Effects of PEEP on systemic venous capacitance.

The aim of the present study was to determine effects of positive end expiratory pressure (PEEP) application on peripheral venous capacitance and relate them to concomitant central hemodynamic disturbances. The venous volume-pressure (V/P) relationships were studied in 6 intact anesthetized pigs to describe the effects of PEEP on systemic venous compliance (computed as the slope of the V/P relationship) and unstressed volume (referred to as the extrapolated volume intercept). Cardiac volumes as well as partitioning of circulating blood volume between central (ITBV) and peripheral (PBV) compartments were assessed by thermo-dye dilution techniques. During a 15 cm H2O PEEP application, venous compliance was reduced by 48%, while unstressed volume was increased by 25% and peripheral blood pooling increased from 63 to 74%. As a result, left heart and right ventricular end diastolic volumes were decreased by 8% and by 44%, respectively. It is concluded that increased venous unstressed volume and reduced compliance depicted the distension of the venous tree secondary to PEEP which acted as an impediment to venous return. As a consequence, cardiac output was reduced because of decreased preload.

Modelling the arterial wall by finite elements.

The mechanical behaviour of the arterial wall was determined theoretically utilizing some parameters of blood flow measured in vivo. Continuous experimental measurements of pressure and diameter were recorded in anesthetized dogs on the thoracic ascending and midabdominal aorta. The pressure was measured by using a catheter, and the diameter firstly, at the same site, by a plethysmograph with mercury gauge and secondly, by a sonomicrometer with ferroelectric ceramic transducers. The unstressed radius and thickness were measured at the end of each experiment in situ. Considering that the viscous component is not important relatively to the nonlinear component of the elasticity and utilizing several equations for Young modulus calculation (thick and thin wall circular cylindrical tube formulas and Bergel's equation) the following values were obtained for this parameter: 0.6 MPa-2 MPa in midabdominal aorta and 2 MPa-6.5 MPa in thoracic ascending aorta. The behaviour of the aorta wall was modelled considering an elastic law and using the finite element program "Lagamine" working in large deformations. The discretized equilibrium equations are non-linear and a unique axi-symmetric, iso-parametric element of 1 cm in length with 8 knots was used for this bi-dimensional problem. The theoretical estimation of radius vessel, utilizing a constant 5 MPa Young modulus and also a variable one, are in good agreement with the experimental results, showing that this finite element model can be applied to study mechanical properties of the arteries in physiological and pathological conditions.

Analysis of endotoxin effects on pulmonary circulation in terms of pressure-flow characteristics.

The purpose of the present work was to explore the hypothesis that pulmonary vasoconstriction secondary to endotoxin insult results mainly from an increase in the critical closing pressure of the pulmonary vessels. Specifically, we reasoned that in the face of a Starling resistor located between pulmonary arteries and left atrium, upstream transmission of increased left atrial pressure (Pla) would be inversely related to the level of the pressure intercept (Pi) obtained by extrapolation from the linear pulmonary arterial pressure (Ppa)--flow (Q degrees) plot. Six dogs (group E) were infused with Escherichia coli endotoxin (0.25 microgram/kg/min) for 2 hr, whereas six additional dogs (group C) served as control. During baseline conditions, Pi approximated LAP in both groups. In group C dogs, increasing LAP at constant Q degrees led to a proportional augmentation of Ppa. In group E dogs, endotoxin resulted in a shift of the Ppa-Q relationships to higher pressures due to both increases in Pi and slope. In addition, changes in Pla over the same range as in control dogs affected Ppa only at the highest levels of Pla. We conclude that endotoxin insult increases the critical closing pressure that exceeds Pla and induces the occurrence of a Starling resistor responsible for the production of an effective vascular waterfall.

Identification of three-element windkessel model: comparison of time and frequency domain techniques.

