Effect of Ouabain in Therapeutic Concentrations on K+ Exchange and Contraction of Human and Rabbit Myocardium

1979 ◽  
Vol 57 (5) ◽  
pp. 415-420 ◽  
Author(s):  
P. A. Poole-Wilson ◽  
E. Galindez ◽  
C. H. Fry
Keyword(s):  
Positive Inotropic Effect ◽  
Sodium Pump ◽  
Interventricular Septum ◽  
Human Myocardium ◽  
Papillary Muscles ◽  
Ventricular Muscle ◽  
No Net Loss ◽  
Rabbit Myocardium

1. Experiments were undertaken on strips of human atrial and ventricular muscle, on right ventricular rabbit papillary muscles and on the rabbit interventricular septum. 2. In all preparations an increase of developed tension after 30 min exposure to ouabain was apparent only at or above a concentration of 10−7 mol/l (73 μg/l). 3. In the rabbit septum there was a net loss of potassium on exposure to ouabain if the concentration was greater than 10−7 mol/l. There was no net loss, or gain, of potassium at lower concentrations. Loss of potassium, indicating inhibition of the sodium pump, could not be dissociated from the positive inotropic effect of ouabain. 4. The greater sensitivity to ouabain of human myocardium in vivo (10−8 mol/l) than in vitro (10−7 mol/l) may be due to cellular changes occurring in isolated preparations.

Metabolic importance of Na+/K+-ATPase activity during sea urchin development.

1997 ◽  
Vol 200 (22) ◽  
pp. 2881-2892 ◽  
Author(s):  
P Leong ◽  
D Manahan
Keyword(s):  
Enzyme Activity ◽  
Atpase Activity ◽  
Sea Urchin ◽  
Sodium Pump ◽  
Sea Water ◽  
Strongylocentrotus Purpuratus ◽  
Lytechinus Pictus ◽  
Stimulation Of

Early stages of animal development have high mass-specific rates of metabolism. The biochemical processes that establish metabolic rate and how these processes change during development are not understood. In this study, changes in Na+/K+-ATPase activity (the sodium pump) and rate of oxygen consumption were measured during embryonic and early larval development for two species of sea urchin, Strongylocentrotus purpuratus and Lytechinus pictus. Total (in vitro) Na+/K+-ATPase activity increased during development and could potentially account for up to 77 % of larval oxygen consumption in Strongylocentrotus purpuratus (pluteus stage) and 80 % in Lytechinus pictus (prism stage). The critical issue was addressed of what percentage of total enzyme activity is physiologically active in living embryos and larvae and thus what percentage of metabolism is established by the activity of the sodium pump during development. Early developmental stages of sea urchins are ideal for understanding the in vivo metabolic importance of Na+/K+-ATPase because of their small size and high permeability to radioactive tracers (86Rb+) added to sea water. A comparison of total and in vivo Na+/K+-ATPase activities revealed that approximately half of the total activity was utilized in vivo. The remainder represented a functionally active reserve that was subject to regulation, as verified by stimulation of in vivo Na+/K+-ATPase activity in the presence of the ionophore monensin. In the presence of monensin, in vivo Na+/K+-ATPase activities in embryos of S. purpuratus increased to 94 % of the maximum enzyme activity measured in vitro. Stimulation of in vivo Na+/K+-ATPase activity was also observed in the presence of dissolved alanine, presumably due to the requirement to remove the additional intracellular Na+ that was cotransported with alanine from sea water. The metabolic cost of maintaining the ionic balance was found to be high, with this process alone accounting for 40 % of the metabolic rate of sea urchin larvae (based on the measured fraction of total Na+/K+-ATPase that is physiologically active in larvae of S. purpuratus). Ontogenetic changes in pump activity and environmentally induced regulation of reserve Na+/K+-ATPase activity are important factors that determine a major proportion of the metabolic costs of sea urchin development.

Demonstration of hysteresis in refractoriness of canine ventricular myocardium

1988 ◽  
Vol 255 (6) ◽  
pp. H1342-H1348
Author(s):  
C. Giorgi ◽  
M. Vermeulen ◽  
R. Cardinal ◽  
P. Savard ◽  
R. Nadeau ◽  
...  
Keyword(s):  
Pulse Width ◽  
Cycle Length ◽  
Ventricular Myocardium ◽  
Ventricular Muscle ◽  
Cycle Lengths ◽  
Long Pulse ◽  
Basic Cycle Length ◽  
Canine Ventricular Myocardium

