A two-compartment model of systemic circulation: Influence of transmural pressure

To study the effect of changes in transmural pressure upon parameters of a two-compartment model of the systemic circulation, a right-heart bypass preparation in 7 dogs separated the venous return into splanchnic and non-splanchnic (termed peripheral, ) flows. Flows from these two channels drained by gravity into an external reservoir. Reservoir blood was returned by a pump to the pulmonary artery. Venous resistances (R_vs and R_vp), arterial resistances (R_as and R_ap), compliances (C_s and C_p) and upstream venous pressures (P_s and P_p) for the splanchnic and peripheral channels were calculated from the steady-state and transient volume shifts which occurred following rapid drops in venous pressure. These parameters were determined at cardiac outputs of 48, 64, 80, 96, and 112 ml·kg⁻¹·min⁻¹. Linear regressions were obtained for venous resistances and compliances against the upstream venous pressure for the associated channel and also for the arterial resistances, against mean arterial pressure (P_a). Over the range of upstream venous pressures and arterial pressure produced by the cardiac output variations, statistically significant dependencies were found for R_vs and C_s against P_s, C_p against P_p, and R_as against P_a The peripheral compartment resistances, R_vp and R_ap, did not display significant dependencies on transmural pressure. A computer simulation of the effects of cardiac output variations induced by volume loading substantiates the conclusions that the observed curvature of pressure—flow relationships is due to increasing splanchnic venous resistance with upstream splanchnic pressure while the observed linearity of volume—flow relationships is due to the offsetting effects of increasing venous resistances and decreasing compliances with increasing upstream venous pressure. Supported in part by NHLBI Grant HL20371.     

Interaction of heart and arterial system

We have studied the interrelation of left ventricle and arterial system in the anesthetized open-thorax cat. The ventricle was characterized by its pump function graph, relating mean ventricular pressure ( ) and mean aortic flow ( ). The pump function graph was determined by means of an artificial periphery and on a beat-to-beat basis. The periphery was characterized by relating mean aortic pressure ( ) and mean flow. Mean aortic and mean left ventricular pressure could be related over a wide range of values by a proportionality factor . In a series of five separate experiments a value of a=1.72±0.14 (mean±SD) was found. This simplified relation allows direct comparison of apparent source resistance (i.e., slope of pump function graph), (R_s), and peripheral resistance (R_p). It was also found experimentally that total external power ( ) could be calculated from mean aortic pressure and mean flow as well as from mean left ventricular pressure and mean flow (thus from the pump function graph) by . The value of c=1.16±0.12 (mean±SD, n=4). Maximum external power was predicted for . In six different cats R_p/R_s ratio in the working point (i.e., mean left ventricular pressure and mean flow when the normal periphery loaded the heart) was found to be R_p/R_s=2.63±0.92. This value could not be shown to differ from that in the point where maximal external power was found, i.e., R_p/R_s=1.81±0.08 (n=6).     

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.     

Effect of alteration of peripheral blood flow on the central circulation in man during supine cycling in different ambient temperatures

Summary Whether the alteration of peripheral circulation caused by changing ambient temperature (T_a) affects central circulatory changes in man during supine cycling was investigated in four well-trained men, who exercised at two levels (117.7 or 176.6 W). Exercise metabolic rate (VO₂) in cold (0 C or 10 C) was the same as it was at 20 C, whereas the cardiac output (CO; CO₂ rebreathing technique) and heart rate were significantly lower (e.g., 176.6 W at 0 C, both p<0.01). In heat (30 C or 40 C), the VO₂ reduced with falling CO and mean arterial blood pressure from those at 20 C (e.g., 176.6 W at 40 C, all cases p<0.01), whereas the peak post-exercise calf blood flow (CBF_p) increased (p<0.01). The VO₂ and stroke volume (SV) were inversely proportional to the ratio of CBF_p to CO/kg body weight (CBF_p/CO) (r>–0.78, p<0.001). Total peripheral resistance (TPR) was related to arteriovenous oxygen difference (A-VO₂ difference) (r>0.78, p<0.001). The TPR and A-VO₂ difference decreased as T_a rose, while CBF_p/CO was almost the same. As CBF_p/CO had exceeded 50 and further progressed, however, the two parameters elevated until the same level as that at 0 C. The present results suggest that during moderately prolonged (16–60 min) supine cycling in different T_a's the central circulatory changes are mainly affected by the altered peripheral blood flow in competing between skin and muscle for blood flow.     

