Pulmonary vasodilatation and augmentation of right ventricular function following terbutaline infusion in severe chronic pulmonary disease

Twenty patients with a median age of 61 years and a median forced expired volume in 1 s (FEV1) after bronchodilating therapy of 0.55 l were studied in order to measure the effect of intravenous terbutaline on bronchial tone, cardiac function, pulmonary haemodynamics, gas exchange, and oxygen transport capacity during rest and in 10 patients during exercise. Terbutaline infusion during rest resulted in an increase in heart rate from 84 to 103 beats min-1 (P less than 0.01), a decrease in mean systemic arterial pressure from 95 to 80 mmHg (P less than 0.02), an unchanged mean pulmonary arterial pressure (18 mmHg), an increase in cardiac index from 2.89 to 3.86 l min-1 m-2 (P less than 0.01), an increase in right ventricular ejection fraction from 45 to 53% (P less than 0.01), an increase in left ventricular ejection fraction from 63 to 67% (NS), an unchanged arterial oxygen tension, and an increase in calculated oxygen delivery from 533 to 638 ml O2 min-1 m-2 (P less than 0.01). During exercise terbutaline infusion resulted in an increase in heart rate from 108 to 120 beats min-1 (P less than 0.05), a decrease in mean systemic arterial pressure from 117 to 106 mmHg (P less than 0.01), a decrease in mean pulmonary arterial pressure from 29 to 22 mmHg (P less than 0.01), an increase in cardiac index from 4.53 to 4.64 min-1 m-2 (NS), an unchanged arterial oxygen tension, and an increase in the calculated oxygen delivery from 834 to 856 ml O2 min-1 m-2 (NS). It was concluded that terbutaline augments right ventricular function: increases right ventricular ejection fraction and decreases right ventricular end-diastolic volume, and further decreases pulmonary vascular resistance without decreasing arterial oxygen tension, and increases oxygen delivery in patients with chronic pulmonary disease during rest and exercise.     

Effects of prolonged recombinant human erythropoietin administration on muscle membrane transport systems and metabolic marker enzymes

Adaptations to chronic hypoxia involve changes in membrane transport proteins. The underlying mechanism of this response may be related to concomitant occurring changes in erythropoietin (Epo) levels. We therefore tested the direct effects of recombinant human erythropoietin (rHuEpo) treatment on the expression of muscle membrane transport proteins. Likewise, improvements in performance may involve upregulation of metabolic enzymes. Since Epo is known to augment performance we tested the effect of rHuEpo on some marker enzymes that are related to aerobic capacity. For these purposes eight subjects received 5,000 IU rHuEpo every second day for 14 days, and subsequently a single dose of 5,000 IU weekly for 12 weeks. Muscle biopsies were obtained before and after 14 weeks of rHuEpo treatment. The treatment increased hematocrit (from 44.7 to 48.8%), maximal oxygen uptake by 8.1%, and submaximal performance by approximately 54%. Membrane transport systems and carbonic anhydrases involved in pH regulation remained unchanged. Of the Na⁺, K⁺-pump isoforms only the density of the α2 subunit was decreased (by 22%) after treatment. The marker enzymes cytochrom c and hexokinase remained unchanged with the treatment. In conclusion, changes in muscle membrane transport proteins and selected muscle enzymes do not contribute to the Epo-induced improvement in performance.     

Erythropoietin concentrations are elevated in the peritoneal fluid of women with endometriosis

