scholarly journals Inhalation of marijuana affects Drosophila heart function

2018 ◽  
Author(s):  
IM Gómez ◽  
MA Rodríguez ◽  
M Santalla ◽  
G Kassis ◽  
JE Colman Lerner ◽  
...  
Keyword(s):  
Heart Rate ◽  
Drosophila Melanogaster ◽  
Side Effects ◽  
Cardiac Function ◽  
Chronic Exposure ◽  
Genetic Model ◽  
Heart Function ◽  
Scientific Evidence ◽  
Calcium Handling

AbstractMedical uses of marijuana have been recently approved in many countries, and after a long ban on research, there is despicable scientific evidence regarding its action and side effects. We investigated the effect of inhalation of vaporized marijuana on cardiac function in Drosophila melanogaster, a suitable genetic model for assessing cardiovascular function. Chronic exposure of adult flies to vaporized marijuana reduces heart rate, increments contractility and prolongs relaxation. These changes are manifested in the cardiomyocytes with no effect in calcium handling, and in the absence of the canonical cannabinoids receptors identified in mammals. Our results are the first evidence of the in vivo impact of phytocannabinoids in D. melanogaster and open new paths for genetic screenings using vaporized compounds, providing a simple and affordable platform prior to mammalian models.

scholarly journals Adrenergic tone benefits cardiac performance and warming tolerance in two teleost fishes that lack a coronary circulation

2021 ◽  
Author(s):  
Andreas Ekström ◽  
Erika Sundell ◽  
Daniel Morgenroth ◽  
Erik Sandblom
Keyword(s):  
Heart Rate ◽  
Cardiac Function ◽  
High Temperatures ◽  
Oxygen Delivery ◽  
Thermal Tolerance ◽  
Heart Function ◽  
Perca Fluviatilis ◽  
Cardiac Performance ◽  
Adrenergic Stimulation

AbstractTolerance to acute environmental warming in fish is partly governed by the functional capacity of the heart to increase systemic oxygen delivery at high temperatures. However, cardiac function typically deteriorates at high temperatures, due to declining heart rate and an impaired capacity to maintain or increase cardiac stroke volume, which in turn has been attributed to a deterioration of the electrical conductivity of cardiac tissues and/or an impaired cardiac oxygen supply. While autonomic regulation of the heart may benefit cardiac function during warming by improving myocardial oxygenation, contractility and conductivity, the role of these processes for determining whole animal thermal tolerance is not clear. This is in part because interpretations of previous pharmacological in vivo experiments in salmonids are ambiguous and were confounded by potential compensatory increases in coronary oxygen delivery to the myocardium. Here, we tested the previously advanced hypothesis that cardiac autonomic control benefits heart function and acute warming tolerance in perch (Perca fluviatilis) and roach (Rutilus rutilus); two species that lack coronary arteries and rely entirely on luminal venous oxygen supplies for cardiac oxygenation. Pharmacological blockade of β-adrenergic tone lowered the upper temperature where heart rate started to decline in both species, marking the onset of cardiac failure, and reduced the critical thermal maximum (CTmax) in perch. Cholinergic (muscarinic) blockade had no effect on these thermal tolerance indices. Our findings are consistent with the hypothesis that adrenergic stimulation improves cardiac performance during acute warming, which, at least in perch, increases acute thermal tolerance.

Abstract 144: Post-myocardial Infarction Therapeutics Using Cardiovascular Progenitor Cells (PC) Derived from Induced Pluripotent Stem Cells (iPSC)

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Yigang Wang
Keyword(s):  
Cardiac Function ◽  
Heart Function ◽  
Vessel Density ◽  
Protective Effects ◽  
Paracrine Factors ◽  
Beneficial Effects ◽  
The Third ◽  
Simplex Virus ◽  
Patch Group