The problem of the parameter identification of the three-element windkessel model is studied. Minimization by least-square technique--LSQ--in time domain and frequential techniques--FFT--are compared. Continuous pressure and flow curves were recorded in the proximal aorta of an open chest dog. Comparison shows very high correlations between the parameter estimations obtained by LSQ and FFT methods. However, systematic differences appear between the calculated values, but do not seem to endanger physiological interpretation of the results.

[Effects of beta-adrenergic receptor blockade on hyperlactacidemia induced by exercise of different intensity]. / Effets du blocage des récepteurs bêta-adrénergiques sur l'hyperlactacidémie induite par des exercices d'intensités différentes.

The effects of beta-adrenergic blockade on the exercise-induced hyperlactatemia (Lap) have been studied in 31 adult male subjects [age: 25 +/- 1 years; body weight: 69 +/- 1 kg; VO2max: 54 +/- 1 ml O2.kg-1.min-1 (mean values +/- SEM)] randomly divided in 3 groups. All exercises were performed on a 10% inclined treadmill. In group 1 (n = 11), the subjects were walking during 20 minutes at 5 km.h-1 (55.6 +/- 1.4% VO2max). In group 2 (n = 10), they were running during 9 minutes at 8 km.h-1 (79.4 + 1.5% VO2max). The subjects of the third group (n = 10) were submitted to a 4 minutes run at 9.5 km.h-1 92 +/- 1.6% VO2max). These exercises were performed 1 hour after ingestion of a placebo or a single dose of 40 mg propranolol, in a double-blind randomized order. Blood samples were drawn at regular time intervals from an antecubital vein. Exercise tachycardia was reduced by about 20% (P less than 0.001) by propranolol in each group. Lap was significantly reduced by 15% by propranolol (P less than 0.005) at the lowest exercise intensity (55.6% VO2max), remained unchanged at 79.4% VO2max and was significantly enhanced by 16% during the recovery period following the run at 92% VO2max. These results clearly showed that the effects of acute beta-adrenergic blockade on Lap depend on exercise intensity.

Contribution of peripheral blood pooling to central hemodynamic disturbances during endotoxin insult in intact dogs.

The aim of the present study was to determine possible effects of Escherichia coli endotoxin on peripheral vascular compliance and relate them to concomitant central hemodynamic disturbances. Endotoxin was infused at 0.25 micrograms/kg.min during 2 h in six anesthetized dogs, while six additional animals served as controls. Vascular compliance of the systemic circulation was calculated in intact animals from the changes in CVP after known changes in systemic blood volume. In control dogs, vascular compliance averaged 2.3 ml/mm Hg.kg body weight. During slow endotoxin infusion, cardiovascular effects were measurable only after a certain period of time had elapsed from the start of endotoxin insult and consisted of hypotension associated with systemic vasodilation. Systemic BP decreased gradually from 124 to 68 mm Hg while vascular compliance was finally increased by 100%, when compared to control values. This latter rise was responsible for a reduction in the cardiac preloads. Pulmonary wedge pressure and CVP were decreased from 7.1 to 3.4 and from 4.5 to 2.6 mm Hg, respectively. However, parallel to the decrease in left ventricular preload, endotoxin induced a progressive decrease in left ventricular afterload. Because of the balance in ventricular loading, cardiac output remained almost unchanged. After volume loading (dextran 30 ml/kg), cardiac output was remarkably increased from 3.28 to 6.24 L/min.m2 while peripheral vasodilation was not affected by this maneuver. It is concluded that low dose endotoxin infusion induces in dogs a hemodynamic pattern similar to human sepsis. The left ventricular loading changes are related to an enhanced systemic vascular compliance from 2.3 to 4.5 ml/mm Hg.kg. High flow shock state is encountered provided peripheral blood pooling is compensated by adequate volume replacement.

[Relation between endurance time and maximal oxygen consumption during supramaximal running]. / Relation entre le temps-limite et la consommation maximale d'oxygène dans la course supramaximale.

