scholarly journals Activation of Na+-H+exchange and stretch-activated channels underlies the slow inotropic response to stretch in myocytes and muscle from the rat heart

2004 ◽  
Vol 559 (1) ◽  
pp. 205-214 ◽  
Author(s):  
Sarah Calaghan ◽  
Ed White
Keyword(s):  
Rat Heart ◽  
Inotropic Response ◽  
Stretch Activated Channels

Systems analysis of digoxin kinetics and inotropic response in the rat heart: effects of calcium and KB-R7943

2004 ◽  
Vol 287 (4) ◽  
pp. H1857-H1867 ◽  
Author(s):  
Michael Weiss ◽  
Myoungki Baek ◽  
Wonku Kang
Keyword(s):  
Rat Heart ◽  
Site Response ◽  
High Capacity ◽  
Left Ventricular ◽  
Limiting Factor ◽  
Inotropic Response ◽  
Influx Rate ◽  
High Affinity ◽  
Reverse Mode ◽  
Kinetics Of

To gain more insight into the mechanistic processes controlling the kinetics of inotropic response of digoxin in the perfused whole heart, an integrated kinetic model was developed incorporating digoxin uptake, receptor binding (Na+-K+-ATPase inhibition), and cellular events linking receptor occupation and response. The model was applied to data obtained in the single-pass Langendorff-perfused rat heart for external [Ca2+] of 0.5 and 1.5 mM under control conditions and in the presence of the reverse-mode Na+/Ca2+ exchange inhibitor KB-R7943 (0.1 μM) in perfusate. Outflow concentration and left ventricular developed pressure data measured for three consecutive doses (15, 30, and 45 μg) in each heart were analyzed simultaneously. While disposition kinetics of digoxin was determined by interaction with a heterogeneous receptor population consisting of a high-affinity/low-capacity and a low-affinity/high- capacity binding site, response generation was >80% mediated by binding to the high-affinity receptor. Digoxin sensitivity increased at lower external [Ca2+] due to higher stimulus amplification. Coadministration of KB-R7943 significantly reduced the positive inotropic effect of digoxin at higher doses (30 and 45 μg) and led to a saturated and delayed receptor occupancy-response relationship in the cellular effectuation model. The results provide further evidence for the functional heterogeneity of the Na+-K+-ATPase and suggest that in the presence of KB-R7943 a reduction of the Ca2+ influx rate via the reverse mode Na+/Ca2+ exchanger might become the limiting factor in digoxin response generation.

α1-adrenoceptor-mediated formation of glycerophosphoinositol 4-phosphate in rat heart: possible role in the positive inotropic response

1999 ◽  
Vol 58 (9) ◽  
pp. 1437-1446 ◽  
Author(s):  
Patrizia Debetto ◽  
Gabriella Cargnelli ◽  
Marinella Antolini ◽  
Sergio Bova ◽  
Lucia Trevisi ◽  
...  
Keyword(s):  
Rat Heart ◽  
Inotropic Response

24-h Langendorff-perfused neonatal rat heart used to study the impact of adenoviral gene transfer

2003 ◽  
Vol 285 (2) ◽  
pp. H907-H914 ◽  
Author(s):  
S. Wiechert ◽  
A. El-Armouche ◽  
T. Rau ◽  
W. -H. Zimmermann ◽  
T. Eschenhagen
Keyword(s):  
Gene Transfer ◽  
Rat Heart ◽  
Ex Vivo ◽  
Neonatal Rat ◽  
Inotropic Response ◽  
Force Of Contraction ◽  
Test Bed ◽  
Efficient Gene ◽  
Neonatal Rat Heart ◽  
The Impact

The human genome project has increased the demand for simple experimental systems that allow the impact of gene manipulations to be studied under controlled ex vivo conditions. We hypothesized that, in contrast to adult hearts, neonatal hearts allow long-term perfusion and efficient gene transfer ex vivo. A Langendorff perfusion system was modified to allow perfusion for >24 h with particular emphasis on uncompromised contractile activity, sterility, online measurement of force of contraction, inotropic response to β-adrenergic stimulation, and efficient gene transfer. The hearts were perfused with serum-free medium (DMEM + medium 199, 4 + 1) supplemented with hydrocortisone, triiodothyronine, ascorbic acid, insulin, pyruvate, l-carnitine, creatine, taurine, l-glutamine, mannitol, and antibiotics recirculating (500 ml/2 hearts) at 1 ml/min. Hearts from 2 day-old rats beat constantly at 135–155 beats/min and developed active force of 1–2 mN. During 24 h of perfusion, twitch tension increased to ∼165% of initial values ( P < 0.05), whereas the inotropic response to isoprenaline remained constant. A decrease in total protein content of 10% and histological examination indicated moderate edema, but actin and calsequestrin concentration remained unchanged and perfusion pressure remained constant at 7–11 mmHg. Perfusion with a LacZ-encoding adenovirus at 3 × 108 active virus particles yielded homogeneous transfection of ∼80% throughout the heart and did not affect heart rate, force of contraction, or response to isoprenaline compared with uninfected controls ( n = 7 each). Taken together, the 24-h Langendorff-perfused neonatal rat heart is a relatively simple, inexpensive, and robust new heart model that appears feasible as a test bed for functional genomics.

