Behavioral and cardiopulmonary effects of dexmedetomidine alone and in combination with butorphanol, methadone, morphine or tramadol in conscious sheep

Objective: To compare cardiopulmonary and sedative effects following administration of dexmedetomidine alone or with butorphanol, methadone, morphine or tramadol in healthy sheep. Study design: Randomized crossover study. Animals: Six Santa Inês sheep, five females, one male, aged 12–28 months and weighing 40.1 ± 6.2 kg. Methods: Sheep were assigned treatments of dexmedetomidine (0.005 mg kg−1; D); D and butorphanol (0.15 mg kg−1; DB); D and methadone (0.5 mg kg−1; DM); D and morphine (0.5 mg kg−1; DMO); or D and tramadol (5.0 mg kg−1; DT). All drugs were administered intravenously with at least 7 days between each treatment. Rectal temperature, heart rate (HR), respiratory rate (fR), invasive arterial pressure, blood gases and electrolytes were measured prior to administration of drugs (baseline, T0) and every 15 minutes following drug administration for 120 minutes (T15–T120). Sedation was scored by three observers blinded to treatment. Results: HR decreased in all treatments and fR decreased in DM at T30 and DMO at T30 and T45. PaCO2 was increased in D, DB and DM compared with baseline, and PaO2 decreased in D at T15 and T45; in DB at T15 to T75; in DM at T15 to T60; in DMO at T15; and in DT at T15, T30 and T75. There was a decrease in temperature in D, DB and DM. An increased pH was measured in D at all time points and in DT at T30–T120. inline image and base excess were increased in all treatments compared with baseline. There were no statistical differences in sedation scores. Conclusions and clinical relevance: The combination of dexmedetomidine with butorphanol, methadone, morphine or tramadol resulted in similar changes in cardiopulmonary function and did not improve sedation when compared with dexmedetomidine alone

Echocardiographic predictors of early in-hospital heart failure during first ST-elevation acute myocardial infarction: does myocardial performance index and left atrial volume improve diagnosis over conventional parameters of left ventricular function?

<p>Abstract</p> <p>Background</p> <p>Left ventricular ejection fraction (LVEF) has been considered a major determinant of early outcome in acute myocardial infarction (AMI). Myocardial performance index (MPI) has been associated to early evolution in AMI in a heterogeneous population, including non ST-elevation or previous AMI. Left atrial volume has been related with late evolution after AMI. We evaluated the independent role of clinical and echocardiographic variables including LVEF, MPI and left atrial volume in predicting early in-hospital congestive heart failure (CHF) specifically in patients with a first isolated ST-elevation AMI.</p> <p>Methods</p> <p>Echocardiography was performed within 30 hours of chest pain in 95 patients with a first ST-elevation AMI followed during the first week of hospitalization. Several clinical and echocardiographic variables were analyzed. CHF was defined as Killip class ≥ II. Multivariate regression analysis was used to select independent predictor of in-hospital CHF.</p> <p>Results</p> <p>Early in-hospital CHF occurred in 29 (31%) of patients. LVEF ≤ 0.45 was the single independent and highly significant predictor of early CHF among other clinical and echocardiographic variables (odds ratio 17.0; [95% CI 4.1 - 70.8]; p < 0.0001). MPI alone could not predict CHF in first ST-elevation AMI patients. Left atrial volume was not associated with early CHF in such patients.</p> <p>Conclusion</p> <p>For patients with first, isolated ST-elevation AMI, LVEF assessed by echocardiography still constitutes a strong and accurate independent predictor of early in-hospital CHF, superior to isolated MPI and left atrial volume in this particular subset of patients.</p

Generation of neutralizing antibodies and divergence of SIVmac239 in cynomolgus macaques following short-term early antiretroviral therapy.

