title: The effect of perioperative insulin treatment on cardiodepression in mild adiposity in mice.
abstract: While most studies focus on cardiovascular morbidity following anesthesia and surgery in excessive obesity, it is unknown whether these intraoperative cardiovascular alterations also occur in milder forms of adiposity without type 2 diabetes and if insulin is a possible treatment to improve intraoperative myocardial performance. In this experimental study we investigated whether mild adiposity without metabolic alterations is already associated with cardiometabolic dysfunction during anesthesia, mechanical ventilation and surgery and whether these myocardial alterations can be neutralized by intraoperative insulin treatment.
  
  
  
  Mice were fed a western (WD) or control diet (CD) for 4 weeks. After metabolic profiling, mice underwent general anesthesia, mechanical ventilation and surgery. Cardiac function was determined with echocardiography and left-ventricular pressure-volume analysis. Myocardial perfusion was determined with contrast-enhanced echocardiography. WD-fed mice were subsequently treated with insulin by hyperinsulinemic euglycemic clamping followed by the same measurements of cardiac function and perfusion.
  
  
  
  Western-type diet feeding led to a 13 % increase in bodyweight, (p < 0.0001) and increased adipose tissue mass, without metabolic alterations. Despite this mild phenotype, WD-fed mice had decreased systolic and diastolic function (end-systolic elastance was 2.0 ± 0.5 versus 4.1 ± 2.4 mmHg/μL, p = 0.01 and diastolic beta was 0.07 ± 0.03 versus 0.04 ± 0.01 mmHg/μL, p = 0.02) compared to CD-fed mice. Ventriculo-arterial coupling and myocardial perfusion were decreased by 48 % (p = 0.003) and 43 % (p = 0.03) respectively. Insulin treatment in WD-fed mice improved echo-derived systolic function (fractional shortening 42 ± 5 % to 46 ± 3, p = 0.05), likely due to decreased afterload, but there was no effect on load-independent measures of systolic function or myocardial perfusion. However, there was a trend towards improved diastolic function after insulin treatment (43 % improvement, p = 0.05) in WD-fed mice.
  
  
  
  Mild adiposity without metabolic alterations already affected cardiac function and perfusion during anesthesia, mechanical ventilation and surgery in mice. Intraoperative insulin may be beneficial to reduce afterload and enhance intraoperative ventricular relaxation, but not to improve ventricular contractility or myocardial perfusion.
authors.affiliation: Department of Anesthesiology, Institute for Cardiovascular Research, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. c.boly@vumc.nl.|Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands. c.boly@vumc.nl.
authors.forename: Chantal A
authors.initials: CA
authors.lastname: Boly
authors.affiliation: Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Etto C
authors.initials: EC
authors.lastname: Eringa
authors.affiliation: Department of Anesthesiology, Catharina Hospital, Eindhoven, The Netherlands.
authors.forename: R Arthur
authors.initials: RA
authors.lastname: Bouwman
authors.affiliation: Department of Anesthesiology, Institute for Cardiovascular Research, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.|Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Rob F P
authors.initials: RF
authors.lastname: van den Akker
authors.affiliation: Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.|Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Frances S
authors.initials: FS
authors.lastname: de Man
authors.affiliation: Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.|Pulmonology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Schalij
authors.affiliation: Department of Anesthesiology, Institute for Cardiovascular Research, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Loer
authors.affiliation: Department of Anesthesiology, Institute for Cardiovascular Research, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: Christa
authors.initials: C
authors.lastname: Boer
authors.affiliation: Department of Anesthesiology, Institute for Cardiovascular Research, VU University Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.|Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Charissa E
authors.initials: CE
authors.lastname: van den Brom
mesh_terms: D050154:Adiposity; D000768:Anesthesia, General / Q000009:adverse effects; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D066273:Diet, Western; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004452:Echocardiography; D006331:Heart Diseases / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D007430:Intraoperative Care; D008297:Male; D055432:Metabolomics; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D012121:Respiration, Artificial / Q000009:adverse effects; D012720:Severity of Illness Index; D013514:Surgical Procedures, Operative / Q000009:adverse effects*; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects; D015430:Weight Gain
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin
keywords: Adiposity; Insulin; Myocardial contraction; Myocardial perfusion; Perioperative period