Calcium fluxes and contractility in isolated guinea pig atrium: effect of A23187

1978 ◽  
Vol 235 (1) ◽  
pp. C13-C19 ◽  
Author(s):  
D. R. Holland ◽  
W. M. Armstrong ◽  
M. I. Steinberg
Keyword(s):  
Guinea Pig ◽  
Myocardial Cell ◽  
Ionophore A23187 ◽  
Inotropic Action ◽  
Tension Development ◽  
Peak Tension ◽  
Time To Peak ◽  
Endogenous Histamine ◽  
Resultant Increase ◽  
45Ca Efflux

The Ca2+ ionophore A23187 (10(-6) to 3 X 10(-5) M) increased the force of contraction is isolated guinea pig atria. In individual twitches, peak tension, maximum rate of tension development, time to peak tension, and total twitch duration were all increased by A23187. Tripelennamine, indomethacin, and atropine did not significantly alter the inotropic effect of A23187. Serotonin produced changes in individual twitches that differed qualitatively and quantitatively from those of A23187. Therefore, the inotropic action of A23187 is probably not mediated by release of endogenous histamine, prostaglandins, acetylcholine, or serotonin. 45Ca influx and efflux were increased by A23187. The enhanced 45Ca efflux exceeded that which would be predicted if the ionophore acted only to increase the passive Ca2+ permeability of the myocardial cell membrane. These results suggest that A23187 facilitates the entry of extracellular Ca2+ into the myocardial cell and the release of intracellular Ca2+ stores into the myoplasm. The resultant increase in intracellular Ca2+ activity could account for the positive inotropic action of A23187.

Effect of hypoxia on mechanical function in the neonatal mammalian heart

1978 ◽  
Vol 235 (5) ◽  
pp. H469-H474 ◽  
Author(s):  
J. M. Jarmakani ◽  
M. Nakazawa ◽  
T. Nagatomo ◽  
G. A. Langer
Keyword(s):  
Glycolytic Pathway ◽  
Mechanical Function ◽  
Maximal Rate ◽  
Half Time ◽  
Perfusion Rate ◽  
Tension Development ◽  
Peak Tension ◽  
Time To Peak ◽  
Newborn Rabbit ◽  
Mammalian Heart

The effect of 30 min of hypoxia followed by reoxygenation on mechanical function was studied in isolated, arterially perfused, neonatal rabbit and dog hearts. All studies were performed at a perfusion rate of 2.5 ml/g-min, at a pacing rate of 60 beats/min and at 27 degrees C. The muscles were perfused with Krebs-Henseleit solutions equilibrated with 95% O2 and 5% CO2 (control) or 95% N2 and 5% CO2 (hypoxia). In the newborn rabbit and dog, both the developed tension (DT) and the maximal rate of tension development (dT/dtmax+) decreased during the first 3 min of hypoxia and then recovered to values not different from control. The effect of hypoxia on DT and dT/dtmax+ was inversely related to age in both the rabbit and dog. The equations describing the decline in DT and dT/dTmax+ during hypoxia and the recovery during reoxygenation were best expressed by two or three exponentials. Time to peak tension and half time to relaxation decreased during hypoxia and the decrease was also inversely related to age. The fact that the newborn was able to maintain normal mechanical function during hypoxia suggests that the newborn is capable of maintaining normal myocardial ATP levels due to enhanced flux through the glycolytic pathway.

Inhibition by theophylline of the early component of canine ventricular contraction

1982 ◽  
Vol 242 (3) ◽  
pp. H349-H358
Author(s):  
M. Endoh ◽  
T. Iijima ◽  
S. Motomura
Keyword(s):  
Mechanical Characteristics ◽  
Calcium Influx ◽  
Myocardial Cell ◽  
Ventricular Muscle ◽  
Late Component ◽  
Ventricular Contraction ◽  
Early Component ◽  
Peak Tension ◽  
Time To Peak ◽  
Plateau Potential

Changes in mechanical characteristics of the isolated canine ventricular muscle were investigated during interaction of isoproterenol with theophylline or caffeine. An early and a late component with time to peak tension of 80 and 150 ms, respectively, were differentiated in a single contraction of the muscle stimulated at 0.5 Hz at 37 degrees C during the interaction of isoproterenol and theophylline, or isoproterenol and caffeine. Isoproterenol increased preferentially the early component and affected only slightly the late one. Theophylline or caffeine elevated the early component less than the late one. In the presence of theophylline + isoproterenol or caffeine + isoproterenol the peak tension was achieved by a late component, whereas the increase in the early one induced by isoproterenol in 3 X 10(-7) M and higher was depressed significantly. During the interaction the rate of twitch relaxation was accelerated further rather than depressed. Changes in action potential indicate that the calcium influx via the myocardial cell membrane during depolarization was increased: the peak plateau potential was significantly elevated by theophylline alone and further by theophylline + isoproterenol. These results indicate that theophylline and caffeine (2 mM) may act intracellularly to inhibit the isoproterenol-induced promotion of the early component without impairing the isoproterenol-induced acceleration of relaxation in the canine ventricular muscle.