Erythropoietin (Epo) is an important regulator of erythropoiesis and stimulates the proliferation of early erythroid precursors as well as the differentiation of late erythroid precursors of the erythroid lineage. However, recent studies have indicated that Epo also has angiogenic properties and plays an important role in the oestrogen-dependent cyclical angiogenesis within the mouse uterus. It was therefore postulated that Epo may be an important angiogenic factor in endometriosis. In order to address this hypothesis the concentration of Epo in peritoneal fluid (PF) was determined in patients with or without endometriosis. PF was collected from patients with endometriosis (n = 42) or without endometriosis (n = 18). Detectable concentrations of Epo were found in all PF samples analysed. The concentration of Epo in PF from patients with endometriosis was significantly higher than that in the control group (13.1 +/- 1.2 mIU/ml versus 7.2 +/- 0.7 mIU/ml, mean +/- SE respectively, P < 0.01). Furthermore, in patients with endometriosis the Epo concentrations in PF from patients with stage I disease (n = 17, 16.6 +/- 3.0 mIU/ml) were significantly higher than those with stage II (n = 8, 10.7 +/- 1.2 mIU/ml, P < 0.03), III (n = 13, 8.4 +/- 1.0 mIU/ml, P < 0.01), IV disease (n = 7, 7.5 +/- 1.0 mIU/ml, P < 0.01). These data suggest that Epo may play a role in the pathogenesis of endometriosis particularly in the initiation of the disease.     

Mechanisms of acute natriuresis in normal humans on low sodium diet

This study evaluates the relative importance of several mechanisms possibly involved in the natriuresis elicited by slow sodium loading, i.e. the renin-angiotensin-aldosterone system (RAAS), mean arterial blood pressure (MAP), glomerular filtration rate (GFR), atrial natriuretic peptide (ANP), oxytocin and nitric oxide (NO). Eight seated subjects on standardised sodium intake (30 mmol NaCl day⁻¹) received isotonic saline intravenously (NaLoading: 20 μmol Na⁺ kg⁻¹ min⁻¹ or ≈11 ml min⁻¹ for 240 min). NaLoading did not change MAP or GFR (by clearance of ⁵¹Cr-EDTA). Significant natriuresis occurred within 1 h (from 9 ± 3 to 13 ± 2 μmol min⁻¹). A 6-fold increase was found during the last hour of infusion as plasma renin activity, angiotensin II (ANGII) and aldosterone decreased markedly. Sodium excretion continued to increase after NaLoading. During NaLoading, plasma renin activity and ANGII were linearly related ( R = 0.997) as were ANGII and aldosterone ( R = 0.999). The slopes were 0.40 p m ANGII (mi.u. renin activity)⁻¹ and 22 p m aldosterone (p m ANGII)⁻¹. Plasma ANP and oxytocin remained unchanged, as did the urinary excretion rates of cGMP and NO metabolites (NO_x). In conclusion, sodium excretion may increase 7-fold without changes in MAP, GFR, plasma ANP, plasma oxytocin, and cGMP- and NO_x excretion, but concomitant with marked decreases in circulating RAAS components. The immediate renal response to sodium excess appears to be fading of ANGII-mediated tubular sodium reabsorption. Subsequently the decrease in aldosterone may become important.     

Increases in central blood volume modulate carotid baroreflex resetting during dynamic exercise in humans

We sought to determine if resetting of the carotid-vasomotor baroreflex function curve during exercise is modulated by changes in central blood volume (CBV). CBV was increased during exercise by altering: (1) subject posture (supine versus upright) and (2) pedal frequency (80 versus 60 revolutions min⁻¹ (r.p.m.)); while oxygen uptake (     ) was kept constant. Eight male subjects performed three exercise trials: upright cycling at 60 r.p.m. (control); supine cycling at 60 r.p.m. (SupEX) and upright cycling at 80 r.p.m. to enhance the muscle pump (80EX). During each condition, carotid baroreflex (CBR) function was determined using the rapid neck pressure (NP) and neck suction (NS) protocol. Although mean arterial pressure (MAP) was significantly elevated from rest (88 ± 2 mmHg) during all exercise conditions ( P < 0.001), the increase in MAP was lower during SupEX (94 ± 2 mmHg) and 80EX (95 ± 2 mmHg) compared with control (105 ± 2 mmHg, P < 0.05). Importantly, the blood pressure responses to NP and NS were maintained around these changed operating points of MAP. However, in comparison to control, the carotid-vasomotor baroreflex function curve was relocated downward and leftward when CBV was increased during SupEX and 80EX. These alterations in CBR resetting occurred without any differences in     or heart rate between the exercise conditions. Thus, increasing CBV and loading the cardiopulmonary baroreflex reduces the magnitude of exercise-induced increases in MAP and CBR resetting. These findings suggest that changes in cardiopulmonary baroreceptor load influence carotid baroreflex resetting during dynamic exercise.     

