Studies on Group B β-Hemolytic Streptococcus. II. Effects on Pulmonary Hemodynamics and Vascular Permeability in Unanesthetized Sheep

Rojas, Jorge; Green, Robert S.; Hellerqvist, Carl G.; Olegård, R; Brigham, Kenneth L.; Stahlman, Mildred T.

doi:10.1203/00006450-198106000-00003

Cited by 68 publications

(49 citation statements)

References 18 publications

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“…According to this "metabolic poison" hypothesis, hemodynamic alterations need not be invoked to account for the development of acidosis in sepsis. This view is consistent with observations in adults with "warm" or high-output sepsis, where Q 0 2 appears not to limit VOz, yet acidosis develops (18)(19)(20)27 "ciitical Q02"; i.e. sepsis increases the value of Q02 below which aerobic metabolism cannot be sustained (cf.…”

Section: Discussionsupporting

confidence: 79%

“…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). Further, we have noted no elevation of CVP during GBS infusion in piglets, suggesting that right ventricular failure does not occur despite markedly elevated pulmonary artery pressures observed in septic piglets.…”

Section: Discussionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 79%

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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“…The pulmonary hypertension reflects an increase in pulmonary vascular resistance, which impairs exchange of oxygen and carbon dioxide. Infusion of live or heat-killed GBS into sheep promptly induces pulmonary hypertension, with little or no effect on systemic pressure (4). This response has been reproduced by many investigators, who also established that the pulmonary hypertension is not a consequence of simple embolization because infusion of latex beads of the same size as GBS caused no change in pulmonary physiology (5).…”

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confidence: 71%

Group B streptococcal phospholipid causes pulmonary hypertension

Curtis

Kim

Wehr

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

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Group B Streptococcus is the most common cause of bacterial infection in the newborn. Infection in many cases causes persistent pulmonary hypertension, which impairs gas exchange in the lung. We purified the bacterial components causing pulmonary hypertension and identified them as cardiolipin and phosphatidylglycerol. Synthetic cardiolipin or phosphatidylglycerol also induced pulmonary hypertension in lambs. The recognition that bacterial phospholipids may cause pulmonary hypertension in newborns with Group B streptococcal infection opens new avenues for therapeutic intervention.G roup B Streptococcus (GBS) is the most frequent cause of sepsis and meningitis in the human newborn (1). Despite prompt treatment with antibiotics, neonates with GBS infection are often quite ill and the fatality rate is 5% (2). Respiratory distress, a prominent sign in these babies, is caused by pulmonary hypertension induced by the GBS infection (3). The pulmonary hypertension reflects an increase in pulmonary vascular resistance, which impairs exchange of oxygen and carbon dioxide. Infusion of live or heat-killed GBS into sheep promptly induces pulmonary hypertension, with little or no effect on systemic pressure (4). This response has been reproduced by many investigators, who also established that the pulmonary hypertension is not a consequence of simple embolization because infusion of latex beads of the same size as GBS caused no change in pulmonary physiology (5). The hypertension is mediated by an increase in thromboxane A 2 , so that treatment with cyclooxygenase inhibitors such as indomethacin or with thromboxane synthesis inhibitors prevents or reverses the increase in pulmonary pressure (5, 6). However, the component(s) of GBS that activate thromboxane synthesis are unknown. Guided by bioassays performed in neonatal lambs (7), we undertook the purification and identification of these components, using standard biochemical techniques. Materials and Methods Purification and Analysis of Pulmonary Hypertensive Compounds fromGBS. Biochemical fractionation procedures were linked in series to develop an initial purification protocol, which was modified to give the final protocol described here. At each step, fractions were assayed for pulmonary arterial hypertensive activity in 3-to 12-day-old lambs of Ϸ5 kg, as described (7). We previously demonstrated that pulmonary arterial pressure measurements were a valid surrogate for measurement of pulmonary vascular resistance in this animal model (7). Fractions were infused peripherally into the femoral vein, not directly into the pulmonary artery. Fractions were considered active if they increased pulmonary arterial pressure by at least 50% in at least two lambs tested on different days.GBS type III, strain 878 was grown to mid-or late-log phase (7), washed with sterile normal saline, heat-killed by incubation in a 60°C water bath for 90 min, pelleted by centrifugation, and resuspended in saline to an OD of 2.0 at 650 nm. Heat-killed GBS (3-gm wet weight) were extracted with 40 ml of ...

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“…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). Leukotrienes and/or endorphins, as well as other compounds, may be involved in these later phases of the host response to bacteremia.…”

Section: Resultsmentioning

confidence: 99%

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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Studies on Group B β-Hemolytic Streptococcus. II. Effects on Pulmonary Hemodynamics and Vascular Permeability in Unanesthetized Sheep

Abstract: Pediatr. Res. 15: 899-904 (1981)

Cited by 68 publications

References 18 publications

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

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

Group B streptococcal phospholipid causes pulmonary hypertension

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

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