Determination of the minmum effective dosages of praziquantel, albendazole, and mebendazole against Clonorchis sinensis infection in rats

In order to determine the minimum effective dosages of praziquantel, albendazole, and mebendazole against Clonorchis sinensis infection in Sprague-Dawley rats, each rat was infected with 30 metacercariae and treated with one of three drugs. The rats were killed and examined 25 days after praziquantel treatment or 11 days after albendazole or mebendazole treatment. The minimum effective dosages were a single dose of praziquantel 375 mg/kg, albendazole 150 mg/kg, and mebendazole 150 mg/kg. Trials are required to determine whether these dosages are useful in the treatment of human clonorchiasis.     

Comparative study of oltipraz versus praziquantel for treatment of schistosomiasis with intestinal manifestation in the Gabon (Schistosoma intercalatum and S. haematobium)

158 school children from Lambarene and its surroundings suffering from intestinal manifestations of schistosomiasis due to Schistosoma intercalatum, Schistosoma haematobium, or mixed infections were randomly allocated to patient groups to be treated with oltipraz and praziquantel respectively. Oltipraz was tested in three dosage regimens, i.e., 1 X 25 mg/kg, 1 X 35 mg/kg, and 2 X 20 mg/kg and compared to 2 X 30 mg/kg praziquantel in each of the treatment groups. 45 days and 90 days after treatment, the children were thoroughly investigated. Rectoscopy was only performed in part of the children. The number of children with viable egg excretion had significantly dropped after therapy (p less than 0.001). Parasitological cure after 90 days was obtained in 86% of patients treated with 2 X 20 mg oltipraz and 90% of patients treated by praziquantel. A comparative effectiveness was achieved with the other dosage regimens of oltipraz, too. The efficacy of the new schistosomicid oltipraz is identical with that of praziquantel for patients with intestinal manifestation. The rectal biopsies taken 45 days and 90 days after therapy still contained numerous eggs which were mostly calcified or granulated.     

Giardiasis treatment in Turkish children with a single dose of ornidazole

This study was designed to compare the treatment efficacy of single dose of ornidazole with 5 d treatments of ornidazole and metronidazole in children with giardiasis. 175 children, between 2 and 15 y old, whose stool samples were found to be positive for Giardia lamblia cysts and/or trophozoites by either saline-Lugol, formalin-ethyl acetate or trichrome staining, were enrolled in the study. Of these children, 105 were treated with a single dose of ornidazole: 35 with 30 mg/kg, 35 with 25 mg/kg and 35 with 20 mg/kg; 35 were treated with 25 mg/kg per day of ornidazole for 5 d in 2 doses and 35 children were treated with 20 mg/kg per day metronidazole for 7 d in 3 doses. All cases were examined on the 7th, 10th and 14th days after treatment by the same methods; clinical symptoms were also evaluated. Giardia lamblia was eradicated in 34 of 35 (97%), 34 of 35 (97%) and 33 of 35 (94%) patients treated with 30, 25 and 20 mg/kg single doses of ornidazole, respectively. Eradication was achieved in all 35 patients treated with 25 mg/kg per day ornidazole for 5 d and in 31 of 35 (89%) patients treated with metronidazole. There was no statistically significant difference among doses of ornidazole (p > 0.05); however, all ornidazole treatment regimens were significantly more effective than metronidazole treatment (p < 0.05). No important side-effects were detected in any patients and clinical symptoms disappeared in all. Single-dose ornidazole treatment could be considered as a proper and effective alternative method for the treatment of giardiasis in children.     

Protective and curative effects of rifampicin in Acanthamoeba meningitis of the mouse

BALB/c mice inoculated nasally with Acanthamoeba culbertsoni, resulting in amebic encephalitis and death 3-7 days, were treated with rifampicin prophylactically (daily for 2 days with 75 and 100 mg/kg) and after infection (daily for 5 days with doses of 10-100 mg/kg). Prophylactic treatment resulted in full protection against infection, as assessed by absence of symptoms of central nervous system malfunction and negative brain culture 10 days after inoculation. Curative treatment was effective at the same doses; however, at doses of 10, 25, and 50 mg/kg, only two of six animals were free of symptoms and infection.     

Eflornithine treatment of refractory Pneumocystis carinii pneumonia in patients with acquired immunodeficiency syndrome.

