Occlusion In Pigs Research Articles

Molecular pathways involved in the cardioprotective effects of intravenous statin administration during ischemia.

The success of therapies targeting myocardial reperfusion injury is limited, while the cardioprotective impact of mitigating ischemia-related damage remains less explored. We have recently shown in a pig model that the intravenous administration of a modified atorvastatin preparation during ischemia attenuates the rise of cardiac ischemia injury biomarkers. In the following study, we sought to investigate the mechanisms behind these ischemia-related cardioprotective effects. Ischemia was induced by 90min total coronary balloon occlusion in pigs fed a normocholesterolemic regime. Fifteen minutes after the onset of ischemia, animals were randomized to receive intravenous atorvastatin preparation (IV-atorva) or vehicle. After ischemia animals were euthanized to assess the effect of IV-atorva treatment on gene and protein levels/activation of senescence-, apoptosis-, and cardioprotective/metabolic-related markers. Proof-of-concept studies were carried out in mice and rats in which treatments or vehicle were administered 15min after initiation of ischemia induced by permanent coronary ligation. Western-blot analyses revealed that in the ischemic myocardium of IV-atorva-treated pigs, RhoA was inactivated, phosphorylation of p53 and caspase-3 was reduced and AMPK was activated with the consequent regulation of the mTOR/raptor-signaling pathway. IV-atorva-treated rats showed, as compared to vehicle, a significant reduction (60%) in scar size assessed at 1month by histological staining, and mice studies demonstrated the causal involvement of AMPK activation in IV-atorva mediated cardioprotective effects. We demonstrate in pigs and rodents that prompt intravenous treatment with atorvastatin during ischemia limits cardiac cell death and reduces infarct size through AMPK signaling.

Short-term Physiologic Consequences of Regional Pulmonary Vascular Occlusion in Pigs.

After pulmonary artery occlusion (mimicking a pulmonary embolism), perfusion is redistributed to the rest of the lung tissue, but the distribution of ventilation is uncertain. Data from anesthetized pigs (uninjured lungs) indicate that the perfusion is redistributed as suspected. Similarly, ventilation is redistributed from nonperfused to perfused lung tissue. This limits the increase in dead space and is accompanied by less density in the occluded lung. Acute unilateral pulmonary arterial occlusion causes ventilation-perfusion mismatch of the affected lung area. A diversion of ventilation from nonperfused to perfused lung areas, limiting the increase in dead space, has been described. The hypothesis was that the occlusion of a distal branch of the pulmonary artery would cause local redistribution of ventilation and changes in regional lung densitometry as assessed with quantitative computed tomography. In eight healthy, anesthetized pigs (18.5 ± 3.8 kg) ventilated with constant ventilatory settings, respiratory mechanics, arterial blood gases, and quantitative computed tomography scans were recorded at baseline and 30 min after the inflation of the balloon of a pulmonary artery catheter. Regional (left vs. right lung and perfused vs. nonperfused area) quantitative computed tomography was performed. The balloon always occluded a branch of the left pulmonary artery perfusing approximately 30% of lung tissue. Physiologic dead space increased (0.37 ± 0.17 vs. 0.43 ± 0.17, P = 0.005), causing an increase in PaCO2 (39.8 [35.2 to 43.0] vs. 41.8 [37.5 to 47.1] mmHg, P = 0.008) and reduction in pH (7.46 [7.42 to 7.50] vs. 7.42 [7.38 to 7.47], P = 0.008). Respiratory system compliance was reduced (24.4 ± 4.2 vs. 22.8 ± 4.8 ml · cm H2O, P = 0.028), and the reduction was more pronounced in the left hemithorax. Quantitative analysis of the nonperfused lung area revealed a significant reduction in lung density (-436 [-490 to -401] vs. -478 [-543 to -474] Hounsfield units, P = 0.016), due to a reduction in lung tissue (90 ± 23 vs. 81 ± 22 g, P < 0.001) and an increase in air volume (70 ± 22 vs. 82 ± 26 ml, P = 0.022). Regional pulmonary vascular occlusion is associated with a diversion of ventilation from nonperfused to perfused lung areas. This compensatory mechanism effectively limits ventilation perfusion mismatch. Quantitative computed tomography documented acute changes in lung densitometry after pulmonary vascular occlusion. In particular, the nonperfused lung area showed an increase in air volume and reduction in tissue mass, resulting in a decreased lung density.