Neutralizing antibodies (NAb) able to react to heterologous viruses are generated during natural HIV-1 infection in some individuals. Further knowledge is required in order to understand the factors contributing to induction of cross-reactive NAb responses. Here a well-established model of experimental pathogenic infection in cynomolgus macaques, which reproduces long-lasting HIV-1 infection, was used to study the NAb response as well as the viral evolution of the highly neutralization-resistant SIVmac239. Twelve animals were infected intravenously with SIVmac239. Antiretroviral therapy (ART) was initiated ten days post-inoculation and administered daily for four months. Viral load, CD4(+) T-cell counts, total IgG levels, and breadth as well as strength of NAb in plasma were compared simultaneously over 14 months. In addition, envs from plasma samples were sequenced at three time points in all animals in order to assess viral evolution. We report here that seven of the 12 animals controlled viremia to below 10(4) copies/ml of plasma after discontinuation of ART and that this control was associated with a low level of evolutionary divergence. Macaques that controlled viral load developed broader NAb responses early on. Furthermore, escape mutations, such as V67M and R751G, were identified in virus sequenced from all animals with uncontrolled viremia. Bayesian estimation of ancestral population genetic diversity (PGD) showed an increase in this value in non-controlling or transient-controlling animals during the first 5.5 months of infection, in contrast to virus-controlling animals. Similarly, non- or transient controllers displayed more positively-selected amino-acid substitutions. An early increase in PGD, resulting in the generation of positively-selected amino-acid substitutions, greater divergence and relative high viral load after ART withdrawal, may have contributed to the generation of potent NAb in several animals after SIVmac239 infection. However, early broad NAb responses correlated with relatively preserved CD4(+) T-cell numbers, low viral load and limited viral divergence

Intraocular pressure and Schirmer tear test values in maned wolf (Chrysocyon brachyurus)

Abstract: The purpose of this study was to establish baseline data on lacrimal quantity (STT-1) and intraocular pressure (IOP) in captive maned wolves. Ten healthy adult maned wolves were contained with a snare pole and muzzle and kept in decubitus of the left side. STT-1 measurement was performed on the lateral third of the lower conjunctival sac for one minute. The cornea was desensitized and intraocular pressure was measured with an tonopen. Average STT-1 in both eyes was 11±5mm.min-1, with no statistical difference between the left and right eye (p=0.960). Average IOP in both eyes was 20±6mmHg, with no statistical difference between the left and right eye (p=0.836). Average STT-1 was lower than, and IOP was the same as normal levels found in dogs. There was no statistical difference in the age of the animals, and STT-1 and IOP values. In the present paper, average maned wolf STT-1 levels were lower compared with those found in dogs, while the IOP was the same in maned wolves as in dogs. Due to the increased incidence in providing emergency care for maned wolf victims of road kill and fires, determination reference values of ocular parameters may improve the correct diagnosis and treatment of the disease

Sedative and cardiopulmonary effects of xylazine alone or in combination with methadone, morphine or tramadol in sheep

To evaluate the cardiopulmonary and sedative effects of xylazine alone or in combination with methadone, morphine or tramadol in sheep. Experimental, prospective, crossover, randomized, blinded study. Six Santa Inês breed sheep (females) aged 12 ± 8 months and weighing 39.5 ± 7.4 kg. Sheep were sedated with each of four treatments in a randomized, crossover design, with a minimum washout period of 7 days between treatments. Treatments were: X [xylazine (0.1 mg kg(-1) )]; XM [xylazine (0.1 mg kg(-1) ) and methadone (0.5 mg kg(-1) )]; XMO [xylazine (0.1 mg kg(-1) ) and morphine (0.5 mg kg(-1) )], and XT [xylazine (0.1 mg kg(-1) ) and tramadol (5 mg kg(-1) )]. Each drug combination was mixed in the syringe and injected intravenously. Sedation, heart rate (HR), mean arterial blood pressure (MAP), rectal temperature (RT°C), respiratory rate (fR ), arterial blood gases and electrolytes were measured before drug administration (T0) and then at 15 minute intervals for 120 minutes (T15-T120). Heart rate significantly decreased in all treatments compared with T0. PaCO2 values in XM and XMO were higher at all time points compared with T0. In treatments X and XM, pH, bicarbonate (HCO3-) and base excess were increased at all time points compared with T0. PaO2 was significantly decreased at T15-T75 in XM, at all time points in XMO, and at T15 and T30 in XT. Sedation at T15 and T30 in XM and XMO was greater than in the other treatments. The combinations of methadone, morphine or tramadol with xylazine resulted in cardiopulmonary changes similar to those induced by xylazine alone in sheep. The combinations provided better sedation, principally at 15 minutes and 30 minutes following administration.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Effects of dexmedetomidine combined with commonly administered opioids on clinical variables in dogs

