Background

Although supplemental fentanyl has been widely used to blunt the hemodynamic responses to laryngoscopic intubation, its residual vagotonic effect may increase the risk of reflex bradycardia. We compared the incidence and severity of significant reflex bradycardia after a bolus injection of equivalent doses of fentanyl and remifentanil (control drug).

Methods

In this prospective, randomized, double-blind study, 220 adult patients undergoing major abdominal surgery were randomly assigned to receive fentanyl (1.5 µg/kg) or remifentanil (1.5 µg/kg). No anticholinergic prophylaxis was administered. Symptomatic reflex bradycardia was defined as a sudden decrease in heart rate to < 50 beats per minute (bpm) or to 50-59 bpm associated with a systolic arterial pressure < 70 mmHg in connection with surgical maneuvers. If bradycardia or hypotension developed, atropine or ephedrine was administered following a predefined treatment protocol.

Results

In total, 188 subjects (remifentanil, 95; fentanyl, 93) were included. The proportion of subjects with symptomatic reflex bradycardia in the fentanyl group was similar to that in the remifentanil group (30.1% vs. 28.4%, respectively). Atropine and/or ephedrine were needed similarly in both groups. The differences between the group of 55 patients who presented with symptomatic reflex bradycardia were not statistically significant with respect to the lowest heart rate, anesthetic depth-related data (bispectral index and end-tidal sevoflurane concentration), or the proportion of causative surgical maneuvers.

Conclusions

Fentanyl (1.5 µg/kg) administered intravenously during anesthetic induction is unlikely to increase the incidence and severity of significant reflex bradycardia in patients undergoing major abdominal surgery.

The effect of aldosterone on connective tissue growth factor (CTGF) was examined in rat embryonic ventricular myocytes. Upon aldosterone treatment, CTGF expression was significantly increased in a dose and time-dependent manner. To explore the molecular mechanism for this upregulation, we examined the role of mineralocorticoid receptor. Pre-treatment of an antagonist (spironolactone) at 5-fold excess of aldosterone blocked the CTGF induction by aldosterone, suggesting that the upregulation was mediated by mineralocorticoid receptor. Aldosterone treatment resulted in activation of ERK1/2, p38 MAPK, and JNK pathways with a more transient pattern in p38 MAPK. Blocking studies using pre-treatment of the inhibitor of each pathway revealed that p38 MAPK cascade may be important for aldosterone-mediated CTGF upregulation as evidenced by the blocking of CTGF induction by SB203580 (p38 MAPK inhibitor), but not by PD098059 (ERK1/2 inhibitor) and JNK inhibitor I. Interestingly, JNK inhibitor I and PD098059 decreased the basal level of CTGF expression. On the other hand, pre-treatment of spironolactone abrogated the p38 MAPK activation, indicating that mineralocorticoid receptor mechanism is linked to p38 MAPK pathway. Taken together, our findings suggest that aldosterone induces CTGF expression via both p38 MAPK cascade and mineralocorticoid receptor and that cross-talk exists between the two pathways.

Peripheral artery disease (PAD) is an important marker for the risk stratification of patients with coronary artery disease (CAD). We investigated the prevalence of PAD in patients undergoing percutaneous coronary intervention (PCI) with CAD and the relationship between ankle-brachial pressure index (ABPI) and CAD severity. A total of 711 patients undergoing PCI for CAD from August 2009 to August 2011 were enrolled. PAD diagnosis was made using the ABPI. The prevalence of PAD was 12.8%. In PAD patients, mean values of right and left ABPI were 0.71 ± 0.15 and 0.73 ± 0.15. Patients with PAD had a higher prevalence of left main coronary disease (14.3% vs 5.8%, P = 0.003), more frequently had multivessel lesions (74.9% vs 52.1%, P < 0.001) and had higher SYNTAX score (18.2 ± 12.3 vs 13.1 ± 8.26, P = 0.002). Using multivariate analysis, we determined that left main CAD (OR, 2.954; 95% CI, 1.418-6.152, P = 0.004) and multivessel CAD (OR, 2.321; 95% CI, 1.363-3.953, P = 0.002) were both independently associated with PAD. We recommend that ABPI-based PAD screening should be implemented in all patients undergoing PCI with CAD, especially in severe cases.

