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13. Postoperative delirium is associated with postoperative cognitive dysfunction at one week after cardiac surgery with cardiopulmonary bypass

Author

Hudetz, Judith A., Byrne, Alison J., Patterson, Kathleen M., Pagel, Paul S., and Warltier, David C.

Subjects
Coronary artery bypass -- Complications and side effects, Delirium -- Risk factors, Cardiac patients -- Psychological aspects, Surgery -- Complications, Surgery -- Risk factors, Psychology and mental health
Abstract

Postoperative delirium with cognitive impairment frequently occurs after cardiac surgery. It was hypothesized that delirium is associated with residual postoperative cognitive dysfunction in patients after surgery using cardiopulmonary bypass. Male cardiac surgical patients (M age = 66 yr., SD = 8; M education = 13 yr., SD = 2) and nonsurgical controls (M age = 62, SD = 7; M education = 12, SD = 2) 55 years of age or older were balanced on age and education. Delirium was assessed by the Intensive Care Delirium Screening Checklist preoperatively and for up to 5 days postoperatively. Recent verbal and nonverbal memory and executive functions were assessed (as scores on particular tests) before and 1 wk. after surgery. In 56 patients studied (n = 28 Surgery; n = 28 Nonsurgery), nine patients from the Surgery group developed delirium. In the Surgery group, the proportion of patients having postoperative cognitive dysfunction was significantly greater in those who experienced delirium (89%) compared with those who did not (37%). The odds of developing this dysfunction in patients with delirium were 14 times greater than those who did not. Postoperative delirium is associated with scores for residual postoperative cognitive dysfunction 1 wk. after cardiac surgery. DOI 10.2466/PR0.105.3.921-932

Published
2009

14. Myocardial interstitial fluid inhibits proliferation and cardiomyocyte differentiation in pluripotent embryonic stem cells

Author

Van Orman, Jordan R., Weihrauch, Dorothee, Warltier, David C., and Lough, John

Subjects
Cell differentiation -- Research, Embryonic stem cells -- Physiological aspects, Heart attack -- Care and treatment, Heart attack -- Research, Biological sciences
Abstract

Several recent studies have demonstrated that the transplantation of pluripotent routine embryonic stem cells (mESCs) can improve or restore the function of infarcted myocardium. Although the extent of remuscularization and its contribution to the restoration of function are unclear, these outcomes are likely strongly influenced by factors in the infarcted and/or ischemic environment. As an initial step toward understanding how the ischemic environment of host myocardium affects transplanted pluripotent cells, we have taken a reductionist approach wherein mESCs are cultured in medium containing ischemic myocardial interstitial fluid (iMIF). iMIF is generated in canine myocardium during eight hourly episodes of transient ischemia and collected on a daily basis, over a 24-day collection period, iMIF strongly reduced the numbers of pluripotent mESCs after 11 days in culture. This inhibitory effect, which was most pronounced for iMIF pools from early time points of the 24-day collection period, resulted from an inhibition of cell proliferation, iMIF also inhibited the differentiation of pluripotent mESCs into cardiomyocytes. By contrast, the expression of vascular smooth muscle and endothelial cell markers was relatively unaffected, consistent with previous findings that iMIF promotes angiogenesis. Taken together, these results suggest that whereas the ischemic/ infarcted environment is favorable to stem cell-mediated angiogenesis, it is hostile to cardiac myogenesis. These findings also imply that observations of mESC-mediated improvement of cardiac function after transplantation of pluripotent cells do not reflect remuscularization. pluripotent mouse embryonic stem cells; vascular smooth muscle; endothelial cells doi:10.1152/ajpheart.00172.2009

Published
2009

16. Isoflurane preconditioning uncouples mitochondria and protects against hypoxia-reoxygenation

Author

Ljubkovic, Marko, Mio, Yasushi, Marinovic, Jasna, Stadnicka, Anna, Warltier, David C., Bosnjak, Zeljko J., and Bienengraeber, Martin

Subjects
Heart cells -- Research, Heart cells -- Physiological aspects, Myocardial ischemia -- Research, Myocardial ischemia -- Physiological aspects, Isoflurane -- Research, Isoflurane -- Physiological aspects, Physiological research, Biological sciences
Abstract

Ischemic cardiac injury can be substantially alleviated by exposing the heart to pharmacological agents such as volatile anesthetics before occurrence of ischemia-reperfusion. A hallmark of this preconditioning phenomenon is its memory, when cardioprotective effects persist even after removal of preconditioning stimulus. Since numerous studies pinpoint mitochondria as crucial players in protective pathways of preconditioning, the aim of this study was to investigate the effects of preconditioning agent isoflurane on the mitochondrial bioenergetic phenotype. Endogenous flavoprotein fluorescence, an indicator of mitochondrial redox state, was elevated to 195 [+ or -] 16% of baseline upon isoflurane application in intact cardiomyocytes, indicating more oxidized state of mitochondria. Isoflurane treatment also elicited partial dissipation of mitochondrial transmembrane potential, which remained depolarized even after anesthetic withdrawal (tetramethyl-rhodamine fluorescence intensity declined to 83 [+ or -] 3 and 81 [+ or -] 7% of baseline during isoflurane exposure and washout, respectively). Mild uncoupling, with preserved ATP synthesis, was also detected in mitochondria that were isolated from animals that had been previously preconditioned by isoflurane in vivo, revealing its memory nature. These mitochondria, after exposure to hypoxia and reoxygenation, exhibited better preserved respiration and ATP synthesis compared with mitochondria from nonpreconditioned animals. Partial mitochondrial depolarization was paralleled by a diminished [Ca.sup.2+] uptake into isoflurane-treated mitochondria, as indicated by the reduced increment in rhod-2 fluorescence when mitochondria were challenged with increased [Ca.sup.2+] (180 [+ or -] 24 vs. 258 [+ or -] 14% for the control). In conclusion, isoflurane preconditioning elicits partial mitochondrial uncoupling and reduces mitochondrial [Ca.sup.2+] uptake. These effects are likely to reduce the extent of the mitochondrial damage after the hypoxic stress. cardioprotection; uncoupling doi: 10.1152/ajpcell.00221.2006.

