Automatic Regulation of Hemodynamic Variables in Acute Heart Failure by a Multiple Adaptive Predictive Controller Based on Neural Networks

Automated drug-delivery systems that can tolerate various responses to therapeutic agents have been required to control hemodynamic variables with heart failure. This study is intended to evaluate the control performance of a multiple adaptive predictive control based on neural networks (MAPC_NN) to regulate the unexpected responses to therapeutic agents of cardiac output (CO) and mean arterial pressure (MAP) in cases of heart failure. The NN components in the MAPC_NN learned nonlinear responses of CO and MAP determined by hemodynamics of dogs with heart failure. The MAPC_NN performed ideal control against unexpected (1) drug interactions, (2) acute disturbances, and (3) time-variant responses of hemodynamics [average errors between setpoints (+35 ml kg⁻¹ min⁻¹ in CO and ±0 mmHg in MAP) and observed responses; 6.4, 3.7, and 4.2 ml kg⁻¹ min⁻¹ in CO and 1.6, 1.4, and 2.7 mmHg (10.5, 20.8, and 15.3 mmHg without a vasodilator) in MAP] during 120-min closed-loop control. The MAPC_NN could also regulate the hemodynamics in actual heart failure of a dog. Robust regulation of hemodynamics by the MAPC_NN was attributable to the ability of on-line adaptation to adopt various responses and predictive control using the NN. Results demonstrate the feasibility of applying the MAPC_NN using a simple NN to clinical situations.     

Fluid volumes and pressor responsiveness in two-kidney rabbits with renal artery stenosis

This study examined body fluid volumes, the pressor responses to norepinephrine (NE), and the cardiovascular responses to NE before and during infusion of an angiotensin II (ANG II) antagonist in two-kidney rabbits with unilateral renal artery stenosis (RAS) of 3 and 30 day duration. Three separate experiments were performed. In the first experiment, plasma volume, extracellular fluid volume, and total body water were measured by the distribution volumes of radioiodinated serum albumin, 35SO4, and tritiated water, respectively. No differences were seen for any of these volumes between the 3- or 30-day RAS rabbits and their controls. In the second experiment, pressor responses to infusions of several doses of NE were examined; rabbits with 3- and 30-day RAS had exaggerated pressor responses to all doses of NE when compared with the control rabbits. In the third experiment, infusion of NE at 800 ng.min-1.kg body wt-1 resulted in more pronounced increases in mean arterial pressure and total peripheral resistance (TPR) in the 3- and 30-day RAS rabbits than in the controls; after infusion of [Sar1-Ile8] ANG II the increases in mean arterial pressure and TPR during NE infusion were blunted and were of the same magnitude as in the control group. In all experiments the 30-day RAS rabbits were hypertensive, whereas the 3-day RAS rabbits were normotensive; also, plasma renin activity (PRA) values were normal in both the 3- and 30-day RAS groups. These studies demonstrated that increases in body fluid volumes are not necessary for pressor and vascular hyperresponsiveness probably is mediated by ANG II, despite normal PRA values.     

Role of alpha 1-adrenoceptors in norepinephrine-induced cardiomyopathy.

This study practically delineated the contribution of alpha-adrenoceptor activation to the pathogenesis of norepinephrine (NE) cardiomyopathy. A total of 64 adult New Zealand white rabbits were used. NE cardiomyopathy was produced in rabbits by a 90-minute intravenous infusion of norepinephrine (2 micrograms/kg/min at infusion rate 0.382 ml/min). Arterial blood pressure and heart rate were constantly monitored. Arterial blood samples were obtained at 30-minute intervals for measurements of pH, blood gases, and glucose. Alpha-adrenoceptor blocking agents, when employed, were given 15 minutes prior to the initiation of NE infusion. Two days after treatment the rabbits were killed. The hearts were examined microscopically and assigned a histologic score. Pretreatment with the alpha 1-adrenoceptor blocker prazosin at 50, 100, or 200 micrograms/kg significantly reduced NE-induced myocardial injury in a dose-related manner. In contrast, the presence of alpha 2-adrenoceptor blocker yohimbine at 2.5 or 5.0 mg/kg was ineffective in preventing the formation of myocardial lesions. These findings suggest that NE cardiomyopathy may result largely from activation of the alpha 1-adrenoceptor system in the rabbit model.     

