Vein Of Pigs Research Articles

Therapeutic inhibition of biomechanically-activated YAP-TAZ signaling prevents vein graft atherosclerosis

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Rembrandt Institute for Cardiovascular Sciences Background Venous bypass grafts may have limited patency due to excessive intimal hyperplasia and accelerated atherosclerosis. YAP-TAZ signaling regulates cellular responses to biomechanical cues, such as disturbed flow or vessel distention as seen in vein grafts. YAP activation leads to inflammation and angiogenesis, which both contribute to vein graft atherosclerosis. Inhibition of YAP-TAZ attenuates naive atherogenesis, but its potential to inhibit intraplaque angiogenesis and reduce vein graft atherosclerosis has not been explored. Methods Saphenous vein progenitor cells (SVPs) were subjected to mechanical strain in vitro to assess YAP activation. IHC to assess YAP-expression was performed on vein grafts from pigs as well as ex vivo cultured human saphenous veins. Furthermore, YAP-IHC was performed on murine vein grafts from hypercholesterolemic ApoE3*Leiden mice harvested at early, mid- and late-stage disease timepoints to assess optimal treatment window. In a separate experiment, mice (n=11-13/group) underwent bypass surgery and were treated with the FDA-approved YAP-TAZ inhibitor Verteporfin (50 mg/kg) or vehicle 3 times/week from day 10 until sacrifice (day 28). Ultrasound was used to longitudinally quantify vascular remodeling. Vein grafts were harvested and processed for morphometric and compositional analysis. Results Mechanical strain induced activation of YAP and its downstream targets (Ctgf, Cyr61) in SVPs, which was inhibited by Verteporfin (confirmed by WB, IP and qPCR). Moreover, YAP was abundantly expressed in pig vein graft lesions, whilst Verteporfin blocked YAP expression in ex vivo cultured human saphenous veins after exposure to disturbed flow. In addition, YAP was increasingly expressed during vein graft lesion development in mice, reaching its peak around day 14, which coincides with the initiation of intraplaque angiogenesis. Furthermore, YAP was predominantly expressed in luminal and adventitial endothelial cells. Analysis of ultrasound demonstrated that Verteporfin prevented vein graft thickening in mice over time. End-point histology revealed that the intima/media ratio was significantly decreased by Verteporfin treatment (37%, p=0.001). Intraplaque angiogenesis was also reduced (34%, p=0.002), whilst neovessel maturation was improved upon verteporfin treatment. The vessel wall ACTA2 content was reduced (42%, p=0.023), whilst collagen was not altered between both groups, indicating that Verteporfin diminished the fibroproliferative response without affecting vessel wall stability. Conclusion Verteporfin inhibited YAP-TAZ activation induced by mechanical strain in vitro (SVPs) as well as ex vivo (cultured human saphenous veins). In vivo, Verteporfin treatment resulted in a significant decrease of vein graft atherosclerosis and intraplaque angiogenesis. Therefore, therapeutic targeting of YAP-TAZ using Verteporfin might be a new candidate to improve vein graft patency.

Abstract 9321: Cardiac Work and End-Organ Perfusion During Biventricular Compared to Left Ventricular Impella and Norepinephrine Support in a Porcine Model of Severe Cardiogenic Shock

Background: Vasopressors are often combined with left ventricular (LV) mechanical support in severe cardiogenic shock to increase end-organ perfusion. Biventricular mechanical support might improve end-organ perfusion at lower cardiac workload compared to LV mechanical support and vasopressor infusion in severe cardiogenic shock. Aim: To compare LV and right ventricular (RV) total cardiac work (pressure-volume area x heart rate x 10 3 ) and organ-specific venous oxygen saturations from the pulmonary artery (SvO 2 ), kidney- and cerebral- veins in pigs with cardiogenic shock treated with biventricular (Bipella) versus ImpellaCP + norepinephrine 0.10 μg/kg/min (Imp+NE). Methods: Cardiogenic shock was induced by injections of microspheres into the left main coronary artery in eight pigs (approx. 70 kg). From conductance catheters in both ventricles, cardiac workload was calculated, and oxygen saturations were attained from the pulmonary artery, internal jugular- and kidney vein. Pigs were allocated in a crossover model to Bipella for 60 minutes (n=4) or Imp+NE for 30 minutes (n=4) and after completion shifted to the opposite treatment. Results are presented as median(Q1;Q3). Results: Bipella effectively unloaded the LV with reduction in LV work compared to Imp+NE (569[410-685] vs 357[206-509] 10 3 ml x mmHg/min, p=0.0078) while RV work was comparable (p=0.74). A significant increase in SvO 2 (66[63-73] vs 49[44-58]%, p=0.01) and cerebral venous oxygen saturations (71[63-77] vs 62[48-66]%, p=0.016) was observed during Imp+NE compared to Bipella, whereas no difference in kidney oxygen saturations was demonstrated (p=0.31). Conclusion: In this porcine study of cardiogenic shock due to left main coronary ischemia, Bipella decreased LV workload, but systemic oxygen delivery was not optimal (Figure). Imp+NE provided a higher LV workload balanced by an improvement in cerebral- and mixed venous oxygen saturation.

