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Articles 1 - 17 of 17
Full-Text Articles in Life Sciences
Ketone Body Metabolism In The Ischemic Heart, Stephen C. Kolwicz Jr.
Ketone Body Metabolism In The Ischemic Heart, Stephen C. Kolwicz Jr.
Health and Exercise Physiology Faculty Publications
Ketone bodies have been identified as an important, alternative fuel source in heart failure. In addition, the use of ketone bodies as a fuel source has been suggested to be a potential ergogenic aid for endurance exercise performance. These findings have certainly renewed interest in the use of ketogenic diets and exogenous supplementation in an effort to improve overall health and disease. However, given the prevalence of ischemic heart disease and myocardial infarctions, these strategies may not be ideal for individuals with coronary artery disease. Although research studies have clearly defined changes in fatty acid and glucose metabolism during ischemia …
Reactive Oxygen Species Damage And Consequences For Mitochondrial Function In The Hibernating Thirteen-Lined Ground Squirrel, Ictidomys Tridecemlineatus, Brynne Duffy
Electronic Thesis and Dissertation Repository
Hibernators experience changes in blood flow, similar to ischemia-reperfusion injury, which may lead to oxidative damage. I hypothesized that suppression of mitochondrial metabolism during hibernation protects against such damage. I compared oxidative damage and antioxidant capacity in tissues and isolated liver mitochondria among summer, torpid, and interbout euthermic thirteen-lined ground squirrels (TLGS). I found less oxidative tissue damage during summer than hibernation, but no mitochondrial differences. I also compared metabolic activity of isolated mitochondria before and after five minutes of anoxia, followed by reoxygenation, among hibernation states and rats. Anoxia-reoxygenation decreased state-three respiration (ST3) in all groups, with rat mitochondria …
The Effect Of Anoxia On Mitochondrial Function In A Hibernator (Ictidomys Tridecemlineatus), Leah Hayward
The Effect Of Anoxia On Mitochondrial Function In A Hibernator (Ictidomys Tridecemlineatus), Leah Hayward
Electronic Thesis and Dissertation Repository
Hibernation protects mammalian tissues against ischemia-reperfusion injury, but the underlying biochemical mechanisms are unknown. I hypothesized that the mechanisms allowing for mitochondrial metabolic flexibility during hibernation permit anoxia tolerance and contribute to tissue ischemia-reperfusion tolerance. I assessed mitochondrial performance before and after five minutes of anoxia in liver mitochondria isolated from thirteen-lined ground squirrels. I compared this anoxia effect among animals that were summer active (SA), or during hibernation (in torpor or interbout euthermia; IBE). Anoxia decreased state 3 respiration in all groups, but mitochondria isolated from torpid squirrels were least affected; these decreases paralleled decreased activity of electron transport …
Role Of Ataxia-Telangiectasia Mutated Kinase In Cardiac Autophagy And Glucose Metabolism Under Ischemic Conditions, Patsy Thrasher
Role Of Ataxia-Telangiectasia Mutated Kinase In Cardiac Autophagy And Glucose Metabolism Under Ischemic Conditions, Patsy Thrasher
Electronic Theses and Dissertations
Ataxia-telangiectasia mutated kinase (ATM), a serine/threonine kinase primarily located in the nucleus, is typically activated in response to DNA damage. Individuals with mutations in ATM gene develop a disease called Ataxia telangiectasia (AT). These individuals are more susceptible to ischemic heart disease and metabolic disorder. Our lab has previously shown that ATM plays a critical role in β-adrenergic receptor (β-AR) - and myocardial infarction (MI)-stimulated myocyte apoptosis and cardiac remodeling. This study tested the hypothesis that ATM plays a critical role in cardiac autophagy and glucose metabolism following MI and ischemia, respectively. Early during MI (4 hours after its onset) …
Hydrogen Sulfide Regulation Of Kir Channels, Junghoon Ha
Hydrogen Sulfide Regulation Of Kir Channels, Junghoon Ha
Theses and Dissertations
