Role of hypotension in altering blood coagulability after endotoxin

1962 ◽  
Vol 202 (3) ◽  
pp. 519-522 ◽  
Author(s):  
Frank A. Carozza ◽  
J. Dixon Hills

Because hypotension, regardless of etiology, profoundly influences blood coagulation, the role of hypotension in altering blood coagulability after endotoxin was investigated. By means of femoral artery catheterization, serial whole blood clotting times were determined in siliconized tubes at 37 C and correlated with mean arterial blood pressures in 1-kg albino rabbits. After duplicate base-line determinations, 200 µg/kg E. coli endotoxin was injected intravenously into nine animals; this quantity of endotoxin was the largest dose not lethal to normal rabbits of the strain employed. Nine control animals received isotonic saline. Blood from the endotoxin-treated group exhibited some accelerated coagulability between 1–2 hr after endotoxin injection and became significantly hypercoagulable ( P < 0.05) during the 3rd and 4th hr. The observed hypercoagulability could not be correlated with the hypotensive arterial blood pressure levels, the mean coefficient of correlation being –0.18. These data suggest that endotoxin-induced hypercoagulability in the rabbit results from specific reactions that are mediated by mechanisms distinct from those known to operate during the hypotensive state per se.

1987 ◽  
Vol 253 (4) ◽  
pp. H980-H984 ◽  
Author(s):  
M. A. Cierpial ◽  
R. McCarty

The role of the maternal environment in the development of hypertension in spontaneously hypertensive (SHR) rats was evaluated using the technique of reciprocal cross fostering. Litters of SHR and Wistar-Kyoto (WKY) normotensive pups were either reared by their natural mothers, in fostered to mothers of the same strain, or cross fostered to mothers of the opposite strain shortly after birth. Litters were weaned at 21 days of age, at which time all pups were weighed. At 18-20 wk of age, resting mean arterial blood pressures (MAP) and heart rates were determined for male subjects from the six groups (2 strains X 3 rearing conditions) via an indwelling tail artery catheter. At weaning, SHR animals weighed less than WKY animals. SHRs fostered to WKY mothers were significantly heavier than control SHRs, and WKYs fostered to SHR mothers were significantly lighter than WKY controls at weaning. These body weight differences were also evident in adulthood. Cross fostering SHR pups to normotensive WKY mothers resulted in a dramatic reduction in resting MAP measured in adulthood. Conversely, cross fostering WKY pups to SHR mothers had no measurable effect on adult resting MAP. We propose that an interaction between characteristics of the SHR maternal environment and a genetic susceptibility in SHR pups is essential in triggering the full expression of the hypertensive phenotype in this animal model of human essential hypertension.


1977 ◽  
Vol 23 (7) ◽  
pp. 1346-1347 ◽  
Author(s):  
D F Devereux ◽  
C A Michas ◽  
S Rice

Abstract Mongrel dogs were treated intravenously with either 1000 units of beef-lung heparin per kilogram of body weight or with isotonic saline, before intravenous administration of E. coli endotoxin. We found significant differences in circulating norepinephrine concentrations between a heparin-pretreatment group (1.89 +/- 0.39 microgram/liter) and the control group (9.83 +/- 4.64 microgram/liter), but none with respect to epinephrine. Systolic blood pressures at 360 min were also significantly (P less than 0.05) different, 148 +/- 6 mmHg as compared with 118 +/- 13.4 mmHg. Evidently heparin pretreatment can decrease circulating norepinephrine concentrations in the endotoxic state and changes in circulating catecholamine concentrations can affect physiological variables.


1975 ◽  
Vol 142 (6) ◽  
pp. 1570-1590 ◽  
Author(s):  
R J Ulevitch ◽  
C G Cochrane ◽  
P M Henson ◽  
D C Morrison ◽  
W F Doe

