[Control of cutaneous blood vessels]. / Le contrôle du réseau vasculaire cutané.

In man, three kinds of sympathetic neurons reach the skin. Some cholinergic neurons stimulate the sweat glands, they are excited by temperature-regulating centers. Adrenergic neurons release noradrenaline and ATP to reduce cutaneous blood flow while cholinergic neurons release acetylcholine and a co-transmitter to dilate skin blood vessels. The excitation of both latter types of nerve cells depends on influences from temperature-regulating centers, baroreceptors and exercise. Moreover, in cutaneous blood vessels, a synthesis of NO is enhanced by an increase of body temperature and overall by direct heating of the skin. Burns are associated with axon reflexes and release of inflammatory mediators. The involvement of these various influences is described.

Detection of early sympathetic cardiovascular neuropathy by squatting test in NIDDM.

OBJECTIVE: To determine the role of the squatting test in the detection of early sympathetic neuropathy in patients with non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: Three groups of nonsmoking, nonobese subjects were studied: 10 healthy subjects, 10 NIDDM patients without autonomic neuropathy (AN), and 10 NIDDM patients with AN defined by the presence of a pathological deep-breathing value. All subjects were given three postural tests: lying-to-standing, sitting-to-standing, and squatting test. Heart rate (HR) and finger arterial pressure were recorded with a noninvasive technique. RESULTS: Blood pressure (BP) fall (expressed as decremental area) was not significantly different among the groups at standing up after sitting or lying. By contrast, a significantly greater BP drop occurred in NIDDM patients with AN (1,123 +/- 245 mm2) compared with NIDDM patients without AN (460 +/- 232 mm2) or normal subjects (429 +/- 138 mm2, P < 0.001). The HR increase after all the orthostatic maneuvers was smaller in diabetic patients with AN (P < 0.01) compared with that recorded in other groups. Significant correlations were observed between BP fall after squatting and either the expiration:inspiration ratio at deep breathing (r = -0.77, P < 0.001) or the duration of diabetes (r = 0.76, P < 0.001). CONCLUSIONS: The intrinsic orthostatic load of the squatting test, which is greater than conventional postural maneuvers, makes the squatting test an easy and useful test to detect early orthostatic dysregulation in NIDDM.

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.

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.

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.

The use of low doses of dopamine in intensive care medicine.

The dopamine alpha- and beta-adrenoceptor dose-response curves are investigated in four patients who are exempt from cardiovascular disease. A dose-related increase in CO, HR and SV is observed with infusion rates of up to 3 micrograms kg-1 min-1. With concentrations greater than 10 micrograms kg-1 min-1, both BP and SVR increase. Low-dose dopamine infusion less than 3 micrograms kg-1 min-1 is investigated in ten other patients. With this infusion rate, a selective renal vasodilation is induced without peripheral or cardiac beta-adrenoceptor activation. Dopamine is responsible for an increase in diuresis FENa, GFR and RBF. These properties are indicated in renal failure, and when haemodynamic support is required in cardiac failure, if an infusion rate of up to 10 micrograms kg-1 min-1 is able to reverse cardiac insufficiency.

[Psychopharmacology and neurohumoral transmission]. / Psychopharmacologie et transmission neuro-humorale.

The authors remind neurobiologists that, if it is necessary to analyze the mechanisms of neurotransmission, it is altogether necessary to integrate them in a circuit. If there is e.g. a noradrenergic transmission, there is neither a noradrenergic function nor a noradrenergic system. Moreover, the same neurone may release different transmittors; the response of the effector depends on its level of excitability; the identification of a mediator--especially in the urine--does not tell how its activity is modulated etc. A few examples are given.

Metabolic clearance of norepinephrine in normotensive and borderline hypertensive subjects.

Metabolic clearance of norepinephrine ( CmNE ) has been calculated in 10 normotensive subjects (NT) and 10 borderline hypertensive subjects (HT) at two different infusion rates of 1-NE. Plasma catecholamines have been determined by radio-enzymatic method from arterial blood samples. In these conditions, CmNE is similar in NT and HT.

[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.