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Biomedical subjects

B L Short

Publications and source records attributed to B L Short.

84 records · Page 5Linked to original sources
PubMed1983

Rat intraperitoneal sepsis--a clinically relevant model.

The pathologic changes in septic shock, a disease state involving several hemodynamic and metabolic parameters, are not completely understood. Because research on animals can provide information vital to treating disease in humans, and because of the increasing constraints on clinical trials with humans, a clinically relevant animal sepsis model has been developed using adult male Sprague-Dawley rats. Sepsis was induced in large numbers of rats by IP injections of discrete quantities of live E coli organisms. The following elements were measured at specific times: MAP, CO, CVP, WBC, platelets, hemoglobin, hematocrit, PT, PTT, fibrinogen, clotting factors, glucose, blood gases, Ca++, Mg++, and TSP. The study shows that the model is easily replicated and relatively inexpensive, and that it can be used for detailed study in rats of several of the pathophysiological states characteristic of sepsis in humans.

Animals↗
PubMed1983

Thromboxane synthetase inhibitors in septic shock.

Thromboxane (TX) has been reported to cause mortality in endotoxin or septic shock. Cyclooxygenase inhibition improves survival in gram-negative or gram-positive shock. The exact level in the prostaglandin system of which the protection occurs is unknown. This study was designed to compare the effects of a cyclooxygenase inhibitor (indomethacin, IND) to a thromboxane synthetase inhibitor (IMI) on survival and on the production of Tx and prostacyclin (PGI2) in a clinically relevant rat gram-negative sepsis model. Three groups were studied: 1) control (N = 35) animals received E coli only; 2) IND (N = 35) treated animals received 3 mg/kg IP; 3) IMI (N = 35) treated animals received 30 mg/kg IP. All drugs were given 1 h after an IP injection of E coli (LD70) organisms. In this model only IND significantly improved survival. IND and IMI significantly blocked the production of Tx seen in septic shock. IND blocked PGI2 production whereas IMI increased the production. These results show that Tx may not be important in the irreversible stages of shock. Shunting prostaglandin production to PGI2 with thromboxane synthetase inhibitors needs to be considered when using this group of compounds. The mechanism of protection by IND remains unknown.

Animals↗
PubMed1982

Improved survival in the suckling rat model of group B streptococcal sepsis after treatment with nonsteroidal anti-inflammatory drugs.

The nonsteroidal anti-inflammatory drugs, indomethacin and ibuprofen, have been shown to increase survival in various animal models of Gram-negative or endotoxin shock. To evaluate the use of these drugs in group B streptococcal sepsis, a clinically similar disease state, a newborn suckling rat model (4 to 5 days old) designed to simulate early-onset group B streptococcal sepsis was used. Sepsis was induced by a subcutaneous injection of group B streptococcal organisms (type III). A mortality ranging from 30% to 90% was used for the study. Indomethacin (3 mg/kg) or ibuprofen (4 mg/kg) treatment was administered by an intraperitoneal injection either at the time of the bacterial injection or after bacteremia (four hours) had occurred. Indomethacin clearly improved survival rates, even when given after bacteremia. Ibuprofen also clearly increased survival when given at the same time as the bacterial injection. Ibuprofen was more effective than indomethacin in the high mortality model (lethal dose for 90% survival of group). These drugs alter mechanisms that may be important in the irreversibility of sepsis and they may become useful adjuvants to our present treatment of early onset group B streptococcal sepsis.

Animals↗
PubMed1981

Indomethacin improves survival in gram-negative sepsis.

A clinically relevant rat model of peritoneal sepsis was developed through the use of (a) intraperitoneal insertion of rat fecal pellets or (b) live E. coli intraperitoneal injections. Therapy with indomethacin and lidocaine were evaluated in this model. Indomethacin alone, or in combination with appropriate antibiotics, significantly improved survival. Lidocaine did not show an increase in survival. These findings suggest that indomethacin may be beneficial in treatment of human sepsis.

Animals↗
PubMed1979

The effect of methylprednisolone on hepatic oxygen supply and plasma lactate and glucose in endotoxemia.

This study was designed to determine the effect of methylprednisolone on the profile of hepatic oxygen supply and selected blood parameters in fasted, male rats administered an LD85 dosage of E coli endotoxin intraperitoneally. Mortality rates within 24 hours were 85% in rats receiving endotoxin only, 9% in rats receiving a 30 mg/kg dosage of methylprednisolone intraarterially one hour subsequent to endotoxin insult, and 0% in methylprednisolone controls. Beginning with the fourth hour, untreated endotoxin rats had significantly higher heart rates and lower plasma glucose; by the sixth or eighth hour there was significantly greater hypocapnia, lower blood pH, and higher plasma lactate levels in comparison to endotoxic rats receiving methylprednisolone. In addition, mean hepatic pO2 between the sixth and seventh hours was 2.6 mm Hg in endotoxic rats, 10.6 mm Hg in endotoxic methylprednisolone rats, and 17.7 mm Hg in methylprednisolone controls. Methylprednisolone controls showed a steady increase of plasma glucose levels through eight hours but were otherwise stable. Maintenance of hepatic circulation is cited as the probable basis for differences of morbidity and mortality between treated and glucocorticoid-treated endotoxic rats.