We have studied the role of complement in lipopolysaccharide (LPS)-induced hypotension and disseminated intravascular coagulation (DIC) by comparing the effects of injection of three preparations of LPS from E. Coli 0111:B4, S. minnesota Re595, and S. marcescens. Injections of nonlethal doses of these LPS preparations into normal rabbits produced decreases in mean arterial blood pressure during a 5-h period. When rabbits treated with cobra venom factor (CoF) to deplete C3 were injected with the various LPS preparations, mean arterial pressures fell at a rate and extent essentially identical to that observed in normal rabbits. Rabbits genetically deficient in C6 also demonstrated LPS-induced hypotensive changes. Only minimal, or no changes in plasma C3 levels or serum CH50 values were detected in normal rabbits after LPS injection. Hypotensive changes were also induced in rabbits when complement was rapidly activated by intravenous injection of CoF. In contrast to the hypotension induced by LPS, the fall in arterial pressure associated with the consumption of complement was short lived and required the rapid consumption of considerable amounts of C3. The occurrence of DIC noted in normal rabbits injected with each preparation of LPS was not inhibited in either rabbits treated with cobra factor or in C6-deficient rabbits. The DIC was most pronounced after injection of Re595 and S. marcescens LPS. Injection of the various LPS preparations produced a rapid disappearance of circulating neutrophils and mononuclear cells, which occurred with the same kinetics and to the same extent in normal, CoF-treated, and C6-deficient rabbits. Injection of either Re595 LPS or S. marcescens LPS produced a biphasic disappearance of circulating 51Cr-platelets. In contrast, injection of 0111:B4 LPS affected only slightly the rate of disappearance of 51Cr-platelets. Depletion of C3 by cobra factor treatment had no effect on the disappearance of platelets in animals injected with 0111:B4. In marked contrast cobra factor treatment greatly reduced the initial rapid disappearance of platelets in rabbits injected with either Re595 or S. marcescens LPS, but had no effect in the secondary disappearance phase.


1977 ◽  
Vol 46 (3) ◽  
pp. 336-341 ◽  
Author(s):  
Arthur I. Kobrine ◽  
Delbert E. Evans ◽  
Hugo V. Rizzoli

✓ Spinal cord blood flow (SCBF) was measured over a wide range of artificially varied mean systemic arterial blood pressures (MAP) in a group of monkeys with alpha adrenergic receptors blocked by the intravenous administration of phenoxybenzamine (Dibenzyline). The SCBF was found to vary linearly with changes in MAP. Autoregulation appeared to have been abolished. These data are cited as evidence for a dominant role of the sympathetic nervous system in control of the spinal circulation.


1984 ◽  
Vol 106 (3) ◽  
pp. 338-345 ◽  
Author(s):  
G. Schaison ◽  
P. Thomopoulos ◽  
D. Leguillouzic ◽  
G. Thomas ◽  
M. Moatti

Abstract. To investigate the respective role of triiodothyronine (T3) and thyroxine (T4) in the regulation of TSH secretion, we studied the action of sodium ipodate and propylthiouracil (PTU) in 11 athyreotic patients. The lT4 replacement dose was adjusted to obtain, in each patient, a normal basal TSH level and a normal TSH response to TRH. In the 5 ipodate-treated patients (single 6 g oral dose), the mean serum T3 level fell by 64% below the baseline value and serum rT3 rose 180% above the baseline. The free T4 index (FT4I) did not change whereas the mean serum TSH concentration increased 280% above baseline values. In the 6 PTU-treated patients (250 mg orally every 6 h for 10 days), serum T3 levels fell 33%, serum rT3 increased up to 82% and the FT4I did not change. The mean serum TSH concentration increased 68% above the baseline value. Thus, the mean percentage increase in serum TSH was less in PTU- than in ipodate-treated patients (68% vs 280%). Statistical analysis of the correlation between the serum T3 decrease (ΔT3) and the serum TSH (ΔTSH) increase demonstrated that for the same T3 diminution, the ipodate-treated group displayed higher increase of TSH than the PTU-treated patients. In the rat, PTU interferes with the 5'-deiodination of T4 in the liver and kidney but not in the pituitary, while ipodate appears to have the same effect in all tissues. If this holds true for human subjects, our data strongly suggest that circulating T4 (through its intrapituitary conversion to T3) shares with serum T3 the capacity to regulate TSH secretion in man.


1994 ◽  
Vol 266 (1) ◽  
pp. R188-R193 ◽  
Author(s):  
M. Keller-Wood

The arginine vasopressin (AVP) responses to hyperosmolality and to hypotension were compared in pregnant and nonpregnant ewes. When the responses to infusion of normal or hypertonic saline were compared, plasma AVP and Na+ concentrations were lower in pregnant ewes than nonpregnant ewes, but the relation between plasma AVP and Na+ concentrations was not altered in the pregnant state. In a second study the AVP response to hypotension, induced by the infusion of 2.5, 5.0, or 10.0 micrograms nitroprusside.kg-1.min-1, was compared in pregnant and nonpregnant ewes. Despite significantly lower mean arterial blood pressures in the pregnant ewes, the mean plasma AVP concentration after infusion of nitroprusside was not increased during pregnancy. Therefore, the relation between mean arterial pressure and AVP was significantly shifted to the left in the pregnant ewes, indicating lower AVP concentrations for a given level of arterial pressure during pregnancy. The results suggest that pregnancy alters the regulation of AVP by arterial pressure but does not affect the regulation of AVP by plasma sodium concentration in the ewe.