Fluid replacement beverages and maintenance of plasma volume during exercise: role of aldosterone and vasopressin

Summary Previous experiments have demonstrated that consumption of a glucose polymer-electrolyte (GP-E) beverage is superior to water in minimizing exercise-induced decreases in plasma volume (PV). We tested the hypothesis that elevated plasma concentrations of vasopressin and/or aldosterone above that seen with water ingestion may explain this observation. Six trained cyclists performed 115 min of constant-load exercise (approximately 65% of maximal oxygen consumption) on a cycle ergometer on two occasions with 7 days separating experiments. Ambient conditions were maintained relatively constant for both exercise tests (29–30° C; 58–66% relative humidity). During each experiment, subjects consumed 400 ml of one of the following beverages 20 min prior to exercise and 275 ml immediately prior to and every 15 min during exercise: (1) distilled water or (2) GP-E drink contents = 7% carbohydrate (glucose polymers and fructose; 9 mmol·1^–1 sodium; 5 mmol·^1–1 potassium; osmolality 250 mosmol·1^–1). No significant difference (P>0.05) existed in mean skin temperature, rectal temperature, oxygen consumption, carbon dioxide production or the respiratory exchange ratio between treatments. Further, no significant differences existed in plasma osmolality and plasma concentrations of sodium, potassium, chloride or magnesium between treatments. Plasma volume was better maintained (P<0.05) in the GP-E trial at 90 and 120 min of exercise when compared to the water treatment. No differences existed in plasma levels of vasopressin or aldosterone between treatments at any measurement period. Further, the correlation coefficients between plasma concentrations of vasopressin and aldosterone and change in PV during exercise were 0.42 (P<0.05) and 0.16 (P>0.05), respectively. Therefore, although these experiments support the notion that a GP-E beverage is superior to water in minimizing exercise-induced disturbances in PV during prolonged exercise, the mechanism to explain this observation is not due to differences in plasma concentrations of vasopressin or aldosterone alone.     

Effect of nasal CPAP treatment on plasma volume, aldosterone and 24-h blood pressure in obstructive sleep apnoea

Polycythaemia, peripheral oedema formation and hypertension have classically been described in association with obstructive sleep apnoea (OSA). However, there is very limited information about blood volume in OSA and how it changes during long-term treatment with nasal continuous positive airway pressure (nCPAP). Plasma (PV) and red-cell volumes (RCV), 24-h ambulatory blood pressure (BP), 24-h natriuresis and morning plasma aldosterone, renin activity and atrial natriuretic peptide in 11 men with a mean age of 47 y (range 37–55), apnoea index (AI) of 55 (22–106), body mass index of 36 (30–43) and seated BP of ≥140/90 mmHg without any medication were measured. BP-measurements were repeated after 3 weeks and all measurements after 3 mo of nCPAP treatment. Aldosterone and 24-h mean heart rates decreased during treatment. Twenty-four-h BP decreased after 3 weeks but that decrease did not persist after 3 mo of treatment. There was a relationship between changes in night-time mean BP and PV and aldosterone. The haematocrit declined in every patient. No significant changes were found in the mean PV or RCV. They were in all instances lower than has earlier been described for normal, non-obese subjects. These data also suggest that OSA causes divergent individual disturbances in blood volume homeostasis which can be corrected by nCPAP.     

Rats exhibit aldosterone-dependent sodium appetite during 24 h hindlimb unloading

