Research progress on the mechanism of epithelial mesenchymal transformation in RPE cells and the treatment of PVR / 国际眼科杂志(Guoji Yanke Zazhi)

@#Proliferative vitreoretinopathy(PVR)is a serious complication arisen from ocular trauma, diabetic retinopathy, vascular retinopathy, inflammatory retinopathy and other ocular diseases. It is also the most important reason for the failure of rhegmatogenous retinal detachment surgery, which is a great threat of visual function. A large number of studies have proved that the main risk factor for PVR is the damage of blood-retinal barrier, in which retinal pigment epithelial(RPE)cells are stimulated by cytokines in the vitreous cavity. RPE cells underwent epithelial-mesenchymal transition(EMT), which transformed into fibroblasts. The cell morphology changed, the tight junctions between cells disappeared, the cell polarity lost, and the proliferation, migration, and invasion abilities were enhanced. A contractile fibrous proliferative membrane is formed on the anterior surface or under the retina. The fibrous proliferative membrane will lead to the retina folds, pull the retina and lead to retinal detachment, which will eventually lead to vision loss or even blindness. Nowadays, plenty of studies investigating the prevention and treatment of PVR have been carried out at home and abroad. In this review, we briefly illustrated the signaling pathways related to epithelial-mesenchymal transformation in RPE cells and the treatment of PVR.

​A Comparative Study of Changes in Left Ventricular Function after Mitral Valve Replacement in Patients with Severe Rheumatic Mitral Regurgitation with and without Mild Mitral Stenosis

Introduction: Presently off- pump CABG has proved itself tobe a safe, cheaper and effective alternative of on- pump CABG.However, it requires manipulation, displacement, positioning& mechanical stabilization of the heart during grafting whichmay cause haemodynamic alteration. Study was done withthe objective of finding out the changes in Central VenousPressure (CVP); Mean Arterial Pressure (MAP); MeanPulmonary Arterial Pressure (MPAP); Right Ventricular EndDiastolic Pressure (RVEDP) & Left Ventricular End DiastolicPressure (LVEDP) while grafting the anterior, lateral &inferior surfaces of heart during off-pump CABG.Material and methods: Over one year time, 50 patients withLVEF ≥40%, undergoing off-pump CABG were monitoredfor the above parameters at various stages of their operation,namely:- 1. During manipulation & shunt introduction,2.During anastomosis without shunt, 3.During anastomosiswith shunt & 4.After anastomosis; while grafting the anterior,lateral & inferior surfaces of heart. These results werecompared with the baseline values of CVP, MAP, MPAP,RVEDP & LVEDP, to look for statistical significance.Results: During manipulation & shunt introduction; CVP(mmHg) significantly increased during Ramus grafting - 12±1.8(p<0.047); and also during OM grafting – 12.6±1.9 (p<0.045),when compared to a baseline value of 9±1.8. The MAP(mmHg) was significantly decreased during manipulation &shunt introduction in Diagonals - 70±5.8 (p<0.046), Ramus- 70±5.8 (p<0.048), OMs - 65±5.8 (p<0.028) & in the Rightterritory - 69±5.9 (p<0.032); as compared with baselineMAP of 76±11.7. During anastomosis without shunt also, theMAP(mmHg) significantly decreased while grafting LAD- 70±3.8 (p<0.048), Diagonals - 68±3.8 (p<0.039), OMs –71.8±4.8 (p<0.039) & Right sided arteries 70.8±4.6 (p<0.039),as compared with baseline MAP values. The MPAP(mmHg)was significantly increased – 18.3±3.7 (p<0.047) as comparedto the baseline value of 16±2.4 during manipulation & shuntintroduction in the OMs.Conclusion: During OPCABG there will be significantalterations in haemodynamics mostly due to mobilizationof the heart, which is necessary to visualise the targetvessels properly & stabilisation of the concerned areawith stabiliser. However, by observing the haemodynamicvariations constantly & by making necessary mechanical &pharmacological adjustments, unnecessary conversion to Onpump technique can be avoided.

