Simulation study of autoregulation responses of peripheral circulation to systemic pulsatility

Background  

This simulation study investigated potential modulations of total peripheral resistance (TPR), due to distributed peripheral vascular activity, by means of a lumped model of the arterial tree and a non linear model of microcirculation, inclusive of local controls of blood flow and tissue-capillary fluid exchange.     

Estrogen effects on osmotic regulation of AVP and fluid balance

To determine estrogen effects on osmotic regulation of arginine vasopressin (AVP) and body fluids, we suppressed endogenous estrogen and progesterone using the gonadotropin-releasing hormone (GnRH) analog leuprolide acetate (GnRHa). Subjects were assigned to one of two groups: 1) GnRHa alone, then GnRHa + estrogen (E, n = 9, 25 +/- 1 yr); 2) GnRHa alone, then GnRHa + estrogen with progesterone (E/P, n = 6, 26 +/- 3). During GnRHa alone and with hormone treatment, we compared AVP and body fluid regulatory responses to 3% NaCl infusion (HSI, 120 min, 0.1 ml. min(-1). kg body wt(-1)), drinking (30 min, 15 ml/kg body wt), and recovery (60 min of seated rest). Plasma [E(2)] increased from 23.9 to 275.3 pg/ml with hormone treatments. Plasma [P(4)] increased from 0.6 to 5.7 ng/ml during E/P and was unchanged (0.4 to 0.6 ng/ml) during E. Compared with GnRHa alone, E reduced osmotic AVP release threshold (275 +/- 4 to 271 +/- 4 mosmol/kg, P < 0.05), and E/P reduced the AVP increase in response during HSI (6.0 +/- 1.3 to 4.2 +/- 0.6 pg/ml at the end of HSI), but free water clearance was unaffected in either group. Relative to GnRHa, pre-HSI plasma renin activity (PRA) was greater during E (0.8 +/- 0.1 vs. 1.2 +/- 0.2 ng ANG I. ml(-1). h(-1)) but not after HSI or recovery. PRA was greater than GnRHa during E/P at baseline (1.1 +/- 0.2 vs. 2.5 +/- 0.6) and after HSI (0.6 +/- 0.1 vs. 1.1 +/- 1.1) and recovery (0.5 +/- 0.1 vs. 1.3 +/- 0.2 ng ANG I. ml(-1). h(-1)). Baseline fractional excretion of sodium was unaffected by E or E/P but was attenuated by the end of recovery for both E (3.3 +/- 0.6 vs. 2.4 +/- 0.4%) and E/P (2.8 +/- 0.4 vs 1.7 +/- 0.4%, GnRHa alone and with hormone treatment, respectively). Fluid retention increased with both hormone treatments. Renal sensitivity to AVP may be lower during E due to intrarenal effects on water and sodium excretion. E/P increased sodium retention and renin-angiotensin-aldosterone stimulation.     

Dynamics of fluid movement between intravascular and interstitial spaces

A model describing the dynamics of the fluid shift between intravascular and interstitial spaces after blood volume modification is proposed. A mathematical expression of the delayed compliance of the vascular and interstitial spaces is given and is taken into consideration in the model. Results of simulations of an experimental system using this model, defined by a set of simultaneous differential equations, are carried out substantiating with good coincidence the experimental findings.     

Dehydration and fluid balance: central effects of angiotensin

Central effects of dehydration are stimulated by osmotic stimuli, the reduced input of volume receptors, and angiotensin II. The subfornical organ (SFO) and organum vasculosum laminae terminalis (OVLT) have become accepted as putative receptor sites for angiotensin II in the brain. The exact quantitative relationship between the hours of water deprivation and the amount of angiotensin generated peripherally and whether that amount is sufficient to induce thirst centrally have not been established, but there is no question that when animals are dehydrated their angiotensin levels rise and the animals are thirsty. Attempts to block centrally the contribution of angiotensin II to thirst have been variable and cholinergic inputs have to be blocked at the same time. Various stimuli for thirst interact in a parallel fashion, and when one stimulus is blocked the other stimuli are still effective. Plasma angiotensin II may induce natural thirst, but how it enters the brain still remains to be explained. Although the SFO and OVLT have no blood-brain barrier, the blood supply to these organs acts as a limited perfusion system whereby blood-borne proteins cannot diffuse far from the capillary bed. A second set of receptors is found on the ventricular surface of the OVLT, as shown by fluorescence labeled angiotensin II. The connection between the SFO and OVLT was cut by discrete knife cuts. Drinking to angiotensin II intraventricularly was not significantly altered but the pressor response was reduced by 50%. These results can be explained by a circuit for drinking passing down below the level of the knife cut and a separate pressor pathway passing dorsally through the area that was cut by the knife. Thirst and pressor neural circuits beginning with angiotensin receptors could explain some of the data accumulated with the AV3V syndrome that occurs when the OVLT and nucleus medianas are destroyed.     

