Endocardium modulates myocardial inotropic response to 5-hydroxytryptamine

1989 ◽  
Vol 257 (6) ◽  
pp. H1790-H1797 ◽  
Author(s):  
A. M. Shah ◽  
L. J. Andries ◽  
A. L. Meulemans ◽  
D. L. Brutsaert

The endocardium modulates contractile performance of subjacent myocardium in isolated heart muscle. We investigated the effects of 5-hydroxytryptamine (5-HT, 0.01-30 microM) on isolated cat papillary muscles with or without intact endocardium (+E or -E, respectively). Selective endocardial damage by 1-s immersion in 1% Triton X-100 caused reduction in half-isometric relaxation time (RT1/2) and isometric twitch tension (TT), but not maximum unloaded shortening velocity (Vmax). 5-HT caused reduction in RT1/2 in endocardium-intact but an increase in endocardium-damaged preparations (at 30 microM: -12.1 +/- 1.8%, +E; +5.2 +/- 1.5%, -E). Mean percent increases in TT were greater in endocardium-damaged muscles (at 30 microM: 37.3 +/- 8.6%, +E; 107.3 +/- 19.5%, -E). In the presence of ketanserin (1 microM), 5-HT reduced RT1/2 in endocardium-intact (at 30 microM: -11.9 +/- 1.3%) but not endocardium-damaged muscles (except slightly at 30 microM) and increased TT at 30 microM by 28.7 +/- 4.9% (+E) and 48.9 +/- 15.6% (-E). In the presence of propranolol (1 microM), 5-HT increased RT1/2 (+E and -E) while increasing TT by 23.3 +/- 7.8% (+E) and 43.5 +/- 2.5% (-E). Endocardium did not influence changes in Vmax. Ketanserin (1 microM), but not propranolol (1 microM), markedly diminished endocardial damage induced by 5-HT (greater than or equal to 10 microM). These results suggest a 5-HT-induced endocardium-mediated "inhibitory" effect (causing earlier isometric relaxation) that is not blocked by ketanserin.

1995 ◽  
Vol 198 (7) ◽  
pp. 1527-1538 ◽  
Author(s):  
D McLister ◽  
E D Stevens ◽  
J P Bogart

Isometric twitch and tetanus parameters, force-velocity curves, maximum shortening velocity (Vmax) and percentage relaxation between stimuli (%R) across a range of stimulus frequencies were determined for a muscle used during call production (the tensor chordarum) and a locomotor muscle (the sartorius) for three species of hylid frogs, Hyla chrysoscelis, H. versicolor and H. cinerea. The call of H. chrysoscelis has a note repetition rate (NRR) approximately twice as fast as the call of H. versicolor (28.3, 42.5 and 56.8 notes s-1 for H. chrysoscelis and 14.8, 21.1 and 27.4 notes s-1 for H. versicolor at 15, 20 and 25 degrees C, respectively). Hyla cinerea calls at a very slow NRR (Approximately 3 notes s-1 at 25 degrees C). Hyla versicolor evolved from H. chrysoscelis via autopolyploidy, so the mating call of H. chrysoscelis is presumably the ancestral mating call of H. versicolor. For the tensor chordarum of H. chrysoscelis, H. versicolor and H. cinerea at 25 degrees C, mean twitch duration (19.2, 30.0 and 52.9 ms, respectively), maximum isometric tension (P0; 55.0, 94.4 and 180.5 kN m-2, respectively), tetanic half-relaxation time (17.2, 28.7 and 60.6 ms, respectively) and Vmax (4.7, 5.2 and 2.1 lengths s-1, respectively) differed significantly (P < 0.05) among all three species. The average time of tetanic contraction to half-P0 did not differ significantly between H. chrysoscelis (14.5 ms) and H. versicolor (15.8 ms) but was significantly longer for H. cinerea (52.6 ms). At 25 degrees C, Vmax differed significantly among the sartorius muscles of H. chrysoscelis, H. versicolor and H. cinerea (5.2, 7.0 and 9.8 lengths s-1, respectively) but mean twitch duration (29.5, 32.2 and 38.7 ms, respectively), P0 (252.2, 240.7 and 285.1 kN m-2, respectively) and tetanic half-relaxation time (56.3, 59.5 and 60.7 ms, respectively) did not differ significantly. The average time of contraction to half-P0 did not differ significantly between H. chrysoscelis (23.7 ms) and H. versicolor (22.9 ms) but was significantly shorter for H. cinerea (15.6 ms). The only consistent contractile differences found in this study between the calling muscle and locomotor muscle of H. chrysoscelis, H. versicolor and H. cinerea were that the calling muscles generated less tension and their force-velocity relationship was much more linear. These differences may be attributable to ultrastructural differences between calling and locomotor muscles.(ABSTRACT TRUNCATED AT 400 WORDS)


1980 ◽  
Vol 238 (1) ◽  
pp. C15-C20 ◽  
Author(s):  
R. H. Fitts ◽  
W. W. Winder ◽  
M. H. Brooke ◽  
K. K. Kaiser ◽  
J. O. Holloszy