Chronic verapamil treatment attenuates the negative inotropic effect of ethanol in diabetic rat myocardium

1994 ◽  
Vol 72 (9) ◽  
pp. 1013-1018 ◽  
Author(s):  
Ricardo A. Brown ◽  
Prashant Bhasin ◽  
Adedapo O. Savage ◽  
Joseph C. Dunbar
Keyword(s):  
Negative Inotropic Effect ◽  
Left Ventricular ◽  
Inotropic Effect ◽  
Diabetic Rat ◽  
Tension Development ◽  
Altered Expression ◽  
Peak Tension ◽  
Time To Peak ◽  
Diabetic Myocardium

It is well established that cardiomyopathy is a consistent feature of diabetic myocardium and that alcohol consumption increases the risk of cardiovascular disease among diabetic subjects. The objective of this investigation was to determine whether acute or chronic verapamil treatment attenuates the negative inotropic effect of ethanol (EtOH) in the diabetic rat heart. Wistar rats were made diabetic with streptozotocin (55 mg/kg, iv). Left-ventricular papillary muscles, from normal and diabetic (8 weeks) rats, were superfused with Tyrode's solution at 30 °C while driven at 0.5 Hz. A subgroup of diabetic and normal animals received daily injections of verapamil (8 mg/kg, ip; 8 weeks), whereas muscles from untreated animals were exposed to verapamil (2 μM) in vitro. Peak tension developed (PTD), time to peak tension (TPT), time to 90% relaxation (RT90), and the maximum velocities of tension development (+VT) and decay (−VT) were determined in the absence and presence of clinically relevant concentrations of EtOH (80–240 mg/dL, i.e., 17.4–52.1 mM). Ethanol at 80 mg/dL reduced PTD, + VT, and −VT only in preparations from diabetic animals. Higher concentrations of EtOH (120–240 mg/dL) decreased PTD, TPT, +VT, and −VT. The negative inotropic effect of EtOH (240 mg/dL) was attenuated only in diabetic myocardium chronically treated with verapamil, whereas acute verapamil treatment potentiated the negative inotropic effect of EtOH in both normal and diabetic myocardium. Thus, chronic verapamil therapy diminishes the negative inotropic effect of EtOH in diabetic myocardium and acute verapamil treatment exaggerates it. Altered expression of membrane-bound calcium channels may be involved in the negative inotropic response to EtOH in long-term diabetes.Key words: ethanol, papillary muscle, inotropism, myocardium, force of contraction, diabetes mellitus.

Comparison of the response of muskrat, rabbit, and guinea pig heart muscle to hypoxia

1982 ◽  
Vol 243 (3) ◽  
pp. R245-R250
Author(s):  
T. McKean ◽  
R. Landon
Keyword(s):  
Heart Rate ◽  
Blood Flow ◽  
Guinea Pig ◽  
Coronary Blood Flow ◽  
Guinea Pigs ◽  
Cell Damage ◽  
Isolated Heart ◽  
Ether Anesthesia ◽  
Peak Tension ◽  
Time To Peak

Papillary muscles were removed from anesthetized muskrats and rabbits and mounted in a muscle chamber maintained at 29 degrees C. Muscles were stimulated at a rate of 12/min and subjected to 30 min of hypoxia followed by 30 min of reoxygenation. Peak tension in muskrats declined less than peak tension in rabbits during oxygen deprivation. During reoxygenation, peak tension in muskrats rapidly returned to control levels and then exceeded control, whereas peak tension in rabbits never recovered. Time to peak tension was largely unaffected in muskrats during hypoxia and decreased in rabbits. During reoxygenation, time to peak tension increased in muskrats and returned to control in rabbits. Hearts from muskrats and guinea pigs were removed under ether anesthesia and perfused retrograde with a physiological saline solution. Developed tension, heart rate, coronary blood flow, and lactate dehydrogenase (LDH) output were monitored. During 30 min of hypoxia, muskrat hearts developed a profound bradycardia compared to guinea pigs. Coronary flow increased in both species but less so in muskrats. Guinea pig hearts developed contracture whereas muskrat hearts relaxed. During reoxygenation heart rate and coronary blood flow returned toward normal but cells released large amounts of LDH, indicating cell damage. It is concluded that the isolated heart of the muskrat, a diving mammal, is better able to deal with hypoxia than the heart of the nondividing guinea pig and rabbit.

scholarly journals Active State in Heart Muscle

1967 ◽  
Vol 50 (3) ◽  
pp. 661-676 ◽  
Author(s):  
Edmund H. Sonnenblick
Keyword(s):  
Heart Muscle ◽  
Mechanical Response ◽  
Electrical Stimulus ◽  
Isometric Tension ◽  
Maximum Intensity ◽  
Active State ◽  
Tension Development ◽  
Peak Tension ◽  
Time To Peak ◽  
Time Required

The course of active state in heart muscle has been analyzed using a modified quick release method. The onset of maximum active state was found to be delayed, requiring 110–500 msec from time of stimulation, while the time to peak isometric tension required 250–650 msec. Further, the time from stimulation to peak tension was linearly related to the time required to establish maximum intensity of active state as well as to the duration of maximum active state. The duration of maximum active state was prolonged (90–220 msec), occupying most of the latter half of the rising phase of the isometric contraction. Norepinephrine (10-5 M) shortened the latency from electrical stimulus to mechanical response, accelerated the onset of maximum active state, increased its intensity, decreased its duration, and accelerated its rate of decline. These changes were accompanied by an increase in the rate of tension development and the tension developed while the time from stimulation to peak isometric tension was abbreviated. Similar findings were shown for strophanthidin (1 µg/ml) although lesser decrements in the duration of maximum active state and time to peak tension were found than with norepinephrine for similar increments in the maximum intensity of active state.

scholarly journals Depolarization-contraction coupling in short frog muscle fibers. A voltage clamp study.