Effect of increased magnesium on recovery from ischemia in rat and rabbit hearts

1982 ◽  
Vol 242 (1) ◽  
pp. H89-H93
Author(s):  
M. M. Bersohn ◽  
K. I. Shine ◽  
W. D. Sterman
Keyword(s):  
Protective Effect ◽  
Rat Heart ◽  
Negative Inotropic Effect ◽  
Ischemic Myocardium ◽  
Inotropic Effect ◽  
Mechanical Function ◽  
Inotropic Response ◽  
Rat Hearts ◽  
Negative Inotropic Response

Perfusates containing high magnesium concentrations have been suggested to have a protective effect for ischemic myocardium, but the mechanism for such an effect is unclear. We investigated the recovery of isolated perfused rabbit and rat hearts from ischemia under varied conditions of increased Mg. Hearts were made ischemic in the presence of normal 1.2 mM Mg or elevated 15 mM Mg. Rabbit hearts, which show minimal alteration in contractility in the presence of 15 mM Mg, were not protected from ischemia by high Mg perfusate. Rat hearts, which have a large negative inotropic response to 15 mM Mg, exhibited significantly better recovery of mechanical function following ischemia in the presence of high Mg than following ischemia with normal Mg. This protective effect was abolished by increasing both Ca and Mg in the perfusate to prevent the decline in contractility that normally occurred with Mg. Reperfusion with 15 mM Mg after ischemia also had no protective effect if the rat heart had been made ischemic in the presence of normal Mg. We conclude that elevated Mg protects ischemic myocardium only under circumstances in which it has a negative inotropic effect before the onset of ischemia, i.e., in the rat heart perfused with normal Ca. These results suggest that the mechanism of protection by high Mg involves sparing of ATP. However, the different responses to Mg of the species studied in these experiments should be a caution against extrapolating such results from rat hearts to other species.

Respective involvements of high- and low- affinity digitalis receptors in the inotropic response of isolated rat heart to ouabain

1986 ◽  
Vol 35 (20) ◽  
pp. 3449-3455 ◽  
Author(s):  
Lionel G. Lelievre ◽  
Danìele Charlemagne ◽  
Christian Mouas ◽  
Bernard Swynghedauw
Keyword(s):  
Rat Heart ◽  
Isolated Rat Heart ◽  
Inotropic Response ◽  
Isolated Rat

Temporal dynamics of inotropic, chronotropic, and metabolic responses during β1- and β2-AR stimulation in the isolated, perfused rat heart

2005 ◽  
Vol 289 (3) ◽  
pp. E412-E418 ◽  
Author(s):  
P. McConville ◽  
R. G. Spencer ◽  
E. G. Lakatta
Keyword(s):  
Rat Heart ◽  
Temporal Dynamics ◽  
High Energy ◽  
Left Ventricular ◽  
Metabolic Responses ◽  
Inotropic Response ◽  
Functional Responses ◽  
Perfused Rat Heart ◽  
Chronotropic Response ◽  
Isolated Perfused Rat Heart

During the β-adrenergic receptor (β-AR)-mediated stress response in the heart, the relations between functional responses and metabolism are ill defined, with the distinction between β1- and β2-AR subtypes creating further complexity. Specific outstanding questions include the temporal relation between inotropic and chronotropic responses and their metabolic correlates. We sought to elucidate the relative magnitudes and temporal dynamics of the response to β1- and β2-AR stimulation and the energy expenditure and bioenergetic state related to these responses in the isolated perfused rat heart. Inotropic [left ventricular developed pressure (LVDP) and dP/d t], chronotropic [heart rate (HR)], and metabolic responses were measured during β1- ( n = 9; agonist: norepinephrine) and β2- ( n = 9; agonist: zinterol) AR stimulation. Myocardial oxygen consumption (MV̇o2) was measured using fiber-optic oximetry, and high-energy phosphate levels and intracellular pH were measured using 31P NMR spectroscopy. A multiple-dose protocol was used, with near-maximal β-AR stimulation at the highest doses. In both β1 and β2 groups, there were dose-dependent increases in LVDP, dP/d t, HR, and MV̇o2. The inotropic response showed more rapid onset, washout, and variation during dose than did the chronotropic response and was closely correlated with MV̇o2. This suggests that the myocardial bioenergetic state is more closely related to the inotropic response than to the chronotropic response. In addition, β1-AR stimulation resulted in a greater magnitude and rate of onset of inotropic and MV̇o2 responses than did β2-AR stimulation during maximal stimulation. However, a similar decrease in intracellular energy charge was seen in the two groups, consistent with a greater rate of oxidative phosphorylation during β1- than during β2-AR stimulation.

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