Pulmonary tumor embolism can be a cause of respiratory failure in patients with cancer even though it occurs rarely. We describe a 56-year-old man who underwent a pulmonary tumor embolectomy using cardiopulmonary bypass on beating heart combined with inferior vena cava embolectomy and right radical nephrectomy. Aggressive surgical treatment in this severe case is necessary not only to reduce the fatal outcome of pulmonary embolism in the short run, but also to improve the oncological prognosis in the long term.

Background/Aims

Identification of patients at high risk for perioperative cardiac events (POCE) is clinically important. This study aimed to determine whether preoperative measurement of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) could predict POCE, and compared its predictive value with that of conventional cardiac risk factors and stress thallium scans in patients undergoing vascular surgery.

Methods

Patients scheduled for non-cardiac vascular surgery were prospectively enrolled. Clinical risk factors were identified, and NT-proBNP levels and stress thallium scans were obtained. POCE was the composite of acute myocardial infarction, congestive heart failure including acute pulmonary edema, and primary cardiac death within 5 days after surgery. A modified Revised Cardiac Risk Index (RCRI) was proposed and compared with NT-proBNP; a positive result for ischemia and a significant perfusion defect (≥ 3 walls, moderate to severely decreased, reversible perfusion defect) on the thallium scan were added to the RCRI.

Results

A total of 365 patients (91% males) with a mean age of 67 years had a median NT-proBNP level of 105.1 pg/mL (range of quartile, 50.9 to 301.9). POCE occurred in 49 (13.4%) patients. After adjustment for confounders, an NT-proBNP level of > 302 pg/mL (odds ratio [OR], 5.7; 95% confidence interval [CI], 3.1 to 10.3; p < 0.001) and a high risk by the modified RCRI (OR, 3.9; 95% CI, 1.6 to 9.3; p = 0.002) were independent predictors for POCE. Comparison of the area under the curves for predicting POCE showed no statistical differences between NT-proBNP and RCRI.

Conclusions

Preoperative measurement of NT-proBNP provides information useful for prediction of POCE as a single parameter in high-risk patients undergoing noncardiac vascular surgery.

The balance between tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) regulates fibrinolysis. PAI-1 expression increases in atherosclerotic arteries and vascular smooth muscle cells (VSMCs) are one of major constituents of atheroma. We investigated the impact of lysophosphatidylcholine (lysoPC), an active component of oxidized low-density lipoprotein, on the plasminogen activator system of the rat VSMCs. The lysoPC stimulated the protein and gene expressions of PAI-1 but did not affect the protein expression of t-PA. Fibrin overlay zymography revealed that lysoPC increased the activity of PAI-1 in the conditioned media, while concurrently decreasing that of free t-PA. Vitamin E inhibited the lysoPC-induced PAI-1 expression. Further, lysoPC increased the intracellular reactive oxygen species (ROS) formation. Caffeic acid phenethyl ester, an inhibitor of NF-κB, blocked this lysoPC effect. Indeed, lysoPC induced the NF-κB-mediated transcriptional activity as measured by luciferase reporter assay. In addition, genistein, an inhibitor of protein-tyrosine kinase (PTK), diminished the lysoPC effect, while 7,12-dimethylbenz[a]anthracene, a stimulator of PTK, stimulated PAI-1 production. In conclusion, lysoPC does not affect t-PA expression but induces PAI-1 expression in the VSMC by mediating NF-κB and the genistein-sensitive PTK signaling pathways via oxidative stress. Importantly, lysoPC stimulates the enzyme activity of PAI-1 and suppresses that of t-PA.

Background and Purpose

The purpose of the present study was to use brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) to identify the mechanism of stroke in patients with Takayasu's arteritis (TA).

Methods

Among a retrospective cohort of 190 TA patients, 21 (3 males and 18 females) with a mean age of 39.9 years (range 15-68 years) who had acute cerebral infarctions were included in lesion pattern analyses. The patients' characteristics were reviewed, and infarction patterns and the degree of cerebral artery stenosis were evaluated. Ischemic lesions were categorized into five subgroups: cortical border-zone, internal border-zone, large lobar, large deep, and small subcortical infarctions.

Results

In total, 21 ischemic stroke events with relevant ischemic lesions on MRI were observed. The frequencies of the lesion types were as follows: large lobar (n=7, 33.3%), cortical border zone (n=6, 28.6%), internal border zone (n=1, 4.8%), small cortical (n=0, 0%), and large deep (n=7, 33.3%). MRA revealed that 11 patients had intracranial artery stenosis.

