Human cardiovascular reactions to simulated hypovolaemia,modified by the opiate antagonist naloxone

Summary Six healthy males were exposed to 20 mm Hg lower body negative pressure (LBNP) for 8 min followed by 40 mm Hg LBNP for 8 min. Naloxone (0.1 mg·kg^–1) was injected intravenously during a 1 h resting period after which the LBNP protocol was repeated. Systolic, mean, and diastolic arterial blood pressures (SAP, MAP, DAP), and central venous pressure (CVP) were obtained using indwelling catheters. Cardiac output (CO), forearm blood flow (FBF), heart rate (HR), left ventricular ejection time (LVET), and electromechanical systole (EMS) were measured non-invasively. Pulse pressure (PP), stroke volume (SV), total peripheral resistance (TPR), forearm vascular resistance (FVR), systolic ejection rate (SER), pre-ejection period (PEP), PEP/LVET and indices for the systolic time intervals (LVETI, EMSI, PEPI) were calculated. During the second LBNP exposure, only two parameters differed from the pre-injection values: DAP at LBNP=40 mm Hg increased from 60.0±4.8 mm Hg to 64.8±4.1mm Hg (N=4, p<0.02) and LVETI at LBNP=20 mm Hg increased from 384.4±5.2 ms to 396.8±6.2 ms (N=6, p<0.02). In connection with the injection, SAP increased from 128.5±4.2 mm Hg to 134.3±5.4 mm Hg (N=6, p<0.025), PP from 56.5+-2.8 mm Hg to 62.7±3.5 mm Hg (N=6, p<0.01), HR from 54.0±3.1min^–1 to 59.2±4.1 min^–1 (N=6, p<0.01), and LVETI from 407.0±5.6 ms to 413.1±6.0 ms (N=6, p<0.02). This study suggests that endorphins do not have a significant action on the cardiovascular system in the compensated stage of hypovolaemic shock in humans. We found, however, weak evidence that naloxone increases SAP, HR, and LVETI during rest.     

Pulse Pressure Method and the Area Method for the Estimation of Total Arterial Compliance in Dogs: Sensitivity to Wave Reflection Intensity

We estimated total arterial compliance (C) in eight anesthetized mongrel dogs with (i) the area method (AM), (ii) the pulse pressure method (PPM), and (iii) the stroke volume-to-pulse pressure ratio (SV/PP). Average compliance was C__AM=1.11 ± 0.7 ml mm Hg¹ using AM; C_PPM=0.60 ± 0.31 ml mm Hg_-1 using PPM and C_SV/PP=0.87 ± 0.49 ml mm Hg^-1 using SV/PP. Mean aortic pressure was 64 ± 23 mm Hg. The overall agreement between C_AM and C_PPM was relatively poor (C_AM=0.15+1.61 C_PPM; r²=0.48), with a consistent overestimation of the area method with respect to the pulse pressure method. There was a significant correlation (r= -0.78) between the relative difference between PPM and AM, and the modulus of the first harmonic of the wave reflection coefficient || which was low in our dog population (0.37 ± 0.18). SV/PP overestimated PPM, but both methods were highly correlated (C_SV/PP=0.06+1.60 C_PPM; r²=0.97). C_SV/PP and C_AM were similar only for || > 0.4. The effect of isolated changes of || on PPM, AM, and SV/PP was studied using the linear wave separation technique. The area method appeared very sensitive to the wave reflection intensity. For low reflection coefficients, the diastolic wave profile was flattened and compliance was overestimated. PPM and SV/PP were relatively independent of || and remained even applicable for || = 0. We believe that the pulse pressure method is the most consistent method for the estimation of total arterial compliance in hemodynamic conditions characterized by a low wave reflection intensity. © 1999 Biomedical Engineering Society. PAC99: 8719Uv, 8719Hh     

Arterial haemodynamics on ventricular hypertrophy in rats with simulated aortic stiffness

Aortic stiffness (AS) exerts significant impact on the cardiovascular risks. We developed a new model to produce AS. The purposes were to evaluate the haemodynamic consequence and to correlate the haemodynamic parameters with the extent of ventricular hypertrophy (VH). We applied silicon gel for embedding of the abdominal and/or thoracic aorta. After 1–4 weeks of AS, the left ventricular weight (LVW), LVW to body weight (BW) ratio (LVW/BW), and the morphological changes in cardiomyotes were quantified for VH. We determined the aortic pressure (AP), stroke volume, cardiac output, total peripheral resistance (TPR), characteristic impedance (Zc), pulse wave reflection (P_b) and pulse wave velocity (PWV). Aortic embedding (AE) increased LVW, LVW/BW, systolic and pulse pressure (PP), Zc, P_b and PWV accompanied by decreases in diastolic pressure and arterial compliance. The magnitude of these haemodynamic and cardiac changes were in an order of combined, thoracic and abdominal AE. Correlation analysis revealed that the VH was well correlated with pulsatile haemodynamics such as Zc, PP, P_b and PWV, while less with steady components (Mean AP and TPR). Our results indicate that pulsatile haemodynamic parameters are significantly elevated after AS. The alterations in pulsatile haemodynamics are the major causes leading to VH.     

