Chaw-Chi Chiu

Giant aneurysm of main pulmonary artery

Aneurysm of the main pulmonary artery is an extremely rare entity. The first successful repair of an aneurysm of the main pulmonary artery was reported in 1971. Since then, surgical correction of the aneurysm of main pulmonary artery has been undertaken in only 6 cases. A thorough survey of the literature, including autopsy cases, medical cases, and surgical cases, shows the aneurysm in the present case to be one of the largest.

Baicalein, an active component of Scutellaria baicalensis Georgi, prevents lysophosphatidylcholine-induced cardiac injury by reducing reactive oxygen species production, calcium overload and apoptosis via MAPK pathways.

BackgroundLysophosphatidylcholine (lysoPC), a metabolite from membrane phospholipids, accumulates in the ischemic myocardium and plays an important role in the development of myocardial dysfunction ventricular arrhythmia. In this study, we investigated if baicalein, a major component of Huang Qui, can protect against lysoPC-induced cytotoxicity in rat H9c2 embryonic cardiomyocytes.MethodsCell viability was detected by the MTT assay; ROS levels were assessed using DCFH-DA; and intracellular free calcium concentrations were assayed by spectrofluorophotometer. Cell apoptosis and necrosis were evaluated by the flow cytometry assay and Hoechst staining. Mitogen-Activated Protein Kinases (MAPKs), which included the ERK, JNK, and p38, and the apoptotic mechanisms including Bcl-2/Bax, caspase-3, caspase-9 and cytochrome c pathways were examined by Western blot analysis. The activation of MAPKs was examined by enzyme-linked immunosorbent assay.ResultsWe found that lysoPC induced death and apoptosis of H9c2 cells in a dose-dependent manner. Baicalein could prevent lysoPC-induced cell death, production of reactive oxygen species (ROS), and increase of intracellular calcium concentration in H9c2 cardiomyoctes. In addition, baicalein also inhibited lysoPC-induced apoptosis, with associated decreased pro-apoptotic Bax protein, increased anti-apoptotic Bcl-2 protein, resulting in an increase in the Bcl-2/Bax ratio. Finally, baicalein attenuated lysoPC-induced the expression of cytochrome c, casapase-3, casapase-9, and the phosphorylations of ERK1/2, JNK, and p38. LysoPC-induced ERK1/2, JNK, and p38 activations were inhibited by baicalein.ConclusionsBaicalein protects cardiomyocytes from lysoPC-induced apoptosis by reducing ROS production, inhibition of calcium overload, and deactivations of MAPK signaling pathways.

Inhibition of mitogen-mediated proliferation of rat vascular smooth muscle cells by labedipinedilol-A through PKC and ERK 1/2 pathway.

Labedipinedilol-A is a novel 1, 4-dihydropyridine type calcium antagonist with alpha-receptor blocking activity. This study investigates the effects of labedipinedilol-A on mitogen-induced proliferation of rat vascular smooth muscle cells (VSMCs). Labedipinedilol-As inhibition on cell proliferation was measured by the tetrazolium salt (XTT) test. Labedipinedilol-A dose-dependently inhibited mitogen-induced DNA synthesis, determined by the incorporation of 5-bromo-2′-deoxyuridine (BrdU). Labedipinedilol-A was also found capable of inhibiting the migration of VSMCs induced by PDGF-BB with an IC50 value of 5.6 μM. In accordance with these findings, labedipinedilol-A revealed blocking of the FBS-inducible progression through G0/G1 to S phase of the cell cycle in synchronized cells. Labedipinedilol-A appeared to cause inhibition of mitogens-induced PKC translocation, suggesting the probable involvement of protein kinase C (PKC) in this cellular response. Labedipinedilol-A reduced both intracellular Ca2+ and the phosphorylation of extracellular signal-regulated protein kinase 1/2 in PDGF-BB-stimulated VSMCs. It also suppressed the levels of proliferative cell nuclear antigen (PCNA) in VSMCs both time- and dose-dependently. These results indicate that labedipinedilol-A may inhibit cell proliferation by attenuating activation of the ERK 1/2 pathway, which is regulated by PKC and Ca2+, suggesting that it may have great potential in the prevention of progressive atherosclerosis.

