Thromboxane-associated pulmonary hypertension during three types of gram-positive bacteremia in piglets.
Thromboxane-associated pulmonary hypertension occurs in animals during intravenous infusion of group B streptococcus (GBS), a gram-positive neonatal pathogen. We postulated that other gram-positive neonatal pathogens, such as Streptococcus fecalis (ENT) and Staphylococcus epidermidis (S. epi) would also induce increased thromboxane synthesis and pulmonary hypertension when infused into piglets. We observed similar hemodynamic and gas exchange abnormalities during stepwise increases in the dose of GBS, Ent, and S. epi (n = 3, 4, and 4 piglets receiving each bacteria, respectively). Pulmonary vascular resistance increased significantly in the absence of acidosis or reduced arterial or mixed venous pO2 at a dose of 2.5 x 10(8) cfu/kg/h for Ent and S. epi. In 14 additional piglets, pulmonary vascular resistance increased markedly after 60 min of intravenous infusion of 4 +/- 1 x 10(8) cfu/kg/h for each organism (p less than 0.05, GBS: 11.7 +/- 1.8 to 75.6 +/- 18.4 mm Hg/liter/min, Ent: 12.7 +/- 1.7 to 64.9 +/- 10.6 mm Hg/liter/min, S. epi: 10.5 +/- 0.8 to 56.9 +/- 6.0 mm Hg/liter/min), and blood thromboxane B2 levels increased (p less than 0.05, GBS: 30 +/- 10 to 1830 +/- 330 pg/ml, Ent: 20 +/- 7 to 1110 +/- 300 pg/ml, S. epi: 31 +/- 9 to 1260 +/- 350 pg/ml). This dose of each bacteria caused a similar degree of mild arterial hypoxemia (57-66 mm Hg). The thromboxane synthetase inhibitor, dazmegrel, completely reversed pulmonary hypertension, reduced TxB2 levels to near baseline values, and partially reversed arterial hypoxemia despite ongoing bacterial infusion. We conclude that thromboxane-associated pulmonary hypertension occurs in piglets during infusion of different gram-positive neonatal pathogens.
D000818:Animals; D000831:Animals, Newborn; D013293:Enterococcus faecalis; D006439:Hemodynamics; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy / Q000209:etiology*; D007093:Imidazoles / Q000627:therapeutic use; D018805:Sepsis / Q000150:complications* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000097:blood / Q000150:complications*; D013212:Staphylococcus epidermidis; D013290:Streptococcal Infections / Q000097:blood / Q000150:complications*; D013292:Streptococcus agalactiae; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors
D007093:Imidazoles; C039242:dazmegrel; D013929:Thromboxane B2; D013930:Thromboxane-A Synthase