Published
2007

18. Alterations in wall shear stress predict sites of neointimal hyperplasia after stent implantation in rabbit iliac arteries

Author

LaDisa, John F., Jr., Olson, Lars. E., Molthen, Robert C., Hettrick, Douglas A., Pratt, Phillip F., Hardel, Michael D., Kersten, Judy R., Warltier, David C., and Pagel, Paul S.

Subjects
Stent (Surgery) -- Research, Arteries -- Research, Heart -- Research, Biological sciences
Abstract

Restenosis resulting from neointimal hyperplasia (NH) limits the effectiveness of intravascular stents. Rates of restenosis vary with stent geometry, but whether stents affect spatial and temporal distributions of wall shear stress (WSS) in vivo is unknown. We tested the hypothesis that alterations in spatial WSS after stent implantation predict sites of NH in rabbit iliac arteries. Antegrade iliac artery stent implantation was performed under angiography, and blood flow was measured before casting 14 or 21 days after implantation. Iliac artery blood flow domains were obtained from three-dimensional microfocal X-ray computed tomography imaging and reconstruction of the arterial casts. Indexes of WSS were determined using three-dimensional computational fluid dynamics. Vascular histology was unchanged proximal and distal to the stent. Time-dependent NH was localized within the stented region and was greatest in regions exposed to low WSS and acute elevations in spatial WSS gradients. The lowest values of WSS spatially localized to the stented area of a theoretical artery progressively increased after 14 and 21 days as NH occurred within these regions. This NH abolished spatial disparity in distributions of WSS. The results suggest that stents may introduce spatial alterations in WSS that modulate NH in vivo. computational fluid dynamics; restenosis; computational modeling; computed tomography; image reconstruction; wall shear stress

Published
2005

20. Cardioprotection by glucose-insulin-potassium: dependence on [K.sub.ATP] channel opening and blood glucose concentration before ischemia

Author

LaDisa, John F., Jr., Krolikowski, John G., Pagel, Paul S., Warltier, David C., and Kersten, Judy R.

Subjects
Hyperglycemia -- Research, Biological sciences
Abstract

We tested the hypothesis that glucose-insulin-potassium (GIK)-induced protection against myocardial infarction depends on ATP-dependent [K.sup.+] ([K.sub.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.sup.-1]*[h.sup.-1]) beginning 75 min before coronary artery occlusion or 5 min before reperfusion. The role of [K.sub.ATP] channels was evaluated by pretreatment with glyburide (0.1 mg/kg). The efficacy of GIK was investigated with increases in blood glucose (BG) concentrations to 300 or 600 mg/dl or experimental diabetes (alloxan/streptozotocin). Infarct size (IS) was 29 [+ or -] 2% of the area at risk in control experiments. GIK decreased (P < 0.05) IS when administered beginning 5 min before reperfusion. This protective action was independent of BG (13 [+ or -] 2 and 12 [+ or -] 2% of area at risk; BG = 80 or 600 mg/dl, respectively) but was abolished in dogs receiving glyburide (30 [+ or -] 4%), hyperglycemia before ischemia (27 [+ or -] 4%), or diabetes (25 [+ or -] 3%). IS was unchanged by GIK when administered before ischemia independent of BG (31 [+ or -] 3, 27 [+ or -] 2, and 35 [+ or -] 3%; BG = 80, 300, and 600 mg/dl, respectively). The insulin component of GIK promotes cardioprotection by [K.sub.ATP] channel activation. However, glucose decreases [K.sub.ATP] channel activity, and this effect predominates when hyperglycemia is present before ischemia. diabetes; hyperglycemia; myocardial infarction

Published
2004

21. Cardiac pharmacological preconditioning with volatile anesthetics: from bench to bedside?

Author

Riess, Matthias L., Stowe, David F., and Warltier, David C.

Subjects
Diabetes -- Research, Biological sciences
Abstract

A steadily increasing number of investigations demonstrate that preconditioning with volatile anesthetics attenuates the deleterious effects of myocardial ischemia and reperfusion injury by an ischemic preconditioning-like mechanism. Thus volatile anesthetics may represent the best choice for anesthesia of patients at risk for myocardial ischemia. However, factors such as old age, coexisting conditions such as diabetes mellitus and the use of oral hypoglycemic drugs or cyclooxygenase inhibitors, timing and duration of myocardial ischemia, and possible constraints of a complicated preconditioning protocol may limit the benefits of this powerful tool under clinical conditions. The purpose of this minireview is to provide a brief overview of the results of basic and clinical research on cardioprotection by volatile anesthetics. age; clinical; diabetes; duration; ischemia-reperfusion injury

