Department Of Anesthesiology,Renji Hospital, Shanghai Second Medical University, Shanghai 200001, China.<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

ZHENG yong-jun, WANG xiang-rui, SU dian-san, ZHAO yan-hua，ZHANG ting-jie.

Abstract

Objective：To study the effect of intracarotid or intravenous injection of propofol on the concentrations of amino acids at different brain areas in rats undergoing cardiopulmonary bypass. 

Methods：Fifty rats were randomly assigned to five groups. Shame group (group SC n=10); group cardiopulmonary bypass (group CPB n=10); group intravenous injection of propofol 2mg.kg^-1.h^-1(group P_2V,n=10); group intravenous injection of propofol 10mg.kg^-1.h^-1 (group P_10v, n = 10); group intracarotid injection of propofol 2mg.kg^-1.h^-1(group P_2A, n = 10). Mean arterial pressure（MAP）and heart rate(HR) were monitored. Changes of the pathology were observed, and concertrations of amino acids were measured.

Results：the pathology injury of brain was attenuated in group P_2A and P_10v, but the pathology injury was not attenuated in group P_2v.The concentrations of Glutamic acid, Asparagic acid, Glycocol, γ-Aminobutyric acid and Taurine increased undergoing CPB. The concentrations of the Glutamic acid, Asparagic acid and Glycocol decreased after CPB in group P_2A and P_10V. γ-Aminobutyric acid increased in group P_2A and P_10V.But the effect in group P_2V was not significant compared with group CPB. Compared with baseline values, MAP and HR in P_2V and P_2A group remained unchanged. But the MAP and HR in P_10V group decreased compared with group CPB and baseline value.

Conclusions：intracarotid injection of propofol attenuated the injury of brain at a fraction of the intravenous dose and with less adverse systemic and cerebrovascular side effects.

Key words：Intracarotid;  cardiopulmonary bypass;  Amino Acid;  Brain;  Rats

Since the advent of cardiopulmonary bypass (CPB) in 1953, cerebral complications from overt stroke to subtle cognitive dysfunction after CPB for cardiac surgery have been well reported with the cardiac surgery were rapidly increased. The etiology of these injuries is probably associated with cerebral microemboli, metabolic abnormality,inflammation global or regional ischemia, and cerebral temperature modulation. Although many measures of cerebral protections have been adopted, the effects of cerebral protection were not ideal. With the widely use of propofol in clinic, the effects of cerebral protection of propofol were documented by more and more researches^[1-2]. Propofol, when used to produce effects of brain protection, result in a significant depression of the cardiovascular system^[3], so during intraoperative period, the apply of propofol for elderly patients,congestive heart failure, critical patients were limited. Compared with intravenous infusion of propofol, substantially high cerebral tissue concentrations can be achieved by intracarotid injection of propofol，but the dose of propofol in intracarotid infusion was more lower than intravenous infusion, and resulted in a more mild depression of the cardiovascular system^. the protection effects of intracarotid infusion of propofol during cardiopulmonary bypass have not been reported recently, so in this study, we aimed at investigating the effect of intracarotid or intravenous injection of propofol on the pathology injury of brain, concentrations of amino acids at different brain areas and cardiac effects in rats undergoing cardiopulmonary bypass. <?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

1  Material and Methods

In total 50 male Sprague Dawley rats, 4～6 months of age, were selected with body weight 380～420g (provided by Shanghai Experimental Animal Center of CAS). All procedures and experimental protocols accorded with the related laws and regulations about animal protection. Animals were given full access to food and water before the experiment.

1.1 Preparation: With a CPB model revised from Mackensen GB, et al^[4]. (Figure 1.), fasted male Sprague-Dawley rats were anesthetized with 4%～6% isoflurane in oxygen in a Plexiglas box. After orotracheal intubation, the lungs were mechanically ventilated to maintain a PaCO₂ of 35～45 mmHg. The arterial blood gas values were managed with α-stat methodology. During surgical preparation, anesthesia was maintained with 1.5%～2.0% isoflurane. Rectal temperature was monitored and servoregulated (by using a variable-temperature water bath-heated blanket) to 37.5 ℃ ± 0.1 ℃ during surgical preparation. The left femoral artery was cannulated with a 22G IV catheter for mean arterial blood pressure monitoring and arterial blood gas analysis. Heparin (500IU.kg^-1) was given through the arterial line. The tail artery was cannulated with a 20G IV catheter as the arterial inflow for CPB. Via a neck incision, a 14G IV catheter with a multiorificed tip for venous drainage was inserted into the right internal jugular vein, and advanced until the tip of the catheter was placed near the junction of the inferior vena cava and right atrium.

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The CPB circuit consisted of a venous reservoir, a peristaltic pump ( Mosterflex digital standard drive pump, Cole-Parmer Instrument Company, USA ), a memebrane oxygenator, and some connecting tubes. The peristaltic pump drained the blood from the venous reservoir, pump the blood to the memebrane oxygenator, and then to artial inflow catheter. CPB pump flow was continuously measured with an in-line flowprobe ( 2N806 flowprobe and T208 volume flowmeter; Transonics Systems, Inc., Ithaca, NY ). The CPB flow was 160～180 ml.kg^-1.min^-1, which is similar to the normal cardiac output in the rat. Complete CPB was assumed by the absence of pulsatility in the monitoring arterial line. The CPB circuit was primed with approximately 20ml bloodless liquid (10ml HES and 10ml Ringer lactate solution). The hematocrit (Hct) during CPB was maintained at 22%～24%.

This study also demonstrated that heart rate increased with intravenous infusion propofol 10mg.kg^-1.h^-1 during  CPB,while mean arterial pressure decreased. And the changes of HR and MAP was not obvious for propofol 2mg.kg^-1.h^-1 infused intracarotidly or intravenously .So this study demonstrated that the inhibitory effect of cardiovascular system was significant for intravenous infusion of propofol 10mg.kg^-1.h^-1，while intravenous or intracarotid infusion of propofol 2mg.kg^-1.h^-1was a relative lack of systemic hypotension during CPB.<?xml:namespace prefix = o ns = "urn:schemas-microsoft-com:office:office" />

In general,this study showed that intracarotid injection of propofol attenuated the injury of brain,inhibited  release of excitory amino acids（Glu, Asp）and inhibitory amino acids（Gly, increased release of inhibitory amino acids (GABA) at a fraction of the intravenous dose and with less adverse systemic and cerebrovascular side effects.

This study revealed the potential benefits of intraarterial propofol with regard to decreasing the dose requirements, lack of systemic side effects. It was a new explore for investigations into the kinetics of intracarotid propofol delivery, and provided a more safely and effectively methods for elderly patients,  congestive heart failure, critical patients, especially in intensive care units during intraoperative period. Moreover, advances in interventional neuroradiology provide unprecedented access to human cerebral circulation that compels us to further investigate the pharmacology of anesthetics delivered by the intraarterial route.

Reference

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