Right ventricular function in patients with chronic obstructive pulmonary disease

Summary Simultaneous right heart catheterization and radionuclide ventriculography were performed in 27 patients with a wide range of chronic obstructive pulmonary disease. Central hemodynamics and radionuclide studies were done at rest and during exercise. In the resting state the right ventricular ejection fraction (RVEF) was in the normal range (43.3±6%). During exercise a significant (p<0.001) decrease of RVEF to 38.8±6.7% occurred. The pumonary artery mean pressures were 19.9±3.8 at rest. During exercise a significant (p<0.001) increase to 41±9.8 mm Hg occurred. There was a linear relationship between pulmonary pressures and RVEF during exercise in patients with pulmonary artery pressures not exceeding 35 mm Hg. In patients with right ventricular end-diastolic wall thickness 6 mm a curvilinear relationship between these parameters could be observed with a flattening of the curve at higher pressures (>35 mm Hg) and lower ejection fractions (<35% RVEF). Radionuclide venticulography cannot substitute for right heart catheterization. Echocardiography is useful for interpretation of right ventricular ejection fractions in advanced chronic obstructive pulmonary disease.Abbreviations CI Cardiac index (l/min/m²) - CO Cardiac output (l/min) - COPD Chronic obstructive pulmonary disease - FEV₁ Forced expiratory volume in the first second (ml) - HR Heart rate (B/min) - PAd Pulmonary artery diastolic pressure (mm Hg) - PAP Pulmonary artery mean pressure (mm Hg) - PAs Pulmonary artery peak pressure (mm Hg) - PVR Pulmonary vascular resistance (dyn·s·cm^–5) - PwP Pulmonary capillary wedge pressure (mm Hg) - RAP Right arterial pressure (mm Hg) - Raw Airway resistance (cm H₂/l/s) - RNV Radionuclide ventriculogram - RV Residual volume (l) - RVEF Right ventricular ejection fraction (%) - RVEDVI Right ventricular enddiastolic volume index (ml/m²) - RVEDVI SVI RVEF (ml/m²) - RVESVI Right ventricular endsystolic index (m²/m²) - SVI Stroke volume index (ml/m²) - TLC Total lung capacity (l) - VC Vital capacity (l)     

Effect of lower-body positive pressure on postural fluid shifts in men

Summary To quantify the effect of 60 mm Hg lower-body positive pressure (LBPP) on orthostatic blood-volume shifts, the mass densities (±0.1 g· l^–1) of antecubital venous blood and plasma were measured in five men (27–42 years) during combined tilt table/antigravity suit inflation and deflation experiments. The densities of erythrocytes, whole-body blood, and of the shifted fluid were computed and the magnitude of fluid and protein shifts were calculated during head-up tilt (60°) with and without application of LBPP. During 30-min head-up tilt with LBPP, blood density (BD) and plasma density (PD) increased by 1.6±0.3 g · l^–1, and by 0.8±0.2 g · l^–1 (±SD) (N=9), respectively. In the subsequent period of tilt without LBPP, BD and PD increased further to +3.6±0.9 g · l^–1, and to +2.0±0.7 g · l^–1 (N=7) compared to supine control. The density increases in both periods were significant (p<0.05). Erythrocyte density remained unaltered with changes in body position and pressure suit inflation/deflation. Calculated shifted-fluid densities (FD) during tilt with LBPP (1006.0±1.1 g · l^–1,N=9), and for subsequent tilt after deflation (1002.8±4.1 g · l^–1,N=7) were different from each other (p<0.03). The plasma volume decreased by 6.0±1.2% in the tilt-LBPP period, and by an additional 6.4±2.7% of the supine control level in the subsequent postdeflation tilt period. The corresponding blood volume changes were 3.7±0.7% (p<0.01), and 3.5±2.1% (p<0.05), respectively. Thus, about half of the postural hemoconcentration occurring during passive head-up tilt was prevented by application of 60 mm Hg LBPP.H. Hinghofer-Szalkay was a European Space Agency fellow on leave from the Physiological Institute, Karl-Franzens-University, A-8010 Graz, Austria.     

