Effects of muscarinic receptor antagonists on acetylcholine-induced contractions of jejunal smooth muscle in horses.

This study investigated the effects of a muscarinic type 1 (M(1)), 2 (M(2)), and 3 (M(3)) antagonists (4-DAMP, pirenzepine, and methoctramine, respectively) on acetylcholine (Ach)-induced contractions of longitudinal jejunal muscle strips of horses. Strips were irrigated with Krebs-Henseleit solution gassed with 95% O(2) and 5% CO(2), and the developed tension in response to Ach was recorded before and after incubation with increasing concentrations of 4-DAMP (10(-8)-10(-6) M), pirenzepine (10(-6)-10(-4) M), and methoctramine (10(-5)-10(-3) M). When competitive antagonism was characterized, the affinity constant (pA(2)) was calculated by Schild plots. A parallel rightward shift in the concentration-response curves was observed after 4-DAMP and pirenzepine. Methoctramine presented a dual effect on the concentration-response curves: lower concentrations induced a parallel rightward shift without altering the maximum intensity of contraction (E(max)), while the highest concentration increased slope of the concentration-response curve and increased E(max). The pA(2) for 4-DAMP and pirenzepine was 9.18 and 7.13, respectively. Acetylcholine-induced contractions of longitudinal jejunal smooth muscle are mediated mainly via M(3) receptors. The complex role of M(2) receptors in jejunal smooth muscle contractions was evident because methoctramine potentiated the contractile response to higher doses of Ach.

Comparative study between atropine and hyoscine-N-butylbromide for reversal of detomidine induced bradycardia in horses.

REASONS FOR PERFORMING STUDY: Bradycardia may be implicated as a cause of cardiovascular instability during anaesthesia. HYPOTHESIS: Hyoscine would induce positive chronotropism of shorter duration than atropine, without adversely impairing intestinal motility in detomidine sedated horses. METHODS: Ten minutes after detomidine (0.02 mg/kg bwt, i.v.), physiological saline (control), atropine (0.02 mg/kg bwt) or hyoscine (0.2 mg/kg bwt) were randomly administered i.v. to 6 horses, allowing one week intervals between treatments. Investigators blinded to the treatments monitored cardiopulmonary data and intestinal auscultation for 90 min and 24 h after detomidine, respectively. Gastrointestinal transit was assessed for 96 h via chromium detection in dry faeces. RESULTS: Detomidine significantly decreased heart rate (HR) and cardiac index (CI) from baseline for 30 and 60 min, respectively (control). Mean ± s.d. HR increased significantly 5 min after atropine (79 ± 5 beats/min) and hyoscine (75 ± 8 beats/min). After this time, HR was significantly higher after atropine in comparison to other treatments, while hyoscine resulted in intermediate values (lower than atropine but higher than controls). Hyoscine and atropine resulted in significantly higher CI than controls for 5 and 20 min, respectively; but this effect coincided with significant hypertension (mean arterial pressures >180 mmHg). Auscultation scores decreased from baseline in all treatments. Time to return to auscultation scores ≥12 (medians) did not differ between hyoscine (4 h) and controls (4 h) but atropine resulted in significantly longer time (10 h). Atropine induced colic in one horse. Gastrointestinal transit times did not differ between treatments. CONCLUSION: Hyoscine is a shorter acting positive chronotropic agent than atropine, but does not potentiate the impairment in intestinal motility induced by detomidine. Because of severe hypertension, routine use of anticholinergics combined with detomidine is not recommended. POTENTIAL RELEVANCE: Hyoscine may represent an alternative to atropine for treating bradycardia.

Prostatic carcinomas with neuroendocrine differentiation diagnosed in needle biopsies, a morphologic study of 7 cases among 465 sequential biopsies in a tertiary cancer center.