Study of Prevalence of Pulmonary Artery Hypertension in Portal Hypertensives Patients in RIMS, Ranchi

Background: The development of pulmonary hypertension i.e.mean pulmonary artery pressure (mPAP) above 25 mmHg withnormal capillary wedge pressure and pulmonary vascularresistance(PVR) above 240 dyn/s/cm−5 in association withelevated pressure in portal circulation is known asportopulmonary hypertension (POPH). Comparing withidiopathic PAH, patients with POPH have a worst survivalprofile, with a 3-year survival of only 38% versus78% foridiopathic PAH. Recent evidence from France shows thatPOPH is the fourth most common form of PAH reported overallin the population-based French National Registry, afteridiopathic PAH and PAH associated with connective tissuediseases and con- genital heart disease. The aim of this studyis to evaluate frequency of POPH in portal hypertensivepatient.Materials and Methods: A cross sectional study of patientadmitted in RIMS, medicine department was performedfulfilling features of portal hypertension with ultrasoundshowing splenomegaly, ascites, portal vein diameter more than13 mm, portal vein velocity less than 15 cm/s and uppergastrointestinal endoscopy showing esophageal varices andpatient with connective tissue disease, congenital heartdisease, left ventricular systolic or diastolic dysfunction,valvular heart disease, lungs disease, sleep related breathingdisorder, chronic hemolytic and myeloproliferative disorderwere excluded. All patient underwent screening withechocardiography for measuring pulmonary artery systolicpressure (PASP) and PASP more than 35 mmHg wereconsidered for POPH which was confirmed with right heartcatheterisation by measuring mean pulmonary artery pressure(mPAP) of more than 25 mmHg.Observation: Among forty-two patient in this study, there werethirty-three male patients and nine female patients. POPH wasseen three female and two male patients with total of five out offorty- two with prevalence of 11.9% out of which 7.1% werefemale and 4.8% were male.Conclusion: Portopulmonary hypertension prevalence is 2–6%. In this study pulmonary hypertension is significantly high inportal hypertensive patient with percentage of 11.9% and moreprevalent in female.

The influence of pVR-IL15 gene adjuvant on immunization with recombinant viruses expressing HBsAg / 中华实验和临床病毒学杂志

Objective@#To explore the influence of pVR-IL15 gene adjuvant on the immune responses of different immunization strategies.@*Methods@#The sequential immunization strategies were used in BALB/c mice with a DNA vaccine, recombinant modified vaccinia virus Ankara and recombinant adenovirus expressing HBsAg respectively and combined with a gene adjuvant pVR-IL15. Cellular and humoral immune responses were evaluated by IFN-γ enzyme-linked immunospot assay (ELISPOT) and enzyme-linked immunosorbent assay (ELISA), respectively.@*Results@#The levels of humoral and cellular immune responses in the immune groups combined with pVR-IL15 were significantly higher than those of the non-combined with pVR-IL15.@*Conclusions@#The pVR-IL15 gene adjuvant can enhance the immune responses induced by the recombinant viruses expressing HBsAg.

Assay for identification of heterozygous single-nucleotide polymorphism (Ala67Thr) in human poliovirus receptor gene.

Background & objectives: It is important to understand the role of cell surface receptors in susceptibility to infectious diseases. CD155 a member of the immunoglobulin super family, serves as the poliovirus receptor (PVR). Heterozygous (Ala67Thr) polymorphism in CD155 has been suggested as a risk factor for paralytic outcome of poliovirus infection. The present study pertains to the development of a screening test to detect the single nucleotide (SNP) polymorphism in the CD155 gene. Methods: New primers were designed for PCR, sequencing and SNP analysis of Exon2 of CD155 gene. DNAs extracted from either whole blood (n=75) or cells from oral cavity (n=75) were used for standardization and validation of the SNP assay. DNA sequencing was used as the gold standard method. Results: A new SNP assay for detection of heterozygous Ala67Thr genotype was developed and validated by testing 150 DNA samples. Heterozygous CD155 was detected in 27.33 per cent (41/150) of DNA samples tested by both SNP detection assay and sequencing. Interpretation & conclusions: The SNP detection assay was successfully developed for identification of Ala67Thr polymorphism in human PVR/CD155 gene. The SNP assay will be useful for large scale screening of DNA samples.

