Physiologic response to a simplified venovenous perfusion-induced systemic hyperthermia system.

Our original venovenous perfusion-induced systemic hyperthermia (vv-PISH) system appeared to significantly improve the survival of patients with lung cancer, but was too complex with numerous dialysis problems. We tested a simplified vv-PISH circuit that includes the Avalon Elite (Avalon Laboratories, LLC, Rancho Dominguez, CA) double lumen cannula, a modified heat exchanger, a water heater/cooler, and a centrifugal pump. The purpose of this study was to evaluate this simplified vv-PISH system (without hemodialyzer) and to investigate the physiologic response to whole-body hyperthermia in pigs. We tested our vv-PISH circuit in healthy adult female swine (n = 7, 55-68 kg). The therapeutic core temperature (42°C), calculated as mean of rectal, bladder, and esophageal temperatures, was achieved in six swine. A maximum difference of 0.5°C was observed between the individual temperature sensor readings, indicating homogeneous heat distribution. Heart rate and mean arterial pressure were transiently altered, but were safely managed. A significant elevation in pulmonary artery pressure occurred during the heating phase, resulting in death of one pig. In all other pigs, pulmonary artery pressure returned to physiologic values during the therapeutic phase. Arterial blood electrolytes were maintained without the need of a dialyzer. Major organ function was within normal parameters. The simplified vv-PISH circuit reliably delivered the hyperthermic dose with no need of dialysis.

Large-animal models of acute respiratory distress syndrome.

Acute respiratory distress syndrome (ARDS) is characterized by an acute inflammatory response that compromises alveolar-capillary membrane integrity. Clinical symptoms include refractory hypoxemia, noncardiogenic edema, and decreased lung compliance. The purpose of this review is to summarize the different ARDS large-animal models in terms of similarity to the clinical disease and underlying pathophysiology. The repeated lavage, oleic acid, endotoxin, and smoke/burn ARDS models will be discussed in this review. While each model has significant benefits, none is without weaknesses. Thus, the choice of large-animal ARDS model must be carefully considered based upon the study focus and investigative team experience.

Ovine smoke/burn ARDS model: a new ventilator-controlled smoke delivery system.

BACKGROUND: Our current ovine smoke/burn acute respiratory distress syndrome (ARDS) model utilizes a manual bee smoker. This smoke delivery system lacks standardization and reproducibility, with 20% of sheep failing to meet ARDS criteria. Time to reach ARDS criteria and survival time are also variable. The mild volutrauma (15 mL/kg) applied after smoke/burn injury may also fail to induce ARDS within 24 h. We hypothesized that these inconsistencies were associated with the bee smoker and the mild volutrauma. In the current study, we addressed these problems to improve the consistency of the smoke/burn ARDS model. METHODS: Adult female sheep (n = 10) were given a 40% total body surface area third degree cutaneous burn and 48 breaths (4 × 12) of cotton smoke under general anesthesia. A modified ventilator was then used to deliver a precise and consistent smoke volume (tidal volume) to the sheep. Additional barotrauma was induced by pressure control ventilation (40 cm H(2)0). When ARDS criteria (PaO(2)/FiO(2) < 200) were met, the ARDS Network low tidal volume ventilation protocol (6-8 mL/kg ideal body weight) was used. RESULTS: Carboxyhemoglobin levels were 81.4% ± 5.6% immediately following smoke injury. All sheep met ARDS criteria within 24 h (12.5 ± 4.9 h). Mean survival time post-injury was 62.1 ± 26.4 h. White blood cells and granulocytes were significantly elevated at 24 h post-smoke/burn injury. Lung tissue at necropsy was consistent with ARDS. CONCLUSIONS: The refinements made to the original ovine smoke/burn ARDS model produce a more reliable time to ARDS onset, injury severity, and time of death.

In vivo examination of hydroxyurea and the novel ribonucleotide reductase inhibitors trimidox and didox in combination with the reverse transcriptase inhibitor abacavir: suppression of retrovirus-induced immunodeficiency disease.

Inhibition of ribonucleotide reductase (RR) has gained attention as a potential strategy for HIV-1 therapy through the success of hydroxyurea (HU) to potentiate the activity of the nucleoside reverse transcriptase inhibitor (NRTI) didanosine (ddI) in clinical trials. However, the use of HU has been limited by its development of hematopoietic toxicity. In this study, the novel RR inhibitors didox (DX; 3,4-dihydroxybenzohydroxamic acid), and trimidox (TX; 3,4,5-trihydroxybenzamidoxime) were evaluated along with HU for anti-retroviral efficacy in LPBM5-induced retro-viral disease (MAIDS) both as monotherapeutic regimens and in combination with the guanine containing NRTI abacavir (ABC). Anti-retroviral drug efficacy was determined by measuring inhibition of splenomegaly, hypergammaglobulinemia, and splenic levels of proviral DNA. In this study, all RRIs tested showed the ability to improve the efficacy of ABC in the MAIDS model by reducing splenomegaly, hypergammaglobulinemia, and splenic proviral DNA levels.