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North Chicago, IL, United States

Vigilante J.A.,Captain James vell Federal Health Care Center
Undersea and Hyperbaric Medicine | Year: 2013

Introduction: A 20-year-old male military recruit who presented for a screening physical for U.S. Naval Diving Duty was found to have family history significant for malignant hyperthermia. He had never been exposed to anesthesia, a trigger for the condition, and had not undergone testing. Medical history was otherwise unremarkable, and the patient was cleared for diving. Methods: Literature search was conducted using Pub-Med/Medline. Keywords included malignant hyperthermia, exertional heat illness, exertional rhabdomyolysis, diving, special operations, military. Results that included cases of malignant hyperthermia were included. Results: Review of the literature reveals that malignant hyperthermia is primary a pharmacogenetic disorder limited to specific anesthetics, with rare reports of environmental triggers. Analysis of the disease, as well as the absence of reported cases of malignant hyperthermia in diving, suggest there is minimal increased risk in diving for subjects without history of exercise intolerance. Conclusion: Individuals with presumed or proven malignant hyperthermia susceptibility seeking activity clearance should be given precautions and undergo careful questioning for history of heat- or exercise-related illness. If negative, it seems reasonable to allow the patient participation in recreational or technical diving. Copyright © 2013 Undersea & Hyperbaric Medical Society, Inc.

Radhakrishnan J.,Rosalind Franklin University of Medicine and Science | Bazarek S.,Rosalind Franklin University of Medicine and Science | Chandran B.,Rosalind Franklin University of Medicine and Science | Gazmuri R.J.,Captain James vell Federal Health Care Center
FASEB Journal | Year: 2015

Cyclophilin-D (Cyp-D) is a mitochondrial matrix peptidyl-prolyl isomerase. Because cyclophilins can regulate nuclear gene expression, we examined whether Cyp-D could regulate mitochondrial gene expression. We demonstrated in HEK 293T cells that transfected Cyp-D interacts with mitochondrial transcription factors B1 and B2 (TFB2M) but not with mitochondrial transcription factor A. We also demonstrated that Cyp-D interacts in vivo with TFB2M. Genetic silencing of Cyp-D and pharmacologic inhibition of Cyp-D markedly reduced mitochondrial transcription to 18 ± 5% (P< 0.05) and 24 ± 3% (P < 0.05) of respective controls. The level of interaction between Cyp-D and TFB2M correlated with the level of nascent mitochondrial RNA intensity (r= 0.896; P= 0.0156). Cyp-D silencing down-regulated mitochondrial transcripts initiated from the heavy strand promoter 2 [i.e., NADH dehydrogenase 1 (ND1) by 11-fold, P< 0.005; cytochrome oxidase 1 (COX1) by 4-fold, P < 0.001; and ATP synthase subunit 6 (ATP6) by 6.5-fold, P< 0.005); but not NADH dehydrogenase 6 (ND6)], which is initiated from the light strand promoter. Cyp-D silencing reduced mitochondrial membrane potential and cellular oxygen consumption (from 59 ± 5 to 34 ± 1 μmoloxygen/min/106 cells, P<0.001);thelatter without a statistically significant reversal after uncoupling electron transport from ATP synthesis, consistent with down-regulation of electron transport complexes. Accordingly, these studies provide novel evidence that Cyp-D could play a key role in regulating mitochondrial gene expression. © FASEB.

Gazmuri R.J.,Rosalind Franklin University of Medicine and Science | Gazmuri R.J.,Captain James vell Federal Health Care Center | Ayoub I.M.,Rosalind Franklin University of Medicine and Science | Radhakrishnan J.,Rosalind Franklin University of Medicine and Science | And 2 more authors.
Resuscitation | Year: 2012