Published
2004

23. Contributors

Author

Adhikary, Sanjib, primary, Aguilar, Jorge, additional, Ahere, Charles, additional, Ahmed, Moustafa, additional, Ahn, Jane C., additional, Akhtar, Shamsuddin, additional, Albert, David B., additional, Aldawoodi, Nasrin N., additional, Algren, John T., additional, Almeida-Chen, Gracie, additional, Amar, David, additional, Anastasian, Zirka H., additional, Aniskevich, Stephen, additional, Aronson, Solomon, additional, Arora, Harendra, additional, Asopa, Amit, additional, Atkins, Joshua H., additional, Augoustides, John G., additional, Azam, Mohammad Fareed, additional, Bachman, Catherine R., additional, Bacon, Douglas R., additional, Badley, Andrew D., additional, Baird, Emily, additional, Baldwin, Alethia, additional, Ball, Ryan, additional, Baluch, Amir, additional, Bandola, David, additional, Banks, Shawn, additional, Barash, Paul G., additional, Barrett, Kathleen E., additional, Beaman, Shawn T., additional, Beathe, Jonathan C., additional, Beatie, Christopher D., additional, Beattie, W. Scott, additional, Bechtle, Perry S., additional, Benzinger, G. Richard, additional, Berkow, Lauren, additional, Berman, Jeffrey M., additional, Bernstein, Wendy K., additional, Berry, Arnold J., additional, Berry, Frederic, additional, Berth, Ulrike, additional, Bethune, Walter, additional, Bhambhani, Sumita, additional, Bharadwaj, Shobana, additional, Bhatt, Neil, additional, Billings, Frederic T., additional, Binstock, Wendy B., additional, Birnbach, David J., additional, Bishop, Michael, additional, Black, Stephanie, additional, Blanchette, Mary A., additional, Blum, James M., additional, Boddu, Krishna, additional, Bonasera, Lara, additional, Boortz-Marx, Richard L., additional, Borel, Cecil O., additional, Botz, Gregory H., additional, Boucek, Charles D., additional, Bradford, William, additional, Brainard, Jason C., additional, Braunfeld, Michelle, additional, Braveman, Ferne R., additional, Bravo-Fernandez, Caridad, additional, Breen, Peter H., additional, Brennan, Marjorie, additional, Brentjens, Tricia, additional, Brockel, Megan A., additional, Brodsky, Jay B., additional, Bromberg, Todd A., additional, Broussard, Adam J., additional, Broussard, Chris, additional, Labrie-Brown, Carmen, additional, Brown, Robert H., additional, Brudney, Charles S., additional, Brull, Sorin J., additional, Brunson, Claude, additional, Bryson, Trent, additional, Buchowski, Jacob M., additional, Budac, Stefan, additional, Bush, Zachary D., additional, Butterworth, John, additional, Calo, Lisbeysi, additional, Canlas, Christopher, additional, Cannon, Ayana, additional, Cantie, Shawn M., additional, Caplan, Lisa, additional, Caruso, Marco, additional, Cattano, Davide, additional, Cauldwell, Charles B., additional, Cavallone, Laura, additional, Cereda, Maurizio, additional, Chalifoux, Thomas M., additional, Chan, Susan, additional, Cheek, Theodore G., additional, Chen, Alexander, additional, Cherry, Samuel A., additional, Cheung, Albert T., additional, Chien, Grace L., additional, Choi, Peter T., additional, Ciarallo, Christopher, additional, Cladis, Franklyn, additional, Clapcich, Anthony J., additional, Clark, Richard B., additional, Cohen, Mindy, additional, Cohen, Neal H., additional, Cohen, Robert I., additional, Cohn, Stephan J., additional, Conran, Aisling, additional, Cook, Richard I., additional, Coombs, Randall F., additional, Corda, David M., additional, Cormican, Daniel, additional, Cousin, Darren, additional, Cowell, Vincent S., additional, Cox, Lyndsey, additional, Craigo, Paula A., additional, Cross, Richard C., additional, Cucchiara, Roy F., additional, Daily, William H., additional, Dalal, Gaurang, additional, Dalal, Priti, additional, Danekas, Michael, additional, Darwish, Ahmed M., additional, Darwish, Ribal, additional, Daves, Suanne M., additional, Davis, Kathleen, additional, Davis, Peter J., additional, De Witt, Bracken J., additional, Delphin, Ellise, additional, Deshpande, Seema, additional, Desiderio, Dawn P., additional, Desvarieux, Tricia, additional, Diaz, Laura K., additional, Diez, Christian, additional, Dixit, Sanjay, additional, Dogra, Meenakshi, additional, Domino, Karen B., additional, Dorhauer, Kathryn, additional, Dorman, Todd, additional, Doussan, Don D., additional, Duke, James, additional, Duncan, Ann C., additional, Dupont, Frank W., additional, Dziewit, Andrew, additional, Easdown, L. Jane, additional, Easley, R. Blaine, additional, Ebert, Thomas J., additional, Eckmann, David M., additional, Egan, Talmage D., additional, Eisdorfer, Seth, additional, Elkassabany, Nabil M., additional, Ellender, Ryan P., additional, Emory, Logan S., additional, Espinosa, Monique, additional, Everett, Lucinda L., additional, Faraday, Nauder, additional, Fehr, James J., additional, Feld, James M., additional, Fenton, Lynn A., additional, Ferguson, Laura H., additional, Fiegel, Matthew, additional, Fields, Aaron M., additional, Finlayson, Gordon N., additional, Finley, Alan, additional, Fischer, Gregory W., additional, Fiskum, Gary, additional, Fitzpatrick, Molly, additional, Flatto, Russell, additional, Fleisher, Lee A., additional, Flower, Ronda, additional, Folgueras, Annette G., additional, Forte, Patrick J., additional, Foss, Joseph F., additional, Fox, Charles J., additional, Furman, William R., additional, Gaiser, Robert, additional, Gambling, David R., additional, Gardiner, Scott, additional, Garvey, Matthew L., additional, Gaupp, Abraham C., additional, Gayer, Steven, additional, Geiduschek, Jeremy M., additional, Gencorelli, Frank, additional, Gewirtz, Eric, additional, Ghani, Ghaleb A., additional, Gibbs, Charles P., additional, Gibson, Jeremy L., additional, Gilbert, Lori, additional, Gingrich, Kevin J., additional, Ginsburg, Gregory, additional, Giordano, Christopher, additional, Goepfert, Christine E., additional, Gomez, Hernando, additional, Gomez, Santiago, additional, Goodman, Alanna E., additional, Goodman, Stephanie R., additional, Gottlieb, Alexandru, additional, Gottlieb, Ori, additional, Gottschalk, Allan, additional, Goudra, Basavana Gouda, additional, Gould, Harry J., additional, Gravenstein, Nikolaus, additional, Graybill, Megan, additional, Greeley, William J., additional, Guffey, Patrick, additional, Haddadin, Ala Sami, additional, Hagen, John G., additional, Hakim, Karim