The effects of thyrotoxicosis on the contractile properties of soleus muscle were examined in rats given 3 mg of T4 and 1 mg of T3 per kg of diet for 6–8 wk. Thyrotoxicosis induced significant decreases in isometric twitch contraction time (CT), one-half relaxation time, and peak twitch tension. The Ca2+ uptake activity of the sarcoplasmic reticulum (SR) was increased in the thyrotoxic muscles; this adaptation in the SR provides a possible mechanism for the alterations in isometric contractile properties. Thyrotoxicosis induced a large increase in fibers classified as type 2, on the basis of an alkali-stable histochemical reaction for ATPase, in the soleus. Although this reaction is commonly interpreted as indicating that a muscle is fast, maximum shortening velocity (Vmax) and Mg2+ activated actomyosin ATPase activity were unaffected in the thyrotoxic soleus. Our findings provide evidence that CT and Vmax can vary independently and that the histochemical ATPase reaction may not always reflect the biochemical properties that make myosin fast or slow. actomyosin ATPase; histochemical ATPase reaction; isometric contraction time; maximum shortening velocity; one-half relaxation time; sarcoplasmic reticulum; skeletal muscle Submitted on April 13, 1979 Accepted on August 7, 1979


1976 ◽  
Vol 230 (6) ◽  
pp. 1701-1707 ◽  
Author(s):  
SM Kilen ◽  
WS Harris

Data are presented which indicate that the mechanism of tension depression and subsequent recovery from dichlorodifluoromethane (Freon 12), an aerosol gas recently described as a potent cardiac depressant agent, differs from that of hypoxia. To analyze these differences, 22 rat papillary muscles, contracting isometrically in a myograph, were studied during and subsequent to 15-min interventions of of hypoxia. Freon 12 with adequate oxygenation, or Freon 12 combined with hypoxia. During each of the three interventions the developed force (F) was markedly depressed, while peak shortening velocity (Vpm) was selectively more depressed by Freon and Freon combined with hypoxia than by hypoxia alone. While hypoxia shortened the time to peak force (TTP) and one-half relaxation time (RT1/2) markedly, Freon 12 with adequate oxygenation slightly shortened RT1/2 (P is less than 0.001) but failed to shorten TTP significantly. In contrast, Freon 12 administered during hypoxia shortened TTP and RT1/2 significantly (P is less than 0.001), more than did hypoxia or Freon 12 alone. Posthypoxic prolongation of TTP and RT1/2 was not seen during recovery from Freon 12. This prolongation was depressed during recovery from Freon 12 given either during hypoxia or during recovery from hypoxia. The results indicate that Freon 12 and hypoxia act synergically, although the mechanisms through which they mediate their actions on myocardial tissue are not identical.


1988 ◽  
Vol 254 (2) ◽  
pp. G201-G209 ◽  
Author(s):  
C. B. Koelbel ◽  
G. van Deventer ◽  
S. Khawaja ◽  
M. Mogard ◽  
J. H. Walsh ◽  
...  

Somatostatin has been shown to inhibit antral motility in vivo. To examine the effect of somatostatin on cholinergic neurotransmission in the canine antrum, we studied the mechanical response of and the release of [3H]acetylcholine from canine longitudinal antral muscle in response to substance P, gastrin 17, and electrical stimulation. In unstimulated tissues, somatostatin had a positive inotropic effect on spontaneous phasic contractions. In tissues stimulated with substance P and gastrin 17, but not with electrical stimulation, somatostatin inhibited the phasic inotropic response dose dependently. This inhibitory effect was abolished by indomethacin. Somatostatin stimulated the release of prostaglandin E2 radioimmunoreactivity, and prostaglandin E2 inhibited the release of [3H]acetylcholine induced by substance P and electrical stimulation. Somatostatin increased the release of [3H]acetylcholine from unstimulated tissues by a tetrodotoxin-sensitive mechanism but inhibited the release induced by substance P and electrical stimulation. These results suggest that somatostatin has a dual modulatory effect on cholinergic neurotransmission in canine longitudinal antral muscle. This effect is excitatory in unstimulated tissues and inhibitory in stimulated tissues. The inhibitory effect is partially mediated by prostaglandins.


2005 ◽  
Vol 29 (11) ◽  
pp. 866-875 ◽  
Author(s):  
Ravi K. Birla ◽  
Gregory H. Borschel ◽  
Robert G. Dennis

1982 ◽  
Vol 52 (2) ◽  
pp. 473-478 ◽  
Author(s):  
R. R. Roy ◽  
I. D. Meadows ◽  
K. M. Baldwin ◽  
V. R. Edgerton

