Gregory K Asimakis

University of Texas Medical Branch at Galveston, Galveston, TX, United States

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Publications (7)28.7 Total impact

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    ABSTRACT: Whole body hyperthermia has been shown to be highly effective in preconditioning cardiac tissue against reperfusion injury. The current study was aimed to assess the ability of regional sublethal laser-induced hyperthermia to precondition cardiac tissue against ischemic-induced myocardial infarction. Diode laser radiation was used to locally heat (42 degrees C) the left ventricle by irradiating the epicardial surface of rat heart for 20 min. As control, another group of animals were treated with whole-body hyperthermia (WBH) for 20 min. After a 4-h recovery period, the left coronary artery was occluded for 30 min followed by 4 h of reperfusion. A significant degree of reduction in infarct size as assessed by percent of at-risk area was observed in animals that were subjected to laser-induced local hyperthermia (15.4 +/- 3.1; n = 5) versus the sham group (49.8 +/- 6.6; n = 5). The degree of cardiac protection induced by local hyperthermia was similar to the protection observed when the animals were preconditioned with WBH. Furthermore, regional laser-induced hyperthermia and WBH induced similar degree of up-regulation of heat shock protein 70 in cardiac tissue. Regional hyperthermia up-regulated heat shock protein in regions of the heart beyond that directly subjected to laser-induced heat stress. Sublethal local heating of the heart with diode laser irradiation can improve myocardial salvage and may provide a practical approach for tissue preconditioning against reperfusion injury.
    Journal of Surgical Research 10/2008; 149(2):177-83. · 2.02 Impact Factor
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    ABSTRACT: Whole-body hyperthermia (WBH) promotes cardiac protection against ischemia/reperfusion injury, in part by up-regulation of heat shock proteins (HSP). Whether heat stress also promotes up-regulation of angiogenic factors or induces endothelial cell proliferation is unknown. We studied the effects of heat stress on up-regulation of vascular endothelial growth factor (VEGF) and growth of new blood vessels following WBH. Anesthetized rats were subjected to WBH at 42 degrees C for 15 min. The control (n=23) and heated (n=55) groups were allowed to recover for 4, 12, 24, 48, or 72 h prior to harvesting the heart for Western Blot and immunohistochemical assessment of VEGF, HSP70, and platelet endothelial cell adhesion molecular-1 (PECAM-1). A significant increase in VEGF and HSP70 expression was observed as early as 4 h post-heating. The Western Blot analysis revealed a close temporal correlation between up-regulation of HSP70 and VEGF. Maximum VEGF and HSP70 expression occurred at 12 and 24 h post-heating in the left and right ventricles, respectively. The right ventricle showed the greatest expression of both VEGF and HSP70. Immunostaining revealed that VEGF was focally increased in the endothelial cells of capillaries, small arteries, and in interstitium. At 48 and 72 h post-heating, multiple areas of extensive capillary proliferation occurred in the epicardial region of the right ventricle. These observations were verified by quantitative analysis of the density of blood vessels as determined by PECAM-1 staining. Our experiments show that sublethal heat stress can lead to upregulation of both VEGF and HSP70 in cardiac tissue and promote focal endothelial proliferation in the heart.
    Life Sciences 11/2006; 79(19):1781-8. · 2.56 Impact Factor
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    ABSTRACT: Recent evidence suggests that sepsis may induce an uncoupling of oxidative phosphorylation. The purpose of this study was to quantify temporal changes in hepatic oxygen consumption and cellular energy state with increasing severity of sepsis and thus assess the interrelationship of these parameters as either primary defect or compensatory response. Pseudomonas aeruginosa was infused intravenously in eight instrumented anesthetized swine inducing a progressive severity of sepsis to shock. Eight other animals served as instrumented controls. Hepatic blood flow, oxygen use, and concentrations of ATP, ADP, AMP, NAD(+), and NADH were measured at baseline