Comparison of Pre-Operative and Post-Operative Post Void Residual Urine Volume in Urogenital Prolapse.

Background: Post Void Residual Urine (PVR) is a key marker for the evaluation of the efficacy of bladder emptying particularly in women with pelvic organ prolapse and lower urinary tract dysfunction. Objectives of the present study were to compare pre and postoperative post void residual urine volume and to know the relation of PVR to urinary symptoms and prolapse. Methods: 65 patients admitted with urogenital prolapse. Detailed history, general physical examination was done as per predesigned and pretested proforma. Grading for prolapse was done by POP-Q, Baden walker halfway. PVR was measured before and after operation Results: Age has shown significant relation with the raised PVR > 50 ml (p=0.007). Out of 65 cases, 11 had second, 48 had third degree and 6 had procedentia according to Baden Walker system. Urge and stress incontinence were complained by 43% and 26% of patients respectively and increased frequency and nocturia was complained by 68% and 65% of patients. Storage symptoms were not significantly associated with degree of prolapse or raised PVR. Straining to void, incomplete emptying and has to reduce to void were present in 42, 46 and 47 patients respectively and showed significant association with degree of prolapse. Except incomplete emptying other two were associated with raised PVR. Conclusion: Vaginal hysterectomy with anterior colporrhaphy was effective procedure in reducing elevated PVR in prolapse patients.

Immunoregulation effect of TIGIT-Fc on macrophages / 中国免疫学杂志

Objective:To prepare the production of TIGIT-Fc fusion protein using H22 cells stably integrated the gene by lentivirus vector , and to explore the immunoregulatory effect on macrophages by TIGIT-Fc.Methods: TIGIT-Fc fusion gene were constructed by molecular cloning.The fusion gene was then subcloned to plasmids contained the secretion signaling peptide .The secrected TIGIT-Fc fusion gene was inserted into the lentivirus backbone vector.The purified lentivirus vector was the used to infect the murine H22 cell line.TIGIT-Fc protein was purified by protein A column from the ascites of H 22-injected C57BL/6 mice.Macrophages stimulated by lipopolysaccharide ( LPS ) was challenged to TIGIT-Fc treatment or control.Cytokine levels was then detected by ELISA.Results: TIGIT-Fc protein was purified from the ascites of H 22-injected mice.PVR was upregulated in LPS-treated macrophages.IL-10 level was upregulated in TIGIT-Fc treated macrophages.Conclusion: TIGIT-Fc promotes the mature macrophages to secrete anti-inflammatory cytokine IL-10.

Outcomes of Relaxing Retinectomy in Patients with Proliferative Vitreoretinopathy

PURPOSE: To report the outcomes of relaxing retinectomy for retinal detachment in patients with proliferative vitreoretinopathy (PVR). METHODS: Sixty-four cases of relaxing retinectomy for PVR with a minimum follow-up of 6 months were retrospectively reviewed. The outcomes included achievement of complete retinal reattachment, PVR recurrence, the mean number of additional operations, visual acuity and incidence of postoperative complications. We analyzed the influence of intraoperative factors including lens status, retinectomy extent, additional scleral buckling, and tamponade agent on primary retinal reattachment. RESULTS: Complete retinal reattachment was achieved in 47 eyes (74.3%) without an additional surgery. PVR recurred in 19 eyes (29.7%) and an additional operation was performed in 17 eyes (26.6%). Fifty-seven (89.1%) eyes showed complete retinal reattachment and 40 eyes (62.5%) had visual acuity of 0.02 or more at the final follow-up visit. Hypotony was the major complication and developed in 10 eyes (15.6%). Eyes undergoing smaller ( or = 180degrees) retinectomy or gas tamponade (p = 0.043 and 0.013, respectively). CONCLUSIONS: Relaxing retinectomy is a useful technique for retinal detachment with PVR, but risk of recurrent proliferation or hypotony should be considered.