Abdel, additional, Hall, Michael, additional, Halliday, N. James, additional, Hannallah, Raafat S., additional, Hansen, Jeremy, additional, Hanson, C. William, additional, Hantler, Charles B., additional, Harris, Andrew P., additional, Hastie, Jonathan, additional, Hawney, Henry A., additional, Heard, Stephen O., additional, Heavner, James E., additional, Hecker, James G., additional, Hein, Elizabeth A., additional, Heitmiller, Eugenie, additional, Helfaer, Mark, additional, Heller, Lori B., additional, Hemphill, Andrew, additional, Hendrickse, Adrian, additional, Hensley, Frederick A., additional, Herrick, Ian A., additional, Hester, Douglas, additional, Heyer, Eric J., additional, Higgins, Michael S., additional, Hines, Roberta, additional, Hogue, Charles W., additional, Holroyd, Kenneth J., additional, Holt, Natalie F., additional, Howell, Simon J., additional, Huda, Faisal, additional, Hude, Keith E., additional, Hughes, Hayden R., additional, Hunter, James M., additional, Hymel, Brad J., additional, Ibinson, James W., additional, Iles, Karen E., additional, Insoft, Robert M., additional, Isono, Shiroh, additional, Ivashkov, Yulia, additional, Jachna, Bozena R., additional, Jankowska, Anna, additional, Janosy, Norah, additional, Jayaraman, Arun L., additional, Jimenez, Nathalia, additional, Johnson, Judy G., additional, Jones, Lyndia, additional, Jooste, Edmund H., additional, Kain, Zeev N., additional, Kalangie, Maudy, additional, Kalarickal, Philip L., additional, Kamel, Ihab, additional, Kang, Mia, additional, Kangrga, Ivan, additional, Kapoor, Ravish, additional, Karl, Helen W., additional, Karsanac, Christopher, additional, Karthik, Swaminathan, additional, Katz, Jeffrey A., additional, Kaye, Alan, additional, Kaye, Adam M., additional, Kaynar, A. Murat, additional, Kenepp, Nancy B., additional, Kertai, Miklos D., additional, Keyes, Mary A., additional, Khan, Sarah, additional, Khoche, Swapnil, additional, Kim, David Y., additional, Kim, Jerry H., additional, King, Kimberly M., additional, Kirsch, Jeffrey, additional, Klopman, Matthew A., additional, Knight, Paul R., additional, Koblin, Donald D., additional, Kofke, W. Andrew, additional, Kopp, Vincent J., additional, Koveleskie, Joseph R., additional, Kowalczyk, Courtney, additional, Kozmenko, Valeriy V., additional, Krummen, Kaylyn, additional, Kudchadkar, Sapna R., additional, Kudrick, Nathan, additional, Kung, Adrienne, additional, Kurth, C. Dean, additional, Kyle, Robert, additional, LaFleur, J. Lance, additional, Lai, Jason G., additional, Lalwani, Kirk, additional, Lanier, William L., additional, Larson, Dawn M., additional, Layman, Richard M., additional, Lee, Chris C., additional, Lema, Mark J., additional, Lenox, W. Casey, additional, Leung, Jacqueline M., additional, Levitt, Roy C., additional, Levy, Jerrold H., additional, Lichtor, J. Lance, additional, Lin, Charles, additional, Lin, Sharon L., additional, Lindeman, Karen S., additional, Lirette, Lesley, additional, Litman, Ronald S., additional, Liu, Qianjin, additional, Liu, Renyu, additional, Liu, Wen-Shin, additional, Lockman, Justin, additional, Loftness, Stanley L., additional, London, Martin J., additional, Lumb, Philip D., additional, Lupa, M. Concetta, additional, Lynn, Anne Marie, additional, Mahendran, Devi, additional, Mako, Jeffrey, additional, Malhotra, Anuj, additional, Malhotra, Vinod, additional, Malinow, Andrew M., additional, Mandabach, Mark G., additional, Mangano, Dennis T., additional, Mansoor, Sobia, additional, Maranets, Inna, additional, Mark, Jonathan B., additional, Markovic, Sinisa, additional, Marsh, H. Michael, additional, Martin, Choendal, additional, Martin, Nicole D., additional, Martz, Douglas, additional, Matei, Veronica A., additional, Mathews, Letha, additional, Maxwell, Lynne G., additional, McArdle, Philip, additional, McCarren, John P., additional, McClain, Brenda C., additional, McClure, Brian, additional, McDade, William A., additional, McGoldrick, Kathryn E., additional, McGrath, Brian J., additional, McHugh, Gregory L., additional, McIlroy, David, additional, McKeown, Jason, additional, McLoughlin, Thomas M., additional, McRae, R. Yan, additional, Meadow, William L., additional, Menda, Sameer, additional, Merritt, William T., additional, Metro, David G., additional, Mets, Berend, additional, Mikhaeil, Hosni, additional, Miller, David W., additional, Miller, Jessica, additional, Minhaj, Mohammed, additional, Mirski, Marek A., additional, Mitter, Nanhi, additional, Mittnacht, Alexander J.C., additional, Modak, Raj K., additional, Moine, Pierre, additional, Monitto, Constance L., additional, Month, Richard C., additional, Moon, Richard E., additional, Moore, Laurel E., additional, Moore, Roger A., additional, Moore, Thomas A., additional, Morrison, Debra E., additional, Moss, Jonathan, additional, Moyers, John R., additional, Muir, Jesse J., additional, Munson-Young, Adam J., additional, Muravchick, Stanley, additional, Murkin, John M., additional, Nagele, Peter, additional, Nagi, Peter A., additional, Nahrwold, Daniel A., additional, Nahrwold, Michael L., additional, Naik, Madhavi, additional, Navaratnam, Manchula, additional, Nebbia, Stephan P., additional, Nelson, Priscilla, additional, Nguyen, Thai T., additional, Nguyen, Viet, additional, Nikolaidis, Stavroula, additional, Nisnevitch, Zoulfira, additional, Njoku, Dolores B., additional, Njoku, Mary J., additional, Norris, Edward J., additional, Nwokolo, Omonele O., additional, Nyhan, Daniel, additional, O'Byrne, William T., additional, Ochroch, Edward A., additional, Oken, Andrew, additional, Orgain, Nathan, additional, Oriol, Nancy E., additional, Orozco, Pedro, additional, Ostermeier, Andreas M., additional, Ovassapian, Andranik, additional, Ozcan, Mehmet S., additional, Padnos, Ira, additional, Pai, Sheela S., additional, Pal, Nirvik, additional, Palaniappan, Dhamodaran, additional, Palmer, Susan K., additional, Palte, Howard D., additional, Pan, Wei, additional, Panzer, Oliver, additional, Pappachan, Sibi, additional, Passannante, Anthony, additional, Patel, Dennis A., additional, Patel, Dilipkumar K., additional, Patel, Kirit M., additional, Patel, Samir, additional, Patel, Shalin, additional, Pathak, Sanup, additional, Patt, Minda L., additional, Pauldine, Ronald W., additional, Pawelek, Olga, additional, Pawelek, Tim, additional, Paydar, Kiarash, additional, Pearl, Ronald