Dynamic Changes of Gut Microbiome and Immune Response During the Acute Stage of Stroke in a Pig Model (P14-012-19)

ObjectivesStroke is a leading cause of mortality and disability in the United States. Secondary injuries induced by inflammation plays a critical role in stroke recovery. This study investigates gut microbiome changes during the acute stage of ischemic stroke to better understand the role of gut microbiome in inflammation in an ischemic stroke pig model. MethodsIschemic stroke was induced by middle cerebral artery occlusion in pigs (n = 7). Fecal samples were collected at pre-stoke (PRE), 1 (1DPS), 3 (3DPS), and 5 days post-stroke (5DPS) to measure gut microbiome composition. Blood samples were collected at 1DPS for white blood cell analysis. ResultsIschemic stroke was confirmed by magnetic resonance imaging at 1DPS. The dominant pre-stroke fecal bacterial phyla (>1% relative abundance) were Firmicutes (89.2%), Bacteroidetes (3.7%), Actinobacteria (2.0%) and Proteobacteria (1.3%). This composition significantly (P < 0.05) differed at 3DPS with a decreased Firmicutes (68.1%) and increased Actinobacteria (3.70%) and Proteobacteria (19.0%), and a trending (P = 0.06) increase among Bacteroidetes (7.6%). At 5DPS, Bacteroidetes (7.6%) remained elevated, but Firmicutes (86.6%), Actinobacteria (2.0%) and Proteobacteria (0.7%) returned to levels similar to PRE. At 1DPS, the α-diversity measured by Shannon index and species evenness were both decreased (P < 0.05), suggesting that overall bacterial diversity decreased immediately after the stroke. β-diversity analysis showed a trend for overall differences over time (P = 0.07), but no differences between specific days were found. Elevated inflammation and neutrophil-to-lymphocyte ratio (NLR) following stroke event have been related to negative functional outcome in stroke patients. At 1DPS, a significant increase in NLR was observed in the stroke pigs compared to those at PRE (P < 0.05), suggesting initiation of inflammatory response following stroke. ConclusionsIschemic stroke altered the gut microbiome composition, reduced microbiome diversity and increased immune response in pigs. Future studies are warranted to investigate systemic and neural inflammation mediated by the alteration of the gut microbiome following ischemic stroke. Funding SourcesThe study was funded by the National Institute of Health and University of Georgia (Faculty Research Grant).

Effect of dexmedetomidine on ischemia-reperfusion injury of liver and kidney tissues in experimental diabetes and hepatic ischemia-reperfusion injury induced rats

Background: Reperfusion following ischemia can lead to more injuries than ischemia itself especially in diabetic patients. The aim of this study was to evaluate the effect of dexmedetomidine on ischemia-reperfusion injury (IRI) in rats with have hepatic IRI and diabetes mellitus.

Reflection of Cardioprotection by Remote Ischemic Perconditioning in Attenuated ST-Segment Elevation During Ongoing Coronary Occlusion in Pigs: Evidence for Cardioprotection From Ischemic Injury.

