Short-term hibernation in adult cardiomyocytes is Po 2 dependent and Ca2+mediated

2001 ◽  
Vol 280 (1) ◽  
pp. H42-H50 ◽  
Author(s):  
Thomas Stumpe ◽  
Jürgen Schrader
Keyword(s):  
Contractile Activity ◽  
Substantial Reduction ◽  
Observation Time ◽  
Energy Status ◽  
Short Term ◽  
Rat Cardiomyocytes ◽  
Lactate Release ◽  
State Observation ◽  
Myocardial Hibernation ◽  
Intracellular Ca

The mechanism of myocardial hibernation, the reversible downregulation of contractile activity on reduction of coronary flow with unchanged cardiac energetics, is presently not understood. The oxygen consumption (V˙o 2), shortening fraction (Δ L), energy status [phosphocreatine (PCr), ATP, and adenosine and lactate release], and free intracellular Ca2+ concentration ([Ca2+]i) were measured in isolated rat cardiomyocytes at precisely controlled ambient Po 2 (Oxystat). When Po 2was reduced from 25 to 6 mmHg, V˙o 2decreased by 50%, while Δ L was downregulated from 11.2 ± 4.1 to 7.6 ± 4.0%, and energy status was unchanged in the steady state (observation time 12 min). Only transiently PCr decreased, and lactate and adenosine release increased. Further reduction of Po 2 (to 3 mmHg) reducedV˙o 2 by 80%, decreased PCr by 35%, moderately increased adenosine and lactate release, and progressively reduced Δ L by 50% (to 5.6 ± 3.3%). All parameters fully recovered during reoxygenation. Po 2-dependent downregulation of Δ Lwas accompanied by a progressive reduction in systolic [Ca2+]i (from 512 ± 110 to 357 ± 91 nmol/l at 6 mmHg and to 251 ± 69 nmol/l at 3 mmHg), whereas diastolic free [Ca2+]i remained unchanged. Therefore, the mechanism of the reversible, Po 2-dependent downregulation of contractile activity (myocardial hibernation) involves a substantial reduction of systolic calcium.

scholarly journals Silica nanoparticles induce cardiotoxicity interfering with energetic status and Ca2+ handling in adult rat cardiomyocytes

2017 ◽  
Vol 312 (4) ◽  
pp. H645-H661 ◽  
Author(s):  
Carlos Enrique Guerrero-Beltrán ◽  
Judith Bernal-Ramírez ◽  
Omar Lozano ◽  
Yuriana Oropeza-Almazán ◽  
Elena Cristina Castillo ◽  
...  
Keyword(s):  
Silica Nanoparticles ◽  
Glutathione Depletion ◽  
Energy Status ◽  
Adrenergic Stimulation ◽  
Rat Cardiomyocytes ◽  
Atp Production ◽  
Adult Rat ◽  
Intracellular Ca ◽  
Rat Myocytes ◽  
Potential Risks

Recent evidence has shown that nanoparticles that have been used to improve or create new functional properties for common products may pose potential risks to human health. Silicon dioxide (SiO2) has emerged as a promising therapy vector for the heart. However, its potential toxicity and mechanisms of damage remain poorly understood. This study provides the first exploration of SiO2-induced toxicity in cultured cardiomyocytes exposed to 7- or 670-nm SiO2 particles. We evaluated the mechanism of cell death in isolated adult cardiomyocytes exposed to 24-h incubation. The SiO2 cell membrane association and internalization were analyzed. SiO2 showed a dose-dependent cytotoxic effect with a half-maximal inhibitory concentration for the 7 nm (99.5 ± 12.4 µg/ml) and 670 nm (>1,500 µg/ml) particles, which indicates size-dependent toxicity. We evaluated cardiomyocyte shortening and intracellular Ca2+ handling, which showed impaired contractility and intracellular Ca2+ transient amplitude during β-adrenergic stimulation in SiO2 treatment. The time to 50% Ca2+ decay increased 39%, and the Ca2+ spark frequency and amplitude decreased by 35 and 21%, respectively, which suggest a reduction in sarcoplasmic reticulum Ca2+-ATPase (SERCA) activity. Moreover, SiO2 treatment depolarized the mitochondrial membrane potential and decreased ATP production by 55%. Notable glutathione depletion and H2O2 generation were also observed. These data indicate that SiO2 increases oxidative stress, which leads to mitochondrial dysfunction and low energy status; these underlie reduced SERCA activity, shortened Ca2+ release, and reduced cell shortening. This mechanism of SiO2 cardiotoxicity potentially plays an important role in the pathophysiology mechanism of heart failure, arrhythmias, and sudden death. NEW & NOTEWORTHY Silica particles are used as novel nanotechnology-based vehicles for diagnostics and therapeutics for the heart. However, their potential hazardous effects remain unknown. Here, the cardiotoxicity of silica nanoparticles in rat myocytes has been described for the first time, showing an impairment of mitochondrial function that interfered directly with Ca2+ handling.