Eflornithine was offered as compassionate treatment of 33 episodes of Pneumocystis carinii pneumonia in 31 patients with acquired immunodeficiency syndrome who were intolerant of and/or unresponsive to conventional trimethoprim-sulfamethoxazole or pentamidine therapy. A full course of eflornithine consisted of ten days at 400 mg/kg/d but no more than 30 g/d in four divided intravenous doses, four days at 300 mg/kg/d in four divided intravenous doses, and then up to six weeks at 300 mg/kg/d in four divided oral doses where tolerated. Of 33 patient-episodes, 15 patients were discharged from the hospital without need for supplemental oxygen after receiving ten or more days of parenteral therapy and were classified as responders. Of the 16 episodes classified as treatment failures, death occurred within the first 10 days of therapy in 12, and supplemental oxygen could not be withdrawn in 4. The other two patients left the hospital without need of oxygen after receiving one and six days of treatment with eflornithine and were not considered evaluable for efficacy. The most serious adverse effect was thrombocytopenia, which occurred in 12 of 19 patients treated for ten days or more. Serious bleeding associated with thrombocytopenia was observed in two patients. Other common adverse effects were anorexia, nausea, and diarrhea. Prior to receiving eflornithine, 13 of 15 responders had received ten or more days of conventional therapy without demonstrating clinical improvement. Two had improved while receiving conventional therapy but were switched to eflornithine because of a treatment-limiting adverse effect of standard therapy. These results suggest that eflornithine may be useful as an alternative therapeutic agent for Pneumocystis carinii pneumonia. Studies designed to determine proper dosage, duration of therapy, and efficacy as primary therapy are warranted.     

Efficacy of tinidazole (Fasigyn) in giardiasis by parasitologic, biochemical, and gut transit studies

Twenty patients (18 M, 2 F; age 16-32 yrs) with symptomatic giardiasis were treated with tinidazole: ten each with a dose of 150 mg twice daily for 7 days, and a single dose of 2 g (50 mg/kg). Stool examination by formalin-ether concentration method was carried out before and one month after treatment. Cure was defined as absence of G lamblia in the stools. Fecal fat excretion (100 g load) and D-xylose absorption (5 g load) were measured before treatment and, if abnormal, repeated one month after treatment. Gut transit time was measured before and one month after treatment by giving radio-opaque beads orally and following their progress fluoroscopically to complete elimination. Parasitologically, all 20 patients were cured. Clinically, there was marked to complete relief of symptoms. Concomitantly, there was significant (p less than 0.01) reduction in fecal fat excretion, improvement in D-xylose absorption, and increase in gut transit time.     

Therapeutic effects of exogenous surfactant enriched with dextran in newborn rabbits with respiratory failure induced by airway instillation of albumin

The aim of the study was to investigate lung function and morphology in newborn rabbits with acute respiratory failure induced by airway instillation of albumin and to test whether the therapeutic effect of exogenous modified natural surfactant could be enhanced by addition of dextran. Rabbits (gestational age 29 days) were ventilated with 100% O2 and tidal volume 8-10 ml/kg. Respiratory failure was induced by tracheal instillation of albumin (50 or 100mg/ml; 2 ml/kg) and the instillation was repeated 15 min later. Surfactant (Curosurf, 200mg/kg) with or without addition of dextran (30 mg/ml) was administered 15 min after the second dose of albumin and animals were then ventilated for another 60 min. In one series of experiments, instillation of albumin was followed by administration of diluted Curosurf (40 mg/kg) with or without dextran (30 mg/ml). Animals with initial lung-thorax compliance (CLT)<0.6 ml/kg cm H2O were directly treated with surfactant without previous instillation of albumin. Animals treated with a larger dose of Curosurf (200mg/kg) showed a significant increase in CLT at 60 min with no difference between groups receiving high or low dose of albumin. Addition of dextran to Curosurf at high dose (200mg/kg) reduced the therapeutic response (P<0.05 vs. Curosurf without dextran). After treatment with low-dose Curosurf (40 mg/kg) CLT increased more prominently after Curosurf+dextran than after non-enriched surfactant (P<0.05). Dextran potentiated the treatment effect of Curosurf at suboptimal dose (40 mg/kg) but not at high dose (200mg/kg) in animals with low-grade surfactant deficiency or respiratory failure induced by airway instillation of albumin.     