The properties and determinants of hysteresis during ventricular effective refractory period (VERP) measurements by an extrastimulus technique were determined in 15 anesthetized open-chest dogs as well as in isolated ventricular muscle (n = 6). VERP was determined both by decreasing the S1-S2 interval and also by increasing S1S2. Hysteresis was then calculated by subtracting the VERP obtained with the decreasing S1S2 from the VERP obtained with the increasing S1S2. The effects of basic cycle length, pulse width, stimulation intensity, and the number of basic drives on VERP and hysteresis were evaluated. VERP was shorter for long pulse width, high stimulation intensities, and shorter basic cycle lengths. These modifications were not associated with significant changes of hysteresis. VERP was shorter during decreasing S1S2 than during increasing S1S2. Hysteresis was greater with 6 basic drive cycles than with 12 (P less than 0.001) in both in vivo and in vitro preparations. The data suggest that 1) hysteresis occurs during VERP measurements; 2) hysteresis is independent of stimulation modality; and 3) hysteresis decreases with the number of basic drive cycles.

Myocardial mechanics predict hemodynamic performance during normal function and alcohol-induced dysfunction in rats

1991 ◽  
Vol 261 (6) ◽  
pp. H1880-H1888
Author(s):  
J. M. Capasso ◽  
P. Li ◽  
P. Anversa
Keyword(s):  
Pressure Rise ◽  
Normal Function ◽  
Left Ventricular ◽  
Isometric Tension ◽  
Papillary Muscles ◽  
Least Squares Regression ◽  
Tension Development ◽  
Myocardial Mechanics

To determine whether mechanical evaluation of muscle tissue removed from the myocardium can be employed as a direct indicator of cardiac contractile performance in situ, isometric and isotonic parameters of muscle mechanics in vitro were correlated with in vivo global functional characteristics of the same heart. Twelve-month-old animals maintained on standard food and water were employed as representative of normal cardiac function. Animals of identical age with left ventricular (LV) dysfunction induced by oral alcohol (30%) ingestion from 4 to 12 mo were utilized to represent depressed cardiac performance. Accordingly, 24 h after the establishment of the hemodynamic profile for a control or experimental heart, the LV posterior papillary muscle was removed from the same heart and examined isometrically and isotonically. Least squares regression analysis was employed to establish a correlation coefficient and P values between various in vitro and in vivo parameters. Hemodynamic measurements were performed under chloral hydrate anesthesia and LV pump performance was evaluated with respect to aortic and ventricular pressures and the rates of rise and decay of the LV pressure trace. Papillary muscles were evaluated with respect to timing parameters of the isometric and isotonic twitch, the first derivative of isometric tension development, and the speed of muscle shortening at increasing physiologic loads. LV peak rate of pressure rise and decay were then correlated with the various isometric and isotonic properties. Myocardial mechanics and hemodynamics revealed depressed function in the papillary muscles and hearts from alcoholic rats. Moreover, significant correlations were found between the LV rate of pressure change (peak +dP/dt and -dP/dt) and both isometric and isotonic twitch measurements.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequency-force relationships of mammalian ventricular muscle in vivo and in vitro

1976 ◽  
Vol 230 (3) ◽  
pp. 631-636 ◽  
Author(s):  
ML Kahn ◽  
F Kavaler ◽  
VJ Fisher
Keyword(s):  
Heart Rate ◽  
Left Ventricle ◽  
Room Temperature ◽  
Physiological Role ◽  
Ventricular Muscle ◽  
Contractile State ◽  
Force Relationship

The change in contractility with increasing heart rate was studied in the left ventricle of dogs and in isolated trabeculae carneae of cats. For some of the studies in situ a transient isovolumic state was created by aortic occlusion. At physiological temperatures the frequency-force relationship is flatter than at room temperature and at the same temperature it is flatter in vivo than in vitro. The frequency-(dF/dt)max relationship is steeper than the frequency-force relationship at both temperatures in vivo and in vitro. The frequency-(dF/dt)max relationship is steeper in vitro than it is in situ, although the discrepancy is less marked than in the case of the frequency-force relationship. It is concluded that "staircase" plays less of a physiological role in adjustment of contractile state in situ than might be inferred from studies of isolated tissue.

scholarly journals Regional variation and differential sensitivity of rat heart protein synthesis in vivo and in vitro

1985 ◽  
Vol 225 (2) ◽  
pp. 487-492 ◽  
Author(s):  
V R Preedy ◽  
D M Smith ◽  
N F Kearney ◽  
P H Sugden
Keyword(s):  
Protein Synthesis ◽  
Regional Variation ◽  
Subcellular Fractionation ◽  
Differential Sensitivity ◽  
Ventricular Muscle ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
The Right

In vivo, fractional rates of protein synthesis in atrial muscle of hearts taken from fed rats were 70% greater than in ventricular muscle. After 3 days starvation, atrial protein synthesis is inhibited, but the inhibition is less than in ventricles. A crude subcellular fractionation of the aqueous homogenates by centrifugation at 32000g showed that the supernatant and precipitate proteins were synthesized at the same rate in the ventricles. The fractional rates of protein synthesis and RNA/protein ratios in the right ventricle were 10% greater than in the left ventricle. Protein synthesis in both of these regions was inhibited equally by starvation. In vitro, rates of protein synthesis in atria and ventricles of anterogradely perfused rat hearts were stimulated by saturating insulin concentrations and were inhibited by starvation, but the effects in atria were smaller than in ventricles. Rates of protein synthesis in atria in vitro were 80-95% of rates in vivo. The heart therefore shows considerable regional variation in rates of protein synthesis in vivo and in vitro, and the sensitivity of protein synthesis in the various regions to interventions such as insulin and starvation differs.