G., additional, Peeters-Asdourian, Christine, additional, Perela, Padmavathi R., additional, Petrovitch, Charise T., additional, Petrozza, Patricia H., additional, Phillips, Dennis, additional, Phillips, Mark C., additional, Piefer, Christine, additional, Pierre, Edgar J., additional, Pinson, S. William, additional, Pivalizza, Evan G., additional, Planinsic, Raymond M., additional, Poldermans, Don, additional, Pomerantz, Joel M., additional, Pope, Jason E., additional, Popescu, Wanda M., additional, Porche, Vivian H., additional, Porhomayon, Jahan, additional, Portnoy, Dmitry, additional, Postle, Corinne K., additional, Primeaux, Paul J., additional, Prough, Donald S., additional, Puskas, Ferenc, additional, Puyo, Carlos A., additional, Quiggle, Forrest, additional, Rabb, Mary, additional, Rae, Bronwyn R., additional, Rafique, Muhammad B., additional, Raiten, Jesse M., additional, Rajagopal, Arvind, additional, Rajagopal, Srinivasan, additional, Rajpal, Gaurav, additional, Ramamoorthy, Chandra, additional, Rampil, Ira J., additional, Ramsay, James G., additional, Ramsey, James A., additional, Rao, Vidya N., additional, Ratsiu, Joana, additional, Read, Selina, additional, Reddy, Ronjeet, additional, Reduque, Leila L., additional, Reich, David L., additional, Ricketts, Karene, additional, Ricks, Cameron, additional, Riedel, Bernhard, additional, Rimal, Jyotsna, additional, Rinehart, Joseph, additional, Riopelle, James M., additional, Rizza, Stacey A., additional, Robertson, Amy C., additional, Robinson, Stephen, additional, Rock, Peter, additional, Rodriguez-Blanco, Yillam F., additional, Roizen, Michael F., additional, Roke, Daniel M., additional, Romeo, Ryan, additional, Rosa, Joseph, additional, Rosen, David A., additional, Rosen, Kathleen, additional, Rosenbaum, Stanley H., additional, Rosenberg, Andrew D., additional, Rosenberg, Andrew L., additional, Rosenberg, Henry, additional, Rosenblatt, Meg A., additional, Roth, Steven, additional, Rothman, Brian, additional, Rountree, Justin L., additional, Rowan, Matthew J., additional, Rozner, Marc, additional, Rubin, Ryan, additional, Rupp, Stephen M., additional, Russell, W. John, additional, Russo, Thomas A., additional, Sabartinelli, Alecia L., additional, Sakai, Tetsuro, additional, Salinas, Orlando J., additional, Samm, Paul L., additional, Samuel, Jibin, additional, Sandven, Tor, additional, Sanford, Ted J., additional, Sappenfield, Joshua W., additional, Saravanan, Ponnusamy, additional, Sathishkumar, Subramanian, additional, Schlichter, R. Alexander, additional, Schnell, Eric, additional, Schreibman, David L., additional, Schubert, Armin, additional, Schulman, Peter, additional, Schultz, Todd A., additional, Schwartz, Alan Jay, additional, Schwartz, Jamie McElrath, additional, Schwartz, Jeffrey J., additional, Scott, Benjamin K., additional, Seltzer, Joseph L., additional, Seres, Tamas, additional, Sessler, Daniel I., additional, Sethna, Navil F., additional, Setty, Amar, additional, Shabaz, Paul W., additional, Shah, Pranav, additional, Shah, Saroj Mukesh, additional, Sharifpour, Milad, additional, Shay, Joanne, additional, Shepherd, Jay, additional, Shiffrin, Jeffrey S., additional, Shindell, Marina, additional, Siker, Daniel, additional, Silverman, Richard, additional, Simon, Brett A., additional, Singh, Nina, additional, Sinha, Ashish C., additional, Sladen, Robert N., additional, Slevin, Kieran A., additional, Sloan, Tod B., additional, Smith, Kathleen, additional, Smith, Timothy E., additional, Smoot, Victoria, additional, Snegovskikh, Denis, additional, Soifer, Betsy Ellen, additional, Solorzano, Molly, additional, Sonner, James M., additional, Sophocles, Aris, additional, Sparrow, James A., additional, Spiegel, Joan, additional, Spiess, Bruce D., additional, Sripada, Ramprasad, additional, Stead, Stanley W., additional, Stearns, Joshua D., additional, Stees, Kelly, additional, Steffey, Clinton, additional, Stemland, Christopher, additional, Stene, John, additional, Stephens, Christopher T., additional, Stierer, Tracey L., additional, Stokes, O. Jameson, additional, Stolp, Bryant W., additional, Stowe, David F., additional, Strickland, Ted, additional, Strom, Suzanne, additional, Sullivan, Erin A., additional, Sumler, Michele, additional, Sun, Dajin, additional, Sun, Lena, additional, Sung, Esther, additional, Swanson, Veronica C., additional, Szolnoki, Judit, additional, Talarico, Joe, additional, Tan, Gee Mei, additional, Tang, Darryl T., additional, Tarasi, Paul, additional, Tempelhoff, René, additional, Tetzlaff, John E., additional, Thorne, Alisa C., additional, Thung, Arlyne, additional, Tilak, Vasanti, additional, Tobin, Kate, additional, Tobin, Joseph R., additional, Tobin, Michael J., additional, Todd, R. David, additional, Tomlinson, Matthew, additional, Toung, Thomas J., additional, Tran, Lien B., additional, Tran, Minh Chau Joe, additional, Tremper, Kevin K., additional, Tsai, Sanyo, additional, Tseng, George S., additional, Tuman, Kenneth J., additional, Tung, Avery, additional, Tung, Cynthia, additional, Twersky, Rebecca, additional, Twite, Mark, additional, Ulatowski, John A., additional, Urban, Michael, additional, Vallejo, Manuel C., additional, Vannucci, Andrea, additional, Varon, Albert J., additional, Vasudevan, Anasuya, additional, Viswanathan, Susheela, additional, Vitin, Alexander A., additional, Voelckel, Wolfgang, additional, Walia, Ann, additional, Wall, Russell T., additional, Wallace, Terrence, additional, Wang, Shu-Ming, additional, Warltier, David C., additional, Waskell, Lucy, additional, Watkins, Scott, additional, Wedel, Denise, additional, Weiss, Stuart J., additional, Weissman, Charles, additional, Weitzel, Nathaen, additional, Weller, Gregory, additional, Whitney, Gina, additional, Whittington, Robert A., additional, Wilkerson, Danny, additional, Wilkes, Nancy C., additional, Williams, Michael, additional, Windsor, Jimmy, additional, Wittels, Bernard, additional, Wolff, Gregory A., additional, Wong, Andrew K., additional, Woods, Stacie N., additional, Wright, A.J., additional, Xie, Zheng, additional, Young, Christopher C., additional, Yuan, Ian, additional, Yudkowitz, Francine S., additional, Zaidan, James R., additional, Zanaboni, Paul, additional, Zapol, Warren M., additional, Zimmerman, Angela, additional, and Zwass, Maurice S., additional