Design of a Surgical Pen-Type Probe for Real-Time Indocyanine Green Fluorescence Emission Diagnosis

Abstract The advantage of handheld type surgical microscope is that the size of the probe is small and light, and that both the working distance (15–30 cm) and field of view (30 deg) can be adjusted. The shortness working distance will minimize the loss of light source energy. However, the currently developed handheld type surgical microscope is still large, heavy, and uses relatively high energy (600 mW/cm2). To address the aforementioned problems, this study aimed to develop a pen-type surgical fluorescence microscope that is compact, portable, and has an adjustable beam angle and working distance. These features enable real-time diagnosis. The pen-type probe consists of a laser diode, CMOS camera, light source brightness control device, filter, and power switch. The IR-cut filter inside the CMOS camera was removed to facilitate transmission of the fluorescence emission wavelength. In addition, a long-pass filter was attached to the camera so that the external light source was blocked and only the fluorescence emission wavelength was allowed to pass through. The performance of the pen-type probe was tested through a large animal experiment. Indocyanine green (2.5 mg/kg) was injected into a pig's vein. Fluorescence emission of 805-830 nm was achieved by irradiating an external light source (785 nm and 4 mW/cm2), and liver-uptake occurred after 2.4 min. The designed pen-type probe was capable of sufficiently fluorescence expression through low-energy irradiation, and the pen-type probe is small and light and easy to handle by hand because both the pen-based laser device and the camera device are integrated. In addition, it is easy to adjust the working distance and field of view.

Minimally invasive ultrasound-guided technique for central venous catheterization via the external jugular vein in pigs.

To describe an ultrasound-guided technique for central venous catheter placement via the external jugular vein (EJV) in pigs. 96 healthy Landrace-Poland China barrows (approx 16 weeks old with a mean weight of 70 kg). Pigs were anesthetized. With ultrasound guidance, a needle was inserted into the EJV without a large incision or cutdown procedure. A guidewire was inserted through the needle into the vein. A modified Seldinger technique was used to advance a catheter into the vessel until the tip was in the cranial vena cava near the right atrium. A trocar was used to create a tunnel through the subcutaneous tissues from the catheter insertion site to between the dorsal borders of the scapulae. The free end of the catheter was passed through that tunnel. An extension was attached to the catheter and secured to the skin. Pigs were euthanized and underwent necropsy at completion of the study for which they were catheterized. Central venous catheters were successfully placed in all 96 pigs and facilitated collection of serial blood samples with minimal stress. Catheters remained in place for a mean of 6 days (range, 4 to 10 days). Necropsy revealed abscesses along the subcutaneous catheter tract in 9 pigs. Twenty pigs had histologic evidence of phlebitis and fibroplasia in the cranial vena cava. The described technique, in combination with extensive socialization, allowed serial collection of blood samples with minimal stress and restraint and is an alternative to surgical cutdown procedures for catheter placement.

Effects of Lysine Cell Mass Supplementation as a Substitute for L-Lysine·HCl on Growth Performance, Diarrhea Incidence, and Blood Profiles in Weaning Pigs.