and then sequentially during the study. Except for an increase in heart rate, there were no temporal changes in measured values for the control animals. For swine receiving P. aeruginosa, hepatic oxygen delivery and consumption increased with early sepsis whereas there were no alterations in the concentrations of adenine nucleotides or NAD(+)/NADH within liver. Septic shock was notable for a decrease in oxygen delivery yet oxygen consumption remained elevated because of an increase in percent oxygen extraction. The hepatic concentrations of ATP and NADH decreased during septic shock. These findings suggest that any sepsis-induced limitation in phosphorylation may be initially compensated by an increase in oxygen use. This study also suggests that decreases in NADH availability may be a principal factor in the decompensation of sepsis to shock.
    Journal of Surgical Research 12/2003; 115(1):139-47. · 2.02 Impact Factor
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    ABSTRACT: Hypothesis. Recent evidence suggests that sepsis may induce an uncoupling of oxidative phosphorylation. The purpose of this study was to quantify temporal changes in hepatic oxygen consumption and cellular energy state with increasing severity of sepsis and thus assess the interrelationship of these parameters as either primary defect or compensatory response.Main outcome measures. Pseudomonas aeruginosa was infused intravenously in eight instrumented anesthetized swine inducing a progressive severity of sepsis to shock. Eight other animals served as instrumented controls. Hepatic blood flow, oxygen use, and concentrations of ATP, ADP, AMP, NAD+, and NADH were measured at baseline and then sequentially during the study.Results. Except for an increase in heart rate, there were no temporal changes in measured values for the control animals. For swine receiving P. aeruginosa, hepatic oxygen delivery and consumption increased with early sepsis whereas there were no alterations in the concentrations of adenine nucleotides or NAD+/NADH within liver. Septic shock was notable for a decrease in oxygen delivery yet oxygen consumption remained elevated because of an increase in percent oxygen extraction. The hepatic concentrations of ATP and NADH decreased during septic shock.Conclusions. These findings suggest that any sepsis-induced limitation in phosphorylation may be initially compensated by an increase in oxygen use. This study also suggests that decreases in NADH availability may be a principal factor in the decompensation of sepsis to shock.
    Journal of Surgical Research - J SURG RES. 01/2003; 115(1):139-147.
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    Gregory K Asimakis, Scott Lick, Cam Patterson
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    ABSTRACT: Reactive oxygen species (ROS) contribute to myocardial stunning. Superoxide dismutase (SOD) is a major defense mechanism against ROS. The purpose of this study was to evaluate the contributions of cytosolic (SOD1) and mitochondrial (SOD2) isoforms to protect against myocardial stunning. Isolated hearts from wild-type, heterozygous (+/-) SOD1 and SOD2 knockout mice received 30 minutes of ischemia followed by 60 minutes of reperfusion. After 60 minutes of reperfusion, the heart rate multiplied by the developed pressure (HRxDP) in the wild-type and SOD1(+/-) hearts recovered to 92 +/- 9 and 85 +/- 7 of preischemic baseline values, respectively (P=NS). In contrast, the HRxDP was significantly lower (63 +/- 7%) in the SOD2(+/-) hearts compared with the wild-type hearts. Western blot analysis and enzymatic activity of tissue lysates confirmed reduction of activities of specific SOD isoforms without compensatory increase in the other isoform in the knockout animals studied. Postischemic functional recovery is more sensitive to a partial deficiency of SOD2 than a partial deficiency of SOD1. Therefore, modulation of the mitochondrial SOD isoform is a critical determinant in the tolerance of the heart to oxidative stress.
    Circulation 03/2002; 105(8):981-6. · 15.20 Impact Factor