Conclusions

Hemodynamic compromise in large-artery stenosis and thromboembolic mechanisms play significant roles in ischemic stroke associated with TA.

Purpose

To determine the risk factors of delayed recanalization of isolated calf vein thrombosis (CVT).

Methods

One hundred fifty limbs of 110 patients with CVT between September 2007 and April 2010 were enrolled. We used ultrasonography for the diagnosis and follow-up examinations of CVT. We calculated recanalization rates at 1 and 3 months after initial diagnosis and analyzed the risk factors associated with delayed recanalization of CVT.

Results

CVTs were located in the muscular calf vein in 110 (73.3%), in the deep calf vein in 18 (12%), and in both in 22 cases (14.7%). Among all CVTs, 94 limbs (63%) were symptomatic. Major risk factors for CVT were orthopedic surgery (87.3%), malignancy (21.3%), and immobilization (15.3%). Sixty-seven patients (60.9%) were treated with oral anticoagulation therapy, while 43 patients by low molecular weight heparin (n = 19) or by conservative methods including elastic compression stockings and ambulation (n = 21). The cumulative recanalization rate at 1 and 3 months was 23% and 82% and it was significantly higher in patients who underwent oral anticoagulation therapy compared with patients without oral anticoagulation therapy (84% vs. 65%, P = 0.008 by log-rank test). Malignancy (odds ratio [OR], 2.789; P = 0.043) and immobilization (OR, 4.191; P = 0.029) were independent risk factors for delayed recanalization of CVT and oral anticoagulation (OR, 0.300; P = 0.020) was an independent factor in promoting recanalization in multivariate analysis.

Conclusion

For patients with isolated CVT, no oral anticoagulation resulted in higher rates of delayed recanalization compared to oral anticoagulation treatment. Immobilization and having malignancy were independent risk factors for delayed recanalization.

Purpose

Hereditary thrombophilia (HT) is a major risk factor for idiopathic pulmonary embolism (iPE) and shows different prevalence among ethnic groups. The prevalence and clinical characteristics of HT in Korean patients with iPE were investigated.

Materials and Methods

Patients with PE on computed tomography (CT) scan were recruited, and those with malignancy were excluded. Patients were divided into iPE and provoked PE (pPE) groups. The presence of HT in the iPE group was assessed by DNA sequencing of the corresponding gene in patients who had low levels of natural anticoagulants. The clinical characteristics of iPE with HT (iPE/HT+) were compared with those of iPE without HT (iPE/HT-) and pPE.

Results

Out of 161 patients, 84 patients had iPE and 77 patients had pPE. Among 54 patients in the iPE group whose coagulation profiles were tested, 28 patients were diagnosed with HT (51.9%; 28/54). Compared with the iPE/HT- and pPE groups, the iPE/HT+ group showed the highest proportion of male patients (71.4%; p<0.001); the youngest mean age (44±14 years; p<0.001); and the highest frequencies for history of venous thromboembolism (64.3%; p<0.001), concurrent deep vein thrombosis (75.0%; p=0.021), and adverse clinical outcomes (42.9%, p<0.001). Protein C deficiency was the most common HT. On molecular genetic tests, causative mutation was identified in 13 patients.

Conclusion

In this study of Korean patients, about half of the patients with iPE had HT. Patients with iPE and HT were mostly young males with deep venous thrombosis (DVT), previous venous thromboembolism (VTE), and frequent adverse clinical outcomes. Therefore, Korean patients with iPE should be tested for HT.

Background

Third-generation hydroxyethyl starch (HES) solutions have been developed to minimize negative effects on hemostasis. In normal pregnancy, the coagulation activity increases, reaching a maximum around term. This study examined the effects of hemodilution with HES 130/0.4 (6%) on blood coagulation in parturients in vivo and in vitro.

Methods

Forty parturients scheduled for cesarean sections were assigned randomly to receive either 500 or 1,000 ml of HES 130/0.4 (6%). Rotation thromboelastometry (ROTEM®) measurements were performed before and after administering HES 130/0.4 (6%). In addition, blood samples obtained from 20 randomly selected parturients were diluted 10% to 40% using HES 130/0.4 (6%), and ROTEM® measurements were performed before and after dilution. The changes from baseline and the effects of dilution were analyzed by ROTEM® parameters.