Effective remission induction of refractory childhood acute nonlymphocytic leukemia by VP-16-213 plus azacitidine

Thirty-eight children and young adults with advanced acute nonlymphocytic leukemia (ANLL) in relapse were treated with VP-16-213 plus azacitidine (5AZ). Each patient had previously received many chemotherapeutic drugs, including anthracyclines and cytarabine. Initially, 16 patients received a 5-day course of VP-16-213 (100 mg/m(2)) daily x 3 days and 5AZ 9150 mg/m(2)) daily x 2 days, repeated after 9-16 days. Since this treatment produced marrow hypoplasia and complete remission (CR) in only one of 16 patients, a more intensive regimen was devised: the remaining 22 patients received a course of VP-16-213 (200 mg/m(2)) daily x 3 days, followed by 5AZ (300 mg/Fm(2)) daily x 2 days, repeated after 1-2 days until the bone marrow became hypoplastic. After two to four courses, 18 patients had marrow hypoplasia and ten of these achieved CR. The proportion of patients achieving CR with the higher doses was significantly greater than that with the initial doses )P less than or equal to 0.05). The toxicity also increased with the higher doses, with major problems due to prolonged pancytopenia. Supportive therapy was required for severe bleeding and infections. We conclude that the intensive treatment with VP-16-213 plus 5AZ can effectively induce remission in patients with refractory advanced acute nonlymphocytic leukemia.     

Treatment of cytomegalovirus pneumonia with ganciclovir and intravenous cytomegalovirus immunoglobulin in patients with bone marrow transplants

STUDY OBJECTIVE: To determine if the combination of ganciclovir and intravenous cytomegalovirus immunoglobulin is effective in patients with cytomegalovirus pneumonia after bone marrow transplant. DESIGN: Consecutive entry trial with treatment for a minimum of 14 days. PATIENTS: Consecutive sample of 25 patients with bone marrow transplants and cytomegalovirus pneumonia after transplant proven by open lung biopsy or bronchoalveolar lavage. Patients with abnormal renal function or concomitant infectious causes of pneumonia, or who were respirator-dependent at diagnosis, were not eligible. INTERVENTIONS: Induction treatment consisted of ganciclovir, 2.5 mg/kg body weight every 8 hours for 14 days, and cytomegalovirus immunoglobulin, 400 mg/kg on days 1, 2, and 7 and 200 mg/kg on day 14. Ganciclovir dosage was adjusted for renal function. Patients who were improved but still symptomatic after 14 days were given maintenance treatment consisting of ganciclovir, 5 mg/kg once daily for an additional 14 days, and immunoglobulin, 200 mg/kg on day 21. Patients with clinical deterioration continued to receive induction doses. Ganciclovir therapy was discontinued if the neutrophil count fell below 500 X 10(6)/L for 2 consecutive days. MEASUREMENT and MAIN RESULTS: Serial tests of renal and liver function, blood counts, and viral cultures of blood, throat, and urine were obtained 3 times a week. Thirteen of twenty-five (52%) patients (95% CI, 31 to 72) survived the initial episode of pneumonia. Viral excretion ceased in 17 of 23 (74%) patients treated more than 96 hours. Proven recurrences of pneumonia occurred in 3 patients and possible recurrences in 2 after treatment was stopped. Three patients developed neutropenia during induction therapy and 6 patients during maintenance therapy. CONCLUSIONS: Survival of 13 (52%) of 25 patients from the initial episode of cytomegalovirus pneumonia with the regimen of ganciclovir and cytomegalovirus immunoglobulin is significantly better (P less than 0.001) than the survival of 13 of 89 (15%) patients using previous antiviral regimens.     

The relapse of Trypanosoma brucei brucei infections after chemotherapy in rabbits

Infections of T. brucei in the rabbit were found to relapse after chemotherapy. The results indicated that 25 mg/kg diminazene aceturate given 3 days after infection resulted in a complete cure but if given 7 days after infection relapses frequently occurred. However, treatment was apparently successful if delayed until 14 or 21 days. Six of the rabbits originally treated with diminazene aceturate on day 7 were treated with suramin 21 days later; in 3 rabbits the infections relapsed. In all rabbits in which drug treatment was not curative, the clinical condition nevertheless improved. An attempt to locate a cryptic focus of infection in rabbits was unsuccessful.     

