title: Increased haemodynamic adrenergic load with isoflurane anaesthesia in type 2 diabetic and obese rats in vivo.
abstract: BACKGROUND
  Increasing numbers of type 2 diabetic and obese patients with enhanced rates of cardiovascular complications require surgical interventions, however they have a higher incidence of perioperative haemodynamic complications, which has been linked to adrenergic dysfunction. Therefore, we aimed to determine how α- and β-adrenoceptor (AR)-mediated haemodynamic responses are affected by isoflurane anaesthesia in experimental type 2 diabetes and obesity in vivo.
  
  
  METHODS
  Sixteen-week old male Zucker type 2 Diabetic Fatty (ZDF) rats, Zucker Obese rats and their lean counterparts (n = 7-9 per group) were instrumented with radio telemeters to record blood pressure and heart rate and with vascular access ports for non-invasive intravenous drug delivery in vivo. Haemodynamic effects of α-AR (phenylephrine; 1-100 μg x kg(-1)) or β-AR (dobutamine; 2-120 μg x kg(-1)) stimulation were assessed under conscious and anaesthetised (isoflurane; 2%) conditions.
  
  
  RESULTS
  Vascular α-AR sensitivity was increased in both diabetic (non-diabetic 80 ± 3 vs. diabetic 95 ± 4 ΔmmHg at 100 μg x kg(-1); p < 0.05) and obese (lean 65 ± 6 vs. obese 84 ± 6 ΔmmHg at 20 μg x kg(-1); p < 0.05) conscious rats. Interestingly, anaesthesia exacerbated and prolonged the increased α-AR function in both diabetic and obese animals (non-diabetic 51 ± 1 vs. diabetic 68 ± 4 ΔmmHg, lean 61 ± 5 vs. obese 84 ± 2 ΔmmHg at 20 μg x kg(-1); p < 0.05). Meanwhile, β-AR chronotropic sensitivity was reduced in conscious diabetic and obese rats (non-diabetic 58 ± 7 vs. diabetic 27 ± 8 Δbpm, lean 103 ± 12 vs. obese 61 ± 9 Δbpm at 15 μg x kg(-1); p < 0.05). Anaesthesia normalised chronotropic β-AR responses, via either a limited reduction in obese (lean 51 ± 3 vs. obese 66 ± 5 Δbpm; NS at 15 μg x kg(-1)) or increased responses in diabetic animals (non-diabetic 49 ± 8 vs. diabetic 63 ± 8 Δbpm, at 15 μg x kg(-1); NS at 15 μg x kg(-1)).
  
  
  CONCLUSIONS
  Long term metabolic stress, such as during type 2 diabetes and obesity, alters α- and β-AR function, its dynamics and the interaction with isoflurane anaesthesia. During anaesthesia, enhanced α-AR sensitivity and normalised β-AR function may impair cardiovascular function in experimental type 2 diabetes and obesity.
authors.affiliation: HeartOtago, Department of Physiology, Otago School of Medical Sciences, University of Otago, Dunedin 9054, New Zealand. carol.bussey@otago.ac.nz.
authors.forename: Carol T
authors.initials: CT
authors.lastname: Bussey
authors.forename: Anne E
authors.initials: AE
authors.lastname: de Leeuw
authors.forename: Regis R
authors.initials: RR
authors.lastname: Lamberts
mesh_terms: D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D009765:Obesity / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker
chemical_list: D018685:Anesthetics, Inhalation; D001786:Blood Glucose; D007530:Isoflurane