Results

Infusions of 500 or 1,000 ml of HES 130/0.4 (6%) in the parturients altered the clot formation time, α angle, and maximal clot firmness, although all remained within normal ranges. HES 130/0.4 (6%) affected in vitro blood coagulation in parturients' blood containing 10, 20, 30, and 40% HES. The clotting time was prolonged at each dilution percentage, but remained within the normal range. Other parameters showed an impairment of the coagulation system.

Conclusions

Blood coagulation in parturients may be compromised at high dilution ratios of HES 130/0.4 (6%) to blood. Nevertheless, the infusion of 1,000 ml of HES 130/0.4 (6%) in normal parturients did not significantly affect blood coagulation.

Background

For patients in the intensive care unit (ICU) or under monitored anesthetic care (MAC), the precise monitoring of sedation depth facilitates the optimization of dosage and prevents adverse complications from underor over-sedation. For this purpose, conventional subjective sedation scales, such as the Observer's Assessment of Alertness/Sedation (OAA/S) or the Ramsay scale, have been widely utilized. Current procedures frequently disturb the patient's comfort and compromise the already well-established sedation. Therefore, reliable objective sedation scales that do not cause disturbances would be beneficial. We aimed to determine whether spectral entropy can be used as a sedation monitor as well as determine its ability to discriminate all levels of propofol-induced sedation during gradual increments of propofol dosage.

Methods

In 25 healthy volunteers undergoing general anesthesia, the values of response entropy (RE) and state entropy (SE) corresponding to each OAA/S (5 to 1) were determined. The scores were then analyzed during each 0.5 mcg/ml- incremental increase of a propofol dose.

Results

We observed a reduction of both RE and SE values that correlated with the OAA/S (correlation coefficient of 0.819 in RE-OAA/S and 0.753 in SE-OAA/S). The RE and SE values corresponding to awake (OAA/S score 5), light sedation (OAA/S 3-4) and deep sedation (OAA/S 1-2) displayed differences (P < 0.05).

Conclusions

The results indicate that spectral entropy can be utilized as a reliable objective monitor to determine the depth of propofol-induced sedation.

Relative expression levels of immune- and non-immune-related mRNAs in chicken intestinal intraepithelial lymphocytes experimentally infected with Eimeria acervulina, E. maxima, or E. tenella were measured using a 10K cDNA microarray. Based on a cutoff of >2.0-fold differential expression compared with uninfected controls, relatively equal numbers of transcripts were altered by the three Eimeria infections at 1, 2, and 3 days post-primary infection. By contrast, E. tenella elicited the greatest number of altered transcripts at 4, 5, and 6 days post-primary infection, and at all time points following secondary infection. When analyzed on the basis of up- or down-regulated transcript levels over the entire 6 day infection periods, approximately equal numbers of up-regulated transcripts were detected following E. tenella primary (1,469) and secondary (1,459) infections, with a greater number of down-regulated mRNAs following secondary (1,063) vs. primary (890) infection. On the contrary, relatively few mRNA were modulated following primary infection with E. acervulina (35 up, 160 down) or E. maxima (65 up, 148 down) compared with secondary infection (E. acervulina, 1,142 up, 1,289 down; E. maxima, 368 up, 1,349 down). With all three coccidia, biological pathway analysis identified the altered transcripts as belonging to the categories of “Disease and Disorder” and “Physiological System Development and Function”. Sixteen intracellular signaling pathways were identified from the differentially expressed transcripts following Eimeria infection, with the greatest significance observed following E. acervulina infection. Taken together, this new information will expand our understanding of host-pathogen interactions in avian coccidiosis and contribute to the development of novel disease control strategies.

Background and Objectives

In our previous study, we found that the gene transfer of a potent derivative of cartilage oligomeric matrix protein Angiopoietin-1 (COMP-Ang-1) substantially prevented hypertension, microvascular rarefaction, and target organ damage in spontaneously hypertensive rats (SHRs). The purpose of the present study was to examine the role of nitric oxide (NO) in the therapeutic effects observed after COMP-Ang-1 gene transfer.

