Surgical Removal of Right-to-Left Cardiac Shunt in the American Alligator (\u3ci\u3eAlligator Mississippiensis\u3c/i\u3e) Causes Ventricular Enlargement But Does Not Alter Apnoea or Metabolism During Diving

Crocodilians have complete anatomical separation between the ventricles, similar to birds and mammals, but retain the dual aortic arch system found in all non-avian reptiles. This cardiac anatomy allows surgical modification that prevents right-to-left (R–L) cardiac shunt. A R–L shunt is a bypass of the pulmonary circulation and recirculation of oxygen-poor blood back to the systemic circulation and has often been observed during the frequent apnoeic periods of non-avian reptiles, particularly during diving in aquatic species. We eliminated R–L shunt in American alligators (Alligator mississippiensis) by surgically occluding the left aorta (LAo; arising from right ventricle) upstream and downstream of the foramen of Panizza (FoP), and we tested the hypotheses that this removal of R–L shunt would cause afterload-induced cardiac remodelling and adversely affect diving performance. Occlusion of the LAo both upstream and downstream of the FoP for ~21 months caused a doubling of RV pressure and significant ventricular enlargement (average ~65%) compared with age-matched, sham-operated animals. In a separate group of recovered, surgically altered alligators allowed to dive freely in a dive chamber at 23°C, occlusion of the LAo did not alter oxygen consumption or voluntary apnoeic periods relative to sham animals. While surgical removal of R–L shunt causes considerable changes in cardiac morphology similar to aortic banding in mammals, its removal does not affect the respiratory pattern or metabolism of alligators. It appears probable that the low metabolic rate of reptiles, rather than pulmonary circulatory bypass, allows for normal aerobic dives

Surgical Removal of Right-to-Left Cardiac Shunt in the American Alligator (\u3ci\u3eAlligator Mississippiensis\u3c/i\u3e) Causes Ventricular Enlargement But Does Not Alter Apnoea or Metabolism During Diving

Crocodilians have complete anatomical separation between the ventricles, similar to birds and mammals, but retain the dual aortic arch system found in all non-avian reptiles. This cardiac anatomy allows surgical modification that prevents right-to-left (R–L) cardiac shunt. A R–L shunt is a bypass of the pulmonary circulation and recirculation of oxygen-poor blood back to the systemic circulation and has often been observed during the frequent apnoeic periods of non-avian reptiles, particularly during diving in aquatic species. We eliminated R–L shunt in American alligators (Alligator mississippiensis) by surgically occluding the left aorta (LAo; arising from right ventricle) upstream and downstream of the foramen of Panizza (FoP), and we tested the hypotheses that this removal of R–L shunt would cause afterload-induced cardiac remodelling and adversely affect diving performance. Occlusion of the LAo both upstream and downstream of the FoP for ~21 months caused a doubling of RV pressure and significant ventricular enlargement (average ~65%) compared with age-matched, sham-operated animals. In a separate group of recovered, surgically altered alligators allowed to dive freely in a dive chamber at 23°C, occlusion of the LAo did not alter oxygen consumption or voluntary apnoeic periods relative to sham animals. While surgical removal of R–L shunt causes considerable changes in cardiac morphology similar to aortic banding in mammals, its removal does not affect the respiratory pattern or metabolism of alligators. It appears probable that the low metabolic rate of reptiles, rather than pulmonary circulatory bypass, allows for normal aerobic dives

Surgical removal of right-to-left cardiac shunt in the American alligator (Alligator mississippiensis) causes ventricular enlargement but does not alter apnoea or metabolism during diving

Crocodilians have complete anatomical separation between the ventricles, similar to birds and mammals, but retain the dual aortic arch system found in all non-avian reptiles. This cardiac anatomy allows surgical modification that prevents right-to-left (R–L) cardiac shunt. A R–L shunt is a bypass of the pulmonary circulation and recirculation of oxygen-poor blood back to the systemic circulation and has often been observed during the frequent apnoeic periods of non-avian reptiles, particularly during diving in aquatic species. We eliminated R–L shunt in American alligators (Alligator mississippiensis) by surgically occluding the left aorta (LAo; arising from right ventricle) upstream and downstream of the foramen of Panizza (FoP), and we tested the hypotheses that this removal of R–L shunt would cause afterload-induced cardiac remodelling and adversely affect diving performance. Occlusion of the LAo both upstream and downstream of the FoP for ∼21 months caused a doubling of RV pressure and significant ventricular enlargement (average ∼65%) compared with age-matched, sham-operated animals. In a separate group of recovered, surgically altered alligators allowed to dive freely in a dive chamber at 23°C, occlusion of the LAo did not alter oxygen consumption or voluntary apnoeic periods relative to sham animals. While surgical removal of R–L shunt causes considerable changes in cardiac morphology similar to aortic banding in mammals, its removal does not affect the respiratory pattern or metabolism of alligators. It appears probable that the low metabolic rate of reptiles, rather than pulmonary circulatory bypass, allows for normal aerobic dives