The anthropometrical and physiological characteristics of elite water polo players

In order to examine the physical and physiological demands of water polo, we assessed the profile of elite water polo players. Nineteen male professional water polo players (age: 25.5±5.0 years, height: 184.5±4.3 cm body mass: 90.7±6.4 kg) underwent body composition assessment by dual-energy X-ray absorptiometry. We also evaluated peak oxygen consumption O_2peak, lactate threshold (LT), energy cost of swimming (C_s), anaerobic capacity and isokinetic shoulder strength. Body fat (%) was 16.8±4.4, lean mass (LM) 75.1±4.9 kg and bone mineral density (BMD) 1.37±0.07 g·cm^–2 . O_2peak was 57.9±7 ml·kg^–1· min^–1 . LT was identified at 3.9±0.7 mmol·l^–1 at a swimming velocity (v) of 1.33±0.05 m·s^–1 with a heart rate of 154±7 bpm, corresponding to an intensity of 83±9 of O_2peak. The average C_s of swimming at the LT was 1.08±0.04 kJ·m^–1 . C_s at LT was correlated to body mass index (BMI) (r=0.22, P=0.04) and to swimming performance at 400 m (r=0.86, P=0.01) and 4×50 m (r=0.84, P<0.01). Internal rotator muscles were stronger compared to the external rotators by a 2:1 ratio. This study provides a quantitative representation of both physical and physiological demands of water polo and proposes a comprehensive battery of tests that can be used for assessing the status of a team.     

Correlation between luminal hydrostatic pressure and proximal tubular fluid reabsorption in the rat kidney

Summary Split-drop experiments were performed to evaluate the effect of changes in luminal hydrostatic pressure on net fluid reabsorption in proximal convoluted tubules of the rat kidney. While hydrostatic pressure in control droplets averaged 28.9±1.03 mm Hg, it increased to a mean of 65.2±3.3 mm Hg during pressure elevation and fell to 10.8±1.04 mm Hg during pressure reduction. In paired measurements in identical tubules net fluid absorption changed from a control value of 2.96±0.14 nl/min·mm to 3.88±0.14 nl/min·mm when luminal pressure was elevated. During pressure reduction net fluid absorption fell from a control of 2.98±0.09 nl/min·mm to 2.26±0.13 nl/min·mm (P<0.001). This dependency of fluid absorption upon hydrostatic pressure was not greatly affected by the finding that microphotography overestimated the true intradroplet volume by 31% during control and by 30.2% and 50% during elevated and reduced pressure respectively. From the relation between the changes of net absorption and luminal hydrostatic pressure an apparent hydraulic conductance of 0.04 nl/min·mm Hg was estimated.     

Untersuchungen zum Verhalten des Pulmonalkreislaufs bei arterieller Hypertonie

Zusammenfassung Bei 18 Patienten mit arterieller Hypertonie ohne Herzinsuffizienzzeichen und 13 Kreislaufgesunden wurden die Mitteldrucke in der A. femoralis, im rechten Vorhof, der Pulmonalarterie und der Pulmonalcapillare blutig gemessen. Das Herzzeitvolumen wurde mit der Farbstoff-und/oder Kälteverdünnungsmethode bestimmt und die Gefäßwiderstände im großen und kleinen Kreislauf errechnet.Der Pulmonalarteriendruck bei Patienten mit arterieller Hypertonie (17,0±5,4 mm Hg) war gegenüber den Normalpersonen (11,8±3,2 mm Hg) signifikant erhöht. Die Zunahme des mittleren Pulmonalarteriendruckes bei Hochdruckpatienten ist überwiegend auf eine Erhöhung des mittleren pulmonalvenösen Drucks zurückzuführen. Der sog. Pulmonalcapillardruck betrug bei Normotonikern 5,8±1,8 mm Hg gegenüber 9,2±3,8 mm Hg bei Hypertonikern. Pulmonalarteriendruck und Pulmonalcapillardruck sind gut korreliert (r=0,91). Wahrscheinlich ist bei Patienten mit arterieller Hypertonie auch der pulmonale Gefäßwiderstand erhöht. Bei Vergleich der Gefäßwiderstandsindices ist die Differenz zwischen Normalpersonen und Hypertonikern signifikant.Die beobachteten Veränderungen bei Hochdruckpatienten spielen sich im oberen Normbereich ab, sind also insgesamt gering.