1991 ◽  
Vol 260 (1) ◽  
pp. R142-R147 ◽  
Author(s):  
E. Grossman ◽  
R. F. Rea ◽  
A. Hoffman ◽  
D. S. Goldstein

It has been difficult to examine clinically the physiological role of central and peripheral alpha 2-adrenoceptors in humans. We simultaneously measured directly recorded peroneal skeletal muscle sympathoneural activity (MSNA) and the rate of appearance (spillover) of norepinephrine (NE) in forearm venous and arterial plasma before and at 15 min during intravenous administration of the alpha 2-blocker yohimbine (Yoh, 125 micrograms/kg bolus, 1 microgram.kg-1.min-1 infusion) in seven normal volunteers. Yoh administration increased mean arterial pressure by 16% (P less than 0.005), heart rate by 8% (P less than 0.05), and forearm vascular resistance by 67% (P less than 0.05). MSNA was increased by 73% (P less than 0.05), NE spillover into arterial blood by 125% (P less than 0.05), and forearm NE spillover (FSO) by 337% (P less than 0.005). Ganglion blockade by trimethaphan during Yoh infusion decreased MSNA to below detection limits and reversed Yoh-induced increases in arterial concentrations of NE and epinephrine. The results demonstrate that Yoh administration increases sympathoadrenal outflow. Because the mean increase of FSO was much larger than that of MSNA, the results suggest that alpha 2-adrenoceptors on sympathetic nerve endings modulate the neuronal release of NE for a given amount of sympathetic nerve traffic in humans; this effect seems prominent in the human limb.


2020 ◽  
Author(s):  
Marina Laplana ◽  
Oriol Yuguero ◽  
Joan Fibla

AbstractBackgroundThe search for a SARS-CoV-2 treatment has emerged as a worldwide priority. We evaluated the role of chloroquine and its derivatives in COVID-19 in Spanish individuals.MethodsWe performed a survey addressed to patients regularly taking chloroquine and its derivatives for the control of their autoimmune diseases. The survey was distributed with special attention to Spanish patient associations centred on autoimmune diseases and rheumatology and to the general population. A sample of untreated subjects was matched to the treated group according to sex, age range and incidence region. COVID-19 disease prevalence was compared between treated and untreated-matched control sample.ResultsA total of 319 surveys of patients regularly taking chloroquine and its derivatives were recovered for further analysis. The prevalence of declared COVID-19 status in the treated group was 5.3% and the mean prevalence among the untreated-matched groups was 3.4%. A community exposition to COVID-19 was associated with a greater prevalence of COVID-19 in both, treated (17.0% vs. 3.2%; p-value<0.001) and untreated groups (13.4% vs. 1.1%; p-value=0.027).ConclusionWe did not find differences of reported COVID-19 cases between treated and untreated groups, indicating a lack of protection by regular administration of chloroquine and its derivative drugs on COVID-19 infection. Of relevance, data indicates that patients that regularly take chloroquine derivatives are exposed to SARS-CoV-2 infection and must take the same protection measures as the general population.


1988 ◽  
Vol 65 (4) ◽  
pp. 1686-1692 ◽  
Author(s):  
A. A. Balgos ◽  
D. C. Willford ◽  
J. B. West

Previous studies on normal subjects and patients with polycythemia have given conflicting results of the effect of polycythemia on pulmonary gas exchange. We studied acutely induced normovolemic polycythemia in the dog and measured arterial blood gases and ventilation-perfusion (VA/Q) relationships using the multiple inert gas elimination technique. The mean base-line hematocrit of 43 +/- 5% was increased to 57 +/- 4 and 68 +/- 8%, respectively, after two exchange transfusions of packed erythrocytes. Subsequent plasma exchange transfusions returned the mean hematocrit to 44 +/- 4%. Polycythemia caused no significant arterial hypoxemia; indeed there was a slight improvement in the alveolar-arterial PO2 difference. The multiple inert gas elimination measurements showed no increase in VA/Q inhomogeneity with no increase in log SD ventilation (V) or log SD blood flow (Q). There was a shift of mean V and mean Q to high VA/Q areas because of a decrease in cardiac output, presumably caused by increased blood viscosity. This study showed no deleterious effects on pulmonary gas exchange within the hematocrit range of 36-76%.


1963 ◽  
Vol 204 (3) ◽  
pp. 467-470 ◽  
Author(s):  
Jiro Nakano ◽  
Christian De Schryver

A study was made on the effect of changes in arterial pulse pressure per se on catecholamine secretion in the anesthetized dog. "Elasticity" bottles were inserted bilaterally in the common carotid arteries in order to change the magnitude of the pulse pressure in the carotid sinus areas without changing the mean arterial blood pressure. It was observed that a marked decrease in the pulse pressure resulted in significant increases in heart rate ( P < 0.005) and catecholamine plasma levels ( P < 0.005). The mechanism and role of this increase in plasma levels of catecholamines are discussed.


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