Forearm plethysmography in the assessment of vascular tone and resistance vasculature design: new methodological insights

Aim: High peripheral resistance and structural alteration in resistance arteries are central phenomena in essential hypertension and have been widely examined by forearm venous occlusion plethysmography; at rest for studying vascular tone, and during reactive hyperaemia for studying vascular structure. This work concerns the influence of venous pressure on hyperaemic vascular resistance (R_min), the reproducibility of hyperaemic and resting vascular resistances (R_rest) and the relation between forearm and total peripheral vascular resistance (TPR). Methods: In four healthy subjects, intravenous and intra‐arterial blood pressures were measured simultaneously with plethysmographic recordings of hyperaemic and resting forearm blood flows. Reproducibility was examined in 15 young and 14 middle‐aged healthy subjects and in 21 untreated hypertensive patients. Results: R _min remained low in the first recorded cardiac cycle, but rose in the second, even though corrected for the venous pressure rise, suggesting vascular tone recovery along with venous congestion. Between‐day reproducibility of R_min was high in middle‐aged normotensive (8.7%) and hypertensive subjects (10.6%), but R_min fell significantly between successive days in the young subjects. R_rest correlated with TPR, but required up to 40 min to reach steady state and showed high day‐to‐day variation in young (21.8%) and hypertensive subjects (16.2%). Conclusions: During hyperaemia, vascular resistance should be measured in the first cardiac cycle following venous occlusion to minimize influences of venous pressure rise and possible tone recovery. R_rest seems to reflect TPR. About 20 subjects may be needed to detect 15% changes between days in R_rest, fewer when concerning R_min and TPR.     

The pattern of cardiovascular alterations induced by infusion of platelet-activating factor in rabbit is modified by pretreatment with H1-H2 receptor antagonists but not by cyclooxygenase inhibition

The intravenous infusion of platelet activating factor (PAF) (0.8 g/kg b.w.) induced ECG and hemodynamic alterations characterized by the following sequential three phases. Phase I (15 sec) consisted of a transient bradycardia with reduction in left ventricular pressure (LVPs), mean arterial pressure (MAP) and cardiac output (CO). Phase II developed within 30 sec and consisted of a rise in cardiac frequency, increase in LVPs, MAP and total peripheral resistances (TPR), which were associated with a decrease in CO. Finally, phase III, that occurred about 90 sec after PAF infusion, was characterized by marked ECG changes (ST segment depression and conduction arrhythmias), a decrease in LVPs and MAP, as well as a rise in TPR and in right atrial pressure (RAP). All these alterations were reversible within 30–60 min. Pretreatment with promethazine and cimetidine, as H₁ and H₂ histamine receptor antagonists, markedly prevented the development of phase II, namely the rise in cardiac frequency, LVPs, MAP and TPR, but did not significantly modify phase I and III. In contrast, pretreatment with indomethacin, an inhibitor of cyclooxygenase, moderatively attenuated, but did not abolish, the three phases of cardiovascular changes induced by PAF infusion.     

Effects of atrial natriuretic peptide on systemic and renal hemodynamics and renal excretory function in patients with chronic renal failure

