Congenital coronary artery anomaly demonstrated by three dimensional 16 slice spiral CT angiography.
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Coronary Vessel Anomalies↗
Biomedical subjects
C Hong
Publications and source records attributed to C Hong.
Immune function, telomerase, and angiogenesis in patients with primary, operable nonsmall cell lung carcinoma: tumor size and lymph node status remain the most important prognostic features.
BACKGROUND: Lung carcinoma usually is advanced at the time of presentation and frequently shows metastatic spread. In recent times, prognostic factors such as c-erbB-2 in patients with breast carcinoma have provided useful information and beneficial therapeutic targets. The objective of this study was to evaluate angiogenesis, immune function, and telomerase expression in patients with nonsmall cell lung carcinoma (NSCLC) to determine their prognostic significance. METHODS: Immunohistochemistry was used to evaluate the expression of human telomerase reverse transcriptase (hTERT; n = 115 patients), interleukin-2r (IL-2r; n = 40 patients), microvessel density (MVD; n = 81 patients), and vascular endothelial growth factor (VEGF; n = 61 patients). Three-year survival follow-up information was available for most patients, and a comprehensive review of clinicopathologic features was carried out. RESULTS: Fifty percent of tumors showed nuclear staining for hTERT, 55% of tumors showed some degree of lymphocyte IL-2r expression, 33% of tumors were recorded with an MVD that was higher than average, and VEGF staining was detected in 85% of tumors. None of the parameters measured had an impact on survival. hTERT expression was correlated with lymph node status. Lymph node status and tumor size were identified as independent prognostic factors. CONCLUSIONS: This study failed to identify a marker of prognosis for patients with NSCLC other than tumor size and lymph node status in this population. Telomerase expression was associated with metastases, raising the possibility that this enzyme is involved in the metastatic process. Tumor cell VEGF expression was identified frequently: This growth factor may have potential as a target for antiangiogenic therapy. Lung carcinoma typically is the result of large numbers of mutations. Further understanding of the biologic implications of these mutations will lead to the development of effective prognostic markers and treatments for patients with NSCLC.
Adult↗
Cyclosporine reduces left ventricular mass with chronic aortic banding in mice, which could be due to apoptosis and fibrosis.
A tacit assumption in studies of left ventricular (LV) hypertrophy is that left ventricular/body weight (LV/BW) reflects the extent of myocyte hypertrophy. The goal of the current investigation was to determine if there was another explanation for the reduced LV/BW observed after inhibiting calcineurin with cyclosporine during the development of pressure overload LV hypertrophy as compared with animals that did not receive cyclosporine. Accordingly, we examined the prevalence of fibrosis and apoptosis and measured cell size in the hearts from mice at 1 and 3 weeks after transverse aortic banding with and without chronic cyclosporine. Although LV/BW, compared to aortic banded vehicle treated mice, was reduced by 30% in aortic banded cyclosporine treated mice, myocyte cross sectional area was similar in both banded groups (346+/-9 microm2 v 336+/-13 microm2). The volume percent interstitial fibrosis was greater in aortic banded cyclosporine treated animals (1.4+/-0.2%) compared with aortic banded vehicle treated animals (0.9+/-0.2%, P<0.05) or in sham animals (0.6+/-0.1%). Surprisingly, lesions including myocytes containing iron were observed and were most prominent in aortic banded cyclosporine treated animals. Apoptosis, quantitated with TUNEL staining as percent of myocytes, was increased in aortic banded cyclosporine treated animals at 7 days (1.6+/-0.4%) compared with aortic banded vehicle treated animals (0.4+/-0.1%, P<0.01) and was still increased at 21 days. Immunoblotting demonstrated a decrease in the phosphorylation of Akt and Bad, and also Bcl-2 levels were reduced in aortic banded cyclosporine treated animals at 7 days compared with aortic banded vehicle treated animals. These proteins protect against apoptosis, and support the concept that cyclosporine inhibited the calcineurin pathway, resulting in enhanced apoptosis. Thus, the decrease in LV/BW in the aortic banded cyclosporine treated animals actually may be due, at least in part, to cell loss and death, as reflected by the enhanced fibrosis and apoptosis and the focal iron deposits in myocytes.