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Pulmonary circulation in arterial hypertension

Summary In 18 hypertensive and 13 normotensive patients pulmonary arterial pressure, pulmonary arterial wedge pressure and right atrial pressure were recorded. Cardiac output was measured by means of the dye-dilution technique and/or the thermodilution technique and pulmonary vascular resistance was calculated.Pressure in the pulmonary artery was significantly elevated in patients with hypertension (17.0±5.5 mm Hg) as compared to healthy subjects (11.8±3.2 mm Hg). The increase of pulmonary arterial pressure is mainly caused by an increase of pulmonary venous pressure (pulmonary wedge pressure 9.2±3.8 mm Hg in hypertensive, 5.8±1.8 mm Hg in normotensive patients). Pulmonary arterial and pulmonary wedge pressure show good correlation (r=0.91). In addition pulmonary vascular resistance is elevated in patients with arterial hypertension.

     

Effects of chronic exposure to cold or hypoxia on ventricular weights and ventricular myoglobin concentrations in guinea pigs during growth

Male guinea pigs were exposed continuously to 5°C for 2–18 weeks (BW=239–1074 g) or to an ambientPO₂=80 mm Hg for 2–14 weeks (BW=244–965g). Control guinea pigs were kept at 22°C and an average ambientPO₂ of 133 mm Hg.The right and the left ventricular free walls were separated from the septum and weighed (RVW and LVW). Myoglobin concentrations [Mb] of the right and the left ventricles were measured. In all animals, total heart weights (THW), RVW and LVW were linearly related to BW. In the control animals, ventricular [Mb] increased with BW for 2–3 weeks after birth but remained unchanged thereafter. In the 5°C animals, after 4 weeks of exposure, [Mb] in the right and the left ventricles was significantly higher than that of the controls. THW also was significantly higher in the 5°C animals. Furthermore, this cold-induced cardiac hypertrophy was due to both right and left ventricular hypertrophy. In hypoxia-acclimated animals, after 14 weeks of exposure toPO₂=80 mm Hg, the [Mb] of the RV was significantly higher than that of the controls, whereas there was no significant difference between the [Mb] of the LV of the control and hypoxic animals. THW was significantly higher in the hypoxic guinea pigs than in the controls or the 5°C animals. The hypoxia-induced cardiac hypertrophy was due to a marked right ventricular hypertrophy while LVW was significantly lower in the hypoxic animals than in the controls     

Effect of exercise on systemic blood pressure and heart rate in horses

Summary Carotid loops were prepared in 3 horses several months prior to the experiments. Systemic blood pressure was recorded at rest and during exercise by insertion of a plastic cannula into the carotid artery. The pressure transducer was fixed at the neck of the animal. The blood pressure signal was transmitted by telemetry.When the horses were standing under the rider, the following results were obtained: heart rate 38±5 beats · min^–1, systolic pressure 115±15, disstolic pressure 83±10, mean pressure 97±12, and pulse pressure 32±9 mm Hg. During steady gallop at a mean speed of 548±90 m · min^–1, heart rate rose to 184±23 beats · min^–1, systolic pressure to 205±23, diastolic pressure to 116±12, mean pressure to 160±20 and pulse pressure to 89±19 mm Hg. These values remained stable throughout the exercise period of 5–6 min.When the horses were exercised at stepwise increasing speed from walk through trot to gallop, both the mean arterial blood pressure and the pulse pressure rose in proportion to the running speed.     

Baroreflex sympathetic activation increases threshold pressure for the pressure-dependent renin release in conscious dogs

Stimulus-response curves relating renal-venous-arterial plasma renin activity difference (P.R.A.-difference) to mean renal artery pressure (R.A.P.) were studied in seven chronically instrumented conscious foxhounds with a daily sodium intake of 6.1 mmol/kg. R.A.P. was reduced in steps and maintained constant for 5 min using an inflatable renal artery cuff and a pressure control system.The stimulus-response curve obtained during control conditions (C) or during common carotid artery occlusion (C.C.O.) could be approximated by two linear sections: a rather flat section or plateau-level of P.R.A.-difference at normal blood pressure or above, and a very steep section between a distinct threshold pressure and 65–70 mm Hg. While the parameters of the curves varied from dog to dog, the curves kept their inique shape in the individual dog for at least 1 week. C.C.O. had no effect on the plateau-level of the P.R.A.-difference (C:0.98±0.14,C.C.O.:0.99±0.14 ng Al·ml^–1·h^–1) and on the slope of the curve below threshold pressure (C:–0.379±0.041,C.C.O: –0.416±0.082 ng Al·ml^–1·h^–1·mm Hg^–1) but shifted the stimulus-response curve to the right and increased threshold pressure (C:92.7±2.8,C.C.O.:109.7±4.1 mm Hg;P<0.05).Renal blood flow, which was measured simultaneously in three of the dogs, showed good autoregulation down to 70 mm Hg under resting conditions and was not affected by C.C.O. except for a 30% reduction of renal blood flow at the lowest pressure step (70 mm Hg).-Adrenergic blockade in 4 of the dogs reduced the plateau-level of the P.R.A.-difference from 0.86±0.19 to 0.36±0.05 ng AI·ml^–1·h^–1 (P<0.05) but had no effect on the increase of threshold pressure elicited by C.C.O.It is concluded that the stimulus-response curve for the pressure-dependent renin release has a remarkable long-term stability in the individual dog. The curve is shifted to the right by a moderate carotid baroreflex increase of renal sympathetic nerve discharge which leaves total renal blood flow largely unchanged. It is suggested that the increase in threshold pressure is independent of -adrenergic effects.This study was supported by the German Research Foundation within the SFB 90, HeidelbergA priliminary part of this investigation has been presented to the meeting of the German Physiological Society, Dortmund, March 1984 [Pflügers Arch (1984) suppl 400:R11,41]     