Eugenodilol : A third-generation β-adrenoceptor blocker, derived from eugenol, with α-adrenoceptor blocking and β2-Adrenoceptor agonist-associated vasorelaxant activities

: Eugenodilol, derived from natural eugenol, was first investigated with in vivo and in vitro models. In our in vivo study, eugenodilol (0.5, 1.0, and 1.5 mg/kg, i.v.) produced dose-dependent hypotensive and bradycardic responses in pentobarbital-anesthetized Wistar rats. Eugenodilol also inhibited the tachycardia and arterial pressor effects induced by (-)isoproterenol and phenylephrine, respectively. In our in vitro study, eugenodilol competitively antagonized (-)isoproterenol-induced positive inotropic and chronotropic effects and tracheal-relaxation responses on isolated guinea pig tissues in a concentration-dependent manner. The apparent pA2 values were 7.88+/-0.12 for right atria, 7.52+/-0.05 for left atria, and 7.33+/-0.15 for trachea, indicating that eugenodilol was a nonselective beta-adrenoceptor blocker. In thoracic aorta experiments, the apparent pA2 values of alpha-adrenoceptor blockade were 7.05+/-0.25 and 6.87+/-0.08 for eugenodilol and labetalol, respectively. In addition, eugenodilol produced cumulative relaxation responses on isolated guinea pig tracheal strips. The effects were competitively antagonized by ICI 118,551 (10(-8)-10(-6) M), a relatively selective beta2-adrenoceptor antagonist. In the radioligand-binding assay, the Ki values of [3H]CGP-12177 binding to rat ventricle and lung membranes were 9.72 and 48.29 nM, respectively, and the value of [3H]prazosin binding to rat brain membrane was 38.72 nM. These results further confirmed the alpha/beta-adrenoceptors-blocking activities of eugenodilol reported in the functional studies. We conclude that eugenodilol is a novel third-generation beta-adrenoceptor blocker with ancillary blocking activity at alpha-adrenoceptors and weak sympathomimetic activity at beta2-adrenoceptors.

Pharmacological effects of an aldehyde type α/β-adrenoceptor blocking agent with vasodilating properties

Abstract KMUP 880723 (0.5, 1.0, and 3.0 mg/kg, iv) produced dose-dependent hypotensive and bradycardia responses in pentobarbital-anesthetized Wistar rats. KMUP 880723 (1.0 mg/kg, iv) also markedly inhibited both the tachycardia effects induced by (−)isoproterenol and arterial pressor responses induced by phenylephrine. In the isolated Wistar rat right atria, left atria, and guinea pig tracheal strips, KMUP 880723 competitively antagonized the (−)isoproterenol-induced positive chronotropic effects, inotropic effects, and tracheal relaxation effects in a concentration-dependent manner. The parallel shift to the right of the concentration–response curve of (−)isoproterenol suggested that KMUP 880723 was a β1/β2-adrenoceptor competitive antagonist. The apparent pA2 values were 6.89±0.10 in the right atria, 7.02±0.09 in the left atria, and 6.59±0.11 in the trachea, indicating that KMUP 880723 was a nonselective β-adrenoceptor blocker. In thoracic aorta experiments, KMUP 880723 also produced a competitive antagonism of norepinephrine-induced contraction with a pA2 value of 7.14±0.06. In isolated rat thoracic aorta, KMUP 880723 more potently relaxed the contractions induced by norepinephrine (3×10−6 M) than those by high K+ (75 mM). In the radioligand-binding assay, the pKi values of [3H]CGP-12177 binding to rat ventricle and lung membranes were 6.56 and 6.40, respectively, and the value of [3H]prazosin binding to rat brain membranes was 6.66. These results further confirmed the α/β-adrenoceptor blocking activities of KMUP 880723 reported in the functional studies. We conclude that KMUP 880723 is a nonselective β-adrenoceptor antagonist with α-adrenoceptor blocking-associated vasorelaxant activity.

