of isoprenaline was slightly but significantly lower at all ages than at 0.5 weeks of age. Up to 2 weeks of age, the maximal inotropic effect of methoxamine was comparable with that of isoprenaline, thereafter it was but markedly less. Phenylephrine behaved like methoxamine, and noradrenaline like isoprenaline. The effect of methoxamine was antagonized by prazosin but not by propranolol; the reverse was true for isoprenaline. Injections at birth of triiodothyronine and dexamethasone exerted minimal effects on the inotropic responses to methoxamine and isoprenaline. Chemical sympathectomy with 6-hydroxydopamine caused supersensitivity to the inotropic effects of isoprenaline but produced subsensitivity to responses to methoxamine at 1 week; effects of methoxamine at 3 and 6 weeks of age were not altered by sympathectomy. No significant differences in α1 or β1-adrenoceptor densities or affinities in ventricular membranes from 7-day-old and adult rats were found. It is concluded that the positive inotropic responses to sympathomimetic amines decline with age, the decline is most marked in the case of α1-adrenoreceptor-mediated effects, and these changes do not appear to be due to a decrease in the number or affinity of α1- and β1-adrenoceptors.Key words: myocardial adrenocepters, methoxamine, isoprenaline, phenylephrine, noradrenaline, ontogeny, inotropic responses.

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Characterization of the histamine receptors in rabbit left atria

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y81-004 ◽

1981 ◽

Vol 59 (1) ◽

pp. 19-24 ◽

Cited By ~ 1

Author(s):

Alicia Polanin ◽

John H. McNeill

Keyword(s):

Left Atrial ◽

Histamine Receptor ◽

Histamine Receptors ◽

Receptor Blockade ◽

Inotropic Response ◽

Receptor Stimulation ◽

Inotropic Effects ◽

Receptor Antagonism ◽

Positive Inotropic Effects

The effects of selective histamine receptor analogs were studied in electrically paced rabbit left atria. Atrial tension was increased by histamine (an H1 and H2 agonist), 4-methylhistamine and impromidine (H2 agonists), and 2-pyridylethylamine (PEA) (an H1 agonist). The responses to histamine and impromidine were not altered by propranolol (1 × 10−7 M) or reserpine pretreatment. However, the responses to 4-methylhistamine and PEA were significantly decreased upon pretreatment with propranolol or reserpine. Promethazine pretreatment (H1 receptor blockade) antagonized the inotropic effects of histamine and PEA but had no effect on the responses to 4-methylhistamine or impromidine. Cimetidine pretreatment (H2 receptor antagonism) competitively blocked the positive inotropic effects of histamine, 4-methylhistamine, and impromidine. These results suggest that the left atrial inotropic response is mediated through H1 and H2 receptor stimulation.

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The effect of theophylline on amine-induced cardiac cyclic AMP and cardiac contractile force

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y77-014 ◽

1977 ◽

Vol 55 (1) ◽

pp. 98-104 ◽

Cited By ~ 11

Author(s):

Terry T. Martinez ◽

John H. McNeill

Keyword(s):

Cyclic Amp ◽

Dose Response ◽

Calcium Metabolism ◽

Response Curve ◽

Contractile Force ◽

Inotropic Response ◽

Inotropic Effects ◽

Rat Atria ◽

Contractile Effect ◽

Cardiac Contractile

In the isolated electrically driven rat atria, theophylline (5 × 10−4 M) produced a small but significant increase in cyclic AMP content which was prevented by reserpine pretreatment. Theophylline was also found to exert a direct contractile effect, unrelated to cyclic AMP, in atria obtained from reserpine-pretreated animals. The norepinephrine inotropic response was attenuated after 3 min, enhanced after 15 min, and abolished after 60 min of exposure to theophylline (5 × 10−4 M). The maximum phenylephrine inotropic response was not significantly changed after 15 min of exposure to theophylline; however, there was a slight shift to the left of the phenylephrine dose–response curve. The effect of theophylline on cyclic AMP appeared to be additive with the norepinephrine and phenylephrine responses. The effect of theophylline on amine-induced cardiac cyclic AMP and contractile force showed no correlation between the contractile and the cyclic AMP effects at the different times tested. It is concluded that the inotropic effects of theophylline in rat atria are not mediated through cyclic AMP; instead, the methylxanthines may exert their effects on the heart through changes in calcium metabolism.