PURPOSE: Neuroendocrine carcinomas (NEC) of the prostate are rare, with only a few series hitherto reported. The objective of this study was to assess in a single institution the clinical and morphologic characteristics of neuroendocrine carcinomas diagnosed in needle core biopsies. MATERIALS AND METHODS: The current study analyses seven cases diagnosed in needle biopsies at a large tertiary regional cancer center from Northeastern Brazil. Two pathologists reviewed specimens retrospectively, and demographic and morphologic characteristics were compared to 458 acinar tumors diagnosed in the same period. RESULTS: There were five small cell carcinomas and two low-grade neuroendocrine carcinomas (carcinoid). NEC were associated with an acinar component in 5/7 cases and the Gleason score of the acinar component was always > 6. The number of cores involved in prostates with NEC was greater (65% compared to 24% of acinar tumors, p < 0.05). The mean PSA at diagnosis was 417.7 (range 5.7-1593, SD 218.3), compared to 100.5 (p = 0.1) of acinar tumors (range 0.3-8545, SD 22.7). Prostates harboring NEC were bigger (p < 0.001, mean volume 240 mL vs. 53 mL of acinar tumors). Treatment of NEC included palliative surgery, chemotherapy, and hormonal therapy. CONCLUSIONS: NEC of the prostate is rare and often associated with a high-grade acinar component. Prostates with NEC tend to be larger and involve a greater number of cores than acinar tumors. PSA at diagnosis does not seem to predict the presence of NE tumors in needle biopsy.

Short-term testicular warming under anesthesia causes similar increases in testicular blood flow in Bos taurus versus Bos indicus bulls, but no apparent hypoxia.

Bull testes must be 4-5 °C below body temperature, with testicular warming more likely to cause poor-quality sperm in Bos taurus (European/British) versus Bos indicus (Indian/zebu) bulls. Despite a long-standing dogma that testicular hyperthermia causes hypoxia, we reported that increasing testicular temperature in bulls and rams enhanced testicular blood flow and O2 delivery/uptake, without hypoxia. Our objective was to determine effects of short-term testicular hyperthermia on testicular blood flow, O2 delivery and uptake and evidence of testicular hypoxia in pubertal Angus (B. taurus) and Nelore (B. indicus) bulls (nine per breed) under isoflurane anesthesia. As testes were warmed from 34 to 40 °C, there were increases (P < 0.0001, but no breed effects) in testicular blood flow (mean ± SEM, 9.59 ± 0.10 vs 17.67 ± 0.29 mL/min/100 g, respectively), O2 delivery (1.79 ± 0.06 vs 3.44 ± 0.11 mL O2/min/100 g) and O2 consumption (0.69 ± 0.07 vs 1.25 ± 0.54 mL O2/min/100 g), but no indications of testicular hypoxia. Hypotheses that: 1) both breeds increase testicular blood flow in response to testicular warming; and 2) neither breed has testicular hypoxia, were supported; however, the hypothesis that the relative increase in blood flow is greater in Angus versus Nelore was not supported. Although these were short-term increases in testicular temperature in anesthetized bulls, results did not support the long-standing dogma that increased testicular temperature does not increase testicular blood flow and an ensuing hypoxia is responsible for decreases in motile, morphologically normal and fertile sperm.

Testicular hyperthermia reduces testosterone concentrations and alters gene expression in testes of Nelore bulls.

Increased testicular temperature reduces sperm motility, morphology and fertility. Our objectives were to characterize effects of testicular hyperthermia (scrotal insulation) on acute testosterone concentrations and gene expression in Bos indicus testes. Nelore bulls (n = 20), ∼27 mo of age, 375 kg, scrotal circumference >31 cm, with ≥30% motile sperm, were allocated into four groups (n = 5/group): non-insulated (Control) and insulation removed after 12, 24, or 48 h. Immediately after insulation, intratesticular temperatures (needle thermocouples) were coolest in Control bulls and warmest in 48-h bulls (mean ± SEM, 35.28 ± 0.31 vs 38.62 ± 0.57 °C, P < 0.05). Bulls were castrated and testes recovered. Testicular testosterone concentrations were higher in Control versus 48-h bulls (3119 ± 973.3 and 295.5 ± 122.8 ng/g of tissue, respectively, P < 0.05). Total RNA was extracted, reverse transcribed and RT-qPCR done. For STAR, mRNA abundance decreased from Control to 48 h (1.14 + 0.32 vs 0.32 + 0.5, P < 0.05). For BCL2, expression decreased from Control to 24 h (1.00 + 0.07 vs 0.70 + 0.12, P < 0.05), but then rebounded. In addition, GPX1 had a 70% increase (P < 0.05) at 48 h, whereas HSP70 had a 34-fold increase (P < 0.05) at 12 h and 2- and 14-fold increases (P < 0.05) at 24 and 48 h, respectively. HSF1, BAX, P53 and CASP 8 remained unchanged. Downregulation of STAR, critical in androgen production, was consistent with reduced testosterone concentrations, whereas increased GPX1 enhanced testicular antioxidative capability. Huge increases in HSP70 conferred protection again apoptosis and cell destruction, whereas reduced BCL2 promoted apoptosis. These findings provided novel insights into acute tissue responses (testosterone and gene activity) to testicular hyperthermia in B. indicus bulls.

