dinoprost and Burns

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Burns; Dinoprost; Female; Humans; Male; Middle Aged; Multiple Organ Failure; Thromboxane B2

Major thermal injury is associated with alterations in both pulmonary and systemic vascular resistance. Pulmonary artery hypertension may lead to right heart dysfunction and pulmonary insufficiency. The effect of thermal injury on vascular reactivity is unknown. Increases in circulating vasoactive substances, as well as alterations in vascular smooth muscle receptor activity, have been hypothesized to occur following thermal injury. We have studied aorta and pulmonary artery vascular sensitivity to five agonists in a 35% full-thickness thermal injury rat model. Vascular reactivity was normal to agonists that constrict vascular smooth muscle via receptor-mediated calcium influx. Unresuscitated and resuscitated burn injury resulted in a decrease in peak tension development to prostaglandin F2 alpha (PGF2 alpha) and potassium, agonists whose effects are mediated via membrane depolarization. Fluid resuscitation synchronous with burning did not alter peak tension development in agonists whose actions were mediated via receptor mechanisms. Peak tension development in resuscitated animals to agonists that affect contraction by depolarization remained deficient. To rule out simple blood loss as the etiology for these changes, the experiment was repeated in rats sustaining an acute 25% blood volume loss. Simple hypovolemia induced no changes in aortic or pulmonary vascular sensitivity. We hypothesize that thermal injury may result in a depolarization of vascular smooth muscle membranes altering voltage-dependent calcium channels.

Topics: Animals; Aorta; Bradykinin; Burns; Dinoprost; Male; Muscle, Smooth, Vascular; Norepinephrine; Potassium; Pulmonary Artery; Rats; Rats, Inbred Strains; Serotonin; Vascular Resistance; Vasoconstriction

A group of 30 burn patients with 36-87% total body surface area (TBSA) burns was studied at 24-48 hr postburn. These included studies of (1) autologous and allogeneic mixed-lymphocyte reactions (MLR); (2) the immunoregulatory influence of mitomycin C-treated T cells, non-T cells, and unfractionated peripheral blood lymphocytes (PBL) on allogeneic MLR; and (3) correlation between the proportions of T-cell subsets defined with monoclonal antibodies (OKT4 and OKT8) and autologous MLR. Studies concerning adherent cell production of thromboxane, prostaglandin E2, and prostaglandin F2a and the immunomodulatory effects of Interleukin 1 (IL-1), Interleukin 2 (IL-2), and a prostaglandin inhibitor, WY-18251, on autologous MLR are presented. The autologous mixed-lymphocyte reaction was depressed in 60% of the burn patients tested. This depressed response correlated closely to the extent of third-degree injury (P less than 0.025) and to TBSA injury greater than 60% (P less than 0.025). A linear correlation was observed between the depression in autologous MLR and a decrease in both the percentage of OKT4+ T cells and the OKT4+/OKT8+ ratio. The response of T cells from burn patients in allogeneic MLR was normal. Age, sex, TBSA of the burn, and size of second-degree burn did not correlate with the abnormalities observed in MLR. Mitomycin C-treated mononuclear cells, purified T cells, or non-T cells from burned patients did not demonstrate any suppressive influence on MLR in normals. Monocyte number and arachidonic acid metabolism were investigated. In addition to increased numbers of monocytes following thermal injury, adherent cells produced increased quantities of thromboxane, prostaglandin E2, and prostaglandin F2a. The effects of Interleukin 1, Interleukin 2, and a prostaglandin inhibitor, WY-18251, were studied in autologous MLR (AMLR) of burned and normal patients. Interleukin 1 and WY-18251 did not induce any significant changes in proliferation in burned patients or normal controls. When compared to cultures without exogenous IL-2, an increase in AMLR was observed following the addition of IL-2 to burn patient cultures at Day 6 and Day 7 of culture. Although the addition of IL-2 did increase proliferation in AMLR of normal controls at Day 6 and Day 7, the enhancement observed for the burn patient cultures represented a restoration to the level of normal control cultures without IL-2. A dose-dependent increase in AMLR was observed in T cells isolated from normal

Topics: Adolescent; Adult; Aged; Antibodies, Monoclonal; Benzimidazoles; Burns; Dinoprost; Dinoprostone; Humans; Interleukin-1; Interleukin-2; Lymphocyte Activation; Lymphocyte Culture Test, Mixed; Middle Aged; Monocytes; Phenotype; Prostaglandin Antagonists; Prostaglandins E; Prostaglandins F; T-Lymphocytes; Thromboxanes; Time Factors