Aims: Ventilation at high respiratory rates is considered detrimental during CPR because it may increase intrathoracic pressure limiting venous return and forward blood flow generation. We examined whether ventilation at high, yet clinically plausible, tidal volumes could also be detrimental, and further examined effects on end-tidal pCO 2 (P ETCO 2). Methods: Sixteen domestic pigs were randomized to one of four ventilatory patterns representing two levels of respiratory rate (min -1) and two levels of tidal volume (ml/kg); i.e., 10/6, 10/18, 33/6, and 33/18 during chest compression after 8min of untreated VF. Results: Data (mmHg, mean±SD) are presented in the order listed above. Ventilation at 33/18 prompted higher airway pressures (p<0.05) and persistent expiratory airway flow (p<0.05) before breath delivery demonstrating air trapping. The right atrial pressure during chest decompression showed a statistically insignificant increase with increasing minute-volume (7±4, 10±3, 12±1, and 13±3; p=0.055); however, neither the coronary perfusion pressure (23±1, 17±6, 18±6, and 21±2; NS) nor the cerebral perfusion pressure (32±3, 23±8, 30±12, and 31±3; NS) was statistically different. Yet, increasing minute-volume reduced the P ETCO 2 demonstrating a high dependency on tidal volumes delivered at currently recommended respiratory rates. Conclusions: Increasing respiratory rate and tidal volume up to a minute-volume 10-fold higher than currently recommended had no adverse hemodynamic effects during CPR but reduced P ETCO 2 suggesting that ventilation at controlled rate and volume could enhance the precision with which P ETCO 2 reflects CPR quality, predicts return of circulation, and serve to guide optimization of resuscitation interventions. © 2011 Elsevier Ireland Ltd.

Aggarwal S.,Franklin University | Loomba R.S.,Medical College of Wisconsin | Arora R.R.,Captain James vell Federal Health Care Center
Journal of Cardiovascular Pharmacology | Year: 2012

A few trials have investigated the efficacy of colesevelam in the reduction of glycemic and lipid outcomes. These meta-analysis pooled data from 8 such trials and found that colesevelam is associated with significant reductions in plasma fasting glucose, hemoglobin A1c, and low-density lipoprotein. Insignificant reductions in high-density lipoprotein and total cholesterol were also noted along with significant increase in triglycerides. This analysis concludes that colesevelam may be of particular benefit in managing type 2 diabetic patients with hyperlipidemia in whom low-density lipoprotein levels are of particular concern. Caution should be taken in patients who have hypertriglyceridemia or low high-density lipoprotein levels before starting therapy. Copyright © 2012 by Lippincott Williams & Wilkins.

Radhakrishnan J.,Rosalind Franklin University of Medicine and Science | Upadhyaya M.P.,Rosalind Franklin University of Medicine and Science | Ng M.,Rosalind Franklin University of Medicine and Science | Edelheit A.,Rosalind Franklin University of Medicine and Science | And 4 more authors.
American Journal of Translational Research | Year: 2013

Objective: We previously reported beneficial myocardial effects during chest compression after administration of high-dose erythropoietin. We hypothesized that erythropoietin also elicits post-resuscitation myocardial benefits partly linked to protection of mitochondrial bioenergetic function. Methods: Two series of 10 rats each underwent ventricular fibrillation for 10 minutes (series-1) and 8 minutes (series-2) and were randomized to erythropoietin (5,000 U/kg) or 0.9% NaCl before chest compression. Dobutamine was infused post-resuscitation in series-2 harvesting their hearts at 120 minutes. Results: During chest compression, a statistically insignificant trend showing progressively higher coronary perfusion pressure in the erythropoietin group was observed consistent with previously reported preservation of left ventricular distensibility. Post-resuscitation, in the absence of dobutamine (series-1) erythropoietin failed to improve post-resuscitation myocardial function or survival; in the presence of dobutamine (series-2) all rats survived and those treated with erythropoietin reversed post-resuscitation myocardial dysfunction yielding higher cardiac work index (CWI; 39±3 vs 25±10 mmHg·ml/kg, p<0.01) and higher mean aortic pressure (MAP; 99±4 vs 83±16, p<0.01) at 120 minutes post-resuscitation. Better myocardial function was associated with lesser increases in plasma cytochrome c, attaining levels which inversely correlated with CWI (p=0.026) and MAP (p=0.025). Hearts from erythropoietin-treated rats had higher phosphorylation levels of cytosolic Akt and higher phosphorylation levels of cytosolic and mitochondrial PKCε and maintained cytochrome c oxidase activity. Conclusion: Erythropoietin activated mitochondrial protective mechanisms that helped maintain bioenergetic function enabling reversal of post-resuscitation myocardial dysfunction in the presence of dobutamine.

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