Simple SummaryLysine cell mass (LCM) is a potential protein and lysine source for pigs. However, the potential value of LCM as a lysine source for the swine diet has not been investigated. Therefore, this study was conducted to evaluate the effects of LCM as an alternative lysine source in diets for weaning pigs. In the first experiment, an increase in dietary LCM from 0 to 1% did not affect the growth performance and diarrhea incidence of weaning pigs. However, in the second experiment, increasing the level of LCM supplementation for replacing L-lysine·HCl from 0% to 100% quadratically decreased the growth performance of weaning pigs such that replacing 0 to 80% of L-lysine·HCl with LCM had no difference in the growth performance, whereas LCM supplementation with 100% replacement of L-lysine·HCl decreased the average daily gain and gain to feed ratio of weaning pigs. We concluded that LCM could be included in the diet for weaning pigs as a substitute of L-lysine·HCl up to 2.8% and 1.76% for phase 1 and phase 2, respectively, without negative impacts on the performance of weaning pigs.This study was conducted to evaluate the effects of lysine cell mass (LCM) as an alternative lysine source in diets for weaning pigs on growth performance, diarrhea incidence, and blood profiles. In experiment 1, a total of 200 weaning pigs, with an average body weight (BW) of 6.89 ± 1.04 kg, were allotted into one of five treatments with four replicates of 10 pigs per pen in a randomized complete block design (RCBD). The dietary treatments were composed of LCM supplementation (0, 0.25, 0.5, 0.75, or 1.0%) with partial replacement of L-lysine·HCl (0 to 0.8% for phase 1 diets and 0 to 0.07% for phase 2 diets). The BW and feed intake were recorded at the end of each phase (d 0 to 14 for phase 1, d 14 to 35 for phase 2), and diarrhea incidence was checked daily throughout the experimental period. Blood samples were taken from the jugular vein of pigs at 2 weeks and 5 weeks to determine the blood profiles of weaning pigs. In experiment 2, a total of 144 weaning pigs with an average BW of 6.44 ± 1.19 kg were allotted into one of six treatments with six replicates of four pigs per pen in RCBD. The dietary treatments were composed of LCM supplementation (0 to 3.5% for phase 1 diets and 0 to 2.2% for phase 2 diets) with replacement of L-lysine·HCl from 0 to 100%. In experiment 1, partial replacement of L-lysine·HCl with 0 to 1% LCM did not affect growth performance and diarrhea incidence of pigs. An increase in the LCM supplementation from 0 to 1% with partial replacement of L-lysine·HCl had no influence on the blood urea nitrogen concentrations, whereas it resulted in a linear decrease (p < 0.05) in the serum IgG concentrations for 5 weeks. In experiment 2, increasing the dietary level of LCM with replacement of L-lysine·HCl quadratically decreased (p < 0.05) ADG and G–F ratio for phase 2 and G–F ratio for the overall period such that 100% replacement of L-lysine·HCl with LCM decreased ADG and G–F ratio of weaning pigs. An increase in the LCM supplementation with replacement of L-lysine·HCl tended to decrease linearly (p < 0.10) the diarrhea incidence of weaning pigs for the overall period and linearly decrease (p < 0.05) the serum IgG concentrations for 2 weeks. In conclusion, partial replacement of L-lysine·HCl with LCM from 0 to 1% had no negative impacts on the growth performance, but 100% replacement of L-lysine·HCl with LCM decreased the growth performance of weaning pigs. Therefore, LCM could be included in the diets for weaning pigs up to 2.8% and 1.76% for phase 1 and phase 2, respectively, as a substitute for L-lysine·HCl without detrimental effects on the performance of weaning pigs.

The method of long-term catheterization of the vena jugularis in pigs

IntroductionThe pig is one of the most valuable in vivo models in biomedical research, however with only a few well-accessible veins suitable for venipuncture. Moreover, most of the known methods of blood collection are suitable only for a limited time period. The aim of the study was to verify an improved method of long-term catheterization of the jugular vein in pigs. MethodsA 420 mm polyurethane catheter 16G tube was surgically inserted using the Seldinger technique. The part of the tube that was not inserted into the vein was threaded through a subcutaneously introduced trocar into the occipital area, where it was well accessible and well protected from damage. The catheters were flushed with sterile 0.9% saline solution and locked with 4% citrate between frequent blood samplings, or with 30% citrate at intervals of 1–2-days. Once a week, the catheters were locked with 4% citrate containing taurolidine for 24 h in order to prevent infection. The method was verified in 14 pigs. ResultsThe catheters were fully functional for up to 11 weeks and no infection or thrombus was observed. DiscussionThis method of catheterization and catheter care allows the realization of long-term experiments with comfortable and stress-free blood sampling.