Published
2011
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24. Reactive oxygen species are critical mediators of coronary collateral development in a canine model

Author

Gu, Weidong, Weihrauch, Dorothee, Tanaka, Katsuya, Tessmer, John P., Pagel, Paul S., Kersten, Judy R., Chilian, William M., and Warltier, David C.

Subjects
Neovascularization -- Research, Biological sciences
Abstract

Recent evidence suggests that reactive oxygen species (ROS) promote proliferation and migration of vascular smooth muscle (VSMC) and endothelial cells (EC). We tested the hypothesis that ROS serve as crucial messengers during coronary collateral development. Dogs were subjected to brief (2 min), repetitive coronary artery occlusions (1/h, 8/day, 21 day duration) in the absence (occlusion, n = 8) or presence of N-acetylcysteine (NAC) (occlusion + NAC, n = 8). A sham group (n = 8) was instrumented identically but received no occlusions. In separate experiments, ROS generation after a single 2-min coronary artery occlusion was assessed with dihydroethidium fluorescence. Coronary collateral blood flow (expressed as a percentage of normal zone flow) was significantly increased (71 [+ or -] 7%) in occlusion dogs after 21 days but remained unchanged (13 [+ or -] 3%) in sham dogs. Treatment with NAC attenuated increases in collateral blood flow (28 [+ or -] 8%). Brief coronary artery occlusion and reperfusion caused ROS production (256 [+ or -] 33% of baseline values), which was abolished with NAC (104 [+ or -] 12%). Myocardial interstitial fluid produced tube formation and proliferation of VSMC and EC in occlusion but not in NAC-treated or sham dogs. The results indicate that ROS are critical for the development of the coronary collateral circulation. angiogenesis; collateral circulation; free radicals; growth substances

Published
2003

25. Expression of VEGF and angiopoietins-1 and -2 during ischemia-induced coronary angiogenesis

Author

Matsunaga, Toshiro, Warltier, David C., Tessmer, John, Weihrauch, Dorothee, Simons, Michael, and Chilian, William M.

Subjects
Ischemia -- Research, Biological sciences
Abstract

The mechanisms underlying coronary capillary growth in response to ischemia are undefined. We hypothesized that the expression of vascular endothelial growth factor (VEGF) and angiopoietin (Ang)/Tie-2 were involved in capillary growth as an adaptation to ischemia. To test this hypothesis we measured capillary density, and the expressions of VEGF, Ang-1, Ang-2, and the Tie-2 receptor and its phosphorylation state during repetitive episodes of myocardial ischemia in chronically instrumented canines. Repetitive episodes of ischemia were induced by multiple (once/hour; 8/day), brief (2 min) occlusions of the left anterior descending coronary artery for 1, 7, 14, or 21 days. A sham group received the same instrumentation as the experimental groups but not the occlusion protocol. Collateral blood flow (microspheres) progressively increased from 9 [+ or -] 3 to 83 [+ or -] 10 ml*[min.sup.-1]*100 [g.sup.-1] on day 21. Capillary density increased at day 7 from 2,378 [+ or -] 53 (sham) to 2,962 [+ or -] 60/[mm.sup.2], but it decreased to 2,594 [+ or -] 39/[mm.sup.2] at day 21. Both VEGF and Ang-2 expression in myocardial interstitial fluid (Western analyses) peaked at day 3 of the repetitive occlusions but waned thereafter. In contrast the expression of Ang-1 remained relatively constant at all times in the occlusion groups. In shams, the expression of VEGF and Ang-2 was low and constant at all times. Tie-2 phosphorylation myocardial decreased decreased at day 7 but increased at 21 days of occlusions (P < 0.05). Our results indicate that capillary density was augmented by myocardial ischemia, but after development of collaterals and restoration of flow to the ischemic zone, capillary density returned to control levels. The change in capillary density paralleled with VEGF and Ang-2 expression but was inversely related to Tie-2 phosphorylation. We speculate the coronary angiogenesis is a coordinated event involving the expression of both VEGF and Ang-2 and that therapeutic angiogenic strategies may ultimately require treatment with more than a single factor. coronary collateral; vascular endothelial growth factor; Tie-2

Published
2003

26. Reactive oxygen species modulate coronary wall shear stress and endothelial function during hyperglycemia

Author

Gross, Eric R., LaDisa, John F., Jr., Weihrauch, Dorothee, Olson, Lars E., Kress, Tobias T., Hettrick, Douglas A., Pagel, Paul S., Warltier, David C., and Kersten, Judy R.

