A5035457721- Cardiac Ischemia and Reperfusion
- Mitochondrial Function and Pathology
- Cardiac electrophysiology and arrhythmias
- Cardiac Arrest and Resuscitation
- Anesthesia and Neurotoxicity Research
- ATP Synthase and ATPases Research
- Nitric Oxide and Endothelin Effects
- Anesthesia and Sedative Agents
- Electron Spin Resonance Studies
- Fuel Cells and Related Materials
- Ion channel regulation and function
- Cardiac Imaging and Diagnostics
- Adipose Tissue and Metabolism
- Metabolism and Genetic Disorders
- Heart Rate Variability and Autonomic Control
- Transplantation: Methods and Outcomes
- Cardiovascular Function and Risk Factors
- Cardiac Arrhythmias and Treatments
- Advanced MRI Techniques and Applications
- Organ Transplantation Techniques and Outcomes
- Anesthesia and Pain Management
- Electrochemical Analysis and Applications
- Cardiac, Anesthesia and Surgical Outcomes
- Neuroscience and Neuropharmacology Research
- Cardiomyopathy and Myosin Studies
Marquette University
2013-2023
Medical College of Wisconsin
2014-2023
Milwaukee VA Medical Center
2012-2022
Veterans Health Administration
2002-2019
Yale University
2016
University of North Carolina at Pembroke
2016
Indianapolis Zoo
2016
American College of Clinical Pharmacy
2016
Cleveland Clinic
2014-2016
University of Amsterdam
2011
Reactive oxygen species (ROS) are believed to be involved in triggering cardiac ischemic preconditioning (IPC). Decreased formation of ROS on reperfusion after prolonged ischemia may part underlie protection by IPC. In heart models, these contentions have been based either the effect scavengers abrogate IPC-induced preservation or a measurement oxidation products reperfusion. Using spectrophotofluorometry at left ventricular wall and fluorescent probe dihydroethidium (DHE), we measured...
The mitochondrion is a vital component in cellular energy metabolism and intracellular signaling processes. Mitochondria are involved myriad of complex cascades regulating cell death vs. survival. Importantly, mitochondrial dysfunction the resulting oxidative nitrosative stress central pathogenesis numerous human maladies including cardiovascular diseases, neurodegenerative diabetes, retinal many which related. This review will examine emerging understanding role mitochondria etiology...
The number of clinically relevant gene-based guidelines and recommendations pertaining to drug prescribing continues grow. Incorporating gene-drug interaction information into the drug-prescribing process can help optimize pharmacotherapy outcomes improve patient safety. However, pharmacogenomic implementation barriers exist such as integration results electronic health records (EHRs), development deployment decision support tools EHRs, feasible models for establishing ambulatory clinics. We...
Background Ropivacaine is believed to have a lower incidence of clinical cardiac side effects than bupivacaine. The aim this study was compare the direct optically pure S(-)-ropivacaine isomer and its nonclinically used R(+)-isomer with both bupivacaine isomers in isolated hearts. hypothesis that differences are distinguished not only by stereoselective actions local anesthetic molecules specific receptors, but also physicochemical triggered replacing butyl- propyl-residual on...
The authors examined direct myocardial and coronary vascular responses to the anesthetic induction agents etomidate, ketamine, midazolam, propofol, thiopental compared their effects on attenuating autoregulation of flow as assessed by changes in oxygen supply/demand relationships. Spontaneous heart rate, atrioventricular conduction time during a trial pacing, left ventricular pressure (LVP), (CF), percent extraction, delivery, consumption (MVo2) were 55 isolated guinea pig hearts divided...
Background Like ischemic preconditioning, certain volatile anesthetics have been shown to reduce the magnitude of ischemia/ reperfusion injury via activation K+ adenosine triphosphate (ATP)-sensitive (K(ATP)) channels. The purpose this study was (1) determine if preconditioning (IPC) and sevoflurane (SPC) increase nitric oxide release improve coronary vascular function, as well mechanical electrical given for only brief intervals before global ischemia isolated hearts; (2) K(ATP) channel...