Suction towards a vessel wall by hemodialysis catheters\u2014the establishment of a new experimental extracorporeal circulation system using pig veins

BackgroundHemodialysis catheters are commonly used for vascular access in patients undergoing blood purification therapies. However, the sudden dysfunction of catheters represents a serious problem, and while we know that the major causative factor is suction between the catheter and the vessel wall, it is very difficult to evaluate this in vivo. Therefore, we created a new experimental system to investigate this phenomenon ex vivo, using pig veins, which allowed us to quantitatively analyze the effect of suction.MethodsWe attempted to create a model system for quantitative evaluation using azygos veins from a pig. Four types of catheters were inserted into an extracted pig vein: true circle type 1, true circle type 2, semi-circle type 1, and semi-circle type 2. We then circulated 50% glycerol solution through the vein at a flow rate (Qv) from 100 to 1000 mL/min. Glycerol solution was also circulated within the catheters at a flow rate (Qb) from 100 to 200 mL/min. We measured the frequency of suction towards the vessel wall ten times, under each experimental schedule, at a Qb of both 100 and 200 mL/min. We then measured the pressure between the pre-Qb pump and the blood circuit, when the arterial side opening was positioned approximately in the center of the blood vessel to prevent catheter suction towards the vessel wall.ResultsSuction towards the vessel wall occurred 8/10 times with the true circle type 1 catheter and 10/10 times with the semi-circle type 2 catheter in the arterial pore of the catheter is only one, when Qb and Qv were 100 and 100 mL/min, respectively. Suction towards the vessel wall occurred 3/10 times with the semi-circle type 2 catheter, when Qb and Qv were 100 and 1000 mL/min, respectively. The true circle type 1 catheter showed a minimum pressure of − 58.6 ± 0.516 mmHg when Qb and Qv were 100 and 300 mL/min, respectively, while the true circle type 2 catheter showed a minimum pressure of − 137 ± 5.96 mmHg when Qb and Qv were 200 and 300 mL/min, respectively.ConclusionsWe successfully established a novel ex vivo evaluation system for catheters using a pig vein which allowed us to recreate the effect of suction from catheters towards a vessel wall in vivo.

Early Detection of Infiltration Induced in the Veins of Pig's Ear and Human's Forearm By Using Bioimpedance: Pilot Study

Early Detection of Infiltration Induced in the Veins of Pig's Ear and Human's Forearm By Using Bioimpedance: Pilot Study

The effects of resolvin D1 on myocardial dysfunction after cardiopulmonary resuscitation in swine and its potential mechanisms