The relationship between speed and the maximal length of time supramaximal runs can be sustained (temps-limite, tlim) has been studied in seven male subjects (physical education students). Within the range of intensity studied, tlim strictly depends on maximal oxygen consumption (VO2max). The relationship between tlim and the relative energy cost of the exercises per unit of time (E), calculated by subtracting the maximal power of aerobic metabolism (Emaxox) from E, removes the interindividual differences of tlim. The function tlim = f(E-Emaxox) is described by an empirical equation of the form: tlim = a.exp[-b(E-Emaxox)] (r = 0.979; P less than 0.001), where the parameters a and b are respectively equal to 330.8 and 0.14 and where tlim, E and Emaxox are respectively expressed in seconds and in watts per kg of body weight.

Effects of intravascular volume expansion on lung fluid balance in a canine model of septic shock.

We tested the early effects of endotoxin on both the permeability of capillary membranes and microvascular pressure. One group of dogs (n = 8) were fluid loaded (30 ml/kg dextran-40) after having been subjected to a 2-h Escherichia coli endotoxin infusion (0.25 micrograms/kg X min). A second control group of animals (n = 6) was submitted to a similar (25 ml/kg) volume loading over an equivalent 30-min period. We estimated extravascular lung water (EVLW), calculated the effective pulmonary capillary pressure, and determined the alveolar-capillary filtration coefficient (Kf) after volume loading. Only the septic animals consistently showed elevated EVLW values consistent with pulmonary edema. The results showed, however, that the Kf calculated for the dogs that received endotoxin was no different from that of control group (Kf = 0.005 ml/kg X min X mm Hg). Instead, endotoxin constricted the pulmonary veins which led to a considerable rise in microvascular hydrostatic pressure above the level at which the lungs could not resist edema formation. We conclude that acute pulmonary edema that follows endotoxin insult and subsequent therapeutic volume replacement is due to an increased filtration force instead of an alteration in the microvascular permeability.

Pulmonary hydrostatic microvascular pressure changes and lung fluid balance during histamine infusion in intact dogs.

The effects of histamine on systemic and pulmonary hemodynamics of dogs were studied in six intact animals. Histamine infusion resulted in an almost immediate, precipitous fall in blood pressure (BP), pulmonary capillary wedge pressure (PCWP), and right atrial pressure (RA) as well as an increase in heart rate. Partial recovery occurred about 5 minutes after infusion was stopped. Cardiac output did not change significantly. Consequently, the calculated peripheral resistance decreased afterwards. Hepatic portal pressure rose significantly after 2 minutes of histamine infusion with partial recovery in about 5 minutes. Suprahepatic venous pressure did not change significantly. Although pulmonary arterial pressure did not necessarily rise, total pulmonary vascular resistance increased in every dog. If the absolute level in pulmonary arterial resistance remained greater (Ra 105 mm Hg/liter-1 min X kg-1) than the level of venous resistance (Rv 70 mm Hg/liter-1 min X kg-1), the relative increase in venous resistance (100%) was higher than the increase in Ra (35%). On the other hand, effective capillary pulmonary pressure remained unchanged. Central blood volume and extravascular lung water increased upon histamine infusion and returned rapidly to baseline when histamine infusion was stopped. No significant changes occurred in either effective pulmonary compliance and arterial blood gas values. Our data lead us to conclude that histamine's major action occurs in the venous pulmonary segments; pulmonary and splanchnic blood pooling is responsible for a fall in cardiac preload; and an increase in extravascular lung water and central blood volume with unchanged effective pulmonary pressure might be explained by an increase in microvascular surface area.

A comparison of Escherichia coli endotoxin single bolus injection with low-dose endotoxin infusion on pulmonary and systemic vascular changes.

