Hemodialysis hypotension is not the result of uremic peripheral autonomic neuropathy.

Five chronic hemodialysis patients with persistent hypotension during dialysis (MAP: 74.2 +/- 3.1 mm Hg) were given a number of standard tests of autonomic nervous system function and compared with eight normotensive hemodialysis patients (MAP: 96.4 +/- 3.4 mm Hg). Tests of efferent sympathetic nerves were normal in both groups, as were plasma catecholamine levels and the cold pressor test. The response to Valsalva maneuver and the venoconstriction reflex were generally abnormal and did not differentiate between the two groups. When adjusted for age and MAP, the baroreceptor slope to a high-pressure stimulus was diminished only in the hypotensive subjects. This result reinforces the previously described finding that many uremic patients do not develop a normal cardioacceleration during hypotension. Although reduced baroreceptor sensitivity may be a factor in the chronic hypotension of some hemodialysis patients, autonomic dysfunction alone is not a sufficient explanation of this phenomenon.     

Effect of bromocriptine treatment on prolactin, noradrenaline and blood pressure in hypertensive haemodialysis patients

Bromocriptine (2.5 mg/day orally) produced a significant fall in supine mean arterial pressure in nine hypertensive haemodialysis patients with high serum prolactin levels, without causing significant changes in heart rate. On bromocriptine, there was a significant decrease in the mean value of both serum prolactin and plasma noradrenaline, without significant changes in the mean value of plasma renin activity. A significant relationship was found between the changes in supine plasma noradrenaline and the changes in supine mean arterial pressure induced by bromocriptine. The increase in mean arterial pressure in response to the tilt test was greater on bromocriptine than on placebo although the changes in plasma noradrenaline were reduced by bromocriptine. Similar results were observed during the cold pressor test. These findings suggest that the arterial pressure-lowering effect of bromocriptine is related to the reduction in sympathetic out-flow. The parallel decrease in serum prolactin raises the question of the possible involvement of dopaminergic mechanisms in the development of hypertension in our patients. Moreover, bromocriptine seems to enhance the vascular response to endogenous noradrenaline.     

Paradoxical withdrawal of reflex vasoconstriction as a cause of hemodialysis-induced hypotension.

Acute hypotension is an important complication of hemodialysis, but the underlying mechanisms remain poorly understood. Because hemorrhage-induced hypovolemia can trigger a sudden decrease in sympathetic activity resulting in bradycardia and vasodilation, we hypothesized that hemodialysis-induced hypovolemia also can trigger the same type of vasodepressor reaction, which would exacerbate the volume-dependent fall in blood pressure. We therefore measured blood pressure, vascular resistance, and sympathetic nerve activity (intraneural microelectrodes) during sessions of maintenance hemodialysis in 7 patients with and 16 patients without a history of hemodialysis-induced hypotension. During hemodialysis, blood pressure at first remained unchanged as calf resistance increased in both hypotension-resistant (from 37 +/- 4 to 49 +/- 5 U, P < 0.05) and hypotension-prone (from 42 +/- 6 to 66 +/- 12 U, P < 0.05) patients; sympathetic activity increased comparably in the subset of patients in whom it could be measured. With continued hemodialysis, calf resistance and sympathetic activity increased further in the hypotension-resistant patients, but in the hypotension-prone patients the precipitous decrease in blood pressure was accompanied by decreases in sympathetic activity, vascular resistance, and heart rate as well as symptoms of vasodepressor syncope. On an interdialysis day, both groups of patients increased vascular resistance normally during unloading of cardiopulmonary baroreceptors with lower body negative pressure and increased heart rate normally during unloading of arterial baroreceptors with infusion of nitroprusside. These findings indicate that in a group of hemodialysis patients without diabetes or other conditions known to impair autonomic reflexes, hemodialysis-induced hypotension is not caused by chronic uremic impairment in arterial or cardiopulmonary baroreflexes but rather by acute, paradoxical withdrawal of sympathetic vasoconstrictor drive producing vasodepressor syncope.     

