Characterization of the Shiga toxin-producing Escherichia coli O26 isolated from human in Poland between 1996 and 2014.

Shiga toxin-producing Escherichia coli (STEC) O26 infections can be comparable with STEC O157 infections in severity of the acute haemolytic-uremic syndrome HUS and long-term sequelae. Among O26 STEC isolates, highly virulent clone O26:H11/H- Sequence Type 29 (ST 29) emerged in Germany in mid-1990s and spread to European countries. However, up to date, no STEC O26:H11/H- belonging to ST29 has been documented in Poland. In this study, we determined the relationship and clonal structure, stx genotypes, plasmid gene profiles and antimicrobial resistance of nine human STEC O26:H11/H- strains from human patients in Poland between 1996 and 2014. Of the 9 human STEC O26:H11/H- strains, two belonged to ST29 and were isolated from two children with HUS and renal failure with sepsis respectively. These strains showed the molecular characteristics of the emerging human-pathogenic ST29 clone (stx1-, stx2a+, eae+, ehxA+, etpD+, katP-, espP-). The remaining STEC O26:H11/H- strains examined in this study, belonged to ST21, with plasmid genes profiles frequently reported in ST21 strains in Europe. STEC O26 infections with serious human health consequences highlight the need of continuous surveillance of non-O157 STEC and implementation of the diagnostic approaches focused on their detection. Significance and impact of the study: These study provides the first data on the occurrence of emerging Shiga toxin-producing Escherichia coli O26:H11 ST 29 clone in human patients in Poland. Those strains show the molecular characteristics of highly virulent new ST29 pathotype (stx1-, stx2a+, eae+ ehxA+, etpD+, katP-, espP-). These results demonstrated prompt efforts to implement diagnostic approaches detection of those pathogen in the European countries.

Pro-inflammatory alterations and status of blood plasma iron in a model of blast-induced lung trauma.

Impact of blast shock waves (SW) with the body wall produces blast lung injuries characterized by bilateral traumatic hemorrhages. Such injuries often have no external signs, are difficult to diagnose, and therefore, are frequently underestimated. Predictive assessment of acute respiratory distress syndrome outcome in SW-related accidents should be based on experimental data from appropriate animal models. Blood plasma transferrin is a major carrier of blood iron essential for proliferative "emergency" response of hematopoietic and immune systems as well as injured tissue in major trauma. Iron-transferrin complexes (Fe3+ TRF) can be quantitatively analyzed in blood and tissue samples with low-temperature EPR techniques. We hypothesized that use of EPR techniques in combination with assays for pro-inflammatory cytokines and granulocytes in the peripheral blood and BAL would reveal a pattern of systemic sequestration of (Fe3+)TRF that could be useful for development of biomarkers of the systemic inflammatory response to lung injury. With this goal we (i) analyzed time-dependent dynamics of (Fe3+)TRF in the peripheral blood of rats after impacts of SW generated in a laboratory shock-tube and (ii) assayed the fluctuation of granulocyte (PMN) counts and expression of CD11b adhesion molecules on the surface of PMNs during the first 24 h after SW induced injury. Sham-treated animals were used as control. Exposure to SW led to a significant decrease in the amount of blood (Fe3+)TRF that correlated with the extent of lung injury and developed gradually during the first 24 h. Thus, sequestration of (Fe3+)TRF occurred as early as 3 h post-exposure. At that time, the steady state concentration of (Fe3+)TRF in blood samples decreased from 19.7+/-0.6 microM in controls to 7.5+/-1.3 microM in exposed animals. The levels of (Fe3+)TRF remained decreased throughout the entire study period. PMN counts increased 5-fold and 3.5-fold over controls respectively, at 3 and 6 h postexposure. These effects were accompanied by an increase in expression of CD11b on the surface membrane of PMNs. Extensive release of cytokines IL-1, IL-6, MCP-1, and MIP-2 was observed in BAL fluid and blood plasma during 24 h postexposure. We conclude that EPR monitoring of blood (Fe3+)TRF can be a useful approach for assessment of systemic pro-inflammatory alterations due to SW-induced lung injury.

Response of in vivo protein synthesis in T lymphocytes and leucocytes to an endotoxin challenge in healthy volunteers.