The purpose of this study was to compare effects of single bolus endotoxin injection with sustained low-dose endotoxin infusion on systemic and pulmonary hemodynamics in anesthetized dogs. When administered as a bolus (.01 mg/kg), endotoxin induced systemic vascular changes whose evolution could be divided into two consecutive phases. In the early phase, marked hepatic venoconstriction caused a rise in portal pressure followed by abrupt decreases in both cardiac output and blood pressure. Mean pulmonary artery pressure remained unchanged. Because of lowered blood flow, both peripheral and pulmonary resistances increased. The rise in the latter was due to a prominent vasoconstriction of pulmonary arteries. Following a partial spontaneous recovery from shock, the late phase was characterized by a low-output state combined with high systemic vascular resistances. In contrast, when endotoxin was given at a slow infusion rate (250 ng/kg/min) over a 2-hour period of time, cardiovascular effects were basically different from the preceding ones, and they were measurable only after a certain period of time had elapsed from the start of endotoxin insult. First, blood pressure decreased gradually, while cardiac output remained almost unchanged. Therefore, peripheral resistance was decreased. Second, in the pulmonary circulation, the site of vasoconstriction was shifted from arteries to veins. We conclude that there is a fundamental difference in the response of the dog's systemic and pulmonary circulation as a function of endotoxin administration as either a bolus or slow infusion. This difference might be due to sudden elevated portal pressure responsible for an abrupt cardiovascular collapse in dogs subjected to bolus injection.

Lack of defective cardiac oxidative metabolism in intact dogs subjected to a prolonged low-dose infusion of Escherichia coli endotoxin.

The aim of the present study was to determine possible direct adverse effects of a 2-hour Escherichia coli endotoxin infusion (50 ng kg-1 min-1) on myocardial oxidative carbohydrate metabolism. The experiments were performed in intact dogs to assay glucose and lactate cardiac uptake and relate them to oxygen consumption (MVO2), CO2 production, and myocardial hemodynamics. Coronary sinus blood flow (CSBF) was measured by thermodilution, and the arteriovenous differences in glucose, lactate, pyruvate, O2, and CO2 were determined by blood samples obtained simultaneously from the carotid artery and sinus coronary. The adequacy of CSBF in meeting cardiac oxygen needs was evaluated by calculating the percentage of anaerobic metabolic rate (% AMR). During endotoxin infusion, CSBF was significantly lowered by 33% while mean aortic blood pressure was decreased by 43%. Cardiac index exhibited a minimal reduction of 14%. Mean arterial blood glucose decreased 30% and arterial lactate increased 100%. Despite the progressively developing hypoglycemia, cardiac glucose uptake increased 140%. Although MVO2 was reduced to 70% of control value, lactate uptake increased 50%. Throughout the experimental period, the % AMR remained negative. Under endotoxin infusion, up to 78% of the cardiac CO2 production was derived from carbohydrate utilization, as compared to 40% prior to endotoxin infusion. Our findings suggest the absence of any toxic action by an endotoxin-sustained infusion on cardiac oxidative metabolism.

[Hemodynamic and respiratory effects of the perfusion of low-dose endotoxin in intact heparinized dogs]. / Effets hémodynamiques et respiratoires de la perfusion de faibles doses d'endotoxine chez le chien intact hépariné.

In the anesthetized dog, a low dose perfusion of endotoxin (50 ng X kg-1 X min-1) produces hemodynamic and metabolic perturbations generally similar to those clinically found in man during the hemodynamic phase of septic shock. These modifications are observed after about 30 minutes following the beginning of the perfusion. They constitute: 1) an arterial vasodilatation responsible for a hypotension without a significant modification of the cardiac output; 2) a drop in the left ventricular filling pressure; 3) a progressive metabolic acidosis; 4) a moderate arterial hypoxia that is independent of an alveolar hypoventilation. To these perturbations is added the contemporary development of a leucopenia associated with a thrombopenia. This mode of endotoxin administration seems to us to constitute a satisfactory experimental model for studying the circulatory injuries due to hyperdynamic septic shock.