Summary We examined the effects of 60 min-hANP infusion (24 ng/min/kg) on glomerular filtration rate (GFR), renal blood flow (RBF), cardiac index (CI) and blood pressure (BP) in 8 patients with chronic renal failure (CRF) with GFR ranging from 18 to 80 ml/min/1.73 m² and in 8 control (C) subjects with normal renal function. Basal plasma levels of ANP and cGMP were elevated in CRF (ANP: 60.6±9.1 vs 13.6±1.9 pmol/l,p<0.05; cGMP: 14.3±2.9 vs 6.6±1.1 pmol/ml,p<0.05). During ANP infusion, peak levels of cGMP were higher in CRF than in C (27.5±3.2 vs. 17.3±1.3 pmol/ml,p<0.05). During ANP infusion, GFR increased in CRF by 70.7±4.2% from 34.5±6.8 to 57.4±9.9 ml/min/1.73m² (p<0.001) as compared to 16.2±1.4% in C (p<0.001 vs CRF). RBF increased in CRF by 43.6±6.4% and in C by 3.1±1.2% (p<0.01). Basal urinary sodium excretion (U_NaV) was slightly lower in CRF than in C but rose to the same level in both groups during ANP infusion. In CRF, as opposed to C, U_NaV remained elevated above baseline after the end of the infusion. The effect of ANP on fractional sodium excretion (FE_Na), however, was more pronounced in C. Basal FE_Na was higher in CRF (12.8±2.5% vs 2.4±1.5% in C,p<0.001), FE_Na remained elevated at 180% over baseline in C sixty minutes after cessation of ANP infusion, while it had returned to baseline in CRF. During ANP infusion, CI increased in CRF after 30 min from 2.91±0.08 to 3.12±0.091/min/m² (p<0.001) and in C from 3.20±0.11 to 3.39±0.13 l/min/m² (p< 0.05). Mean arterial BP was higher in CRF and its decrease was greater than in C (21.1±2.7% vs 9.1±1.0%,p<0.001). In patients with CRF GFR, RPF, and CI remained significantly elevated and BP was still significantly decreased 60 min after ANP infusion. Total peripheral vascular resistance (TPR) was elevated in CRF and declined during ANP infusion in both CRF and C. The decline of TPR was sustained and more pronounced in CRF than in C. Renal vascular resistance (RVR) was high in CRF and dropped by nearly 50% during ANP infusion, whereas only a moderate decline in RVR during ANP application was observed in C. Thus, exogenous ANP had greater and prolonged effects on systemic hemodynamics and renal function in CRF than in C. They may be due to higher levels of ANP following ANP infusion and appear to be mediated by a more sustained formation of the second messenger cGMP.Abbreviations ANP atrial natriuretic peptide - CRF chronic renal failure; - GFR glomerular filtration rate - FF filtration fraction - ERPF effective renal plasma flow - ERBF effective renal blood flow - BP blood pressure - MAP mean arterial blood pressure - HR heart rate - SV stroke volume - CO cardiac output - CI cardiac index - TPR total peripheral resistance - RVR renal vascular resistance - U_NaV urinary sodium excretion - FE_Na fractional sodium excretion - PRA plasma renin activity - ECFV extracellular fluid volume - PAH paminohippuric acid Dedicated to Prof. Dr. med. F. Krück on the occasion of his 70th birthday     

Systemic nitric oxide clamping in normal humans guided by total peripheral resistance

Aim: We wanted to stabilize the availability of nitric oxide (NO) at levels compatible with normal systemic haemodynamics to provide a model for studies of complex regulations in the absence of changes in NO levels. Methods: Normal volunteers (23–28 years) were infused i.v. with the nitric oxide synthase (NOS) inhibitor N^G-nitro-l -arginine methyl ester (l -NAME) at 0.5 mg kg⁻¹ h⁻¹. One hour later, the NO donor sodium nitroprusside (SNP) was co-infused in doses eliminating the haemodynamic effects of l -NAME. Haemodynamic measurements included blood pressure (MABP) and cardiac output (CO) by impedance cardiography. Results: l -NAME increased MABP and total peripheral resistance (TPR, 1.02 ± 0.05 to 1.36 ± 0.07 mmHg s mL⁻¹, mean ± SEM, P < 0.001). With SNP, TPR fell to a stable value slightly below control (0.92 ± 0.05 mmHg s mL⁻¹, P < 0.05). CO decreased with l -NAME (5.8 ± 0.3 to 4.7 ± 0.3 L min⁻¹, P < 0.01) and returned to control when SNP was added (6.0 ± 0.3 L min⁻¹). A decrease in plasma noradrenaline (42%, P < 0.01) during l -NAME administration was completely reversed by SNP. Plasma renin activity decreased during l -NAME administration and returned towards normal after addition of SNP. In contrast, plasma aldosterone was increased by l -NAME and remained elevated. Conclusions: Concomitant NOS inhibition and NO donor administration can be adjusted to maintain TPR at control level for hours. This approach may be useful in protocols in which stabilization of the peripheral supply of NO is required. However, the dissociation between renin and aldosterone secretion needs further investigation.     