In vivo determination of protein synthesis in immune cells reflects metabolic activity and immunological activation. An intravenous injection of endotoxin to healthy volunteers was used as a human sepsis model, and in vivo protein synthesis of T lymphocytes and leucocytes was measured. The results were related to plasma concentrations of selected cytokines, peripheral cell counts and subpopulations of immune cells. The subjects (n = 8 + 8) were randomized to an endotoxin (4 ng/kg) or a saline group. In vivo protein synthesis was determined twice: before and 1-2.5 h after the endotoxin/saline injection. Protein synthesis decreased in isolated T lymphocytes, but increased in leucocytes. Plasma levels of TNF-alpha, IL-8, IL-6, IL-1 ra and IL-10 were elevated, whereas IL-2 and IFN-gamma, produced predominantly by T lymphocytes, did not change in response to endotoxin. Neutrophils increased, whereas lymphocytes and monocytes decreased 2.5 h after the endotoxin injection. Flow cytometry revealed a drop in total CD3+ T lymphocytes and CD56+ natural killer cells, accompanied by an increase in CD15+ granulocytes. In summary, in vivo protein synthesis decreased in T lymphocytes, while the total leucocyte population showed a concomitant increase immediately after the endotoxin challenge. The changes in protein synthesis were accompanied by alterations in immune cell subpopulations and in plasma cytokine levels.

A combined stress hormone infusion decreases in vivo protein synthesis in human T lymphocytes in healthy volunteers.

In vivo protein synthesis decreases in mononuclear cells following a combined stress hormone infusion given to healthy volunteers as a human trauma model. Here, the purpose was to further investigate this finding and to measure in vivo protein synthesis in isolated T lymphocytes. Furthermore, the effects of stress hormones on the lymphocyte subpopulations and mononuclear cells, characterized by flow cytometry and phytohemagglutinin (PHA)-induced and unstimulated proliferative responses in vitro, were elucidated. Healthy volunteers (n = 16) were randomized into 2 groups to receive either a stress hormone or a saline infusion for 6 hours. In vivo protein synthesis was studied before and after the treatment by measuring the incorporation of stable isotopically-labeled phenylalanine into lymphocyte and mononuclear cell proteins. Protein synthesis decreased after stress hormone infusion in both cell populations: in T lymphocytes from 13.0% +/- 0.7%/d (mean +/- SD) to 8.6% +/- 2.1%/d (P <.01) and in mononuclear cells from 13.3% +/- 1.2%/d to 6.3 +/- 2.0%/d (P <.001). No change in proliferative responsiveness in vitro was observed. The stress hormone infusion produced a decrease in the percentage of T helper CD3/CD4 from 41% to 18% (P <.001), T cytotoxic CD3/CD8 from 27% to 15% (P <.001), as well as total T CD3 cells from 69% to 35% (P <.001). There was an increase in the percentage of natural killer (NK) cells CD16/CD56 from 17% to 55% (P <.001). Determination of phenotypes expressed on activated T lymphocytes showed that CD3/HLA-DR was unchanged and CD3/CD25 decreased from 14% to 7% (P <.01) in the stress hormone group. The study showed that the decrease of in vivo protein synthesis was 34% in T lymphocytes as compared with 53% in mononuclear cells, when determined immediately after a 6-hour stress hormone infusion. This change was associated with a pronounced decrease in all lymphocyte subpopulations, except for the NK cells, which increased substantially.

Aprotinin and transfusion requirements in orthotopic liver transplantation: a multicentre randomised double-blind study. EMSALT Study Group.

BACKGROUND: Intraoperative hyperfibrinolysis contributes to bleeding during adult orthotopic liver transplantation. We aimed to find out whether aprotinin, a potent antifibrinolytic agent, reduces blood loss and transfusion requirements. METHODS: We did a randomised, double-blind, placebo-controlled trial in which six liver-transplant centres participated. Patients undergoing primary liver transplantation were randomly assigned intraoperative high-dose aprotinin, regular-dose aprotinin, or placebo. Primary endpoints were intraoperative blood loss and transfusion requirements. Secondary endpoints were perioperative fluid requirements, postoperative blood transfusions, complications, and mortality. FINDINGS: 137 patients received high-dose aprotinin (n=46), regular-dose aprotinin (n=43), or placebo (n=48). Intraoperative blood loss was significantly lower in the aprotinin-treated patients, with a reduction of 60% in the high-dose group and 44% in the regular-dose group, compared with the placebo group (p=0.03). Total amount of red blood cell (homologous and autologous) transfusion requirements was 37% lower in the high-dose group and 20% lower in the regular-dose group, than in the placebo group (p=0.02). Thromboembolic events occurred in two patients in the high-dose group, none in the regular-dose group, and in two patients in the placebo group (p=0.39). Mortality at 30 days did not differ between the three groups (6.5%, 4.7%, and 8.3%; p=0.79). INTERPRETATION: Intraoperative use of aprotinin in adult patients undergoing orthotopic liver transplantation significantly reduces blood-transfusion requirements and should be routinely used in patients without contraindications.

