Contribution of Kinins to Endotoxin Shock in Unanesthetized Rhesus Monkeys

Nies, Alan S.; Forsyth, Ralph P.; Williams, Hibbard E.; Melmon, Kenneth L.

doi:10.1161/01.res.22.2.155

Cited by 135 publications

(55 citation statements)

References 19 publications

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“…Un-der sterile conditions, a series of three thoracotomies were performed on nine healthy female Suffolk sheep weighing [22][23][24][25][26][27] kg. An intravenous dose of pentobarbital (10)(11)(12)(13)(14)(15) mg/kg) was given to facilitate endotracheal intubation.…”

Section: Methodsmentioning

confidence: 99%

Bradykinin Production and Increased Pulmonary Endothelial Permeability during Acute Respiratory Failure in Unanesthetized Sheep

O’Brodovich¹,

Stalcup²,

Pang³

et al. 1981

J. Clin. Invest.

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A B S T R A C T To investigate mechanisms of pulmonary edema in respiratory failure, we studied unanesthetized sheep with vascular catheters, pleural balloons, and chronic lung lymph fistulas. Animals breathed either a hypercapnic-enriched oxygen (n = 5) or a hypercapnic-hypoxic (n = 5) gas mixture for 2 h. Every 15 min blood gases, pressures, cardiac output, lymph flow (Qlym), plasma and lymph albumin (mol wt, 70,000), IgG (mol wt, 150,000), IgM (mol wt, 900,000), and blood bradykinin concentrations were determined. In both groups, cardiac output and pulmonary arterial pressures increased, whereas left atrial pressures were unchanged. Acidosis alone (arterial pH = 7.16, Paco2 = 81 mm Hg, Pao2 = 250 mm Hg) resulted in a doubling of lymph flow, a small increase in protein flux, and a decrease in lymph to plasma protein concentration (L/P) ratio for all three proteins. Acidotic-hypoxic animals (arterial pH = 7.16, Paco2 = 84 mm Hg, Pao2 = 48 mm Hg) tripled Qlym. In these animals the increase in lymphatic flux of albumin, IgG, and IgM was significantly (P < 0.05) greater than that seen in either the acidosis alone group or in animals where left atrial pressures were elevated (n = 5; P < 0.05). Also, their percent increase in flux of the large protein (IgM) was greater than for the small protein (albumin) (P < 0.05). With acidosis alone, only pulmonary arterial bradykinin concentration increased (1.27+0.25 ng/ml SE), whereas acidosis plus hypoxia elevated both pulmonary arterial bradykinin

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Section: Methodsmentioning

confidence: 99%

Bradykinin Production and Increased Pulmonary Endothelial Permeability during Acute Respiratory Failure in Unanesthetized Sheep

O’Brodovich¹,

Stalcup²,

Pang³

et al. 1981

J. Clin. Invest.

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“…Other methods of measuring respiration in unanesthetized monkeys requires restraint in a primate chair or other type of movement restriction (Wettstein et al, 1990;Nies et al, 1968), which inevitably leads to significant stress which affects the vital functions. To address this issue, we developed a whole-body plethysmograph that permits simultaneous measurement of the respiration rate, tidal volume, and minute volume in freely mobile monkeys while keeping the stress to a minimum.…”

Section: Introductionmentioning

confidence: 99%

Measurement of respiratory function using whole-body plethysmography in unanesthetized and unrestrained nonhuman primates

et al. 2010

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-Extended term, continuous measurement and observation of drug responses were performed to examine the feasibility of a custom-made whole-body plethysmograph for measuring respiratory function in unanesthetized, unrestrained monkeys. Using this apparatus, respiratory function (respiration rate, tidal volume, and minute volume) was observed for 23 hr in unanesthetized, unrestrained cynomolgus monkeys (Macaca fascicularis). The respiration rate, tidal volume, and minute volume in the light period (7:00 to 19:00) reached approximately 30% to 50% higher values than in the dark period (19:00 to 7:00), thus clearly exhibiting circadian variation in the cynomolgus monkey respiratory functions. Administration of morphine (10 mg/kg, s.c.) resulted in sustained reduction in tidal volume and minute volume, and ketamine (30 mg/kg [sub-anesthetic dose], i.m.) also produced sustained reduction in respiration rate, tidal volume, and minute volume. With dimorpholamine (1 mg/kg, i.v.) or caffeine (10 mg/kg, s.c.), respiration rate, tidal volume, and minute volume increased. Physiological saline (1 ml/kg, s.c. and 0.1 ml/ kg, i.v.) and chlorpromazine (10 mg/kg, s.c.) produced no clear-cut changes in respiration rate, tidal volume, or minute volume. From the above results, we conclude that our custom-made whole-body plethysmograph is useful for measuring respiratory function in unanesthetized and unrestrained monkeys.

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“…Endotoxemia increases plasma protease activity ( 13-17) and promotes the activation ofthe blood contact system contributing to disseminated intravascular coagulation, hypotension, and neutrophil activation ( 18). It appears that endotoxin activates the coagulation through both a direct effect and by influencing endothelial cell function (19)(20)(21)(22).…”

Section: Introductionmentioning

confidence: 99%

Endotoxin-induced pulmonary dysfunction is prevented by C1-esterase inhibitor.

Guerrero

Velasco²,

Rodriguez³

et al. 1993

J. Clin. Invest.

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In septic shock, hypotension, disseminated intravascular coagulation, and neutrophil activation are related to the activation of the blood coagulation contact system. This study evaluates in dogs the effect of the Cl-esterase inhibitor (C1-INH), a main inhibitor of the blood coagulation contact system, on the cardiovascular and respiratory dysfunction associated with endotoxic shock. Two groups were included: controls, which received Escherichia coli endotoxin, and a C1-INH group in which Cl-INH was infused before E. coli endotoxin administration.In both groups, endotoxin produced hypodynamic shock; however, the decrease in the systolic index and the ventricular systolic work indexes were greater in controls than the C1-INH group. In controls, the arterial 02 partial pressure decreased by 30% and the alveolo-arterial 02 difference increased by 625%, these parameters remained unchanged in the C1-INH group. Hypoxemia was associated with increased intrapulmonary shunt, decreased blood coagulation contact factors, and decreased C3c. In contrast, C1-INH administration prevented endotoxin-induced hypoxemia, the increase in intrapulmonary shunt, and the decrease in blood coagulation contact factors.This study shows that, in dogs with endotoxic shock, pulmonary dysfunction is associated with an activation of the blood coagulation contact phase system. An inhibition of this system by C1-INH prevented the hypoxemia induced by endotoxic shock. (J. Clin. Invest. 1993.91:2754-2760

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Contribution of Kinins to Endotoxin Shock in Unanesthetized Rhesus Monkeys

Cited by 135 publications

References 19 publications

Bradykinin Production and Increased Pulmonary Endothelial Permeability during Acute Respiratory Failure in Unanesthetized Sheep

Bradykinin Production and Increased Pulmonary Endothelial Permeability during Acute Respiratory Failure in Unanesthetized Sheep

Measurement of respiratory function using whole-body plethysmography in unanesthetized and unrestrained nonhuman primates

Endotoxin-induced pulmonary dysfunction is prevented by C1-esterase inhibitor.

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