Inwardly rectifying potassium (Kir) channels establish and regulate the resting membrane potential of excitable cells in the heart, brain and other peripheral tissues. Phosphatidylinositol- 4,5-bisphosphate (PIP2) is a key direct activator of ion channels, including Kir channels. Gasotransmitters, such as carbon monoxide (CO), have been reported to regulate the activity of Kir channels by altering channel-PIP2 interactions. We tested, in a model system, the effects and mechanism of action of another important gasotransmitter, hydrogen sulfide (H2S) thought to play a key role in cellular responses under ischemic conditions. Direct administration of sodium hydrogen sulfide (NaHS), as an exogenous H2S source, …
Deletion Of Cardiac Mir-17-92 Cluster Increases Ischemia/ Reperfusion Injury Via Pten Upregulation, Meeta B. Prakash
Deletion Of Cardiac Mir-17-92 Cluster Increases Ischemia/ Reperfusion Injury Via Pten Upregulation, Meeta B. Prakash
Theses and Dissertations
The miR-17- 92 cluster is necessary for cell proliferation and development of the cardiovascular system. Deletion of this cluster leads to death in neonatal mice. The role of this cluster still needs to be defined following ischemia and reperfusion. Methods and Results: Adult male mice were injected with Tamoxifen- was to induce inducible cardiac-specific miR-17- 92-deficient (miR-17- 92-def: MCM:TG:miR-17- 92 flox/flox ) and wild type (WT: MCM:NTG:miR-17-92 flox/flox ) mice were subjected to 30 minutes of myocardial ischemia via left anterior descending coronary artery ligation followed by reperfusion for 24 hours. Post I/R survival (48%) and ejection fraction were reduced, …
Modifications Of Myofilament Structure And Function During Global Myocardial Ischemia, Mike K. Woodward
Modifications Of Myofilament Structure And Function During Global Myocardial Ischemia, Mike K. Woodward
Masters Theses
Cardiac arrest is a prevalent condition with a poor prognosis, attributable in part to persistent myocardial dysfunction following resuscitation. The molecular basis of this dysfunction remains unclear. We induced cardiac arrest in a porcine model of acute sudden death and assessed the impact of ischemia and reperfusion on the molecular function of isolated cardiac contractile proteins. Cardiac arrest was electrically induced, left untreated for 12 min, and followed by a resuscitation protocol. With successful resuscitations, the heart was reperfused for 2 h (IR2) and the muscle harvested. In failed resuscitations, tissue samples were taken following the failed efforts (IDNR). Actin …
Manipulation Of The Microbiome And Its Impact On Functional Recovery Following Ischemic Stroke, Michal Jandzinski
Manipulation Of The Microbiome And Its Impact On Functional Recovery Following Ischemic Stroke, Michal Jandzinski
Honors Scholar Theses
Each year, nearly 800,000 individuals residing in the United States will have a stroke. Of these, about 130,000 cases will prove fatal while many of the survivors will be forced to live with disability for the remainder of their lives. Out of all strokes over 87% are ischemic strokes. The widespread incidence of this debilitating condition costs the United States an estimated $36.5 billion dollars every single year. Despite this, clinicians are armed with very little to combat the disease. Recent research developments have brought about the rise in awareness about the importance of the microbiome, the various gut flora …
C.Elegans As A Diabetes & Ischemia Model: Identification Of Genetic And Cellular Changes That Modulate The Survival Of Hyperglycemia And Oxygen-Deprivation, Anastacia M. Garcia, Mary L. Ladage, Brian K. Mcfarlin, Rajeev K. Azad, Pamela A. Padilla
C.Elegans As A Diabetes & Ischemia Model: Identification Of Genetic And Cellular Changes That Modulate The Survival Of Hyperglycemia And Oxygen-Deprivation, Anastacia M. Garcia, Mary L. Ladage, Brian K. Mcfarlin, Rajeev K. Azad, Pamela A. Padilla
International Journal of Exercise Science: Conference Proceedings