Acute aortic dissection type A with acute coronary involvement: a novel classification.

BACKGROUND Acute coronary involvement (ACI) due to acute aortic dissection (AAD) type A is potentially fatal. We examined selected patients with AAD type A, which had evolved over 14 years, and acute coronary involvement. The purpose of this study was to determine the characteristics of patients with ACI due to AAD type A. METHODS Between 1997 and 2011, we recruited 20 patients (14.1%) with ACI (14 men, 6 women; mean age: 51.8 ± 11.8 years; age range: 35-79 years) from 142 patients who had undergone surgical repair of AAD type A. RESULTS We propose a novel 4-category classification scheme based on the surgical pathological findings. The right coronary artery was involved in 15 patients, and the left was involved in 5 patients. Fourteen patients had preoperative myocardial ischemia. In the other 6 patients, acute coronary involvement was found intraoperatively. Patients with ACI were significantly younger than those without ACI (51.8 ± 11.8 vs. 61.0 ± 11.8; p = 0.001), a lower prevalence of intramural hematoma (5.0% vs. 32.8%; p = 0.011), a higher aortic regurgitation rate (95.0% vs. 53.5%; p = 0.001). Patients presenting with ACI had an in-hospital mortality rate of 20.0% (4/20), while those without ACI had an in-hospital mortality rate of 19.7% (24/122). CONCLUSIONS Acute coronary involvement due to AAD type A is not always associated with coronary malperfusion. Patients with ACI were much younger, had a higher aortic regurgitation rate, and, less commonly, had intramural hematoma. This new classification scheme would make it more convenient for surgeons to decide on treatment options for this special cohort.

Aortic smooth muscle relaxants KMUP-3 and KMUP-4, two nitrophenylpiperazine derivatives of xanthine, display cGMP-enhancing activity : Roles of endothelium, phosphodiesterase, and K+ channel

The cellular mechanisms of vasorelaxant effects of newly synthesized KMUP-3 and KMUP-4 were investigated in rat aortic smooth muscle (RASM). KMUP-3 (7-[2-[4-(4-nitrobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) and KMUP-4 (7-[2-[4-(2-nitrobenzene)piperazinyl]ethyl]-1,3-dimethylxanthine) elicited concentration-dependent relaxation of endothelium-intact and denuded RASM precontracted with phenylephrine. Relaxant responses were also produced by the PDE inhibitors theophylline, milrinone, rolipram, and zaprinast (1 nM-100 μM). The relaxant responses of KMUP-3 and KMUP-4 were reduced by endothelium removal and by the presence of the NOS inhibitor L-NAME (100 μM), the sGC inhibitor ODQ (1 μM), the adenylyl cyclase (AC) inhibitor SQ 22536 (100 μM), and the prostaglandin inhibitor indomethacin (10 μM). Additionally, the vasorelaxations of both agents were also attenuated by pretreatment with the nonselective K+ channel blocker TEA (10 mM), the KATP channel blocker glibenclamide (1 μM), the voltage-dependent K+ (KV) channel blocker 4-AP (100 μM), and Ca2+-dependent K+ (KCa) channel blockers apamin (1 μM) and charybdotoxin (ChTX, 0.1 μM). In addition, elevated extracellular K+ (80 mM) interferes with KMUP-3- and KMUP-4-induced vasorelaxations. Preincubation with both agents (1 μM) significantly enhanced the dilator responses of isoproterenol and SNP. KMUP-3 and KMUP-4 inhibited PDE activities and increased cAMP and cGMP levels in primary culture of RASM that were inhibited by SQ 22536 and ODQ, respectively. In cultured HUVECs, KMUP-3 and KMUP-4 (0.1 μM), more potent than YC-1, significantly increased the expression of eNOS protein. In summary, KMUP-3 and KMUP-4 induce aortic relaxations through both endothelium-dependent and -independent mechanisms. Mechanisms of vasorelaxation induced by both compounds involve multiple processes, such as accumulation of cyclic nucleotides partly as a result of PDE inhibition, K+-channel activation, and indomethacin-sensitive endothelium function.