The influence of a respiratory acidosis on the exercise blood lactate response

Summary The purpose of the present study was to examine the influence of a respiratory acidosis on the blood lactate (La) threshold and specific blood La concentrations measured during a progressive incremental exercise test. Seven males performed three step-incremental exercise tests (20 W · min^–1) breathing the following gas mixtures; 21% O₂ balance-nitrogen, and 21% O₂, 4% CO₂ balance-nitrogen or balance-helium. The log-log transformation of La oxygen consumption (VO₂) relationship and a 1 mmol ·1^–1 increase above resting values were used to determine a La threshold. Also, theVO₂ corresponding to a La value of 2 (La2) and 4 (La4) mmol · 1^–1 was determined. Breathing the hypercapnic gas mixtures significantly increased the resting partial pressure of carbon dioxide (PCO₂) from 5.6 kPa (42 mm Hg) to 6.1 kPa (46 mm Hg) and decreased pH from 7.395 to 7.366. During the incremental exercise test,PCO₂ increased significantly to 7.2 kPa (54 mm Hg) and 6.8 kPa (51 mm Hg) for the hypercapnic gas mixtures with nitrogen and helium, respectively, and pH decreased to 7.194 and 7.208. In contrast, bloodPCO₂ decreased to 4.9 kPa (37 mm Hg) at the end of the normocapnic exercise test and pH decreased to 7.291. A blood La threshold determined from a log-log transformation [1.20 (0.28) 1·min^–1] or as an increase of 1 mmol·1^–1[1.84 (0.46) 1·min^–1] was unaffected by the acid-base alterations. Similarly, theVO₂ corresponding to La2 and La4 was not affected by breathing the hypercapnic gas mixtures [2.12 (0.46) 1·min^–1 and 2.81 (0.52) 1·min^–1, respectively]. Blood La values were reduced significantly at maximal exercise while breathing the hypercapnic gas mixtures (5.72±1.34 mmol ·1^–1) compared with the normocapnic test (6.96±1.14 mmol·1^–1). It is concluded that respiratory-induced acid-base manipulations due to the inspiration of 4% CO₂ have a negligible influence on the blood La response during a progressive exercise test at low and moderate power outputs. Lower blood La values are observed at maximal exercise with an induced respiratory acidosis but this negative influence is less than what has been reported for an induced metabolic acidosis.     

Patients with adult respiratory distress syndrome (ARDS) demonstrate in vivo neutrophil activation associated with diminished binding of neutrophil-specific monoclonal antibody 31D8

Neutrophils (PMNs) from patients with adult respiratory distress syndrome (ARDS) were assessed for light scattering, membrane potential, and phagocytic responses using fluorescent probes and flow cytometry to evaluate individual cells. Qualitative and quantitative oxidant responses were measured by nitroblue tetrazolium (NBT) and cytochromec reduction assays, respectively. The results were correlated with the proportion of cells binding the PMN subset-specific monoclonal antibody 31D8. Despite an increased forward scatter signal (4.3±1.6 vs. 1.3±1.1 ARDS vs. control,P=0.041) and spontaneous NBT test (12.6±4.7% vs. 2.5 ±0.8% positive, ARDS vs. control,P=0.033) indicating in vivo priming of ARDS PMNs, there were no significant differences between ARDS and control PMNs in assays of stimulated membrane potential, NBT, and O·₂ ^– production or phagocytosis. However, positive correlations between the degree of prestimulus forward light scatter and subsequent O·₂ ^– production to FMLP (r=0.673,P=0.006) and between the percentage of bands and the O·₂ ^– response to PMA (r=0.660,P =0.003), suggest that the great variability of the ARDS PMN functional responses may relate to varying degrees of in vivo cell priming and/or deactivation. ARDS PMNs demonstrated a significantly lower percentage of 31D8 positive cells (73.4 ±7.5% vs. 94.5±1.6%,P=0.012) and a lower level of 31D8 staining when compared to normals (60.1±10.4% of control level,P=0.001). The lower 31D8 expression did not directly correlate with any functional parameter tested or with the proportion of immature cells. However, patients receiving an intravenous PGE₂1-infusion demonstrated a significant increase in 31D8 staining relative to controls and inhibition of PMA-stimulated O·₂ ^– production. The data suggest that the function of PMNs from ARDS patients varies widely and reflects great in vivo variation in cell priming. While the mechanism responsible for the lowered expression of the 31D8 antigen and its apparent modulation by PGE₁ is unknown, 31D8 may be an indirect marker for in vivo stress factors that regulate the preferential release of a structurally distinct PMN subset from the bone marrow.This work was supported in part by NIH grant P30-DK35747, a University of California, Davis, Dean's Research Grant, and The Upjohn Company.     