Animals↗
Reduction in intraocular pressure after laser in situ keratomileusis.
PURPOSE: To investigate whether intraocular pressure (IOP) measured on the nasal side is affected after laser in situ keratomileusis (LASIK). SETTING: The Glaucoma Service, Dr. Hong's Eye Clinic, Seoul, Korea. METHODS: In 83 patients, IOP was prospectively measured with the Goldmann tonometer at the central (Tcenter) and nasal (Tnasal) areas of the cornea before and after LASIK. The Tcenter and Tnasal IOP between baseline and 1, 3, and 6 months postoperatively was compared. The correlation between ablation depth, amount of treatment, refractive change, and change in central corneal thickness and Tcenter change was evaluated. RESULTS: Six months after LASIK, Tcenter IOP decreased 3.9 mm Hg (25.2%) and Tnasal IOP decreased 2.0 mm Hg (12.7%) (P < .001, P = .02, respectively). The Tnasal measurement was 1.8 mm Hg higher than the Tcenter measurement (P < .001). Significant correlation between each corneal parameter and the Tcenter reduction at 1 month did not continue to 6 months (P > .05). CONCLUSION: At each follow-up, Tnasal IOP was statistically lower than at baseline, although the reduction was not as great as that of Tcenter IOP. A 2 to 3 mm Hg drop in Tnasal up to 6 months after LASIK should be expected. An alternative would be to measure IOP with the Tono-Pen on the nasal side to fit the tip to the relatively unchanged nasal side of the cornea.
Adult↗
Role of cytokine gene polymorphisms in acute rejection and renal impairment after liver transplantation.
Although immunosuppressive regimens are effective, rejection occurs in up to 50% of patients after orthotopic liver transplantation (OLT), and there is concern about side effects from long-term therapy. Knowledge of clinical and immunogenetic variables may allow tailoring of immunosuppressive therapy to patients according to their potential risks. We studied the association between transforming growth factor-beta, interleukin-10, and tumor necrosis factor alpha (TNF-alpha) gene polymorphisms and graft rejection and renal impairment in 121 white liver transplant recipients. Clinical variables were collected retrospectively, and creatinine clearance was estimated using the formula of Cockcroft and Gault. Biallelic polymorphisms were detected using polymerase chain reaction-based methods. Thirty-seven of 121 patients (30.6%) developed at least 1 episode of rejection. Multivariate analysis showed that Child-Pugh score (P =.001), immune-mediated liver disease (P =.018), normal pre-OLT creatinine clearance (P =.037), and fewer HLA class 1 mismatches (P =.038) were independently associated with rejection. Renal impairment occurred in 80% of patients and was moderate or severe in 39%. Clinical variables independently associated with renal impairment were female sex (P =.001), pre-OLT renal dysfunction (P =.0001), and a diagnosis of viral hepatitis (P =.0008). There was a significant difference in the frequency of TNF-alpha-308 alleles among the primary liver diseases. After adjustment for potential confounders and a Bonferroni correction, the association between the TNF-alpha-308 polymorphism and graft rejection approached significance (P =.06). Recipient cytokine genotypes do not have a major independent role in graft rejection or renal impairment after OLT. Additional studies of immunogenetic factors require analysis of large numbers of patients with appropriate phenotypic information to avoid population stratification, which may lead to inappropriate conclusions.
Adult↗
ECG-gated reconstructed multi-detector row CT coronary angiography: effect of varying trigger delay on image quality.