In vivo protein synthesis of circulating human T lymphocytes does not respond to a cortisol challenge within 24 h.

BACKGROUND: Although immunocompetence is often measured by assessing responsiveness of lymphocytes to mitogenic stimulation in vitro, this approach may not reflect the in vivo situation. The aim of this investigation was to determine in vivo the protein synthesis rate (FSR) in isolated T lymphocytes and to study the effect of a short-term cortisol infusion on FSR. METHODS: Healthy volunteers (n=24) were randomised into 4 groups. A continuous cortisol infusion (6 microg kg(-1) min(-1)) during 6 h was given to groups 1 and 2, whereas groups 3 and 4 served as control groups and received saline infusion. Protein synthesis was studied before and after 6 h of the cortisol/saline infusion (groups 1 and 3) or 24 h after the start of the infusion (groups 2 and 4). FSR was determined in vivo by the flooding method. The isotopic enrichment of phenylalanine in plasma and lymphocyte protein was determined with gas chromatography-mass spectrometry. RESULTS: The FSR in T lymphocytes was 13.6+/-0.9%/24 h as a mean value (+/-SD) of the first determination in 4 groups. There was no significant difference in FSR from the baseline value immediately after the cortisol infusion (group 1: 13.3+/-1.4%/24 h vs 13.5+/-2.8%/24 h) or 24 h after the start of the infusion (group 2: 13.6+/-0.7%/24 h vs 12.3+/-2.4%/24 h). CONCLUSION: The metabolic activity of circulating T lymphocytes, as reflected by a quantitative measurement of in vivo protein synthesis of human T lymphocytes, was not affected by the increased level of cortisol.

Maximal exercise performance-impairing effects of simulated blast overpressure in sheep.

Lung contusion has been identified as a primary blast injury. These experiments addressed a fundamental and overt endpoint of primary blast injury, incapacitation (performance decrement). Respiration, hemodynamics, and blood gases were measured in sheep undergoing incremental exercise challenge before and 1 h after simulated blast exposure of the thorax. Pathologic examination of lung tissue was performed after exposure and exercise testing. Blast overpressure was simulated in the laboratory using a compressed air-driven shock tube. Three levels of lung injury (Levels 1-3, 'Trivial', 'Slight', and 'Moderate' injury, respectively) were examined for effects on maximal oxygen consumption (VO[2max]), an index of cardiorespiratory fitness. Resting hemodynamics and blood gases were relatively normal an hour after exposure, immediately before exercise. However, Levels 1-3 lung injury were associated with average 4.8, 29.9 and 49.3% VO(2max). decreases, respectively. These performance decrements for Levels 2 and 3 were significantly different from respective controls (non-exposed). Exercise caused significant hemoconcentration in sheep under control conditions, before exposure (resting 9.5 +/- 0.9, end-exercise 11.8 +/- 0.9 g/100 ml). Blast exposure resulted in average decreases of 4.9 +/- 3.4, 12.8 +/- 4.0, and 12.6 +/- 3.3% in exercise-induced hemoconcentration for Levels 1-3 injury, respectively. Normal exercise-induced hemodynamic increases were also attenuated after exposure. Levels 2 and 3 injury resulted in average 22.6 +/- 2.9 and 18.5 +/- 11.2% stroke volume decreases, and also 22.3 +/- 8.4 and 29.0 +/- 14.2% cardiac output decreases, respectively, during exercise. While blast lung pathology and pulmonary function changes could account for post-blast performance decrements, these experiments suggest that in sheep, early after exposure, diminished hemoconcentration and cardiac disfunction may also contribute to decreased exercise performance.

Evaluation of lethality estimates for combustion gases in military scenarios.