Novel in vivo and in vitro mechanisms of positive inotropic effect of atractylodin

2020 ◽  
Author(s):  
Li Gao ◽  
Yuwei Wang ◽  
Wenhui Zhang ◽  
Xiaojia Zhu ◽  
Qianwen Gao ◽  
...  
Keyword(s):  
Positive Inotropic Effect ◽  
Inotropic Effect

scholarly journals Characterization of an in vitro model for the study of the short and prolonged effects of myocardial ischaemia and reperfusion in man

2000 ◽  
Vol 99 (5) ◽  
pp. 443-453 ◽  
Author(s):  
Jin-Gang ZHANG ◽  
Sudip GHOSH ◽  
Colin D. OCKLEFORD ◽  
Manuel GALIÑANES
Keyword(s):  
Myocardial Ischaemia ◽  
In Vitro Model ◽  
Human Myocardium ◽  
Right Atrial ◽  
Tissue Viability ◽  
Ischaemia And Reperfusion ◽  
Mtt Reduction ◽  
Vitro Model

The mechanisms underlying myocardial ischaemia and reperfusion-induced injury have been investigated, mainly by using animal experimental preparations in vitro and in vivo, but little is known of the process in human myocardium. The present studies characterize an in vitro model using human myocardium for the study of early and delayed effects of ischaemia and reperfusion. The right atrial appendage was manually sliced and incubated in buffer through which was bubbled O2/CO2 (19:1, v/v) for various time periods. Lactate dehydrogenase (LDH) leakage, 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl-2H-tetrazolium bromide (MTT) reduction, oxygen consumption, nucleotide levels and tissue morphology were all investigated as markers of myocardial injury. The specimens remained stable and viable up to 24 h, but had significantly deteriorated by 48 h. The preparation responded to ischaemia in a time-related manner. Tissue viability was reduced by 25% after 30 min ischaemia, declined to 60% after 60 min ischaemia and to 75% after 120 min ischaemia. Interestingly, the tissue was more susceptible when ischaemia was induced after 24 h of aerobic incubation. The effects of the duration of reperfusion were investigated after a fixed 60 min ischaemic insult. The results of LDH leakage suggest that reperfusion injury is mainly sustained within the first 2 h of reperfusion. However, the results of MTT reduction show that there is a progressive decrease in tissue viability over the 24 h reperfusion period, possibly reflecting the occurrence of tissue necrosis and apoptosis at different reperfusion times. In conclusion, the data provide evidence that the incubation of human atrial tissue in vitro is stable, and slices are viable for at least 24 h, which permits the study of early and delayed consequences of ischaemia and reperfusion in the human myocardium.

scholarly journals Rates of protein turnover in vivo and in vitro in ventricular muscle of hearts from fed and starved rats

1984 ◽  
Vol 222 (2) ◽  
pp. 395-400 ◽  
Author(s):  
V R Preedy ◽  
D M Smith ◽  
N F Kearney ◽  
P H Sugden
Keyword(s):  
Protein Synthesis ◽  
Protein Degradation ◽  
Protein Turnover ◽  
Synthesis Rate ◽  
Protein Synthesis Rate ◽  
Ventricular Muscle ◽  
Degradation Rates ◽  
Perfused Hearts

Starvation of 300 g rats for 3 days decreased ventricular-muscle total protein content and total RNA content by 15 and 22% respectively. Loss of body weight was about 15%. In glucose-perfused working rat hearts in vitro, 3 days of starvation inhibited rates of protein synthesis in ventricles by about 40-50% compared with fed controls. Although the RNA/protein ratio was decreased by about 10%, the major effect of starvation was to decrease the efficiency of protein synthesis (rate of protein synthesis relative to RNA). Insulin stimulated protein synthesis in ventricles of perfused hearts from fed rats by increasing the efficiency of protein synthesis. In vivo, protein-synthesis rates and efficiencies in ventricles from 3-day-starved rats were decreased by about 40% compared with fed controls. Protein-synthesis rates and efficiencies in ventricles from fed rats in vivo were similar to values in vitro when insulin was present in perfusates. In vivo, starvation increased the rate of protein degradation, but decreased it in the glucose-perfused heart in vitro. This contradiction can be rationalized when the effects of insulin are considered. Rates of protein degradation are similar in hearts of fed animals in vivo and in glucose/insulin-perfused hearts. Degradation rates are similar in hearts of starved animals in vivo and in hearts perfused with glucose alone. We conclude that the rates of protein turnover in the anterogradely perfused rat heart in vitro closely approximate to the rates in vivo in absolute terms, and that the effects of starvation in vivo are mirrored in vitro.