心脏和脑循环功能相互影响的动力学模型

心脏和脑血管疾病是医学研究的热点。本文整合心脏、体循环和脑循环,构建了循环系统的整体动力学模型,力图揭示心脏和脑循环功能的相互影响。结论表明,从血液动力学角度,不但心脏特性变化会对脑循环产生影响,脑血管异常也会对心血管功能（如血压）发生作用。     

Inhibin-like effects of interstitial testis fluid: effects on serum FSH and androgen-binding protein in epididymis

Application of rat interstitial testis fluid (ITF) to orchidectomized rats diminishes significantly the rise of FSH in serum following castration. The effect is seen for 12-24 hours on day 3 and 50 after orchidectomy but not at 48 hours in rats treated 50 days after orchidectomy. LH levels are not significantly affected. These observations are assumed to be related to an inhibin-like activity in ITF. Therefore ITF (after extraction with ether) is given to intact animals and the testicular parameter of FSH, the androgen-binding protein (ABP), is measured by "steady-state" PAGE. Unexpectedly, ABP concentrations increase. At present, this effect cannot be explained. It is concluded that ITF contains only small amounts of inhibin and will be no good source for further studies.     

Effect of lectins on the interactions between human peripheral blood lymphocytes and monocytes

Interactions between normal human peripheral blood T lymphocytes and monocytes were investigated by measuring the in vitro cellular adherence of these cells in the presence and in the absence of mitogens. Concanavalin A (Con A), lentil lectin (Lc), and phytohemagglutinin (PHA) in mitogenic doses increased 15 to 20 times the binding of T lymphocytes to monocytes. The lectin-induced binding was similar to that produced by neuraminidase-gal-actose-oxidase treatment. A good correlation was found between the early cellular adherence induced by these lectins and by neuraminidase-galactose-oxidase and the blastogenesis of the T lymphocytes measured after 3 days of culture by [³H]thymidine uptake. However, wheat germ agglutinin (WGA), a nonmitogenic lectin, also increased the binding of T lymphocytes to monocytes. Addition of specific carbohydrates completely inhibited the cellular interactions induced by lectins. Peanut agglutinin (PNA) induced adherence of lymphocytes only after treatment of these cells with neuraminidase. Striking differences were not found between the lectin-induced adherence observed with autologous and heterologous cells. Killing of monocytes abolished entirely the lectin-induced adherence of lymphocytes, however killed T lymphocytes were still able to interact weakly with live monocytes. Dexamethasone was found to be a potent inhibitor of mitogen-induced cellular interactions.     

Biotic and abiotic interactions between surface and interstitial systems in rivers

Water chemistry and community assemblages of surface and interstitial invertebrates were studied at seven sues on the French Rivers Rhône and Am at surface and at 50 cm depth into the bed sediments Chemical factors allowed differentiation of surface water from groundwater and detection of water exchanges defining clear downwelling and upwelling zones At some sites, interstitial water showed both surface and phreatic conditions, characterizing the underflows of the Rhone or of the Am In the interstitial area, most taxa showed no significant correlations with water chemistry Some epigean and hypogean fauna showed correlations with certain factors Clear relationships appeared between the water exchanges and the distribution of surface and interstitial faunas In interstitial samples, epigean and some hypogean species characterized the downwelling zones while others seemed to be strictly linked to the upwelling zones In surface samples, the presence of hypogean species was associated with regions of groundwater upwelling     

Vagal inhibitory effects on peripheral circulation in acute coronary occlusion.