To meet the military objective of determining criteria for incapacitation and lethality from toxic gas exposures, a series of small animal tests and data analyses were conducted. Carbon monoxide (CO), a narcotic gas and nitrogen dioxide (NO2), an irritant gas, along with carbon dioxide (CO2) were tested individually and in the following mixtures: (CO + CO2), (NO2 + CO2) and (NO2 + CO + CO2). A group of six animals was exposed to each of the gases and their combinations, lethality and biophysical data were collected. We conclude that our observations of lethality from single toxic gases can be correlated with a fractional effective dose (FED) description, in which external concentrations are corrected for minute volume changes. Multiple gas exposures clearly demonstrate synergistic effects because lethality rates greatly exceed those expected from statistically independent causes. Simple addition of the FED values, however, overstates the effect and implies a competition between the narcotic and irritant gas effects. The N-Gas model, while being an additive FED model, does not appear to be in a form that could guide the setting of military exposure standards.

Effect of a short-term infusion of glutamine on muscle protein metabolism postoperatively.

The acute effect of a short-term postoperative infusion of glucose supplemented with glutamine (0.285 g/kg body weight), on muscle protein metabolism, was studied by analyses of free amino acid concentrations and determinations of protein synthesis. A glutamine-glucose infusion was given for 5.5 h to 6 patients 2-3 days after elective surgery for colon cancer. The free glutamine concentration was 5.72 +/- 0.96 mmol/kg wet weight (ww) before and 6.14 +/- 1.10 mmol/kg ww 4 h after the glutamine infusion. The rate of protein synthesis was 1.26 +/- 0.15%/24 h before the infusion and 1.12 +/- 0.16%/24 h during its latter part. The percentage of polyribosomes was 42.2 +/- 3.4% before and 40.9 +/- 1.3% after the infusion. The results showed no difference in these biochemical parameters, indicating that a short-term infusion of glutamine given postoperatively is insufficient to affect protein metabolism in human skeletal muscle.

[Detection of antibodies of Borrelia burgdorferi among inhabitants of north-eastern Poland]. / Obecnosc przeciwcial przeciwko Borrelia burgdorferi wsród mieszkanców pólnocno-wschodniej Polski.

The aim of this work was to estimate the detection of antibodies against Borrelia burgdorferi among inhabitants in North Eastern Poland 1765 persons from Bialystok, Lomza and Suwalki voivodships were examined. Among them 1101 persons were from high-risk of exposition to ticks group (forest workers, people living close to forests). 418 (23.68%) persons from group of 1765 had antibodies against B.b. There was no difference of incidence of antibodies against B.b. in high-risk group and the others. The results show that North Eastern Poland is the endemic region of occurrence of B.b.

Nitrogen dioxide-induced acute lung injury in sheep.

Lung mechanics, hemodynamics and blood chemistries were assessed in sheep (Ovis aries) before, and up to 24 h following, a 15-20 min exposure to either air (control) or approximately 500 ppm nitrogen dioxide (NO2). Histopathologic examinations of lung tissues were performed 24 h after exposure. Nose-only and lung-only routes of exposure were compared for effects on NO2 pathogenesis. Bronchoalveolar lavage fluids from air- and NO2-exposed sheep were analyzed for biochemical and cellular signs of NO2 insult. The influence of breathing pattern on NO2 dose was also assessed. Five hundred ppm NO2 exposure of intubated sheep (lung-only exposure) was marked by a statistically significant, albeit small, blood methemoglobin increase. The exposure induced an immediate tidal volume decrease, and an increase in both breathing rate and inspired minute ventilation. Pulmonary function, indexed by lung resistance and dynamic lung compliance, progressively deteriorated after exposure. Maximal lung resistance and dynamic lung compliance changes occurred at 24 h post exposure, concomitant with arterial hypoxemia. Bronchoalveolar lavage fluid epithelial cell number and total protein were significantly increased while macrophage number was significantly decreased within the 24 h post-exposure period. Histopathologic examination of lung tissue 24 h after NO2 revealed patchy edema, mild hemorrhage and polymorphonuclear and mononuclear leukocyte infiltration. The NO2 toxicologic profile was significantly attenuated when sheep were exposed to the gas through a face mask (nose-only exposure). Respiratory pattern was not significantly altered, lung mechanics changes were minimal, hypoxemia did not occur, and pathologic evidence of exudation was not apparent in nose-only, NO2-exposed sheep. The qualitative responses of this large animal species to high-level NO2 supports the concept of size dependent species sensitivity to NO2. In addition, when inspired minute ventilation was used as a dose-determinant, a linear relationship between NO2 dose and lung resistance was found. The importance of these findings, NO2 dose-determinants, and the utility of sheep as a large animal inhalation model are discussed.

