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Superoxide radical production by mitochondrial respiratory complexes I and III is decreased by ischemic preconditioning
Vol. 209, No. 3S, September 2009
Surgical Forum Abstracts
The development of an intraoperative imaging system to visualize these microdeposits of neoplastic cells at resection margins has been proposed. The emergence of targeted nanoprobes that optically enhance neoplastic cells makes this technology feasible. Our goal is to develop an endoscope to visualize small quantities of tumor cells.
RESULTS:
METHODS: A modified thoracoscope was engineered to visualize tissues labeled with visible (or NIR) fluorescent nanoparticles called quantum dots (QDs). The prototype was developed with several distinct components: a light source that orients the thoracoscope, excites QDs at characteristic wavelengths, and a digital video system equipped to capture, filter, localize, and quantify a specific QD wavelength. In vivo testing in a chicken thorax was used to qualitate the optics and quantitate the minimal tumor quantity that could be visualized with the thoracoscope. RESULTS: Results demonstrated a proof-of-concept with the initial prototype light source able to achieve in vivo QD visualization through the modified endoscope. Minimal tumor nodules undetectable by conventional endoscopes were readily visualized with optical enhancement by nanoparticle technology and device implementation. Tumor deposits as small as 5 mm that could not be visualized by conventional thoracoscopes were visualized with the optically enhanced device. CONCLUSIONS: The prototype thoracoscope is capable of detecting tumor deposits that remain in a surgical bed. As nanoparticles and QDs continue to evolve into sensitive targeting agents, this system could detect residual disease at resection margins and will ultimately improve surgical outcomes.
Superoxide radical production by mitochondrial respiratory complexes I and III is decreased by ischemic preconditioning Juan A Crestanello MD, Daniel S Lee BS, Gregory Steinbaugh PhD, Douglas Pfeiffer PhD, Jay Zweier MD The Ohio State University Medical Center, Columbus, OH INTRODUCTION: Mitochondria respiratory complexes I and III are the major producers of superoxide radical during ischemia reperfusion (IR). While ischemic preconditioning (IPC) preserves mitochondria respiratory complex activity during IR, it is unclear what the effect of IPC on mitochondria superoxide production is. We sought to investigate the effect of IPC on superoxide production by respiratory complex I and III during IR. METHODS: Hearts (6 per group) were subjected to: (A) CONTROL: 30 minutes of equilibration, (B) IR: 30 minutes of equilibration, 30 minutes of ischemia, and 30 minutes of reperfusion, or (C) IPC: 10 minutes of equilibration, two 5-minute episodes of IPC, 30 minutes of ischemia, and 30 minutes of reperfusion. Mitochondria were isolated at the end of the experiments, and superoxide production by complex I, III, and I & III was assessed by EPR spectroscopy using DMPO as spin trap. Substrates (S) and blockers (B) used were glutamate-malate (S) and rotenone (B) for complex I; glutamatemalate (S) and antimycin A (B) for complex I & III; and succinate (S), rotenone (B), and antimycin A (B) for complex III.
Superoxide Production by Complexes (units/mg protein): I
I&III
III
S33
State 3 Respiration (ng atoms O/mg protein)
CONTROL
480 ⫾ 56
2,146 ⫾ 264
1,316 ⫾ 252
IR
457 ⫾ 78
3,338 ⫾ 349⌿
3,270 ⫾ 408⌿
103 ⫾ 10 56 ⫾ 6⌿
IPC
351 ⫾ 42⌿
2,364 ⫾ 334ⴱ
2,070 ⫾ 164ⴱ
84 ⫾ 6ⴱ
Data: Mean ⫾ SEM. ⴱp⬍0.05 vs IR. ⌿p⬍0.05 vs CONTROL.
CONCLUSIONS: IR worsens mitochondria respiratory function (state 3) and increases superoxide production by complexes I & III and III. IPC improves state 3 respiration during reperfusion and decreases superoxide production by respiratory complexes I & III and III. Decreasing mitochondrial generation of reactive oxygen species preserves mitochondria function and may be the key mechanism underlying the prevention of apoptosis, cell death, and myocardial dysfunction seen during IPC.
