Porcine models of non-bacterial thrombotic endocarditis (NBTE) and infective endocarditis (IE) caused by Staphylococcus aureus: a preliminary study.

BACKGROUND AND AIM OF THE STUDY: Non-bacterial thrombotic endocarditis (NBTE) and, in particular, infective endocarditis (IE), are serious and potentially life-threatening diseases. An increasingly important agent of human IE is Staphylococcus aureus, which typically causes an acute endocarditis with high mortality. The study aim was to evaluate the pig as a model for non-bacterial as well as S. aureus-associated endocarditis, as these models would have several advantages compared to other laboratory animal models. METHODS: Fourteen animals underwent surgery with placement of a plastic catheter in the left side of the heart. Six of the pigs did not receive a bacterial inoculation and were used to study the development of NBTE. The remaining eight pigs were inoculated intravenously once or twice with S. aureus, 10(5)-10(7) cfu/kg body weight. Two bacterial strains were used: S54F9 (porcine) and NCTC8325-4 (human). Clinical examination, echocardiography and bacterial blood cultures were used to diagnose and monitor the development of endocarditis. Animals were euthanized at between two and 15 days after catheter placement, and tissue samples were collected for bacteriology and histopathology. RESULTS: Pigs inoculated with 10(7) cfu/kg of S. aureus strain S54F9 developed clinical, echocardiographic and pathologic signs of IE. All other pigs, except one, developed NBTE. Serial blood cultures withdrawn after inoculation were positive in animals with IE, and negative in all other animals. CONCLUSION: S. aureus endocarditis was successfully induced in pigs with an indwelling cardiac catheter after intravenous inoculation of 10(7) cfu/kg of S. aureus strain S54F9. The model simulates typical pathological, clinical and diagnostic features seen in the human disease. Furthermore, NBTE was induced in all but one of the pigs without IE. Thus, the pig model can be used in future studies of the pathogenesis, diagnosis and therapy of NBTE and S. aureus endocarditis.

Therapy of haematogenous osteomyelitis--a comparative study in a porcine model and Angolan children.

BACKGROUND: It is generally accepted that surgery is necessary for the proper treatment of chronic haematogenous osteomyelitis (HO) in children. However, the correct timing of surgery and the technique most effective for debridement of infectious bone tissue is debated. Theoretically, large animal models of HO can be used for refinement and testing of surgical protocols. We report, to our knowledge for the first time, a porcine model of HO exposed to surgical treatment together with our surgical experiences with Angolan children suffering from chronic HO. MATERIALS AND METHODS: Surgically-debrided bone tissue from the children and pigs were analyzed microbiologically and histopathologically together with the entire operated bones from the pigs. RESULTS: It was illustrated that surgical intervention on porcine bones with experimentally-induced HO is representative of the handling of the condition in children. The porcine HO model can easily be used for refinement and application of surgical techniques used in order to cure children with HO.

A new technique for modeling of hematogenous osteomyelitis in pigs: inoculation into femoral artery.

A new inoculation technique has been developed and applied in a porcine model of juvenile hematogenous osteomyelitis. Following the success of the model, we describe the inoculation technique in detail to enable its replication in future studies. The technique was based on an anatomical feature of the femoral artery that enables inoculation into the artery using a simple surgical procedure. Inoculation in the femoral artery is advantageous because the localization of lesions constitutes a discriminative model of the naturally occurring hematogenous osteomyelitis in long bones, usually involving femur and tibia in children. The procedure was performed under general anesthesia and consisted of five major steps: (1) Exposure of the right femoral artery, (2) retrograde catheterization, (3) inoculation of bacteria, (4) hemostasis of the arterial puncture site using compression, and (5) suturing of the wound in two layers.

Local osteogenic expression of cyclooxygenase-2 and systemic response in porcine models of osteomyelitis.

It is suggested that cyclooxygenase 2 (COX-2) derived prostaglandins contributes to the progressive bone loss seen in osteomyelitis lesions. In the present study we examined the expression of COX-2 in bones from 23 pigs with experimental osteomyelitis. Osteomyelitis was induced with Staphylococcus aureus and groups of animals were euthanized following 6 h, 12 h, 24 h, 2 days, 5 days, 11 days and 15 days, respectively. Expression of COX-2 was evaluated immunohistochemically and combined with characterization of morphological changes in bone tissue. Furthermore, the serum concentrations of alkaline phosphatase and haptoglobin were measured. Extensive COX-2 expression by osteoblasts was present 2 days after inoculation together with many activated osteoclasts. Simultaneously, the serum concentration of alkaline phosphatase decreased whereas the haptoglobin concentration increased. This is the first in vivo study showing an early wave of COX-2 mediated bone resorption during osteomyelitis. Therefore, treatment aiming to reduce the break down of bone tissue directed by the COX-2 pathway might be suggested early in the course of the disease.