Reduction of infarct size by remote ischemic perconditioning (perRIC) is evident only after several hours reperfusion. To develop a potential real-time estimate of cardioprotection by perRIC, we have analyzed the time course of ST-segment elevation. Anesthetized open-chest pigs were subjected to 60-minute coronary occlusion and 180-minute reperfusion (placebo; n=19). PerRIC (n=18; 4×5 min/5 min hindlimb occlusion/reperfusion) was induced 20 minutes after coronary occlusion. Regional myocardial blood flow was measured with microspheres, areas of no-reflow with thioflavin-S, area at risk with blue dye, and infarct size with triphenyl tetrazolium chloride staining. Phosphorylation of protein kinase B α/β/γ, extracellular signal-regulated kinase 1/2, and signal transducer and activator of transcription 3 was determined by Western blot. ST-segment elevation was analyzed in a V2-like ECG-lead at baseline, 5- and 55-minute coronary occlusion, and 10-, 30-, 60-, and 120-minute reperfusion. Transmural blood flow at 5-minute coronary occlusion was not different between perRIC (0.029±0.015 mL/min per gram; mean±SD) and placebo (0.024±0.018 mL/min per gram) as was area at risk (perRIC: 24±6% of the left ventricle; placebo: 21±4%). Areas of no-reflow tended to be smaller with perRIC (9±12% of area at risk versus 15±14% with placebo; P=0.13). Infarct size with perRIC was 23±12% of area at risk versus 40±11% with placebo (P<0.001). PerRIC increased phosphorylation of signal transducer and activator of transcription 3 at 120-minute reperfusion by 196±142% versus 109±120% with placebo (P=0.047). The time courses of ST-segment elevation in perRIC and placebo protocols, respectively, were different (P=0.017). With similar ST-segment elevation at 5-minute coronary occlusion (perRIC 282±34 µV; placebo 259±28 µV), partial recovery of ST-segment elevation between 5- and 55-minute coronary occlusion was more pronounced with perRIC than placebo (by 111±84 versus 15±94 µV; P=0.028). Infarct size reduction by perRIC is reflected in the ST-segment elevation during coronary occlusion in pigs, supporting the notion of protection from ischemic injury.

Use of small volume hypertonic acetate dextran during aortic occlusion in pigs: assessment of blood flow and antioxidant status in tissues

OBJETIVO Solucoes hipertonicas e hiperoncoticas podem reduzir as necessidades de fluidos e o edema tissular, melhorar a perfusao e reduzir a incidencia de paraplegia associada com pincamento aortico com reperfusao subsequente. Foram avaliados os potenciais beneficios de uma solucao de hipertonica de acetato de sodio mais dextrana sobre a reperfusao pos isquemica. Avaliamos o fluxo sanguineo e a capacidade antioxidante do plasma, a medula espinal e o musculo esqueletico acima e abaixo da oclusao aortica, bem como o figado, rim e pâncreas. METODO A aorta de porcos anestesiados (n = 5-6/grupo ) foi ocluida ao nivel de T9 durante 30 min; os animais receberam 4 ml/kg acetato de Sodio + dextrana (HAD) ou 8,4% de NaHCO3 ( Controle ). Os porcos foram sacrificados 1h mais tarde. RESULTADOS Ao reduzir-se o fluxo de sangue a zero na medula espinal e musculo distal, observou-se duplicacao do fluxo espinal e aumento de 6 vezes no musculo proximal. Durante a reperfusao, o fluxo de sangue em todas as regioes voltaram aos niveis basais, sem diferencas estatisticas entre HAD e Controles. A taxa de peroxidacao lipidica no plasma foi menor em HAD que nos controles. O musculo distal apresentou niveis de glutationa 41% mais baixa e atividades significativamente mais baixas dos enzimas antioxidantes glutationa-peroxidase e redutase, catalase, superoxido dismutase em comparacao com o musculo proximal. A medula espinal distal exibiu niveis 2,5 vezes mais elevados de malondialdeido e 50% maior de atividade catalase comparados com medula espinal proximal. Para qualquer tecido, diferencas significativas na capacidade antioxidante ou evidencia de peroxidacao lipidica favoreceram o grupo HAD em comparacao com os controles. CONCLUSAO HAD apresentou vantagens discretas sobre o bicarbonato em relacao ao fluxo de sangue e status antioxidante de medula espinal e muscular apos este periodo de oclusao aortica seguida de reperfusao.

Spinal Cord Early Ischemic Preconditioning Activates the Stabilized Fraction of β-Catenin After Thoracoabdominal Aortic Occlusion in Pigs