Increased calcium loading and inotropy without greater cell death in hypoxic rat cardiomyocytes

1998 ◽  
Vol 275 (6) ◽  
pp. H2272-H2282 ◽  
Author(s):  
Richard P. Kondo ◽  
Carl S. Apstein ◽  
Franz R. Eberli ◽  
Douglas L. Tillotson ◽  
Thomas M. Suter
Keyword(s):  
Cell Death ◽  
High Glucose ◽  
Deleterious Effect ◽  
Cell Injury ◽  
Contractile Function ◽  
Short Term ◽  
Rat Cardiomyocytes ◽  
Metabolic Substrate ◽  
Calcium Loading ◽  
Intracellular Ca

To test whether contractile function in “hypoxic” myocytes treated with high glucose (19.5 mM) can be improved by increasing intracellular Ca2+ without accelerating cell contracture or death, we challenged metabolically inhibited, paced myocytes with high extracellular Ca2+ concentration ([Ca2+]o) and measured simultaneously cell shortening and intracellular Ca2+ concentration ([Ca2+]i). NaCN exposure at a physiological [Ca2+]olevel (1.2 mM) caused a decline of contractile function to 58 ± 8% of the pre-NaCN value ( P < 0.001) but increased systolic and diastolic [Ca2+]iby 104 ± 17 and 37 ± 9% above baseline ( P < 0.01), respectively. Consequent doubling of [Ca2+]oto 2.4 mM, in the presence of NaCN, immediately restored contractile function, and twitch amplitude after 18 min was 123 ± 14% ( P < 0.001) of baseline pre-NaCN values, whereas systolic [Ca2+]iincreased further to 225 ± 63% ( P< 0.05) and diastolic [Ca2+]ito 73 ± 16% above baseline ( P < 0.01). This marked increase in [Ca2+]ihad no deleterious effect on myocyte diastolic function or survival. These results suggest that if adequate metabolic substrate is provided, contractile function in metabolically inhibited, hypoxic myocytes can be restored by increasing [Ca2+]iwithout causing short-term cell injury.

scholarly journals WALANT–Epinephrine injection may lead to short term, reversible episodes of critical oxygen saturation in the fingertips

2021 ◽  
Vol 141 (3) ◽  
pp. 527-533
Author(s):  
P. Moog ◽  
M. Dozan ◽  
J. Betzl ◽  
I. Sukhova ◽  
H. Kükrek ◽  
...  
Keyword(s):  
Blood Flow ◽  
Oxygen Saturation ◽  
Substantial Reduction ◽  
Tissue Perfusion ◽  
Critical Levels ◽  
Short Term ◽  
Doppler Flowmetry ◽  
Epinephrine Injection ◽  
Venous Oxygen Saturation

Abstract Introduction Although the WALANT technique’s long-term safeness has been demonstrated in many studies, there are only few data investigating its short-term effects on tissue perfusion and oxygen levels. It was hypothesized that, temporarily, critical levels of tissue perfusion may occur. Methods Seventeen patients, who were scheduled for different procedures in WALANT technique, were injected with 5–7 ml of 1% Articain containing 1:200,000 epinephrine at the finger base. Capillary-venous oxygen saturation, hemoglobin volume in the capillaries, and relative blood flow in the fingertips were recorded once per second by white light spectrometry and laser Doppler flowmetry before, during and after injection for an average of 32 min. Results Clinically, no persistent tissue malperfusion was observed, and there were no postoperative complications. Capillary-venous oxygen saturation was reduced by ≥ 30% in seven patients. Critical levels of oxygen saturation were detected in four patients during 13 intervals, each lasting for 132.5 s on average. Oxygen saturation returned to noncritical values in all patients by the end of the observation period. Blood flow in the fingertips was reduced by more than 30% in nine patients, but no critical levels were observed, as with the hemoglobin. Three patients demonstrated a reactive increase in blood flow of more than 30% after injection. Conclusions Injection of tumescent local anesthesia containing epinephrine into finger base may temporarily cause a substantial reduction in blood flow and lead to critical levels of oxygen saturation in the fingertips. However, this was fully reversible within minutes and does not cause long-term complications.