Effect of angiotensin-ll blockade on systemic and hepatic haemodynamics and on the renin-angiotensin-aldosterone system in cirrhosis with ascites

We have studied the effect of angiotensin-II blockade with saralasin on the cardiovascular and hepatic hemodynamics and on the renin-angiotensin-aldosterone system in fourteen patients with cirrhosis and ascites. Control measurements showed that most of the patients had a low mean arterial pressure, high plasma volume, normal or high cardiac index, low peripheral resistance and high plasma renin activity and aldosterone concentration. The wedged hepatic venous pressure was increased in each patient and the estimated hepatic blood flow was normal in most of them. Overall, saralasin induced a significant reduction of the mean arterial pressure, cardiac index and peripheral resistance. The decrease of the peripheral resistance was greater than that of the cardiac index. Six of the patients developed a marked reduction of the mean arterial pressure with low doses of saralasin (1--2.5 microgram/kg/min), and they had significantly higher plasma renin activity and lower mean arterial pressure than the remaining eight patients who showed a slight or no hypotensive response in spite of infusing saralasin up to a dose of 10 micrograms/kg/min. Overall, the decrease of the mean arterial pressure correlated directly with the baseline values of plasma renin activity. Angiotensin-II blockade induced a significant reduction of the wedged hepatic venous pressure. The hepatic blood flow did not show any significant change. The decrease of the wedged hepatic venous pressure was directly related to the reduction of the mean arterial pressure and also to the control plasma renin activity. Our study indicates that in most patients with cirrhosis, ascites and high plasma renin activity, arterial pressure is maintained by the effect of endogenous angiotensin II on the peripheral vasculature, and we suggest that a pre-existing arterial hypotension secondary to an arteriolar vasodilatation is the cause of renin release in these patients. Our results also show that angiotensin-II blockade is accompanied by a reduction of the post-sinusoidal hepatic vascular resistance.     

高龄老年透析患者应用3种透析方法对预防血透相关性低血压的作用比较

目的探讨高龄老年透析患者应用可调钠透析、低温透析以及常规常温透析对预防血透相关性低血压的作用比较。方法选择高龄老年患者血透中经常出现低血压反应的规律血液透析患者10例,采用单盲法,自身对照设计,每个患者分别接受标准透析、可调钠透析、低温透析,每种方案为期4周。分别测量患者超滤量、血肌酐、尿素氮、血清钠以及血压等指标。结果3种透析方式在透析效率方面无显著差别,但可调钠血液透析、低温血液透析与常规透析相比,低血压发生率明显降低。结论对血液透析过程中有低血压倾向的高龄老年患者,可选用低温血液透析或可调钠血液透析。     

Hemodynamic effects of the converting enzyme inhibitor teprotide in normal- and high-renin hypertension

The hemodynamic effects of the converting enzyme inhibitor teprotide (SQ 20881) were investigated in five patients with normal plasma renin activity who were normotensive during the study (group I), in five patients with hypertension and normal plasma renin activity (group II), and in five patients with hypertension and high plasma renin activity (group III). No significant hemodynamic changes were observed during teprotide administration in group I. In group II there was a decrease in mean arterial pressure by 10 +/- 2% (p < 0.005) that was associated with a decrease by 16 +/- 7% (p < 0.05) in stroke volume and cardiac output, possibly due to venodilatation and without a concurrent change in total peripheral resistance. In group III the larger decrease of 19 +/- 4% (p < 0.005) in mean arterial pressure was due to a decrease by 30 +/- 3% (p < 0.005) in peripheral resistance. In this group stroke volume and cardiac output increased by 13 +/- 2% (p < 0.025). There were no compensatory changes in heart rate despite the decrease in mean arterial pressure and vasodilatation. These results indicate that teprotide decreases arterial pressure by a dual hemodynamic mechanism. Cardiac output is increased by teprotide in patients with high-renin hypertension who exhibit the greatest decrements in peripheral resistance.     