Diet represents an exogenous influence that often yields colossal effects on an individual’s phenotype, physiology, long-term health and disease risk. The overconsumption of dietary sugars for example, has contributed to significant increases in obesity and type 2 diabetes, health issues that are costly both in terms of dollars and human life. Additionally, individuals with these conditions have compromised oxygen delivery and thus, an increased vulnerability to other oxygen-deprivation related disease states, including cardiovascular disease, ischemic strokes, vascular and coronary diseases and myocardial infarction. While human and other mammalian studies have shown that individuals with type 2 diabetes have a worse …
Reactive Hyperemia Occurs Via Activation Of Inwardly-Rectifying Potassium Channels And Na+/K+-Atpase In Humans, Anne R. Crecelius, Jennifer C. Richards, Gary J. Luckasen, Dennis G. Larson, Frank A. Dinenno
Reactive Hyperemia Occurs Via Activation Of Inwardly-Rectifying Potassium Channels And Na+/K+-Atpase In Humans, Anne R. Crecelius, Jennifer C. Richards, Gary J. Luckasen, Dennis G. Larson, Frank A. Dinenno
Anne R. Crecelius
Rationale: Reactive hyperemia (RH) in the forearm circulation is an important marker of cardiovascular health, yet the underlying vasodilator signaling pathways are controversial and thus remain unclear. Objective: We hypothesized that RH occurs via activation of inwardly rectifying potassium (KIR) channels and Na+/K+-ATPase and is largely independent of the combined production of the endothelial autocoids nitric oxide (NO) and prostaglandins in young healthy humans. Methods and Results: In 24 (23±1 years) subjects, we performed RH trials by measuring forearm blood flow (FBF; venous occlusion plethysmography) after 5 minutes of arterial occlusion. In protocol 1, we studied 2 groups of 8 …
Sigma Receptor Activation Mitigates Toxicity Evoked By The Convergence Of Ischemia, Acidosis And Amyloid-Beta, Adam Alexander Behensky
Sigma Receptor Activation Mitigates Toxicity Evoked By The Convergence Of Ischemia, Acidosis And Amyloid-Beta, Adam Alexander Behensky
USF Tampa Graduate Theses and Dissertations
Stroke is the fifth leading cause of death in the United States and a major cause of long-term disability in industrialized countries. The core region of an ischemic stroke dies within minutes due to activation of necrotic pathways. Outside of this core region is the penumbral zone, where some perfusion is maintained via collateral arteries. Delayed cell death occurs in this area due to the triggering of apoptotic mechanisms, which expands the ischemic injury over time. The cellular and molecular events that produce the expansion of the ischemic core continue to be poorly understood. The increases in the amyloid precursor …
Characterization Of Blood-Derived Human Progenitor Cells For Vascular Regeneration, David Putman
Characterization Of Blood-Derived Human Progenitor Cells For Vascular Regeneration, David Putman
Electronic Thesis and Dissertation Repository
Cardiovascular disease (CVD) remains a leading cause of premature death worldwide. Despite advances in treatment of ischemic diseases including myocardial infarction and peripheral arterial disease (PAD) there remains a need for effective revascularization therapies. Although early cell therapy trials investigated use of MNC from autologous bone marrow, emerging evidence indicates that purified progenitor cell populations are required to induce optimal vascular regeneration. In addition, autologous cells show reduced efficacy due to CVD-related progenitor dysfunction. This thesis presents preclinical studies characterizing several blood-derived cell types for the development of cellular therapies to treat PAD, focusing on the use of allogeneic umbilical …
Effects Of Ischemia And Reperfusion On The Local Regulation Of Oxygen Consumption, Tissue Oxygenation And Blood Supply In Rat Skeletal Muscle., Sami Dodhy
Theses and Dissertations
In resting muscle, blood flow is regulated to meet the demand for O2 by the tissue. A modified ischemia (I)/reperfusion(R) investigation was systematically run and PISFO2, PaO2, Q and VO2 were observed. Twenty-nine spinotrapezius muscles from male Sprague-Dawley rats (284±20 grams) were surgically exteriorized for intravital microscopy to test a model relating blood flow, O2 supply and O2 demand. The model can aid in the understanding of the regulation of tissue PO2. The interstitial PO2 (PISFO2) and perivascular PO2 (PaO2) measurements were made using phosphorescence quenching microscopy (PQM). O2 consumption (VO2) values were obtained with a quasi-continuous, flash-synchronized, pressurized airbag …
