Transient hyperaemic response to assess vascular reactivity of skin: effect of locally iontophoresed acetylcholine,bradykinin, epinephrine and phenylephrine

Background. Recently, the transient hyperaemic response (THR)to brief compression (20 s) of the brachial artery has beendescribed as a way to assess vascular reactivity of the forearmskin. We studied the effects of locally iontophoresed vasoactiveagents on this response in 20 male volunteers. Methods. An iontophoresis chamber attached to the anterior forearmpermitted simultaneous administration of drugs by iontophoresisand measurement of skin blood flow-flux by laser Doppler probe.Three THR tests were performed before and after iontophoresisby compressing the brachial artery with digital pressure for20 s and then releasing. The following were iontophoresed: saline0.9% (iontophoresis vehicle control), acetylcholine, bradykinin,epinephrine and phenylephrine. The THR ratio (THRR) was calculatedas F2/F1 where F1 was baseline blood flow-flux immediately beforecompression and F2 was peak blood flow-flux after release. Results. When compared with saline 0.9%, acetylcholine and bradykininincreased median F1 from 9.2 (range 5.2–23.8) to 22.1(8.7–61.5) and from 4.8 (3.0–23.2) to 15.0 (2.5–31.8),respectively, and reduced THRR from 1.26 (1.07–2.2) to0.99 (0.93–1.04) and from 1.63 (1.06–2.58) to 1.09(0.93–1.19), respectively. Epinephrine, but not phenylephrine,caused a significant reduction in F1 from 9.2 (5.2–23.8)to 4.0 (1.5–22.3). Neither epinephrine nor phenylephrinehad significant effect on THRR. Conclusions. Iontophoresed acetylcholine and bradykinin significantlyincrease the flow-flux and impair THR in forearm skin, furthervalidating the concept that THR represents true vasodilatationduring arterial occlusion. In addition, iontophoresis of vasoconstrictorsdoes not appear to have any consistent effect. Br J Anaesth 2003; 90: 446–51     

The role of the splanchnic circulation in the regulation of total intravascular volume during alpha adrenergic receptor stimulation

Previous studies have not defined the contribution of the splanchnic circulation to the total intravascular volume change associated with selective alpha adrenergic receptor stimulation. Since the splanchnic circulation is responsible for the total volume changes associated with other types of selective autonomic receptor stimulation, the present study was undertaken to examine the influence of alpha adrenergic receptor stimulation on splanchnic intravascular volume, the hemodynamic mechanism responsible for the splanchnic volume change, and the contribution of the splanchnic volume change to the change in total volume. In 35 anesthetized dogs, blood from the vena cavae was drained into an extracorporeal reservoir and returned to the right atrium at a constant rate so that changes in total intravascular volume could be measured as reciprocal changes in reservoir volume. Phenylephrine infusion (100 g/min) for 20 min in 28 dogs was associated with a decrease in total volume of 64±17 (SEM) ml (P<0.0001). The response was abolished by either alpha adrenergic blockade or evisceration but was not attenuated by beta adrenergic blockade, sinoaortic baroreceptor denervation, ganglionic blockade, or splenectomy. In 5 animals with separate splanchnic perfusion and drainage, total and splanchnic volumes decreased 59±8 ml (P<0.0001) and 317±20 ml (P<0.0001), respectively, while transhepatic vascular resistance increased 17±4 cm H₂O·min/l (P<0.0001). These responses were abolished after alpha adrenergic blockade. Thus, splanchnic volume decreases with alpha adrenergic receptor stimulation, despite an increase in hepatic resistance to splanchnic, venous outflow. The splanchnic volume decrement is entirely responsible for the total volume decrement.The study was supported by NHLBI Grant 1 R23-HL27185, Grant 11-203-812 from the American Heart Association of Greater Hartford, Inc., and the Duberg Cardiovascular Research Fund. Dr. Rutlen was the Duberg Scholar in Cardiovascular Disease when the study was performed.This work was presented in part at the 1982 Scientific Sessions of the American Heart Association (Circ. 66:II-311)     