Regional changes in sympathetic nerve activity and baroreceptor reflex function and arterial plasma levels of catecholamines, renin and vasopressin during naloxone-precipitated morphine withdrawal in rats

The aim of the study was to examine regional changes in sympathetic nerve activity (SNA) and baroreceptor function and arterial plasma catecholamines, arginine vasopressin (AVP) and plasma renin activity during morphine withdrawal in chloralose-anesthetized rats. Dependence was induced by s.c. morphine base pellets. Adrenal, renal and splanchnic SNA and SNA from the lumbar sympathetic chain were recorded before and after i.v. injections of naloxone. Baroreceptor function was examined with phenylephrine-induced increases in mean arterial pressure. In separate experiments, arterial plasma norepinephrine, epinephrine, dopamine, plasma renin activity and AVP were measured before and after naloxone-precipitated withdrawal. Naloxone administration elicited an increase in mean arterial pressure and heart rate. Although renal SNA was inhibited by approximately 50%, adrenal SNA and lumbar SNA increased by approximately 400 and 80%, respectively. Splanchnic SNA did not change significantly. The baroreceptor-mediated inhibition of adrenal SNA was facilitated while that for renal SNA was attenuated. The arterial plasma level of norepinephrine was doubled and epinephrine increased almost 20-fold. AVP increased about 15-fold, whereas plasma renin activity showed only a minor increase after naloxone. This study shows that a marked differentiation of the SNA response occurs during morphine withdrawal in rats, which suggests an interaction between opioid receptors and the control of regional sympathetic output. Furthermore, large amounts of AVP and epinephrine are released, which probably contribute to the cardiovascular changes seen in the withdrawal phase.     

Cardiovascular and endocrine responses during the cold pressor test in subjects with cervical spinal cord injuries

OBJECTIVE: To investigate cardiovascular regulation and endocrine responses during the cold pressor test in patients with chronic spinal cord injury (SCI). DESIGN: Experimental and control study. SETTING: University laboratory, department of rehabilitation medicine, in Japan. PARTICIPANTS: Eight quadriplegic subjects with complete spinal cord transection at the C6 to C8 level and 6 age-matched healthy subjects. INTERVENTIONS: Cardiovascular and endocrine responses were examined during 2 minutes of control, 3 minutes of ice-water immersion of the foot, followed by a 3-minute recovery. MAIN OUTCOME MEASURES: Blood pressure, heart rate, the Borg 15-point Rating of Perceived Pain Scale, and blood samples for measurement of plasma norepinephrine, epinephrine, plasma renin activity, plasma aldosterone, and arginine vasopressin. RESULTS: The rise in the mean arterial blood pressure during the cold pressor test in patients with SCI (baseline, 81.6+/-3.7mmHg; increased by 30%+/-6.1%) was significantly (P<.05) higher than that in healthy subjects (baseline, 101.2+/-4.5mmHg; increased by 20%+/-4.5%). The SCI subjects had no change in heart rate throughout the test, in contrast to the tachycardia noted in normal subjects. Baseline plasma norepinephrine in SCI subjects (63.0+/-18.3pg/mL) was significantly lower than in normal subjects (162.3+/-19.6pg/mL) and plasma norepinephrine increased significantly during the cold pressor test in both groups. CONCLUSIONS: In the SCI subjects, a reflex sympathetic discharge through the isolated spinal cord results in a more profound rise in mean blood pressure during ice-water immersion. This response was free of inhibitory impulses from supraspinal center and baroreceptor reflexes, either of which might restrain the increase in blood pressure.     

Plasma renin and serum dopamine-beta-hydroxylase during orthostatic hypotension in quadriplegic man

To determine whether orthostatic hypotension in patients with cervical spinal cord lesions is the result of impaired sympathetic nerve response and/or impaired renin release, serum dopamine-beta-hydroxylase (DbetaH) activity and plasma renin activity (PRA) were examined during passive tilting in 6 quadriplegic patients and in 6 able-bodied control subjects. Serum DbetaH was measured by an isotopic enzymatic method and PRA by radioimmunoassay. Following head-up tilting, quadriplegic subjects demonstrated a prompt, significant decrease in mean arterial pressure (MAP) and increase in heart rate (HR). DbetaH and PRA both increased significantly 15 minutes after tilt. In normal subjects, although HR increased, MAP was unchanged; DbetaH and PRA did not increase significantly during head-up tilt. The finding of increased DbetaH during tilt hypotension in quadriplegic patients provides evidence that reflex sympathetic nerve stimulation persists despite cervical cord transection. Increased PRA may be attributed to decreased renal perfusion pressure and increased sympathetic stimulation during tilt hypotension. These data suggest that orthostatic hypotension in quadriplegia patients cannot be attributed solely to failure of the sympathetic nervous system or the renin-angiotensin system to respond to the stimulus of orthostasis.     