In vivo blockade of tumor necrosis factor-alpha in patients with rheumatoid arthritis: longterm effects after repeated infusion of chimeric monoclonal antibody cA2

OBJECTIVE: To investigate the longterm consequences of tumor necrosis factor-alpha (TNF-alpha) blockade in patients with rheumatoid arthritis (RA), to compare changes after repeated infusion of cA2 monoclonal antibody with those occurring after the initial treatment, and to investigate significant correlations of cellular or serological changes to the duration of clinical benefit for each patient. METHODS: A clinical trial testing TNF-alpha monoclonal antibody cA2 in treatment of RA showed this therapeutic agent is highly effective. A dosage of 1 mg/kg or 10 mg/kg cA2, given in a single infusion, was compared to placebo. After clinical relapse all patients were (re)treated with 3 or 10 mg/kg cA2. In parallel to this clinical study, we investigated cellular and molecular changes induced by in vivo blockade of TNF-alpha. RESULTS: After an initial transient increase, T lymphocyte counts were not significantly different from starting values throughout the observation period. Monocyte counts as well as serum interleukin 6 (IL-6) and soluble intercellular adhesion molecule 1 (sICAM-1) concentrations remained decreased for several weeks after infusion. After a repeated infusion, increases in numbers of T cells and decreases in monocytes and IL-6 and sICAM-1 concentrations were evident again. Changes in cell counts, however, were smaller, especially in the group initially treated with the low dose (1 mg/kg), despite a higher retreatment dosage of 3 or 10 mg/kg cA2. Similarly, in this group decrease of IL-6 and sICAM-1 concentrations was less pronounced, was delayed to Day 7 after infusion, and lasted for a shorter period than seen after initial treatment. CONCLUSION: We conclude that in vivo TNF-alpha blockade leads to prolonged cellular and serological changes. This effect appears to be less pronounced after repeated infusion of cA2 compared to the initial treatment, mainly in the low dose group.     

Monitoring the therapeutic efficacy of antimalarials against uncomplicated falciparum malaria in Thailand

Increasing antimalarial drug-resistance is an important problem in Thailand. The results of monitoring the antimalarial efficacy are used in decision-making about using antimalarials to treat uncomplicated falciparum malaria in Thailand. In 2002, 552 patients with uncomplicated malaria were treated according to the Thai National Drug Policy, with mefloquine 25 mg/kg plus artesunate 12 mg/kg and primaquine 30 mg in divided doses for 2 days in high-mefloquine-resistant areas; mefloquine 15 mg/kg plus primaquine 30 mg in non- or low-mefloquine-resistant areas; mefloquine 15 mg/kg plus artesunate 12 mg/kg and primaquine 30 mg in divided doses for 2 days or Coartem (6-dose regimen for adult contains 480 mg artemether and 2880 mg lumefantrine) plus primaquine 30 mg given over 3 days in moderate-mefloquine-resistant areas. The study shows that mefloquine, artesunate plus mefloquine, and artemether plus lumefantrine are effective in the treatment of uncomplicated malaria in most areas of Thailand except for Ranong and Kanchanaburi, where the first-line treatment regimen should be revised.     

Chemotherapy of autochthonous myeloid leukemias (Chloroleukemias) in Wistar rats

Summary After injection of 15 mg/kg ethylnitrosourea (ENU) weekly for 15 weeks to adult male Wistar rats (total dose: 225 mg/kg) about 10% of the animals developed myeloid leukemias (chloroleukemias), which resemble the chronic myeloid leukemia in man (CML) (peripheral blood picture, tissue infiltration, chronic course as compared to immature-cell rat leukemias). Monotherapy with busulfan effected no remissions. The median survival time after daily treatment with busulfan was 29.5 days (range: 7–70); it was significantly shorter than that of untreated controls (median: 47.5 days, range: 22–81). After weekly application of 20 mg/kg and 50 mg/kg Cyclophosphamide the median survival time increase to 69.5 (range: 26–114) and 61.5 (range: 20–92) days, respectively. Rate and duration of remissions after repeated weekly single doses of cyclophosphamide were positively correlated with the increase in single dose; the high dose-intermittent treatment with 50 mg/kg CPA/week yielded complete remissions in all treated animals. Despite these remissions, however, no significant increase in survival time could be observed in comparison with untreated controls.The comparability of autochthonous chloroleukemias in the rat with human CML is discussed.     

The effect of N-nitro-L-arginine methyl ester on morphine-induced changes in the plasma corticosterone and testosterone levels in mice.

