Cardiovascular Changes in Group B Streptococcal Sepsis in the Piglet: Response to Indomethacin and Relationship to Prostacyclin and Thromboxane A2

Runkle, Beatriz; Goldberg, Ronald N.; Streitfeld, Murray M.; Clark, Martin R.; Buron, Elena; Setzer, Emmalee S.; Bancalari, Eduardo

doi:10.1203/00006450-198409000-00014

Cited by 113 publications

(111 citation statements)

References 9 publications

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“…Continued infusion of living GBS organisms into animals has been shown to lead to cardiovascular collapse (3,4). Similar hemodynamic derangements probably occur in infected humans and much of the morbidity and mortality of grampositive septicemia may be due to these phenomena.…”

Section: Resultsmentioning

confidence: 99%

“…However, pulmonary hypertension is only one of several circulatory derangements observed after injection of organisms into animals. Prolonged bacterial infusions ultimately lead to circulatory shock and collapse (3,4). In addition, pulmonary lymph flow and pulmonary vascular permeability to protein increase following GBS infusion, which may lead to pulmonary edema formation (13,14).…”

Section: Resultsmentioning

confidence: 99%

“…Clinically these infants may manifest the persistent pulmonary hypertension syndrome wherein continued right-to-left extrapulmonary shunting occurs because of abnormally elevated pulmonary artery pressure and resistance (1,2). Infusions of GBS into experimental animals have been shown to cause marked hemodynamic alterations in the pulmonary and systemic circulations (3)(4)(5).…”

Section: Anova Analysis Of Variancementioning

confidence: 99%

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Hemodynamic Responses of Chronically Instrumented Piglets to Bolus Injections of Group B Streptococci

et al. 1988

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ABSTRACT. Group B P-hemolytic Streptotocci cause pulmonary hypertension when injected into animals and may precipitate the persistent pulmonary hypertension syndrome in infected human neonates. W e used chronically instrumented piglets to study the effects of repeated injections of heat-killed group B Streptococcus (GBS) type 111. Daily exposure to G B S was associated with a 2-fold or greater potentiation of pulmonary and systemic hypertensive responses after 1 wk. Throughout experimentation, pulmonary pressure changes were more marked than systemic changes. After establishing a dose-response relationship, we chose a control dose that produced intermediate hypertensive responses. W e then evaluated the effects of antibody and various drugs on the hypertensive responses. Preincubation of organisms with rabbit antiserum containing type-specific antibody enhanced the responses. Beta endorphin blockade with naloxone had little or no effect; leukotriene synthesis inhibition also did not affect responses. Both indomethacin, a cyclooxygenase inhibitor, and dazmegrel, a specific thromboxane synthesis inhibitor, blocked the hypertensive responses to GBS. It appears that repeated doses of GBS potentiate the hypertensive responses, a process that we hypothesize may be mediated by development of type-specific antibody a s type-specific antibody levels rose during potentiation. It is likely that thromboxane Az is the effector of the pulmonary and systemic hypertensive responses to GBS injection, because thromboxane inhibition by dazmegrel was a s effective a s indomethacin in blocking these effects. Thromboxane synthesis blockade may prove useful in management of hemodynamic disturbances accompanying severe bacterial infec- It is well known that gram-negative bacterial sepsis and endotoxemia are associated with profound hemodynamic disturbances. More recently, gram-positive bacteria, especially group B Streptococcus, have also been shown to be associated with circulatory disturbances in infected noenates. Clinically these infants may manifest the persistent pulmonary hypertension syndrome wherein continued right-to-left extrapulmonary shunting occurs because of abnormally elevated pulmonary artery pressure and resistance (1,2). Infusions of GBS into experimental animals have been shown to cause marked hemodynamic alterations in the pulmonary and systemic circulations (3-5).We developed a chronically instrumented piglet preparation that permitted repeated injections of heat-killed GBS in conscious animals. We first evaluated the effects of repeated injections of the same organism to test the hypothesis that repeated exposure to GBS was associated with changes in the hypertensive responses. We then attempted to modify the hypertensive responses with immunologic and pharmacologic probes in order to gain insight into the mechanisms underlying these GBSinduced responses. MATERIALS AND METHODSPiglets. Twelve juvenile female piglets weighing 6.8 + 2.1 kg (mean + SD, range 4.4-1 1.8 kg) were anesthetized and mechanically ventilated...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Anova Analysis Of Variancementioning

confidence: 99%

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Hemodynamic Responses of Chronically Instrumented Piglets to Bolus Injections of Group B Streptococci

et al. 1988

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“…6), lambs (19), or piglets (1,3,17,18). We have demonstrated previously that hypovolemia, although a common consequence of sepsis (19,20), is not a hemodynamic prerequisite for reduction of CO or Q 0 2 in septic piglets (1-4).…”