透析低血压与非透析低血压血容量状况的分析

目的分析血液透析和超滤过程中透析相关低血压的发生与血容量变化的关系.探讨症状性透析低血压的防治策略.方法以过去3月内发生过症状性透析低血压为观测组(23例),设无透析低血压的为对照组(28例).应用超声血容量检测仪比较透析低血压者和正常对照者在透析超滤过程中血容量的变化特点、以及血压、心率的相应变化.结果低血压组的透析间体重增加量、超滤量明显高于对照组(P＜0.02).透析1小时后相对血容量、血压的下降程度超过对照组(P＜0.05);而反射性的心率增快方面,低血压组低于对照组(P＜0.05).结论血容量下降是发生低血压的重要机制,尤其是透析者伴有心血管功能损害时,更易发生透析低血压.而提高血容量是治疗症状性透析低血压的关键措施.     

Endogenous opiate peptides may limit norepinephrine release during hemorrhage

The involvement of the sympathetic nervous system in the cardiovascular response to hemorrhage and subsequent opiate receptor blockade was studied in conscious rabbits. Plasma catecholamines were measured by high-pressure liquid chromatography to indirectly assess sympathetic activity. Arterial blood samples were drawn at four times during the experiment: 1) before hemorrhage; 2) after a 15% blood loss; 3) after mean arterial blood pressure decreased to less than 40 mm Hg; and 4) 2 min after an i.v. injection of naloxone (3 mg/kg) or saline. Rapid removal of 15% of the total blood volume (approximately equal to 8 ml/kg) increased heart rate and plasma norepinephrine. Plasma epinephrine and blood pressure remained at control levels. Further hemorrhage (approximately equal to 16 ml/kg) produced a sudden decrease in blood pressure and a large increase in plasma epinephrine. Plasma norepinephrine was not significantly different from the previous sample. Subsequent injection of naloxone significantly increased plasma norepinephrine and blood pressure compared to the saline-treated group. Plasma epinephrine was similar in the two groups. These studies suggest that naloxone may exert its pressor effect during hemorrhagic hypotension in the conscious rabbit by blocking a naturally occurring, opiate peptide-mediated inhibition of norepinephrine release. The results are consistent with a peptidergic limit on sympathetic activity being responsible for the decrease in blood pressure seen during acute hemorrhage.     

Role of the Sympathetic Nervous System in Regulating Renin and Aldosterone Production in Man

Several lines of evidence have been developed indicating that the sympathetic nervous system may play a role in mediating the renal and adrenocortical secretory responses to upright posture and sodium deprivation. Despite concurrent increases in arterial blood pressure, the plasma renin activity of normal subjects increased both in response to the infusion of catecholamines (norepinephrine: epinephrine, 10:1) and in response to stimulation of the sympathetic nervous system by cold. Aldosterone excretion was also increased by catecholamine infusion. In normal subjects the stimuli of upright posture and of sodium depletion both resulted in increases in urinary catecholamines, plasma renin activity, and urinary aldosterone. A patient with severe autonomic insufficiency did not experience normal elevations of urinary catecholamines, plasma renin activity, or urinary aldosterone in response to upright posture or sodium deprivation, despite a substantial fall in arterial blood pressure. When orthostatic hypotension was prevented by infusion of catecholamines, however, increases in plasma renin activity and in aldosterone excretion were observed.     