Mutation and association analysis of the PVR and PVRL2 genes in patients with non-syndromic cleft lip and palate

Orofacial clefts (OFC; MIM 119530) are among the most common major birth defects. Here, we carried out mutation screening of the PVR and PVRL2 genes, which are both located at an OFC linkage region at 19q13 (OFC3) and are closely related to PVRL1, which has been associated with both syndromic and non-syndromic cleft lip and palate (nsCLP). We screened a total of 73 nsCLP patients and 105 non-cleft controls from the USA for variants in PVR and PVRL2, including all exons and encompassing all isoforms. We identified four variants in PVR and five in PVRL2. One non-synonymous PVR variant, A67T, was more frequent among nsCLP patients than among normal controls, but this difference did not achieve statistical significance.

Role of HGF/c-Met in Serum-Starved ARPE-19 Cells

PURPOSE: Hepatocyte growth factor (HGF) and its receptor (HGFR/c-Met) regulate motility, mitogenesis, and morphogenesis in a cell type-dependent fashion. We report the role of HGF and c-Met on stress-induced ARPE-19 human retinal pigment epithelial (RPE) cells in this study. METHODS: The cells were cultured either with or without serum. Southern and Western blot analyses were done to determine the expression patterns of HGF/c-Met in serum-starved ARPE-19 cells. The cell proliferation pattern in serum-starved condition was analyzed using MTS assay. Inhibition level of cell proliferation was analyzed using a neutralizing monoclonal antibody against c-Met (2 microgram/ml). RESULTS: Abnormal cell proliferation and scattering of ARPE-19 cells was observed under serum starvation. HGF/c-Met were expressed in serum-starved ARPE-19 cells. ARPE-19 cell proliferation was also enhanced with recombinant HGF treatment. Neutralization against c-Met inhibited the proliferation of serum-deprived ARPE-19 by 64.5% (n=9, S.D. 5.5%). Serum starvation appears to induce epithelial-mesenchymal transition of ARPE-19 cells, resulting in scatter, and the expression of alpha-smooth muscle actin (alpha-SMA), a marker for fibrosis. CONCLUSIONS: In conclusion, c-Met induced under non-physiologic conditions has significant effects on the activation of RPE cells.

RPE Cell Apoptosis by the Combination Treatment of SAHA and Lactacystin

PURPOSE: To establish a new therapeutic strategy for proliferative vitreoretinopathhy (PVR), we examined the effect of combined treatment with HDAC inhibitor SAHA and proteasome inhibitor lactacystin in human retinal pigment epithelial (RPE) cells, ARPE-19. METHODS: Viability was determined by trypan blue exclusion assay. Mitochondrial membrane potential (MMP) was measured by flow cytometry. Proteasome activity was measured by fluorophotometry. The expression and degradation of apoptosis-related proteins were assesssed by Western blotting. Subcellular location of apoptosis-related factors was monitored by confocal miscroscopy. RESULTS: A single treatment with 5 micro M SAHA or 10 micro M lactacystin did not reduce cell viability. However, combination treatment with 5 micro M SAHA and 10 micro M lactacystin substantially reduced the viability, because the mixture induced the reduction of MMP and nuclear condensation or fragmentation. Moreover, the combination treatment triggered the activation of caspase-3 and the production of PARP cleavage products. These data indicate that the combination treatment efficiently induces apoptosis in ARPE-19 cells. However, co-treatment of SAHA did not augment the proteasome inhibitory activity of lactacystin, nor did co-treatment of lactacystin augment acetylation of histones. It is notable that while p53 and CAD were observed in the mitochondria of cells treated with SAHA, they were translocated into the nucleus after the combination treatment. CONCLUSIONS: These results suggest that the combination treatment of SAHA and lactacystin effectively induced apoptosis in ARPE-19 cells. Further work is warranted to develop this combination therapy as a novel therapeutic strategy for PVR.