Continuous measurement of renal intratubular pressures with a combined pressure transducer microperfusion system

Summary A method has been developed which permits continuous recording of intratubular pressures and simultaneous infusion of test solution at rates of 0–50 nl/min through a single microcapillary. Design and operation of the system is described which consists of an ultraminiature pressure transducer, a micro-perfusion pump and the probing microcapillary. Sealing of the latter was achieved by a screw collar which permits rapid replacement of capillaries without deleterious pressure spikes. At optimal supply voltage the recorded signal was independent of input voltage changes (up to ± 100 mV) and directly proportional to a) pressure applied to the microcapillary tip and b) flow rate through the capillary. — As example the pressure increments following local infusion into the proximal convolution of indigocarmine stained saline or reabsorption inhibitors at a rate of 10 nl/min was measured. During the infusion of 10% mannitol intratubular pressure rose to a plateau and remained above control levels. Application of potassium cyanide (1.5×10^–10 M/min) resulted in a gradual pressure increase starting at the onset of the intratubular perfusion. A qualitative similar rise was observed during administration of furosemide (2.2×10^–11 M/min), however the effect exhibited a time delay of several minutes.

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Abbreviations P Pressure on pressure sensitive diaphragm (gauge pressure) in cm H₂O - P _tub Intratubular pressure - P _tub Rise of intratubular pressure, when perfusion is turned on - P _x Pressure due to resistance of capillary tip; - Perfusion rate (nl/ml) - R Flow resistance of capillary tip, measured either in the aqueous phase on the kidney (R _surface) or in the tubular lumen (R _lumen) - U (P=O) Zero pressure output voltage - f.s. Full scale Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.     

Changes of collateral perfusion pressure and segmental coronary resistances during reactive hyperemia in anesthetized dogs

Changes of collateral perfusion pressure (CPP) and segmental coronary resistances during reactive hyperemia were studied in nine chloralose-urethan-morphine anesthetized open-chest dogs. Coronary perfusion pressure was controlled by a cannula in the left main coronary artery and inflow measured by an electromagnetic flowmeter. The first or second diagonal branch of the left anterior descending coronary artery was cannulated and perfused from a carotid artery; inflow was abolished by embolization with latex microspheres (diameter: 25±5 ) and peripheral coronary pressure was assumed to represent CPP. Segmental coronary resistances were defined as follows: Proximal coronary resistance (R₁) was calculated from the difference between coronary perfusion pressure and CPP devided by coronary inflow. Distal coronary resistance (R₂) was calculated from CPP divided by coronary inflow. Reactive hyperemia was produced by interruption of coronary inflow for 15 s and analysed at 30 s and 60 s of reperfusion when cardiac function had recovered. At baseline, R₁ was 0.52±0.04 mm Hg x min ×100 g/ml (RU) and R₂ 0.63±0.07 RU. At 30 s, R₁ was reduced by 19±3% (P<0.01) this was less (P<0.05) than R₂ which was reduced by 32±3% (P<0.01). At 60 s R₁ and R₂ were reduced by 11±2% and 13±2%, respectively; this was not significantly different. Accordingly, CPP (baseline: 59±4 mm Hg) at 30 s was reduced by 7±2% (P<0.03), at 60 s the reduction was not significant. The data suggest that reactive hyperemia, as a model of metabolic coronary dilatation, may reduce CPP equivalent to a coronary steal phenomenon.     

G tolerance and the vasoconstrictor reserve

Purpose

Because leg arterial stiffness is higher in subjects with high G tolerance, we hypothesized that subjects with high G tolerance would have larger capacity for vasoconstriction.

Methods

Sixteen subjects, eight with high and eight with low G tolerance (H and L group, respectively), were exposed to a cold pressor test (CPT) in supine and upright posture. Heart rate (HR), mean arterial pressure (MAP) and cardiac output (CO) were measured, and total peripheral resistance (TPR) and stroke volume (SV) were calculated.

Results

In the supine position, CPT increased TPR more in the H group; 31 ± 18 % than in the L group; 11 ± 7 % (p < 0.05). The L group had larger increases in CO than the H group; 17 ± 16 vs. 3.4 ± 7 % (p = 0.06). In the upright position, the H group had a larger MAP response to CPT than the L group; 26 ± 14 vs. 14 ± 7 % (p = 0.06). The H group, but not the L group, had significant increases in TPR whereas the L group had significant increases in CO and SV.

Conclusions

In response to CPT, the high G tolerance group elevated MAP by increasing TPR, whereas the low G tolerance group showed a dependency on increased CO. The H group seemed to have a larger vasoconstrictor reserve. The results further suggest that vasoconstrictor reserve capacity could constitute the link between the recent finding that indicates a relationship between G tolerance and arterial distensibility in the legs.     