Mesocaval and distal splenorenal shunts: Effect on hepatic function,hepatic hemodynamics,and portal systemic encephalopathy

Summary The effect of the mesocaval interposition shunt (n=12) and the distal splenorenal shunt (n=9) on the wedged hepatic venous pressure, the estimated hepatic blood flow, quantitative hepatic function, and the rate of portal systemic encephalopathy was evaluated in 21 patients who had bled from esophageal varices. After mesocaval shunt the wedged hepatic venous pressure was significantly reduced by 42% (from 26±3 mm Hg to 15±5 mm Hg,P<0.001) compared to 16% only (from 25±3 mm Hg to 21±2 mm Hg,P<0.005) after distal splenorenal shunt. The estimated hepatic blood flow also decreased significantly after mesocaval shunt by 61% (from 1.45±0.46 l/min to 0.56±0.25 l/min,P<0.001) compared to 29% (from 1.29±0.32 l/min to 0.91±0.39 l/min,P<0.05) after distal splenorenal shunt. Despite significantly different influences of both types of shunt operations on wedged hepatic venous pressure and estimated hepatic blood flow (P<0.001), postoperative changes of hepatic function were comparable in both groups of patients. The galactose elimination capacity, the initial plasma disappearance rate of Bromsulphalein, and the plasma ratio of valine, leucine, and isoleucine to phenylalanine and tyrosine were reduced by 13%, 26%, and 29%, respectively, after mesocaval shunt, compared to 12%, 25%, and 17% after distal splenorenal shunt. Only two patients of the mesocaval shunt group with the largest decrease in estimated hepatic blood flow developed portal systemic encephalopathy postoperatively, and the distal splenorenal shunt patients with their minor hemodynamic sequelae remained free of portal systemic encephalopathy.Abbreviations AP Serum alkaline phosphatase - BSP Bromsulphalein - BSP-k_i Initial plasma disappearance rate constant of BSP - BSP-45 min Plasma retention of BSP 45 min after i.v. injection - C_a Concentration of ICG in arterial blood - C_hv Concentration of ICG in hepatic venous blood - ChE Serum cholinesterase - DSRS Distal splenorenal shunt - EHBF Estimated hepatic blood flow - E-ICG Hepatic extraction of ICG - FHVP Free hepatic venous pressure - GEC Galactose elimination capacity - GPT Serum glutamic pyruvic transaminase - HCT Hematocrit - ICG Indocyanine green - MCS Mesocaval shunt - MRUS Maximal rate of urea synthesis - NCT Number-connection test - PHG Portohepatic gradient - PSE Portal systemic encephalopathy - PT Prothrombin time - PVP Portal venous pressure - R Removal of ICG - V + L + I/P + T Molar ratio of valine + leucine + isoleucine/phenylalanine + tyrosine - WHVP Wedged hepatic venous pressure     

In vivo heat shock preconditioning mitigates calcium overload during ischaemia/reperfusion in the isolated, perfused rat heart

Heat shock (HS) pretreatment of the heart is effective in mitigating the deleterious effects of ischaemia/reperfusion. The main objective of this study was to determine whether the beneficial effect of HS is associated with the preservation of intracellular Ca²⁺ handling in the ischaemic/reperfused, isolated rat heart. Twenty-four hours after raising body core temperature to 42 °C for 15 min, rat hearts were perfused according to Langendorff and subjected to 30 min ischaemia followed by 20 min reperfusion. Cyclic changes of cytoplasmic calcium ion [Ca²⁺_i] levels were measured by surface fluorometry using Indo-1 AM. Reperfused HS hearts showed improved recovery of contractile function compared with control hearts: end-diastolic pressure: 45±11 vs. 64±22 mm Hg; developed pressure: 72±12 vs. 41±20 mm Hg; maximum rate of pressure increase (+dP/dt_max): 1,513±305 vs. 938±500 mm Hg/s; maximum rate of pressure decrease (–dP/dt_max): –1,354±304 vs. –806±403 mm Hg/s. HS hearts displayed a significantly lower end-diastolic cytosolic [Ca²⁺] ([Ca²⁺]_i) after reinstallation of flow. The dynamic parameters of the Ca²⁺_i transients, i.e. the maximum rate of increase/decrease (±dCa²⁺_i/dt_max) and amplitude, did not differ between reperfused control and HS hearts. The novel finding of this study is that improved performance of the HS-preconditioned heart after an ischaemic insult is associated with a reduced end-diastolic Ca²⁺_i load, and most likely, preserved Ca²⁺ sensitivity of the myocardial contractile machinery.     