The Effect of Antiproliferative Drugs on the Collagen Matrix Cultured with Retinal Pigment Epithelial Cell and Choroidal Fibroblast

PURPOSE: Epiretinal membrane in proliferative vitreoretinopathy (PVR) may cause tractional retinal detachment after vitreoretinal surgery. It has been thought that the proliferative membrane is mainly composed of choroidal fibroblasts and retinal pigment epithelial cells. Inspite of the technical advances, the treatment of PVR is still difficult. Therefore, the need for phamarcologic treatment of proliferative vitreoretinopathy is increasing. METHODS: In vitro models of proliferative vitreoretinopathy allow to identify the factors which may inhibit proliferation and contraction of collagen matrix by choroidal fibroblast and retinal pigment epithelial cells. Cultured choroidal fibroblasts and the RPE cells were plated to the collagen matrix and antiproliferative drugs was tested. RESULTS: Each antiproliferative drug showed the inhibition of collagen matrix contraction at following concentration: colchicine(0.1 microgram/ml), puromycin(1~10 microgram/ml), cytochalasin B(0.05 microgram/ml). Transmission electron micrograph of collagen matrices showed dense collagen fibers surrounding choroidal fibroblast and fine collagen fibers surrounding RPE cell. Scanning electron micrograph of collagen matrices contaning colchicine, puromycin, or cytochalasin B showed that collagen fibers were well preserved without distortion. All collagen matrices containing RPE cells showed more fine collagen fibers than those containing choroidal fibroblasts. CONCLUSION: Colchicine, puromycin, cytochalasin B showed inhibitory effect on cell mediated contraction in addition to potent antiproliferative effect. Retinal pigment epithelial cell played less significant role in causing PVR than choroidal fibroblast.

Changes of Blood Gases, Plasma Catecholamine Concentrations and Hemodynamic Data in Anesthetized Dogs during Graded Hypoxia Induced by Nitrous Oxide / 영남의대학술지

The sympathoadrenal system plays an important role in homeostasis in widely varing external environments. Conflicting findings, however, have been reported on its response to hypoxia. We investigated the effect of hypoxia an the sympathoadrenal system in dogs under halothane anesthesia by measuring levels of circulating catecholamines in response to graded hypoxia. Ten healthy mongreal dogs were mechanically ventilated with different hypoxic gas mixtures. Graded hypoxia and reoxygenation were induced by progressively decreasing the oxygen fraction in the inhalation gas mixture from 21%(control) to 15%, 10% and 5% at every 5 minutes, and then reoxygenated with 60% oxygen. Mean arterial pressure, central venous pressure and mean pulmonary arterial pressure were measured directly using pressure transducers. Cardiac output was measured by the thermodilutional method. For analysis of blood gas, saturation and content, arterial and mixed venous blood were sampled via the femoral and pulmonary artery at the end of each hypoxic condition. The concentration of plasma catecholamines was determined by radioenzymatic assay. According to the exposure of graded hypoxia, not only did arterial and mixed venous oxygen tension decreased markedly at 10% and 5% oxygen, but also arterial and mixed venous oxygen saturation decreased significantly. An increased trend of the oxygen extraction ratio was seen during graded hypoxia. Cardiac output, mean arterial pressure and systemic vascular resistance were unchanged or increased slightly. Pulmonary arterial pressure(PAP) and pulmonary vascular resistance(PVR) were increased by 55%, 76% in 10% oxygen and by 82%, 95% in 5% oxygen, respectively(p<0.01). The concentrations of plasma norepinephrine, epinephrine and dopamine increased by 75%, 29%, 24% in 15% oxygen and by 382%, 350%, 49% in 5% oxygen. These data suggest that the sympathetic nervous system was activated to maintain homeostasis by modifying blood flow distribution to improve oxygen delivery to tissues by hypoxia, but hemodynamic changes might be blunted by high concentration of nitrous oxide except PAP and PVR. It would be suggested that hemodynamic changes might not be sensitive index during hypoxia induced by high concentration of nitrous oxide exposure.

