Hemodynamic responses of chronically instrumented piglets to bolus injections of group B streptococci.
Group B beta-hemolytic Streptotocci cause pulmonary hypertension when injected into animals and may precipitate the persistent pulmonary hypertension syndrome in infected human neonates. We used chronically instrumented piglets to study the effects of repeated injections of heat-killed group B Streptococcus (GBS) type III. Daily exposure to GBS 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. We 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 as type-specific antibody levels rose during potentiation. It is likely that thromboxane A2 is the effector of the pulmonary and systemic hypertensive responses to GBS injection, because thromboxane inhibition by dazmegrel was as effective as indomethacin in blocking these effects. Thromboxane synthesis blockade may prove useful in management of hemodynamic disturbances accompanying severe bacterial infections in humans.
Philips
J B
JB
Department of Pediatrics, University of Alabama at Birmingham 35294.
Lyrene
R K
RK
Godoy
G
G
Graybar
G
G
Barefield
E
E
Sams
J E
JE
Gray
B M
BM
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D005260:Female; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D007093:Imidazoles / Q000627:therapeutic use; D007213:Indomethacin / Q000627:therapeutic use; D009270:Naloxone / Q000627:therapeutic use; D013290:Streptococcal Infections / Q000150:complications / Q000503:physiopathology*; D013292:Streptococcus agalactiae / Q000276:immunology; D013552:Swine
D000907:Antibodies, Bacterial; D007093:Imidazoles; C039242:dazmegrel; D009270:Naloxone; D007213:Indomethacin