Hindlimb unloading (HU) is an animal model of microgravity and bed rest. In these studies, we examined the role of ingestive behaviours in regulating body fluid balance during 24 h HU. In the first experiment, all rats were given distilled water to drink while two groups were also given access to a sodium chloride solution (0.9% or 1.8%). Water and saline intakes were measured before, during and after 24 h of HU. Rats reduced water intake during 24 h HU in all conditions. During HU, rats increased their intakes of both saline solutions (0.9% NaCl ( n = 11): control 7.8 ± 3 ml; HU 18.2 ± 4 ml; recovery 8.9 ± 2.5 ml; 1.8% NaCl ( n = 7): control 1.0 ± 0.4 ml; HU 3.8 ± 0.3 ml; recovery 1.2 ± 0.5 ml). Although water intake decreased there was no reduction in total fluid intake when saline was available. Plasma volumes were reduced during HU compared to rats in a normal posture when only water was available to drink (control ( n = 11) versus HU ( n = 11): 4.0 ± 0.2 versus 3.4 ± 0.2 ml (100 g body weight)⁻¹). When 0.9% saline was available in addition to water, plasma volumes after 24 h HU were not different from rats in a normal posture (control ( n = 11) versus HU ( n = 12): 4.3 ± 0.4 versus 4.3 ± 0.1 ml (100 g body weight)⁻¹). Plasma aldosterone but not plasma renin activity was significantly elevated after 24 h HU. Central infusions of spironolactone blocked the increased intake of 1.8% saline that was associated with 24 h HU. Thus, HU results in an aldosterone-dependent sodium appetite and the ingestion of sodium may help maintain plasma volume.     

Plasma volume changes induced by sequential ultrafiltration-hemodialysis and sequential hemodialysis-ultrafiltration

Isolated ultrafiltration (UF) has been shown to preserve plasma volume (PV) by means of a high plasma refilling rate, mediated by a rapid rise in oncotic pressure. This mechanism contributes to the good tolerance of sequential ultrafiltration-hemodialysis (SUH). This study compared PV changes induced by SUH and sequential hemodialysis-ultrafiltration (SHU). Seven dialysis patients underwent two sets of SUH and SHU, in which 2 h of UF (approximately equal to 3L) respectively preceded or followed 2 h of no-weight-change hemodialysis (ISO HD). VEM (volume of extravascular mobilization), VEM/VUF (percent of plasma refilling rate) and delta PV were calculated by mathematical formulas. Results showed: 1) a high VEM/VUF during the UF period, either before or after ISO HD: 80 and 77% respectively; 2) a significant increase in PV during ISO HD after UF, compared to ISO HD before UF: + 229 ml and + 43 ml, P less than 0.05; 3) VEM/VUF significantly higher during SUH than during SHU: 87 and 80%, P less than 0.01. In conclusion, the decrease in PV was lower in SUH than in SHU (11 vs. 19%, P less than 0.001) because the plasma refilling persisted through the ISO HD period.     

Prolonged administration of recombinant human erythropoietin increases submaximal performance more than maximal aerobic capacity

The effects of recombinant human erythropoietin (rHuEpo) treatment on aerobic power (VO₂max) are well documented, but little is known about the effects of rHuEpo on submaximal exercise performance. The present study investigated the effect on performance (ergometer cycling, 20–30 min at 80% of maximal attainable workload), and for this purpose eight subjects received either 5,000 IU rHuEpo or placebo every second day for 14 days, and subsequently a single dose of 5,000 IU/placebo weekly/10 weeks. Exercise performance was evaluated before treatment and after 4 and 11 weeks of treatment. With rHuEpo treatment VO₂max increased (P < 0.05) by 12.6 and 11.6% in week 4 and 11, respectively, and time-to-exhaustion (80% VO₂max) was increased by 54.0 and 54.3% (P < 0.05) after 4 and 11 weeks of treatment, respectively. However, when normalizing the workload to the same relative intensity (only done at time point week 11), TTE was decreased by 26.8% as compared to pre rHuEpo administration. In conclusion, in healthy non-athlete subjects rHuEpo administration prolongs submaximal exercise performance by about 54% independently of the approximately 12% increase in VO₂max.     

