The effects of pentoxifylline on pulmonary function following smoke inhalation.

Bronchopulmonary injury secondary to smoke inhalation is a significant comorbid factor following major thermal trauma. The present study evaluates the effects of pentoxifylline (PTX) on pulmonary function in an ovine model of inhalation injury. Following smoke exposure to produce a moderate inhalation injury, 16 animals were divided into two groups. Group 1 animals (n = 8) were untreated; Group 2 animals (n = 8) were treated continuously with pentoxifylline following smoke exposure. The animals were observed in the unintubated, awake state for 48 hr. Cardiopulmonary variables and blood gases were measured serially. Ventilation perfusion distribution (VA/Q), analyzed using the multiple inert gas elimination technique, and bronchoalveolar lavage (BAL) were performed at 48 hr. The wet to dry lung weight ratio was measured following necropsy. In Group 2, the progressive hypoxemia observed following smoke inhalation was attenuated with less VA/Q mismatching than in Group 1 (P < 0.05). Pulmonary hypertension secondary to increased vascular resistance was also attenuated in Group 2 (P < 0.05). In BAL fluid, polymorphonuclear leukocytes, total protein content, and conjugated dienes were less in Group 2 than in Group 1 (P < 0.05). Plasma-conjugated diene levels were also lower in Group 2 at 48 hr. Extravascular lung water and decrease in lung compliance were greater in Group 1. There was less morphologic evidence of airway injury in Group 2 compared to Group 1. The improvement of pulmonary function following treatment with PTX suggests that this agent may be useful in the management of smoke inhalation injury.

The effect of elevated levels of thromboxane on host response to tumor.

Previous studies have demonstrated that human malignancies can synthesize large amounts of thromboxane. It has also been reported that thromboxane can significantly alter multiple components of physiologic and immunologic function. We investigated the effect of elevated levels of thromboxane on host response to tumor using multiple rat models, and the long acting thromboxane analogue U-46619. Administration of the thromboxane analogue was not found to significantly alter the growth of primary tumors or peritoneal metastases. The analogue was found to significantly decrease mean survival time with a pulmonary metastases model. The thromboxane analogue failed to alter macrophage cytotoxicity, lymphocyte cytotoxicity, T lymphocyte subset numbers, or lymphocyte blastogenic response. Administration of the thromboxane analogue decreased the rate of lymphocyte metabolism of glucose and decreased lymphocyte intracellular adenosine deaminase activity. In conclusion, elevated thromboxane levels do not appear to alter primary tumor growth or host immune function, but do decrease resistance to pulmonary metastases.

Effect of prostaglandin E in multiple experimental models. VIII. Effect on host response to metastatic tumor.

Prostaglandin E (PGE) is produced by certain tumors and is reported to decrease primary tumor growth. We evaluated its effect in multiple tumor models utilizing a 1 week course of the long acting PGE derivative dimethyl-PGE (dPGE) at a dosage of 100 micrograms/kg/day vs. a lactated Ringers control. For all tumor models, a suspension of 1 x 10(6) colon carcinoma cells were injected into Wistar-Furth rats. When the suspension was injected subcutaneously and the drug was begun at the time of tumor challenge, there was no effect on survival. When the tumor was injected intraperitoneally or intravenously and the drug begun at the time of tumor challenge, dPGE decreased survival time. When the tumor was administered intravenously but dPGE was delayed for 5 days, there was no effect on survival time. When rats were given a 1 week course of dPGE or saline, dPGE was found not to alter natural killer (NK) cell cytotoxicity, macrophage cytotoxicity, spontaneous lymphocyte blastogenesis, or mitogen stimulated blastogenesis. dPGE failed to alter lymphocyte metabolism of glucose in nonstimulated lymphocytes, but decreased the rate of glucose metabolism and adenosine deaminase activity in mitogen stimulated lymphocytes. In conclusion, PGE appears to enhance metastatic growth of tumor lines where it does not alter primary tumor growth. This effect does not appear immunologically mediated.

Alterations in host defense associated with anesthesia and blood transfusions. II. Effect on response to endotoxin.

The effect of blood transfusions and anesthesia on host response to endotoxin was evaluated in multiple Lewis rat models. The rats were randomized to receive A'Sogaloff Cancer Institute rat blood, pentobarbital sodium, or lactated Ringer's solution and, at either 2 or 7 days following administration of these agents, were challenged with intravenous endotoxin. Neither blood transfusions nor anesthesia altered mortality when administered 2 days before endotoxin challenge. However, blood transfusions administered 7 days before endotoxin challenge were found to prolong survival, to prevent endotoxin-induced alterations in T-lymphocyte subsets, and to decrease plasma tumor necrosis factor levels. In conclusion, blood transfusions appear to depress immune function in a beneficial manner in endotoxin shock.

