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Biomedical subjects

L T Archer

Publications and source records attributed to L T Archer.

At least 37 records · Page 2Linked to original sources
PubMed1982

Current management of the septic shock patient: experimental basis for treatment.

Experimental research has shown that following the intravenous infusion of animals with bacteria or endotoxin a myriad of adverse vascular events occur resulting in deficient organ perfusion and cell death. The primary goals of therapy for sepsis and septic shock, therefore, should include elimination of the source of infection and/or infectious agents and prevention or reversal of adverse vascular events. The following review describes the evolution of an effective therapy for shock consisting of steroid in combination with antibiotic and discusses its relevance and application for humans in severe sepsis or septic shock.

Animals↗
PubMed1982

Does LD100 E coli shock cause myocardial failure?

We have documented that myocardial dysfunction occurs in canine endotoxin shock and have designed this study to determine the effect of lethal live E coli-induced shock on the myocardium. Small adult heart "donor" dogs (wt range 6-9 kg) were infused with LD100 E coli (N = 12) or saline (N = 16) for 30 minutes. Two hours later, heart transfer surgery was initiated and once completed the isolated working left ventricle was allowed to equilibrate in the extracorporeal circuit of a "support" dog (wt range 22-32 kg). Myocardial performance was then evaluated by changing mean aortic pressure while controlling cardiac output. Three to five hours after E coli infusion, marked myocardial dysfunction occurred in 75% of the hearts as evidenced by increased left ventricular and diastolic pressures and depressed peak positive and negative dP/dt at every mean aortic pressure tested compared with control hearts. Myocardial efficiency and power were depressed, oxygen uptake was elevated, and coronary blood flow was unchanged in E coli-treated compared with control hearts. Data support the presence of heart dysfunction in gram-negative septic shock.

Animals↗
PubMed1981

Effectiveness of steroid/antibiotic treatment in primates administered LD100 Escherichia coli.

Early aggressive therapy with maintenance infusions of methylprednisolone sodium succinate and gentamicin sulfate significantly increases the probability for survival of baboons given LD100 Escherichia coli. The present study was designed to determine if baboons would recover when initiation of treatment was delayed until they had sustained E. coli-induced systemic hypotension for a period of approximately three hours. Sixteen adult baboons were each administered a two-hour infusion of LD100 E. coli. All eight untreated animals died within 42 hours. Five of the eight baboons treated after approximately three hours of hypotension with methylprednisolone sodium succinate and gentamicin sulfate survived. Treated animals had significantly higher blood glucose and insulin levels and lower blood urea nitrogen concentrations than baboons receiving E. coli alone. E. coli blood concentrations were lower in the treated than in the untreated baboon group by the sixth hour (less than 0.02). Heart rates increased in all animals but were not as high in the treated baboons. Both groups experienced similar decreases in mean systemic arterial pressure, PCO2, base excess, leukocyte, lymphocyte, and platelet concentrations, and increases in creatinine and lactate concentrations. Data from the present study indicate that the probability of recovery from shock is significantly increased even when initiation of steroid/antibiotic therapy is postponed until baboons have experienced sustained systemic hypotension.

Animals↗
PubMed1981

Elevated plasma vasopressin concentrations during endotoxin and E. coli shock.

Plasma vasopressin concentrations, measured by radioimmunoassay, were remarkably elevated during endotoxin and E. coli shock. The concentrations were often above 500 pg/ml in dogs and above 300 pg/ml in baboons; they reached 1200 pg/ml in two dogs and 1800 pg/ml in another. Plasma concentration in a quiet, hydrated subject is 4 pg/ml; osmoregulation is maximally effective at 20 pg/ml. Elevation of plasma vasopressin occurred by 15 minutes after beginning infusion of endotoxin or E. coli and reached concentrations of 200-350 pg/ml with a decrease in cardiac output but before hypotension, which suggests decreased thoracic blood volume and decompression of left atrial stretch receptors. Even higher vasopressin levels were associated with a reduction of arterial blood pressure. The typical pattern was an early peak elevation followed by a sustained plateau of plasma vasopressin concentration in dogs and baboons with endotoxin and/or E. coli-induced circulatory shock.

Animals↗
PubMed1981

Does sodium pentobarbital anesthesia compromise clearance of bacteria or survival of dogs in lethal E coli shock?