Objective: We sought to assess the cardiac protective effects after MI of (1) PC differentiated directly into cardiomyocytes (CM) and endothelial cells (EC) to the site of injury, or (2) paracrine factors released from PC. Methods: These concepts were evaluated by using iPSC-derived PC genetically modified to express the herpes simplex virus thymidine kinase (TK) under the control of cardiomyocyte (NCX1) or endothelial cell (VE-cadherin) specific promoters. PC expressing the TK permitted ablation at the first week or the third week by iv ganciclovir (GCV). If GCV applied at the first week, but not at the third week, altered cardiac function, we would conclude that myocardial contractile recovery depends on CM and EC-derived from iPSC. If the beneficial effects on cardiac function persisted after GCV was given at the third week, we would surmise that the PC effect was via by a paracrine action. MI created by ligation of LAD, the cell patch with PC was applied to the scarred myocardium. Rats were treated with GCV at 1 or 3 weeks to ablate implanted PC. Echocardiography, vessel density, and histological analysis were used to obtain endpoints for this study. Result: In vivo : The levels of IGF-1α and VEGF released from ischemic tissues were significant higher in the cell patch group. Heart function, infarction size, and vessel density were significantly improved after cell patch treatment. However, this beneficial effect on cardiac function was completely abolished in the group given GCV at week 1, but only partially abolished in the group given GCV at week 3 compared to the untreated cell patch group. Conclusions: Taken together, these data support our conclusion that iPSC-derived cardiovascular lineages (CM and EC) contribute directly to an improved cardiac performance and attenuated remodeling, and that paracrine factors also play a supporting role in the restoration of heart function after MI.

scholarly journals Age-dependent changes in electrophysiology and calcium handling: implications for pediatric cardiac research

2020 ◽  
Vol 318 (2) ◽  
pp. H354-H365 ◽  
Author(s):  
Luther M. Swift ◽  
Morgan Burke ◽  
Devon Guerrelli ◽  
Marissa Reilly ◽  
Manelle Ramadan ◽  
...  
Keyword(s):  
Heart Rate ◽  
Postnatal Development ◽  
Cardiac Electrophysiology ◽  
Disease Modeling ◽  
Calcium Transient ◽  
Atrioventricular Conduction ◽  
Calcium Handling ◽  
Multiparametric Imaging ◽  
Whole Heart

Rodent models are frequently employed in cardiovascular research, yet our understanding of pediatric cardiac physiology has largely been deduced from more simplified two-dimensional cell studies. Previous studies have shown that postnatal development includes an alteration in the expression of genes and proteins involved in cell coupling, ion channels, and intracellular calcium handling. Accordingly, we hypothesized that postnatal cell maturation is likely to lead to dynamic alterations in whole heart electrophysiology and calcium handling. To test this hypothesis, we employed multiparametric imaging and electrophysiological techniques to quantify developmental changes from neonate to adult. In vivo electrocardiograms were collected to assess changes in heart rate, variability, and atrioventricular conduction (Sprague-Dawley rats). Intact, whole hearts were transferred to a Langendorff-perfusion system for multiparametric imaging (voltage, calcium). Optical mapping was performed in conjunction with an electrophysiology study to assess cardiac dynamics throughout development. Postnatal age was associated with an increase in the heart rate (181 ± 34 vs. 429 ± 13 beats/min), faster atrioventricular conduction (94 ± 13 vs. 46 ± 3 ms), shortened action potentials (APD80: 113 ± 18 vs. 60 ± 17 ms), and decreased ventricular refractoriness (VERP: 157 ± 45 vs. 57 ± 14 ms; neonatal vs. adults, means ± SD, P < 0.05). Calcium handling matured with development, resulting in shortened calcium transient durations (168 ± 18 vs. 117 ± 14 ms) and decreased propensity for calcium transient alternans (160 ± 18- vs. 99 ± 11-ms cycle length threshold; neonatal vs. adults, mean ± SD, P < 0.05). Results of this study can serve as a comprehensive baseline for future studies focused on pediatric disease modeling and/or preclinical testing. NEW & NOTEWORTHY This is the first study to assess cardiac electrophysiology and calcium handling throughout postnatal development, using both in vivo and whole heart models.

Alterations of heart function and Na+-K+-ATPase activity by etomoxir in diabetic rats

1999 ◽  
Vol 86 (3) ◽  
pp. 812-818 ◽  
Author(s):  
Kiminori Kato ◽  
Donald C. Chapman ◽  
Heinz Rupp ◽  
Anton Lukas ◽  
Naranjan S. Dhalla
Keyword(s):  
Heart Rate ◽  
Cardiac Function ◽  
Atpase Activity ◽  
Binding Sites ◽  
Heart Function ◽  
Diabetic Rats ◽  
Left Ventricular ◽  
Carnitine Palmitoyltransferase ◽  
Heart Weight ◽  
High Affinity