Effect of prostaglandin E in multiple experimental models. IV. Effect on resistance to endotoxin and tumor necrosis factor shock.

Administration of a long-acting prostaglandin E, 16,16-dimethyl-PGE (dPGE), to rats improves their survival of bacterial peritonitis. We examined the mechanism of this protective effect with reference to its interaction with the release of cachectin (TNF). Sixty rats received saline, 20 micrograms/kg dPGE, or 80 micrograms/kg dPGE 12 hr prior to endotoxin and continuing for 48 hr. Survival rates for the saline, 20 micrograms/kg dPGE, and 80 micrograms/kg dPGE groups were 0, 40, and 85%, respectively. Forty rats received saline or 80 micrograms/kg dPGE, with the initial dose being 3 hr following endotoxin challenge and continuing for 48 hr. Survival rates for both groups were 0%. Sixty rats received saline or 80 micrograms/kg dPGE at 12 and 1 hr prior to endotoxin. Two hours after challenge, they were sacrificed and plasma TNF levels were assayed. The plasma TNF level in saline-treated rats was 22.72 +/- 0.83 ng/ml and in the dPGE-treated group, 16.03 +/- 1.13 ng/ml (P less than 0.001).

Effect of blood transfusions on immune function. Part VI. Effect on immunologic response to tumor.

Transfusions are reported to increase the incidence of tumor metastasis in clinical studies and primary tumor growth in animal studies. We evaluated the effect of transfusions on immunologic response to primary and metastatic tumors in multiple rat models. One half of the animals were administered lactated Ringer's solution and one half ACI rat blood at the time of tumor challenge. In 80 rats a slow-growing colon tumor was implanted subcutaneously. At 4 months there were no significant differences in tumor size or leukocyte infiltration of the tumor. Similar results were obtained with a rapidly growing colon cancer. Analysis of T-lymphocyte subpopulations in both groups showed no differences. Rats transfused at the time of intravenous challenge with a suspension of 1 x 10(6) tumor cells had a mean survival time of 38.3 +/- 0.8 days and the control group had a mean survival time of 41.1 +/- 0.8 days (p = 0.016). One week after transfusion, natural killer cell lysis of tumor cells at a 100:1 effector/target cell ratio was 18.0% +/- 1.8% in the transfusion group and 23.0% +/- 1.3% in the control group (p = 0.034). In conclusion, transfusions in multiple rat cancer models did not affect primary tumor growth or the host's immunologic response to it but did significantly impair natural killer cell function and survival with tumor metastases.

Effect of prostaglandin E in multiple experimental models. VII. Effect on resistance to sepsis.

The immunosuppression seen following burn injury has frequently been attributed to elevated prostaglandin E levels. We evaluated the contribution of elevated prostaglandin E levels on susceptibility to infectious complications utilizing multiple mouse models. The administration of 100 micrograms/kg of the long-acting derivative of prostaglandin E, 16,16-dimethyl-prostaglandin E, was found to improve survival in C3/HEN mice challenged with 1 x 10(8) Escherichia coli organisms intraperitoneally. The administration of indomethacin was found to decrease survival in the same model. With C3/HEJ (endotoxin-resistant) mice, indomethacin was found to increase mortality rates in animals challenged with 1 x 10(8), 1 x 10(9) or 1 x 10(10) Escherichia coli organisms. These findings suggest that elevated prostaglandin E levels seen in burn patients may not be responsible for the postburn increased susceptibility to infectious complications.

Effect of prostaglandin E in multiple experimental models. VI. Effect on T-cell subsets.

Burn injuries have been shown to impair immune function. One of the hypotheses for the etiology of the immunosuppression is that burn injuries result in an elevation of prostaglandin E (PGE) levels which then impair leukocyte function. We evaluated the effect of PGE levels on immune function in multiple animal models utilizing T cell subset levels for our immunologic measurements. Elevations in PGE levels were achieved by administering 16,16-dimethyl-prostaglandin E (dPGE) and reductions by administering indomethacin. The animal models included burned rats, burned-septic rats, and nonburned rats. Neither indomethacin nor dPGE administration resulted in alterations of any of the T cell subset populations in our models.

A survey of cats and dogs for fleas: with particular reference to their role as intermediate hosts of Dipylidium caninum.

Three species of fleas, viz. Ctenocephalides felis, Ctenocephalides canis, and Pulex irritans were found in an examination of 81 cats and 48 dogs in Wellington. C. felis was the most prevalent flea in cats, and C. canis predominated in dogs. It is speculated that C. felis, and its primary host the cat, may assume greater medical and veterinary significance than C. canis. In an examination of 1578 fleas for cysticercoids of the dog tapeworm, Dipylidium caninum, all were found negative. These results do not necessarily reflect the availability of cysticercoids in the environment, and the reasons for this are discussed.