Uneven myocardial hypothermia among cardiac chambers during hypothermic myocardial preservation.

During the development of methods to protect the heart from ischaemic injury, attention has been focused on protection of the left ventricle. In an attempt to assess right heart preservation. 55 consecutive patients undergoing open heart surgery were studied. Mean aortic cross-clamp time was 59.3 +/- 29.4 min. Temperature probes were inserted into the right atrium (RA), right ventricle (RV), and left ventricle (LV). During cardioplegia, the mean myocardial temperatures of RA, RV and LV were 19.1 degrees +/- 4.1 degrees C, 12.7 degrees +/- 4.8 degrees C and 7.3 degrees +/- 3.4 degrees C, respectively. Of the LV temperature measurements, 67.2% were 10 degrees C or lower. By contrast, 94.1% of RA measurements and 58.5% of RV measurements were above 10 degrees C. The inhomogeneity of chamber temperatures was observed irrespective of the patients disease or age and whether the atrium or right ventricle were open or not. Hearts with mitral regurgitation (MR), in contrast to mitral stenosis and stenoinsufficiency, had higher LV temperatures, similar to those in the RV. We conclude that there is uneven hypothermia among the three cardiac chambers during hypothermic cardioplegic arrest, regardless of disease states except MR and regardless of age and procedure performed.

Exogenous Lipoid Pneumonia: Serial Chest Plain Roentgenography and High-Resolution Computerized Tomography Findings

Between May 1988 and July 2002, six patients with pneumonia due to diesel, animal, or vegetable oil aspiration were admitted to Kaohsiung Medical University Hospital. The purpose of this study was to demonstrate distinctive radiographic findings of oil‐induced lipoid pneumonitis on initial serial chest roentgenograms and high‐resolution computerized tomography (CT) scans. Initial chest roentgenograms (n = 6), CT scans (n = 6), and roentgenography and CT follow‐up studies were analyzed retrospectively by two chest radiologists and two surgeons, focusing on the pattern and distribution of parenchymal abnormalities. The most common location was the right middle lobe, followed by the right lower lobe, the left lower lobe, and the lingular lobe. Follow‐up chest roentgenograms (n = 6) showed complete disappearance of the parenchymal lesions in only one patient and partial decrease in the extent of lesions in five patients. Lipoid pneumonia presents non‐specific findings on chest roentgenography. It is commonly located in both lower and the right middle lobes. On high‐resolution CT, the lesions appear most commonly as areas of consolidation, ground‐glass attenuation mixed with paving pattern, and poorly defined nodules.

Baicalein Inhibits HMGB1 Release and MMP-2/-9 Expression in Lipopolysaccharide-Induced Cardiac Hypertrophy

Myocardial dysfunction, a common complication after sepsis, significantly contributes to the death of patients with septic shock. In the search for potentially effective drugs to decrease mortality from sepsis, we investigated the cardioprotective effects of baicalein, a flavonoid present in the root of Scutellaria baicalensis, on lipopolysaccharide (LPS)-induced pro-inflammatory cytokine production and matrix metalloproteinase-2 and -9 (MMP-2/-9) expression. We found that baicalein significantly attenuated LPS-induced cardiac hypertrophy and counteracted reactive oxygen species (ROS) generation in neonatal rat cardiomyocytes. In addition, pretreatment with baicalein inhibited LPS-induced early (e.g., tumor necrosis factor-α (TNF-α) and interleukin-6) and late (e.g., high mobility group box 1 (HMGB1) pro-inflammatory cytokine release, inducible nitric oxide synthase (iNOS) expression and NO production. Finally, baicalein also significantly down-regulated the expression of MMP-2/-9 and attenuated HMGB1 translocation from the nucleus to the cytoplasm. These results suggest that baicalein can protect cardiomyocytes from LPS-induced cardiac injury via the inhibition of ROS and inflammatory cytokine production. These cardioprotective effects are possibly mediated through the inhibition of the HMGB1 and MMP-2/-9 signaling pathways.