Recent reports have indicated that circulating leukocytes play a prominent role in promoting survival in endotoxin and live E coli shock. Anesthesia has been reported to compromise host defense by depressing phagocytic activity. This study was designed to determine whether sodium pentobarbital would adversely affect leukocyte concentrations, E coli clearance, blood glucose concentrations, and survival of dogs in lethal E coli shock. A leukocytosis was produced in some dogs using daily sublethal intravenous injections of E coli endotoxin for 3 days. Three groups of dogs were challenged with LD100 E coli: Group A (saline-pretreated, normal leukocyte count, unanesthetized); Group B (endotoxin-pretreated, leukocytotic, anesthetized); and Group C (endotoxin-pretreated, leukocytotic, unanesthetized). Groups B and C reduced circulating E coli concentrations similarly but significantly more than Group A. All animals in Group A died, all in Group C lived, and 67% in Group B lived. The reduction in survival in Group B was probably due to the marked hemoconcentration in the anesthetized dogs which were unable to drink, rather than a compromise of their host defense. Inasmuch as phagocytic activity was similar between anesthetized and unanesthetized dogs, results suggest that barbiturate anesthesia is not deleterious to host defense.

Anesthesia↗
PubMed1981

Survival of primates in lethal septic shock following delayed treatment with steroid.

We recently developed a methylprednisolone sodium succinate (MPSS)/gentamicin sulfate (GS) regimen that prevented death in baboons given a 2-hour infusion of LD100 E coli (J. Surg. Res. 28:151, 1980). Steroid treatment was begun in that study 30 minutes after initiation of E coli. Our current aim was to determine if baboons would survive if MPSs treatment was delayed until all E coli were infused and severe hypotension had ensued. Fourteen lightly anesthetized baboons (P.c. cynocephalus) were administered E. coli and seven were then treated with MPSS and GS for 10 hours. All nontreated baboons died, while six of seven treated animals survived. In the treated group, hypoglycemia and hypoinsulinemia were reversed, tachycardia was reduced and neutrophil recovery was improved. Baboons with delayed MPSS, however, evidenced diminished perfusion and recovered more slowly than those with earlier MPSs treatment. In conclusion, primates in septic shock are clearly protected with delayed steroid/antibiotic therapy.

Animals↗
PubMed1981

Vasopressin release during sepsis and septic shock in baboons and dogs.

Plasma vasopressin concentration was measured by radioimmunoassay in lightly anesthetized baboons and dogs before and during experimental Escherichia coli septic shock. Since vasopressin is a potent vasoconstrictor, and activator of clotting factors and a myocardial depressant, we postulated that, if found in substantial amounts in the plasma, vasopressin may contribute to the physiopathology of the septic shock syndrome. Quite high plasma vasopressin concentrations were found in both baboons and dogs. In the baboons, increased plasma vasopressin concentrations occurred, while mean arterial blood pressure was still within normal limits and remained elevated for as long as 12 hours during septic shock. Plasma vasopressin concentrations of this magnitude have been previously reported only with direct hypothalamic stimulation or after hypotensive shock secondary to hemorrhage.

Animals↗
PubMed1980

Mechanisms of impaired cardiac function by vasopressin.

The mechanisms by which elevated levels of vasopressin (ADH) in man and animals cause serious myocardial dysfunction, evidenced by arrhythmias, reduction in cardiac output and coronary blood flow, are not settled. Experiments were conducted in 16 isolated working left ventricles to examine their metabolic and hemodynamic responses to the infusion of vasopressin and the combination of vasopressin and epinephrine. Contractile performance was evaluated by analysis of positive dP/dt, contractile element velocities, and ventricular work-curves using stroke work/end-diastolic pressure. Relaxation parameters, including negative dP/dt and the early diastolic relaxation time constant, were also studied. Coronary blood flow was reduced 22% or less by vasopressin while cardiac output was maintained at a constant level. Myocardial oxygen consumption, lactate and potassium balances were determined from arterial and coronary sinus concentrations. Vasopressin produced myocardial dysfunction indicated by decrements in contractile and relaxation indices, without evidence of global ischemia. Epinephrine restored the mechanical performance to normal without significant change in coronary blood flow, myocardial oxygen consumption, or lactate and potassium balance.

Animals↗
PubMed1980

Endogenous anticoagulation during extracorporeal perfusion: generation of a heparinlike inhibitor.

