In vitro Measurements of Oxygen Consumption of Human Heart Muscle

Nature ◽  
1963 ◽  
Vol 197 (4869) ◽  
pp. 802-803
Author(s):  
J. N. NORMAN ◽  
T. A. DOUGLAS ◽  
G. SMITH ◽  
C. HENDERSON
Keyword(s):  
Oxygen Consumption ◽  
Heart Muscle ◽  
Human Heart ◽  
In Vitro Measurements

scholarly journals Modelling and Simulation for Preclinical Cardiac Safety Assessment of Drugs with Human iPSC-Derived Cardiomyocytes

2020 ◽  
Vol 122 (4) ◽  
pp. 209-257 ◽  
Author(s):  
Philipp Kügler
Keyword(s):  
Drug Safety ◽  
Heart Muscle ◽  
Cardiac Electrophysiology ◽  
Human Heart ◽  
Cardiac Activity ◽  
Muscle Cells ◽  
Estimation Methods ◽  
Proarrhythmic Risk ◽  
Heart Muscle Cells

Abstract As a potentially life threatening side effect, pharmaceutical compounds may trigger cardiac arrhythmias by impeding the heart’s electrical and mechanical function. For this reason, any new compound needs to be tested since 2005 for its proarrhythmic risk both during the preclinical and the clinical phase of the drug development process. While intensive monitoring of cardiac activity during clinical tests with human volunteers constitutes a major cost factor, preclinical in vitro tests with non cardiac cells and in vivo tests with animals are currently under serious debate because of their poor extrapolation to drug cardiotoxicity in humans. For about five years now, regulatory agencies, industry and academia are working on an overhaul of the cardiac drug safety paradigm that is built a) on human heart muscle cells, that can be abundantly bioengineered from donor stem cells without ethical concerns (human induced pluripotent stem cell derived cardiomyocytes, hiPSC-CMs), and b) on computational models of human cardiac electrophysiology both at the cellular and the organ level. The combined use of such human in vitro and human in silico models during the preclinical phase is expected to improve proarrhythmia test specificity (i.e. to lower the false-positive rate), to better inform about the need of thorough heart monitoring in the clinic, and to reduce or even replace animal experiments. This review article starts by concisely informing about the electrical activity of the human heart, about its possible impairment due to drug side effects, and about hiPSC-CM assays for cardiac drug safety testing. It then summarizes the mathematical description of human cardiac electrophysiology in terms of mechanistic ODE and PDE models, and illustrates how their numerical analysis may provide insight into the genesis of drug induced arrhythmias. Finally, this paper surveys proarrhythmic risk estimation methods, that involve the simulation of human heart muscle cells, and addresses opportunities and challenges for future interdisciplinary research.

Effects of epinephrines on metabolism and contraction of cat papillary muscle

1964 ◽  
Vol 206 (3) ◽  
pp. 525-530 ◽  
Author(s):  
Kwang Soo Lee ◽  
Dai Hyun Yu
Keyword(s):  
Oxygen Consumption ◽  
Papillary Muscle ◽  
Heart Muscle ◽  
Mechanical Efficiency ◽  
Metabolic Efficiency ◽  
Metabolic State ◽  
Cat Papillary Muscle ◽  
Sympathomimetic Amines ◽  
Tissue Contents

The change of metabolic state and contractility of heart induced by epinephrine and norepinephrine was studied in in vitro preparations of cat papillary muscle. The oxygen consumption, glycogen content, energy-rich phosphate content, and contractility of muscles were measured simultaneously whenever possible by techniques described previously. It was found that these amines did not change significantly the tissue contents of energy-rich phosphate compounds and glycogen in these conditions. The oxygen consumption and contractility of muscles were markedly influenced by the sympathomimetic amines. The change of metabolic efficiency as measured by the ratio, contractile tension : total Qo2, following the administration of these amines were dependent on the condition of heart muscles at the time of administration of these agents. Thus, when muscles were fresh, the metabolic efficiency was not significantly changed by the amines. However, when muscles were in the hypodynamic state, the amines were found to increase the metabolic efficiency of the heart muscle significantly. This suggests that the metabolic state of heart muscle should be taken into consideration whenever the influence of these sympathomimetic amines on the mechanical efficiency of heart is investigated.

Oxygen Consumption of Post-Mortem Human Heart Muscle.