Subjects
Hyperglycemia -- Physiological aspects, Coronary heart disease -- Physiological aspects, Biological sciences
Abstract

Hyperglycemia is associated with generation of reactive oxygen species (ROS), and this action may contribute to accelerated atherogenesis. We tested the hypothesis that hyperglycemia produces alterations in left anterior descendlng coronary artery (LAD) wall shear stress concomitant with endothelial dysfunction and ROS production in dogs (n = 12) instrumented for measurement of LAD blood flow, velocity, and diameter. Dogs were randomly assigned to receive vehicle (0.9% saline) or the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (tempo]) and were administered intravenous infusions of v-glucose to achieve target blood glucose concentrations of 350 and 600 mg/dl (moderate and severe hyperglycemia, respectively). Endothelial function and ROS generation were assessed by coronary blood flow responses to acetylcholine (10, 30, and 100 ng/kg) and dihydroethidium fluorescence of myocardial biopsies, respectively. Indexes of wall shear stress were calculated with conventional fluid dynamics theory. Hyperglycemia produced dose-related endothelial dysfunction, increases in ROS production, and reductions in oscillatory shear stress that were normalized by tempo]. The results suggest a direct association between hyperglycemia-induced ROS production, endothelial dysfunction, and decreases in oscillatory shear stress in vivo. coronary artery disease; diabetes; oscillatory shear stress; oxidant stress

Published
2003

27. Contributors

Author

Abel, Ted G., primary, Afonin, Olga N., additional, Allen, Paul D., additional, Andrews, J. Jeffrey, additional, Ang-Lee, Michael, additional, Apfel, Christian C., additional, Arnold, William P., additional, Aronson, Solomon, additional, Bader, Angela M., additional, Baker, David, additional, Baraka, Anis, additional, Barbeito, Atilio, additional, Barker, Steven J., additional, Bar-Yosef, Shahar, additional, Berde, Charles B., additional, Berkowitz, Darryl H., additional, Birnbach, David J., additional, Bogod, David, additional, Brockwell, Russell C., additional, Brown, David L., additional, Browne, Ingrid M., additional, Cahalan, Michael K., additional, Camporesi, Enrico M., additional, Campos, Javier H., additional, Cassorla, Lydia, additional, Coté, Charles J., additional, Dalens, Bernard J., additional, Deutschman, Clifford S., additional, Dieckmann, Peter, additional, Diwan, Sudhir, additional, Drummond, John C., additional, Dutton, Richard P., additional, Eckmann, David M., additional, Eger, Edmond I., additional, Eich, Christoph, additional, Eng, Matthew R., additional, Eriksson, Lars I., additional, Eskaros, Stephen M., additional, Farber, Neil E., additional, Feldman, Marc Allan, additional, Fischer, Stephen P., additional, Fleisher, Lee A., additional, Flood, Pamela, additional, Fukuda, Kazuhiko, additional, Gaba, David M., additional, Ganter, Michael T., additional, Gelb, Adrian W., additional, Gelman, Simon, additional, Glass, Peter S.A., additional, Glick, David B., additional, Goodnough, Lawrence T., additional, Goswami, Sumeet, additional, Grasso, Salvatore, additional, Gray, Andrew T., additional, Greeley, William J., additional, Gregory, George A., additional, Grigore, Alina M., additional, Grissom, Thomas E., additional, Gropper, Michael A., additional, Haddad, Fouad Salim, additional, Hanson, C. William, additional, Hauser, Michael C., additional, Hedenstierna, Göran, additional, Heitmiller, Eugenie S., additional, Hemmings, Hugh C., additional, Henderson, John, additional, Hillel, Zak, additional, Hofer, Christoph K., additional, Horlocker, Terese T., additional, Howard, Steven K., additional, Huang, Yuguang, additional, Hüpfl, Michael, additional, Hurley, Robert W., additional, Ichinose, Fumito, additional, Irefin, Samuel A., additional, Johnson, Ken B., additional, Joris, Jean L., additional, Kaye, Alan D., additional, Kelz, Max B., additional, Kindscher, James D., additional, Kohl, Benjamin A., additional, Kopf, Andreas, additional, Lachmann, Burkhard, additional, Lam, Arthur M., additional, Landesberg, Giora, additional, Larson, Merlin D., additional, Lee, Jae-Woo, additional, Lema, Guillermo, additional, Leslie, Kate, additional, Lien, Cynthia A., additional, Litt, Lawrence, additional, Liu, Linda, additional, Lubarsky, David A., additional, Mahla, Michael E., additional, Malhotra, Vinod, additional, Mark, Jonathan B., additional, Martin, Jackie L., additional, Martinez, Elizabeth A., additional, Martinez-Ruiz, Ricardo, additional, Jeevendra Martyn, J.A., additional, Mascia, Luciana, additional, Mashour, George A., additional, Maze, Mervyn, additional, McCunn, Maureen, additional, McEvoy, Matthew D., additional, McGlinch, Brian P., additional, Mets, Berend, additional, Miller, Ronald D., additional, Monk, Terri G., additional, Moon, Richard E., additional, Mori, Kenjiro, additional, Moss, Jonathan, additional, Mushlin, Phillip S., additional, Nagele, Peter, additional, Naguib, Mohamed, additional, Nakao, Shinichi, additional, Namiki, Akiyoshi, additional, Nathan, Aruna T., additional, Neligan, Patrick J., additional, Newman, Stanton P., additional, Nicholau, Dorre, additional, Niemann, Claus U., additional, Nishanian, Ervant, additional, Norris, Edward J., additional, Nuevo, Florian R., additional, Nussmeier, Nancy A., additional, O'Connor, Christopher J., additional, O'Hara, Jerome, additional, Pagel, Paul S., additional, Papadakos, Peter J., additional, Patel, Anil, additional, Patel, Piyush M., additional, Pauldine, Ronald, additional, Pearce, Robert A., additional, Perouansky, Misha, additional, Pessah, Isaac N., additional, Pittet, Jean-François, additional, Pratt, Phillip F., additional, Pronovost, Peter J., additional, Rall, Marcus, additional, Rampil, Ira J., additional, Ranieri, V. Marco, additional, Rasmussen, Lars, additional, Reves, J.G., additional, Ricci, Zaccaria, additional, Riopelle, James M., additional, Rockford, Melissa, additional, Roizen, Michael F., additional, Ronco, Claudio, additional, Rosenbaum, Stanley H., additional, Roth, Steven, additional, Rothenberg, David M., additional, Rozner, Marc A., additional, Sarwar, Muhammad F., additional, Schroeder, Rebecca A., additional, Schwartz, Allan Jay, additional, Schwartz, Andrew, additional, Schwarzenberger, Johanna C., additional, Schwinn, Debra A., additional, Searles, Bruce E., additional, Sessler, Daniel I., additional, Seubert, Christoph N., additional, Shafer, Steven L., additional, Shaw, Andrew, additional, Shingu, Koh, additional, Sieber, Frederick E., additional, Simpson, Sir Peter, additional, Sinha, Ashish C., additional, Sladen, Robert N., additional, Slaughter, Thomas F., additional, Slinger, Peter D., additional, Souter, Michael J., additional, Stafford-Smith, Mark, additional, Stanski, Donald R., additional, Stein, Christoph, additional, Stensrud, Paul E., additional, Strichartz, Gary R., additional, Stygall, Jan, additional, Sudheendra, Vijayendra, additional, Sun, Lena S., additional, Sweitzer, BobbieJean, additional, Szocik, James, additional, Tempe, Deepak K., additional, Tremper, Kevin K., additional, Tuman, Kenneth J., additional, Urban, Michael K., additional, Van Norman, Gail A., additional, Vezina, Daniel P., additional, Viby-Mogensen, Jørgen, additional, Waisel, David B., additional, Warltier, David C., additional, Wedel, Denise J., additional, Weissman, Charles, additional, White, Paul F., additional, White, Roger D., additional, Wiener-Kronish, Jeanine P., additional, Wu, Christopher L., additional, Yamakage, Michiaki, additional, Yost, C. Spencer, additional, Young, William L., additional, Yuan, Chun-Su, additional, Zapol, Warren M., additional, Zhou, Jie, additional, and Zwass, Maurice S., additional