Section: Discussionmentioning

confidence: 99%

Oxygen Delivery, Oxygen Consumption, and Metabolic Acidosis during Group B Streptococcal Sepsis in Piglets

et al. 1987

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ABSTRACT. The development of metabolic acidosis during neonatal sepsis with group B streptococci (GBS) has been attributed to progressive tissue ischemia resulting from reduced oxygen delivery (Q02). Using an animal model of GBS disease, we attempted to test this hypothesis by comparing the development of metabolic acidosis in two groups of piglets with comparably diminished systemic Q 0 2 , one septic and one not. Eighteen anaesthetized piglets were instrumented to observe aortic pressure, cardiac output, arterial and mixed venous blood gases, oxygen content, and hemoglobin concentration. Q 0 2 , oxygen consumption, and oxygen extraction ratio were calculated. Six piglets (group I ) received continuous infusion of live GBS organisms; six piglets (group 2) received continuous infusion of phenylephrine (PE), beginning with 10-pg/kg/min and increasing a s required to match the PE-induced reduction in Q 0 2 to the fall observed in the group 1 (GBS) piglets at each 30-min interval. Group 3 piglets ( n = 6) received 0.9% saline and served a s controls. No differences in either cardiac output or Q 0 2 were noted comparing GBS and P E piglets a t any time interval from 0 -180 minutes. At 120, 150, and 180 minutes, both Q 0 2 and cardiac output were lower in G B S and P E piglets compared to controls. Despite equivalent reductions in cardiac output and Q 0 2 , only GBS piglets developed significant metabolic acidosis, while pH and base deficit for P E piglets did not differ from controls. Oxygen consumption did not differ significantly among the three experimental groups a t any observation time. Oxygen extraction ratio did not differ comparing P E and GBS piglets at any observation time. We conclude that the reduction of Q02 effected by G B S infusion in piglets is not, in itself, sufficient to account for the development of metabolic acidosis during these experiments. (Pediatr Res 22: 509-512, 1987 BD, base deficit PE, phenylephrine PEEP, positive end expiratory pressure PA, pulmonary artery HR, heart rate Hb, hemoglobin ANOVA, 3-way analysis of varianceWe have previously described an animal model of septic shock (1-4) which resembles sepsis in human infants in many aspects (5-10). Using infusion of live GBS in piglets, we have demonstrated that GBS sepsis reduces both systemic and regional blood flow, elevates pulmonary artery pressure, elevates systemic and pulmonary vascular resistance, and is associated with the progressive development of metabolic acidosis.We (2, 4) and others (I I , 12) have speculated that acidosis during neonatal GBS sepsis can been attributed to progressive tissue ischemia resulting from reduced QO*. Using our animal model of GBS disease, we attempted to test this hypothesis by comparing the development of metabolic acidosis in two groups of piglets with comparably diminished systemic QOz, one septic and one not. We report here that septic piglets in whom QO? was reduced by GBS infusion became significantly more acidotic than non-septic piglets whose QOz was reduced by infusion of PE. MATERI...

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“…Rowen and colleagues reported that exposure of human monocytes to GBS induced secretion of leukotriene B 4 [13]. Animal models indicate that additional lipid metabolic products, including the eicosanoids thromboxane A 2 , prostacyclin, and prostaglandin E 2 mediate hemodynamic and other physiological responses in GBS infections [14][15][16][17]. The specific component(s) of GBS and the mechanism(s) responsible for eicosanoid synthesis are not completely understood.…”

Section: Introductionmentioning

confidence: 99%

Induction of cyclooxygenase-2 by human monocytes exposed to group B streptococci

Maloney

Thompson

Hill

et al. 2000

Journal of Leukocyte Biology

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Group B streptococcal (GBS) infections are associated with high morbidity and mortality. The molecular pathways mediating the pathophysiological events in GBS infection are not fully delineated. Cyclooxygenases (COX) are the enzymes that convert arachidonate to active eicosanoids. To identify the effects of GBS on eicosanoid metabolism and regulatory mechanisms, we exposed human monocytes to GBS and found that they secreted prostaglandin E 2 , prostacyclin, and thromboxane A 2 . Exposure to GBS caused monocytes to express COX-2 mRNA and protein in both a time-and concentration-dependent manner that correlated with eicosanoid production. COX-1 protein was unchanged. Addition of the anti-inflammatory cytokines interleukin (

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Cardiovascular Changes in Group B Streptococcal Sepsis in the Piglet: Response to Indomethacin and Relationship to Prostacyclin and Thromboxane A2

Cited by 113 publications

References 9 publications

Hemodynamic Responses of Chronically Instrumented Piglets to Bolus Injections of Group B Streptococci

Hemodynamic Responses of Chronically Instrumented Piglets to Bolus Injections of Group B Streptococci

Oxygen Delivery, Oxygen Consumption, and Metabolic Acidosis during Group B Streptococcal Sepsis in Piglets

Induction of cyclooxygenase-2 by human monocytes exposed to group B streptococci

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