Rocío Navarrete

Histological Study of the Influence of Plasma Rich in Growth Factors (PRGF) on the Healing of Divided Achilles Tendons in Sheep

BACKGROUND The use of plasma rich in growth factors (PRGF) has been proposed to improve the healing of Achilles tendon injuries, but there is debate about the effectiveness of this therapy. The objective of the present study was to evaluate the histological effects of PRGF, which is a type of leukocyte-poor platelet-rich plasma, on tendon healing. METHODS The Achilles tendons of twenty-eight sheep were divided surgically. The animals were randomly divided into four groups of seven animals each. The repaired tendons in two groups received an infiltration of PRGF intraoperatively and every week for the following three weeks under ultrasound guidance. The tendons in the other two groups received injections with saline solution. The animals in one PRGF group and one saline solution group were killed at four weeks, and the animals in the remaining two groups were killed at eight weeks. The Achilles tendons were examined histologically, and the morphometry of fibroblast nuclei was calculated. RESULTS The fibroblast nuclei of the PRGF-treated tendons were more elongated and more parallel to the tendon axis than the fibroblast nuclei of the tendons in the saline solution group at eight weeks. PRGF-treated tendons showed more packed and better oriented collagen bundles at both four and eight weeks. In addition to increased maturation of the collagen structure, fibroblast density was significantly lower in PRGF-infiltrated tendons. PRGF-treated tendons exhibited faster vascular regression than tendons in the control groups, as demonstrated by a lower vascular density at eight weeks. CONCLUSIONS PRGF was associated with histological changes consistent with an accelerated early healing process in repaired Achilles tendons in sheep after experimental surgical disruption. PRGF-treated tendons showed improvements in the morphometric features of fibroblast nuclei, suggesting a more advanced stage of healing. At eight weeks, histological examination revealed more mature organization of collagen bundles, lower vascular densities, and decreased fibroblast densities in PRGF-treated tendons than in tendons infiltrated with saline solution. These findings were consistent with a more advanced stage of the healing process. CLINICAL IMPLICATIONS Based on the findings in this animal model, PRGF infiltration may improve the early healing process of surgically repaired Achilles tendons.

Cardiotrophin-1 reduces ischemia/reperfusion injury during liver transplant

BACKGROUND Orthotopic liver transplantation (OLT) is currently the elective treatment for advanced liver cirrhosis and acute liver failure. Ischemia/reperfusion damage may jeopardize graft function during the postoperative period. Cardiotrophin-1 (CT-1) has demonstrated cytoprotective properties in different experimental models of liver injury. There is no evidence to demonstrate its potential use in the prevention of the ischemia/reperfusion injury that occurs during OLT. The present study is the first report to show that the administration of CT-1 to donors would benefit the outcome of OLT. MATERIALS AND METHODS We tested the cytoprotective effect of CT-1 administered to the donor prior to OLT in an experimental pig model. Hemodynamic changes, hepatic histology, cell death parameters, activation of cell signaling pathways, oxidative and nitrosative stress, and animal survival were analyzed. RESULTS Our data showed that CT-1 administration to donors increased animal survival, improved cardiac and respiratory functions, and reduced hepatocellular injury as well as oxidative and nitrosative stress. These beneficial effects, related to the activation of AKT, ERK, and STAT3, reduced caspase-3 activity and diminished IL-1β and TNF-α expression together with IL-6 upregulation in liver tissue. CONCLUSIONS The administration of CT-1 to donors reduced ischemia/reperfusion injury and improved survival in an experimental pig model of OLT.

Postoperative analgesic effects of dexketoprofen, buprenorphine and tramadol in dogs undergoing ovariohysterectomy

The objective of this study was to compare the postoperative analgesic effects of dexketoprofen, tramadol, and buprenorphine in dogs undergoing ovariohysterectomy. Seventy-five adult female dogs were randomly assigned to receive an intravenous injection (IV) of 1mg/kg of dexketoprofen (D), 0.02 mg/kg of buprenorphine (B) or 2mg/kg of tramadol (T). Pain assessment was performed during 48 h after ovariohysterectomy using a dynamic interactive visual analogue scale (DIVAS) and Glasgow composite measure pain scale (CMPS-SF). Rescue analgesia was required in 43%, 21%, and 5% of dogs in the B, T, and D groups, respectively, with significant differences between B and D (p=0.010) groups. The DIVAS and CMPS-SF values of the B group were significantly higher than those of the T and D groups. The most common undesirable effect was dysphoria in dexketoprofen group. Tramadol and dexketoprofen provide superior postoperative analgesia compared with buprenorphine in dogs undergoing ovariohysterectomy.