Microgeographic Proteomic Networks of the Human Colonic Mucosa and Their Association With Inflammatory Bowel Disease.

Background & aimsInteractions between mucosal cell types, environmental stressors, and intestinal microbiota contribute to pathogenesis in inflammatory bowel disease (IBD). Here, we applied metaproteomics of the mucosal-luminal interface to study the disease-related biology of the human colonic mucosa.MethodsWe recruited a discovery cohort of 51 IBD and non-IBD subjects endoscopically sampled by mucosal lavage at 6 colonic regions, and a validation cohort of 38 no-IBD subjects. Metaproteome data sets were produced for each sample and analyzed for association with colonic site and disease state using a suite of bioinformatic approaches. Localization of select proteins was determined by immunoblot analysis and immunohistochemistry of human endoscopic biopsy samples.ResultsCo-occurrence analysis of the discovery cohort metaproteome showed that proteins at the mucosal surface clustered into modules with evidence of differential functional specialization (eg, iron regulation, microbial defense) and cellular origin (eg, epithelial or hemopoietic). These modules, validated in an independent cohort, were differentially associated spatially along the gastrointestinal tract, and 7 modules were associated selectively with non-IBD, ulcerative colitis, and/or Crohn's disease states. In addition, the detailed composition of certain modules was altered in disease vs healthy states. We confirmed the predicted spatial and disease-associated localization of 28 proteins representing 4 different disease-related modules by immunoblot and immunohistochemistry visualization, with evidence for their distribution as millimeter-scale microgeographic mosaic.ConclusionsThese findings suggest that the mucosal surface is a microgeographic mosaic of functional networks reflecting the local mucosal ecology, whose compositional differences in disease and healthy samples may provide a unique readout of physiologic and pathologic mucosal states

Microgeographic Proteomic Networks of the Human Colonic Mucosa and Their Association With Inflammatory Bowel DiseaseSummary

Background & Aims: Interactions between mucosal cell types, environmental stressors, and intestinal microbiota contribute to pathogenesis in inflammatory bowel disease (IBD). Here, we applied metaproteomics of the mucosalâluminal interface to study the disease-related biology of the human colonic mucosa. Methods: We recruited a discovery cohort of 51 IBD and non-IBD subjects endoscopically sampled by mucosal lavage at 6 colonic regions, and a validation cohort of 38 no-IBD subjects. Metaproteome data sets were produced for each sample and analyzed for association with colonic site and disease state using a suite of bioinformatic approaches. Localization of select proteins was determined by immunoblot analysis and immunohistochemistry of human endoscopic biopsy samples. Results: Co-occurrence analysis of the discovery cohort metaproteome showed that proteins at the mucosal surface clustered into modules with evidence of differential functional specialization (eg, iron regulation, microbial defense) and cellular origin (eg, epithelial or hemopoietic). These modules, validated in an independent cohort, were differentially associated spatially along the gastrointestinal tract, and 7 modules were associated selectively with non-IBD, ulcerative colitis, and/or Crohnâs disease states. In addition, the detailed composition of certain modules was altered in disease vs healthy states. We confirmed the predicted spatial and disease-associated localization of 28 proteins representing 4 different disease-related modules by immunoblot and immunohistochemistry visualization, with evidence for their distribution as millimeter-scale microgeographic mosaic. Conclusions: These findings suggest that the mucosal surface is a microgeographic mosaic of functional networks reflecting the local mucosal ecology, whose compositional differences in disease and healthy samples may provide a unique readout of physiologic and pathologic mucosal states. Keywords: Inflammatory Bowel Disease, Mucosal, Networks, Ecology, Metaproteomic