PURPOSE: To evaluate the effectiveness of electrocardiographically (ECG)-gated retrospective image reconstruction for multi-detector row computed tomographic (CT) coronary angiography in reducing cardiac motion artifacts and to evaluate the influence of heart rate on cardiac image quality. MATERIALS AND METHODS: Sixty-five patients with different heart rates underwent coronary CT angiography. Raw helical CT data and ECG tracings were combined to retrospectively reconstruct at the defined consecutive z position with a temporal resolution of 250 msec per section. The starting points of the reconstruction were chosen between 30% and 80% of the R-R intervals. The relationships between heart rate, trigger delay, and image quality were analyzed. RESULTS: Optimal image quality was achieved with a 50% trigger delay for the right coronary artery and 60% for the left circumflex coronary artery. Optimal image quality for the left anterior descending coronary artery was equally obtained at 50% and 60% triggering. A significant negative correlation was observed between heart rate and image quality (P <.05). The best image quality was achieved when the heart rate was less than 74.5 beats per minute. CONCLUSION: To achieve high image quality, the heart rate should be sufficiently slow. Selection of appropriate trigger delays and a decreasing heart rate are effective to reduce cardiac motion artifacts.
Adult↗
Multislice helical CT of focal and diffuse lung disease: comprehensive diagnosis with reconstruction of contiguous and high-resolution CT sections from a single thin-collimation scan.
OBJECTIVE: We tested breath-held 1-mm multislice helical CT for obtaining both contiguous and high-resolution CT sections of the chest from a single set of raw data. SUBJECTS AND METHODS: Seventy patients with suspected focal and diffuse lung disease were allocated into two groups for comparison. The first group (n = 35) underwent multislice helical CT of the chest with 1-mm collimation and a pitch of 6. From the raw data, 5-mm contiguous and 1.25-mm high-resolution CT sections were reconstructed. The second group (n = 35) underwent conventional single-slice helical CT and high-resolution CT. High-resolution CT sections and 5-mm scans were rated for overall image quality, spatial resolution, subjective signal-to-noise ratio, diagnostic value, depiction of bronchi and parenchyma, and motion and streak artifacts. The 5-mm scans were also rated for contrast resolution and depiction of the heart and vessels. Radiation dose was calculated. RESULTS: We rated 5-mm multislice helical CT superior to 5-mm single-slice helical CT, having a significantly higher total score (p = 0.0001). No significant difference (p = 0.986) was found between multislice and single-slice high-resolution CT sections. Radiation dose was 5.55 mSv for multislice helical CT and 5.50 mSv for single-slice helical CT. CONCLUSION: Contiguous chest scans of superior quality and high-resolution CT sections of equal image quality compared with single-slice helical CT can be obtained using multislice helical CT. Therefore, a comprehensive diagnosis is feasible in patients with suspected focal and diffuse lung disease by obtaining a single scan.
Adult↗
Balanced ultrafiltration, modified ultrafiltration, and balanced ultrafiltration with modified ultrafiltration in pediatric cardiopulmonary bypass.
This study evaluates the effect of balanced ultrafiltration, modified ultrafiltration, and balanced ultrafiltration with modified ultrafiltration on inflammatory mediators in children's open-heart surgery. Eighty children with congenital heart disease were randomly divided into four groups: control group (C group); balanced ultrafiltration group (BUF group); modified ultrafiltration group (MUF group); and balanced ultrafiltration with modified ultrafiltration group (B+M group). Clinical data of these groups were similar. Tumor necrosis factor (TNF), interleukin-8(IL-8), and E-selectin were measured at the beginning of cardiopulmonary bypass (CPB), 30 min later, at the cessation of CPB, at the cessation of MUF (MUF group and B+M group), and 2 hours postoperatively. During CPB, the concentrations of TNF, IL-8, and E-selectin increased significantly in C and MUF groups and did not change significantly in BUF and B+M groups. In the period of MUF, TNF and IL-8 increased; whereas, E-selectin did not change. The study shows that ultrafiltration can filter out the inflammatory mediators, but only BUF can decrease the concentrations of them. Moreover, MUF only can concentrate blood. Combining both techniques has both effects, but the effect of BUF was offset by MUF.