Plasma catecholamine concentrations during a 72-hour aminophylline infusion in children with acute asthma

To explore the possibility that theophylline may act through adrenomedullary secretion of catecholamines, we examined the time courses of plasma norepinephrine (NE), epinephrine (E), and theophylline concentrations and peak expiratory flow (PEF) in nine children with an acute exacerbation of asthma receiving a 72-hour constant infusion of aminophylline. These measurements were made before (baseline) and at 2, 24, 48, and 72 hours after the infusion began. Plasma theophylline concentrations were kept constant in a near midpoint therapeutic range (mean +/- SEM, 14.1 +/- 1.3 to 16.1 +/- 1.1 micrograms/ml) during the 24- to 72-hour infusion periods. Compared with the respective baseline values (383.8 +/- 56.0 and 67.6 +/- 11.8 pg/ml for NE and E), the following postinfusion plasma catecholamines reached statistically significant difference: 664.0 +/- 125.1 pg/ml for NE at 24 hours (p less than 0.05), and 214.9 +/- 57.8, 233.7 +/- 82.2, and 137.6 +/- 39.4 pg/ml for E at 2, 24, and 48 hours (p less than 0.01). Despite the fact that similar plasma theophylline concentrations were maintained, plasma E, which peaked at 24 hours after dose, returned toward the baseline at the end of infusion (99.7 +/- 24.1 pg/ml), whereas this trend was not observed for NE. The postinfusion PEF increased (p less than 0.01) in a stepwise fashion, compared with the baseline, as the infusion progressed. The change in PEF correlated significantly (p less than 0.002) with plasma theophylline concentrations but not with the increase in plasma E from the baseline. Theophylline concentrations did not correlate with the increase in plasma NE or E from the baseline.(ABSTRACT TRUNCATED AT 250 WORDS)     

苯肾上腺素预输注防治老年人脊麻后低血压的临床研究

目的 评估预防性输注苯肾上腺素用于防治老年人脊麻后低血压的疗效和安全性。方法 将2017年1月~4月在本院行骨科下肢手术且年龄超过60岁的52例患者,随机分为P组和C组,每组26例。两组患者均使用0.5%布比卡因2 ml进行腰麻,P组在腰麻注药后立即静脉给予苯肾上腺素（100 μg/ml）1 ml/min,C组给予生理盐水1 ml/min。观察两组患者的术中MAP、每例患者低血压、高血压、心动过缓的发作次数,发作低血压、高血压、心动过缓的患者数,初次低血压的发作时刻,术中最低和最高MAP,苯肾上腺素和液体的总使用量,术后6 h、24 h、48 h发生心电图改变的患者数以及肌钙蛋白增加的患者数。结果 P组MAP高于C组,初次低血压的发作时刻大于C组,差异有统计学意义（P＜0.05）。P组每例患者低血压的发作次数少于C组,差异有统计学意义（P＜0.05）。两组患者发生低血压的患者数、术中最低和最低MAP比较,差异无统计学意义（P＞0.05）。P组患者的无低血压发作的累计比例高于C组,差异有统计学意义（P＜0.05）。两组患者术中发生高血压和心动过缓例数、每例患者高血压和心动过缓的发作次数、术中液体总使用量比较,差异无统计学意义（P＞0.05）。P组的苯肾上腺素总使用量高于C组（P＜0.05）。两组患者在术后6 h、24 h均未发生心电图异常改变情况。P组患者在术后48 h内未发生心电图异常改变情况,C组有2例患者（7.69%）在术后48 h发生了心电图异常改变,两组差异无统计学意义（P＞0.05）。C组患者在术后6 h、24 h、48 h发生肌钙蛋白定量升高的患者数均高于P组,但差异无统计学意义（P＞0.05）。结论 预防性输注苯肾上腺素可有效防治老年人脊麻后低血压,减少低血压发作次数,延迟低血压发作时间,提高手术麻醉的安全性。     