[Energetic equivalent of the production of plasma lactate during running of supramaximal intensity]. / Equivalent énergétique de la production du lactate plasmatique dans la course d'intensité supramaximale.

The energy equivalent of plasma lactate production (ELAp) represents the amount of energy that can be derived from the anaerobic glycolysis per kg body weight when the peak plasma lactate concentration (LAp) after exercise increases by 1 mM. ELAp has been calculated from the relationship between the oxygen deficit (Do2) and LAp in 32 subjects. LAp and oxygen uptake measurements were made during constant speed supramaximal running until exhaustion or during the course of constant-speed supramaximal runs of different duration interrupted by 8- to 10- min resting periods. The relationship between Do2 and LAp is described by a linear equation where the slope is equal to ELAp. This equation is: Do2 = 12.3 + 2.4 LAp (r = 0.958; P less than 0.001), where Do2 is expressed in ml O2/kg and LAp in mmol/litre (mM). These findings validate LAp measurements as an index of the anaerobic metabolism during supramaximal running.

[An animal model of hyperdynamic septic shock: hemodynamic effects of injection of low doses of endotoxin in the dog]. / Recherche d'un modèle animal du choc septique hyperdynamique: effets hémodynamiques de l'injection de faibles doses d'endotoxine chez le chien.

In anaesthetized dogs, low dose endotoxin perfusion (250 ng kg-1 min-1 during 20 min) resulted, after a delay of 15-40 min, in a decrease of mean arterial pressure (from 127 to 106 mm Hg), a transient increase in cardiac output (from 2.2 to 2.9 L/min), a fall of systemic vascular resistance (from 60 to 41 mm Hg L-1 min-1) and an increase in heart rate (from 109 to 156/min). This haemodynamic pattern is similar to the so called "hyperdynamic" initial phase of clinical septic shock.

The arterial baroreflex and the cardiopulmonary reflex in borderline hypertension.

An elevation of the cardiopulmonary baroreflex control of the forearm vascular resistances due to an impairment of the arterial baroreflex has been postulated in borderline hypertension. The purpose of the study is to verify this hypothesis. The arterial baroreflex sensitivity, measured by the phenylephrine method is similar in borderline hypertensive and normotensive subjects of the same age. The forearm and the splanchnic vascular resistances are studied in borderline hypertension and normotension during leg negative body pressure at -40 and -70 mmHg. Baseline forearm resistances are higher in borderline hypertension. The increase of forearm resistance is similar in borderline hypertension and normotension when variations are expressed in percentage of the basal values. The elevation of plasma norepinephrine is similar in the two groups. The tachycardia and the elevation of splanchnic resistances are similar in borderline hypertensive and normotensive subjects. We conclude that: The arterial baroreflex is acting normally in borderline hypertension. The cardiopulmonary baroreflex control of the forearm vascular resistances is normal in borderline hypertension. The elevation of the basal forearm vascular resistances is not due to a sympathetic hyperactivity.

Effect of protein-supplemented fasting on the fuel-hormone response to prolonged exercise in obese subjects.