The immediate pressor response to saralasin in man: evidence against sympathetic activation and for intrinsic angiotensin II-like myotropism

The cardiovascular and hormonal effects of intravenous saralasin (0.5, 1 and 5 micrograms min-1 kg-1) were assessed in nine tetraplegic patients (with complete cervical spinal cord transaction above the sympathetic outflow) and in six normal subjects. In the tetraplegic patients, saralasin caused an immediate transient pressor response which was not dose-dependent and substantially greater than the pressor response in normal subjects. The pressor response in the tetraplegic patients was not accompanied by a rise in levels of plasma noradrenaline. In the tetraplegic patients, after alpha-adrenoceptor blockade with thymoxamine (1 mg kg-1 h-1), twice the dose of intravenous noradrenaline was needed to induce the same pressor response. The pressor response to saralasin (5 micrograms kg-1 min-1), however, was unaffected by thymoxamine. Saralasin caused minimal changes in levels of plasma renin activity and plasma aldosterone in both groups. There was no relationship between basal plasma renin activity and the pressor response in either group. We therefore conclude that the immediate transient pressor response to saralasin in man is not due to central sympathetic stimulation, is unlikely to be due to peripheral sympathetic activation and is probably the result of intrinsic angiotensin II-like myotropism.     

Do elderly patients with an excessive fall in blood pressure on standing have evidence of autonomic failure?

1. Blood pressure, heart rate and plasma catecholamine responses were examined in two groups of elderly subjects distinguished by blood pressure responses to standing. Subjects in the control group showed a fall of less than 15 mmHg in systolic blood pressure on standing; subjects in the orthostatic hypotension group had falls of more than 20 mmHg systolic and 10 mmHg diastolic blood pressure on standing. 2. The heart pressure response on standing showed no significant difference between the two groups. 3. The orthostatic hypotension patients had lower plasma noradrenaline concentrations than the control patients (P less than 0.01) in the supine position, but during 10 min standing there was no significant difference in noradrenaline levels between the groups, and the percentage increase of noradrenaline levels in the orthostatic hypotension group was greater (P less than 0.05) than in the control group. 4. In the supine position, diastolic blood pressure was higher (P less than 0.05) in the orthostatic hypotension group than in the control group. 5. We conclude that impairment of baroreceptor function is not involved in most cases of orthostatic hypotension in the elderly, nor is there reduction of sympathetic nervous activity. We suggest that mechanical changes or adrenoreceptor dysfunction are more likely to be important factors in orthostatic hypotension in the elderly.     

Dopaminergic Influence on the Cardiovascular and Hormonal Responses to Cold Stress in Hypertensive Patients

Immersion of one hand into ice water (cold pressor test) in eight hypertensive subjects induces elevation of mean arterial pressure, increase in heart rate, and no significant changes of plasma renin activity and plasma aldosterone concentrations. Domperidone, a DA2 dopaminergic antagonist, attenuates heart rate increase induced by the cold pressor test, and the combination of bromocriptine, a known DA2 dopaminergic agonist, with domperidone again provoked a heart rate increase during the cold pressor test. Domperidone caused an increase of both plasma renin activity and plasma aldosterone concentrations, which were reversed by bromocriptine. These results suggest that a dopamine-receptor stimulation is taking place during the cold pressor test.     

Role of Renal Prostaglandins in Sympathetically Mediated Renin Release in the Rat

Renal prostaglandins (PG) appear to mediate renin release due to stimulation of the intrarenal baroreceptor, but not that due to activation of the macula densa. However, as the role of PG in sympathetically mediated renin release remains unclear, a possible interrelationship between these factors was examined in conscious rats. Hydralazine increased the serum renin levels from 3.1+/-0.8 to 16.7+/-3.0 ng/ml per h at a dose of 1 mg/kg. Indomethacin (5 mg/kg) suppressed urinary PGE(2) and PGF(2alpha) excretion by 89 and 74%, respectively, arachidonate hypotension by 82%, and inhibited the elevated renin levels from hydralazine by 100% without altering the hypotensive effect of the drug. Another PG synthetase inhibitor, meclofenamate, was also effective in attenuating hydralazine-induced renin release, urinary PGE(2) and PGF(2alpha) excretion, and arachidonate hypotension. Isoproterenol, a nonselective beta-adrenergic agonist, increased heart rate, lowered blood pressure, and also stimulated the release of renin when administered intraperitoneally. However, intrarenal infusion of the drug only resulted in increased renin release. Indomethacin inhibited isoproterenol-induced renin release by 66 and 67%, respectively, without altering the hemodynamic effects associated with the intraperitoneal administration of the drug. The selective beta(1) agonist, H133/22, increased the release of renin and heart rate in a dose-related manner without altering blood pressure. H133/22-induced renin release was inhibited by 80% by indomethacin pretreatment. Finally, intrarenal infusions of dibutyryl cyclic AMP (3 mg/kg per min) increased the serum activity from 4.1+/-0.2 to 20.4+/-3.9 ng/ml per h without altering mean arterial pressure. Indomethacin inhibited this renin response to dibutyryl cyclic AMP by 96%. Thus, renal PG appear to be important mediators of sympathetically stimulated renin release acting as a site distal to the beta-adrenergic receptor.     