Cardiopulmonary Bypass↗
[The effects of sodium butyrate on proliferation, differentiation and apoptosis in immortalized esophageal epithelial cells].
OBJECTIVE: To study the effects of sodium butyrate on proliferation, differentiation and apoptosis of immortalized esophagus epithelial cells. METHODS: SHEE, an immortalized human fetal esophageal epithelial cell line induced by HPV18 E6E7, was cultivated in culture flasks and 24-well plates. Two experiment groups of cultured cells were treated with 1 and 5 mmol/L of sodium butyrate respectively for 4 days, and one group of untreated cells set aside as control. The numbers of cloned cells were calculated. The ultra-structure of SHEE cells was examined by transmission electron microscopy (TEM). The cell cycle and number of apoptotic cells were measured by flow cytometry, Ki-67 and cytokeratin of cells were detected by immunohistochemistry method and F-actin of cells labeled with phalloidin was examined by laser confocal scanning microscopy. RESULTS: Colony formations showed a significant decrease in the 2 experiment groups after 4 days of culture (P < 0.01). In the 1 mmol/L group, the cells at S phase were diminished and arrested at G(0)/G(1) phase. Compared with control group, Ki-67 positive cells were found decreased, while F-actin and cytokeratin were increased. Apoptotic cells in 5 mmol/L group were increased markedly. CONCLUSIONS: Sodium butyrate may induce SHEE cells growth arrest, differentiation and apoptosis. The effects depend on sodium butyrate concentration and time of exposure. Whether it can be used in combination with other anticancer drugs should be further studied.
Actins↗
Ultrastructure of the skin mechanoreceptors of the Chinese giant salamander, Andrias davidianus.
The ultrastructure of two kinds of mechanoreceptive organs, pit organs and neuromasts, in the skin of adult giant salamanders (Andrias davidianus) was studied by transmission electron microscopy. Neuromasts and pit organs differ in their types of synapses, the spatial distribution of kinocilia on sensory cells, and in the degree to which sensory cells are separated by processes of the supporting cells; the two organs probably serve complementary functions. The neuromasts in A. davidianus differ from those of other salamanders in the orientation of kinocilia, in the extent of intrusion of supporting cells into the sensory layer, in the degree of thickening of the synaptic membranes, in the distribution of synaptic spheres, and by the absence of a cupula.
Animals↗
[Initial experiences with multi-slice detector spiral CT in diagnosis of arteriosclerosis of coronary vessels].
PURPOSE: Multi-row-detector-spiral-CT (MSCT) allows for 250 ms effective exposure time. The purpose of this study was to demonstrate the possibilities and limitations of this CT technology for non enhanced and contrast enhanced investigation of the coronary arteries. METHODS: Investigation of the coronary arteries without contrast medium for quantification of coronary calcifications was performed in an obese patient (140 kg) with MSCT and electron beam CT (EBCT). In 56 patients contrast enhanced CT angiography of the coronary arteries was performed to determine image quality depending on the heart rate. RESULTS: In the obese patient superior image quality could be achieved with MSCT allowing for reliable quantification of coronary calcifications. With MSCT angiography of the coronary arteries good image quality was achieved in patients with a heart rate of 59 +/- 8 beats per minute. CONCLUSION: Even if there are limitations in patients with higher heart rates with an effective exposure time of 250 ms MSCT has clear advantage of image quality in the assessment of non enhanced and contrast enhanced coronary arteries.
Adult↗
Exhaled nitric oxide following leukotriene E(4) and methacholine inhalation in patients with asthma.
