A5036714759- Cardiac Ischemia and Reperfusion
- Anesthesia and Neurotoxicity Research
- Cardiac, Anesthesia and Surgical Outcomes
- Cardiac Arrest and Resuscitation
- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Clinical Nutrition and Gastroenterology
- Diet and metabolism studies
- Hemodynamic Monitoring and Therapy
- Anesthesia and Sedative Agents
- Cardiovascular Function and Risk Factors
- Fatty Acid Research and Health
- Intensive Care Unit Cognitive Disorders
- Respiratory Support and Mechanisms
- Adipose Tissue and Metabolism
- Organ Transplantation Techniques and Outcomes
- Electron Spin Resonance Studies
- MicroRNA in disease regulation
- Osteoarthritis Treatment and Mechanisms
- Cancer, Stress, Anesthesia, and Immune Response
- Renal function and acid-base balance
- Cancer, Lipids, and Metabolism
- Bone health and osteoporosis research
- Chemotherapy-induced cardiotoxicity and mitigation
- Cardiac electrophysiology and arrhythmias
University of Alberta
2014-2024
Pain and Rehabilitation Medicine
2010-2016
Marymount University
2007-2012
Northwestern University
2012
Williams & Associates
2012
University Hospital of Zurich
1998-2010
University of Zurich
1996-2010
Roche (Switzerland)
2007-2010
Swiss Integrative Center for Human Health
1996-2010
University of Pittsburgh
2010
Background Volatile anesthetics induce pharmacological preconditioning in cardiac tissue. The purpose of this study was to test whether volatile mediate effect by activation the mitochondrial adenosine triphosphate-sensitive potassium (mitoK(ATP)) or sarcolemmal K(ATP) (sarcK(ATP)) channel rat ventricular myocytes and evaluate signaling pathways involved. Methods A cellular model ischemia with subsequent hypoosmolar trypan blue staining served determine effects 5-hydroxydecanoate, a...
Background Perioperative beta-blockade has been shown to improve long-term cardiac outcome in noncardiac surgical patients. A possible mechanism for the reduced risk of perioperative myocardial infarction is attenuation excitotoxic effects catecholamine surges by beta-blockade. It was hypothesized that beta-blocker-induced alteration stress response responsible reported improvements cardiovascular outcome. Several variables associated with use were also evaluated. Methods Sixty-three...
BACKGROUND-Catecholamine-induced apoptosis is mediated by activation of the beta-adrenergic signaling pathway. We tested hypothesis that beta(1)- and beta(2)-adrenergic receptor (AR) subtypes differentially affect in adult rat ventricular myocytes vitro. METHODS AND RESULTS-Myocytes were first exposed to norepinephrine (NE) alone (10 mcmol/L) or NE+atenolol (AT) for 12 hours. AT, a beta(1)-selective AR antagonist, abolished NE-induced increase nick end-labeling (TUNEL)-positive cells...
Postischemic administration of volatile anesthetics activates reperfusion injury salvage kinases and decreases myocardial damage. However, the mechanisms underlying anesthetic postconditioning are unclear.Isolated perfused rat hearts were exposed to 40 min ischemia followed by 1 h reperfusion. Anesthetic was induced 15 2.1 vol% isoflurane (1.5 minimum alveolar concentration) administered at onset In some experiments, atractyloside (10 microm), a mitochondrial permeability transition pore...
Background Mesenchymal stem cells (MSC) are self-renewing clonal progenitor of nonhematopoietic tissues that exhibit a marked tropism to wounds and tumors. The authors' studies aimed at exploring how local anesthetics would affect MSC biology. Methods Proliferation, colony formation, in vitro wound healing, bone differentiation assays culture-expanded bone-marrow-derived murine were performed the presence increasing concentrations lidocaine, ropivacaine, bupivacaine. Cytotoxicity was...
Background Two preconditioning stimuli should induce a more consistent overall cell protection. We hypothesized that remote ischemic (RIPC, second stimulus) applied during isoflurane inhalation (first would provide protection to the myocardium of patients undergoing on-pump coronary artery bypass grafting. Methods In this placebo-controlled randomized controlled study, in RIPC group received four 5-min cycles 300 mmHg cuff inflation/deflation leg before aortic cross-clamping. Anesthesia...
The flux of Ca2+ from the endoplasmic reticulum (ER) to mitochondria regulates metabolism. Within tumor tissue, metabolism is frequently repressed, leading chemotherapy resistance and increased growth mass. Therefore, altered ER–mitochondria could be a cancer hallmark, but only few regulatory proteins this mechanism are currently known. One candidate redox-sensitive oxidoreductase TMX1 that enriched on mitochondria-associated membrane (MAM), site flux. Our findings demonstrate cells with low...
