Thoracoscopic lobectomy is associated with a lower incidence of major complications, including atrial fibrillation, compared with lobectomy by means of thoracotomy. The underlying factors responsible for this advantage should be analyzed to improve the safety and outcomes of other thoracic procedures.
Darrabie MD, Arciniegas AJ, Mishra R, Bowles DE, Jacobs DO, Santacruz L. AMPK and substrate availability regulate creatine transport in cultured cardiomyocytes. Am J Physiol Endocrinol Metab 300: E870 -E876, 2011. First published March 1, 2011; doi:10.1152/ajpendo.00554.2010.-Profound alterations in myocellular creatine and phosphocreatine levels are observed during human heart failure. To maintain its intracellular creatine stores, cardiomyocytes depend upon a cell membrane creatine transporter whose regulation is not clearly understood. Creatine transport capacity in the intact heart is modulated by substrate availability, and it is reduced in the failing myocardium, likely adding to the energy imbalance that characterizes heart failure. AMPK, a key regulator of cellular energy homeostasis, acts by switching off energy-consuming pathways in favor of processes that generate energy. Our objective was to determine the effects of substrate availability and AMPK activation on creatine transport in cardiomyocytes. We studied creatine transport in rat neonatal cardiomyocytes and HL-1 cardiac cells expressing the human creatine transporter cultured in the presence of varying creatine concentrations and the AMPK activator 5-aminoimidazole-4-carboxamide-1--D-ribonucleoside (AICAR). Transport was enhanced in cardiomyocytes following incubation in creatine-depleted medium or AICAR. The changes in transport were due to alterations in Vmax that correlated with changes in total and cell surface creatine transporter protein content. Our results suggest a positive role for AMPK in creatine transport modulation for cardiomyocytes in culture. myocardial creatine content; cardiac energy metabolism; adenosine 5=-monophosphate-activated protein kinase; cardiac failure CREATINE (Cr) and its phosphorylated form phosphocreatine (PCr), together with creatine kinases (CK), comprise a system that helps maintain ATP stores in cardiac and skeletal myocytes (23). During cardiac hypertrophy and heart failure, the myocardium exhibits marked changes in energy metabolism, including changes in substrate utilization, as well as in the content of high-energy metabolites. The PCr/ATP ratio decreases (9,19
OBJECTIVE
We sought to evaluate the effect of tumor size, location, and clinical nodal status on outcomes after thoracoscopic lobectomy for lung cancer.
METHODS
All patients who underwent attempted thoracoscopic lobectomy for lung cancer between June 1999 and October 2010 at a single institution were reviewed. A model for morbidity including published risk factors as well as tumor size, location, and clinical N status was developed by multivariable logistic regression.
RESULTS
During the study period, 916 thoracoscopic lobectomies met study criteria: 329 for peripheral, clinical N0 tumors ≤3cm and 504 for tumors that were central, clinical node positive, or >3cm; tumor location could not be documented for 83 patients. Conversions to thoracotomy occurred in 36 patients (4%); patients with clinically node positive disease had higher conversion rates [11 conversions in 153 clinical N1-N3 patients (7.2%) vs 25 in 763 clinical N0 patients (3.3%), p=0.03]. Overall operative mortality was 1.6% (14 patients) and morbidity was 32% (296 patients). Although patients with larger tumors (p=0.006) and central tumors (p=0.01) had increased complications by univariate analysis, tumor size >3cm (p=0.17) and central location (p=0.5) did not significantly predict overall morbidity in multivariate analysis. Clinical node status did not predict increased complications by univariate or multivariate analysis. Significant predictors of morbidity in multivariable analysis were increasing age, decreasing FEV1, prior chemotherapy, and congestive heart failure.
CONCLUSIONS
Thoracoscopic lobectomy for lung cancers that are central, clinically node positive, or larger than 3 cm does not confer increased morbidity compared to peripheral, clinical N0 cancers that are smaller than 3 cm.
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