The inotropic effect of atrial natriuretic factor in the anesthetized rabbit

This study was designed to investigate whether atrial natriuretic factor (ANF) administered over the physiological, pathological and pharmacological range has a negative inotropic action on the heart. Anesthetized rabbits were infused with increasing doses of ANF (0.05, 0.25 and 0.5g kg^–1min^–1), while measuring hemodynamic variables including the maximum rate of change of left ventricular pressure (dP/dt _max) as an index of inotropic state. Plasma levels of immunoreactive ANF (iANF) were measured to relate the hemodynamic changes to actual plasma levels of the peptide. Administration of ANF was associated with decreases in blood pressure, left ventricular pressure and dP/dt _max so that after 0.5 g kg^–1 min^–1 infusion, these variables had decreased by 21±2 mmHg, 21±5.3 mmHg and 925±175 mmHg/s, respectively (P<0.01). There were no significant changes in right atrial pressure, left ventricular end-diastolic pressure or heart rate. Since dP/dt _max can be influenced by changing hemodynamic variables and baroreflex changes, a second group of rabbits was studied in which afterload and heart rate were held artificially constant. Again, in this group of rabbits, infusions of ANF led to decreasing inotropic state, so that at the highest infusion rate, a 14% decrease in dP/dt _max was observed (P<0.05). By comparison, hydralazine, a drug which causes active vasodilatation but no direct inotropic action, significantly (P<0.01) decreased blood pressure, left ventricular pressure and dP/dt _max when infused at a rate of 10 g kg^–1 min^–1. However, in animals in which afterload was controlled, hydralazine did not affect any of the variables measured. The results indicate that ANF does have a negative inotropic action in the anesthetized rabbit.     

The effect of acute mental stress on limb vasodilation is unrelated to total peripheral resistance

Mental stress can trigger myocardial infarction, with poor vascular responses to stress implicated as a pathway. Vascular stress reactivity can be assessed by different methods, such as total peripheral resistance (TPR) and forearm blood flow (FBF). Little is known about how these vascular assessments are linked. This was examined in two separate studies. Healthy men (Study 1: N = 29, Study 2: N = 23) completed rest and mental arithmetic (Study 1: 8 min, Study 2: 16 min). In both studies, heart rate, mean arterial pressure, and FBF increased in response to stress. In Study 1, no changes in TPR were seen, but Study 2 found stress‐induced increases in TPR. FBF was not linked to TPR at any time (all ps > .05). It appears that limb vasculature and TPR responses to stress do not give the same information about impairments of the vasculature. These findings are relevant to the interpretation of prior research findings and the design of future studies on stress and vascular responses.     

Non‐linear dependence of interstitial fluid pressure on joint cavity pressure and implications for interstitial resistance in rabbit knee

Aims: Synovium retains lubricating fluid in the joint cavity. Synovial outflow resistance estimated as dP_j/d (P_j, joint fluid pressure and trans‐synovial flow) is greater, however, than expected from interstitial glycosaminoglycan concentration. This study investigates whether subsynovial fluid pressure increases with intra‐articular pressure, as this would reduce the estimated resistance estimate. Methods: Interstitial fluid pressure (P_if) was measured as a function of distance from the joint cavity in knees of anaesthetized rabbits, using servo‐null pressure‐measuring micropipettes and using an external ‘window’. Joint fluid pressure P_j was either endogenous (?2.4 ± 0.4 cmH₂O, mean ± SEM) or held at ～4, 8 or 15.0 cmH₂O by a continuous intra‐articular saline infusion that matched the trans‐synovial interstitial drainage rate. Results: At endogenous P_j the peri‐articular P_if was subatmospheric (?1.9 ± 0.3 cmH₂O, n = 19). At raised P_j the P_if values became positive. Gradient dP_if /dx was ～20 times steeper across synovium than subsynovium. P_if close to the synovium–subsynovium border () increased as a non‐linear function of P_j to 1.4 ± 0.2 cmH₂O (n = 23) at P_j = 4.3 ± 0.1 cmH₂O : 2.3 ± 0.2 cmH₂O (n = 17) at P_j = 7.6 ± 0.2 cmH₂O: and 3.0 ± 0.4 cmH₂O (n = 26) at P_j = 15 ± 0.2 cmH₂O (P = 0.03, anova ). Conclusions: Synovial resistivity is ～20× subsynovial resistivity. The increase in with P_j means that true synovial resistance d()/d is overestimated 1.5× by dP_j/d. This narrows but does not eliminate the gap between analysed glycosaminoglycan concentration, 4 mg ml^?1, and the net interstitial biopolymer concentration of 11.5 mg ml^?1 needed to generate the resistance.     