Effects of the nitric oxide synthase inhibitor, N-nitro-L-arginine methyl ester (L-NAME, 30 mg/kg i.p.), on morphine-induced changes in the plasma corticosterone and testosterone levels were studied in male mice. Acute morphine administration (15 and 30 mg/kg i.p.) enhanced the corticosterone level after 1 and 2 hr (at a dose of 30 mg/kg only). A 4-day treatment with increasing doses of morphine, from 15 to 50 mg/kg i.p., increased the plasma corticosterone concentration at 2 hr after the last injection. Single administration of L-NAME (30 mg/kg i.p.) had no effect on the corticosterone level, whereas its repeated injections (30 mg/kg i.p., twice a day for four days) elevated the hormone concentration at 2 hr after the last dose. Pretreatment of mice with L-NAME enhanced the stimulatory effects of both acute and repeated morphine administration on the corticosterone level. D-NAME (30 mg/kg i.p.), an inactive form of the nitric oxide synthase inhibitor, had no effect on the morphine-induced changes in the corticosterone level. Acute morphine administration had no effect on the plasma testosterone level after 1 or 2 hr, whereas repeated drug injections decreased the hormone concentration after 2 hr. Single or repeated L-NAME administration did not influence the testosterone level in either control or morphine-treated animals. The above results indicate that inhibition of nitric oxide synthase enhances the stimulatory effect of morphine on corticosterone secretion, but does not influence the inhibitory effect of repeated morphine on the plasma testosterone concentration in mice.     

Ambilhar in the treatment of Schistosoma japonicum infection and as an egg suppressant for mass treatment.

Ambilhar or niridazole at a dose of 25 mg per kg body weight for 7 days was found ineffective against Sl japonicum infection. Longer period of treatment for 10 to 14 days gave impressive stool negative conversion and egg reduction rates but with moderately severe reactions, the most alarming of which was hallucination. To minimize toxicity, the daily dose was reduced but given for a longer duration so that the total amount of the drug given per kilogram body weight was approximately the same as the 25 mg pre kg per day for 10 to 14 days. Of the two treatment schedules tried, the 15 mg per kg per day for 24 days was found relatively effective. Although the drug with this treatment regimen was well tolerated, a drop-out of 50.8% was observed. Ambilhar was therefore tried as an egg suppressant. With a 10-day treatment, all patients were again positive after 6 months. Egg reduction rates during the 6 months stool follow-up ranged from 69.8 to 93.5%. Further trials using this dose to be repeated every 3 to 6 months is contemplated.     

Therapy of chronic graft-v-host disease in a rat model

Chronic graft-v-host disease (GVHD) is the most frequent late complication of allogeneic bone marrow (BM) transplant. To test different treatments, we used a rat model of chronic GVHD which clinically, histologically, and immunologically resembles the disease occurring after human marrow transplant. The following treatments were administered: azathioprine 50 mg/kg/day plus prednisone 1 mg/kg/every other day; Cyclosporine (CsA) 30 mg/kg/day; CsA 30 mg/kg/day plus prednisone 1 mg/kg/every other day; thalidomide 50 mg/kg/day; thalidomide 10 mg/kg/day; CsA 10 mg/kg/day; and thalidomide 10 mg/kg/day plus CsA 10 mg/kg/day. All drugs were administered by gavage. Half of the animals (six of 12) treated with azathioprine plus prednisone every other day responded to treatment. The majority of animals (seven of 12) treated with CsA died early. The addition of prednisone every other day did not improve survival. The surviving animals treated with CsA (with or without prednisone) responded to treatment. Half of the animals treated with each of the above regimens had recurrent or progressive disease after therapy was discontinued. Thalidomide treatment was successful in the majority of animals (16 of 18). The addition of low-dose CsA to low-dose thalidomide resulted in a faster rate of response (12.1 +/- 1.8 v 28.2 +/- 1.6 days). We conclude that both thalidomide and thalidomide plus CsA appear promising in this model as treatment for chronic GVHD.     

Assessment of therapeutic efficacy of chloroquine for vivax malaria in Thailand

Chloroquine-resistant Plasmodium vivax has been reported in some Asian countries. In 2003, 161 patients infected with vivax malaria were treated according to the Thai National Drug Policy, with oral chloroquine (approximately 25 mg base/kg body weight, administered over 3 days) followed by primaquine on day 28 (15 mg daily for 14 days). All the patients were initially cured after chloroquine treatment, clearing their parasitemias within 7 days. Only one patient presented with parasitemia at 28 days. These data indicate that chloroquine is still effective for the treatment of patients with vivax malaria in Thailand.     