Differential aerobic exercise-induced changes in plasma aldosterone between African Americans and Caucasians

Aldosterone influences the kidney's regulation of blood pressure (BP), but aldosterone can contribute to the pathogenesis of hypertension. Blood pressure is reduced with aerobic exercise training (AEX), but the extent to which plasma aldosterone (PA) levels change is unclear. The purpose of this study was to determine whether 6 months of AEX changed PA levels, 24 h sodium (Na(+)) excretion and BP in prehypertensive and hypertensive subjects and whether these changes differed according to ethnicity. The study was performed in the Kinesiology Department at the University of Maryland, College Park, and 35 (22 Caucasian; 13 African American) sedentary prehypertensive and hypertensive subjects completed 6 months of AEX. Blood samples were collected under fasting and supine conditions, and PA was measured by radioimmunoassay. In total population aerobic exercise training increased maximal oxygen consumption (24 +/- 0.8 versus 28 +/- 1 ml kg(-1) min(-1), P < 0.001) and decreased PA levels (97 +/- 11 versus 72 +/- 6 pg ml(-1), P = 0.01), body mass index (28 +/- 0.5 versus 28 +/- 0.5 kg m(-2), P = 0.004) and weight (85 +/- 2 versus 83 +/- 2 kg, P = 0.003). Aerobic exercise training decreased PA levels (from 119 +/- 16 to 81 +/- 7 pg ml(-1), P = 0.02) in the Caucasians but there was no change in BP or Na(+) excretion. African American participants had no significant changes in PA levels, BP and Na(+) excretion. Plasma aldosterone levels were 47% lower at baseline (P = 0.01) and 30% lower after AEX (P = 0.04) in African American participants compared with Caucasians. Baseline (P = 0.08) and final PA levels (P = 0.17) did not differ between the two groups after accounting for baseline and final intra-abdominal fat, respectively. The reduction in PA levels with AEX appeared to be driven by the change in PA levels in Caucasian participants. Fat distribution contributed to the ethnic differences in PA levels.     

罗哌卡因对结肠癌细胞增殖和裸鼠人结肠癌皮下瘤生长的影响

目的:探究罗哌卡因对结肠癌细胞增殖及肿瘤生长的影响。方法:罗哌卡因处理细胞,CCK8 检测细胞活性,确定用药浓度;肿瘤成球实验检测细胞增殖;流式检测细胞凋亡及细胞周期;Western blot 检测细胞增殖、凋亡标记蛋白及细胞周期标记蛋白的表达。复制结肠癌Xenograft 模型,统计肿瘤生长情况及裸鼠存活率,Tunel 法检测细胞凋亡情况。结果:根据CCK8 实验结果确定罗哌卡因给药浓度分别为20、50、100 μg/ ml。罗哌卡因能显著抑制癌细胞集落形成(17.80±0.51,P<0.001) 和增殖标记蛋白Ki67 (0.32±0.68,P<0.01) 、PCNA(0.14±0.24,P<0.01) 的表达,并体现量效关系。罗哌卡因还可明显促进癌细胞凋亡(12.80±1.24,P<0.01) 和凋亡标记蛋白caspase-3(1.76±1.43,P<0.001)、caspase-9 (1.61±1.26,P<0.001) 的表达。同时,罗哌卡因能诱导细胞发生G2 期阻(40.5%,P<0.01) ,促进周期标记蛋白p53 的表达(1.16±0.65,P<0.01) ,抑制Cyclin A 的表达(0.12±0.12,P<0.05) 。此外,罗哌卡因可显著抑制肿瘤生长(1 247.60±1.37,P<0.01) ,提高结肠癌裸鼠的生存率及诱导肿瘤组织细胞凋亡(78.00±1.45,P<0.001) ,且具有量效关系。结论:罗哌卡因能抑制结肠癌细胞增殖和结肠癌皮下瘤的生长。     