Effects of epinephrine, phenoxybenzamine, and propranolol on maximal exercise in sheep.

The mixed adrenergic agonist, epinephrine (10 micrograms/kg, i.v.), the beta-adrenergic receptor antagonist, propranolol (0.2 mg/kg, i.v.), or the alpha-adrenergic receptor antagonist, phenoxybenzamine (1 mg/kg, i.v.), were administered to sheep immediately before maximal incremental exercise. The effects of each of these drugs on hemoglobin (Hb) concentration during maximal exercise and on maximal exercise performance were investigated. The maximal incremental exercise protocol began at 4.0 km/h and 0% grade and finished at 5.6 km/h and 12% grade, with speed or grade increases every 1.5 minutes. Maximal exercise in control (untreated) sheep caused a mean 42% increase in hematocrit and 44% increase in Hb. This exercise-induced increase in Hb was unaffected by propranolol but was partially blocked by phenoxybenzamine. Epinephrine caused an immediate increase in Hb which abated during the early minutes of exercise and then subsequently increased toward the end of the exercise challenge. Maximum oxygen consumption (VO2) in control sheep was 47.6 +/- 6.7 ml/min per kilogram. Maximum VO2 after epinephrine, 51.6 +/- 8.7 ml/min per kilogram, was not significantly different from control. Maximum VO2 after propranolol and phenoxybenzamine, 35.4 +/- 15.3 and 40.8 +/- 8.2 ml/min per kilogram, respectively, were both significantly less than control exercise (P < 0.05).

Physiological responses of sheep to two hours anaesthesia with diazepam-ketamine.

The cardiopulmonary effects of repeated intravenous injections of a combination of diazepam and ketamine for anaesthesia were evaluated in six domestic sheep. Induction doses of 0.375 mg/kg and 7.5 mg/kg were followed by maintenance doses of 0.188 mg/kg and 3.75 mg/kg every 15 minutes for 105 minutes. Although this dosing regimen produced the desired anaesthetic effects, it caused untoward cardiopulmonary effects. Salient features of multiple dosing with diazepam and ketamine were hypoventilation, respiratory acidosis and an increase in both systemic and pulmonary vascular resistance.

Cardiopulmonary effects of a tiletamine-zolazepam combination in sheep.

To assess the effects on heart and lung function, a tiletamine-zolazepam (TZ) anesthetic combination was evaluated in 10 Dorset-type ewes. Ewes were randomly allotted to 2 equal groups. Ewes of groups 1 and 2 were given a single bolus of TZ (12 and 24 mg/kg of body weight, IV, respectively) at time zero. Hemodynamic, pulmonary, and ventilation variables were measured at 15-minute intervals to 120 minutes. Blood gas variables were evaluated at 5-minute intervals for the first 30 minutes, then at 15-minute intervals to 120 minutes. In all sheep, TZ administration induced rapid, smooth induction, with gradual and unremarkable recovery. Anesthesia duration was not significantly different between groups (mean +/- SD, 39 +/- 5 and 40 +/- 14 minutes for groups 1 and 2, respectively). Immediate drug effects included apnea, decreased mean arterial blood pressure, and arterial hypoxemia. Cardiac output was significantly decreased in both groups at all times after drug administration. Significant changes in group-1 ewes included increased pulmonary and systemic vascular resistances and decreased inspired minute ventilation, tidal volume, and respiratory airflow. Significant changes in group-2 ewes included increased systemic vascular resistance and decreased pulmonary arterial pressure, inspired minute ventilation, and respiratory airflow. Both drug dosages induced apneustic breathing patterns and caused significant changes in arterial and venous blood hemoglobin concentrations and PCV. Tiletamine-zolazepam is useful for intermediate-duration anesthesia in sheep.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of conditioning and maximal incremental exercise on oxygen consumption in sheep.