Effects of hypotension on cutaneous and subcutaneous blood flow in anaesthetized humans

Summary The aim of this study was to determine the effect of controlled hypotension on subcutaneous and cutaneous haemodynamics in humans. Moderate hypotension was achieved with nitroglycerin (NTG) and sodium nitroprusside (SNP) infusion during narconeuroleptanalgesia in seven patients. Subcutaneous and cutaneous blood flow were measured by a superficial and deep heat clearance (HC) technique. The mean arterial pressure ( ) decreased by 23%–30% and heart rate (f _c) increased but only during NTG infusion (+22%; P < 0.02). Subcutaneous and cutaneous blood flows remained unchanged despite a significant decrease in calculated cutaneous resistance (NTG: –26%, P < 0.01; SNP: –34%, P < 0.02)) and subcutaneous vascular resistance changed only with SNP (–31%, P < 0.02). After hypotension was discontinued the subcutaneous blood flow decreased (–13%, P = 0.05), whereas subcutaneous vascular resistance returned to its control values. An inverse relationship was found between f _c and (NTG: r = –0.525, P < 0.01; SNP: r = –0.622, P < 0.01) as well as with subcutaneous blood flow (NTG: r = –0.653, P < 0.001; SNP: r = –0.573, P < 0.01). In addition, we found oscillatory changes in deep HC values which differed in magnitudes (NTG 0.22 (SEM 0.09) W · m^–1 · °C^–1 vs SNP 0.42 (SEM 0.1) W · m^t–1 · °C^–1, P< 0.01) and frequencies (NTG 0.02 (SEM 0.006) Hz vs SNP 0.01 (SEM 0.002) Hz, P < 0.01). Despite unchanged blood flow, the effects of controlled hypotension on cutaneous and subcutaneous haemodynamics were different depending on the type of drug. These differences may have been related to counterregulatory responses and/or to direct vascular effects.     

Influences on central hemodynamics in hemorrhage of β2-adrenergic vascular control mechanisms

Central hemodynamic responses evoked by standardized hemorrhage (exsanguination of 20 ml×kg bwt^-1) were followed during 2 h in cats with intact and blocked vascular β₂-adrenoceptors using the ‘selective’β₂-blocker, ICI 118, 551. In the first 10 min after bleeding blood pressure and cardiac output (CO) decreased and total peripheral resistance (TPR) increased by the same amount in the ‘intact’ and β₂-blocked animals. Whereas blood pressure later on reached approximately the same hypotension level in both groups, other hemodynamic variables were distinctly different. In the ‘intact’ animals there was a gradual, partial recovery of stroke volume (SV) and CO in the face of a restoration to control of TPR. In the β₂-blocked animals TPR continued to increase in the face of a maintained low CO and declining SV. The lower SV in the latter group was ascribed to abolition of β₂-adrenergic restoration of plasma volume via absorption of tissue fluid into the circulation. The gradual decline of TPR in the ‘intact’ animals was attributed to β₂-adrenergic dilator interaction with constrictor influences on the resistance vessels. It is concluded that β-adrenergic vascular control mechanisms help to improve nutritional tissue blood flow during hemorrhage by increasing plasma volume, and hence venous return and CO, and by decreasing TPR. These reflex, β₂-adrenergic circulatory events are similar to those aimed at in current shock therapy by transfusion and vasodilator treatment.     

