Biomedical Engineering and Bioengineering Commons^™

99mTc-Labeled C2a Domain Of Synaptotagmin I As A Target-Specific Molecular Probe For Noninvasive Imaging Of Acute Myocardial Infarction, Ming Zhao, Xiaoguang Zhu, Shundong Ji, Jundong Zhou, Kutlan S. Ozker, Wei Fang, Robert C. Molthen, Robert S. Hellman

Biomedical Engineering Faculty Research and Publications

Abstract: The exposure of phosphatidylserine (PtdS) is a common molecular marker for both apoptosis and necrosis and enables the simultaneous detection of these distinct modes of cell death. Our aim was to develop a radiotracer based on the PtdS-binding activity of the C2A domain of synaptotagmin I and assess ^99mTc-C2A-GST (GST is glutathione S-transferase) using a reperfused acute myocardial infarction (AMI) rat model. Methods: The binding of C2A-GST toward apoptosis and necrosis was validated in vitro. After labeling with ^99mTc via 2-iminothiolane thiolation, radiochemical purity and radiostability were tested. Pharmacokinetics and biodistribution were studied in healthy rats. …

Cardioprotection By Glucose-Insulin-Potassium: Dependence On KAtp Channel Opening And Blood Glucose Concentration Before Ischemia, John F. Ladisa, John G. Krolikowski, Paul S. Pagel, David C. Warltier, Judy R. Kersten

Biomedical Engineering Faculty Research and Publications

We tested the hypothesis that glucose-insulin-potassium (GIK)-induced protection against myocardial infarction depends on ATP-dependent K⁺ (K_ATP) channel activation and is abolished by hyperglycemia before the ischemia. Dogs were subjected to a 60-min coronary artery occlusion and 3-h reperfusion in the absence or presence of GIK (25% dextrose; 50 IU insulin/l; 80 mM/l KCl infused at 1.5 ml·kg⁻¹·h⁻¹) beginning 75 min before coronary artery occlusion or 5 min before reperfusion. The role of K_ATP channels was evaluated by pretreatment with glyburide (0.1 mg/kg). The efficacy of GIK was investigated with increases in blood …

Adenosine Type 1 (A ) Receptors Mediate Protection Against Myocardial 1 Infarction Produced By Chronic, Intermittent Ingestion Of Ethanol In Dogs, Franz Kehl, John G. Krolikowski, John F. Ladisa, Judy R. Kersten, David C. Warltier, Paul S. Pagel

Biomedical Engineering Faculty Research and Publications

Background: Chronic consumption of small amounts of ethanol protects myocardium from ischemic injury. We tested the hypothesis that adenosine type 1 (A₁) receptors mediate these beneficial effects.

Methods: Dogs (n=37) were fed with ethanol (1.5 g/kg) or water mixed with dry food twice per day for 12 weeks, fasted overnight before experimentation, and instrumented for measurement of hemodynamics. Dogs received intravenous drug vehicle (50% polyethylene glycol in 0.1 N sodium hydroxide and 0.9% saline over 15 min) or the selective A₁ receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 0.8 mg/kg over 15 min) and were subjected …

Mechanism Of Preconditioning By Isoflurane In Rabbits: A Direct Role For Reactive Oxygen Species, Katsuya Tanaka, Dorothee Weihrauch, Franz Kehl, Lynda M. Ludwig, John F. Ladisa, Judy R. Kersten, Paul S. Pagel, David C. Warltier

Biomedical Engineering Faculty Research and Publications

LARGE quantities of reactive oxygen species (ROS) released during reperfusion after coronary artery occlusion damage proteins responsible for intracellular homeostasis, produce tissue injury, depress contractile function, and increase myocardial infarct size. In contrast, small quantities of ROS may exert beneficial effects during ischemia and reperfusion when released before a prolonged ischemic event. ROS derived from mitochondria during a brief ischemic episode produce preconditioning. Free radical scavengers administered during ischemic preconditioning (IPC) markedly attenuate the protective effect of the preconditioning stimulus on infarct size. These data suggest that IPC is mediated in part by small quantities of ROS released during preconditioning. …