Adrenergic influence on glucocounterregulation in man

Summary To investigate the adrenergic role in glucocounterregulatory mechanisms, single-blind randomised studies were performed in 7 normal males during severe insulin-induced hypoglycaemia with or without adrenergic blockade. Intravenous phentolamine administration (5 mg stat and 0.5 mg/ min) did not interfere with the restoration of euglycaemia from hypoglycaemia. However, recovery of blood glucose in the presence of propranolol (3 mg/ 3 min and 0.8 mg/min) was retarded when compared with control studies (mean plasma glucose levels ±SEM, 50±6 mg/dl versus 66±4 mg/dl at 120 min after insulin administration) despite appropriate glucagon, epinephrine, cortisol, and growth hormone responses. Plasma norepinephrine response was unaffected by propranolol but augmented threefold by phentolamine. Increases in plasma lactate, pyruvate and non-esterified fatty acids were blunted with propranolol while rebound non-esterified fatty acid was observed with phentolamine infusion. These data suggest that complete recovery of blood glucose from severe hypoglycaemia requires full sympathetic nervous system activity despite the integrity of other counterregulatory mechanisms.     

Demonstration of intrathecal and systemic morphine and ST-91 effects on fed canine upper gut motility

We studied the effects of opioid and adrenergic agonists and antagonists given systemically intravenously and intrathecally on postprandial antral and small bowel motility in a chronic conscious dog model. We studied eight dogs with a surgically implanted thoracic spinal intrathecal injection catheter, and six gastrointestinal manometric perfusion catheters. Morphine given intrathecally or intravenously induced propagated clusters of intestinal pressure activity in the fed dogs. The minimal effective dose for morphine was 150 g/kg by the intrathecal route and 450 g/kg by the intravenous route. ST-91 (an ₂-adrenergic agonist) profoundly inhibited antral and small intestinal pressure activity with similar minimal effective dose (100 g/kg) and duration of effect for both intravenous and intrathecal routes. Neither naloxone (3000 g/kg) nor combined phentolamine (1500 g/kg) with propranolol (300 g/kg) altered postprandial antral or small intestinal motility. The capacity of pharmacologic agents to block morphine-induced activity fronts when administered in the same compartment (intravenously or intrathecally) was investigated. The minimally effective morphine-antagonist dose for naloxone was similar intrathecally and intravenously (36 g/kg for both routes). ST-91 (100 g/kg) when given intrathecally or intravenously blocked morphine-induced clustered phasic pressure activity while simultaneously abolishing postprandial small intestine phasic pressure activity. These data suggest the presence of opioid and ₂-adrenergic receptors in the spinal cord that can modulate gastrointestinal motility in the postprandial state. Pharmacological interactions between these systems occur at spinal and target organ levels.     

β2肾上腺素能受体基因多态在重症肌无力发病机制中的作用

目的 探讨β2肾上腺素能受体(β2-AR)基因16位、27位密码子遗传多态在重症肌无力(myasthenia gravis,MG)发病机制中的作用.方法 应用聚合酶链反应-限制性片段长度多态(PCR-RFLP)方法和PCR产物直接测序检测88例MG患者组和91名性别、年龄相匹配的健康对照(HC)的β2-AR基因16位点和27位点多态分布特征.结果 β2-AR基因16位点Arg/Arg、Arg/Gly和Gly/Gly基因型频率在MG组依次为44.4%、38.6%和17.0%,HC组依次为29.7%、58.2%和12.1%,两组间差异有统计学意义(X~2=6.898,P=0.032).Arg和Gly的等位基因频率在MG组分别为63.6%和36.4%,HC组为58.8%和41.2%,两组间差异无统计学意义.β2-AR基因27位点Gln/Gln、Gln/Glu和Glu/Glu基因型频率在MG组依次为77.3%、20.4%和2.3%,HC组依次为78.0%、18.7%和3.3%,两组间差异无统计学意义.Gln和Glu等位基因频率在MG组为87.5%和12.5%,HC组为87.4%和12.6%,两组间差异无统计学意义.两组的基因型多态分布均符合Hardy-Weinberg定律.结论 β2-AR 16位点基因多态可能是MG发病的独立危险凶素,27位点基因多态与MG发病无明确相关性.