Materials and Methods

To exclude the NO-mediated effects in COMP-Ang-1 gene therapy, the SHRs were treated with an NO synthase (NOS) inhibitor, Nw-nitro-L-arginine methyl ester (L-NAME) before the electrophoretic gene transfer.

Results

The pretreatment with L-NAME induced a severe and sustained increase in systolic blood pressure (BP) in a LacZ plasmid transferred control SHR. However, the electrophoretic transfer of a COMP-Ang-1 plasmid instead of LacZ plasmid in L-NAME-pretreated SHRs substantially blocked the development of hypertension without any significant difference in comparison with L-NAME-untreated COMP-Ang-1 plasmid transferred groups. In addition, the COMP-Ang-1 plasmid transfer substantially attenuated microvascular rarefaction and arteriole remodeling in the heart and kidney, which might account for the mild histological alterations observed in the COMP-Ang-1 plasmid transferred group, in contrast to the severe fibrosis and necrosis seen in the LacZ plasmid controls.

Conclusion

These therapeutic outcomes of COMP-Ang-1 gene transfer even in NOS inhibited SHRs suggested that the antihypertensive effect of COMP-Ang-1 was not merely secondary to NO-mediated vasorelaxation, but it may be associated with its ability to protect the vascular endothelium probably via an NO-independent mechanism which serves to attenuate microvascular rarefaction and target organ damage, and also to prevent hypertension by reducing peripheral vascular resistance.

Background and Objectives

The role of preoperative transthoracic echocardiography (TTE) for the risk stratification has not been well investigated yet. We compared the predictive power of TTE with N-terminal pro-brain natriuretic peptide (NT-proBNP), a representative biomarker that predicts perioperative cardiovascular risk, and investigated whether these tests have incremental value to the clinically determined risk.

Subjects and Methods

We evaluated the Revised Cardiac Risk Index (RCRI), TTE, and NT-proBNP in 1,923 noncardiac surgery cases. The primary endpoint was a perioperative major cardiovascular event (PMCE), which was defined by any single or combined event of secondary endpoints including myocardial infarction, development of pulmonary edema, or primary cardiovascular death within 30 days after surgery.

Results

All echocardiographic parameters including left ventricular ejection fraction, regional wall motion score index, and transmitral early diastolic velocity/tissue Doppler mitral annular early diastolic velocity (E/E') were predictive of PMCE (c-statistics=0.579±0.019 to 0.589±0.015), but none of these parameters were better than the clinically determined RCRI (c-statistics=0.594±0.019) and were inferior to NT-proBNP (c-statistics=0.748±0.019, p<0.001). The predictive power of RCRI {adjusted relative risk (RR)=1.4} could be improved by addition of echocardiographic parameters (adjusted RR=1.8, p<0.001), but not to that extent as by addition of NT-proBNP to RCRI (adjusted RR=3.7, p<0.001).

Conclusion

TTE was modestly predictive of perioperative cardiovascular events but was not superior to NT-proBNP. Moreover, it did not have incremental value to the clinically determined risk. The results of our study did not support the use of routine echocardiography before noncardiac surgery.

Background

Atrial fibrillation (AF) is the most common cardiac arrhythmia. Magnesium has been reported to be effective in reducing the incidence or prophylaxis of AF. Magnesium is also an essential constituent of many enzyme systems and plays a physiological role in coagulation regulation. The aim of the present study was to examine the effects of magnesium, whether magnesium infusion might decrease the incidence of AF and induce hypocoagulable state in patients with AF, who were undergoing mitral valve annuloplasty.

Methods

This prospective laboratory study was performed using blood from patients with AF undergoing mitral valve annuloplasty. The radial artery was punctured with a 20 gauge catheter and used for monitoring continuous arterial pressure and blood sampling. After anesthesia induction, 4 g of magnesium was mixed with 100 ml normal saline and infused for 5 minutes. Magnesium, calcium, activated clotting time (ACT) and thromboelastographic parameters were checked before and 60 minutes after the magnesium infusion. The electrocardiography changes after magnesium infusion were also checked before commencing cardiopulmonary bypass.

Results

After magnesium infusion, the serum level of magnesium increased significantly but serum calcium did not change significantly. ACT did not change significantly before or after magnesium infusion. The thromboelastographic parameters showed no significant changes before or after magnesium infusion. None of the patients converted to sinus rhythm from AF after the magnesium infusion.