氟西汀通过上调海马内溴结构域蛋白4的表达改善慢性束缚应激所致小鼠的抑郁样行为

目的 探讨氟西汀（FLX）对慢性束缚应激（CRS）所致小鼠抑郁样行为及海马内溴结构域蛋白4（BRD4）表达的影响。 方法 24只雄性昆明小鼠随机分为生理盐水对照（NS）组、抑郁模型（CRS）组、氟西汀干预（CRS+FLX）组。慢性束缚应激3周建立小鼠抑郁模型,应激的第8天至第21天 CRS+FLX组于应激前30 min腹腔注射氟西汀（10mg/kg）,NS组及CRS组注射等体积生理盐水。采用糖水偏好实验、喷糖实验、强迫游泳实验、新旧事物识别实验和旷场实验检测各组小鼠行为变化;采用Western blotting及Real-time PCR法检测小鼠海马BRD4蛋白和mRNA的表达情况。 结果 与NS组相比,CRS组小鼠表现出明显的抑郁样行为,包括糖水偏好百分比显著降低（P<0.01）,喷糖实验舔糖时间缩短（P<0.05）,强迫游泳不动时间增加（P<0.01）,新事物辨别指数降低（P<0.0001）,抗抑郁药FLX干预可逆转CRS所诱导的上述抑郁样行为表现（P<0.05）;与NS组相比,CRS组小鼠海马BRD4蛋白及mRNA的表达明显下调（1.;0000 ± 0.04577 比 0.08337 ± 0.01658;1.0000 ± 0.04379 比 0.6672 ± 0.03193,P<0.05）,而FLX可上调抑郁小鼠海马BRD4蛋白及mRNA的表达（0.08337 ± 0.01658 比 0.4983 ± 0.08574;0.6672 ± 0.03193比0.8572 ± 0.03181,P<0.05）。 结论 氟西汀可能通过上调海马BRD4的表达改善小鼠抑郁样行为。     

The influence of small fibre muscle mechanoreceptors on the cardiac vagus in humans

We have previously shown that activation of muscle receptors by passive stretch (PS) increases heart rate (HR) with little change in blood pressure (BP). We proposed that PS selectively inhibits cardiac vagal activity. We attempted to test this by performing PS during experimental alterations in vagal tone. Large decreases in vagal tone were induced using either glycopyrrolate or mild rhythmic exercise. Milder alterations in vagal tone were achieved by altering carotid baroreceptor input: neck pressure (NP) or neck suction (NS). PS of the triceps surae was tested in 14 healthy human volunteers. BP, ECG and respiration were recorded. PS alone caused a significant decrease ( P < 0.05) in R–R interval (962 ± 76 ms at baseline compared to 846 ± 151 ms with PS), and showed a reduction in HR variability, which was not significant. The decrease in R–R interval with PS was significantly less ( P < 0.05, n = 3) following administration of glycopyrrolate (−8.1 ± 4.5 ms) compared to PS alone (−54 ± 11 ms), and also with PS during handgrip (+10 ± 10 ms) compared with PS alone (−74 ± 15 ms) ( P < 0.05, n = 5). Milder reductions in vagal activity (NP) resulted in a small but insignificant further decrease in R–R interval in response to PS (−107 ± 17 ms compared to PS alone −96 ± 13 ms, n = 5). Mild increases in vagal activity (NS) during PS resulted in smaller decreases in R–R interval (−39 ± 5.5 ms) compared to PS alone (−86 ± 17 ms) ( P < 0.05, n = 8). BP was not significantly changed by stretch in any tests. The results indicate that amongst muscle receptors there is a specific group activated by stretch that selectively inhibit cardiac vagal tone to produce tachycardia.     

Influence of serotonin on total intravascular capacity in the anaesthetized dog

The influence of serotonin on intravascular volume in the total capacitance circulation has not previously been examined. Thus, blood was drained from the venae cavae to an extracorporeal reservoir and returned to the right atrium at a constant rate so that total intravascular volume changes could be recorded as the inverse of changes in reservoir volume in 31 anaesthetized dogs. Serotonin (588 +/- 47 micrograms) in the left atrium was associated with an initial decrease in intravascular volume of 39 +/- 12 ml (P less than 0.01) followed by an increase of 129 +/- 31 ml (P less than 0.01) above control at 20 min. Mean arterial pressure increased from a control of 74 +/- 4 mmHg to 99 +/- 7 mmHg (P less than 0.01) initially and then decreased to 64 +/- 5 mmHg (P less than 0.05) at 20 min. Following ganglionic blockade with mecamylamine, serotonin caused only a decrease in intravascular volume, which was 73 +/- 12 ml (P less than 0.01) at 20 min. 5-HT2 and alpha-adrenergic blockade with ketanserin did not attenuate the early decrease in intravascular volume. 5-Carboxamidotryptamine (82 +/- 39 micrograms), a 5-HT1 agonist, was associated with only an increase in intravascular volume, which was 82 +/- 13 ml (P less than 0.01) at 20 min and which was abolished after ganglionic blockade. Thus, serotonin causes a biphasic change in total intravascular volume. The initial decrease in intravascular volume is not mediated by a reflex or by 5-HT1, 5-HT2, or alpha-adrenergic receptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Interrelations between age and plasma renin,aldosterone and cortisol,urinary catecholamines,and the body sodium/volume state in normal man