OBJECTIVE To evaluate cardiopulmonary, sedative, and antinociceptive effects of dexmedetomidine combined with commonly administered opioids in dogs. ANIMALS 8 healthy Beagles. PROCEDURES Dogs were sedated by IM administration of each of 7 treatments. Treatments comprised dexmedetomidine (0.01 mg/kg; Dex) and the same dose of dexmedetomidine plus butorphanol (0.15 mg/kg; Dex-But), meperidine (5 mg/kg; Dex-Mep), methadone (0.5 mg/kg; Dex-Meth), morphine (0.5 mg/kg; Dex-Mor), nalbuphine (0.5 mg/kg; Dex-Nal), or tramadol (5 mg/kg; Dex-Tram). Cardiorespiratory and arterial blood gas variables and sedative and antinociceptive scores were measured before drug injection (time 0; baseline) and at 15-minute intervals for 120 minutes. RESULTS Heart rate was reduced at all time points after injection of Dex-But, Dex-Mep, Dex-Meth, and Dex-Mor treatments. There was a significant reduction of mean arterial blood pressure for Dex-But, Dex-Mep, and Dex-Mor treatments at all time points, compared with baseline. There was a significant decrease in respiratory rate, compared with the baseline value, for Dex, Dex-But, Dex-Meth, and Dex-Tram treatments from 15 to 120 minutes. A significant decrease in arterial blood pH was detected from baseline to 120 minutes for all treatments, with differences among Dex, Dex-Mep, and Dex-Mor. Reduction in Pao2 was greater for the Dex-Mep treatment than for the other treatments. The highest sedation scores were detected for Dex-Mep and Dex-Meth treatments. Antinociceptive effects were superior for Dex-But, Dex-Meth, Dex-Mor, and Dex-Nal treatments. CONCLUSIONS AND CLINICAL RELEVANCE Drug combinations caused similar cardiorespiratory changes, with greater sedative effects for Dex-Mep and Dex-Meth and superior antinociceptive effects for Dex-But, Dex-Meth, Dex-Mor, and Dex-Nal

Behavioral and cardiopulmonary effects of dexmedetomidine alone and in combination with butorphanol, methadone, morphine or tramadol in conscious sheep

Objective: To compare cardiopulmonary and sedative effects following administration of dexmedetomidine alone or with butorphanol, methadone, morphine or tramadol in healthy sheep. Study design: Randomized crossover study. Animals: Six Santa Inês sheep, five females, one male, aged 12–28 months and weighing 40.1 ± 6.2 kg. Methods: Sheep were assigned treatments of dexmedetomidine (0.005 mg kg−1; D); D and butorphanol (0.15 mg kg−1; DB); D and methadone (0.5 mg kg−1; DM); D and morphine (0.5 mg kg−1; DMO); or D and tramadol (5.0 mg kg−1; DT). All drugs were administered intravenously with at least 7 days between each treatment. Rectal temperature, heart rate (HR), respiratory rate (fR), invasive arterial pressure, blood gases and electrolytes were measured prior to administration of drugs (baseline, T0) and every 15 minutes following drug administration for 120 minutes (T15–T120). Sedation was scored by three observers blinded to treatment. Results: HR decreased in all treatments and fR decreased in DM at T30 and DMO at T30 and T45. PaCO2 was increased in D, DB and DM compared with baseline, and PaO2 decreased in D at T15 and T45; in DB at T15 to T75; in DM at T15 to T60; in DMO at T15; and in DT at T15, T30 and T75. There was a decrease in temperature in D, DB and DM. An increased pH was measured in D at all time points and in DT at T30–T120. inline image and base excess were increased in all treatments compared with baseline. There were no statistical differences in sedation scores. Conclusions and clinical relevance: The combination of dexmedetomidine with butorphanol, methadone, morphine or tramadol resulted in similar changes in cardiopulmonary function and did not improve sedation when compared with dexmedetomidine alone