Published
2010
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30. Isoflurane-induced preconditioning is attenuated by diabetes

Author

Tanaka, Katsuya, Kehl, Franz, Gu, Weidong, Krolikowski, John G., Pagel, Paul S., Warltier, David C., and Kersten, Judy R.

Subjects
Physiology -- Research, Hyperglycemia -- Research, Heart attack -- Research, Diabetes -- Complications, Biological sciences
Abstract

Volatile anesthetics stimulate, but hyperglycemia attenuates, the activity of mitochondrial ATP-regulated [K.sup.+] channels. We tested the hypothesis that diabetes mellitus interferes with isoflurane-induced preconditioning. Acutely instrumented, barbiturate-anesthetized dogs were randomly assigned to receive 0, 0.32, or 0.64% end-tidal concentrations of isoflurane in the absence or presence of diabetes (3 wk after administration of alloxan and streptozotocin) in six experimental groups. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size (triphenyltetrazolium staining) was 29 [+ or -] 3% (n = 8) of the left ventricular area at risk in control experiments. Isoflurane reduced infarct size (15 [+ or ] 2 and 13 [+ or -] 1% during 0.32 and 0.64% concentrations; n = 8 .and 7 dogs, respectively). Diabetes alone did not alter infarct size (30 [+ or -] 3%; n = 8) but blocked the protective effects of 0.32% (27 [+ or -] 2%; n = 7) and not 0.64% isoflurane (18 [+ or -] 3%; n = 7). Infarct size was directly related to blood glucose concentrations in diabetic dogs, but this relationship was abolished by higher concentrations of isoflurane. The results indicate that blood glucose and end-tidal isoflurane concentrations are important determinants of infarct size during anesthetic-induced preconditioning. hyperglycemia; myocardial infarction; volatile anesthetics

Published
2002

40. Acute hyperglycemia abolishes ischemic preconditioning in vivo

Author

Kersten, Judy R., Schmeling, Todd J., Orth, Karl G., Pagel, Paul S., and Warltier, David C.

Subjects
Reperfusion injury -- Research, Ischemia -- Research, Hyperglycemia -- Research, Dogs -- Research, Biological sciences
Abstract

Research was conducted to test the hypothesis that acute hyperglycemia changes the protection generated by ischemic preconditioning. Acutely instrumented dogs were exposed to a prolonged coronary artery occlusion and reperfusion and ischemic preconditioning was induced by occlusion-reperfusion periods. Results indicate that acute hyperglycemia adversely regulates myocardial injury in reaction to ischemia in vivo.

Published
1998

43. Protamine inhibits coronary collateral development in a canine model of repetitive coronary occlusion

Author

Kersten, Judy R., Pagel, Paul S., and Warltier, David C.

Subjects
Coronary arteries -- Obstruction, Heart -- Contraction, Regional blood flow -- Analysis, Biological sciences
Abstract

A study of the suppression of coronary collateral development due to chronic myocardial ischemia in dogs by protamine in saline- and protamine-treated dogs that are subjected to left anterior descending coronary artery (LAD) occlusions confirms the inhibition by protamine. Control dogs exhibit a time-dependent enhancement in collateral blood flow due to ischemic myocardium, consecutive lowering of flow debt payment and progressive normalization of myocardial contractile function during LAD occlusion, indicating coronary collateral development. Protamine-treated dogs retain regional contractile dysfunction and postocclusive reactive hyperemic responses.

Published
1995

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