The Effect of Retinoic Acid on Experimentally-Induced Proliferative Vitreoretinopathy in the Rabbit

The proliferative vitreoretinopathy was a complication followed by operation of rhegmatogenous retinal detachment. It was the mot, comon cause of a failure of retinal detachment surgery. It was characterized by the growth of cellular fibrous membrance in detached both retinal side and vitreous and also developed by giant retinal dialysis, posterior segmental trauma, excessive cryotherapy, endophthalmitis, retianl vascular disease. In order to prevent and treat of proliferative vitreoretinopathy, various methods of operation and drugs have been researched. We executed the experiment using the rabbit to observe the effect of retinoic acid that is known by inhibition of migration and proliferation of retinal pigment epithelial cell and fibroblast in vitro. With 121 eyes of rabbit, we induced the proliferative vitreoretinopathy by injecting of human retinal pigment epithelial cell, human fibroblast, and rabbit fibroblast into eyeball of rabbits. The extent of proliferative vitreoretinopathy was compaired by injecting those cells with the group that was injected by retinoic acid and control. The result was that in those cell groups, the extent of proliferative vitreoretinopathy was significantly higher in the rabbit fibroblast group than the other two groups(P<0.05). And in the groups that were injected retinoic acid, when subconjuctivaly injected(0.3mg/0.3ml), proliferative vitreoretinopathy was effectively suppressed and when intravitrealy injected (0.05mg/0.1ml), vitreoretinopathy was more increased than the control group. This result was probably caused by high concentration of retinoic acid in vitreous and further evaluation with various concentration of retinoic acid is needed. In conclusion, we recommend a rabbit fibroblast and subconjunctival injection of retinoic acid for the study on the suppressive effect of proliferative vitreoretinopathy.

The Experimental study of Injections of Cultured Fibroblasts into the Rabbit Vitreous

The major cause of failure of retinal detachment surgery is proliferative vitreoretinopathy(PVR). This disorder is characterized by the formation of the contractile cellular membrane on both surfaces of retina and within the vitreous cavity. These cellular membranes contract and thereby cause traction retinal detachment. The pathogenesis of this disorder is not fully understood. The authors developed a consistent model of proliferative vitreoretinopathy in the rabbit by partially digesting the post. Vitreous with repeated injection and aspiration of 1 IU of hyaluronidase before injection of 250,000 homologous dermal fibroblasts. All experimental rabbit eyes had vitreous opacity and hyperemia of the optic disc head. The progression of PVR was rapid and moderately severe. On day 1, 13 of 15 eyes(87%) had vitreous strand formation alone(Grade 1 PVR). One day 3, all 15 eyes(100%) had vitreous strand formation. We have developed a model of proliferative vitreoretinopathy in the rabbit. After intravitreal autotransplantation of tissue cultured homologous skin fibroblasts, we observed high rate of vitreous strand formation in the vitreous cavity. This experimental model will be useful for studying the pathogenesis of proliferative vitreoretinopathy and evaluating potential treatment for its prevention.

The Effect of Daunorubicin on Experimental Proliferative Vitreoretinopathy

Proliferative vitreoretinopathy (PVR) is a main cause of failure in retinal reattachment surgery. There have been many studies about the inhibition of proliferative vitreoretinophthy with several drugs. Authors investigated the inhibitory effect of proliferative vitreoretinopathy and retinal toxicity with various concentration of daunorubicin after intravitreal injection into the eyes of the pigmented rabbit. 7 pigment rabbit (11eyes) were used as subjects. After lensectomy and vitrectomy, control group was injected dermal fibroblast and F-BSS, and treatment group was injected dermal fibroblast and 5, 10, 15, 30 nmol Daunorubicin. At two weeks after intravitreal injection, both group were enucleated and examined with gross finding, light--microscopy, and electronmicroscopy. In all control group, proliferative vitreoretinopathy was found, but only preretinal membrane formation was found in 5, 10 nmol Daunorubicin injected group. In 15 nmol Daunorubicin injected group, the retina structure was preserved normally. In 30 nmol Daunorubicin injected group, the retinal outer segment was degenerated in microscopic finding. These results show that Daunorubicin has a potent effect on proliferative vitreoretinopathy, especially in 15 nmol, but retinal toxicity is suspected in marethan 30 nmol.