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Positive inotropic effects of ouabain in isolated cat ventricular myocytes in sodium-free conditions

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00203.2002 ◽

2002 ◽

Vol 283 (5) ◽

pp. H2045-H2053 ◽

Cited By ~ 16

Author(s):

Manabu Nishio ◽

Stuart W. Ruch ◽

J. Andrew Wasserstrom

Keyword(s):

Atpase Activity ◽

Voltage Clamp ◽

Ventricular Myocytes ◽

Inotropic Response ◽

Inotropic Effects ◽

Cellular Effects ◽

Positive Inotropic Effects ◽

Intracellular Ca ◽

Atpase Inhibition ◽

External K

The inotropic and toxic effects of cardiac steroids are thought to result from Na+-K+-ATPase inhibition, with elevated intracellular Na+(Na[Formula: see text])causing increased intracellular Ca2+(Ca[Formula: see text]) via Na-Ca exchange. We studied the effects of ouabain on cat ventricular myocytes in Na+-free conditions where the exchanger is inhibited. Cell shortening and Ca[Formula: see text] transients (with fluo 4-AM fluorescence) were measured under voltage clamp during exposure to Na+-free solutions [LiCl or N-methyl-d-glucamine (NMDG) replacement]. Ouabain enhanced contractility by 121 ± 55% at 1 μmol/l ( n = 11) and 476 ± 159% at 3 μmol/l ( n = 8) (means ± SE). Ca[Formula: see text] transient amplitude was also increased. The inotropic effects of ouabain were retained even after pretreatment with saxitoxin (5 μmol/l) or changing the holding potential to −40 mV (to inactivate Na+ current). Similar results were obtained with both Li+ and NMDG replacement and in the absence of external K+, indicating that ouabain produced positive inotropy in the absence of functional Na-Ca exchange and Na+-K+-ATPase activity. In contrast, ouabain had no inotropic response in rat ventricular myocytes (10–100 μmol/l). Finally, ouabain reversibly increased Ca2+overload toxicity by accelerating the rate of spontaneous aftercontractions ( n = 13). These results suggest that the cellular effects of ouabain on the heart may include actions independent of Na+-K+-ATPase inhibition, Na-Ca exchange, and changes in Na[Formula: see text].

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Effects of Ions, Ouabain, Epinephrine, and Tetrodotoxin on Glucose Metabolism and on Contractility in the Perfused Guinea Pig Heart

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y72-087 ◽

1972 ◽

Vol 50 (6) ◽

pp. 584-593 ◽

Cited By ~ 1

Author(s):

E. Benmouyal

Keyword(s):

Glucose Metabolism ◽

Guinea Pig ◽

Glucose Utilization ◽

Contractile Force ◽

Additive Effects ◽

Guinea Pig Heart ◽

Inotropic Effects ◽

Antagonistic Effects ◽

Positive Inotropic Effects ◽

Opposite Action

In the perfused guinea pig heart, the rate of glucose-U-14C oxidation to 14CO2 was directly related to the external ratio [Ca2+]/[Na+]2. The metabolic stimulatory effects of ouabain were concentration-dependent, and those brought about by epinephrine were not prevented by the presence of ouabain or added Ca2+. The increased glucose utilization produced by ouabain or Ca2+ was reduced by tetrodotoxin (TTX), whereas that produced by epinephrine or reduced extracellular Na+ (100 mM) was not. It was also found that TTX inhibited the positive inotropic effects of Ca2+ and ouabain, but did not reduce the contractile force during perfusion in presence of epinephrine or at 100 mM Na+. It is concluded that (a) ouabain (or Ca2+) and epinephrine, producing additive effects, have different modes of action; (b) TTX and ouabain (or Ca2+) have antagonistic effects, probably resulting from their opposite action on calcium movements.

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ALTERNATIVE ROUTES TO INNOVATION — THE EFFECTS OF CULTURAL AND STRUCTURAL FIT

International Journal of Innovation Management ◽

10.1142/s1363919620500061 ◽

2019 ◽

Vol 24 (01) ◽

pp. 2050006

Author(s):

DAG INGVAR JACOBSEN ◽

TORE HILLESTAD ◽

BIRGITTE YTTRI ◽

JARLE HILDRUM

Keyword(s):

Response Rate ◽

Organic Structure ◽

Configurational Approach ◽

Culture Strength ◽

Individual Effects ◽

Collective Phenomenon ◽

The Individual ◽

Alternative Routes ◽

Innovative Culture ◽

The Empirical Analysis

A configurational approach to organizations assumes that structural and cultural characteristics must be in “fit” to produce the wanted outcome. With a focus on innovation, this study examines empirically to what extent innovative activities with a large, global telecom company are produced by an innovative culture, an innovative structure, as well as the fit between the two. Based on an extensive survey (N = 21064, response rate = 65) of employees in seven countries in Europe and Asia, data was aggregated to unit level as culture by nature is a collective phenomenon. The empirical analysis detected both the individual effects of culture strength and homogeneity, structure, as well as the fit between the two. The results indicate that an innovative culture and an organic structure indeed fosters innovation, but that, somewhat surprisingly, there are not effects of the fit between the two. Both practical and theoretical implications are discussed.

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