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.kg-1) or β-AR (dobutamine; 2-120 μg.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.kg-1; p < 0.05) and obese (lean 65 ± 6 vs. obese 84 ± 6 δmmHg at 20 μg.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.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.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.kg-1) or increased responses in diabetic animals (non-diabetic 49 ± 8 vs. diabetic 63 ± 8 δbpm, at 15 μg.kg-1; NS at 15 μg.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.