Pneumonectomy after chemotherapy in NSCLC: Early and long-term results Pierpaolo Maietta MD, PhD, Mario Massimo MD, Alfonso Maiorino MD Second University of Naples, Naples, Italy INTRODUCTION: Results of pneumonectomy after chemotherapy are controversial, and the procedure is often considered as potentially dangerous. METHODS: Records of patients who underwent pneumonectomy after chemotherapy for non–small cell lung cancer in a single institution in a 6-year period were reviewed retrospectively. RESULTS: One hundred eighteen patients had pneumonectomy after chemotherapy. Indications for preoperative chemotherapy were N2 disease, 74; potentially resectable T4 disease, 17; doubtful resectability, 18; stage IV disease (nodule on another ipsilateral lobe), 4; and participation in a randomized trial on induction chemotherapy in initial stages, 5. Chemotherapy protocols were platinum-based. Imaging reevaluation showed complete, partial, minor response, and disease stability in 0, 24, 39, and 55 patients, respectively. Operative mortality was 5.9% (7 of 118), consisting of 4 of 54 after pneumonectomy and 3 of 64 after left pneumonectomy. Bronchopleural fistula caused 1 death. No factor among those evaluated (sex, age, comorbidities, forced expiratory volume in 1 second, symptoms, side and location of tumor; indication for operation, number of cycles, and response to chemotherapy; extent of resection, TNM status, pathologic stage) predicted postoperative death. Median and overall 5-year survival was 22 months and 23.7%, respectively. At univariate analysis, pathologic stage, T status, and the occurrence of postoperative complications influenced 5-year survival. At multivariate analysis, T status (p ⫽ 0.0054), the occurrence of postoperative complications (p ⫽ 0.0015) and clinical response to induction chemotherapy (p ⫽ 0.028) were identified as independent predictors of 5-year survival. CONCLUSIONS: Pneumonectomy after chemotherapy has acceptable mortality. Long-term results are encouraging.
Surgical Forum Abstracts
The development of an intraoperative imaging system to visualize these microdeposits of neoplastic cells at resection margins has been proposed. The emergence of targeted nanoprobes that optically enhance neoplastic cells makes this technology feasible. Our goal is to develop an endoscope to visualize small quantities of tumor cells.
RESULTS:
METHODS: A modified thoracoscope was engineered to visualize tissues labeled with visible (or NIR) fluorescent nanoparticles called quantum dots (QDs). The prototype was developed with several distinct components: a light source that orients the thoracoscope, excites QDs at characteristic wavelengths, and a digital video system equipped to capture, filter, localize, and quantify a specific QD wavelength. In vivo testing in a chicken thorax was used to qualitate the optics and quantitate the minimal tumor quantity that could be visualized with the thoracoscope. RESULTS: Results demonstrated a proof-of-concept with the initial prototype light source able to achieve in vivo QD visualization through the modified endoscope. Minimal tumor nodules undetectable by conventional endoscopes were readily visualized with optical enhancement by nanoparticle technology and device implementation. Tumor deposits as small as 5 mm that could not be visualized by conventional thoracoscopes were visualized with the optically enhanced device. CONCLUSIONS: The prototype thoracoscope is capable of detecting tumor deposits that remain in a surgical bed. As nanoparticles and QDs continue to evolve into sensitive targeting agents, this system could detect residual disease at resection margins and will ultimately improve surgical outcomes.