Effects of endotoxin infusion on mean systemic filling pressure and flow resistance to venous return

Mean systemic filling pressure (P _sf) is an indicator of the filling state of the systemic circulation. Cardiac output (Q) is related linearly to the difference betweenP _sf and central venous pressure (P _cv), according to:Q = (P _sf –P _cv)/R _sf, whereR _sf is the flow resistance downstream from the sites where blood pressure is equal toP _sf In 16 anaesthetized pigs we evaluatedP _sf,R _sf andQ during baseline conditions, continuous endotoxin infusion and after subsequent fluid loading.P _sf andR _sf were determined from simultaneous measurements ofQ andP _cv at seven levels of lung inflation. The following results were obtained.P _sf was 8.1 ±1.8 mm Hg (mean ± SD) during baseline conditions, increased after endotoxin infusion to 9.9 ± 3.2 mm Hg (P = 0.04) and remained the same after infusion of 18 ml · kg^–1 of Ringer's lactate.R _sf increased from 0.34 ± 0.07 to 0.80 ± 0.34 mm Hg · ml^–1 · s by endotoxin and decreased after fluid infusion to 0.58 ± 0.14.Q changed inversely proportional toR _sf (P = 0.001).R _sf changes were highly correlated with the changes in total systemic flow resistance (R _S) (P < 0.001). Endotoxin caused haemoconcentration and a decrease in plasma volume. The stability ofP _sf during endotoxin infusion and after volume loading indicate that the stressed volume was well maintained and changes in blood volume are compensated by changes in nonstressed volume. The increase inR _sf can be attributed to arteriolar vasoconstriction, venous vasoconstriction and haemoconcentration.     

Evidence for a subgroup of essential hypertensives with non-suppressible excretion of aldosterone during sodium loading

Summary In patients with grade I and II essential hypertension studied during sodium loading (Na⁺ excretion above 175 meq·d^–1) we found a bimodal behaviour of aldosterone excretion and could distinguish two groups of patients: In the major part of essential hypertensives sodium loading led to a suppression of aldosterone excretion below 6 µg·d^–1, which is the highest control value during sodium loading, with an average of 2.7±1.4 (SD) µg·d^–1. Aldosterone excretion in a second group of patients was not suppressible below 6 µg·d^–1 despite forced sodium loading; it resulted in an average value of 10.0±3.0 (SD) µg·d^–1. During sodium deprivation or free sodium intake, aldosterone excretion in the first group of patients followed exactly the behaviour of normotensive controls, while in the second group of essential hypertensives the correlation of aldosterone excretion and log. Na excretion or log. Na⁺/K⁺ ratio in 24 h urine (r=–0.59) was far below the control value ofr=–0.87. Serum potassium concentration during sodium loading was significantly (p<0.001) lower (3.81±0.44 meq·l^–1) in the essential hypertensives with non-suppressible aldosterone excretion compared to those with suppressible aldosterone excretion (4.26±0.37 meq·l^–1). The blood pressure response to treatment with 200 mg spironolactone·d^–1 was better (p<0.05) in patients with non-suppressible aldosterone excretion compared to the essential hypertensives with normal aldosterone regulation. The plasma renin activity of both groups of patients was not significantly different, however, a tendency prevailed towards lower PRA-values in the patient group with non-suppressible aldosterone excretion during sodium loading.With the technical help of Mrs. R. Schendschilorz and Mrs. G. Suckau     

Effects of diadenosine polyphosphates,ATP and angiotensin II on cytosolic Ca2+ activity and contraction of rat mesangial cells