To examine the role of changes in myocardial metabolism in cardiac dysfunction in diabetes mellitus, rats were injected with streptozotocin (65 mg/kg body wt) to induce diabetes and were treated 2 wk later with the carnitine palmitoyltransferase inhibitor (carnitine palmitoyltransferase I) etomoxir (8 mg/kg body wt) for 4 wk. Untreated diabetic rats exhibited a reduction in heart rate, left ventricular systolic pressure, and positive and negative rate of pressure development and an increase in end-diastolic pressure. The sarcolemmal Na+-K+-ATPase activity was depressed and was associated with a decrease in maximal density of binding sites (Bmax) value for high-affinity sites for [3H]ouabain, whereas Bmax for low-affinity sites was unaffected. Treatment of diabetic animals with etomoxir partially reversed the depressed cardiac function with the exception of heart rate. The high serum triglyceride and free fatty acid levels were reduced, whereas the levels of glucose, insulin, and 3,3′,-5-triiodo-l-thyronine were not affected by etomoxir in diabetic animals. The activity of Na+-K+-ATPase expressed per gram heart weight, but not per milligram sarcolemmal protein, was increased by etomoxir in diabetic animals. Furthermore, Bmax (per g heart wt) for both low-affinity and high-affinity binding sites in control and diabetic animals was increased by etomoxir treatment. Etomoxir treatment also increased the depressed left ventricular weight of diabetic rats and appeared to increase the density of the sarcolemma and transverse tubular system to normalize Na+-K+-ATPase activity. Therefore, a shift in myocardial substrate utilization may represent an important signal for improving the depressed cardiac function and Na+-K+-ATPase activity in diabetic rat hearts with impaired glucose utilization.

scholarly journals Genetic variation affecting heart rate in Drosophila melanogaster

1999 ◽  
Vol 74 (2) ◽  
pp. 121-128 ◽  
Author(s):  
J. ROBBINS ◽  
R. AGGARWAL ◽  
R. NICHOLS ◽  
G. GIBSON
Keyword(s):  
Heart Rate ◽  
Drosophila Melanogaster ◽  
Heart Function ◽  
Susceptibility Gene ◽  
Natural Populations ◽  
Model Organism ◽  
Genetic Dissection ◽  
Wild Type ◽  
Quantitative Genetic ◽  
Wide Range

Heart rate in pre-pupae of Drosophila melanogaster is shown to vary over a wide range from 2·5 to 3·7 beats per second. Quantitative genetic analysis of a sample of 11 highly inbred lines indicates that approaching one-quarter of the total variance in natural populations can be attributed to genetic differences between flies. A hypomorphic allele of the potassium channel gene ether-a-gogo, which is homologous to a human long-QT syndrome susceptibility gene (HERG), has a heart rate at the low end of the wild-type range, but this effect can be suppressed in certain wild-type genetic backgrounds. This study provides a baseline for investigation of pharmacological and other physiological influences on heart rate in the model organism, and implies that quantitative genetic dissection will provide insight into the molecular basis for variation in normal and arrhythmic heart function.

Isolated hemoperfused heart model of slaughterhouse pigs

2001 ◽  
Vol 24 (4) ◽  
pp. 215-221 ◽  
Author(s):  
D. Modersohn ◽  
S. Eddicks ◽  
C. Grosse-Siestrup ◽  
I. Ast ◽  
S. Holinski ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Heart Function ◽  
Animal Experiments ◽  
Laboratory Animals ◽  
Coronary Perfusion ◽  
Balloon Catheters ◽  
Wide Range ◽  
Infusion Of Norepinephrine

A model of hemoperfused slaughterhouse pighearts is described providing a wide range of applications which leads to a reduction in animal experiments. The size of a pigheart, heart rate, coronary perfusion, metabolism, etc. are more comparable to conditions in patients than those in hearts of small laboratory animals. Global heart function can be assessed either by measuring stroke volume, ejection fraction, Emaxetc. in the working model or by measuring intraventricular pressure with balloon catheters in the isovolumetric model. Regional cardiac function can be measured by sonomicrometry and ischemic and non-ischemic areas can be compared. Local metabolic changes are measurable as well with microdialysis. Cardiac function can be kept on any given functional level by infusion of norepinephrine in spite of the fact that functional parameters are lower without adrenergic drive in vitro than in vivo. Stable heart function can be maintained for several hours with only 500 to 1000 ml of blood because the blood is permanently regenerated by a special dialysis system. This model can be applied in many research projects dealing with reperfusion injuries, inotropic, antiarrhythmic or arrhythmogenic effects of certain drugs, immunological rejection, evaluation of imaging systems (NMR, echocardiography etc.) or cardiac assist devices.