Summary Interrelations between age and plasma renin, aldosterone and cortisol levels, urinary catecholamines, plasma and blood volumes, exchangeable body sodium and blood pressure were studied in 28 young (19 to 29 years), 16 middle-aged (32 to 58 years) and 15 elderly (60 to 74 years) healthy subjects. Supine and upright plasma renin and supine aldosterone levels decreased while urinary noradrenaline excretion rate increased progressively with aging (r0.34;p<0.05), with significant differences in mean values between young and elderly subjects (p<0.02). There was also an age-related decrease in upright plasma aldosterone concentration, although this was not statistically significant. Furthermore, mean plasma cortisol concentrations increased in response to upright posture in elderly (+50%;p<0.02), but not in young (–10%) or middle-aged (–8%) subjects. Blood pressure correlated with age (r=0.35;p<0.05) or noradrenaline excretion rate (r=0.34) in the entire study population and with blood volume in the elderly (r=0.68), but not in the young or middle-aged study groups. There were no significant age-related differences in the body sodium/volume state, basal plasma cortisol levels or urinary adrenaline excretion rate, and plasma renin or aldosterone levels did not correlate with these parameters or with blood pressure. It is concluded that the influence of age on plasma renin or aldosterone levels, plasma cortisol responsiveness to upright posture, and urinary noradrenaline excretion should be taken into consideration, whenever these factors have to be interpreted in patients with arterial hypertension or other clinical disorders. Furthermore, these data are consistent with the possibility that in normal man increases in supine blood pressure with aging may be related at least partly to concomitant changes in free peripheral noradrenaline.This investigation was supported by the Swiss National Science Foundation     

Pulmonary haemodynamics in obstructive sleep apnoea

SUMMARY  The time course of right ventricular output (RVO) and transmural pulmonary artery pressure (PAP) changes, detected beat-by-beat, were analysed in a sample of obstructive sleep apnoea (OSA) episodes recorded in six patients with OSA syndrome. RVO showed a trend to a decrease during apnoeas, due to a decrease in heart rate, and decreased further in the immediate post-apnoeic period, due to a decrease in right ventricular stroke volume [post-apnoeic RVO = 82.6 ± 9.3 (SD) % of the value in the immediate pre-apnoeic period; P <0.01]. Both systolic and diastolic transmural PAP showed a progressive increase throughout apnoeas (from 23.7 ± 7.3 to 29 ± 6.9 and from 9.1 ± 4.4 to 14.3 ± 3.3 mmHg, respectively, from early to late apnoeic period; P <0.01), and similarly high values in the late apnoeic and in the immediate post-apnoeic period. Therefore, cardiac output and arterial pressure in the pulmonary circulation undergo simultaneous inverse changes in OSA, similar to what was previously shown in the systemic circulation. Although these data cannot define accurately the behaviour of pulmonary vascular resistance, they suggest that pulmonary vascular resistance could also undergo continuous oscillations in OSA, with recurring peaks detectable between apnoea termination and the immediate post-apnoeic period.     