The effect of subtenon injection of methylprednisolone acetate on the breakdown of blood retinal barrier after cryotherapy

Using computerized vitreous fluorophotometry (VFP, Fluorotron(TM)), we examined the effect of cryotherapy on the blood retinal barrier (BRB) and the effect of subtenon injection of methylprednisolone acetate (Depomedrol(R)). In experiment 1, the right eyes of the 13 pigmented rabbits were treated with heavy cryotherapy after baseline VFP readings. The freezes were applied at 6 places in each quadrant around the equator are in two rows, a total of 24 places circumferentially. The left eyes were reserved as controls. In 6 rabbits (cryo with steroid group), Depomedrol(R) 10 mg of Depomedrol was injected into subtenon space after cryotherapy. The other 7 rabbits were treated with cryotherapy only (cryo only group). The VFP readings were taken 1, 3, 5, and 7 days, 2, 3, 5, and 7 weeks after cryotherapy. Cryotherapy increased the breakdown of BRB significantly. The peak VFP readings were obtained 5 days after cryotherapy in the cryo only group and 7 days after cryotherapy in the cryo with steroid group. In the cryo only group, the severity of the breakdown of BRB was higher than in the cryo with steroid group, and the increased VFP readings could not be normalized until 7 weeks after cryotherapy. In experiment 2, both eyes of the 8 pigmented rabbits were treated with medium cryotherapy after baseline VFP readings. The freezes were applied at 3 places in the superior temporal quadrant and at 3 places in the superior nasal quadrant, a total of 6 places. Depomedrol(R) 10 mg was injected into subtenon space after cryotherapy in the right eyes only. The VFP readings were taken 1, 3, 5, 7, 10, and 14 days after cryotherapy. In this experiment, cryotherapy did not increase the breakdown of BRB. But in the right eye, the severity of the breakdown of BRB was significantly lower than in the left eye 7 and 10 days after cryotherapy. These results suggest that Depomedrol(R) can decrease the severity of the breakdown of BRB after cryotherapy, and may be useful in the prevention of proliferative vitreoretinopathy (PVR).

Effect of Positive End-expiratory Pressure(PEEP) of Contra-lateral Lung on Redistribution of Pulmonary Blood Flow during One-lung Atelectasis / 대한마취과학회지