Comparison of the cardio-respiratory effects of methadone and morphine in conscious dogs.

The effects of methadone and morphine were compared in conscious dogs. Six animals received morphine sulfate (1 mg/kg) or methadone hydrochloride (0.5 mg/kg [MET0.5] or 1.0 mg/kg [MET1.0]) intravenously (i.v.) in a randomized complete block design. Cardiopulmonary variables were recorded before (baseline), and for 120 min after drug administration. One outlier was not included in the statistical analysis for hemodynamic data. Morphine decreased heart rate (HR) compared to baseline from 30 to 120 min (-15% to -26%), while cardiac index (CI) was reduced only at 120 min (-19%). Greater and more prolonged reductions in HR (-32% to -46%) and in CI (-24% to -52%) were observed after MET1.0, while intermediate reductions were recorded after MET0.5 (-19 to -28% for HR and -17% to -27% for CI). The systemic vascular resistance index (SVRI) was increased after methadone; MET1.0 produced higher SVRI values than MET0.5 (maximum increases: 57% and 165% for MET0.5 and MET1.0, respectively). Compared to morphine, oxygen partial pressure (PaO(2)) was lower (-12% to -13%) at 5 min of methadone (0.5 and 1.0 mg/kg), while carbon dioxide partial pressure (PaCO(2)) did not change significantly. It was concluded that methadone induces cardiovascular changes that are dose-related and is a more potent cardiovascular depressant agent than morphine in conscious dogs.

Sedative and cardiorespiratory effects of acepromazine or atropine given before dexmedetomidine in dogs.

To test the hypothesis that acepromazine could potentiate the sedative actions and attenuate the pressor response induced by dexmedetomidine, the effects of acepromazine or atropine were compared in six healthy adult dogs treated with this alpha2-agonist. In a randomised block design, the dogs received intravenous doses of either physiological saline, 0.05 mg/kg acepromazine or 0.04 mg/kg atropine, 15 minutes before an intravenous dose of 5 microg/kg dexmedetomidine. The dogs' heart rate was reduced by 50 to 63 per cent from baseline and their mean arterial blood pressure was increased transiently from baseline for 20 minutes after the dexmedetomidine. Atropine prevented the alpha2-agonist-induced bradycardia and increased the severity and duration of the hypertension, but acepromazine did not substantially modify the cardiovascular effects of the alpha2-agonist, except for a slight reduction in the magnitude and duration of its pressor effects. The dexmedetomidine induced moderate to intense sedation in all the treatments, but the dogs' sedation scores did not differ among treatments. The combination of acepromazine with dexmedetomidine had no obvious advantages in comparison with dexmedetomidine alone, but the administration of atropine before dexmedetomidine is contraindicated because of a severe hypertensive response.

Effects of 6% Tetrastarch and Lactated Ringer's Solution on Extravascular Lung Water and Markers of Acute Renal Injury in Hemorrhaged, Isoflurane-Anesthetized Healthy Dogs.