Effects of small changes of blood volume on oxygen delivery and tissue oxygenation

Circulatory effects of small (approximately 10%) changes in blood volume were examined in resting and exercising dogs: controls; group A (-200 ml blood); group B (+200 ml blood); group C (+200 ml 6% dextran). In exercise, cardiac output (Q) increased more in Group A than controls (510.4 ml . kg-1 . min-1 compared to 429.6 ml . kg-1 . min-1; P less than 0.05); oxygen delivery (cardiac output x arterial O2 content) and mixed venous oxygen tension (PVO2) were unchanged from exercising controls. Hypervolemia (group B) did not change Q or O2 delivery compared to controls, but caused a greater reduction in exercise PVO2 (29.3 mmHg compared to 33.1 mmHg in controls; P less than 0.01). Resting PVO2 as raised in group C (50.0 mmHg compared to 46.3 mmHg; P less than 0.05) and exercise PVO2 was reduced less (35.5 mmHg compared to 33.1 mmHg in controls; P less than 0.05). O2 delivery in exercise was higher than in controls (123.4 ml . kg-1 . min-1 compared to 94.3 ml . kg-1 . min-1; P less than 0.001). During exercise, O2 consumption was raised from base line to 34.9 ml . kg-1 . min-1 in controls and raised further to 41.4 ml . kg-1 . min-1 in group A, 44.4 ml . kg-1 . min-1 in group B, and 41.2 ml . kg-1 . min-1 in group C (P less than 0.01). Changes of blood volume that lie within physiological limits thus significantly modify the circulatory response to changed O2 requirements, and also change the metabolic cost of exercise.     

Renal potassium bicarbonate release in humans exposed to an acute volume load

Summary Cells of the renal medulla regulate their volume by transmembrane ion movements when exposed to large changes in osmolality. Since renal cells in culture release KHCO₃ in response to hypotonic stress [11], we investigated the effect of an acute water load on urinary KHCO₃ excretion in 5 healthy individuals. Water diuresis was induced by the ingestion of 1.51 hypoosmolal fluid (22 mosm/kg H₂O) over 15 min. The rate of urinary volume excretion increased from an initial value of 1.4 ml/min to 9.3 ml/min after 75 min. Urinary osmolality dropped from an initial value of 940±32 mosm/kg H₂O to 74±4 mosm/kg H₂O (n = 5). The decrease of osmolality was accompanied by the transient release of potassium and bicarbonate. Peak values of KHCO₃ excretion were observed between 30 and 45 min after the onset of the experiment corresponding to the drop of urinary osmolality. The magnitude of renal potassium release correlated significantly (r=0.93; P < 0.05) with endogenous plasma aldosterone concentrations measured prior to the experiment in the 5 volunteers. We conclude that medullary epithelial cells release KHCO₃ when exposed to hypotonic stress. The volume regulatory response is upregulated by aldosterone.Abbreviations ADH antidiuretic hormone - MDCK Madin-Darby canine kidney     

Plasma endothelin-1 during central hypovolaemia in man.

Endothelin-1 (ET-1) is a potent vasoconstricting peptide with effect on resistance as well as capacitance vessels. We followed ET-1 in arterial plasma together with heart rate (HR), central venous pressure (CVP), mean arterial pressure (MAP), and thoracic electrical impedance (TI) in seven men during central hypovolaemia induced by 50 degrees head-up tilt. During tilting plasma ET-1 increased from 1.1 +/- 0.2 to 1.4 +/- 0.3 pmol l-1 (mean +/- SE) concomitant with an increase in total peripheral resistance (TPR) (from 15 +/- 2 to 25 +/- 3 mmHg min l-1) (P < 0.01), and HR (from 67 +/- 2 to 94 +/- 5 beats min-1) (P < 0.01) while MAP remained unchanged. CVP decreased (from 1.8 +/- 0.9 to -1.6 +/- 1.0 mmHg) (P < 0.01) during tilting and remained unchanged during sustained tilt despite further reduction of central blood volume as recorded by TI. Presyncopal symptoms occurred after 28 +/- 6 min associated with decreases in HR (to 70 +/- 6 beats min-1), MAP (from 90 +/- 3 to 52 +/- 4 mmHg) and TPR (to 11 +/- 2 mmHg min l-1) (P < 0.01). At this time plasma ET-1 reached its highest level of 1.6 +/- 0.3 pmol l-1 (P < 0.01). Data show that head-up tilt is associated with increased plasma concentrations of ET-1 which may play a role in maintaining vascular tone in situations with a reduced central blood volume.