Objective To establish a porcine model of cardiopulmonary resuscitation to explore the effectiveness of resolvin D1 in improving post-resuscitation myocardial dysfunction and its potential mechanisms. Methods Twenty-eight male domestic pigs weighing 36±3 kg were utilized. The pig model was established by 8 mins of untreated ventricular fibrillation and then 5 mins of cardiopulmonary resuscitation. The animals were randomly divided into 4 groups (n=7 each): sham operation group (group S), cardiopulmonary resuscitation group (group CPR), low-dose resolvin D1 group (group LRD), and high-dose resolvin D1 group (group HRD). The animals in group S only got the general preparation without the procedure of cardiac arrest and resuscitation. At 5 min after resuscitation, the doses of resolvin D1 0.3 μg/kg and 0.6 μg/kg were respectively injected via the femoral vein of pigs in LRD and HRD groups, and meanwhile the equal volume of vehicle was given into the animals in the other two groups. At 3 h, 6 h and 24 h after resuscitation, the changes of stroke volume (SV) and global ejection fraction (GEF) were evaluated by a PiCCO monitor, and meanwhile the concentration of cardiac troponin I (cTNI) in serum was measured. At 24 h after resuscitation, the pigs were sacrificed, and myocardial tissue was obtained for the determination of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and superoxide dismutase (SOD) activity. Results Compared with group S, significantly decreased SV and GEF and markedly increased concentration of serum cTNI were observed in the other three groups with post-resuscitation myocardial dysfunction (all P<0.05). Compared with group CPR, the values of SV and GEF were significantly increased while the concentration of serum cTNI was significantly decreased in LRD and HRD groups[SV(ml): 28±5, 31±5 vs. 23±4 at 3 hrs, 32±3, 36±6 vs. 27±6 at 6 hrs, 35±5, 41±5 vs. 29±5 at 24 hrs; GEF(%): 17±2, 19±2 vs. 14±1 at 3 hrs, 20±2, 23±3 vs. 16±3 at 6 hrs, 23±2, 26±3 vs. 20±2 at 24 hrs; cTNI (pg/ml): 247±34, 230±26 vs. 324±56 at 3 hrs, 553±37, 501±34 vs. 611±44 at 6 hrs, 436±23, 371±29 vs. 553±47 at 24 hrs, all P<0.05]. Compared with group LRD, myocardial function and serum markers were further significantly improved in group HRD (all P<0.05). The inflammation and oxidative stress in myocardial tissue were observed in all the animals experiencing cardiac arrest and resuscitation, which were indicated by increased levels of TNF-α, IL-6 and MDA and decreased SOD activity. Compared with group CPR, the levels of TNF-α, IL-6 and MDA were significantly decreased while SOD activity was significantly increased in LRD and HRD groups[TNF-α(pg/ml): 442±87, 218±55 vs. 653±112; IL-6(pg/ml): 563±68, 403±61 vs. 824±117; MDA(nmol/mg): 3.95±0.96, 2.54±1.21 vs. 6.37±1.26; SOD(U/mg): 2.27±0.93, 3.36±0.74 vs. 0.89±0.31, all P<0.05]. The morbidity of myocardial inflammation and oxidative stress were further significantly ameliorated in group HRD evidenced by the figure of biomarkers compared with group LRD (all P<0.05). Conclusions Resolvin D1 can improve post-resuscitation myocardial dysfunction in a dose-dependent manner in swine, and the mechanism is related to the inhibition of inflammation and oxidative stress. Key words: Cardiac arrest; Cardiopulmonary resuscitation; Myocardial dysfunction; Cardiac injury; Resolvin D1; Inflammation; Oxidative stress; Swine

Intestinal fate of dietary zinc and copper: Postprandial net fluxes of these trace elements in portal vein of pigs

In pig, the assessment of bioavailability of dietary trace minerals with classical approaches such as relative bioavailability estimates or digestive tract balances have often generated inconsistent responses. In the present study, net portal-drained-viscera fluxes were monitored after a meal to assess intestinal absorption of zinc (Zn) or copper (Cu) according to dietary sources and levels of these trace minerals. Twelve pigs were surgically equipped with portal and carotid catheters and a portal ultrasonic flow probe for 12-h postprandial measurements. In a cross-over design, pigs received boluses of inorganic (I) or organic (O) dietary Cu and Zn at adequate (A, 20 and 200mg, respectively) or high (H, 40 and 400mg, respectively) level just before a 0.8-kg meal (semi-purified diet). Whatever treatments, arterial Zn increased by 72% at 45min postprandial and gradually declined thereafter (P<0.01). Arterial Zn were greater by 11% after O than I (P=0.02) and by 19% after H than A (P<0.01) meals. Net portal-drained-viscera fluxes of Zn during the first 240min postprandial were greater by 44% after O than I (P=0.10) and by 51% after H than A (P=0.07) meals. For Cu, portal-drained-viscera fluxes of Cu up to 240min postprandial were greater (P=0.03) after A than H meals. Those results suggest that Zn is absorbed rapidly, likely in the upper digestive tract of pigs and, whatever dietary levels, more efficiently after O meals. It appears that H levels of both Zn and Cu interfered with intestinal absorption of Cu and/or stimulate post-absorption enterocyte sequestration of this mineral.