Paraplegia after thoracoabdominal aortic surgery is a devastating complication attributed to motor neurons loss and dysfunction, due to spinal cord ischemia. β-Catenin is a protein that has been associated with cell survival and healing and many studies have correlated this protein with late ischemic preconditioning (IPC). Herein we investigate the potential contribution of β-catenin in an early IPC animal model, and its relationship with heat shock protein 70 (Hsp70), suggesting a possible role of this protein as a first window of protection. A total of 42 pigs were used in an experimental thoracoabdominal aortic occlusion model. Twelve animals were used for neurologic evaluation and were randomly assigned to 2 groups (A and B). The remaining 30 animals were used in experiments for biologic measurements and innunohistochemical studies, and were randomly assigned to 5 groups (1-5). Western blotting analysis and immunoprecipitations were performed to study the levels of β-catenin and its binding relationship with Hsp70. The cellular distribution of β-catenin at various time-points was investigated by immunohistochemical studies. According to neurologic evaluation, the animals in the IPC+ischemia group had significantly better neurologic scores compared with those in the ischemia group, indicating a protective role for IPC. The biologic measurements demonstrated a significant (P=0.03) increase in β-catenin levels and translocation of the protein in the nucleus at the end of ischemic preconditioning. Our results suggest a significant role of β-catenin in early IPC protection of spinal cord after thoracoabdominal occlusion, as IPC seems to trigger the activation of the β-catenin stabilized fraction and, thus, its survival pathway.

Mechanism and diagnostic potential of reciprocal ECG changes induced by acute coronary artery occlusion in pigs

Reciprocal ST-segment depression simulating additional subendocardial ischemia is commonly observed in ST-segment elevation myocardial infarction. To study the mechanism and characterization of the whole reciprocal electrocardiogram (ECG) patterns induced by acute coronary artery occlusion at different locations in the absence of additional subendocardial ischemia in pigs. Conventional 12-lead ECG and/or local extracellular epicardial, mid-myocardial, and endocardial electrograms were recorded during the acute occlusion of right coronary (RC) and left anterior descending (LAD) coronary arteries in the in situ (n = 9) or in the isolated perfused (n = 5) pig hearts. Mid-RC occlusion induced reciprocal ST-segment depression (-0.43 ± 0.14 mV; P<.01) and S-wave deepening (-0.74 ± 0.23 mV; P<.01) in anterior ECG leads. Mid-LAD occlusion induced reciprocal S-wave deepening (-0.43 ± 0.37 mV; P = .02) but not ST-segment depression in inferior leads. Proximal LAD induced reciprocal ST-segment depression (-0.21 ± 0.20 mV; P = .03) and S-wave deepening (-0.56 ± 0.58 mV; P = .04) in inferior leads. Reciprocal QRS widening was observed only during proximal LAD occlusion. Local extracellular recordings did not show significant reciprocal QRS and ST-segment changes. In the absence of additional subendocardial ischemia, acute coronary artery occlusion induces reciprocal ST-segment and S-wave changes in the 12-lead ECG that allow better differentiation between proximal and mid-LAD occlusion. Reciprocal ECG changes depend on conventional lead system design and not on the transmission of injury currents from the ischemic border zone to distant normal myocardium.

Invited Commentary

Koomalsingh and colleagues [1] describe an experiment in which a composite inflatable balloon–patch was sutured over the infarct area at risk at the time of circumflex coronary artery occlusion in pigs [1]. Optimal balloon inflation was determined at 1 week, and that degree of inflation was continued until week 4. Briefly, at week 1, stroke volume improved when the balloon was inflated with either 6 or 8 mL of saline. At 4 weeks, left ventricular (LV) volumes were stable, and stroke volume was improved in animals treated with the balloon patch compared to control.

Hepatic and Abdominal Carbon Dioxide Measurements Detect and Distinguish Hepatic Artery Occlusion and Portal Vein Occlusion in Pigs

