In humans, cardiovascular disease begins in young adulthood and is more prevalent in males than females. However, little is known about vascular function during transition to adulthood in males. The aim of this study was to define changes in production of endothelium-derived nitric oxide (NO) and coronary arterial responses during puberty. Plasma was collected from juvenile (2-3 mo of age) and adult (5-6 mo of age) male pigs (n = 8/group) for measurement of NO, and aortic endothelial cells were collected for measurement of mRNA and protein for endothelial NO synthase (eNOS). Although plasma NO was higher in juvenile (67.0 +/- 25.6 microM) than in adult (15.0 +/- 7.1 microM) male pigs, eNOS protein was similar in both groups. However, levels of mRNA for eNOS were lower in aortic endothelial cells from juvenile pigs. In rings of coronary arteries suspended in organ chambers for measurement of isometric force and contracted with PGF2alpha, relaxations to an alpha2-adrenergic agonist were significantly inhibited by indomethacin only in juvenile pigs [EC50 (-log M), 6.7 +/- 0.3 with indomethacin and 7.7 +/- 0.3 under control conditions]. NG-monomethyl-l-arginine (l-NMMA) inhibited relaxations in both groups. On the contrary, in the presence of indomethacin, relaxations to bradykinin were inhibited by l-NMMA only in arteries from adult pigs [EC50 (-log M), 8.9 +/- 0.3 with indomethacin and 8.6 +/- 0.3 with addition of l-NMMA]. These results suggest that hormonal changes associated with sexual maturity may affect posttranscriptional and/or translational regulation of eNOS protein and result in lower plasma NO in adult male pigs. In addition, endothelium-derived inhibitory cyclooxygenase products seem to predominate in juveniles.

Miller. Effect of puberty on coronary arteries from female pigs.

The activity of trovafloxacin was compared with those of vancomycin and penicillin in a model of Streptococcus sanguis species group (trovafloxacin MIC, 0.125 g/ml) and Streptococcus mitis species group (trovafloxacin MIC, 0.125 g/ml) experimental endocarditis. Rabbits with catheter-induced aortic valve vegetations were given no treatment, trovafloxacin at 15 mg/kg of body weight three times a day (t.i.d.), vancomycin at 15 mg/kg twice a day, or penicillin at 1.2 ؋ 10 6 IU t.i.d. After 3 days of treatment, the animals were sacrificed; cardiac valve vegetations were aseptically removed and cultured quantitatively. Penicillin was as active as vancomycin as measured by in vivo clearance of bacteria. Trovafloxacin was less active (P < 0.05) than vancomycin or penicillin against S. sanguis species group infection but had similar efficacy against S. mitis species group infection. Quinolones, despite MICs in the susceptible range, may not be active for serious infections caused by some viridans group streptococci.Trovafloxacin, a fluoroquinolone antimicrobial agent, has activity in vitro against many gram-positive cocci which is superior to that of several other quinolone antimicrobial agents (2). This activity includes activity against viridans group streptococci (2). Viridans group streptococci are the etiological agents in 30 to 40% of cases of native valve endocarditis (7). Patients with viridans group streptococcal endocarditis receive parenteral therapy with either penicillin G or ceftriaxone with or without an aminoglycoside, or with vancomycin administered alone (8). The potential role of trovafloxacin and of other new orally administered fluoroquinolones for the treatment of viridans group streptococcal endocarditis or other serious viridans group streptococcal infection is unknown. An oral antimicrobial regimen for the treatment of such infections in compliant patients would be convenient, would eliminate potential complications related to the use of intravenous therapy, and would likely be cost-effective.The purpose of our study was to investigate whether the activity in vitro of trovafloxacin against viridans group streptococci is predictive of activity in vivo in a rabbit model of experimental endocarditis.(This study was reported in part at the 37th Interscience Conference on Antimicrobial Agents and Chemotherapy, Toronto, Canada, 28 September to 1 October 1997.)Trovafloxacin was obtained from Pfizer (Groton, Conn.), vancomycin hydrochloride was obtained from Lederle (Wayne, N.J.), and penicillin was obtained from Wyeth-Ayerst (Philadelphia, Pa.).MICs for 50 viridans group streptococcal isolates obtained from patients with infection, including 30 from patients with infective endocarditis, were determined by a standard microtube dilution assay, and minimum bactericidal concentrations (MBCs) were determined with a 0.1-ml subculture onto blood agar plates (6).The trovafloxacin MIC at which 90% of the isolates were inhibited (MIC 90 ) was 0.25 g/ml (range, Յ0.125 to 0.6 g/ml), and the trovafloxacin MBC at whi...

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