Effects of Methylprednisolone on the Response to Group B Streptococcal Toxin in Sheep

Rojas, Jorge; Palme, Charlotte; Ogletree, Martin L.; Hellerqvist, Carl G.; Brigham, Kenneth L.; Stahlman, Mildred T.

doi:10.1203/00006450-198411000-00017

Cited by 10 publications

(13 citation statements)

References 16 publications

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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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Section: Resultsmentioning

confidence: 99%

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

et al. 1988

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“…Protein content of blood and lymph was analyzed by a modified biuret method on an automated analysis system (Auto Analyzer Technicon Instruments Corp., Tarrytown, NY). TXB2 and 6-keto-prostaglandin F,, concentrations in lung lymph were measured with a radioimmunoassay as previously described in detail (6). Arterial blood gas determinations were made with a blood gas analyzer (Corning model 158, Corning Medical and Scientific, Medfield, MA).…”

Section: Methodsmentioning

confidence: 99%

“…Leukopenia and increased lymph protein clearance following GBS toxin can be blocked by pretreatment with methylprednisolone (6). Granulocytes have, therefore, been implicated as mediators of the vascular damage (4).…”

mentioning

confidence: 99%

“…Severe disease presents with respiratory failure, leukopenia, and cardiovascular collapse. Isolation of a toxin from type 111 GBS cultures obtained from an infant who died with GBS pneumonia, has provided a tool for studies of the pathophysiology involved in this disease (2)(3)(4)(5)(6). Infusion of this toxin into sheep causes a Zphase reaction with initial pulmonary hypertension associated with tachypnea, chills, and fever, followed by a second phase characterized by increased flow of lung lymph, rich in protein, indicating an increased vascular permeability.…”

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confidence: 99%

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The Role of Granulocytes in the Pulmonary Response to Group B Streptococcal Toxin in Young Lambs

et al. 1987

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ABSTRACT. Marked leukopenia and sequestration of granulocytes in the lung are consistently seen in severe early onset group B streptococcal (GBS) disease in human infants. To investigate the role of granulocytes as potential mediators in the pulmonary pathophysiology of this disease, the effects of intravenously administered GBS type 111 toxin were studied in young lambs before and after granulocyte depletion with hydroxyurea. Granulocyte depletion markedly reduced the 4-fold increase in total lung resistance and the decrease in dynamic compliance observed after GBS toxin. Granulocyte depletion significantly attenuated the pulmonary hypertension, hypoxemia and increased minute ventilation present during the first phase of the response (0.5-1 h after GBS toxin). It did not significantly alter the increase in body temperature, the marked increase in lung lymph thromboxane BZ concentrations during the first phase or the increase in lung lymph flow and protein clearance during the second phase of the response (3.5-5 h after GBS toxin). The results indicate that granulocytes are involved as mediators of the changes in lung mechanics seen after GBS toxin infusion in young lambs. Granulocytes contribute to the pulmonary hypertension and decrease in arterial oxygenation, but other mediators appear to be responsible for the injury of the vascular endothelium. (Pediatr Res 21: 159-165, 1987) Abbreviations Cdyn, dynamic compliance GBS, group B streptococcus LIP, lymph/plasma protein ratio P,,, pulmonary artery pressure RIA, resistance to air flow across the lungs TXB2, thromboxane B2 TGV, thoracic gas volume VT, tidal volume Vmi., minute ventilation P,,, pleural pressure V, flow Pa,, airway opening pressure P,,, transpulmonary pressure SG,, specific conductance f, frequency

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“…An increase in lung lymph concentration of TXBZ. which is a stable metabolite of TXA:, coincidcs with the first phasc of thc toxin rcaction (13,14). Prcvcnting TXAZ formation by indomcthacin abolished pulmonary hypcrtcnsion during the first phasc, implying that TXAZ might be one of the mcdiators responsible for the scvcrc hcmodynamic and lung function changcs sccn in the GBS toxic shock syndromc (13).…”

mentioning

confidence: 99%

Thromboxane Receptor Blockade (SQ 29,548) in Group B Streptococcal Toxin Challenge in Young Lambs

et al. 1994

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Effects of Methylprednisolone on the Response to Group B Streptococcal Toxin in Sheep

Cited by 10 publications

References 16 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

The Role of Granulocytes in the Pulmonary Response to Group B Streptococcal Toxin in Young Lambs

Thromboxane Receptor Blockade (SQ 29,548) in Group B Streptococcal Toxin Challenge in Young Lambs

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