Nitric oxide (NO) is a molecular gas that can be recovered in higher levels from the exhaled gas of subjects with asthma than from subjects without asthma. However, the precise mechanisms responsible of promoting increased fraction of expired nitric oxide (FE(NO)) in asthma are unknown. As leukotriene antagonism has been shown to reduce FE(NO) in patients with asthma, we hypothesized that leukotrienes mediate the increased FE(NO) encountered in this condition. Furthermore, because leukotriene antagonism stabilizes serum eosinophil markers during reductions in inhaled corticosteroid doses, and FE(NO) has been shown to correlate with sputum eosinophils in asthma, we reasoned that the effect of leukotrienes on FE(NO) might be mediated by eosinophils recruited to the airway by leukotrienes. To test this hypothesis, we performed methacholine and leukotriene (LT) E(4) bronchoprovocation challenges in 16 subjects with atopic asthma and measured FE(NO) and sputum differential counts before and after bronchoprovocation. We then compared FE(NO) in the seven subjects who developed increased sputum eosinophils following LTE(4) inhalation with values measured after methacholine inhalation in these seven subjects. Following LTE(4) inhalation, eosinophils rose from 4.01 +/- 0.89% pre-LTE(4) to 8.33 +/- 1.52% post-LTE(4). The mean change in sputum eosinophils from baseline after LTE(4) inhalation was larger than that after methacholine inhalation (+4.31 +/- 1.25% versus -1.14 +/- 0.93%). After LTE(4) inhalation, FE(NO) levels did not differ from prechallenge baseline or from levels following methacholine inhalation (ANOVA p > 0.05). These data indicate that neither LTE(4) nor recruitment of eosinophils into the airway by LTE(4) is a sufficient stimulus to acutely increase FE(NO) in subjects with asthma.
Administration, Inhalation↗
The alteration of mitochondria is an early event of arsenic trioxide induced apoptosis in esophageal carcinoma cells.
It is accepted that inorganic arsenic trioxide is an inducer of apoptosis for many types of cancer. Our previous studies have demonstrated that arsenic trioxide induces apoptosis of esophageal carcinoma cells. Administration of arsenic trioxide results in the inhibition of growth and survival of tumor cells. Esophageal carcinoma cells treated with arsenic trioxide for 3 days demonstrated a typical morphological appearance of apoptosis. To further examine molecular mechanism of arsenic trioxide induced apoptosis of esophageal carcinoma cells, we have investigated the early changes of the apoptotic cell induced by arsenic trioxide. Our results indicated that arsenic trioxide induced apoptosis of esophageal carcinoma cells occurs as early as 2 h after treatment. Annexin-v staining has further proved that the phosphatidylserine is exposed at 2 h. The early morphological change of arsenic trioxide treated cells was in the mitochondria. Arsenic trioxide treated cells displayed aggregated mitochondria. It induces accumulation of high electron-density amorphous substances, swollen and disruption of mitochondria in oesophageal carcinoma cells after 2 h treatment. The alteration of mitochondria induced by arsenic trioxide seems to occur before the condensation of chromatin. Thus, our data demonstrated that the primary target of arsenic trioxide induced apoptosis of esophageal carcinoma cells may be the mitochondria. It is possible that arsenic trioxide is a mitochondriotoxic agent.
Antineoplastic Agents↗
Detection, quantitation, and identification of residual aminopenicillins by high-performance liquid chromatography after fluorescamine derivation.
A high-performance liquid chromatographic (HPLC) method with fluorescence detection after precolumn fluorescamine derivation was developed to detect residues of two aminopenicillins, amoxicillin (AMPC) and ampicillin (ABPC), in bovine serum. Proteins in serum samples spiked with each of these penicillins were precipitated with sodium tungstate and sulfuric acid, centrifuged, and removed by passage through a C18 solid-phase extraction cartridge. After precolumn treatment of the extraction products of AMPC and ABPC with fluorescamine solution, HPLC analysis with fluorescence spectrophotometric detection at an excitation wavelength of 390 nm and an emission wavelength of 485 nm was performed to identify these products. Two mobile phases were used for residual analysis by the isocratic HPLC system. An ODP column (polyvinyl alcohol bonded with an octadecyl functional group) that can be used with strongly alkaline mobile phases (pH 2.0 to 13) was selected, and the column temperature was set at 40 degrees C. A mobile phase comprising 100-mM K2HPO4 solution and acetonitrile (72:28, vol/vol), which yielded AMPC and ABPC retention times of 4.1 and 7.9 min, respectively, was suitable for detection of residual ABPC but not for residual AMPC because interference was caused by peaks of other extracted substances. When a mobile phase comprising a different ratio of 100-mM K2HPO4 solution and acetonitrile (78:22, vol/vol) was used, the retention times of AMPC and ABPC were 7.3 and 26.3 min, respectively, and both penicillins could be analyzed using this system. The calculated standard curves of the reaction products with both mobile phases were linear, and the correlation coefficients were greater than 0.999. The lower limit of detection was 10 ng/ml for both penicillins. Analysis of extracts from bovine serum spiked with AMPC and ABPC at a concentration of 1 microg/ml yielded recovery rates of 102.2 +/- 5.5% and 79.0 +/- 5.2%, respectively. This detection method may be useful for routine laboratory testing of AMPC and ABPC.