scholarly journals The Intestine of Drosophila melanogaster: An Emerging Versatile Model System to Study Intestinal Epithelial Homeostasis and Host-Microbial Interactions in Humans

2019 ◽  
Vol 7 (9) ◽  
pp. 336 ◽  
Author(s):  
Florence Capo ◽  
Alexa Wilson ◽  
Francesca Di Cara
Keyword(s):  
Drosophila Melanogaster ◽  
Genetic Model ◽  
Current Knowledge ◽  
Cell Lineage ◽  
Model Organism ◽  
Model System ◽  
Microbial Interactions ◽  
Stem Cell Lineage ◽  
Bowel Diseases

In all metazoans, the intestinal tract is an essential organ to integrate nutritional signaling, hormonal cues and immunometabolic networks. The dysregulation of intestinal epithelium functions can impact organism physiology and, in humans, leads to devastating and complex diseases, such as inflammatory bowel diseases, intestinal cancers, and obesity. Two decades ago, the discovery of an immune response in the intestine of the genetic model system, Drosophila melanogaster, sparked interest in using this model organism to dissect the mechanisms that govern gut (patho) physiology in humans. In 2007, the finding of the intestinal stem cell lineage, followed by the development of tools available for its manipulation in vivo, helped to elucidate the structural organization and functions of the fly intestine and its similarity with mammalian gastrointestinal systems. To date, studies of the Drosophila gut have already helped to shed light on a broad range of biological questions regarding stem cells and their niches, interorgan communication, immunity and immunometabolism, making the Drosophila a promising model organism for human enteric studies. This review summarizes our current knowledge of the structure and functions of the Drosophila melanogaster intestine, asserting its validity as an emerging model system to study gut physiology, regeneration, immune defenses and host-microbiota interactions.

Abstract 18382: Rna Splicing Regulated by A2bp1 is Essential for Cardiac Function in Zebrafish

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Karen S Frese ◽  
Benjamin Meder ◽  
Andreas Keller ◽  
Jan Haas ◽  
Steffen Just ◽  
...  
Keyword(s):  
Cardiac Function ◽  
Rna Sequencing ◽  
Functional Role ◽  
Heart Function ◽  
Mrna Splicing ◽  
Complex Nature ◽  
Zebrafish Embryos ◽  
Splicing Regulator

Objective: Alternative splicing (AS) is one of the key mechanisms for the proteomic and functional diversity of eukaryotes. However, the complex nature of AS, its associated regulators and their targets are only partially understood. In the present study we investigated the transcriptomic diversity in the zebrafish heart using RNA-Sequencing and elucidated the functional role of the splicing regulator A2BP1 in vivo. Results: Using RNA-Sequencing we characterized the cardiac transcriptome of 48 hours post fertilization (hpf) old zebrafish embryos and compared the expression of genes and their isoforms to whole fish tissue. Besides the known cardiac genes, we found several previously described genes, highly expressed in cardiac tissue. The analysis of RNA-Seq data indicates that 14% of all genes expressed in the heart undergo AS by single exon-skipping/inclusion. To determine the effect of splicing factors on mRNA splicing we investigated the functional role of splicing regulator a2bp1 in vivo by using the zebrafish as a model organism. Morpholino-mediated a2bp1 knockdown in zebrafish embryos led to progressive cardiac contractile dysfunction, suggesting an important role of a2bp1 in maintenance of cardiac function. Splicing analysis revealed that loss of a2bp1 does not result in a completely splicing failure, but rather alters the splicing pattern of specific target genes. Here we identified novel spliceforms and potentialy novel targets of splicing factor a2bp1. Splice-junction blockage experiments showed that a balanced isoform expression of the targets actn3a, hug, ktn1, ptpla and camk2g is necessary for maintaining cardiac function in zebrafish. We assume, that the a2bp1-knockdown phenotype is not caused by missplicing of specific targets rather by the cumulative effect of many splicing abnormalities. Conclusion: Our study reveal a novel splicing regulator that is necessary for normal heart function. We showed that dysfunction of a2bp1 not only leads to heart failure, but show that a2bp1 mediates the splicing of different transcripts which might mediate the observed phenotype. Our results highlight the importance of balanced mRNA splicing in the heart and represents intriguing opportunities for novel therapeutic approaches.