Non-Invasive Thrombolysis Using Microtripsy in a Porcine Deep Vein Thrombosis Model

Histotripsy is a non-invasive therapeutic technique that uses ultrasound generated from outside the body to create controlled cavitation in targeted tissue, and fractionates it into acellular debris. We have developed a new histotripsy approach, termed microtripsy, to improve targeting accuracy and to avoid collateral tissue damage. This in vivo study evaluates the safety and efficacy of microtripsy for non-invasive thrombolysis in a porcine deep vein thrombosis model. Acute thrombi were formed in left femoral veins of pigs (∼35 kg) by occluding the vessel using two balloon catheters and infusing with thrombin. Guided by real-time ultrasound imaging, microtripsy thrombolysis treatment was conducted in 14 pigs; 10 pigs were euthanized on the same day (acute) and 4 at 2 wk (subacute). To evaluate vessel damage, 30-min free-flow treatment in the right femoral vein (no thrombus) was also conducted in 8 acute pigs. Blood flow was successfully restored or significantly increased after treatment in 13 of the 14 pigs. The flow channels re-opened by microtripsy had a diameter up to 64% of the vessel diameter (∼6 mm). The average treatment time was 16 min per centimeter-long thrombus. Only mild intravascular hemolysis was induced during microtripsy thrombolysis. No damage was observed on vessel walls after 2 wk of recovery, venous valves were preserved, and there was no sign of pulmonary embolism. The results of this study indicate that microtripsy has the potential to be a safe and effective treatment for deep vein thrombosis in a porcine model.

This issue of ACTA

This issue of ACTA

High expression of ubiquitin-specific peptidase 39 is associated with the development of vascular remodeling.

Vascular remodeling is the primary cause underlying the failure of angioplasty surgeries, including vascular stenting, transplant vasculopathy and vein grafts. Multiple restenosis-associated proteins and genes have been identified to account for this. In the present study, the functions of ubiquitin-specific peptidase 39 (USP39) were investigated in the context of two vascular remodeling models (a mouse common carotid artery ligation and a pig bilateral saphenous vein-carotid artery interposition graft). USP39 has previously been observed to be upregulated in ligated arteries, and this result was confirmed in the pig vein graft model. In addition, Transwell assay results demonstrated that vascular smooth muscle cell (VSMC) migration was suppressed by lentiviral vector-mediated downregulation of USP39 and enhanced by upregulation of USP39. Furthermore, knockdown of USP39 inhibited VSMC cell proliferation and the expression of cyclin D1 and cyclin-dependent kinase 4, as analyzed via cell counting, MTT assay and western blotting. These results suggest that USP39 may represent a novel therapeutic target for treating vascular injury and preventing vein-graft failure.

58-01: Stent-based isolation of pulmonary veins

Purpose: Atrial fibrillation is the most common arrhythmia in adults. Current therapies are hampered by high recurrence rates. We investigated a stent-based contactless energy transfer to isolate pulmonary veins in pigs. Methods: Nitinol self-expanding implants were positioned in the pulmonary veins of pigs. Using electromagnetic wireless energy transfer principles, implants were heated in a controlled fashion. Using an electrophysiological sensing and pacing catheter, signals were checked before and after the ablation, and conduction block persistence acutely and after one month were checked. Results: 11 animals were successfully treated. Implantation and wireless energy transfer were safely performed in all animals. While pacing with adequate conduction was successful in all animals prior to the ablation, conduction block was shown acutely in all eleven animals and chronically in seven animals. No periprocedural complications occurred, and the seven chronic animals remained in excellent shape until their sacrifice at one month. Histology confirmed the physical findings. The table shows the most relevant results (N°8-10 are acute sacrifices, 1–3 sacrificed at 1 month, 4–7 and 11 sacrificed at 3 months). Summary and Conclusions: We have –for the first time- proven that complete isolation of pulmonary veins using a contactless externally applied energy source to correctly positioned implants is safe and feasible, and that long-term isolation of pulmonary veins can thus be accomplished

STENT-BASED ISOLATION OF PULMONARY VEINS

Atrial fibrillation is the most common arrhythmia in adults. Current therapies are hampered by high complication and recurrence rates. We investigated a stent-based contactless energy transfer to isolate pulmonary veins in pigs. Nitinol-based self-expanding implants were positioned in the pulmonary