Conclusions

A magnesium infusion did not influence the course of AF and coagulation in patients during prebypass period with AF undergoing mitral valve annuloplasty.

Background

Since 2009, database construction of anesthesia-related adverse events has been initiated through the legislation committee of the Korean Society of Anesthesiologists (KSA), based on expert consultation referrals provided by police departments, civil courts, and criminal courts.

Methods

This study was a retrospective descriptive analysis of expert consultation referrals on surgical anesthesia-related cases between December 2008 and July 2010.

Results

During the given period, 46 surgical anesthesia-related cases were referred to the KSA legislation committee for expert consultation. Because six cases were excluded due to insufficient data, 40 cases were included in the final analysis. Of 40 cases, 29 (72.5%) resulted in death. Respiratory events were most common in both surviving/disabled and dead patients (36.4 vs. 51.7%, respectively; P > 0.05). Overall, respiratory depression due to the drugs used for monitored anesthesia care (MAC) was the most common specific mechanism (25%), in which all but one case (profound brain damage) resulted in death. In all of these cases, surgeons or physicians provided MAC without the help of anesthesiologists.

Conclusions

Overall, the most common damaging mechanism was related to respiratory depression due to sedatives or anesthetics used for MAC. Almost all MAC injury cases are believed to be preventable with the use of additional or better monitoring and an effective response to initial physiological derangement. Thus, it is essential to establish practical MAC guidelines and adhere to these guidelines strictly to reduce the occurrence of severe anesthesia-related adverse outcomes.

Background

Nucleoplasty is a minimally invasive spinal surgery using a Coblation® technique that creates small voids within the disc. The purpose of this study was to evaluate the efficacy of cervical nucleoplasty in patients with cervical disc disorder.

Methods

Between March 2008 and December 2009, 22 patients with cervical disc disorders were treated with cervical nucleoplasty after failed conservative treatment. All procedures were performed under local anesthesia, and fluoroscopic guidance and voids were created in the disc with the Perc™ DC Spine Wand™. Clinical outcomes were evaluated by the Modified Macnab criteria and VAS score at preprocedure, postprocedure 1 month, and 6 months.

Results

Six patients had one, eight patients had two and eight patients had three discs treated; a total of 46 procedures was performed. Mean VAS reduced from 9.3 at preprocedure to 3.7 at postprocedure 1 month and to 3.4 at postprocedure 6 months. There was no significant complication related to the procedure within the first month. Outcomes were good or excellent in 17/22 (77.3%) cases. Postprocedure magnetic resonance imaging was acquired in two patients after two months showing morphologic evidence of volume reduction of protruded disc material in one patient but not in the other.

Conclusions

Percutaneous decompression with a nucleoplasty using a Coblation® technique in the treatment of cervical disc disorder is a safe, minimally-invasive and less uncomfortable procedure, with an excellent short-term clinical outcome.

Background

Laparoscopic cholecystectomy (LC) has traditionally been performed under general anesthesia, however, owing in part to the advancement of surgical and anesthetic techniques, many laparoscopic cholecystectomies have been successfully performed under the spinal anesthetic technique. We hoped to determine the feasibility of segmental epidural anesthesia for LC.

Methods

Twelve American Society of Anesthesiologists class I or II patients received an epidural block for LC. The level of epidural block and the satisfaction score of patients and the surgeon were checked to evaluate the efficacy of epidural block for LC.

Results

LC was performed successfully under epidural block, with the exception of 1 patient who required a conversion to general anesthesia owing to severe referred pain. There were no special postoperative complications, with the exception of one case of urinary retention.

Conclusions

Epidural anesthesia might be applicable for LC. However, the incidence of intraoperative referred shoulder pain is high, and so careful patient recruitment and management of shoulder pain should be considered.

Background and Objectives

The reliability and usefulness of the right ventricular (RV) Tei index (RTX) remains controversial because it has not been possible to simultaneously measure RV inflow and outflow. However, dual pulsed-wave Doppler (DPD) enables flow velocities to be obtained at different sampling sites simultaneously. In this study we evaluated the feasibility and reliability of RTX values obtained by DPD (RTXDPD).

Subjects and Methods

Forty-one patients who underwent cardiac catheterization and echocardiography for RV volume or pressure overloading conditions were evaluated. Symptom-limited exercise treadmill testing with expired gas analysis was performed and maximal exercise capacity was measured.