BACKGROUND: Tetrastarch can cause acute kidney injury (AKI) in humans with sepsis, but less likely to result in tissue edema than lactated Ringer's solution (LRS). OBJECTIVES: Compare effects of volume replacement (VR) with LRS and 6% tetrastarch solution (TS) on extravascular lung water (EVLW) and markers of AKI in hemorrhaged dogs. ANIMALS: Six healthy English Pointer dogs (19.7-35.3 kg). METHODS: Prospective crossover study. Animals underwent anesthesia without hemorrhage (Control). Two weeks later, dogs hemorrhaged under anesthesia on 2 occasions (8-week washout intervals) and randomly received VR with LRS or TS at 3 : 1 or 1 : 1 of shed blood, respectively. Anesthesia was maintained until 4 hour after VR for EVLW measurements derived from transpulmonary thermodilution cardiac output. Neutrophil gelatinase-associated lipocalin (NGAL) and creatinine concentrations in plasma and urine were measured until 72 hour after VR. RESULTS: The EVLW index (mL/kg) was lower at 1 hour after TS (10.0 ± 1.9) in comparison with controls (11.9 ± 3.4, P = 0.04), and at 4 hour after TS (9.7 ± 1.9) in comparison with LRS (11.8 ± 2.7, P = 0.03). Arterial oxygen partial pressure-to-inspired oxygen fraction ratio did not differ among treatments from 0.5 to 4 hour after VR. Urine NGAL/creatinine ratio did not differ among treatments and remained below threshold for AKI (120,000 pg/mg). CONCLUSIONS AND CLINICAL IMPORTANCE: Although TS causes less EVLW accumulation than LRS, neither fluid produced evidence of lung edema (impaired oxygenation). Both fluids appear not to cause AKI when used for VR after hemorrhage in healthy nonseptic dogs.

Comparison of Transpulmonary Thermodilution and Calibrated Pulse Contour Analysis with Pulmonary Artery Thermodilution Cardiac Output Measurements in Anesthetized Dogs.

BACKGROUND: Transpulmonary thermodilution (TPTDCO ) and calibrated pulse contour analysis (PCACO ) are alternatives to pulmonary artery thermodilution cardiac output (PATDCO ) measurement. HYPOTHESIS: Ten mL of ice-cold thermal indicator (TI10 ) would improve the agreement and trending ability between TPTDCO and PATDCO compared to 5 mL of indicator (TI5 ) (Phase-1). The agreement and TA between PCACO and PATDCO would be poor during changes in systemic vascular resistance (SVR) (Phase-2). ANIMALS: Eight clinically normal dogs (20.8-31.5 kg). METHODS: Prospective, experimental study. Simultaneous TPTDCO and PATDCO (averaged from 3 repetitions) using TI5 and TI10 were obtained during isoflurane anesthesia combined or not with remifentanil or dobutamine (Phase-1). Triplicate PCACO and PATDCO measurements were recorded during phenylephrine-induced vasoconstriction and nitroprusside-induced vasodilation (Phase-2). RESULTS: Mean bias (limits of agreement: LOA) (L/min), percentage bias (PB), and percentage error (PE) were 0.62 (-0.11 to 1.35), 16%, and 19% for TI5 ; and 0.33 (-0.25 to 0.91), 9%, and 16% for TI10 . Mean bias (LOA), PB, and PE were 0.22 (-0.63 to 1.07), 6%, and 23% during phenylephrine; and 2.12 (0.70-3.55), 43%, and 29% during nitroprusside. Mean angular bias (radial LOA) values were 2° (-10° to 14°) and -1° (-9° to 6°) for TI5 and TI10 , respectively (Phase-1), and 38° (5°-71°) (Phase-2). CONCLUSIONS AND CLINICAL IMPORTANCE: Although TI10 slightly improves the agreement and trending ability between TPTDCO and PATDCO in comparison to TI5 , both volumes can be used for TPTDCO in replacement of PATDCO . Vasodilation worsens the agreement between PCACO and PATDCO . Because of PCACO 's poor agreement and trending ability with PATDCO during SVR changes, this method has limited clinical application.

The effects of atropine and methotrimeprazine on the epinephrine-induced arrhythmias in halothane-anesthetized dogs.