Daily Adaptive Changes in Blood Chemistry of Pigs Exposed to Heat Stress

Animals and humans exposed to heat stress (HS) conditions may modify their physiology and metabolism to maintain homeostasis. In the dessert regions of the world, they have to adapt to great changes in ambient temperature (AT) within 24‐h periods, from thermo neutral (TN) AT early in the morning to stressful high AT in the afternoon. An experiment was conducted with six pigs (45 kg BW), individually housed, during the summer of Northwestern Mexico to analyze the impact of HS as well as the diurnal changes in AT on their blood chemistry. First, the pigs were housed under natural HS conditions (30.4 – 41.1° C, HS) during 14 d. Then, the pigs were moved to an air‐conditioned room (22.6–25.1 °C, TN) for two weeks. Blood samples were collected from the jugular vein of pigs at 0600, 1200 and 1600 h, during the last three days under HS, and again on the last day under TN conditions. Samples were processed to obtain serum in which blood chemistry parameters were analyzed. Heat stress reduced the serum concentration of cholesterol, total proteins, albumin, globulin, phosphorus, and Ala‐amino‐transferase (P&lt;0.05); indirect bilirubin tended to reduce (P&lt;0.10), and calcium tended to increase (P&lt;0.10). As for the diurnal changes in AT, Ca SC decreased at 1200 and 1600 h (P&lt;0.001) as compared with that at 0600; cholesterol also reduced at 1600 h compared to 0600 h (P&lt;0.05). These changes indicate that HS animals modify their physiology and that some factors such as blood proteins, cholesterol and calcium are modified along the day in order to maintain pig homeostasis.Support or Funding InformationCONACYT, México. Ciencia básica 2012, 00181348.

Modified In Vivo Lung Perfusion for Local Chemotherapy: A Preclinical Study With Doxorubicin

Invivo lung perfusion (IVLP) is a promising adjuvant treatment of lung metastases, allowing the localized delivery of drugs to the lungs without systemic exposure. Previous experimental and clinical data resulted in variable efficacy and frequent toxicity. Our objectives were to demonstrate the feasibility and safety of a novel protective IVLP technique coupled with the delivery of sarcoma-based chemotherapy to the lung. The left pulmonary artery and veins in pigs were cannulated and clamped. Left lung IVLP was performed for 4 hours. Doxorubicin (Dox) at a standard clinical dose of 75 mg/m(2) was used, followed by 150 and 225 mg/m(2). Dox 75 mg/m(2) combined with ifosfamide (Ifos) 6 g/m(2) was also tested. After IVLP, blood reperfusion was allowed for 4 hours. Lung physiology was assessed and biopsy samples were obtained for histologic assessment of acute lung injury (ALI), inflammatory profile, and cell death. Lung tissue levels, perfusate, and plasma levels of Dox were measured during the procedure. Lungs treated with Dox 75 mg/m(2) alone or combined with Ifos showed stable function throughout the procedure, without evidence of ALI (p= 0.12 and p=0.36, respectively). Tissue levels of Dox were 70.3 μg/g homogeneously distributed in the lung (p= 0.12). No drug was detected systemically. Dox 150 mg/m(2) and 225 mg/m(2) showed incremental ALI. IVLP for 4 hours with Dox 75 mg/m(2) alone or combined with Ifos was well tolerated, without measurable ALI. High drug levels in perfusate and lungtissue were found without systemic leakage. A dose-related toxicity was observed with increases in Dox doses.

Effects of corn type and fasting time before slaughter on growth and plasma index in weaning pigs.