scholarly journals IP3R1 regulates Ca2+ transport and pyroptosis through the NLRP3/Caspase-1 pathway in myocardial ischemia/reperfusion injury

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Guixi Mo ◽  
Xin Liu ◽  
Yiyue Zhong ◽  
Jian Mo ◽  
Zhiyi Li ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Cell Model ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Caspase 1 ◽  
Intracellular Ca ◽  
Myocardial Ischemia Reperfusion

AbstractIntracellular ion channel inositol 1,4,5-triphosphate receptor (IP3R1) releases Ca2+ from endoplasmic reticulum. The disturbance of IP3R1 is related to several neurodegenerative diseases. This study investigated the mechanism of IP3R1 in myocardial ischemia/reperfusion (MI/R). After MI/R modeling, IP3R1 expression was silenced in myocardium of MI/R rats to explore its role in the concentration of myocardial enzymes, infarct area, Ca2+ level, NLRP3/Caspase-1, and pyroptosis markers and inflammatory factors. The adult rat cardiomyocytes were isolated and cultured to establish hypoxia/reperfusion (H/R) cell model. The expression of IP3R1 was downregulated or ERP44 was overexpressed in H/R-induced cells. Nifedipine D6 was added to H/R-induced cells to block Ca2+ channel or Nigericin was added to activate NLRP3. IP3R1 was highly expressed in myocardium of MI/R rats, and silencing IP3R1 alleviated MI/R injury, reduced Ca2+ overload, inflammation and pyroptosis in MI/R rats, and H/R-induced cells. The binding of ERP44 to IP3R1 inhibited Ca2+ overload, alleviated cardiomyocyte inflammation, and pyroptosis. The increase of intracellular Ca2+ level caused H/R-induced cardiomyocyte pyroptosis through the NLRP3/Caspase-1 pathway. Activation of NLRP3 pathway reversed the protection of IP3R1 inhibition/ERP44 overexpression/Nifedipine D6 on H/R-induced cells. Overall, ERP44 binding to IP3R1 inhibits Ca2+ overload, thus alleviating pyroptosis and MI/R injury.

Cross-bridge cycling gives rise to spatiotemporal heterogeneity of dynamic subcellular mechanics in cardiac myocytes probed with atomic force microscopy

2010 ◽  
Vol 298 (3) ◽  
pp. H853-H860 ◽  
Author(s):  
Evren U. Azeloglu ◽  
Kevin D. Costa
Keyword(s):  
Contractile Activity ◽  
Major Axis ◽  
Neonatal Rat ◽  
Pharmacological Treatments ◽  
Rat Cardiomyocytes ◽  
Force Microscopy ◽  
Cross Bridge ◽  
Apparent Modulus ◽  
Atomic Force ◽  
And Function

To study how the dynamic subcellular mechanical properties of the heart relate to the fundamental underlying process of actin-myosin cross-bridge cycling, we developed a novel atomic force microscope elastography technique for mapping spatiotemporal stiffness of isolated, spontaneously beating neonatal rat cardiomyocytes. Cells were indented repeatedly at a rate close but unequal to their contractile frequency. The resultant changes in pointwise apparent elastic modulus cycled at a predictable envelope frequency between a systolic value of 26.2 ± 5.1 kPa and a diastolic value of 7.8 ± 4.1 kPa at a representative depth of 400 nm. In cells probed along their major axis, spatiotemporal changes in systolic stiffness displayed a heterogeneous pattern, reflecting the banded sarcomeric structure of underlying myofibrils. Treatment with blebbistatin eliminated contractile activity and resulted in a uniform apparent modulus of 6.5 ± 4.8 kPa. This study represents the first quantitative dynamic mechanical mapping of beating cardiomyocytes. The technique provides a means of probing the micromechanical effects of disease processes and pharmacological treatments on beating cardiomyocytes, providing new insights and relating subcellular cardiac structure and function.