Acute ventilation-perfusion mismatching resulting from inhalative smoking of the first cigarette in the morning

Summary The effect of the first cigarette in the morning on the airway resistance (R _aw) which can be measured by body-plethysmography was investigated in 70 inhaling cigarette smokers. The test population showed a significant (P<0.0005) fall in R _aw 8 min after smoking. A further study (n = 16) showed that the fall in R _aw was most likely to be attributable to a decrease in the trapped air. The effect of the first cigarette in the morning on the arterial blood gases and on the alveolar-arterial oxygen difference P(A-a)O₂ and carbon dioxide difference P(A-a)CO₂ was investigated in 12 inhaling cigarette smokers. Smoking gave rise to a significant (P < 0.0005) fall in the partial pressure of oxygen (PaO₂) with compensatory overventilation. At the same time, the P(A-a)O₂ and the P(A-a)CO₂ increased significantly (P<0.01 and P<0.05, respectively). This effect could be observed for up to 24 min after smoking. In addition, the flow of blood in the pulmonary capillaries was measured in 28 test subjects with the nitrous oxide method ( _{N 2O}) before, and 18–22 min after, smoking the first cigarette in the morning. After smoking, there was a significant (P<0.0005) fall in the _{N 2 O} by an average of 11.3%. The decrease in the R _w the fall in the PaO₂ with compensatory overventilation, the increase in P(A-a)O₂ and P(A-a)O₂ and the decrease in the _{N 2 O} are interpreted as manifestations of pronounced acute ventilation-perfusion mismatching induced by smoking.Abbreviations Cdyn dynamic compliance - Cdyn 40a dynamic compliance at 40 breaths/min - _{N 2}O pulmonary capillary blood flow measured by the N₂O method - P(A-a)a alveolararterial pressure difference - Pa arterial partial pressure - P _AOa alveolar pressure difference measured in the pressure-flow curve at zero flow - R _awa airway resistance - sGaw specific airway conductance - SVI stroke volume index - TGV thoracic gas volume - BSA body surface area     

Time-dependent effects of aldosterone on sodium transport and cell membrane resistances in rabbit distal colon

Aldosterone stimulates Na⁺-absorption in rabbit distal colon. Due to circadian variations in plasma aldosterone level, Na⁺-transport varies in this epithelium. In vitro measurements (Ussing-chambers) yielded a transepithelial voltage (V _t ) of 13±1.6 mV for low-transporting epithelia (LT) and 25.7±2 mV for high-transporting epithelia (HT). However, the comparison of transepithelial conductance (G _t ) in LT epithelia (2.73±0.21 mS/cm²) and HT epithelia (2.96±0.41 mS/cm²) revealed no difference. Colons from both groups were stimulated by exogenous aldosterone (4 h prior to experiment). The transepithelial values changed as follows: LT epithelia showed a significantly increased V _t (26.1±4 mV) and G _t (3.74±0.23 mS/cm²), whereas in HT epithelia both parameters remained unchanged. Transepithelial amiloride-sensitive conductance was higher in HT than in LT. However, only in LT epithelia aldosterone increased this conductance. To get a more detailed view of the action of aldosterone, we used intracellular microelectrodes to calculate the resistances of apical (R _a ), basolateral (R _bl ) and paracellular (R _p ) pathway. The calculation of the resistances was based on a lumped equivalent circuit model and changes in R _a were induced by 50 M/l mucosal amiloride. Comparison of the control tissues revealed a lower R _bl only in HT tissues. In both groups stimulation by exogenous aldosterone led to a marked decrease of R _a . Furthermore R _bl was reduced to the same value as in HT control tissues. A leak resistance (R _l) was found, which was modulated by aldosterone in LT- and in HT epithelia. Differences in amiloride-sensitive transepithelial conductance between both epithelia groups could be explained by a regulation of r _l . Along with the regulation of the R _p the results indicate that the effects of exogenous aldosterone depended on the transport state of the rabbit distal colon. In LT epithelia aldosterone only influenced the resistances of the transcellular pathway. In HT epithelia aldosterone decreased cellular resistances and increased the paracellular resistance. Possible reasons of the augmented R _p are discussed.Abbreviations V _t transepithelial potential difference (mV) - R _r transepithelial resistance ( · cm²) - G _t transepithelial conductance (mS/cm²) - I _sc calculated short circuit current (A/cm²) - V _a apical membrane potential difference (mV) - V _bl basolateral membrane potential difference (mV) - voltage divider ratio ( = R _a /R _bl ) - voltage divider ratio ( = R _a /R _bl ) after amiloride - R _a apical membrane resistance ( · cm²) R _a = R _l · R _a ^/Na /(R _l + R _a ^/Na ) - R _a ^/Na apical membrane resistance to Na, ( · cm²) - R _bl basolateral membrane resistance ( · cm²) - R _c cellular resistance ( of apical and basolateral resistance) ( · cm²) - R _l leak resistance located in the apical membrane ( · cm²) - R _p resistance of the paracellular pathway ( · cm²) - G _a apical membrane conductance (mS/cm²) - G _bl basolateral membrane conductance (mS/cm²) - G _l apical leak conductance (compare R _l ) (mS/cm²) - G _p paracellular conductance (mS/cm²) - G _t transepithelial conductance (mS/cm²) - HF hard feces period - SF soft feces period - HT_contr high transporting control epithelia - LT_contr low transporting control epithelia - HT_aldo aldosterone pretreated high transporting epithelia - LT_aldo aldosterone pretreated low transporting epithelia; the prime designates data obtained after addition of amiloride     