Computer control of the infusion of vasoactive drugs

In the Cardiac Surgical Intensive Care Unit (CICU) of the University of Alabama Hospital in Birmingham, Alabama, the mean arterial pressure (MAP) is regulated by computer (H-P 21 MX) controlled infusion of vasodilating agents and has been performed in 1100 hypertensive patients following open heart surgery. The MAP controller was developed based on investigation of the dynamics of the physiological responses of hypertensive patients to trimethaphan camsylate (Arfonad) and sodium nitroprusside (Nipride). Representative responses were selected for investigation by digital simulation of a computer programmed version of a proportional-integral-derivative (PID) controller algorithm. The PID controller parameters were tuned to elicit a response with acceptable settling time and minimal overshoot during the time course of the simulated MAP. Eight IMED 929 (IMED Corporation, San Diego, CA) digitally controlled infusion pumps interfaced with our computer based CICU system are used to regulate the blood pressure of patients following cardiac surgery. A microprocessor based blood pressure controller employing this algorithm has been developed and is being evaluated. For system design, analysis, and evaluation, the essential aspects of the arterial blood pressure (MAP) and its response to nitroprusside has been modeled. The arterial pressure is considered the sum of nonstationary stochastic background activity and a change due to the nitroprusside (characterized by a transfer function). The model was applied to the simulation of a clinically used controller and has provided insight into responses observed in the treatment of patients. The model is presently being used for computer-aided design and evaluation of an adaptive controller.     

参附注射液联合去甲肾上腺素对脓毒症休克兔舌下微循环的影响

目的:观察参附注射液联合去甲肾上腺素对脓毒症休克兔舌下微循环的影响。方法:30只新西兰兔,随机分为5组:假手术组(Sham组)、模型组(Model组)、去甲肾上腺素组(NE组)、参附注射液组(SFI组)和参附注射液联合去甲肾上腺素组(SFI+NE组),每组各6只。Sham组只进行相应手术操作,不进行造模处理,其余各组经兔耳缘静脉注射脂多糖(LPS,2mg/kg)建立脓毒症休克模型,模型复制成功后给予乳酸钠林格注射液30ml/kg补液1h。NE组在模型建立后通过微量注射泵以2.0μg/kg/min的速度给予去甲肾上腺素(40μg/ml)6h;SFI分别于造模前、休克时、休克后1h和休克后2h给予参附注射液(2.5ml/kg)。SFI+NE组同时按NE组和SFI组处理方法进行干预;Model组和Sham组在模型建立后给予等体积的生理盐水(分6h持续泵入)。各组动物于建模前、休克时以及休克后1h、3h和6h时通过电生理记录仪和舌下微循环成像系统分别采集平均动脉压(MAP)和舌下微循环各指标[包括:血管密度(TVD)、微血管血流指数(MFI)、异质性指数(HI)、灌注血管比例(PPV)、灌注血管密度(PVD)],并比较各组各指标的差异。结果:基线状态下各组各指标之间无统计学差异(P>0.05),休克时除Sham组外,各组各指标之间无统计学差异(P>0.05)。休克3h、6h时,SFI+NE组MAP较Model组、NE组、SFI组均有明显改善(P<0.05)。休克6h时,NE组、SFI组MAP较Model组升高(P<0.05)。休克1h时,TVD、MFI、HI、PPV、PVD各指标在NE组、SFI组和SFI+NE组间均无明显统计学差异(P>0.05),与Model组相比,SFI组和SFI+NE组TVD、SFI组和NE组PVD有明显改善(P<0.05)。休克3h时,TVD、MFI、PPV各指标SFI+NE组与NE组、SFI组相比无明显统计学差异(P>0.05),SFI组MFI、PVD指标较Model组有明显改善(P<0.05),SFI组PVD指标较NE组、SFI+NE组有明显改善(P<0.05)。休克6h时,SFI组MFI指标与Model组、NE组、SFI+NE组相比有明显改善(P<0.05)。其余各指标差异在各时间点各组间比较无统计学意义(P>0.05)。结论:参附注射液联合去甲肾上腺素相比于单独应用参附注射液或去甲肾上腺素可明显改善脓毒症休克兔的MAP,但对TVD、MFI、HI、PPV和PVD微循环指标的改善作用,与单独用药疗效相当。     