Ischemia Impairs Vasodilation In Skeletal Muscle Resistance Artery, Kyle Remington Struthers
Ischemia Impairs Vasodilation In Skeletal Muscle Resistance Artery, Kyle Remington Struthers
Master's Theses
Functional vasodilation in arterioles is impaired with chronic ischemia. We sought to examine the impact of chronic ischemia and age on skeletal muscle resistance artery function. To examine the impact of chronic ischemia, the femoral artery was resected from young (2-3mo) and adult (6-7mo) mice and the profunda femoris artery diameter was measured at rest and following gracilis muscle contraction 14 days later using intravital microscopy. Functional vasodilation was significantly impaired in ischemic mice (14.4±4.6% vs. 137.8±14.3%, p<0.0001 n=8) and non-ischemic adult mice (103.0±9.4% vs. 137.8±14.3%, p=0.05 n=10). In order to analyze the cellular mechanisms of the impairment, a protocol was developed to apply pharmacological agents to the experimental preparation while maintaining tissue homeostasis. Endothelial and smooth muscle dependent vasodilation were impaired with ischemia, 39.6 ± 13.6% vs. 80.5 ± 11.4% and 43.0 ± 11.7% vs. 85.1 ± 10.5%, respectively. From this data, it can be supported that smooth muscle dysfunction is the reason for the observed impairment in arterial vasodilation.
In Vivo Measurement Of Rat Skeletal Muscle Oxygen Consumption Following Brief Periods Of Ischemia With Reperfusion As Assessed By Phosphorescence Quenching Microscopy, William Nugent
Theses and Dissertations
Brief periods of skeletal muscle ischemia (ischemic pre-conditioning) alter cellular metabolism in a way that confers protection over subsequent ischemic episodes. The mechanisms behind this effect have been studied indirectly through assays for the byproducts of ATP synthesis and in vitro studies of cellular signaling cascades and ROS generation. There have been no direct, in vivo assessments of the changes in respiration during reperfusion. We employed phosphorescence quenching microscopy in conjunction with a flow-arrest technique to assess the influences of external, pressure-induced 1- to 10-min focal ischemia on interstitial oxygenation (PISFO2) and the consumption of oxygen (VO2) in spinotrapezius muscles …
Long-Term Cardioprotection With Phosphodiesterase-5 Inhibition Against Ischemia-Reperfusion Injury: Role Of Nitric Oxide., Vladimir Paul Daoud
Long-Term Cardioprotection With Phosphodiesterase-5 Inhibition Against Ischemia-Reperfusion Injury: Role Of Nitric Oxide., Vladimir Paul Daoud
Theses and Dissertations
Recent studies have shown that the potent phosphodiesterase-5 (PDE-5) inhibitor, sildenafil citrate, induces a powerful cardioprotective effect against ischemia-reperfusion (I/R) injury in rabbit and mouse hearts. However, the effect of this drug in inducing long-term protection against I/R injury remains unknown. The goal of this study was to identify the duration of the protective window of sildenafil citrate as well as vardenafil, a more potent PDE-5 inhibitor. Rabbits were treated with sildenafil (0.7 mg/kg, iv), vardenafil (0.143 mg/kg), or an equivalent volume of saline. After 24 hrs, 48 hrs, 96 hrs, or 7 days of sildenafil treatment, the hearts were …
Novel Strategies In Cardioprotection Against Ischemia/Reperfusion Injury, Fadi N. Salloum
Novel Strategies In Cardioprotection Against Ischemia/Reperfusion Injury, Fadi N. Salloum
Theses and Dissertations
Cell damage represents a major pathomechanism in many diseases of high clinical interest, such as myocardial infarction (MI), where it plays an important role in ischemia-reperfusion (I/R) injury. Considerable progress has been made towards identifying physiological and pharmacological agents that play a key role in myocardial preconditioning against I/R injury and also elucidating the molecular changes leading to such protection.Second messengers in cellular signaling pathways, such as cGMP have been well implicated as key players in ischemic and pharmacological preconditioning (PC) of the heart. Phosphodiesterase type 5 (PDE-5) is an enzyme that specifically hydrolyzes cGMP thereby decreasing its tissue concentration. …