ATP-sensitive K+ channel opening in inner mitochondrial membranes protects hearts from ischemia-reperfusion (I/R) injury. Opening of the Big conductance Ca2+-sensitive (BK(Ca)) is now also known to elicit cardiac preconditioning. We investigated role pharmacological BK(Ca) on inducing preconditioning during I/R and O2-derived free radicals modulating protection by putative (m)BK(Ca) opening. Left ventricular (LV) pressure (LVP) was measured with a balloon transducer guinea pig isolated...
We recently demonstrated a role for altered mitochondrial bioenergetics and reactive oxygen species (ROS) production in Ca(2+)-sensitive K(+) (mtK(Ca)) channel opening-induced preconditioning isolated hearts. However, the underlying mechanism by which mtK(Ca) opening causes ROS to trigger is unknown. hypothesized that submaximal influx as result of enhanced electron flow at fully charged membrane potential (DeltaPsi(m)). To test this hypothesis, we measured effects NS-1619, putative opener,...
Reactive oxygen species (ROS) are largely responsible for cardiac injury consequent to ischemia and reperfusion, but, paradoxically, there is evidence suggesting that anesthetics induce preconditioning (APC) by generating ROS. We hypothesized sevoflurane generates the ROS superoxide (O2·−), APC attenuates O2·− formation during ischemia, this attenuation reversed bracketing with scavenger manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) or putative mitochondrial adenosine...
Damage to the mitochondrial electron transport chain (ETC) occurs during ischaemia. Blockade of flow in ETC just before ischaemia with reversible complex I inhibitor amobarbital protects isolated mitochondria against ischaemic damage and preserves oxidative phosphorylation cytochrome c content. We hypothesized that brief perfusion would improve cardiac recovery decrease infarct size after reperfusion (IR) by preserving redox state reducing superoxide (O2−•) generation, turn Ca2+ accumulation...
Background The noble gas xenon (Xe) has been used as an inhalational anesthetic agent in clinical trials with little or no physiologic side effects. Like nitrous oxide, Xe is believed to exert minimal unwanted cardiovascular effects, and like the vapor concentration achieve 1 minimum alveolar (MAC) for humans high, i.e., 70-80%. In current study, concentrations of up 80% were examined possible myocardial effects isolated, erythrocyte-perfused guinea pig hearts on altering major cation...
We postulated that anesthetic preconditioning (APC) is triggered by reactive oxygen/nitrogen species (ROS/RNS). used the isolated guinea pig heart perfused withl-tyrosine, which reacts with ROS and RNS to form strong oxidants, principally peroxynitrite (ONOO − ), then forms fluorescent dityrosine. scavengers superoxide dismutase, catalase, glutathione (SCG) NO· synthesis inhibitor N G -nitro-l-arginine methyl ester (l-NAME) were given 5 min before after sevoflurane stimuli. Drugs washed out...
Background The local anesthetic bupivacaine is an equal mixture of two optically active isomers known to exert different cardiotoxic profiles in vivo. Enantiomer-specific forms may have differential effects on cardiovascular function, specifically cardiac electrophysiology. authors' aim was determine if there were any direct functional differences the isomers. isolated heart used avoid possible indirect bupivacaine, such as autonomic nervous and hormonal influences, well preload afterload...
Mitochondria generate reactive oxygen species (ROS) dependent on substrate conditions, O(2) concentration, redox state, and activity of the mitochondrial complexes. It is well known that FADH(2)-linked succinate induces reverse electron flow to complex I transport chain this process generates superoxide (O(2)(*-)); these effects are blocked by blocker rotenone. We demonstrated recently + rotenone-dependent H(2)O(2) production in isolated mitochondria increased mildly activation putative big...
Background Protein kinase C (PKC) and reactive oxygen species (ROS) are known to have a role in anesthetic preconditioning (APC). Cardiac by triggers other than volatile anesthetics, such as opioids or brief ischemia, is be isoform selective, but the required for APC not known. The authors aimed identify PKC that involved elucidate relative positions of activation ROS formation signaling cascade. Methods Isolated guinea pig hearts were subjected 30 min ischemia 120 reperfusion. Before either...