Effect of tail suspension on haemodynamics in intact and sympathectomized rats

The effect of a 2-week tail suspension on mean arterial pressure (MAP) and pulse interval (PI) was studied in conscious chronically instrumented intact and sympathectomized rats. Sympathectomy was induced by 6-hydroxydopamine (100 mg·kg^–1, i.v.), injected 1 day before, and on days 5 and 10 of suspension. During suspension the intact rats had the same levels of MAP and PI as the intact controls. After release from suspension their MAP did not change: PI decreased (by 9%), but only for 1 h. Sympathectomy augmented the haemodynamic changes after release from suspension: tachycardia (10%) and hypotension (19%) were observed during the entire recording period (2 h). Therefore, in rats, post-suspension hypotension becomes apparent only after elimination of sympathetic influences. In spite of unaltered systemic parameters, intact post-suspension rats showed diminished responses to intravenous administration of tyramine (100 μg·kg^–1) and phenylephrine (1–2 μg·kg^–1). In addition, they showed augmented haemodynamic changes associated with natural behaviour. The increase of MAP and the decrease of PI on transition from rest to movement were more pronounced in the intact post-suspension rats than in the control rats (MAP 8.3% vs 4.5%, PI 15% vs 9%). In control rats the spectrum power density of low-frequency (0.0195–0.25 Hz) MAP fluctuations depended only weakly on behavioural activity, whereas in post-suspension intact rats it was profoundly augmented during movements (by 170%). Since the rapid adjustment of haemodynamics to behavioural activity is controlled by the sympathetic nervous system, the unbalanced condition of the cardiovascular system after suspension may reflect an altered sympathetic nerve control of the circulation. Electronic Publication     

Sex differences in pressure diuresis/natriuresis in rabbits

We tested for sex-related differences in the pressure diuresis/natriuresis relationships in anaesthetized, renally denervated rabbits, using an extracorporeal circuit to perfuse the left kidney with the rabbit's own blood, through a series of step-wise increases in renal artery pressure (RAP) (from 65 to 130 mmHg). Urine flow, sodium excretion, and the fractional excretions of sodium and urine increased with increasing RAP, and were greater in male than in female rabbits at all levels of RAP-tested. However, these apparent sex-related differences in the acute pressure diuresis/natriuresis relationships were not reflected in alterations in chronic regulation of mean arterial pressure (MAP). Thus, in rabbits on a normal salt diet (0.85 g day(-1)), resting conscious MAP was significantly greater in males (87 +/- 3 mmHg) compared with females (77+/-1 mmHg). Chronically increasing daily salt intake to 4.98 g day(-1) for 28 days had no significant effect on resting conscious MAP in either sex. Thus, although our observations indicate sex differences, at least under the present experimental conditions, in the factors regulating extracellular fluid volume, these do not appear to have a major impact in setting the level of MAP in the long term.     

Norepinephrine and epinephrine responses during orthostatic intolerance in healthy elderly men

In young individuals, orthostatic intolerance is associated with marked increases in plasma epinephrine (EPI) concentrations and attenuated rises in plasma norepinephrine (NE) concentrations. This study investigated the cardiovascular, EPI and NE responses of healthy elderly males during orthostatic stress. Twelve men (68 +/- 1 yr) with a recent history of orthostatic hypotension and who exhibited orthostatic intolerance (HYPO) during 90 degrees head-up tilt (HUT) were compared with 12 men (69 +/- 1 yr) without a history of orthostatic hypotension and who remained normotensive (NORMO) throughout 90 degrees HUT. Beat-by-beat recordings of heart rate (HR), mean (MAP), systolic (SBP), diastolic (DBP), and pulse (PP) pressures were made throughout 90 degrees HUT. Blood samples obtained during supine rest and 90 degrees HUT were analyzed for changes in EPI and NE concentrations, hematocrit, hemoglobin and plasma volume. Compared to supine rest, orthostatic intolerance was characterized by significant reductions (p < 0.0001) in MAP, SBP, DBP, and PP. The HR, MAP, SBP, DBP, and PP at the termination of 90 degrees HUT was significantly lower (p < 0.0001) for HYPO than NORMO. The 90 degrees HUT position resulted in significant increases (p < 0.01) in NE for both HYPO and NORMO, with the rise in NE significantly lower (p < 0.05) in HYPO. There were no differences between groups regarding EPI concentrations at the termination of 90 degrees HUT. These results suggest that the magnitude of arterial pressure (AP) reduction does not influence the EPI response during orthostasis in healthy elderly men. However, marked reductions in AP, leading to orthostatic intolerance, are associated with inadequate increases in NE in these individuals.     