The normal response of the pulmonary vasculature to one-lung atelectasis is an increase in pulmonary vascular resistance (PVR). The mechanism of the increase in PVR is thought to be due almost entirely to hypoxic pulmonary vasoconstriction (HPV). Regional HPV results in blood flow diversion from hypoxic regions to normoxic regions. The expected pulmonary shunt is thereby reduced and the arterial oxygen tension increased. PEEP improves the arterial oxygen tension as a result of increasing functional residual capacity (FRC) and decreasing intrapulmonary shunt. The aims of the present studies were to observe blood flow diversion from atelectatic lung to normoxic lung and to prove a sustained redistribution of pulmonary blood flow from ventilated with PEEP to atelectatic regions. This study evaluated the interactions between HPV and PEEP. Eight mongrel dogs were anesthetized with pentobarbital. Left pulmonary blood flow was measured with eletromagnetic flow probes following left lateral thoracotomy. Pulmonary arterial pressures, PCWP, systemic arterial pressures were measured via indwelling catheter. Cardiac output was determined by thermodilution in triplicate. The right lung was ventilated continuosly with 100% O2, while left lung was ventilated with 100 O2 (control phase), and unventilated for 60 min. of atelectasis. PEEP of 5 and 10 cmH2O was ed to the right lung. During two-lung ventilation with 100 oxygen, cardiac output was 2890+/-880 ml/min. (mean SD) and left pulmonary blqod flow was 1100+/-220 ml/min. Left lung atelectasis resulted in a reduction of the percent left blood flow compared with cardiac output from 41+/-10% to 29+/-7% at 15 min and to 22+/-9% at 60 min (p<0.05). The ratio of left pulmonary blood flow to mean pulmonary artery pressure decreased from 51+/-25 ml/min/ mmHg in control to 19+/-7 ml/min/mmHg at 60 min (p<0.05). Left pulmonary vascular resistance increased gradually (p<0.01). Arterial oxgen tension was the lowest at 15 min (165+/-66 mmHg) and increased subsequently (p<0.01). Intrapulmonary shunt was 27+/-6% in, control phase and abruptly increased to 37+/-6% at 15 min after atelectasis and decreased to 34+/-10% at 60 min. When 10 cmH2O PEEP was applied to the right hung during left lung atelectasis, the percent ratio of left pulmonary blood flow to cardiac output was significantly increased from 22+/-9% at 60 min of left lung atelectasis to 34+/-8% (p<0.05). Left pulmonary vascular resistance significantly decreased as compared with 45 and 60,min of left lung atelectasis (p<0.05). Arterial oxygen tension incresed by PEEP of 5 and 10 cmH to 257+/-74 mmHg and 252+/-92 mmHg compared with 164+/-65 mmHg and 177+/-28 mmHg at 15 and 30 min. of left lung atelectasis (p<0.05). The present study demonstrated that the response to acute atelectasis is a regional increase in pulmonary vascular resistance and a sustained diversion of blood flow away from the atelectatic lung. In this study, the application of 10 cmH2O PEEP resulted in a redistribution of pulmonary blood flow from normoxic lung to atelectatic lung and didn't affect arterial oxygenation. We conclude that when employing the technique of one-lung anesthesia, PEEP to improve oxygenstion should be cautiously applied and a search for the maximum oxygenation and a minimum redistribution might be started, in an attempt to find the optimal PEEP.

Effect of Intravitreal Silicone Oil and Gas Tamponade to Proliferative Vitreoretinopathy(PVR)

Silicone oil is widely used as a retinal tamponade in the treatment of PVR. But reproliferation of membrane can occur under the silicone oil. Formerly, silicone oil was believed to suppress the proliferation of membrane, but recently, there were reports that silicone oil might actually promote proliferation of membrane, and recommended to use long-lasting gas rather than silicone oil. But it is known that proliferation of membrane can also occur in the eye in which intraocular gas has been used. So a careful study to compare the effect of intraocular gas and silicone oil to proliferation of membrane is needed. Rabbits are divided into three groups. Retinal tears were made in all the groups. in control group, no further surgery was done, and in the other two group, perfluoropropane gas was injected into the vitreous cavity. The intraocular gas was left unchanged(gas group), or it was exchanged with silicone oil 3 days later(silicone oil group). The fundus was examined periodically, and the eyeball was removed at 1, 2, 4, and 8 weeks after surgery for histopathologic study with light and electron microscope. Both intravitreal gas and silicone oil were shown to increase the formation of proliferative membrane compared to control group, but there was no statistically significant difference between them.

Effect of Cryotherapy on Proliferative Vitreoretinopathy(PVR)

Cryotherapy is blamed for inducing or aggravating PVR, by releasing retinal pigment epithelial(RPE) cells. These are based on the fact that PVR rarely occurs in non-operated eye, and many of PVR patients have received cryotherapy during surgery. Nontheless, in eyes with diathermy also developed PVR, and although there have been many experiments, the effect of cryotherapy on inducing PVR was not proven experimentally in the living eye. We made retinal tears in the living rabbit eyes, and applied cryotherapy on one eye of each rabbit. The result was compared histopathologically with noncryothermized control eye. There was no statistically significant difference between the two groups concerning the migration of RPE, and the proliferation of RPE. Although the formation of epiretinal membrane was more obvious in the cryothermized group, the difference was not statistically significant.