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.

Ischemia in isolated interventricular septa: mechanical events

1976 ◽  
Vol 231 (4) ◽  
pp. 1225-1232 ◽  
Author(s):  
KI Shine ◽  
AM Douglas ◽  
N Ricchiuti
Keyword(s):  
Nitrogen Atmosphere ◽  
Ischemia And Reperfusion ◽  
Mechanical Function ◽  
Maximal Rate ◽  
Temperature Dependent ◽  
Tension Development ◽  
Time To Peak ◽  
Rate Of Decline ◽  
Rate Limiting ◽  
Mechanical Recovery

Isolated blood-perfused rabbit interventricular septa were adapted for studies of global ischemia by enclosure in a constant-humidity nitrogen atmosphere. During ischemia, developed tension (DT) and maximal rate of relaxation (-dP/dt) declined monoexponentially, lambda = 0.39 min-1 at 37 degrees C and 72 beats/min with a Q10 of 1.4 for DT and a Q10 of 1.9 for -dP/dt. After a 60- to 90-s delay the maximal rate of tension development (+dP/dt) declined at the same rate as DT. Time-to-peak tension (TPT) shortened immediately with ischemia but action potential duration shortened after 60-90 s. Calcium at a concentration of 5 mM slowed the rate of decline of +dP/dt to lambda = 0.26 min-1. Upon reperfusion after 10 min of ischemia the rates of recovery of DT, +dP/dt, and -dP/dt were similar, lambda = 0.21-0.23 min-1, and were not temperature dependent. The magnitude of recovery was 10-17% less at 37 degrees C than 28 degrees C. Potassium at a concentration of 10 mM did not alter the rate of decline of mechanical function, but significantly (P less than 0.01) increased the magnitude of mechanical recovery. The results suggest depletion and/or repletion of single compartments as the rate-limiting steps in ischemia and reperfusion.

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.

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.

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.

scholarly journals SERCA2a gain of function in patient-derived R14Del hiPSC-CMs

2021 ◽  
Vol 154 (9) ◽  
Author(s):  
Beatrice Badone ◽  
Carlotta Ronchi ◽  
Francesco Lodola ◽  
Claudia Maniezzi ◽  
Marem Eskandr ◽  
...  
Keyword(s):  
Functional Data ◽  
Pluripotent Stem Cell ◽  
Protein Localization ◽  
Induced Pluripotent Stem Cell ◽  
Field Stimulation ◽  
Half Time ◽  
Time To Peak ◽  
Activation Mechanisms ◽  
Natural Inhibitor ◽  
Induced Pluripotent

Phospholamban (PLN) is the natural inhibitor of the sarco/endoplasmic reticulum Ca2+ ATPase (SERCA2a). Heterozygous PLN-R14del mutation is associated with an arrhythmogenic dilated cardiomyopathy (DCM), whose pathogenesis has been attributed to SERCA2a “superinhibition.” The aim of the project is to test in human induced pluripotent stem cell–derived cardiomyocytes (hiPSC-CM) harvested from a PLN-R14del carrier whether (1) Ca2+ dynamics and protein localization were compatible with SERCA2a superinhibition and (2) functional abnormalities could be reverted by pharmacological SERCA2a activation with PST3093. Ca2+ transients (CaT) were recorded at 36°C in hiPSC-CMs clusters during field stimulation. SERCA2a and PLN were immunolabeled in single hiPSC-CMs. Mutant (MUT) preparations were compared with isogenic WT ones obtained by mutation reversal. WT and MUT differed for the following properties: (1) CaT time to peak (tpeak) and half-time of CaT decay were shorter in MUT, (2) several CaT profiles were identified in WT, whereas “hyperdynamic” ones largely prevailed in MUT, (3) whereas tpeak rate-dependently declined in WT, it was shorter and rate independent in MUT, and (4) diastolic Ca2+ rate-dependently accumulated in WT, but not in MUT. When applied to WT, PST3093 changed all of the above properties to resemble those of MUT; when applied to MUT, PST3093 had no effect. Preferential perinuclear SERCA2a-PLN localization was lost in MUT hiPSC-CMs. In conclusion, functional data converge to argue for PLN-R14del incompetence in inhibiting SERCA2a in the tested case, thus weakening the rationale for therapeutic SERCA2a activation. Mechanisms alternative to SERCA2a superinhibition should be considered in the pathogenesis of DCM, including dysregulation of Ca2+-dependent transcription.

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.