在线血容量监测在血液透析患者个体化治疗中的应用

目的通过在线血容量（Bloodvolume，BV）监测血液透析过程中相对血容量（Relativebloodvolume，RBV）变化，探讨其在血液透析（Hemodialysis，HD）相关低血压及高血压中的作用。方法选择同济大学附属东方医院肾内科47例维持性HD患者，根据其血压情况将患者分为正常血压（Normal blood pressure，NBP）组14例、症状性低血压（Dialysis-Symptomatic hypotension，SH）组18例，难治性高血压（Dialysis-refractory hypertension，RH）组15例，应用在线BV监测观察HD中RBV、血压、超滤量（Ultrafiltration volume，UV）、平均动脉压（Meanarterial pressure，MAP）的变化。实验分三阶段进行，第一、二阶段为上述指标观察期，第三阶段为干预调整期。进而比较分析各阶段、各组患者各项指标的变化规律。结果NBP、SH、RH各组的RBV变化差异均存在显著性（P〈0．05），根据SH组不同的RBV变化，分别进行上调干体重或改变超滤方式，SH发生率明显下降（P〈0．05）；对RH组患者加强超滤，其MAP较前显著下降（P〈0．05）。结论不同血压表现的HD患者RBV的变化差异存在显著性，监测HD中RBV变化可以对合理设定HD患者的干体重、减少SH发生、控制RH，提高透析安全性，进而制定个体化透析方案提供重要信息。     

维持性血液透析患者透析过程中发生有效血容量不足时血压波动特征及其与透析开始时血压的比较

目的探讨慢性肾功能衰竭患者在血液透析超滤治疗过程中引发的有效血容量不足临床症状,对症状形成时的血压变化进行临床分析。方法选取2016年10月至2019年2月在阳泉煤业(集团)有限责任公司总医院肾内科维持性血液透析患者146例,共进行39658例次血液透析。发生可确定的血容量不足出现的临床症状病例3527例次。分析透析早期(>0~≤60 min)、中期(>60~≤180 min)、后期(>180~≤240 min)各时间段发生血容量不足时的临床症状特点。对透析中的低血压、高血压、维持血压进行定义,统计临床症状出现时各种血压发生率。将临床症状出现时测得的平均动脉压(mean arterial pressure,MAP)与其透析开始时的MAP进行比较,对MAP的演变过程进行分类。对透析间期干体质量增加量即≥5%或<5%在透析超滤中引发临床症状的发病情况给予统计。分析透析中超滤过速、过量外的其他导致血容量不足临床症状的因素。结果血容量不足出现的临床症状发生率为8.9%(3527/39658)。有效血容量不足引发的临床症状在透析的各时间段均有表现,有其发病特点。血压指标不能准确反映临床症状发生必有的相关联性。透析>0~≤60 min发生的有效血容量不足多与超滤量过多、过快有关,共发病493例次,其中低血压341例次,占69.1%(341/493);高血压79例次,占16.1%(79/493);维持血压73例次,占14.8%(73/493)。透析>60~≤180 min,临床症状发生率增加,与持续或过量超滤有关,共发病1306例次,其中低血压1003例次,占76.8%(1003/1306);高血压179例次,占13.7%(179/1306);维持血压124次,占9.5%(124/1306)。透析>180~≤240 min是临床症状的高发时间段,与持续的超滤并超出干体质量设置有关,共发病1728例次,其中低血压1408例次,占81.5%(1408/1728);高血压发生减少,但仍有顽固性高血压病例。血容量不足临床症状出现时,1989例次表现为渐降型低血压,容易引起临床关注;763例次表现为骤降型低血压,临床症状出现前血压较稳定,出现时血压骤然下降;446例次临床症状出现时较透析前有明显升高,给临床症状的判断带来困难;329例次维持了透析前的血压。过度水潴留在全程透析临床症状均有发作,总次数显著增多。一般水潴留发生次数少,多发生于透析>180~≤240 min。血浆胶体和晶体渗透压影响血浆再充盈,透析超滤方式的改变以及透析温度对血压和血容量变化有影响。结论慢性肾功能衰竭血液透析治疗的患者,因其发病特点和治疗的特殊性,透析超滤过程易发生有效血容量不足引起的相关临床症状。而临床症状的出现并不与血压变化同步,提高对血容量不足临床症状认识,做到早发现、早处置,有利于后续血液透析的安全治疗,较好的完成超滤目标值。     