甲苯达唑、阿苯达唑及其代谢物实验治疗小鼠继发性细粒棘球蚴病的研究

在疗程为10～14d时,甲苯达唑对小鼠继发性细粒棘球蚴病的最低有效剂量为25mg/kg/d,阿苯达唑的为100mg/kg/d。在所用的疗程下,甲苯达唑的剂量较阿笨达唑100～300mg/kg/d低3～11倍时,它们的疗效相仿,但甲苯达唑100mg/kg/d的疗效则优于剂量大l～2倍的阿苯达唑。甲苯达唑与阿苯达唑合并治疗未能明显提高疗效,但此2种药物并用吡喹酮治疗则疗效明显提高。实验证明阿苯达 唑亚砜的疗效优于阿苯达唑,而阿苯达唑用则无效。     

Percutaneous treatment of coronary bifurcations: lesion preparation before provisional bare metal stenting and subsequent immunosuppression with oral prednisone. The IMPRESS-Y study

Aim of the study was to assess the clinical and angiographic efficacy of oral treatment with prednisone at immunosuppressive dosage after percutaneous coronary interventions (PCI) in patients with bifurcation lesions treated with elective bare metal stent (BMS) implantation in the main-branch (MB) and provisional stenting in the side-branch (SB). Twenty-five patients were treated on 29 bifurcation lesions (58 vessel segments). Lesion preparation before stenting was performed with atherectomy in 7 cases, and balloon PCI over double wires in all other cases; none was treated directly with stents. The mean length of stents implanted in the MB was 19.6 +/- 4.9 mm (10-30 mm). Balloon PCI was successful in 23 of 29 SB and provisional stenting was needed in 6 SB (21%). All patients received oral prednisone according to the immunosuppressive protocol previously reported (1 mg/kg/day/10 days, 0.5 mg/kg/day/20 days, 0.25 mg/kg/day/15 days). At 12 months, one patient had recurrence of angina (4%) and two patients underwent repeated target lesion revascularization (8%). No patient died or had stent thrombosis. Quantitative coronary analysis was performed in all patients at 8 months. Global restenosis rate per vessel was 8.6% (5/58), and 17.2% (5/29) per lesion. The restenosis rate and late lumen loss were 3.4% and 0.36 +/- 0.6 mm, and 13.8% and 0.47 +/- 0.46 mm in the MB and the SB, respectively. Single stent implantation in the MB and provisional stenting of the SB is feasible in most cases after adequate lesion preparation. The systemic treatment with oral prednisone after BMS implantation offers good clinical and angiographic results even in the difficult setting of bifurcation lesions.     

Hemodynamic and respiratory effects of thyrotropin-releasing hormone and epinephrine in anaphylactic shock

Thyrotropin-releasing hormone (TRH) has been shown to increase mean arterial pressure during anaphylactic shock. The hemodynamic mechanism of action and the effect of TRH on the respiratory system during anaphylactic shock are not known. A rabbit model of anaphylaxis was used to determine the effect of TRH, epinephrine (EPI), and normal saline (NS) on various cardiovascular and respiratory parameters during anaphylactic shock. Anaphylactic shock was induced by antigen challenge in 31 sensitized animals. After a 25% decrease in mean arterial pressure, they were randomly treated with TRH (2 mg/kg), EPI (0.005 mg/kg), or NS (10 mL/kg). Blood was drawn at baseline and at the end of the experiment for laboratory analysis. Cardiac and respiratory parameters were monitored continuously and measured at baseline, at onset of shock (time zero), and at time intervals for 30 minutes. Animals were treated with repeated doses during the first 15 minutes as needed to maintain mean arterial pressure above shock level. Five of ten TRH-, five of 11 EPI-, and six of ten NS-treated animals survived. The TRH-treated group required fewer doses than the other groups and had increased heart rate, mean arterial pressure, peripheral vascular resistance, respiratory rate, and minute ventilation as well as decreased stroke volume index and lung compliance compared with the NS-treated group. EPI treatment resulted in increased minute ventilation and decreased pulmonary airway resistance compared with NS treatment. The EPI group also had a higher postsurvival epinephrine level than the other groups. No difference in right atrial pressure, cardiac index, acid-base status, pO2, A- a gradient, lung weight, lactate, or norepinephrine levels was found.(ABSTRACT TRUNCATED AT 250 WORDS)