Animals↗
PubMed1978

Hepatic oxygen supply and plasma lactate and glucose in endotoxic shock.

Hepatic oxygen supply and selected blood parameters were recorded in fasted male rates given 20--30 mg/kg Escherichia coli endotoxin intraperitoneally. Mortality was 70% within 24 hours. Measurements during the initial eight hours postendotoxin recorded no differences of hematocrit, systemic arterial pressure, or arterial pO2 between survivors and eventual nonsurvivors. However, by the sixth or eighth hour nonsurvivors showed significantly higher plasma lactate, lower plasma glucose and blood pH, and a greater degree of hypocapnea. In addition, a mean hepatic pO2 had decreased from 25.2 mm Hg during the control to 3.8 mm Hg after six hours. A decline of hepatic oxygen supply also occurred in surviving rats but was significantly less severe. Control rats showed a mild degree of respiratory alkalosis but were otherwise stable over eight hours. The relationship of hepatic oxygen supply to differences of plasma lactate and glucose is discussed. Failure of hepatic circulation is cited as the probable cause of extensive liver anoxia and related developments in nonsurviving endotoxic rats.

Acid-Base Equilibrium↗
PubMed1977

Role of colonic bacteria in the pathophysiology of fecal peritonitis.

This study was designed to clarify the role of colonic bacteria in the reactions accompanying fecal peritonitis. Rats were subjected to septic or nonseptic peritonitis induced by fresh fecal suspensions or suspensions pretreated with heat or antibiotic. Measurements during 8 hr in rats with septic peritonitis recorded bacteremia, hypoglycemia dn progressive hemoconcentration, lactacidemia, and hypocapnea. Mortality was 100% by 24 hr. Nonseptic peritonitis produced significantly lesser degrees of hemoconcentration and hypocapnea. Plasma lactate remained in control ranges while plasma glucose concentrations increased slightly. Mortality was 5% in 24 hr. Parameters in control rats were stable over 8 hr. Hepatic oxygen supply was estimated in each group by multiple platinum wire electrodes. Severe hepatic hypoxia was recorded by 6 hr in rats with septic peritonitis. By contrast, nonseptic peritonitis caused a comparatively mild degree of hypoxia. The pathophysiologic developments in septic rats appear to be largely the result of hypovolemia induced by colonic bacteria. Administration of a colloid solution was effective in preventing its development.

Animals↗
PubMedDate not supplied

Aluminum toxicity and albumin.

During a study of priming solutions for extracorporeal membrane oxygenation (ECMO) in the intensive care nursery, it was discovered that those solutions using certain brands of 25% albumin contained aluminum levels within the toxic range. When the brand was changed to a brand known to have a lower aluminum (Al) content, a marked drop in priming solution Al levels was measured. The heat exchanger was examined as a possible source of soluble Al. No evidence of elevated Al levels was found in fluids perfusing this heat exchanger when compared with a stainless steel heat exchanger. The Al content of various blood products was evaluated along with various brands of 5% albumin and 25% albumin.

Albumins↗
PubMedDate not supplied

Maximum blood flow rates for arterial cannulae used in neonatal ECMO.

The arterial cannulae used in neonatal ECMO cause hemolysis and red blood cell damage at elevated blood flows. Hemolysis in extracorporeal circuits has been found to occur with shear stress greater than 132 dynes/cm2, turbulence as measured by Reynold's number greater than 1,000, and velocity greater than 120 to 200 cm/sec. These parameters need to be considered when sizing the proper arterial cannula for a required flow rate. In-vitro measurements of the pressure drop across six arterial cannulae at varying flow rates were performed using human blood with a hematocrit of 43%. Shear stress, Reynold's number, velocity, and pressure drop were calculated for each catheter at flow rates from 50 to 1,000 cc/min. The maximum mean flow rate to maintain the shear stress, Reynold's number, velocity, and pressure drop within the accepted range, was determined for each cannula. Recommended maximum blood flow rates for each of the six cannulae are given. Internal diameter, length, and cannula geometry appear to be the factors most affecting the flow achievable without causing red blood cell damage and hemolysis. Ten French Biomedicus, 10 French Cook, and 10 French Elecath arterial cannulae appear best suited to deliver the range of blood flow rates used in neonatal ECMO.

Blood Flow Velocity↗