Hemodialysis hemodynamics in an animal model: effect of using an acetate-buffered dialysate

Acetate-buffered dialysis (procedure A) was performed in conscious, nonuremic, splenectomized dogs. In some animals, dialysis was repeated after sympathectomy with 6-hydroxydopamine. During procedure A, hemodynamic changes were most pronounced 1 minute after starting dialysate flow (acute phase), and included a marked rise in cardiac output, pulse rate, and mean pulmonary artery pressure, but no change in mean arterial pressure (MAP) in intact animals. However, a precipitous fall in MAP was noted in sympathectomized dogs. Plasma acetate levels at this time averaged 2.0 +/- 0.5 mmol/L. Six to 30 minutes into procedure A, hypotension could be demonstrated in the intact, but not in the sympathectomized animals, at which time plasma acetate levels averaged 2.2 to 2.7 mmol/L. At 60 to 90 minutes into dialysis, when plasma acetate levels averaged 3.0 +/- 0.8 mmol/L, hypotension with procedure A was no longer significantly greater than with bicarbonate-buffered dialysis (procedure B). Plasma acetate levels at 30 to 90 minutes correlated with the change in cardiac output (r = 0.86, P less than 0.05) and total peripheral resistance (r = -0.76, P less than 0.05), but not with the decrease in MAP (r = -0.43, P not significant). Substantial hemodynamic changes were not seen when bicarbonate-buffered dialysis was used. Our results suggest that acute hypotension during procedure A in the dog model is prevented by an intact sympathetic nervous system. Hypotension occurring later during procedure A is difficult to demonstrate and does not appear to be accentuated after chemical sympathectomy. During procedure A the increase in cardiac output correlates with plasma acetate level.     

Central sympathoinhibitory action of ketanserin in rats

The effect of ketanserin on sympathetic efferent nerve activity which was recorded from the postganglionic renal nerve, inferior cardiac nerve and preganglionic adrenal nerve was studied in buffer nerve-intact rats. Intravenous administration of ketanserin (0.05-5.0 mg/kg) produced bradycardia and a reduction of mean arterial pressure dose-dependently. Renal nerve activity and inferior cardiac nerve activity also were reduced by ketanserin. After i.v. administration, baroreceptor afferent nerve activity did not increase, but actually decrease. Moreover, i.v. and i.c.v. administration of ketanserin caused a decrease in preganglionic adrenal nerve activity accompanied with hypotension and bradycardia. Ketanserin (0.5 mg/kg i.v.) and clonidine (3 micrograms/kg i.v.) produced equihypotension and bradycardia. On the other hand, the ketanserin-induced reduction of renal nerve activity was milder than that induced by clonidine. The present findings confirmed that ketanserin has a central sympathoinhibitory action. This central action of ketanserin may play an important role in ketanserin-induced bradycardia and may be partially responsible for ketanserin-induced hypotension.