血压自动控制系统应用于抗失血性休克的实验研究

本文设计的８模型血压自适应控制系统，试用于造成失血休克模型的家兔的血压自控治疗，２２只休克家兔中１８只能控制血压于预置水平。根据血压控制期间药物输注速率变化规律，可将２２只家兔分为三类，剂量上升型、剂量下降型和迟钝型。实验表明多模型血压自适应控制系统应用于失血性休克家兔的血压控制治疗是可行的，能做到剂量个体化，按需给药。在血压控制期间显示的药物输注速率变化能在一定程度上反映机体休克状况，有可能为及     

酚妥拉明对失血性休克家兔微循环血流动力学的影响

本研究旨在探讨酚妥拉明对失血性休克微循环血液灌流的作用.两组家兔——生理盐水对照组(n=7)和酚妥拉明治疗组(n=8),麻醉后放血至血压为5.33～6.00kPa以造成重度失血性休克.维持60min后将5mg酚妥拉明加入25ml生理盐水中静脉滴注(对照组仅滴注等量生理盐水),同时将放出的全部血液回输.观察休克及用药前后平均动脉血压、心率和肠系膜微循环变化.用显微电视录像静像步进技术测定毛细血管口径、血流速度及血流量.酚妥拉明滴往后,心率略加快,血压明显下降,血流速度和血流量显著降低,毛细血管口径两组间无明显差异.表明休克时酚妥拉明单独应用可使血压严重下降,从而加重肠系膜毛细血管的血流障碍.     

Effects of nafamostat mesilate on ADP-induced platelet aggregation and disaggregation in hemodialysis patients

Nafamostat mesilate (NM), a synthetic protease inhibitor, is the most commonly used anticoagulant in the setting of extracorporeal circulation (ECC) in patients with bleeding tendency. It inhibits both platelet aggregation and activation of coagulation factors. Although it has been reported that NM disaggregates aggregated platelets, little is known about such an effect in the setting of hemodialysis therapy (HD). We examined the effects of NM on adenosine 5'-diphosphate (ADP)-induced platelet aggregation and disaggregation using platelet-rich plasma obtained from 6 HD patients. The platelet aggregation was stimulated by 3 microM ADP and change of aggregation was monitored by an aggregometer. NM adjusted to the final concentrations of 0.1 (1.9 x 10(-7)), 1.0 (1.9 x 10(-6)), 10, (1.9 x 10(-5)), and 100 (1.9 x 10(-4)) microg/ml (M) or veronal-buffered saline (VBS) as control was added before or after to the stimulation of ADP. NM not only inhibited platelet aggregation, but also disaggregated already aggregated platelets at concentrations of 1.0 microg/mln or higher. Moreover, NM almost completely disaggregated at 100 microg/ml. This NM concentration of 1.0 microg/ml was lower than the therapeutic concentration in ECC of HD (i.e., 10 M(-5)). Both inhibitory and disaggregatory effects of NM expressed a dose-related dependency. Our results suggest that NM can exert both aggregation inhibitory and disaggregatory effects on platelets of HD patients within the therapeutic concentration.     

Effects of insulin on experimental catecholamine cardiomyopathy.

We have recently shown that insulin attenuates norepinephrine (NE) dose-response curves in both isolated cardiac muscle and intact heart preparations. Accordingly, an intact rabbit model was used to determine if insulin would reduce the extent of myocardial damage following a standard NE infusion. Each animal was given pentobarbital, 30 mg/kg, and heart rate, arterial pressure, glucose, blood gases, and pH were measured. NE (2 microgram/min/kg) was given intravenously for 90 minutes. After 48 hours the rabbits were killed and the hearts were examined microscopically and assigned a histologic score. Florid lesions were present in 17 of 24 sections (71%) from 12 animals. They were characterized by myofiber necrosis and an intense cellular reaction. However, only 5 of 40 sections (12.5%) from 20 rabbits given insulin (10 units/kg) 30 minutes before the NE infusion showed advanced lesions (P less than 0.001). The mean histologic score was reduced from 1.7 to 1.0 (P less than 0.001). The frequency of advanced lesions increased to 86% in animals given a higher dose of NE (3 microgram/kg/min) and was reduced to 53% by pretreatment with insulin. A dosage of 5 units/kg was as effective as 10 units/kg, but rabbits given 1 unit/kg manifested cardiomyopathic changes identical to those in rabbits not pretreated with insulin. No differences in heart rate, arterial pressure, PO2, or pH were evident between the groups. It is concluded that large doses of insulin reduce myocardial damage produced by NE in this model. This may be linked with the phenomenon of insulin inhibition of the inotropic action of NE.     