1958 ◽  
Vol 99 (1) ◽  
pp. 246-247
Author(s):  
W. C. Ullrick ◽  
E. A. Lentini ◽  
S. C. Sommers
Keyword(s):  
Oxygen Consumption ◽  
Heart Muscle ◽  
Human Heart ◽  
Post Mortem

IN VITRO EFFECTS OF ETOMIDATE ON THE CONTRACTILITY OF FAILING HUMAN HEART MUSCLE

1998 ◽  
Vol 89 (Supplement) ◽  
pp. 186A
Author(s):  
Juraj Sprung ◽  
Monique O. Hughes ◽  
Christine S. Moravec
Keyword(s):  
Heart Muscle ◽  
Human Heart ◽  
In Vitro Effects

Picosecond acoustics in vegetal cells: Non-invasive in vitro measurements at a sub-cell scale

Ultrasonics ◽  
2010 ◽  
Vol 50 (2) ◽  
pp. 202-207 ◽  
Author(s):  
B. Audoin ◽  
C. Rossignol ◽  
N. Chigarev ◽  
M. Ducousso ◽  
G. Forget ◽  
...  
Keyword(s):  
Non Invasive ◽  
In Vitro Measurements

scholarly journals Necrostatin-1 Supplementation to Islet Tissue Culture Enhances the In-Vitro Development and Graft Function of Young Porcine Islets

2021 ◽  
Vol 22 (16) ◽  
pp. 8367
Author(s):  
Hien Lau ◽  
Shiri Li ◽  
Nicole Corrales ◽  
Samuel Rodriguez ◽  
Mohammadreza Mohammadi ◽  
...  
Keyword(s):  
Tissue Culture ◽  
Oxygen Consumption ◽  
Insulin Secretion ◽  
Oxygen Consumption Rate ◽  
Consumption Rate ◽  
In Vitro Development ◽  
Porcine Islets ◽  
Vitro Development

Pre-weaned porcine islets (PPIs) represent an unlimited source for islet transplantation but are functionally immature. We previously showed that necrostatin-1 (Nec-1) immediately after islet isolation enhanced the in vitro development of PPIs. Here, we examined the impact of Nec-1 on the in vivo function of PPIs after transplantation in diabetic mice. PPIs were isolated from pancreata of 8–15-day-old, pre-weaned pigs and cultured in media alone, or supplemented with Nec-1 (100 µM) on day 0 or on day 3 of culture (n = 5 for each group). On day 7, islet recovery, viability, oxygen consumption rate, insulin content, cellular composition, insulin secretion capacity, and transplant outcomes were evaluated. While islet viability and oxygen consumption rate remained high throughout 7-day tissue culture, Nec-1 supplementation on day 3 significantly improved islet recovery, insulin content, endocrine composition, GLUT2 expression, differentiation potential, proliferation capacity of endocrine cells, and insulin secretion. Adding Nec-1 on day 3 of tissue culture enhanced the islet recovery, proportion of delta cells, beta-cell differentiation and proliferation, and stimulation index. In vivo, this leads to shorter times to normoglycemia, better glycemic control, and higher circulating insulin. Our findings identify the novel time-dependent effects of Nec-1 supplementation on porcine islet quantity and quality prior to transplantation.

scholarly journals Oxygen consumption in mouse skeletal muscles stimulated Na-permeability in vitro

1989 ◽  
Vol 49 ◽  
pp. 169
Author(s):  
Hideto Awano ◽  
Tetsuya Hasegawa ◽  
Masakazu Nishimura ◽  
Osamu Yagasaki ◽  
Katsuaki Ito
Keyword(s):  
Oxygen Consumption ◽  
Skeletal Muscles ◽  
Na Permeability

Proximal tubule dysfunction in cystine-loaded tubules: effect of phosphate and metabolic substrates

1996 ◽  
Vol 271 (3) ◽  
pp. F717-F722
Author(s):  
G. Bajaj ◽  
M. Baum
Keyword(s):  
Oxygen Consumption ◽  
Proximal Tubule ◽  
Tricarboxylic Acid Cycle ◽  
Dimethyl Ester ◽  
Proximal Tubules ◽  
Intracellular Atp ◽  
Metabolic Substrates ◽  
Rate Of Oxygen Consumption ◽  
Intracellular Phosphate

Intracellular cystine loading by use of cystine dimethyl ester (CDME) results in a generalized inhibition in proximal tubule transport due, in part, to a decrease in intracellular ATP. The present study examined the importance of phosphate and metabolic substrates in the proximal tubule dysfunction produced by cystine loading. Proximal tubule intracellular phosphorus was 1.8 +/- 0.1 in control tubules and 1.1 +/- 0.1 nmol/mg protein in proximal tubules incubated in vitro with CDME P < 0.001). Infusion of sodium phosphate in rabbits and subsequent incubation of proximal tubules with a high-phosphate medium attenuated the decrease in proximal tubule respiration and prevented the decrease in intracellular ATP with cystine loading. Tricarboxylic acid cycle intermediates have been shown to preserve oxidative metabolism in phosphate-depleted proximal tubules. In proximal tubules incubated with either 1 mM valerate or butyrate, there was a 42 and 34% reduction (both P < 0.05) in the rate of oxygen consumption with cystine loading. However, tubules incubated with 1 mM succinate or citrate had only a 13 and 14% P = NS) reduction in the rate of oxygen consumption, respectively. These data are consistent with a limitation of intracellular phosphate in the pathogenesis of the proximal tubule dysfunction with cystine loading.

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