Amoxicillin↗
A nine-year prospective study on the incidence of childhood type 1 diabetes mellitus in China.
To investigate the epidemiological characteristics of childhood type 1 diabetes mellitus in China, newly diagnosed cases of type 1 diabetes with an onset age under 15 years were retrospectively registered by 23 local centers in China following a standardized protocol on the basis of the nationwide registry established by the WHO DiaMond Project China Participating Center, Chinese Academy of Preventive Medicine (CAPM). A population of about 24 million children were covered in the defined areas. A two-sample capture-recapture method was used to estimate case ascertainment. Between 1988 and 1996, 903 diabetic cases were registered in 9 ethnic groups. The overall ascertainment corrected incidence rate (IR) was 0.59 per 100,000 person-year. The IR was 0.52/100,000 (95% CI: 0.50-0.54) for males and 0.66/100,000 (95% CI: 0.64-0.68) for females. The standardized ascertainment corrected IR by the national age-specific population in 1990 was 0.57 per 100,000 person-year. The incidence among various ethnic groups ranged from 0.25/100,000 to 3. 06/100,000. The IRs increased with northern latitude, and the IR of Han population was significantly higher in North China compared with South China (0.67 versus 0.53 per 100,000 respectively, P < 0.01). A correlation model of incidence and calendar time showed that the IR increased significantly between 1988 and 1996 (r = 0.86, P = 0.0027). The relative risk (RR) of type 1 diabetes mellitus for different age-groups estimated by a Poisson regression model showed that taking RR as 1.00 for age-group from 0 to 4 years, the RR for age-group from 5 to 9 year and from 10 to 14 year was 2.30 and 3.60 respectively. The standardized ascertainment corrected IR of childhood type 1 diabetes mellitus in China in much lower than in other countries. The geographic and ethnic variability of the incidence suggests that both genetic and environmental factors play a role in the development of childhood diabetes in China.
Adolescent↗
[Morphological changes of mitochondria in apoptosis of esophageal carcinoma cells induced by As(2)O(3)].
OBJECTIVE: In order to make clear how As(2)O(3) targets the cells of esophageal carcinoma, the morphology of mitochondria and expression of bcl-2/bax were selected to study the SHEEC1 cell line during early apoptosis. METHODS: The esophageal carcinoma cell line SHEEC1 was treated by As(2)O(3) with concentrations of 1, 2 and 3 micromol/L for the periods of 2, 4, 6, 12 and 24 h. Annexin-V-Fluorescein and DNA histogram were used to detect the early apoptotic cells by flow cytometry. The morphologic changes of the apoptotic cells were examined by means of light and electron microscopy. Changes in mitochondria of living cells were detected with Rhodamin 123 fluorescent probe by fluorescent microscopy. The expression of bcl-2 and bax in floating cells were determined by immunohistochemical procedures. RESULTS: Typical apoptotic morphological changes were found in SHEEC1 at 24 h after As(2)O(3) treatment. Cells in the early stage of apoptosis were detected by Annexin-V labeled at 4 h. The ultrastructural alterations of mitochondria were found as following: within 4 h after administrating As(2)O(3), mitochondrial hyperplasia with small electron-dense materials in its matrix was the earliest manifestation of cell injury. At 6 h progressive mitochondrial swelling lead to balloon-like appearance and its outer membrane disrupted at 12 h. In all groups, down regulated expression of bcl-2 and over expression of bax were always found in damaged cells. CONCLUSION: In the SHEEC1 cell line morphological changes of mitochondria are the early events in apoptosis induced by As(2)O(3) and apoptosis is closely related to over expression of bax and down-regulating expression of bcl-2. It is possible that As(2)O(3) is a mitochondriotoxic anticancer agent for esophageal carcinoma.