Hepatic artery (HA) occlusion and portal vein (PV) occlusion are the most common vascular complications after liver transplantation with an impact on mortality and retransplantation rates. The detection of severe hypoperfusion may be delayed with currently available diagnostic tools. Hypoperfusion and anaerobically produced lactic acid lead to increases in tissue carbon dioxide. We investigated whether the continuous assessment of the intrahepatic and intra-abdominal partial pressure of carbon dioxide (PCO(2) ) could be used to detect and distinguish HA and PV occlusions in real time. In 13 pigs, the HA and the PV were fully occluded (n = 7) or gradually occluded (n = 6). PCO(2) was monitored intrahepatically and between loops of small intestine. The hepatic and intestinal metabolism was assessed with microdialysis and PV as well as hepatic vein blood samples, and the results were compared to clinical parameters for the systemic circulation and blood gas analysis. Total HA occlusion led to significant increases in hepatic PCO(2) and lactate, and this was accompanied by significant decreases in the partial pressure of oxygen and glucose. PV occlusion induced a significant increase in intestinal PCO(2) (but not hepatic PCO(2) ) along with significant increases in intestinal lactate and glycerol. Gradual HA occlusion and PV occlusion caused steady hepatic and intestinal PCO(2) increases, respectively. Systemic clinical parameters such as the blood pressure, heart rate, and cardiac output were affected only by PV occlusion. In conclusion, even gradual HA occlusion affects liver metabolism and can be reliably identified with hepatic PCO(2) measurements. Intestinal PCO(2) increases only during PV occlusion. A combination of hepatic and intestinal PCO(2) measurements can reliably diagnose the affected vessel and depict the severity of the occlusion, and this may emerge as a potential real-time clinical monitoring tool for the postoperative course of liver transplantation and enable early interventions.

Early Ischaemic Preconditioning of Spinal Cord Enhanced the Binding Profile of Heat Shock Protein 70 with Neurofilaments and Promoted its Nuclear Translocation after Thoraco-abdominal Aortic Occlusion in Pigs

Objective(s)Heat shock protein 70 (Hsp70) is detected in substantial amounts in normal neurons and this basal content may protect a cell against harmful conditions without the need for additional synthesis. Herein, we investigate the potential protective role of these basal levels of Hsp70, in an early ischaemic preconditioning (IPC) experimental model, suggesting a possible role of this protein as a first window of protection. Design, material and methodsForty-two pigs were used in an experimental thoraco-abdominal aortic occlusion model. Twelve animals (two groups) were used for neurological evaluation. The remaining 30 animals (five groups) were used for immunoprecipitation and immunohistochemical studies. These were performed to study the binding relationship of Hsp70/cytoskeleton elements and the cellular distribution of Hsp70, respectively. ResultsThe IPC + ischaemia-group showed significant better neurologic scores compared with those of the ischaemia group, indicating a protective role for IPC (P = 0.003). The immunoprecipitations demonstrated that early IPC increased significantly the binding profile of Hsp70/neurofilaments (P = 0.025). In addition, translocation of Hsp70 into the nucleus was observed, which was conserved until the sustained ischaemia. ConclusionsThese results indicate that Hsp70 may have an important role in early IPC of the spinal cord, by protecting neurofilaments and by ensuring the functionality and the integrity of the nucleus, at the time the intensive insult begins.

Electrophysiological Consequences of Experimental Branch Retinal Vein Occlusion in Pigs and the Effect of Dorzolamide

To study the electrophysiological consequences of experimental branch retinal vein occlusion (BRVO) in pigs and the effect of dorzolamide. BRVO was induced in 16 pigs by diathermia. At 4 weeks animals were examined with multifocal electroretinography (mfERG) before and after dorzolamide or vehicle. The direct component P1 (outer retina) and indirect component iN1 (inner retina) were analyzed. Ophthalmoscopy, fundus photography, and fluorescence angiography were performed. BRVO eyes displayed signs of retinal damage and ischemia on ophthalmoscopy, fundus photography, and fluorescence angiography. mfERGs were affected by surgery; amplitude ratios (BRVO/healthy) were less than one (P1 = 0.30 [0.20-0.45]; iN1 = 0.35 [0.23-0.54]), and implicit time ratios were above one (1.04 [1.03-1.06] and 1.03 [1.02-1.05)]. In healthy eyes, iN1 amplitudes after treatment normalized to baseline (after/before) were lower in dorzolamide-treated animals than in the vehicle group (P = 0.05). After dorzolamide iN1 amplitude ratios (BRVO/healthy) were significantly higher than after vehicle (P = 0.01) and were not significantly different from one (0.97 [0.74-1.26]), indicating that the iN1 amplitudes in BRVO eyes were not different from those in healthy eyes after dorzolamide. BRVO in pig eyes examined by mfERG is a promising model for testing new treatment strategies in retinal ischemia. The local effects of BRVO are detectable on the mfERG and can be altered by dorzolamide. The decreased iN1 amplitudes caused by dorzolamide in healthy eyes were not seen in BRVO eyes possibly because of an increase in preretinal oxygen tension and improved function of the ischemic retina counteracting the effect of inner retinal acidification.

