Dual implantation of a radio-telemeter and vascular access port allows repeated hemodynamic and pharmacological measures in conscious lean and obese rats

Abstract

Expansion of physiological knowledge increasingly requires examination of processes in the normal, conscious state. The current study describes a novel approach combining surgical implantation of radio-telemeters with vascular access ports (VAPs) to allow repeated hemodynamic and pharmacological measures in conscious rats. Dual implantation was conducted on 16-week-old male lean and obese Zucker rats. Continued viability one month after surgery was observed in 67% of lean and 44% of obese animals, giving an overall 54% completion rate. Over the five-week measurement period, reliable and reproducible basal mean arterial pressure and heart rate measures were observed. VAP patency and receptor-independent vascular reactivity were confirmed by consistent hemodynamic responses to sodium nitroprusside (6.25 µg/kg). Acutely, minimal hemodynamic responses to repeated bolus administration of 0.2 mL saline indicated no significant effect of increased blood volume or administration stress, making repeated acute measures viable. Similarly, repeated administration of the β-adrenoceptor agonist dobutamine (30 µg/kg) at 10 min intervals resulted in reproducible hemodynamic changes in both lean and obese animals. Therefore, our study demonstrates that this new approach is viable for the acute and chronic assessment of hemodynamic and pharmacological responses in both lean and obese conscious rats. This technique reduces the demand for animal numbers and allows hemodynamic measures with minimal disruption to animals' welfare, while providing reliable and reproducible results over several weeks. In conclusion, dual implantation of a radio-telemeter and VAP introduces a valuable technique for undertaking comprehensive studies involving repeated pharmacological tests in conscious animals to address important physiological questions.

Effect of type 2 diabetes, surgical incision, and volatile anesthesia on hemodynamics in the rat

“…The ZDF animals displayed the characteristics of an uncontrolled type 2 diabetic animal model with hyperglycemia, hyperinsulinemia, and obesity due to increased adiposity. Under conscious baseline conditions, the type 2 diabetic animals were normotensive with a markedly lower HR, which is in agreement with previous studies (Marsh et al 2007;Radovits et al 2009;Bussey et al 2014b;Thaung et al 2015). The lower HR in the diabetic animals relates to the intrinsic properties of the pacemaker cells in the sinoatrial node as the difference is also observed in isolated heart preparations without autonomic control (Thaung et al 2015).…”

“…To address this we used our recently developed approach that allows determination of how a surgical incision (under anesthesia) affects mean arterial blood pressure (MAP) and HR regulation compared to anesthesia alone and conscious conditions (Bussey et al. , ). Type 2 diabetic (Zucker Diabetic Fatty [ZDF]) rats and their nondiabetic littermates were implanted with a vascular access port and a radiotelemetric transmitter to inject intravenous drugs and to measure in vivo abdominal aortic blood pressure, respectively.…”

“…The lowering effects of anesthesia on blood pressure and HR are augmented during diabetes (Amour et al 2004;Crespo et al 2011;Oakley and Emond 2011). Recently, we showed that long-term metabolic adaptations, associated with type 2 diabetes and obesity, altered the aand b-adrenergic function, and its acute interaction with isoflurane anesthesia (Bussey et al 2014b). However, the interaction of anesthesia with a surgical intervention during the perioperative setting in type 2 diabetes is unknown and might have a significant impact on blood pressure and HR regulation.…”

“…Therefore, we aimed in this study to determine the effect of type 2 diabetes on the interaction between hemodynamics, anesthesia, and surgical incision. Because we recently showed in rats in vivo that type 2 diabetes impaired b-adrenergic function during volatile anesthesia (Bussey et al 2014b), we hypothesized that a surgical incision (laparotomy) on top of anesthesia would further impair blood pressure and HR regulation in the rats with diabetes. To address this we used our recently developed approach that allows determination of how a surgical incision (under anesthesia) affects mean arterial blood pressure (MAP) and HR regulation compared to anesthesia alone and conscious conditions (Bussey et al 2014a(Bussey et al , 2014b.…”

“…Because we recently showed in rats in vivo that type 2 diabetes impaired b-adrenergic function during volatile anesthesia (Bussey et al 2014b), we hypothesized that a surgical incision (laparotomy) on top of anesthesia would further impair blood pressure and HR regulation in the rats with diabetes. To address this we used our recently developed approach that allows determination of how a surgical incision (under anesthesia) affects mean arterial blood pressure (MAP) and HR regulation compared to anesthesia alone and conscious conditions (Bussey et al 2014a(Bussey et al , 2014b. Type 2 diabetic (Zucker Diabetic Fatty [ZDF]) rats and their nondiabetic littermates were implanted with a vascular access port and a radiotelemetric transmitter to inject intravenous drugs and to measure in vivo abdominal aortic blood pressure, respectively.…”