The importance of nervous and humoral mechanisms in the control of cardiac performance in the Atlantic cod Gadus morhua at rest and during non-exhaustive exercise

1988 ◽  
Vol 137 (1) ◽  
pp. 287-301 ◽  
Author(s):  
M. Axelsson
Keyword(s):  
Heart Rate ◽  
Cardiac Output ◽  
Stroke Volume ◽  
Gadus Morhua ◽  
Positive Inotropic Effect ◽  
Atlantic Cod ◽  
Inotropic Effect ◽  
Response Curves

The nervous regulation of heart rate and stroke volume in the Atlantic cod Gadus morhua was investigated both in vivo, during rest and exercise, and in vitro. The cholinergic and adrenergic influences on the heart were estimated in experiments with injections of atropine and sotalol. At rest the cholinergic and adrenergic tonus on the heart were 38% and 21%, respectively (ratio 1.81:1). At the end of an exercise period, the cholinergic tonus had decreased to 15% but the adrenergic tonus had increased to 28% (ratio 0.54:1). The results suggest that variation of the cholinergic tonus on the heart is a major factor in the regulation of the heart rate. In one group of fish, cardiac output was also measured, allowing calculation of stroke volume. Cardiac output increased significantly during exercise, and this effect persisted in the presence of both atropine and sotalol, although the increase in heart rate was reduced or abolished. The persisting increase in cardiac output during exercise is due to an increase in stroke volume, reflecting a Starling relationship. In the presence of the adrenergic neurone-blocking agent bretylium, a positive inotropic effect on isolated, paced atrial and ventricular strips was observed. In the atrial preparations the effect persisted after 24 h. The effect was prevented by pretreatment with sotalol or cocaine, but potentiated by phentolamine pretreatment. This shows that bretylium exerts its neurone-blocking action after being taken up into the adrenergic nerves, and suggests that the positive inotropic effect of bretylium observed in vivo is due to release of endogenous catecholamines. The concentration-response curves for adrenaline on isolated spontaneously beating atrial preparations showed that the concentrations of catecholamines necessary to produce appreciable effects on the heart are higher than the concentrations found in cod plasma during ‘stress’ situations (handling and exhaustive swimming).

The energetics of rat papillary muscles undergoing realistic strain patterns

2001 ◽  
Vol 204 (21) ◽  
pp. 3765-3777
Author(s):  
L. J. Mellors ◽  
C. J. Barclay
Keyword(s):  
Muscle Length ◽  
Mechanical Efficiency ◽  
Male Rats ◽  
Papillary Muscles ◽  
Work Output ◽  
Muscle Energetics ◽  
Relaxation Period ◽  
Muscle Dynamics

SUMMARYStudies of cardiac muscle energetics have traditionally used contraction protocols with strain patterns that bear little resemblance to those observed in vivo. This study aimed to develop a realistic strain protocol, based on published in situ measurements of contracting papillary muscles, for use with isolated preparations. The protocol included the three phases observed in intact papillary muscles: an initial isometric phase followed by isovelocity shortening and re-lengthening phases. Realistic papillary muscle dynamics were simulated in vitro (27°C) using preparations isolated from the left ventricle of adult male rats. The standard contraction protocol consisted of 40 twitches at a contraction rate of 2 Hz. Force, changes in muscle length and changes in muscle temperature were measured simultaneously. To quantify the energetic costs of contraction, work output and enthalpy output were determined, from which the maximum net mechanical efficiency could be calculated. The most notable result from these experiments was the constancy of enthalpy output per twitch, or energy cost, despite the various alterations made to the protocol. Changes in mechanical efficiency, therefore, generally reflected changes in work output per twitch. The variable that affected work output per twitch to the greatest extent was the amplitude of shortening, while changes in the duration of the initial isometric phase had little effect. Decreasing the duration of the shortening phase increased work output per twitch without altering enthalpy output per twitch. Increasing the contraction frequency from 2 to 3 Hz resulted in slight decreases in the work output per twitch and in efficiency. Using this realistic strain protocol, the maximum net mechanical efficiency of rat papillary muscles was approximately 15 %. The protocol was modified to incorporate an isometric relaxation period, thus allowing the model to simulate the main mechanical features of ventricular function.

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