Preoxygenated hemoglobin-based oxygen carrier HBOC-201 annihilates myocardial ischemia during brief coronary artery occlusion in pigs

Because of their ability to perfuse remote regions and deliver oxygen, hemoglobin-based oxygen carriers (HBOCs) may be considered in the treatment of several ischemic conditions such as acute coronary syndromes or high-risk percutaneous intervention. Here we studied the effects of intracoronary infusion of ex vivo preoxygenated HBOC-201 during brief total coronary artery occlusion (CAOs) on myocardial oxygenation and left ventricular (LV) function in a large animal model and investigated the influence of HBOC-201 temperature and infusion rate on these effects. Thirteen open-chest anesthetized swine were instrumented for measurement of global and regional LV function and metabolism. CAOs were induced by inflating an intracoronary balloon catheter; preoxygenated HBOC-201 (12 g/dL) was infused distally through the central lumen of the balloon catheter. Animals underwent consecutive 3-min CAOs interspersed by 30 min of reperfusion, accompanied by different HBOC-201 infusion rates (0, 15, 23, 30, 40, and 50 ml/min) and/or two infusion temperatures (18 degrees C or 37 degrees C) in random order. CAO elicited immediate loss of systolic shortening (SS) in the ischemic region (19 +/- 1% at baseline vs. -3 +/- 2% at end of CAO), resulting in decreases in maximum rate of rise in LV pressure (15 +/- 5%) and stroke volume (12 +/- 4%; all P < 0.05). Balloon deflation resulted in marked coronary reactive hyperemia (to 472 +/- 74% of baseline), increases in coronary venous concentrations of adenosine + inosine (to 218 +/- 26% of baseline; both P < 0.05) and rapid restoration of SS toward baseline. HBOC-201 ameliorated the CAO-induced changes in SS, stroke volume, reactive hyperemia, and coronary venous adenosine + inosine. The effects were temperature and flow dependent with full preservation of SS at 50 ml/min HBOC-201 of 37 degrees C. In conclusion, intracoronary preoxygenated HBOC-201 preserved myocardial oxygenation and LV function in swine during CAO in a dose- and temperature-dependent manner. In our study setting, preoxygenated HBOC-201 can match the oxygen delivery role of endogenous blood in the heart on an almost equivalent-volume basis.

Effect of physical training on hind limb blood flow with femoral artery occlusion in pigs

Physical training (PT) is an important regimen for intermittent claudicants. To develop collateral circuit supporting the large muscle mass in large mammals, requires development of large caliber conduit vessels. To study whether PT enhances to develop large collateral conduits, male Yucatan pigs (35 kg) received femoral artery occlusion. Flow probes were placed on each external iliac artery and the pigs were given a stress test each wk for eight wks (@1‐5 mile/h). BP in the thoracic aorta was monitored. Pigs were either kept in cage activity (Sed) or ran on treadmill @ 3.5 mi/hr for 35 min/d, for 8 wks (Tr). BP during exercise declined (35%) after PT. Peak BF through the iliac artery observed increased in both Sed and Tr pigs similarly over 8 wks (643±83 to 913±26 ml/min). This increase in BF is similar to the 250±25 ml/min measured in the unobstructed contralateral femoral artery during the same exercise intensity. Thus the increased BF was attributed to collateral flow via the newly formed collateral vessels that were later verified angiographically. BF though the iliac artery remained modestly elevated post‐exercise, compared to the non‐obstructed contralateral iliac artery, characteristic of an ischemic hyperemia response. Our findings demonstrate that a robust collateral vessel development occurs following occlusion of the supply vessel in a large mammal.Supported by NIH P01HL 52490

