Mary Osbakken

Dr. Osbakken graduated from the University of Illinois with her undergraduate degree and Master’s degree in Physiology before coming to Jefferson to complete a PhD in Physiology. After graduating in 1969 she began teaching at Beaver College (now Arcadia University) and concurrently pursuing a Master’s in Biomedical Engineering from Drexel University. She then went on to earn an M.D. from Temple University Medical School. Dr. Osbakken completed her internship at Pennsylvania Hospital before taking fellowships in Cardiology and Nuclear Magnetic Resonance at Temple University Medical School, University of Pennsylvania Medical School, and Massachusetts General Hospital. After her fellowships she worked at Hershey Medical Center and later at University of Pennsylvania. Dr. Osbakken then entered the biotech and pharmaceutical fields working at Bristol-Myer-Squibb, Covance, Sanofi-Aventis, and Inotek. She currently runs her own consulting firm working with biotechs, startups, and pharmaceutical companies

The Role of Sodium in Diabetic Cardiomyopathy

Cardiovascular complications are the major cause of mortality and morbidity in diabetic patients. The changes in myocardial structure and function associated with diabetes are collectively called diabetic cardiomyopathy. Numerous molecular mechanisms have been proposed that could contribute to the development of diabetic cardiomyopathy and have been studied in various animal models of type 1 or type 2 diabetes. The current review focuses on the role of sodium (Na+) in diabetic cardiomyopathy and provides unique data on the linkage between Na+ flux and energy metabolism, studied with non-invasive 23Na, and 31P-NMR spectroscopy, polarography, and mass spectroscopy. 23Na NMR studies allow determination of the intracellular and extracellular Na+ pools by splitting the total Na+ peak into two resonances after the addition of a shift reagent to the perfusate. Using this technology, we found that intracellular Na+ is approximately two times higher in diabetic cardiomyocytes than in control possibly due to combined changes in the activity of Na+–K+ pump, Na+/H+ exchanger 1 (NHE1) and Na+-glucose cotransporter. We hypothesized that the increase in Na+ activates the mitochondrial membrane Na+/Ca2+ exchanger, which leads to a loss of intramitochondrial Ca2+, with a subsequent alteration in mitochondrial bioenergetics and function. Using isolated mitochondria, we showed that the addition of Na+ (1–10 mM) led to a dose-dependent decrease in oxidative phosphorylation and that this effect was reversed by providing extramitochondrial Ca2+ or by inhibiting the mitochondrial Na+/Ca2+ exchanger with diltiazem. Similar experiments with 31P-NMR in isolated superfused mitochondria embedded in agarose beads showed that Na+ (3–30 mM) led to significantly decreased ATP levels and that this effect was stronger in diabetic rats. These data suggest that in diabetic cardiomyocytes, increased Na+ leads to abnormalities in oxidative phosphorylation and a subsequent decrease in ATP levels. In support of these data, using 31P-NMR, we showed that the baseline β-ATP and phosphocreatine (PCr) were lower in diabetic cardiomyocytes than in control, suggesting that diabetic cardiomyocytes have depressed bioenergetic function. Thus, both altered intracellular Na+ levels and bioenergetics and their interactions may significantly contribute to the pathology of diabetic cardiomyopathy

Near-Infrared Spectroscopy for the Evaluation of Anesthetic Depth

The standard-of-care guidelines published by the American Society of Anesthesiologists (ASA) recommend monitoring of pulse oximetry, blood pressure, heart rate, and end tidal CO2 during the use of anesthesia and sedation. This information can help to identify adverse events that may occur during procedures. However, these parameters are not specific to the effects of anesthetics or sedatives, and therefore they offer little, to no, real time information regarding the effects of those agents and do not give the clinician the lead-time necessary to prevent patient “awareness.” Since no “gold-standard” method is available to continuously, reliably, and effectively monitor the effects of sedatives and anesthetics, such a method is greatly needed. Investigation of the use of functional near-infrared spectroscopy (fNIRS) as a method for anesthesia or sedation monitoring and for the assessment of the effects of various anesthetic drugs on cerebral oxygenation has started to be conducted. The objective of this paper is to provide a thorough review of the currently available published scientific studies regarding the use of fNIRS in the fields of anesthesia and sedation monitoring, comment on their findings, and discuss the future work required for the translation of this technology to the clinical setting

Near-Infrared Spectroscopy for the Evaluation of Anesthetic Depth

The standard-of-care guidelines published by the American Society of Anesthesiologists (ASA) recommend monitoring of pulse oximetry, blood pressure, heart rate, and end tidal CO 2 during the use of anesthesia and sedation. This information can help to identify adverse events that may occur during procedures. However, these parameters are not specific to the effects of anesthetics or sedatives, and therefore they offer little, to no, real time information regarding the effects of those agents and do not give the clinician the lead-time necessary to prevent patient "awareness." Since no "gold-standard" method is available to continuously, reliably, and effectively monitor the effects of sedatives and anesthetics, such a method is greatly needed. Investigation of the use of functional near-infrared spectroscopy (f NIRS) as a method for anesthesia or sedation monitoring and for the assessment of the effects of various anesthetic drugs on cerebral oxygenation has started to be conducted. The objective of this paper is to provide a thorough review of the currently available published scientific studies regarding the use of f NIRS in the fields of anesthesia and sedation monitoring, comment on their findings, and discuss the future work required for the translation of this technology to the clinical setting

Creatine kinase kinetics studied by phosphorus-31 nuclear magnetic resonance in a canine model of chronic hypertension-induced cardiac hypertrophy

AbstractTo determine whether cardiac hypertrophy secondary to chronic renovascular hypertension is associated with altered in vivo myocardial metabolism, phosphorus-31 nuclear magnetic resonance saturation transfer techniques were used to study creatine kinase (CK) kinetics in six chronically hypertensive dogs with moderate cardiac hypertrophy and eight control dogs. The forward rate constant of CK and the flux of phosphocreatine to adenosine triphosphate were determined in both groups of dogs before and during norepinephrine administration (1 μg/kg per min), used to increase heart rate × systolic blood pressure (rate-pressure product), cardiac output and oxygen consumption.Baseline and norepinephrine-induced changes in rate-pressure product, cardiac output and oxygen consumption were similar in both groups of dogs, as were baseline forward rate constant and flux of phosphocreatine to adenosine triphosphate. However, the norepinephrine-induced changes in forward rate constant and flux were significantly less in hypertensive than in control dogs (p < 0.05) even though changes in hemodynamic and functional variables were similar in both groups.These data demonstrate that moderate myocardial hypertrophy is associated with altered CK kinetics, which do not appear to affect the heart's ability for global mechanical recruitment at this stage in the hypertensive process. It is possible that the changes in myocardial enzyme kinetics may contribute to diastolic dysfunction previously reported in this model and may be a precursor for ultimate development of heart failure if hypertension is maintained for prolonged periods.The data also suggest that the heart of moderately hypertensive animals may work less per gram muscle and that it may have greater metabolic efficiency because it can maintain lower adenosine diphosphate levels (as indicated by lower forward rate constant of CK) than those of control hearts. However, it appears that either the CK system has a large safety factor such that the lower forward rate constant and flux found in hypertensive dogs is sufficient to support normal global mechanical function or that the phosphocreatine shuttle is not a critical factor in maintaining mechanical function in the moderately hypertrophied heart