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    ABSTRACT: Background. Improved methods of donor heart preparation before preservation could allow for prolonged storage and permit remote procurement of these organs. Previous studies have shown that overexpression of heat-shock protein 72 provides protection against ischemic cardiac damage. We sought to determine whether rats subjected to heat stress with only 6-hour recovery could acquire protection to a subsequent heart storage for 12 hours at 4°C.Methods. Three groups of animals (n = 10 each) were studied: control, sham-treated, and heat-shocked rats (whole-body hyperthermia 42°C for 15 minutes). After 12-hour cold ischemia hearts were reperfused on a Langendorff column. To confirm any differences in functional recovery, hearts were then subjected to an additional 15-minute period of warm global ischemia after which function and lactate dehydrogenase enzyme leakage were measured.Results. Heat-shocked animals showed marked improvements compared with controls in left ventricular developed pressure (63 ± 4 mm Hg versus 44 ± 4 mm Hg, p < 0.05) heart rate × developed pressure (13,883 ± 1,174 beats per minute × mm Hg versus 8,492 ± 1,564 beats per minute × mm Hg, p < 0.05), rate of ventricular pressure increase (1,912 ± 112 mm Hg/second versus 1,215 ± 162 mm Hg/second, p < 0.005), rate of ventricular pressure decrease (1,258 ± 89 mm Hg/second versus 774 ± 106 mm Hg/second, p < 0.005). Diastolic compliance and lactate dehydrogenase release were improved in heat-shocked animals compared with controls and sham-treated animals. Differences between heat-shocked animals and control or sham-treated animals were further increased after the additional 15-minute period of warm ischemia. Western blot experiments confirmed increased heat-shock protein 72 levels in heat-shocked animals (> threefold) compared with sham-treated animals and controls.Conclusions. Heat shock 6 hours before heart removal resulted in marked expression of heat-shock protein 72 and protected isolated rat hearts by increased functional recovery and decreased cellular necrosis after 12-hour cold ischemia in a protocol mimicking that of heart preservation for transplantation. Protection was further confirmed after an additional 15-minute period of warm ischemia.
    The Annals of Thoracic Surgery 01/1999; · 3.45 Impact Factor
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    ABSTRACT: Background. Previous studies have shown that expression of the inducible 70-kD heat-shock protein (HSP72) by whole-body hyperthermia is associated with protection against ischemia-reperfusion injury. To develop techniques for regional elevation of heat-shock proteins that prevent extracardiac sequelae during whole-body hyperthermia, we sought to determine if local heating of the heart in vivo provides protection against ischemia-reperfusion injury in the rat.Methods. A thermal probe was used to locally heat rat hearts at two adjacent sites on the epicardial surface of the left ventricle. Rats were subjected to either 30 minutes of sham surgery (control; n = 10) or two local applications of the probe at 42.5° to 43.5°C for 15 minutes each (n = 9). After 4 hours, rats were subjected to 30 minutes of regional ischemia followed by 120 minutes of reperfusion. Hearts were removed and area at risk and infarct area were determined.Results. Localized heat stress resulted in a significant limitation of infarct size in heat-treated animals versus controls (mean ± standard error of the mean infarct area/area at risk = 4.3% ± 0.85 versus 19.2% ± 3.4%; p < 0.005). Western blot experiments confirmed elevated HSP72 expression in left (heated) and right (nonheated) ventricular samples from treated animals (n = 6; left ventricular = 5.5-fold; right ventricular = 3.7-fold) compared with sham-operated controls. Controls treated with the probe at 37°C (n = 4) showed no increases in HSP72.Conclusions. Local heating of the heart is associated with elevated levels of HSP72 and improved myocardial salvage. The increase in expression of HSP72 is not limited to the heated region, but extends into nonheated regions of the heart as well. This may lead to the development of new techniques that improve methods of myocardial revascularization and heart transplantation procedures.
    The Annals of Thoracic Surgery 05/1998; · 3.45 Impact Factor

Publication Stats

119 Citations
12 Downloads
318 Views
28.70 Total Impact Points

Institutions

  • 1998–2008
    • University of Texas Medical Branch at Galveston
      • • Department of Pathology
      • • Center for Biomedical Engineering
      • • Department of Surgery
      Galveston, TX, United States