This study aimed at investigating the influence of protein-supplemented fasting (PSF) on the tolerance and the fuel-hormone response to endurance exercise in the severely obese subject. For this purpose, eight obese men (27 +/- 2 yr, 182 +/- 7 per cent of ideal body weight) exercised on a horizontal treadmill (4 km/h) during 3 h before and after 13 d of PSF (Alburone, 70 g protein/day). Because of the 8.9 +/- 0.7 kg weight loss and the corresponding lower energy cost, exercise oxygen consumption decreased from 1.6 +/- 0.1 (before PSF) to 1.4 +/- 0.1 l/min (after PSF). In contrast, mean exercise heart rate was identical (119 +/- 5/min) in both conditions, resulting in a lower oxygen pulse after PSF. The mean respiratory quotient measured during exercise was lower after PSF (0.72 +/- 0.01 vs 0.75 +/- 0.01 2 P less than 0.05), thus demonstrating a higher fat utilization. This was supported by a higher exercise-induced plasma free fatty acid (FFA) mobilization after PSF (delta plasma FFA: + 675 +/- 101 vs + 376 +/- 121 mumol/l, 2 P less than 0.05). This metabolic adaptation mainly results from two mechanisms: a significantly lower plasma IRI at rest and during exercise after PSF (5.7 +/- 0.8 vs 11.4 +/- 1.4 microunits/ml, 2 P less than 0.001); and a lower basal blood glucose (4.2 +/- 0.2 vs 4.6 +/- 0.1 mmol/l) and an earlier decrease of glucose (30th vs 90th min) during exercise after PSF, suggesting a relative depletion of the carbohydrates stores. The lipolytic hormones (glucagon, epinephrine, norepinephrine, cortisol, growth hormone) did not significantly increase during exercise after PSF when compared to exercise before PSF; thus, their role in the enhanced FFA mobilization appears less important. Only two of our eight subjects were unable to achieve the third hour of exercise after PSF; however, no major clinical events or electrocardiographical disturbances were observed in any of the eight subjects. In conclusion, moderate exercise can be tolerated at least for 2 h during PSF when appropriate fluid, mineral and vitamin therapy is given. Under these conditions it induces a preferential utilization of fat-derived substrates and selectively augments fat mobilization which favors weight loss. For these reasons, moderate exercise can be recommended under strict medical supervision as part of all weight reduction therapy.

Effect of protein-supplemented fasting on metabolic and hormonal responses to epinephrine infusion in obese subjects.

The present study aimed at investigating the effects of an epinephrine (EPI) intravenous infusion (10 micrograms/min for 30 min) in normal subjects and in obese patients before and after 13 days of protein-supplemented fasting (PSF, 70 g protein/day). Blood glucose, plasma free fatty acids (FFA), lactate, insulin (IRI) and glucagon were determined before, during (15, 30 min) and after (+30 and +60 min) the EPI infusion. 1. When compared to lean control subjects, obese patients exhibited a less marked rise in blood glucose and a more important increase in plasma FFA, EPI infusion decreased IRI plasma levels in normals but not in the obese. Plasma glucagon was lower in the obese under basal conditions and their A cell reactivity to EPI was clearly reduced. 2. Comparison of the results obtained in obese patients before and after PSF revealed that EPI-induced blood glucose rise was not altered despite lower basal values after PSF. Plasma lactate response was impaired, probably because of the depletion in muscle glycogen. Reduction in basal plasma IRI was associated with a significantly higher FFA mobilization. Abnormally low basal EPI-stimulated glucagon concentrations persisted after PSF despite concomitant reductions in blood glucose and plasma IRI.

[Changes in plasma volume in submaximal exertion of short duration]. / Modifications du volume plasmatique lors d'exercices d'intensité submaximale et de durée brève.

Changes in plasma fluid volume and hyperlactacidemia were measured in nine healthy young men who had been running 10 min on a motor-driven treadmill (work rate from 40 to 90% V0, max). Our results show that there is a linear relationship between reduction of plasma fluid volume and intensity from 50% of max. For a given intensity the reduction of plasma fluid volume is a function of hyperlactacidemia.

[Decreased secretion of epinephrine during protein-supplemented fasting in obese subjects (author's transl)]. / Diminution de la sécrétion d'adrénaline au cours de la diète hypocalorique protélique chez l'obèse.

The protein-supplemented fasting induces a progressive but moderate decrease in blood glucose (-26%) and a marked rise in plasma free fatty acids levels (+ 43%). Nevertheless the secretion of epinephrine by the adrenal medulla, as indirectly estimated by the ratio of the basal urinary elimination to the recovery percentage from the urine of an epinephrine infusion, shows a significant decrease (- 36%) during the protein diet. Thus the enhanced lipolysis does not result from an adrenergic overactivity but merely depends upon the marked reduction in the plasma insulin level (- 38%).