This issue of Acta

This issue of Acta is dominated by paediatric ophthalmology. The cover illustrations show fundus photographs and optical coherence tomography (OCT) images from a girl with 3-hydroxyacyl-CoA dehydrogenase deficiency as reported by Teär Fahnehjelm et al. in this issue. Teär Fahnehjelm discusses the role of paediatric ophthalmologists and their interaction with paediatricians. The second editorial is the yearly report by the Editor in Chief on the state of the journal. Berker & Batman, in Ankara, review several approaches to the surgical treatment of central retinal vein occlusion. Teär Fahnehjelm et al., in Stockholm, found dry eye to be common in children treated with stem-cell transplantation, particularly in patients treated with high levels of cyclosporine A. These children need intensive ophthalmological care. Lindqvist et al., in Trondheim, found that children born prematurely with very low birth weight are at risk for poor binocular function and eye movement in adolescence, whereas this does not apply to very low birth weight children who are born at term. Lavezzo et al., in São Paulo, found that newborn babies blink their eyes slower and less frequently than 4–6-year-old children. Uretmen et al., in Turkey, report that accommodative esotropia developed in 50% of children who underwent surgical treatment for presumed infantile esotropia. Teär Fahnehjelm et al., in Sweden, describe the ocular characteristics of a group of children with 3-hydroxyacyl-CoA dehydrogenase deficiency with variable degrees of chorioretinal pathology and visual impairment. Soliman et al., in Copenhagen and Egypt, propose that OCT analysis can predict the visual outcome 1 month following laser photocoagulation for diffused diabetic macular oedema. Maca et al., in Vienna, used the retinal thickness analyser to demonstrate that cystoid macular oedema is common in children with uveitis – even some with good visual acuity. Mahdizadeh et al., in Iran, found that retinal cryopexy did not benefit the anatomical reattachment rate from scleral buckling surgery. Donati et al., in Geneva, found that both necrosis and apoptosis are involved in neuronal cell death following experimental retinal vein occlusion in pigs. Krøyer et al., in Copenhagen, described the effect of acute retinal pigment epithelial loss, which destroyed scotopic but not photopic retinal function in a 68-year-old woman. Bertschinger et al., in Geneva, used the Vryghem macular function test and found this to be reliable in predicting postoperative visual acuity after cataract surgery. Cillino et al., in Italy, found Gore-Tex® implants to be useful adjuvants in glaucoma filtration surgery. Yoeruek et al., in Tübingen, used Avastin® eyedrops to reduce corneal damage and neovascularization following experimental chemical burns to the cornea. Al-Jamal & Kivelä describe an optic nerve tumour leading to progressive visual loss in a young man. I hope that this issue of Acta offers an opportunity to brush up on our knowledge in paediatric ophthalmology and provides educational opportunities in all subspecialties of ophthalmology.

Localized-Low Attenuation of the Lung on Thin-Section CT in Experimentally Induced Pulmonary Arterial Occlusion with Balloon Catheter in Pigs

Purpose: To determine whether a localized low-attenuation (LLA) is induced on a thinsection CT (TSCT) during an acute pulmonary arterial occlusion in pigs. Materials and Methods: In eight pigs, 14 sites of the descending pulmonary artery were obstructed using balloon catheters. The lung TSCTs were obtained immediately after pulmonary artery obstruction (n=13), 10 min (n=10), 30 min (n=14) and 60 min (n=14) after pulmonary artery obstruction at the end of expiration. The TSCTs were also obtained after balloon-deflation at the end of expiration (n=11) and with the balloon-reinflation at inspiration (n=6). Results: Of the 14 sites of pulmonary artery obstruction, 11 (79%) showed LLA. However, LLA progressively became fainter or disappeared on a follow-up CT in seven sites. When the balloon was deflated, 10 of the 11 sites measured showed no change in lung attenuation. After full inspiration, LLA disappeared in three of the six sites. The corresponding areas of LLA on the CT showed a statistically significant increase compared to the baseline CT immediately after inflation (p = 0.021) and 30 minutes after inflation (p =0.041), and after balloon deflation (p =0.036). Conclusion: LLA was induced by acute pulmonary artery obstruction. However, LLA, gradually faded over the 60 minutes following obstruction. LLAs were maintained despite the restoration of pulmonary arterial flow, but disappeared as a result of a full inspiration. Thus, LLA might be caused by air trapping.