Studies were done to define the coagulation defect that develops in hemodynamically stable anesthetized dogs perfused on our arteriovenous extracorporeal system without added heparin. After 45 min, the dogs developed whole blood clotting times (WBCT) greater than 24 h. There was an associated decrease in ADP-induced platelet aggregation and a drop in factor V, VIII, and X levels of 75.8, 33.5, and 46.8%, respectively. Despite an increase in fibrinogen degradation products, there was no significant change in fibrinogen level or platelet count. An inhibitor of thrombin and factor Xa clotting of plasma appeared that was "heparinlike", because it stimulated the inactivation of factor Xa by antithrombin III (ATIII) but not by O-methyl isoureamodified ATIII. Thrombin inhibition by ATIII was also stimulated. The inhibitor was heat stable, adsorbed by BaSO4, and neutralized by protamine. Infusion of protamine sulfate into two perfused dogs neutralized the inhibitor and brought the WBCT from greater than 24 h to less than control. Six dogs developed inhibitor levels equivalent to 0.98 to 6.15 U/ml heparin. Five eviscerated dogs in which the hepatic artery was ligated developed peak plasma inhibitor levels of 3.2 +/- 1.0 U/ml. Thus, the endogenous heparinlike inhibitor is a major contributor to the anticoagulated state induced with our perfusion system and may have an extrahepatic origin.

Animals↗
PubMed1980

Does sodium pentobarbital anesthesia compromise phagocytosis of E coli in vitro?

Recent reports have suggested that anesthesia may weaken host defense mechanisms during shock and depress the activities of circulating leukocytes. The purpose of this study was to assay the effects of sodium pentobarbital anesthesia on glucose uptake and survival of leukocytes, and mortality of E coli organisms in vitro. In vitro experiments were performed on canine blood before and after the in vivo administration of anesthesia and the in vitro addition of E coli. Glucose uptake in vitro increased equally in blood obtained from either awake or anesthetized dogs following incubation with organisms. Live organism concentrations were similarly reduced before and after anesthesia during a two hour in vitro incubation period. Total neutrophil numbers fell equally after two hours of incubation with or without anesthesia, due to the presence of E coli. These data support the view that a surgical level of anesthesia is not deleterious to circulating phagocytes during E coli-induced shock.

Anesthesia↗
PubMed1979

Prolonged shock in the monkey following live E coli organism infusion.

Responses of the rhesus monkey to the administration of live Escherichia coli organisms during an observation of 0--27 hours were studied. Nine monkeys were infused for 30 minutes with live E coli organisms, the dose ranging between 7.6 X 10(9) and 3.0 X 10(11) organisms/kg. Three of nine animals survived for 24 hours or longer. Nonsurvivors demonstrated significant hypotension, hypoglycemia, and hypoinsulinemia, while survivors showed lesser degrees of physiologic derangement. Findings were hepatic sinusoidal fibrin thrombi and hepatocellular damage accompanied by elevated serum enzymes. The kidney did not show glomerular fibrin thrombi; however, tubular lesions were clearly evident and increases in blood urea nitrogen levels and endogenous creatinine were documented. Lungs of animals surviving longer contained fewer polymorphonuclear leukocytes and platelets than were seen in acute shock studies. This study emphasizes the importance of monitoring the nonhuman primate during an extended time period, since many significant pathophysiologic responses occur after eight hours of observation.

Animals↗
PubMed1979

Extracorporeal perfusion without anticoagulation and the response to endotoxin.

The results of this study show that an extracorporeal perfusion system without anticoagulation can be established in the dog under certain conditions. The exact mechanisms merit further investigation. It also points to a model to study the effects of endotoxin without heparin interference and as another model for studying the canine blood coagulation system.

Animals↗
PubMed1979

Effects of methylprednisolone sodium succinate on clearance of live E coli from the peripheral blood of dogs.

Corticosteroids have been reported to potentiate infections, and yet recent clinical and experimental studies have documented their therapeutic effectiveness in both septic and endotoxin shock. This study was designed to determine if methylprednisolone sodium succinate (MP) affects the clearance of live E coli organisms from peripheral blood of dogs. The experimental group was pretreated with 30 mg/kg of MP, and controls received equal volumes of saline. Both control and MP-pretreated dogs significantly reduced the number of E coli in peripheral blood by almost two orders of magnitude; however, there was no significant difference in clearance of E coli organisms between the two groups. An initial leukopenia occurred in both groups after E coli injections; however, the subsequent development of leukocytosis in the MP group was significantly greater at +6 hours. Rectal temperatures were higher in the MP group from +1 through +4 hours than in the controls. Hyperglycemia developed initially in both groups, followed by a progressive hypoglycemia, with survivors returning to near normal blood glucose concentrations. Hemoconcentration occurred in both groups, with higher hematocrits being associated with mortality. Results support the view that methylprednisolone sodium succinate does not affect the clearance of live E coli organisms.

Animals↗