Novel affinity-purified antibodies against human SGLT1 (hSGLT1) and SGLT2 (hSGLT2) were used to localize hSGLT2 in human kidney and hSGLT1 in human kidney, small intestine, liver, lung, and heart. The renal locations of both transporters largely resembled those in rats and mice; hSGLT2 and SGLT1 were localized to the brush border membrane (BBM) of proximal tubule S1/S2 and S3 segments, respectively. Different to rodents, the renal expression of hSGLT1 was absent in thick ascending limb of Henle (TALH) and macula densa, and the expression of both hSGLTs was sex-independent. In small intestinal enterocytes, hSGLT1 was localized to the BBM and subapical vesicles. Performing double labeling with glucagon-like peptide 1 (GLP-1) or glucose-dependent insulinotropic peptide (GIP), hSGLT1 was localized to GLP-1-secreting L cells and GIP-secreting K cells as has been shown in mice. In liver, hSGLT1 was localized to biliary duct cells as has been shown in rats. In lung, hSGLT1 was localized to alveolar epithelial type 2 cells and to bronchiolar Clara cells. Expression of hSGLT1 in Clara cells was verified by double labeling with the Clara cell secretory protein CC10. Double labeling of human heart with aquaporin 1 immunolocalized the hSGLT1 protein in heart capillaries rather than in previously assumed myocyte sarcolemma. The newly identified locations of hSGLT1 implicate several extra renal functions of this transporter, such as fluid absorption in the lung, energy supply to Clara cells, regulation of enteroendocrine cells secretion, and release of glucose from heart capillaries. These functions may be blocked by reversible SGLT1 inhibitors which are under development.
Background—
A possible relationship between increased perioperative risk during coronary artery bypass grafting (CABG) and previous percutaneous coronary intervention (PCI) is debatable. We sought to determine the impact of previous PCI on patient outcome after elective CABG.
Methods and Results—
Between January 2000 and January 2005, 2626 consecutive patients undergoing first-time isolated elective CABG as the primary revascularization procedure (group 1) were evaluated for in-hospital mortality and major adverse cardiac events (MACEs) and were compared with 360 patients after single PCI (group 2) and with 289 patients after multiple PCI sessions (group 3) before elective CABG. Unadjusted univariate and risk-adjusted multivariate logistic-regression analysis revealed previous multiple PCIs to be strongly associated with in-hospital mortality (odds ratio [OR], 2.24; 95% confidence interval [CI], 1.52 to 3.21;
P
<0.001) and MACEs (OR, 2.28; 95% CI, 1.38 to 3.59;
P
<0.001). To control for selection bias, a computed propensity-score matching based on 13 patient characteristics and preoperative risk factors was performed separately comparing group 1 versus 2 and group 1 versus 3. After propensity matching, conditional logistic-regression analysis confirmed previous multiple PCIs to be strongly associated with in-hospital mortality (OR, 3.01; 95% CI, 1.51 to 5.98;
P
<0.0017) and MACEs (OR, 2.31; 95% CI, 1.45 to 3.67;
P
<0.0004).
Conclusions—
In patients with a history of multiple PCI sessions, perioperative risk for in-hospital mortality and MACEs during subsequent elective CABG is increased.
Perioperative cTnI elevation after CABG separates among patients with graft-related, non-graft-related, and without PMI, however, not earlier than 12 h after surgery.
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