A 2 × 2 factorial experiment was conducted to evaluate the effects of dietary corn type (waxy corn [WC] vs. nonwaxy corn [NC]) and fasting period (2 h vs. 12-16 h) before slaughter on growth and plasma index in weaning pigs. Twenty-four crossbred barrows (8.26 ± 0.47 kg) were allotted to 4 treatments with 6 replications of 1 pig per replicate metabolism cage. Waxy corn contained less fat, a lower amylase:amylopectin ratio, more CP, and more starch than NC. Pigs fed the WC diet had lower jejunum digesta pH compared with those fed the NC diet ( < 0.05). Maltase activity in the jejunum and ileum mucosa ( < 0.01), sucrose activity in the ileum mucosa ( < 0.01), and amylase activity in the pancreas and jejunum digesta ( < 0.05) were increased in pigs fed the WC diet relative to those fed the NC diet. But the total tract apparent digestibility (TTAD) of starch and CP was lower for the WC group ( < 0.05). Ingestion of the NC diet resulted in higher ( < 0.05) ADG and ADFI in the second week but did not affect ADG ( = 0.091) and the feed:gain ratio (F:G; = 0.077) during the whole experiment period. The plasma glucose ( < 0.01) concentration was higher and high-density lipoprotein cholesterol (HDL-C; < 0.01) concentrations was lower in the hepatic portal vein in pigs fed the WC diet relative to those fed the NC diet. Fasting 2 h before slaughter decreased the jejunum and ileum digesta pH compared with the 12-h fasting group ( < 0.01). Villus height increased in the duodenum ( < 0.01) and jejunum ( < 0.05) and the villus height:crypt depth ratio increased in the duodenum ( < 0.05) of pigs after shortening the fasting period before slaughter. Shortening the fasting time before slaughter resulted in higher plasma glucose ( < 0.05) concentrations and a higher HDL-C:low-density lipoprotein cholesterol (LDL-C) ratio ( < 0.05) whereas the LDL-C ( < 0.05) concentrations were reduced in the hepatic portal vein. The results of this experiment indicate that although the production performance of both WC and NC diets is equal, the glucose concentration is higher and HDL-C is lower in the portal vein for the WC diet, and fasting time before slaughter has an influence on the plasma index and intestinal morphology in weaning pigs.

Safety of long-term dietary supplementation with L-arginine in pigs.

This study was conducted with a swine model to determine the safety of long-term dietary supplementation with L-arginine-HCl or L-arginine free base. Beginning at 30 days of age, pigs were fed a corn- and soybean meal-based diet (31.5 g/kg body weight/day) supplemented with 0, 1.21, 1.81 or 2.42 % L-arginine-HCl (Experiment 1) or with 0, 1, 1.5 or 2 % L-arginine (Experiment 2). The supplemental doses of 0, 1, 1.5, and 2 % L-arginine provided pigs with 0, 315, 473, and 630 mg L-arginine/kg body weight/day, respectively, which were equivalent to 0, 286, 430, and 573 mg L-arginine/kg body weight/day, respectively, in humans. At 121 days of age (91 days after initiation of supplementation), blood samples were obtained from the jugular vein of pigs at 1 and 4 h after feeding for hematological and clinical chemistry tests. Dietary supplementation with L-arginine increased plasma concentrations of arginine, ornithine, proline, albumin and reticulocytes, while reducing plasma concentrations of ammonia, free fatty acids, triglyceride, cholesterol, and neutrophils. L-Arginine supplementation enhanced protein gain and reduced white-fat deposition in the body. Other variables in standard hematology and clinical chemistry tests, serum concentrations of insulin, growth hormone and insulin-like growth factor-I did not differ among all the groups of pigs. These results indicate that dietary supplementation with L-arginine (up to 630 mg/kg body weight/day) is safe in pigs for at least 91 days. Our findings help guide clinical studies to determine the safety of long-term oral administration of L-arginine to humans.

Morphologic description of great cardiac vein in pigs compared to human hearts

IntroductionIn spite of its importance as an experimental model, the information on the great cardiac vein in pigs is sparse.ObjectiveTo determine the morphologic characteristics of the great cardiac vein and its tributaries in pigs.Methods120 hearts extracted from pigs destined to the slaughterhouse with stunning method were studied. This descriptive cross-over study evaluated continuous variables with T test and discrete variables with Pearson χ square test. A level of significance P<0.05 was used. The great cardiac vein and its tributaries were perfused with polyester resin (85% Palatal and 15% Styrene) and then subjected to potassium hydroxide infusion to release the subepicardial fat. Calibers were measured, and trajectories and relations with adjacent arterial structures were evaluated.ResultsThe origin of the great cardiac vein was observed at the heart apex in 91 (76%) hearts. The arterio-venous trigone was present in 117 (97.5%) specimens, corresponding to the open expression in its lower segment and to the closed expression in the upper segment in the majority of the cases (65%). The caliber of the great cardiac vein at the upper segment of the paraconal interventricular sulcus was 3.73±0.79 mm. An anastomosis between the great cardiac vein and the middle cardiac vein was found in 59 (49%) specimens.Conclusion The morphological and biometric characteristics of the great cardiac vein and its tributaries had not been reported in prior studies, and due to their similitude with those of the human heart, allows us to propose the pig model for procedural and hemodynamic applications.