1984 ◽  
Vol 84 (1) ◽  
pp. 133-154 ◽  
Author(s):  
C Caputo ◽  
F Bezanilla ◽  
P Horowicz
Keyword(s):  
Muscle Fibers ◽  
Tension Development ◽  
Contraction Coupling ◽  
Maximum Tension ◽  
Peak Tension ◽  
Relaxation Phase ◽  
Time To Peak ◽  
Intracellular Ca ◽  
Charge Movements ◽  
Internal Potential

Short muscle fibers (1.5 mm) were dissected from hindlimb muscles of frogs and voltage clamped with two microelectrodes to study phenomena related to depolarization-contraction coupling. Isometric myograms obtained in response to depolarizing pulses of durations between 10 and 500 ms and amplitudes up to 140 mV had the following properties. For suprathreshold pulses of fixed duration (in the range of 20-100 ms), the peak tension achieved, the time to peak tension, and contraction duration increased as the internal potential was made progressively more positive. Peak tension eventually saturates with increasing internal potentials. For pulse durations of greater than or equal to 50 ms, the rate of tension development becomes constant for increasing internal potentials when peak tensions become greater than one-third of the maximum tension possible. Both threshold and maximum steepness of the relation between internal potential and peak tension depend on pulse duration. The relation between the tension-time integral and the stimulus amplitude-duration product was examined. The utility of this relation for excitation-contraction studies is based on the observation that once a depolarizing pulse configuration has elicited maximum tension, further increases in either stimulus duration or amplitude only prolong the contractile response, while the major portion of the relaxation phase after the end of a pulse is exponential, with a time constant that is not significantly affected by either the amplitude or the duration of the pulse. Hence, the area under the tension-response curve provides a measure of the availability to troponin of the calcium released from the sarcoplasmic reticulum in response to membrane depolarization. The results from this work complement those obtained in experiments in which intramembrane charge movements related to contractile activation were studied and those in which intracellular Ca++ transients were measured.

Characterization of positive inotropic effect of colforsin dapropate hydrochloride, a water-soluble forskolin derivative, in isolated adult rat cardiomyocytes

1999 ◽  
Vol 77 (4) ◽  
pp. 225-234 ◽  
Author(s):  
Rikako Miyake ◽  
Hiroyuki Yoshida ◽  
Kouichi Tanonaka ◽  
Yuki Miyamoto ◽  
Hideharu Hayashi ◽  
...  
Keyword(s):  
Calcium Transient ◽  
Water Soluble ◽  
Inotropic Action ◽  
Shortening Velocity ◽  
Adult Rats ◽  
Camp Content ◽  
Rat Cardiomyocytes ◽  
Positive Inotropic Action ◽  
Time To Peak ◽  
Rate Of Increase

The present study was undertaken to characterize the positive inotropic action of colforsin dapropate hydrochloride (NKH477), a novel water-soluble forskolin derivative, on isolated cardiomyocytes of adult rats. Simultaneous measurements of cellular contraction and intracellular calcium concentration ([Ca2+]i) were carried out. The effects of isoprenaline and ouabain on these parameters were also determined for comparison. The contraction and maximum [Ca2+]i of NKH477-, isoprenaline-, or ouabain-treated cells were increased concentration dependently. Peak shortening of NKH477-treated cells was positively correlated with the shortening velocity and inversely with the time to peak shortening. Maximum, but not minimum, [Ca2+]i in NKH477-treated cells was correlated with the rate of increase in [Ca2+]i and inversely with the time to maximum [Ca2+]i. Similar results were obtained with isoprenaline. In contrast, ouabain increased both maximum and minimum [Ca2+]i. Treatment with either NKH477 or isoprenaline increased cellular cAMP content, but treatment with ouabain did not. These results suggest that the positive inotropic action of NKH477 is associated with an increase in [Ca2+]i and acceleration of its kinetics.Key words: adenylate cyclase, calcium transient, colforsin dapropate, isoprenaline, ouabain.

Inotropic Action and Myocardial Uptake of Digoxin and Betamethyldigoxin in Isolated Guinea Pig Atria

2009 ◽  
Vol 40 ◽  
pp. 545-552 ◽  
Author(s):  
Hannu Allonen ◽  
Esko Iisalo ◽  
Jussi Kanto ◽  
Kalevi Pihlajamäki
Keyword(s):  
Guinea Pig ◽  
Myocardial Uptake ◽  
Inotropic Action ◽  
Guinea Pig Atria
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