Glucagon-like peptide-1 reduces hepatic glucose production indirectly through insulin and glucagon in humans

The effect of glucagon-like peptide-1 (GLP-1) on hepatic glucose production and peripheral glucose utilization was investigated with or without infusion of somatostatin to inhibit insulin and glucagon secretion in 13 healthy, non-diabetic women aged 59 years. After 120 min 3-³H-glucose infusion, GLP-1 was added (4.5 pmol kg^?1 bolus + 1.5 pmol kg^?1 min^?1). Without somatostatin (n = 6), GLP-1 decreased plasma glucose (from 4.8 ± 0.2 to 4.2 ± 0.3 mmol L^?1, P = 0.007). Insulin levels were increased (48 ± 3 vs. 243 ± 67 pmol L^?1, P = 0.032), as was the insulin to glucagon ratio (P = 0.044). The rate of glucose appearance (R_a) was decreased (P = 0.003) and the metabolic clearance rate of glucose (MCR) was increased during the GLP-1 infusion (P = 0.024 vs. saline). Also, the rate of glucose disappearance (R_d) was reduced during the GLP-1 infusion (P = 0.004). Since R_a was reduced more than R_d, the net glucose flow was negative, which reduced plasma glucose. Somatostatin infusion (500 μg h^?1, n = 7) abolished the effects of GLP-1 on plasma glucose, serum insulin, insulin to glucagon ratio, R_a, R_d, MCR and net glucose flow. The results suggest that GLP-1 reduces plasma glucose levels mainly by reducing hepatic glucose production and increasing the metabolic clearance rate of glucose through indirectly increasing the insulin to glucagon ratio in healthy subjects.     

Peripheral and brachial blood pressure during standardized occupation-related tests in normotensive and mild hypertensive men and women

We investigated the usefulness of peripheral blood pressure (BP) measurement in the assessment of strain in occupational physiology. Our hypothesis was that the brachial and peripheral BP reflect physiologically different events under various occupation-related demands in normotensive (NT) and hypertensive (HT) people. A group of 20 female and 20 male subjects with unmedicated mild hypertension that had been diagnosed by ambulatory blood pressure monitoring [awake time systolic/diastolic BP (BP_s/BP_d) 142.9 (SD 11.3)/86.4 (SD 6.2) mmHg] and 40 NT matched by age and sex [BP_s/BP_d 120.0 (SD 9.8)/75.6 (SD 5.9) mmHg] attended a laboratory session to undertake mental arithmetic tasks, a fingergrip test and submaximal cycle ergometry. Brachial and peripheral BP as well as heart rate were measured using a sphygmomanometer and an continuously automatic blood pressure measuring device on the finger, respectively. The peripheral BP_s was higher than brachial BP_s, BP_d was similar for peripheral and brachial BP except during cycle ergometry. Associations between the levels of brachial and peripheral BP depended on demands and did not explain more than 42% of the common variance. The highest correlations between the two BP methods were observed during habituation, recovery and mental demands, and weak correlations during cycle ergometry. For peripheral BP_s and BP_d we found significant correlations in all phases of the test (r=0.58 to 0.86, P < 0.001), also in ergometry (NT r=0.62, P < 0.001, HT r=0.53, P < 0.001), in contrast to the brachial BP. Peripheral BP differentiated the two BP groups (57.5%–72.5% correctly classified) which had been grouped by daily measurement of brachial BP, but brachial BP was superior in this respect with 65.0%–87.5% being correctly classified. These results supported the suggestion that the combined measurement of peripheral and brachial BP provides complementary information regarding physiological changes in NT and HT in different situations. Accepted: 30 August 1999