Treating Ischemic Left Ventricular Dysfunction With Hypertonic Saline Administered After Coronary Occlusion in Pigs

The effects of hypertonic saline on ventricular function are controversial, whether it is increasing contractility or preload. There are no data, however, on the influence of hypertonic saline in a stunned myocardium. This study was prospective and randomized in order to analyze the effects of hypertonic saline solution (7.5%) on myocardial function and systemic hemodynamics in a porcine model of ischemia and reperfusion. A university teaching hospital, animal research laboratory. Twelve adult domestic swine. Myocardial stunning was produced by the complete occlusion of the proximal left anterior descending artery for 15 minutes followed by reperfusion. Five minutes after reperfusion, the animals were assigned to receive 4 mL/kg of hypertonic saline (n = 7) or normal saline (n = 5) over 10 minutes. Pressure-tipped catheters were placed in the left ventricular cavity and aorta. The dimensions of the left ventricle were measured with ultrasonic microcrystals. Cardiac output was measured with transit time ultrasound. Data were recorded continuously and compared before the occlusion, 5 minutes after reperfusion, and at the end of the infusion. Compared with baseline, ventricular function was significantly depressed after left anterior descending artery occlusion. Left ventricular dP/dT and its end-systolic pressure-volume slope decreased (38% and 52%, respectively; p < 0.05), with a concomitant increase in systemic vascular resistance. The administration of hypertonic saline significantly improved left ventricular function (Emax 1,422 +/- 198 mmHg/mL, and dP/dT 3.2 +/- 0.4 mmHg/s v normal saline group values of 1,156 +/- 172 and 2.5 +/- 0.5, respectively; p < 0.05), cardiac output (2.5 +/- 0.5 v 1.84 +/- 0.4 L/min, p < 0.05), and lowered systemic vascular resistance (from 28.8 +/- 2.3 to 23.5 +/- 1.4, p < 0.05), with no significant changes with normal saline administration. After transient myocardial ischemia, hypertonic saline administered over a short period of time acts as an inodilator by increasing contractility while simultaneously lowering systemic vascular resistance.

Effects of sevoflurane and propofol on ischaemia–reperfusion injury after thoracic-aortic occlusion in pigs

Thoraco-abdominal-aneurysm surgery predicts high mortality. Propofol and sevoflurane are commonly used anaesthetics for this procedure. Halogenated anaesthetics induce organ protection similar to ischaemic preconditioning. We investigated which anaesthetic regimen would lead to a better protection against ischaemia-reperfusion injury induced by temporary thoracic-aortic occlusion. Following initial fentanyl-midazolam anaesthesia for surgical preparation, 18 pigs were randomly assigned to two groups: group one received propofol (n=9) and group two sevoflurane (n=9) before, during, and after lower body ischaemia in an investigator blinded fashion. Ten animals without aortic occlusion served as time controls (propofol, n=5; sevoflurane, n=5). For induction of ischaemia, the thoracic aorta was occluded by a balloon-catheter for 90 min. After 120 min of reperfusion, the study anaesthetics were discontinued and fentanyl-midazolam re-established for an additional 180 min. Goal-directed therapy was performed during reperfusion. Fluid and catecholamine requirements were assessed. Serum samples and intestinal tissue specimens were obtained. Severe declamping shock occurred in both study groups. While norepinephrine requirements in the sevoflurane group were significantly reduced during reperfusion (P<0.05), allowing cessation of catecholamine support in 4/9 animals, all 9/9 animals were still catecholamine dependent at the end of the experiment in the propofol group. Serum activities of lactate dehydrogenase, aspartate transaminase, and alanine aminotransferase were lower with sevoflurane (P<0.05). Small intestine tissue specimens did not differ histologically. Use of sevoflurane compared with propofol attenuated the haemodynamic sequelae of reperfusion injury in our model. Release of serum markers of cellular injury was also attenuated.

Comparison of the Anti-Arrhythmic Effects of Lidocaine and Riluzole Immediately Post-Coronary Artery Occlusion in Pigs

Comparison of the Anti-Arrhythmic Effects of Lidocaine and Riluzole Immediately Post-Coronary Artery Occlusion in Pigs

Comparative effects of left ventricular performance, arterial hemodynamics, and left ventriculo-arterial (VA) coupling of two models of coronary artery occlusion in pigs

Comparative effects of left ventricular performance, arterial hemodynamics, and left ventriculo-arterial (VA) coupling of two models of coronary artery occlusion in pigs