The effects of atropine and methotrimeprazine on epinephrine-induced ventricular arrhythmias were evaluated in halothane-anesthetized dogs. Ten mixed-breed dogs were assigned to 3 treatments (saline, atropine, and methotrimeprazine) in a randomized complete block design. Anesthesia was induced and maintained with halothane (1.5 minimum alveolar concentration) in oxygen. Controlled ventilation was used throughout to maintain eucapnia. Saline, atropine (0.05 mg/kg, i.v.) or methotrimeprazine (0.5 mg/kg, i.v.) were administered and, 5 minutes later the arrhythmogenic dose of epinephrine (ADE) was measured by i.v. infusion of progressively increasing infusion rates of epinephrine, until the ventricular arrhythmia criterion was met (at least 4 ectopic ventricular contractions (EVCs) during a 15-second period). Data were analyzed using a student's t-test for ADE values and multivariate profile analysis for heart rate (HR), arterial blood pressure (ABP), and rate pressure product (RPP). The ADE increased in atropine- and methotrimeprazine-treated groups, whereas 1 and 4 animals from these groups did not develop any ventricular arrhythmia, respectively. Epinephrine induced multiform premature ventricular contractions (PVCs) in the atropine group, whereas ventricular escape beats were observed in the control and methotrimeprazine groups. Heart rate and RPP decreased, and ABP increased at the time of ADE observation in the control group. Epinephrine infusion in the atropine group caused marked increases in HR, ABP, and RPP, which were associated with pulsus alternans in 2 animals. It was concluded that 1) the presence of cholinergic blockade influences the type of ventricular arrhythmia induced by epinephrine; 2) increased ADE values recorded following atropine administration must be cautiously interpreted, since in this situation the PVCs were associated with signs of increased myocardial work and ventricular failure; and 3) the use of a broader arrhythmia criterion (EVCs instead of PVCs) may not allow a direct comparison between ADE values, since it includes ventricular arrhythmias mediated by different mechanisms.

Effects of four anaesthetic protocols on the neurological and cardiorespiratory variables of puppies born by caesarean section.

Twenty-four bitches which had been in labour for less than 12 hours were randomly divided into four groups of six. They all received 0.5 mg/kg of chlorpromazine intravenously as premedication, followed 15 minutes later by either 8 mg/kg of thiopentone intravenously (group 1), 2 mg/kg of ketamine and 0.5 mg/kg of midazolam intravenously (group 2), 5 mg/kg of propofol intravenously (group 3), or 2.5 mg/kg of 2 per cent lidocaine with adrenaline and 0.625 mg/kg of 0.5 per cent bupivacaine with adrenaline epidurally (group 4). Except for group 4, the bitches were intubated and anaesthesia was maintained with enflurane. The puppies' heart and respiratory rates and their pain, sucking, anogenital, magnum and flexion reflexes were measured as they were removed from the uterus. The puppies' respiratory rate was higher after epidural anaesthesia. In general the puppies' neurological reflexes were most depressed after midazolam/ketamine, followed by thiopentone, propofol and epidural anaesthesia.

Reduction of humeroulnar congenital elbow luxation in 8 dogs by using the transarticular pin.

The purpose of this study was to evaluate the clinical and radiographic outcome in 8 dogs of surgical reduction of congenital humeroulnar luxation by using the transarticular pin. Five cases were bilateral and 3 were unilateral, for a total of 13 elbows. The treatment was performed in animals between 45 and 150 days of age. Articular stabilization was achieved by using a transarticular pin driven from the caudal aspect of the olecranon into the body of the humerus or into the distal condyle and distal metaphysis of the humerus. The follow-up period was between 1 and 19 months. There were 5 postsurgical reluxations, 3 related to the insertion of the pin into the humeral condyle and 2 related to the insertion into the humeral body. These animals needed further surgery. Six animals showed near normal return to limb function and 2 had lameness. We conclude that the use of the transarticular pin is an effective and simple method for the treatment of humeroulnar congenital elbow luxation.

Efeitos do modo ventilatório sobre variáveis hemogasométricas em equinos submetidos à mudança de decúbito durante a anestesia geral inalatória com halotano / Effects of the ventilatory regimen on arterial blood gas variables in horses that underwent a change in body position during halothane anesthesia