Antineoplastic Agents↗
[Catalysis kinetics-fluorescence analysis studies on Fe(III)-H2O2-furfural-7-amino-8-hydroxy-5-sulfo-quinoline system].
This paper reports that hydrogen peroxide oxidized furfural-7-amino-8-hydroxy-5-sulfo-quinoline(F7A8Q5S) under the catalysis of Fe(III). Results indicated that the fluorescence of F7A8Q5S was weak, but that of the oxidation product was strong. The peak was at lambda ex/lambda em = 330/405 (nm). The calibration curve of Fe(III) is linear between 0.0-40.0 micrograms.L-1, and the determination limit is 4.68 ng.L-1. So a new catalysis fluorescence analysis method was set up for the determination of trace amounts of Fe(III), based on its catalytic effect on F7A8Q5S oxidized by H2O2. This proposed method has been successful applied to the determination of Fe(III) in alloy samples.
Calibration↗
Cyclosporine attenuates pressure-overload hypertrophy in mice while enhancing susceptibility to decompensation and heart failure.
Left ventricular hypertrophy (LVH) is a compensatory mechanism to cope with pressure overload. Recently, a calcineurin pathway mediating LVH and its prevention by cyclosporine was reported. We examined whether calcineurin mediates LVH due to pressure overload in mice. Pressure overload was induced by aortic banding in 53 mice (32 treated with cyclosporine [25 mg. kg-1. d-1], 21 treated with vehicle). There were 17 sham-operated mice (9 treated with vehicle, 8 treated with cyclosporine). At 3 weeks after surgery, LV weight to body weight was greater in the nontreatment banded group (4.39+/-0. 16 mg/g) than in the cyclosporine-treated banded group (3.95+/-0.14 mg/g, P<0.05), with both groups being greater compared with the entire group of sham-operated mice (3.02+/-0.04 mg/g). The pressure gradient between the ascending and abdominal aorta was not different between the cyclosporine-treated (49.6+/-6.1 mm Hg) and nontreatment groups (48.7+/-4.6 mm Hg). Although LV systolic pressure was lower in the cyclosporine-treated banded animals, LV systolic wall stress was similar in the nontreatment banded group and in the cyclosporine-treated group. However, LV dP/dt was lower (P=0.05) in the cyclosporine-treated banded group (4774+/-656 mm Hg/s) than in the nontreatment banded group (6604+/-516 mm Hg/s). During the protocol, 23 of 32 mice in the cyclosporine-treated group and 9 of 21 mice in the nontreatment group died. All deaths occurred within 10 days after surgery. Deaths caused by heart failure were 7.2-fold higher (P<0.05) in the cyclosporine-treated group, whereas deaths due to other causes were not different between the 2 groups. In addition, LV function of mice was assessed at 48 hours after banding; LV ejection fraction measured with echocardiography was lower (P<0.05) in the cyclosporine-treated banded group (66+/-3.0%) than in the nontreatment banded group (79+/-1.5%), whereas LV systolic wall stresses were similar. Calcineurin phosphatase activity was depressed similarly in both cyclosporine-treated groups compared with both nontreatment groups. Thus, cyclosporine could attenuate, but not prevent, LVH at the expense of inhibiting an important compensatory mechanism in response to pressure overload, resulting in reduced LV wall stress and function and increased susceptibility to decompensation and heart failure.
Animals↗