Objective: We tested whether ischemic postconditioning (IPostC) is protective in remodeled myocardium. Methods: Post-myocardial infarct (MI)-remodeled hearts after permanent coronary artery ligation and one kidney clip (1K1C) hypertensive of male Wistar rats were exposed to 40 min ischemia followed by 90 reperfusion. IPostC was induced six cycles 10 s reperfusion interspersed no-flow ischemia. Activation injury salvage kinases measured using Western blotting vitro kinase activity assays....
Doxorubicin (DXR) is a widely used and efficient anticancer drug. However, its application limited by the risk of severe cardiotoxicity. Impairment cardiac high-energy phosphate homeostasis an important manifestation both acute chronic DXR cardiotoxic action. Using Langendorff model perfused rat heart, we characterized effects 1-h perfusion with 2 or 20 microM on two key kinases in energy metabolism, creatine kinase (CK) AMP-activated protein (AMPK), related them to functional responses...
Background Mitochondrial adenosine triphosphate-sensitive potassium (mitoK(ATP)) channels play a pivotal role in mediating cardiac preconditioning. The effects of intravenous anesthetics on this protective channel have not been investigated so far, but would be importance with respect to experimental as well clinical medicine. Methods Live cell microscopy was used visualize and measure autofluorescence flavoproteins, direct reporter mitoK(ATP) activity, response the highly selective opener...
Endothelial cells can be protected against cytokine-induced toxicity by volatile anesthetics. The authors tested whether inhalation of sevoflurane at subanesthetic concentrations provides protection postocclusive endothelial dysfunction induced ischemia-reperfusion injury the forearm in humans.Five healthy male volunteers were enrolled this study with crossover design. Each subject was randomly exposed to 15 min ischemia presence or absence sevoflurane. Sevoflurane inhaled 0.5-1 vol%...
Abstract Background: Neuraxial blockade is used as primary anesthetic technique in one third of surgical procedures. The authors tested whether bisoprolol would protect patients at risk for cardiovascular complications undergoing surgery with spinal block. Methods: performed a double-blinded, placebo-controlled, multicenter trial to compare the effect that placebo on 1-yr composite outcome including mortality, nonfatal myocardial infarction, unstable angina, congestive heart failure, and...
Background DNA chips facilitate genomic-wide exploration of gene expression. The authors hypothesized that ischemic (IPC) and anesthetic preconditioning (APC) would differentially modulate expression in hearts. Methods Affymetrix rat U34A were used to explore the transcriptional response IPC APC, sustained ischemia (110 min) without reperfusion, time-matched perfusion isolated was induced by three cycles 5 min ischemia, APC 1.5 minimum alveolar concentration isoflurane min). For each heart,...
Anesthetic gases modulate gene expression and provide organ protection. This study aimed at identifying myocardial transcriptional phenotypes to predict cardiovascular biomarkers function in patients undergoing off-pump coronary artery bypass graft surgery.In a prospective randomized trial, elective surgery were allocated receive either the anesthetic gas sevoflurane (n = 10) or intravenous propofol 10). Blood samples collected perioperatively determine cardiac troponin T, N-terminal...
Reversible phosphorylation of mitochondrial proteins is essential in the regulation respiratory function, energy metabolism, and mitochondrion-mediated cell death. We hypothesized that protein plays a critical role cardioprotection during pre postconditioning, two most efficient anti-ischaemic therapies. Using phosphoproteomic approaches, we investigated profiles phosphorylated Wistar rat heart mitochondria protected by pharmacological postconditioning elicited isoflurane. Sixty-one spots...
Background Intralipid® administration at reperfusion elicits protection against myocardial ischemia-reperfusion injury. However, the underlying mechanisms are not fully understood. Methods Sprague-Dawley rat hearts were exposed to 15 min of ischemia and 30 in absence or presence 1% administered onset reperfusion. In separate experiments, reactive oxygen species (ROS) scavenger N-(2-mercaptopropionyl)-glycine was added either alone with Intralipid®. Left ventricular work activation Akt,...
Control of Ca 2+ flow from the ER to mitochondria by calnexin balances output energy production pathways.
We tested whether exposure to anabolic-androgenic steroids (AASs) would induce apoptosis in adult rat ventricular myocytes vitro. Myocytes were exposed stanozolol (STZ), testosterone enanthate (TE) and (T) (0.1 μmol/L, 1 10 100 μmol/L) for 20 h. The percentage of undergoing was determined by terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) found be increased when compared control at STZ μmol/L 12 ± 2% (mean SD), 42 3%; TE 11 2%, 21 3%, 62 2%; T 40 3% (P < 0.001 vs....
Microarray analyses indicate that ischemic and pharmacological preconditioning suppress overexpression of the non-long terminal repeat retrotransposon long interspersed nuclear element 1 (LINE-1, L1) after ischemia-reperfusion in rat heart. We tested whether L1 is mechanistically involved postischemic myocardial damage. Isolated, perfused hearts were treated with antisense or scrambled oligonucleotides (ODNs) against for 60 min exposed to 40 ischemia followed by reperfusion. Functional...