Increase in the blood pressure and decrease in the norepinephrine release in the ventrolateral medulla during intraventricular administration of hypertonic NaCl

Norepinephrine (NE) release in the ventrolateral medulla (VLM) was serially measured in anesthetized male Wistar rats during the rise in the blood pressure (BP) produced by acute intraventricular (ICV) administration of hypertonic (1.5 M) NaCl. Catecholamine release was determined by a brain microdialysis method using high performance liquid chromatography and electrochemical detector. The release of NE in the VLM was significantly decreased after ICV 1.5 M NaCl. In another set of rats, the pressor response to acute ICV 1.5 M NaCl was attenuated by selective administration of NE to the VLM using the microdialysis method. Chronic and continuous ICV infusion of 1.5 M NaCl to conscious rats caused an increase in BP on day 10 which was associated with a decrease in NE release in the VLM; concomitant ICV infusion of NE or of a synthetic NE precursor,l-threo-3,4-dihydroxyphenylserine (l-DOPS) prevented the rise in BP as well as the reduction in NE release. These results suggest that a decrease in the NE release of the VLM may contribute to the change in BP induced by ICV infusion of hypertonic saline.     

Nitric oxide and thyroid gland: modulation of cardiovascular function in autonomic-blocked anaesthetized rats

We have previously reported that acute administration of N(G)-nitro-l-arginine methyl ester (L-NAME) increases the mean arterial pressure (MAP) and heart rate (HR) in autonomic-blocked (CAB) anaesthetized rats. In the present study we examined whether thyroid and adrenal glands are involved in these pressor and chronotropic responses. Sprague-Dawley rats were studied after bilateral vagotomy and ganglionic blockade with hexamethonium (10 mg kg(-1)), and stabilization of MAP with infusion of phenylephrine (PE) (6 microg kg(-1) min(-1)). The rats were divided into groups: L, CAB; PE, CAB + PE bolus (6 microg kg(-1)); L-TX, thyroidectomy + CAB; L-AX, adrenalectomy + CAB; TX, only thyroidectomy; C, CAB. L, L-AX and L-TX groups received a bolus of l-NAME (7.5 mg kg(-1)). Triiodothyronine (T3), thyroxin (T4) and thyrotropin (TSH) levels were measured in L and L-TX rats before and after l-NAME administration. Reduced nicotamide adenine dinucleotide (NADPH) diaphorase activity was determined in heart and aorta of the TX group. The pressor response induced by l-NAME was similar in all groups. l-NAME-induced-tachycardia was associated with this rise in MAP. Adrenalectomy did not modify this chronotropic response, but it was attenuated by thyroidectomy. Thyroidectomy by itself decreased the circulating levels of T3 but it had no effect on the plasma levels of T4 and TSH. L and L-TX groups showed similar levels of circulating T4 and TSH, meanwhile the plasma level of T3 decreased in the L group. Nitric oxide synthase (NOS) activity in atria as well as in aorta was greater in the TX group compared with C. When autonomic influences are removed, the thyroid gland modulates intrinsic heart rate via a mechanism that involves, at least in part, the nitric oxide pathway.     

Neurovascular and hemodynamic responses to hyperinsulinemia in healthy postmenopausal women

Acute hyperinsulinemia produces sympathetic activation, vasodilation, and cardiovascular changes in healthy young men. Postmenopausal period is accompanied by sympathetic, vascular and cardiovascular changes. Nevertheless, the effects of acute insulin infusion were not known in postmenopausal women. To study this aspect, 26 postmenopausal healthy women were submitted to an euglycemic hyperinsulinemic clamp performed during 120 min. Heart rate (HR: ECG), blood pressure (BP: oscillometric method), forearm blood flow (FBF: plethysmography), plasma norepinephrine (NE), plasma epinephrine (EP), and cardiovascular autonomic modulation (spectral analysis of R-R interval and BP variabilities) were measured before and during the clamp. Glycemia was kept similar to baseline during the clamp (84.6+/-1.2mg/dl versus 87.1+/-1.6 mg/dl), while plasma insulin increased significantly to a level of 89.3+/-5.6 microU/ml. Insulin infusion significantly increased plasma NE (+45+/-17 pg/ml), EP (+20+/-9 pg/ml), and low to high frequency ratio of R-R interval variability (LH/HF: 1.2+/-0.4), but did not change low frequency component of BP variability. FBF (+0.7+/-0.2 ml min(-1)100ml(-1)) was also significantly enhanced by hyperinsulinemia. HR and systolic BP increased with insulin infusion (+4+/-1 bat/min and +6+/-2 mmHg, respectively, P<0.05), while diastolic BP did not change. In conclusion, in healthy postmenopausal women, acute hyperinsulinemia produces sympathetic activation, and vasodilation, which results in HR and systolic BP enhancements, with no change in diastolic BP. This pattern of response is similar to the one usually observed in healthy young men.     