Comparison of thermodilution, lithium dilution, and pulse contour analysis for the measurement of cardiac output in 3 different hemodynamic states in dogs

OBJECTIVE To (1) evaluate lithium dilution (LiDCO) and transpulmonary thermodilution (PiCCOTD ) in relation to traditional thermodilution (PAC-TD) for determining cardiac output (CO) in 3 different hemodynamic states in dogs and to (2) compare the continuous CO values obtained using power analysis (PulseCO) with continuous PiCCO (PiCCOc). DESIGN Prospective randomized study. SETTING University research laboratory. ANIMALS Fourteen healthy Beagles. INTERVENTIONS CO was measured using PAC-TD, LiDCO, and PiCCOTD in 3 different hemodynamic states induced in random order and defined on the basis of the mean arterial pressure (MAP). Normodynamic state was defined as the baseline MAP and 1 MAC sevoflurane. The hypodynamic state was induced with a deep level of sevoflurane anesthesia. The hyperdynamic state was induced with noradrenaline. After these measurements were obtained in each hemodynamic state, CO was monitored continuously for 30 min using PulseCO and PiCCOc. Agreement was assessed using Bland-Altman analysis and intraclass correlation coefficients, and a trend score was determined for the continuous CO measurements. MEASUREMENTS AND MAIN RESULTS There was good agreement among the 3 modalities of CO measurement in each hemodynamic state. The mean CIPAC-TD /CIPICCOTD bias was -0.04 ± 1.19 L/min/m(2) (limits of agreement, -2.37/1.93 L/min/m(2) ), and the mean CIPAC-TD /CILiDCO bias was -0.11 ± 1.55 L/min/m(2) (limits of agreement, -3.04/2.93 L/min/m(2) ). The mean CIPulseCO -CIPiCCOc bias was -0.04 ± 1.91 L/min/m(2) (limits of agreement, -1.95/1.87 L/min/m(2) ), which suggested good agreement. The CIPulseCO -CIPiCCOc trend score, calculated from 252 paired comparisons, was 93.3% positive after zone exclusion (∆CI < 15%). CONCLUSIONS Both LiDCO and PiCCOTD agreed well with PAC-TD for the measurement of CO under different hemodynamic conditions. Moreover, PiCCOc appears to be an accurate method for monitoring continuous CO in dogs as its performance for measurement was similar to that of PulseCO.

Evaluation of spectral entropy to measure anaesthetic depth and antinociception in sevoflurane-anaesthetised Beagle dogs

The use of spectral entropy to determine anaesthetic depth and antinociception was evaluated in sevoflurane-anaesthetised Beagle dogs. Dogs were anaesthetised at each of five multiples of their individual minimum alveolar concentrations (MAC; 0.75, 1, 1.25, 1.5 and 1.75 MAC), and response entropy (RE), state entropy (SE), RE-SE difference, burst suppression rate (BSR) and cardiorespiratory parameters were recorded before and after a painful stimulus. RE, SE and RE-SE difference did not change significantly after the stimuli. The correlation between MAC-entropy parameters was weak, but these values increased when 1.75 MAC results were excluded from the analysis. BSR was different to zero at 1.5 and 1.75 MAC. It was concluded that RE and RE-SE differences were not adequate indicators of antinociception and SE and RE were unable to detect deep planes of anaesthesia in dogs, although they both distinguished the awake and unconscious states.

A comparison of the effect of convection against diffusion in hemodynamics and cytokines clearance in an experimental model of septic shock.

BACKGROUND Replacement therapies based on the use of convection have value for the removal of inflammatory mediators. Such therapies have been proposed for the management of septic shock, but diffusion has not proved useful in this scenario, unless high-flow membranes are used. The exact role of diffusion in these cases remains to be clarified because continuous replacement therapies are usually delivered with low-flow membranes and mixed convection-diffusion modalities. However, studies specifically addressing this problem have not been performed. Our aim was to define the efficacy of hemofiltration (convection) and hemodialysis (diffusion) in cytokine clearance and hemodynamic improvement in an experimental model of septic shock. METHODS Shock was induced in 15 beagle dogs (weight 10–15 kg) by infusion of 1 mg/kg of ultrapure Escherichia coli lipopolysaccharide diluted in 20 mL saline for 10 minutes. Five animals were followed without interventions (controls), five animals were treated with convection (100 mL kg−1 h−1) for 6 hours, and five animals were treated with diffusion (100 mL kg−1 h−) for 6 hours. RESULTS All subjects in the control group died during the study, whereas all treated subjects survived. Mean arterial pressure, cardiac output, systolic variability volume, systemic vascular resistances, dPMax, and pulmonary compliance improved in treated subjects. However, the differences in mean arterial pressure and cardiac output were significant only in the convection group and not in the diffusion-treated group. Tumor necrosis factor &agr; rose equally in all groups and decreased only in treated subjects. Interleukin 6 rose in the three groups but decreased only in the convection group and remained unchanged in the control and diffusion groups. CONCLUSION Convection and diffusion improved survival and hemodynamic parameters in a septic shock model. Improvement was more pronounced with convection, a difference that may be explained by convective clearance of cytokines.

Anaesthetic and cardiorespiratory effects of a constant-rate infusion of alfaxalone in desflurane-anaesthetised sheep.