Pharmacological evidence for two types of myocardial sarcoplasmic reticulum Ca2+ release

1991 ◽  
Vol 260 (3) ◽  
pp. H785-H795
Author(s):  
C. Lynch
Keyword(s):  
Sarcoplasmic Reticulum ◽  
Local Anesthetics ◽  
Papillary Muscles ◽  
Initial Tension ◽  
Tension Development ◽  
Short Cycle ◽  
Peak Tension ◽  
Low Concentrations ◽  
Cycle Lengths ◽  
Initial Delay

Contractions of guinea pig papillary muscles were studied at 37 degrees C under a variety of conditions and stimulation rates that markedly alter the pattern of tension development. When rested-state contractions (RSCs) were enhanced by treatments that increase intracellular adenosine 3',5'-cyclic monophosphate (0.1-1 microM isoproterenol, 1-10 microM forskolin), a markedly enhanced late peak tension developed after a 100-ms delay. Such late peak tension was selectively depressed by local anesthetics (200-400 microM procaine, 4-10 microM tetracaine, or 0.5-1 mM ethyl aminobenzoate). In contrast, 0.1-1 microM ryanodine had little effect on late peak tension, whereas 5 mM caffeine reduced the delay before tension development. Inotropic interventions such as increased external Ca2+ concentration or the Ca2+ channel agonist BAY K 8644 did not elicit such distinct late peaking RSCs. Rapid initial tension development observed under a variety of situations (short cycle lengths, stimulation rates of 0.25 Hz plus isoproterenol, decreased external Na+ concentration) was markedly depressed by 0.01-1 microM ryanodine and by caffeine, whereas local anesthetics had little effect. These results suggest two pharmacologically distinct types of sarcoplasmic reticulum Ca2+ release: 1) Ca2+ that accumulates during prior depolarizations is released immediately upon depolarization and decreased by ryanodine and caffeine; 2) extracellular Ca2+ that enters the myocyte is accumulated and released after an initial delay and is selectively depressed by low concentrations of local anesthetics.

Permeability of mammalian heart capillaries to sucrose and inulin

1964 ◽  
Vol 206 (5) ◽  
pp. 985-991 ◽  
Author(s):  
David E. Schafer ◽  
John A. Johnson
Keyword(s):  
Capillary Permeability ◽  
Perfusion Rate ◽  
Interstitial Diffusion ◽  
Permeability Coefficients ◽  
Ringer’S Solution ◽  
Mammalian Heart ◽  
Maximum Value ◽  
Tissue Content ◽  
Capillary Membrane ◽  
Heart Capillaries

Rabbit hearts were perfused with modified Ringer's solution containing 10 g sucrose or inulin per liter. After various perfusion times, ventricular samples were analyzed for their content of the respective saccharide. The tissue content of sucrose rose to half its apparent maximum value in approximately 6 sec; the corresponding time for inulin was approximately 90 sec. We concluded that at the high perfusion rates employed (40 ml/min per heart) inulin permeation is limited by passage across the capillary membrane and is practically unaffected by perfusion rate and interstitial diffusion, while sucrose permeation is limited partly by passage across the capillary membrane and partly by perfusion rate. We calculated capillary permeability coefficients of 0.4 x 10–5 cm/sec for inulin and 11 x 10–5 cm/sec for sucrose.

Effect of rate changes on strength and time course of contraction of papillary muscle

1963 ◽  
Vol 204 (3) ◽  
pp. 451-457 ◽  
Author(s):  
Jan Koch-Weser
Keyword(s):  
Entire Range ◽  
Maximum Rate ◽  
Time Course ◽  
Normal Development ◽  
Papillary Muscles ◽  
Ventricular Muscle ◽  
High Frequencies ◽  
Peak Tension ◽  
Time To Peak ◽  
Opposing Effect

The influence of 14 frequencies of contraction (between 0.2 and 300 beats/min) on the development of tension and on the time course of contraction was determined in 40 isometrically contracting, isolated cat papillary muscles at 38 C. Only cylindrical muscles with radius <0.43 mm were included, since this was found to be the maximum thickness compatible with normal development of tension at high frequencies. Increases in frequency were associated over the entire range with decreases in the time to peak tension (total 40%) and in the relaxation time (total 49%), and increases in the maximum rate of development of tension (total 560%) and in the peak tension developed (total 340%). These findings indicate that changes in heart rate alter both the degree of activation of the contractile elements and the duration of their active state. It is concluded that the opposing effect of both of these changes must be considered in any analysis of the influence of alterations in rate or rhythm of the heart on the strength of contraction of mammalian ventricular muscle.

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