Cerebral reactive hyperaemia and arterial pressure in anaesthetized goats

The effects of arterial pressure on cerebral reactive hyperaemia were studied in anaesthetized goats measuring electromagnetically middle cerebral artery flow and performing arterial occlusions of 5–30 s. Under normotension (mean arterial pressure, MAP = 11± 0.3 kPa), reactive hyperaemia (peak hyperaemic flow to control flow and repayment to debt ratios) increased, and cerebrovascular resistance during peak hyperaemic flow decreased, as ischaemia duration lengthened; the virtual maximal changes were obtained after 20 s ischaemia. During hypertension by aorta constriction (MAP = 18 ± 0.7 kPa) or by i. v. infusion of noradrenaline (MAP = 19 ± 0.8 kPa) middle cerebral artery flow did not change significantly and cerebrovascular resistance increased 25 and 46%, respectively (P < 0.05). During both types of hypertension reactive hyperaemia was over 50% higher, and the decrement in cerebrovascular resistance during peak hyperaemic flow was also higher, than under normotension. During hypotension by constriction of the inferior vena cava (MAP = 5 ±.5 kPa) or by i. v. infusion of isoproterenol (MAP = 6±.5 kPa), middle cerebral artery flow decreased 35% or did not change, and cerebrovascular resistance decreased 41 and 45 %, respectively (P < 0.05). In these conditions, reactive hyperaemia and the decrement in cerebrovascular resistance during peak hyperaemic flow were reduced SOY, and it was similar in both types of hypotension. The absolute levels of cerebrovascular resistance obtained during peak hyperaemia were similar during normotension, hypertension and hypotension. Thus, arterial pressure is a main determinant of postocclusive cerebral reactive hyperaemia, and myogenic mechanisms may be of significance in determining the early stage of cerebral reactive hyperaemia after brief ischaemias. Adrenergic mechanisms might be of minor significance in this type of cerebral reactive hyperaemia.     

Catecholamine responses to histamine infusion in man

To evaluate the effects of histamine-induced hypotension on plasma catecholamine levels, eight normal men, aged 20 to 40 years, were infused with incremental doses of histamine starting at 0.2 microgram/kg/min at a 30 degree tilt position with monitoring of blood pressure (BP) and heart rate. Histamine dosage was increased every 5 minutes by 0.1 to 0.2 microgram/kg/min until mean BP fell greater than 15 mm Hg or a dosage of 1.6 micrograms/kg/min was reached. Plasma catecholamine samples were taken between the fourth and fifth minute of each histamine dosage. Identical measurements were made during nitroglycerin-induced hypotension in these subjects. Histamine produced threefold greater increases in heart rate and plasma norepinephrine (NE) levels than did nitroglycerin for comparable decreases in BP. Although NE levels increased twofold to fivefold from baseline with histamine infusion, epinephrine levels increased minimally at the highest doses or not at all. Our data demonstrate that histamine selectively releases NE from adrenergic nerve terminals without significant adrenal catecholamine release. We suggest that neural NE release plays an important role in the cardiac effects of histamine.     

Intravenous infusion of hyperosmotic NaCl solution induces acute cor pulmonale in anesthetized rats

Intravenous hyperosmotic NaCl infusion is an effective treatment for circulatory shock. However, a fast infusion rate (2 mL/kg at the rate of 1 mL/s) induces transient hypotension. This response has been reported to be due to decreased total peripheral resistance and/or decreased cardiac performance. Although the hypotension is transient and recovers within 2 min without detrimental consequences, it is important to understand the associated hemodynamics and mechanisms. We found that the hypotensive effect was larger with intravenous NaCl infusion than with intra-aortic infusion, indicating that change in cardiac performance played a more significant role than change in peripheral resistance. NaCl infusion induced an increase in pulmonary vascular resistance and central venous pressure and a decrease in right ventricular dP/dt max, suggesting acute cor pulmonale. Diastolic ventricular crosstalk-induced left ventricular failure was also observed. Hyperosmotic NaCl-induced hypotension was therefore mainly due to a combination of acute cor pulmonale and left ventricular failure.