A prospective, randomised, blinded controlled study was performed to determine the anaesthetic and cardiorespiratory effects of a constant-rate infusion (CRI) of alfaxalone in 12 sheep anaesthetised with desflurane, and undergoing experimental orthopaedic surgery. Sheep were sedated with dexmedetomidine (4 μg/kg, intravenously) and butorphanol (0.3 mg/kg, intravenously). Anaesthesia was induced with alfaxalone (1 mg/kg/minute to effect, intravenously) and maintained with desflurane in oxygen and alfaxalone 0.07 mg/kg/minute or saline for 150 minutes (range 150–166 minutes). The anaesthetic induction dose of alfaxalone, the desflurane expiratory fraction required for anaesthetic maintenance, cardiorespiratory measurements and blood-gases were recorded at predetermined intervals. Quality of sedation, anaesthetic induction and recovery were assessed. The alfaxalone induction dose was 1.7 mg/kg (1.2 to 2.6 mg/kg). The desflurane expiratory fraction was lower (22 per cent) in sheep receiving alfaxalone CRI (P = 0). Also, heart rate (P = 0), cardiac index (P = 0.002), stroke index (P = 0) and contractility (P = 0) were higher, and systemic vascular resistance (P = 0.002) was lower. Although respiratory rate tended to be higher with alfaxalone, there was no difference in PCO2 between the groups. Recovery times were significantly longer in sheep given alfaxalone (25.4 v 9.5 minutes) but recovery quality was similar. Alfaxalone reduced requirements of desflurane and maintained similar cardiorespiratory function, but recovery time was more prolonged.

Relationship of bispectral index to hemodynamic variables and alveolar concentration multiples of sevoflurane in puppies.

The relationships between bispectral index (BIS), cardiovascular variables and minimum alveolar concentration (MAC) multiples of sevoflurane in puppies were determined. Five puppies were anesthetized with sevoflurane on two occasions. First, the individual sevoflurane MAC values were determined for each puppy. Secondly, dogs were anesthetized with sevoflurane at each of 5 MAC multiples, 0.75, 1, 1.25, 1.5 and 1.75 MAC administered in random order. Hemodynamic parameters and BIS data were collected for 20min. Somatic stimulus was then applied and the same parameters and data were collected for 6min. Correlation between BIS and end tidal sevoflurane and between BIS and hemodynamic parameters were studied. We found positive significant correlation in both cases. BIS is lower in puppies that in adults at the same alveolar anesthetic concentrations and sevoflurane appears to be a safe anesthetic in puppies.

Bladder mucosal CO2 compared with gastric mucosal CO2 as a marker for low perfusion states in septic shock.

Recent reports indicate the possible role of bladder CO2 as a marker of low perfusion states. To test this hypothesis, shock was induced in six beagle dogs with 1 mg/kg of E. coli lipopolysaccharide, gastric CO2 (CO2-G) was measured with a continuous monitor, and a pulmonary catheter was inserted in the bladder to measure CO2 (CO2-B). Levels of CO2-B were found to be lower than those of CO2-G, with a mean difference of 36.8 mmHg (P < 0.001), and correlation between both measurements was poor (r 2 = 0.16). Even when the correlation between CO2-G and ΔCO2-G was narrow (r 2 = 0.86), this was not the case for the relationship between CO2-B and ΔCO2-B (r 2 = 0.29). Finally, the correlation between CO2-G and base deficit was good (r 2 = 0.45), which was not the case with the CO2-B correlation (r 2 = 0.03). In our experience, bladder CO2 does not correlate to hemodynamic parameters and does not substitute gastric CO2 for detection of low perfusion states.

Effectiveness of pre-peritoneal continuous wound infusion with lidocaine for pain control following ovariohysterectomy in dogs.

This study compared the post-operative analgesic efficacy of continuous lidocaine administration with that of intramuscular (IM) methadone in dogs undergoing ovariohysterectomy. Thirty-eight dogs were divided randomly into two groups. Following surgery, the lidocaine group (L) received a continuous lidocaine infusion (2 mg/kg/h) through a wound catheter inserted in the pre-peritoneal space; the control group (C) received methadone (0.2 mg/kg IM). A dynamic and interactive visual analogue scale (DIVAS), the Scale-Form Glasgow Composite Measure Scale (CMPS-SF), mechanical wound thresholds, heart rate, respiratory rate and blood pressure were assessed pre-operatively and 2, 4, 6, 18, and 24 h after surgery. The presence of the wound catheter prevented the evaluator from remaining blinded to group allocations. Plasma lidocaine and cortisol levels were measured 2, 6, 18, and 24 h after surgery. There were no intergroup differences in any pain assessment scale scores at any time point. Stable intravenous lidocaine levels were observed. Four animals in the control group but none in the lidocaine group required rescue analgesia. There were no differences in complication rates between groups. Continuous locoregional lidocaine delivered via a wound catheter between the parietal peritoneum and abdominal muscle offers effective analgesia in dogs during ovariohysterectomy and appears to be a promising analgesic option in veterinary surgery.