Urea hydrolysis and inorganic N in a Luvisol after application of fertiliser containing rare-earth elements

Soil Research ◽  
2003 ◽  
Vol 41 (4) ◽  
pp. 741 ◽  
Author(s):  
Xingkai Xu ◽  
Zijian Wang ◽  
Yuesi Wang ◽  
Kazuyuki Inubushi
Keyword(s):  
Rare Earth ◽  
Rare Earths ◽  
Substantial Reduction ◽  
Application Rate ◽  
Urea Hydrolysis ◽  
High Rate ◽  
Short Term ◽  
N Content ◽  
N Fertilisers ◽  
Hydrolysis Of

In recent decades, Chinese agriculturists have used rare-earth-containing fertilisers as basal fertilisers together with N fertilisers (e.g. urea). We studied urea hydrolysis and its hydrolysis products in a laboratory experiment using urea-N fertiliser with rare earths at rates from 0.5 to 50% (w/w). The results indicated that application of rare earths at a high rate could result in a short-term inhibition of urea hydrolysis and an increase in soil (NH4+ + NO3– + NO2–)-N content. When the application rate of rare earths was higher than 5% of the applied urea-N (corresponding to 10 mg/kg soil), soil exchangeable NH4+-N content increased significantly following the hydrolysis of the applied urea. Increasing the application rate of rare earths appeared to reduce the content of soil urea-derived (NO3– + NO2–)-N. A substantial reduction in soil pH was found immediately after application of rare earths and urea. We conclude that application of rare earths at >10 mg/kg may lead to a substantial increase in the content of urea-derived N in the soil, via the inhibition of urea hydrolysis and nitrification.

Effects of ischemia and myogenic activity on active and passive mechanical properties of rat cerebral arteries

2002 ◽  
Vol 283 (6) ◽  
pp. H2268-H2275 ◽  
Author(s):  
Rebecca J. Coulson ◽  
Naomi C. Chesler ◽  
Lisa Vitullo ◽  
Marilyn J. Cipolla
Keyword(s):  
Contractile Activity ◽  
Cerebral Arteries ◽  
Biomechanical Properties ◽  
Short Term ◽  
Mechanical Stiffness ◽  
Middle Cerebral Arteries ◽  
Male Wistar Rats ◽  
Myogenic Activity ◽  
Activity Dependent

Passive (papaverine induced) and active (spontaneous pressure induced) biomechanical properties of ischemic and nonischemic rat middle cerebral arteries (MCAs) were studied under pressurized conditions in vitro. Ischemic (1 h of occlusion), contralateral, and sham-operated control MCAs were isolated from male Wistar rats ( n = 22) and pressurized using an arteriograph system that allowed control of transmural pressure (TMP) and measurement of lumen diameter and wall thickness. Three mechanical stiffness parameters were computed: overall passive stiffness (β), pressure-dependent modulus changes ( E inc,p), and smooth muscle cell (SMC) activity-dependent changes ( E inc,a). The β-value for ischemic vessels was increased compared with sham vessels (13.9 ± 1.7 vs. 9.1 ± 1.4, P < 0.05), indicating possible short-term remodeling due to ischemia. E inc,p increased with pressure in the passive vessels ( P < 0.05) but remained relatively constant in the active vessels for all vessel types, indicating that pressure-induced SMC contractile activity (i.e., myogenic reactivity) in cerebral arteries leads to the maintenance of a constant elastic modulus within the autoregulatory pressure range. E inc,a increased with pressure for all conditions, signifying that changes in stiffness are influenced by SMC activity and vascular tone.