Diadenosine polyphosphates (Ap _n A) are known to influence cellular Ca²⁺ activity ([Ca²⁺]_i) in several cells. Their vasoactive potency has been described in various systems including the kidney. We examined the effects of diadenosine polyphosphates, adenosine 5-triphosphate (ATP) and angiotensin II (Ang II) on cytosolic Ca²⁺ activity of mesangial cells (MC) in culture obtained from normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. [Ca²⁺]_i was measured as a fluorescence ratio F ₃₄₀/F ₃₈₀ with the fura-2 technique using three excitation wavelengths (340 nm, 360 nm and 380 nm) and a photon counting tube. Resting [Ca²⁺]_i was not significantly different in MC from WKY and SHR rats and was measured as 132±9 nmol/l (n=65) and 114±12 nmol/l (n=36), respectively. Diadenosine polyphosphates (Ap₃A–Ap₆A) increased [Ca²⁺]_i transiently with an initial peak and a secondary plateau phase comparable to the effects of ATP or Ang II. Increases in [Ca²⁺]_i induced by all these agonists were not significantly different between MC of WKY and SHR rats. ATP, Ap₃A, Ap₄A, Ap₅A, Ap₆A (each 5 mol/l) increased the fura-2 fluorescence ratio initially by 0.66±0.09 (n=33), 0.52±0.08 (n=18), 0.25±0.05 (n=16), 0.09±0.06 (n=7), 0.09±0.04 (n=11), respectively. A half-maximal initial increase in the fura-2 fluorescence ratio was reached at 22 nmol/l, 0.9 mol/l, 2.0 mol/l and 4.0 mol/l with Ang II, Ap₃A, ATP and Ap₄A, respectively. Ap₄A (100 mol/l, n=18) led to a reversible contraction of MC. Diadenosine polyphosphates increase [Ca²⁺]_i in rat MC, in a similar manner to ATP or Ang II and lead to a contraction of MC, suggesting that these nucleotides are also involved in the control of glomerular haemodynamics.     

Right atrial pressure and forearm blood flow during prolonged exercise in a hot environment

Right atrial pressure (RAP) at rest is known to be reduced by an increase in skin blood flow (SkBF) in a hot environment. However, there is no clear evidence that this is so during exercise. To clarify the effect of the increase in SkBF on RAP during exercise, we measured forearm blood flow (FBF) (as an index of SkBF) and RAP continuously using a Swan-Ganz catheter in five male volunteers exercising on a cycle ergometer at 60% of peak aerobic power for 50 min in a hot environment (30°C, relative humidity 20%). Cardiac output increased from 5.5±0.21/min at rest to 17.9±1.21/min (mean±SE, P<0.01) in the first 10 min of exercise and then remained steady until the end of exercise. FBF did not change significantly during the first 5 min, but then increased from 2.7±0.5 ml/100 ml per min at rest to 10.8±1.7 ml/100 ml per min (P<0.001) by 25 min as pulmonary arterial blood temperature (T _b) rose from 37.0±0.1°C to 38.1±0.1°C (P<0.001). FBF then reached a plateau, despite a continuing increase in T _b. RAP increased significantly from 4.3±0.8 to 7.6±1.2 mm Hg (P<0.001) during the first 5 min of exercise and then gradually declined to 6.1±1.0 mm Hg by 25 min (P<0.001 vs. 5 min) and further to 5.7±1.0 mm Hg by 50 min, a value not significantly higher than at rest. This reduction in RAP during exercise was significantly correlated with the increase in FBF (r=–0.97, P<0.001) with a regression equation of RAP=–0.25×FBF+8.8. These results suggest that the decrease in RAP after 5 min exercise was caused by an increase in SkBF during exercise in a hot environment.Part of this work has been published in abstract form [FASEB J 5A1400 (1991)]     

Initial cardiovascular response on change of posture from squatting to standing

Summary The immediate cardiovascular responses on active change from the squatting (control) to the standing position differ from those obtained in the lying-to-standing manoeuvre. Without exception, the first beat after changing from squatting to standing showed a decrease in systolic, diastolic and mean pressure by 2.0±1.1 kPa (14.6±8.3 mm Hg), 1.4±1.7 kPa (10.6±12.6 mm Hg) and 1.9±1.0 kPa (13.9±7.3 mm Hg), respectively. During the 4^th or 5^th pulse after standing the pulse pressure was significantly higher than when lying (P<0.01). Mean pressure reached a minimum of 7.7±1.9 kPa (57.8±14.4 mm Hg) after 7.1±1.1s. Thereafter the blood pressure increased to a new level within about 15 s. 11 of 16 subjects demonstrated a biphasic heart rate (HR) response. The maximum HR was reached after 11.0±2.4 s of standing. In all experiments, the peaks in HR were distinctly delayed after the blood pressure clips. We conclude that an arterial baroreflex could be implicated in the immediate HR increase after a squatting-tostanding manoeuvre. The subsequent time course of the initial HR response, however, might be induced by other mechanisms.