To assess the suitability of sheep for exercise studies, the effect of incremental exercise and conditioning on oxygen consumption (VO2) was studied. Six sheep were adapted to a treadmill and subsequently trained 8 weeks. The sheep were then studied, in random order, using 3 incremental exercise protocols (EX-1, EX-2, and EX-3). The protocols were chosen to approximate high (EX-1), moderate (EX-2), and low (EX-3) intensity exercise by varying treadmill speed and incline. The sheep were then conditioned for an additional 12 weeks and retested on the EX-2 protocol. During exercise, VO2, gas exchange ratio (R), and rectal temperatures (Tb) were recorded. All 3 protocols resulted in significant increases in VO2, R, and Tb (P less than 0.05). Maximum VO2 for EX-1, 49.9 +/- 5.0 ml/min/kg of body weight, was significantly greater than maximum VO2 for EX-2 and EX-3, 37.8 +/- 6.5 and 42.3 +/- 6.0 ml/min/kg, respectively (P less than 0.05), whereas maximum R and maximum Tb were similar. After the additional 12-week conditioning, time on the treadmill increased 40% from 9.58 +/- 0.87 to 13.4 +/- 0.44 minutes, and maximum VO2 increased 27% to 48.1 +/- 9.1 ml/min/kg. These data indicated that maximum VO2 varied with intensity of the exercise, 12 weeks of maximal exercise conditioning was sufficient to produce a measurable training effect (ie, increase endurance and maximum oxygen consumption) and sheep are suitable for maximal exercise studies where VO2 measurements are desired.

The cardiovascular response of sheep to tiletamine-zolazepam and butorphanol tartrate anesthesia.

Butorphanol tartrate (0.5 mg/kg intravenously [IV]) was administered to six ewes (group 1), 10 minutes before administration of tiletamine-zolazepam (12 mg/kg IV). In six ewes (group 2), butorphanol tartrate and tiletamine-zolazepam were administered simultaneously. Time of administration of butorphanol did not alter hemodynamics or duration of anesthesia significantly. Anesthesia was adequate for 25 to 45 minutes (mean, 31 min) in group 1. The sheep in group 2 were anesthetized effectively for 25 to 50 minutes (mean, 39 min). Neither dosing regimen caused significant changes in right atrial pressure, heart rate, pulmonary vascular resistance, or pulmonary capillary wedge pressure. Mean arterial blood pressure (MABP) decreased an average of 18% from baseline values of 113 mm Hg to a minimum of 84 mm Hg at minute 60 in group 1, and from 111 mm Hg to 92 mm Hg at minute 75 in group 2. The decrease was significant only for group 1. Cardiac output (CO) was significantly decreased 24% from 6.6 L/min at minute 45 in group 1, and 32% from 6.3 L/min at minute 15 in group 2. Systemic vascular resistance (SVR) was increased significantly at minute 15, 11% in group 1 and 37% in group 2. Mild respiratory acidosis was measured by significant decreases in arterial pO2 and pH and a significant increase in pCO2 without significant changes in HCO3-. Results of this study show that (1) tiletamine-zolazepam and butorphanol tartrate produce adequate anesthesia for 25 to 50 minutes; (2) the cardiovascular and anesthetic effects of the dosing schedules were similar; and (3) tiletamine-zolazepam and butorphanol result in decreased CO and MABP with a concomitant increase in SVR, and mild respiratory acidosis.

The cardiorespiratory effects of diazepam-ketamine and xylazine-ketamine anesthetic combinations in sheep.

The cardiorespiratory dynamics and anesthetic effects of intravenously administered diazepam-ketamine (0.375 mg kg-1/7.5 mg kg-1) and xylazine-ketamine (0.1 mg kg-1/7.5 mg kg-1) were investigated in six domestic sheep (Ovis aries). The depth of analgesia and sedation was evaluated and the effects of the anesthetic drug combinations on hemodynamics and pulmonary mechanics were monitored before, and up to 90 minutes after, drug administration. Diazepam-ketamine and xylazine-ketamine induced effective anesthesia for periods lasting 15 minutes and 25 minutes, respectively. Both drug combinations caused transient respiratory acidosis. However, no profound effects on respiration or pulmonary function were observed. Neither anesthetic regimen caused significant effects on heart rate or pulmonary hemodynamics, but they caused significant decreases in cardiac output. Xylazine-ketamine resulted in a significant decrease in mean systemic arterial blood pressure (Psa) with a concurrent decrease in systemic vascular resistance (SVR). Diazepam-ketamine caused a significant increase in SVR without affecting Psa. Xylazine-ketamine may be contraindicated in animals with compromised heart function because of its hypotensive effects. Otherwise, both drug combinations, in the doses used, can provide short-term anesthesia suitable for minor surgical procedures and painful experimental maneuvers.