Compararam-se os efeitos da ventilação espontânea (V E) e controlada (V C) em equinos submetidos à mudança de decúbito durante anestesia. Dezesseis animais foram equitativamente divididos em dois grupos: V E e V C. Os procedimentos cirúrgicos foram iniciados com os animais em decúbito lateral esquerdo (DLE) e, após 75 minutos, os animais foram reposicionados em decúbito lateral direito (DLD). Análises hemogasométricas do sangue arterial foram realizadas após 30 e 75 minutos com os animais posicionados em cada decúbito (M1 e M2 no DLE e M3 e M4 no DLD, respectivamente). Durante a V E, observaram-se hipercapnia (PaCO2 >45mmHg), acidose respiratória (pH <7,35), redução significativa da oxigenação sanguínea após 75min da mudança de decúbito (M4: 205,8±124,7mmHg) em relação aos valores de PaO2 observados antes da mudança de posicionamento (M1: 271,8±84,8mmHg). A Vc foi associada a valores de PaCO2 e pH mais próximos da normalidade bem como resultou em valores de PaO2 significativamente maiores (52 a 96 por cento de elevação nos valores médios) que a V E. Conclui-se que a mudança de decúbito, em equinos anestesiados com halotano e mantidos sob V E, resulta em hipercapnia, acidose respiratória e diminuição dos valores de PaO2. A instituição de V C, desde o início da anestesia, previne a acidose respiratória, além de resultar em valores de PaO2 mais próximos do ideal para animais respirando O2 a 100 por cento.

The effects of spontaneous (SV) and controlled ventilation (CV) were compared in horses undergoing changes in body position during anesthesia. Sixteen animals were equally distributed in two groups: SV and CV. All surgical procedures were commenced on left lateral recumbency (LLR) and 75 minutes later the animals were repositioned on right lateral recumbency (RLR). Arterial blood gas analyses were performed at 30 and 75 minutes after each recumbency (M1 and M2 for LLR and M3 and M4 for RLR). Hypercapnia (PaCO2 >45mmHg), respiratory acidosis (pH <7.35), and significant decrease in PaO2 after 75min of change in body position (M4: 205.8±124.7mmHg) in comparison to PaO2 values before the change of position (M1: 271.8±84.8mmHg) were observed during SV. When compared to the SV group, CV resulted in significantly higher PaO2 levels (52 to 96 percent increase). It was concluded that the change in the body position in spontaneously ventilating halothane-anesthetized horses causes impairment in arterial oxygenation. The use of CV since the beginning of anesthesia prevents the respiratory acidosis and maintains arterial oxygen levels that are closer to values expected during the use of 100 percent O2.

The effect of changing the mode of ventilation on the arterial-to-end-tidal CO2 difference and physiological dead space in laterally and dorsally recumbent horses during halothane anesthesia.

OBJECTIVE: To evaluate the effect of changing the mode of ventilation from spontaneous to controlled on the arterial-to-end-tidal CO2 difference [P(a-ET)CO2] and physiological dead space (VD(phys)/VT) in laterally and dorsally recumbent halothane-anesthetized horses. STUDY DESIGN; Prospective, experimental, nonrandomized trial. ANIMALS: Seven mixed breed adult horses (1 male and 6 female) weighing 320 +/- 11 kg. METHODS: Horses were anesthetized in 2 positions-right lateral and dorsal recumbency-with a minimum interval of 1 month. Anesthesia was maintained with halothane in oxygen for 180 minutes. Spontaneous ventilation (SV) was used for 90 minutes followed by 90 minutes of controlled ventilation (CV). The same ventilator settings were used for both laterally and dorsally recumbent horses. Arterial blood gas analysis was performed every 30 minutes during anesthesia. End-tidal CO2 (PETCO2) was measured continuously. P(a-ET)CO2 and VD(phys)NT were calculated. Statistical analysis included analysis of variance for repeated measures over time, followed by Student-Newman-Keuls test. Comparison between groups was performed using a paired t test; P < .05 was considered significant. RESULTS: P(a-ET)CO2 and VD(phys)/VT increased during SV, whereas CV reduced these variables. The variables did not change significantly throughout mechanical ventilation in either group. Dorsally recumbent horses showed greater P(a-ET)CO2 and VD(phys)/VT values throughout. PaCO2 was greater during CV in dorsally positioned horses. CONCLUSIONS AND CLINICAL RELEVANCE: Changing the mode of ventilation from spontaneous to controlled was effective in reducing P(a-ET)CO2 and physiological dead space in both laterally and dorsally recumbent halothane-anesthetized horses. Dorsal recumbency resulted in greater impairment of effective ventilation. Capnometry has a limited value for accurate estimation of PaCO2 in anesthetized horses, although it may be used to evaluate pulmonary function when paired with arterial blood gas analysis.