The reflex adjustments of the peripheral circulation in response to acute coronary occlusion were studied in anesthetized dogs with isolated vascular beds perfused at constant flow. Coronary occlusion caused significant increases in perfusion pressure which averaged 27 +/- 4 mmHg in the hindlimb, 19 +/- 8 mmHg in skeletal muscle, and 13 + 5 mmHg in the mesenteric artery. These responses were less than half those caused by a similar decrease in aortic pressure obtained with hemorrhage. Coronary occlusion caused no significant changes in renal and paw circulations, while marked vasoconstriction resulted from hemorrhage. When aortic pressure was maintained constant throughout the duration of coronary occlusion, there was a significant vasodilatation in all beds studied. After vagotomy, coronary occlusion caused a constrictor response similar in magnitude to that caused by hemorrhage in each vascular bed and the dilator responses to occlusion at constant aortic pressure were abolished. Both constrictor and dilator changes were prevented by alpha-adrenergic blockade. Mechanical distension of the left ventricle in four dogs with carotid sinus nerves cut caused a significant reflexdilatation in the hindlimb. Thus, coronary occlusion initiates an inhibitory reflex mediated by vagal afferents which opposes peripheral vasoconstriction most effectively in the renal and paw circulations.     

A comparison of the effects of aspirin and histamine on fluid balance in the recruited lung

Salicylate administration has been reported to increase the flow of protein-rich lymph from lungs of animals, however, the mechanism of this response is unclear. In the present study we measured pulmonary hemodynamics and lung fluid and lung fluid and protein flux in anesthetized sheep, surgically prepared for the collection of lung lymph, in order to examine the possible effect of aspirin (ASP) on lung vascular permeability. ASP was given during recruitment of pulmonary microvascular surface area induced by sustained elevation of left atrial pressure (Pla) (Group 1) or continuous infusion of adenosine triphosphate (ATP) (Group 2). We compared the results of ASP administration to those found in similarly prepared animals given histamine (H) during like periods of increased Pla (Group 3) or ATP infusion (Group 4). ASP administration resulted in increased lymphatic protein clearance (Cp) in both Groups 1 and 2. In Group 1, following the characteristic increase in lung lymph flow (Q1) and fall in the ratio of lung lymph to plasma protein concentration (L/P) produced by Pla elevation, ASP administration resulted in a further increase in Q1 and a significant increase in L/P. The results found in ASP animals are qualitatively similar to those observed in Groups 3 and 4 after H. While we cannot specifically rule out a hemodynamic effect of the drug, our results suggest the increased protein flux observed following ASP administration was mediated at least in part through and increase in lung microvascular permeability.     

Model analogues in the study of cephalic circulation

Simple laboratory models are useful to demonstrate cardiovascular principles involving the effects of gravity on the distribution of blood flow to the heads of animals, especially tall ones like the giraffe. They show that negative pressures cannot occur in collapsible vessels of the head, unless they are protected from collapse by external structures such as the cranium and cervical vertebrae. Negative pressures in the cerebral-spinal fluid (CSF) can prevent cerebral circulation from collapsing, and the spinal veins of the venous plexus can return blood to the heart in essentially rigid vessels. However, cephalic vessels outside the cranium are collapsible, so require positive blood pressures to establish flow; CSF pressure and venous plexus flow are irrelevant in this regard. Pressures in collapsible vessels reflect pressures exerted by surrounding tissues, which may explain the observed pressure gradient in the giraffe jugular vein. Tissue pressure is distinct from interstitial fluid pressure which has little influence on pressure gradients across the walls of major vessels.     

Effect of induced hypothermia on the systemic circulation

Studies of the systemic circulation in dogs (n = 5) during hypothermia showed that cardiac output, mean arterial pressure, total peripheral resistance, pulse rate, work L. V. is reduced and the stroke volume is increased. The authors think that these effects are probably due to metabolic alterations during hypothermia.     

Regulation of peripheral and systemic blood circulation in rats in conditions of acute nitrite hypoxia

Regulation of the systemic and peripheral hemodynamics in the conditions of acute nitrite hypoxia (doses of NaNO₂ 10, 30, and 50 mg/kg of the body mass) were studied on white male rats. It was shown that NaNO₂ causes a quick dose-dependent decrease in the blood pressure with an intensification of the parasympathetic tonus and development of bradycardia. The hemodynamics was restored as the oxygen capacity of the blood decreased with an increase in the sympathetic tonus and development of tachycardia. The role of intracardial metasympathetic structures and the renin-angiotensin system in cardiovascular adaptation to hypoxia was established. Adaptation to nitrite hypoxia is accomplished by a coordinated interaction of neurogenic and humoral factors. A combination of pharmacological agents, which include separate links of regulator systems of the organism, leads to failure of the adaptation process.