Chronic overload of a skeletal muscle by removing its synergists produces hypertrophy and marked changes in its metabolic and biochemical properties. In this study alterations in the contractile properties of the plantaris 12–14 wk after bilateral removal of the soleus and gastrocnemius were investigated. In situ isometric and isotonic contractile properties of overloaded plantaris (OP), normal plantaris (NP), and normal soleus (NS) were tested at 33 +/- 1 degree C. Op were 97% heavier than NP and produced 43 and 46% higher twitch (Pt) and tetanic (Po) tensions. However, NP produced more tension per cross-sectional area than OP (mean 26.2 vs. 21.6 N/cm2; P less than 0.001). Isometric twitch time to peak tension (TPT) and half-relaxation time (1/2RT) were significantly longer in OP (mean 36.4 vs. 32.5 ms and 23.9 vs. 18.4 ms). Mean maximum shortening velocity (Vmax, mm/s per 1,000 sarcomeres) were 34.1 for NP and 18.1 for OP (P less than 0.001). The degree of conversion toward the Vmax of NS was 74% compared with only 19 and 14% for TPT and 1/2RT. OP produced a higher proportion of Po at a given stimulation frequency than NP and showed less fatigue than NP after repetitive stimulation. Chronic overload of the fast plantaris modified to varying degrees the contractile properties studied toward that resembling a slow muscle. Although the maximum tension of OP was markedly enhanced it was not in proportion to the increase in muscle mass.


1986 ◽  
Vol 164 (5) ◽  
pp. 1407-1421 ◽  
Author(s):  
J E Gabay ◽  
J M Heiple ◽  
Z A Cohn ◽  
C F Nathan

We examined the subcellular location of bactericidal factors (BF) in human neutrophils, using an efficient fractionation scheme. Nitrogen bomb cavitates of DIFP-treated PMN were centrifuged through discontinuous Percoll gradients, each fraction extracted with 0.05 M glycine, pH 2.0, and tested for the killing of Escherichia coli. greater than 90% of BF coisolated with the azurophil granules. After lysis of azurophils, 98% of azurophil-derived BF (ADBF) sedimented with the membrane. ADBF activity was solubilized from azurophil membrane with either acid or nonionic detergent (Triton X-100, Triton X-114). Bactericidal activity was linear with respect to protein concentration over the range 0.3-30 micrograms/ml. 0.1-0.3 microgram/ml ADBF killed 10(5) E. coli within 30 min at 37 degrees C. At 1.4 micrograms/ml, 50% of 2 X 10(5) bacteria were killed within 5 min. ADBF was effective between pH 5-8, with peak activity at pH 5.5. Glucose (20 mM), EDTA (1-25 mM), and physiologic concentrations of NaCl or KCl had little or no inhibitory effect on ADBF. ADBF killed both Gram-positive and Gram-negative virulent clinical isolates, including listeria, staphylococci, beta-hemolytic streptococci, and Pseudomonas aeruginosa. Thus, under these conditions of cell disruption, fractionation, extraction, and assay, almost all BF in human PMN appeared to be localized to the membrane of azurophilic granules as a highly potent, broad-spectrum, rapidly acting protein(s) effective in physiologic medium. Some of these properties appear to distinguish ADBF from previously described PMN bactericidal proteins.


2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Malte Tiburcy ◽  
James E Hudson ◽  
Dirk Ziebolz ◽  
Wolfram H Zimmermann

Background: Tissue engineering of heart muscle from human pluripotent stem cells holds great potential for in vitro studies, disease modeling, and cardiac replacement therapy. A number of variables may however affect maturation and function of human cardiomyocytes (CM) in tissue engineered heart muscle (EHM). Here, we hypothesized that defined non-myocyte (NM) populations support structural and functional maturation of EHM. Methods and Results: To investigate the role of non-myocytes (NM) for heart muscle assembly in vitro we generated EHM from purified CM (93±1.5% actinin+) and a mixture of CM and NM (70/30%). Notably, only the NM-supplemented EHM generated measurable forces (0.8±0.1 mN, n=9) with anisotropically aligned cardiomyocytes. Depending on pluripotent stem cell line and differentiation protocol the NM compartment may vary considerably. To further define the influence of the NM compartment we generated EHM from HES2-derived CM with undefined NM, i.e the NM typically derived during cardiac differentiation, and defined NM (fibroblasts). Defined EHM were more mature with higher forces and lower variability between experimental series (defined: 9.8±0.9 nN/CM, undefined: 4.7±1.4 nN/CM, n=10/9), higher EC50 for calcium, and enhanced inotropic response to isoprenaline despite comparable CM:NM composition of 1:1. Increased actinin protein per CM, a reduction of MLC2V/2A double positive CM, and evidence of CM cycle withdrawal indicated enhanced ventricular maturation in defined EHM. Next, we tested whether defining cell composition and NM in iPS-derived EHM will yield a comparable functional phenotype to HES2-EHM. In agreement with the above data, defined iPS-EHM displayed advanced functional maturation with high specific forces, comparable calcium EC50, and inotropic response to isoprenaline. Summary and Conclusions: Here we demonstrate that defining the NM compartment is essential for optimized human heart muscle formation and maturation in vitro. Moreover, our data provide (1) evidence for the applicability of EHM in modelling of heart muscle development and (2) a strong rationale for the need to define CM and NM compartments in tissue engineered myocardium to reduce variability in applications such as disease modelling.


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