Results

RTX by conventional flow Doppler (RTXCFD, 0.262±0.164) was similar to RTXDPD (0.253±0.117, p=NS), whereas RTX by tissue Doppler echocardiography (RTXTDE, 0.447±0.125) was significantly larger than RTXDPD (p<0.001). Based on multiple regression analysis, maximal exercise capacity was independently related to RTXDPD (β=-0.60, p<0.001), mid-RV dimension (β=-0.26, p=0.012), left ventricular ejection fraction (β=0.22, p=0.023), and early diastolic tricuspid annular velocity (β=0.21, p=0.048).

Conclusion

It is feasible and reliable to evaluate RV function using RTXDPD values. However, to evaluate the clinical usefulness of RTXDPD, additional studies are required with a large number of patients and long-term follow-up.

The serine/threonine kinase Akt has been shown to play a role of multiple cellular signaling pathways and act as a transducer of many functions initiated by growth factor receptors that activate phosphatidylinositol 3-kinase (PI3K). It has been reported that phosphorylated Akt activates eNOS resulting in the production of NO and that NO stimulates soluble guanylate cyclase (sGC), which results in accumulation of cGMP and subsequent activation of the protein kinase G (PKG). It has been also reported that PKG activates PI3K/Akt signaling. Therefore, it is possible that PI3K, Akt, eNOS, sGC, and PKG form a loop to exert enhanced and sustained activation of Akt. However, the existence of this loop in eNOS-expressing cells, such as endothelial cells or astrocytes, has not been reported. Thus, we examined a possibility that Akt phosphorylation might be enhanced via eNOS/sGC/PKG/PI3K pathway in astrocytes in vivo and in vitro. Phosphorylation of Akt was detected in astrocytes after KA treatment and was maintained up to 72 h in mouse hippocampus. 2 weeks after KA treatment, astrocytic Akt phosphorylation was normalized to control. The inhibition of eNOS, sGC, and PKG significantly decreased Akt and eNOS phosphorylation induced by KA in astrocytes. In contrast, the decreased phosphorylation of Akt and eNOS by eNOS inhibition was significantly reversed with PKG activation. The above findings in mouse hippocampus were also observed in primary astrocytes. These data suggest that Akt/eNOS/sGC/PKG/PI3K pathway may constitute a loop, resulting in enhanced and sustained Akt activation in astrocytes.

Flash pulmonary edema typically exhibits sudden onset and resolves rapidly. It generally is associated with bilateral renal artery stenosis or unilateral stenosis in conjunction with a single functional kidney. We describe a patient who presented with flash pulmonary edema treated by percutaneous therapy with stent implantation. Our case is unique in that the flash pulmonary edema occurred in the setting of unilateral renal artery stenosis with bilateral functioning kidneys.

Background and Objectives

The purpose of this study was to investigate 1) the beneficial effect of bosentan treatment (125 mg twice daily) on exercise capacity and echocardiographic variables and 2) the profiles and frequency of adverse events in Korean patients with World Health Organization (WHO) class III or IV pulmonary artery hypertension (PAH).

Subjects and Methods

Twelve patients who received bosentan treatment were investigated in an open label manner. One patient was excluded in the final analyses due to a prohibited concomitant medication. A 6-minute walk test and echocardiography were performed at baseline and after 12 weeks of treatment.

Results

The administration of bosentan for 12 weeks resulted in a significant improvement in exercise capacity (measured with the 6-minute walking distance), WHO functional capacity, and in echocardiographic variables. Bosentan treatment was associated with a decrease in the maximal tricuspid regurgitation jet velocity {from 4.7 m/sec (95% confidence interval, 3.89-5.45) at baseline to 4.4 m/sec (95% confidence interval, 3.61-5.1) at 12 weeks, p=0.03} and systolic pulmonary arterial pressure {from 105 mmHg (95% confidence interval, 74.4-135.6) at baseline to 93 mmHg (95% confidence interval, 66.3-120.1) at 12 weeks, p=0.04}. Treatment with bosentan at a dose of 125 mg twice a day was not associated with life-threatening side effects, although a higher incidence of elevated liver enzymes compared to previous studies was noted.