A model of low-flow ischemia and reperfusion in single, beating adult cardiomyocytes

1999 ◽  
Vol 277 (2) ◽  
pp. H788-H798 ◽  
Author(s):  
Thane G. Maddaford ◽  
Cecilia Hurtado ◽  
Salisha Sobrattee ◽  
Michael P. Czubryt ◽  
Grant N. Pierce
Keyword(s):  
Contractile Activity ◽  
Ischemia Reperfusion ◽  
Lactate Concentration ◽  
Low Flow ◽  
Ischemia And Reperfusion ◽  
Ischemic Insult ◽  
Oxygen Derived Free Radicals ◽  
Adult Cardiomyocytes ◽  
Intracellular Ca ◽  
Two Parameters

The present study was undertaken to comprehensively characterize low-flow ischemia and reperfusion in single adult cardiomyocytes and to determine whether it is important to control contractile activity. The ischemia-mimetic solution was hypoxic, acidic (pH 6.0), and deficient in glucose but contained elevated KCl. Cardiomyocytes were stimulated to contract throughout ischemia and during reperfusion with control perfusate. After the ischemia-reperfusion insult, cells exhibited poor recovery of active cell shortening, a decrease in passive cell length, increased frequency of necrosis, lower ATP content, and evidence of the generation of oxygen-derived free radicals within the cells. Intracellular lactate concentration increased, pH decreased, and Ca2+ transients were depressed during the ischemic insult, but the latter two parameters recovered partially on reperfusion. Basal intracellular Ca2+ concentration was elevated during ischemia and early into reperfusion. Recovery was attenuated in cells that were electrically stimulated to contract throughout ischemia. The duration of ischemia, stimulation frequency, and composition of the ischemia-mimetic solution were important variables. The inclusion of 10 mM lactate in the ischemia-mimetic solution significantly aggravated all the parameters examined above. Our data demonstrate that 1) an ischemia-mimetic solution administered to single, isolated adult cardiomyocytes can reproduce many of the responses observed in whole hearts, 2) caution should be used in adding lactate to an ischemic solution, and 3) it is important to stimulate contractile activity throughout ischemia to reproduce the effects of ischemia in whole hearts.

Long- and Short-Term Regulation of the Na+-K+-Pump in Skeletal Muscle

Physiology ◽  
1996 ◽  
Vol 11 (1) ◽  
pp. 24-30 ◽  
Author(s):  
T Clausen
Keyword(s):  
Skeletal Muscle ◽  
Muscle Activity ◽  
Contractile Activity ◽  
Short Term ◽  
Hormonal Stimulation ◽  
Growth And Nutrition ◽  
Force Recovery ◽  
Contractile Performance ◽  
Stimulation Of

In skeletal muscle, activity and capacity of the Na+ -K+ pump are controlled by several hormones, contractile activity, growth, and nutrition. Acute or chronic reduction of the pump capacity inhibits contractile performance. Conversely, acute hormonal stimulation of the Na+ -K+ pump leads to marked, rapid force recovery in muscles where contractility is suppressed by high extracellular K+.

scholarly journals Different Densities of Na-Ca Exchange Current in T-Tubular and Surface Membranes and Their Impact on Cellular Activity in a Model of Rat Ventricular Cardiomyocyte

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
M. Pásek ◽  
J. Šimurda ◽  
G. Christé
Keyword(s):  
Action Potential ◽  
Transport Systems ◽  
Duration Of Action ◽  
Rat Cardiomyocytes ◽  
Adult Rat ◽  
Before And After ◽  
Action Potential Waveform ◽  
Intracellular Ca ◽  
Tubular Membranes ◽  
Potential Waveform

The ratio of densities of Na-Ca exchanger current (INaCa) in the t-tubular and surface membranes (INaCa-ratio) computed from the values ofINaCaand membrane capacitances (Cm) measured in adult rat ventricular cardiomyocytes before and after detubulation ranges between 1.7 and 25 (potentially even 40). Variations of action potential waveform and of calcium turnover within this span of theINaCa-ratio were simulated employing previously developed model of rat ventricular cell incorporating separate description of ion transport systems in the t-tubular and surface membranes. The increase ofINaCa-ratio from 1.7 to 25 caused a prolongation of APD (duration of action potential at 90% repolarisation) by 12, 9, and 6% and an increase of peak intracellular Ca2+transient by 45, 19, and 6% at 0.1, 1, and 5 Hz, respectively. The prolonged APD resulted from the increase ofINaCadue to the exposure of a larger fraction of Na-Ca exchangers to higher Ca2+transients under the t-tubular membrane. The accompanying rise of Ca2+transient was a consequence of a higher Ca2+load in sarcoplasmic reticulum induced by the increased Ca2+cycling between the surface and t-tubular membranes. However, the reason for large differences in theINaCa-ratio assessed from measurements in adult rat cardiomyocytes remains to be explained.

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