Relation of glycosylated hemoglobin to in vivo cardiac function in response to dobutamine in spontaneously diabetic BB Wor rats

1994 ◽  
Vol 72 (7) ◽  
pp. 722-727 ◽  
Author(s):  
Tom L. Broderick ◽  
Stephen J. Kopp ◽  
June T. Daar ◽  
Fred D. Romano ◽  
Dennis J. Paulson
Keyword(s):  
Heart Rate ◽  
Cardiac Function ◽  
Metabolic Control ◽  
Contractile Function ◽  
Glycosylated Hemoglobin ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Insulin Dependent ◽  
Myocardial Contractile

The contribution of metabolic control to in vivo myocardial contractile function in response to β1-adrenergic stimulation was determined in the spontaneously diabetic BB Wor rat. The study involved a group of insulin-dependent BB Wor rats showing marked variations in metabolic control, assessed by the level of glycosylated hemoglobin (gHb). These diabetic BB rats were divided into moderate and severe (%gHb > 14) diabetic groups. A group of Wistar rats and diabetes-resistant BB Wor rats served as controls. In vivo myocardial contractile function was measured under basal conditions and after i.v. dobutamine infusions in anesthetized rats, using a catheter-tip pressure transducer inserted into the left ventricle. No dramatic differences in heart rate with dobutamine stimulation were observed between the moderate, severe diabetic, and diabetes-resistant groups. However, heart rate was lower in Wistar control rats compared with these groups. Systolic left ventricular pressure was depressed in severe diabetic rats compared with Wistar controls. In addition, positive dP/dt was significantly less in the severe diabetic group at the highest doses of stimulation, whereas negative dP/dt was depressed under basal conditions and remained so with increasing doses of dobutamine. In the diabetic group maximal systolic left ventricular pressure, rate–pressure product, and negative dP/dt responses to dobutamine were all inversely correlated with gHb. These results indicate that changes in metabolic control of the insulin-dependent BB diabetic rat can contribute to a depressed myocardial contractile function.Key words: glycosylated hemoglobin, cardiac function, dobutamine, BB rat.

KATP channel knockout worsens myocardial calcium stress load in vivo and impairs recovery in stunned heart

2007 ◽  
Vol 292 (4) ◽  
pp. H1706-H1713 ◽  
Author(s):  
Richard J. Gumina ◽  
D. Fearghas O'Cochlain ◽  
Christopher E. Kurtz ◽  
Peter Bast ◽  
Darko Pucar ◽  
...  
Keyword(s):  
Diastolic Pressure ◽  
Gene Knockout ◽  
Heart Function ◽  
Dobutamine Stress ◽  
Left Ventricular ◽  
Calcium Handling ◽  
Rate Pressure Product ◽  
Metabolic Demand ◽  
Male And Female

Gene knockout of the KCNJ11-encoded Kir6.2 ATP-sensitive K+ (KATP) channel implicates this stress-response element in the safeguard of cardiac homeostasis under imposed demand. KATP channels are abundant in ventricular sarcolemma, where subunit expression appears to vary between the sexes. A limitation, however, in establishing the full significance of KATP channels in the intact organism has been the inability to monitor in vivo the contribution of the channel to intracellular calcium handling and the superimposed effect of sex that ultimately defines heart function. Here, in vivo manganese-enhanced cardiac magnetic resonance imaging revealed, under dobutamine stress, a significantly greater accumulation of calcium in both male and female KATP channel knockout (Kir6.2-KO) mice compared with sex- and age-matched wild-type (WT) counterparts, with greatest calcium load in Kir6.2-KO females. This translated, poststress, into a sustained contracture manifested by reduced end-diastolic volumes in KATP channel-deficient mice. In response to ischemia-induced stunning, male and female Kir6.2-KO hearts demonstrated accelerated time to contracture and increased peak contracture compared with WT. The outcome on reperfusion, in both male and female Kir6.2-KO hearts, was a transient reduction in systolic performance, measured as rate-pressure product compared with WT, with protracted increase in left ventricular end-diastolic pressure, exaggerated in female knockout hearts, despite comparable leakage of creatine kinase across groups. Kir6.2-KO hearts were rescued from diastolic dysfunction by agents that target alternative pathways of calcium handling. Thus KATP channel deficit confers a greater susceptibility to calcium overload in vivo, accentuated in female hearts, impairing contractile recovery under various conditions of high metabolic demand.

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