Conclusion

Bosentan at a dose of 125 mg twice daily is considered a clinically optimal, safe dose and can be used as a valuable treatment option in Korean PAH patients with WHO functional capacity III or IV, though close monitoring of liver function is required.

Hereditary hemorrhagic telangiectasia (HHT) is an inherited disorder that is characterized by abnormal communication between the arteries and veins in the skin, mucosa, and various organs. HHT has been reported to show significant phenotypic variability and genetic heterogeneity with wide ethnic and geographic variations. Although mutations in the endoglin (ENG) and activin A receptor type II-like 1 (ACVRL1) genes have been known to cause HHT for more than 10 yr, little is known about the clinical features or genetic background of Korean patients with HHT. In addition, mutations in mothers against decapentaplegic homolog 4 (SMAD4) are also seen in patients with the combined syndrome of juvenile polyposis and HHT. This study examined five Korean patients with the typical manifestations of HHT such as frequent epistaxis and pulmonary arteriovenous malformations. Direct sequencing of the ENG and ACVRL1 genes revealed one known mutation, ENG c.277C>T, in one patient and two novel mutations, ENG c.992-1G>C and ACVRL1 c.81dupT in two patients, respectively. The remaining two patients with negative results were screened for SMAD4 mutations as well as gross deletions of ENG and ACVRL1 using multiple ligation-dependent probe amplification, but none was detected. Despite the small number of patients investigated, we firstly report Korean patients with genetically confirmed HHT, and show the genetic and allelic heterogeneity underlying HHT.

Objective

To evaluate mid-term imaging, clinical follow-up, and restenosis rates from patients that had undergone percutaneous transluminal renal artery angioplasty (PTRA) for symptomatic renal artery fibromuscular dysplasia (FMD).

Materials and Methods

Between March 1999 and July 2006, 16 consecutive renal artery FMD patients underwent PTRA for poorly controlled hypertension. The patients were enrolled into this retrospective study after receiving 19 primary and four secondary PTRAs in 19 renal artery segments. Follow-up monitoring of blood pressure, use of antihypertensive medication, and the serum creatinine level after PTRA were assessed at 1, 3, 6, 9, 12 months, and each following year. The degree of restenosis was evaluated with computed tomographic angiography (CTA) after PTRA at 6, 12 months, and every year if possible. Technical and clinical success rates for the treatment of FMD, and restenosis rates for the renal artery were evaluated.

Results

The technical success rate for primary PTRA was 79% (15/19) and the complication rate was 16% (3/19). Hypertension improved in 80% (12/15) of the patients after four weeks follow-up, and was finally cured or improved in 93% (14/15) during the mean follow-up period of 23.6 months. There was a cumulative 22% (4/18) restenosis rate during the follow-up period. All of the patients were treated with a second PTRA without complications and all of the patients were cured of hypertension after the second PTRA.

Conclusion

Percutaneous transluminal renal artery angioplasty for clinically symptomatic renal FMD is technically and clinically successful and safe to perform. For all patients with restenosis, there was a good response after undergoing a second PTRA.

Ehlers-Danlos syndrome (EDS) is a hereditary disorder of the connective tissue. EDS type IV (EDS IV), the vascular type of the disease, is characterized by easy bruising, thin skin with visible veins, and spontaneous rupture of the large arteries, uterus, or bowel. EDS IV is caused by mutations in the gene for type III procollagen (COL3A1). However, recent studies suggest that the causative mutation of EDS IV is not homogeneous. We report our experience with three patients presenting with clinical features of type IV EDS. A 48-yr-old woman presented with acute aortic dissection (patient 1) and 36-yr-old and 21-yr-old women presented with carotid-cavernous fistula (patients 2 and 3, respectively). All three patients bruised easily. Two patients (patients 1 and 3) had thin transparent skin with visible veins. Genetic analysis of COL3A1 revealed a Gly732Val (c.2195G>T) mutation in patient 1 and a duplication of 15 base pairs (c.3221_3235dup) which resulted in an interposition of five amino acids (p.Gly1074_Pro1078dup) in patient 2. However, no mutations were observed in COL3A1 or transforming growth factor β receptors 1 and 2 in patients 3, which might be either due to a deletion of single or multiple exons in the COL3A1 gene or due to a genetic heterogeneity. This is the first report of genetically confirmed cases of EDS IV in Korea.