Superoxide radical production by mitochondrial respiratory complexes I and III is decreased by ischemic preconditioning Juan A Crestanello MD, Daniel S Lee BS, Gregory Steinbaugh PhD, Douglas Pfeiffer PhD, Jay Zweier MD The Ohio State University Medical Center, Columbus, OH INTRODUCTION: Mitochondria respiratory complexes I and III are the major producers of superoxide radical during ischemia reperfusion (IR). While ischemic preconditioning (IPC) preserves mitochondria respiratory complex activity during IR, it is unclear what the effect of IPC on mitochondria superoxide production is. We sought to investigate the effect of IPC on superoxide production by respiratory complex I and III during IR. METHODS: Hearts (6 per group) were subjected to: (A) CONTROL: 30 minutes of equilibration, (B) IR: 30 minutes of equilibration, 30 minutes of ischemia, and 30 minutes of reperfusion, or (C) IPC: 10 minutes of equilibration, two 5-minute episodes of IPC, 30 minutes of ischemia, and 30 minutes of reperfusion. Mitochondria were isolated at the end of the experiments, and superoxide production by complex I, III, and I & III was assessed by EPR spectroscopy using DMPO as spin trap. Substrates (S) and blockers (B) used were glutamate-malate (S) and rotenone (B) for complex I; glutamatemalate (S) and antimycin A (B) for complex I & III; and succinate (S), rotenone (B), and antimycin A (B) for complex III.
Superoxide Production by Complexes (units/mg protein): I
I&III
III
S33
State 3 Respiration (ng atoms O/mg protein)
CONTROL
480 ⫾ 56
2,146 ⫾ 264
1,316 ⫾ 252
IR
457 ⫾ 78
3,338 ⫾ 349⌿
3,270 ⫾ 408⌿
103 ⫾ 10 56 ⫾ 6⌿
IPC
351 ⫾ 42⌿
2,364 ⫾ 334ⴱ
2,070 ⫾ 164ⴱ
84 ⫾ 6ⴱ
Data: Mean ⫾ SEM. ⴱp⬍0.05 vs IR. ⌿p⬍0.05 vs CONTROL.
CONCLUSIONS: IR worsens mitochondria respiratory function (state 3) and increases superoxide production by complexes I & III and III. IPC improves state 3 respiration during reperfusion and decreases superoxide production by respiratory complexes I & III and III. Decreasing mitochondrial generation of reactive oxygen species preserves mitochondria function and may be the key mechanism underlying the prevention of apoptosis, cell death, and myocardial dysfunction seen during IPC.
Pneumonectomy after chemotherapy in NSCLC: Early and long-term results Pierpaolo Maietta MD, PhD, Mario Massimo MD, Alfonso Maiorino MD Second University of Naples, Naples, Italy INTRODUCTION: Results of pneumonectomy after chemotherapy are controversial, and the procedure is often considered as potentially dangerous. METHODS: Records of patients who underwent pneumonectomy after chemotherapy for non–small cell lung cancer in a single institution in a 6-year period were reviewed retrospectively. RESULTS: One hundred eighteen patients had pneumonectomy after chemotherapy. Indications for preoperative chemotherapy were N2 disease, 74; potentially resectable T4 disease, 17; doubtful resectability, 18; stage IV disease (nodule on another ipsilateral lobe), 4; and participation in a randomized trial on induction chemotherapy in initial stages, 5. Chemotherapy protocols were platinum-based. Imaging reevaluation showed complete, partial, minor response, and disease stability in 0, 24, 39, and 55 patients, respectively. Operative mortality was 5.9% (7 of 118), consisting of 4 of 54 after pneumonectomy and 3 of 64 after left pneumonectomy. Bronchopleural fistula caused 1 death. No factor among those evaluated (sex, age, comorbidities, forced expiratory volume in 1 second, symptoms, side and location of tumor; indication for operation, number of cycles, and response to chemotherapy; extent of resection, TNM status, pathologic stage) predicted postoperative death. Median and overall 5-year survival was 22 months and 23.7%, respectively. At univariate analysis, pathologic stage, T status, and the occurrence of postoperative complications influenced 5-year survival. At multivariate analysis, T status (p ⫽ 0.0054), the occurrence of postoperative complications (p ⫽ 0.0015) and clinical response to induction chemotherapy (p ⫽ 0.028) were identified as independent predictors of 5-year survival. CONCLUSIONS: Pneumonectomy after chemotherapy has acceptable mortality. Long-term results are encouraging.