Biomedical subjects

G Gong

Publications and source records attributed to G Gong.

At least 37 records · Page 2Linked to original sources

PubMed2000

Metaplastic carcinoma of the breast: mammographic and sonographic findings.

PURPOSE: We investigated the mammographic, sonographic, and pathologic findings in metaplastic carcinoma of the breast. METHODS: The mammographic (n = 16) and sonographic (n = 11) findings in 16 patients with metaplastic carcinoma of the breast were analyzed retrospectively along with pathologic findings. Whenever possible, results of preoperative fine-needle aspiration biopsy and immunohistochemical studies were obtained. RESULTS: All patients presented with a palpable breast mass. The mean size of the lesions at pathologic examination was 4.2 cm. On mammography, 15 patients had a mass (1 patient had 2 masses), and 1 patient had only clustered microcalcifications without an associated mass. The mean longest diameter of the 16 masses on mammography was 4.6 cm. Eleven lesions (69%) were round to ovoid in shape, 13 lesions (81%) showed ill-defined or obscured margins, and 10 lesions (63%) showed associated architectural distortion. On sonography, 6 (55%) of 11 lesions were round to ovoid, 9 lesions (82%) had well-defined margins, and 6 lesions (55%) showed complex echogenicity with solid and cystic components. At pathologic examination, 4 of these 6 lesions showed hemorrhagic or cystic necrosis. Axillary lymph nodes were positive in 6 (40%) of 15 patients in whom axillary node dissection was performed. CONCLUSIONS: Metaplastic carcinoma of the breast manifests as a rapidly growing, mammographically ill-defined round mass with associated architectural distortion on mammograms. Complex echogenicity with solid and cystic components may be seen sonographically and is related to hemorrhagic or cystic necrosis seen pathologically.

Adult↗

PubMed2000

Clustering of breast microcalcifications: revisited.

AIM: To verify the diagnostic value of the traditional definition of 'clustering' of microcalcifications (more than five in the area of 1 cm(2)or 1 cm(3)) on mammography in the differential diagnosis of benign and malignant breast disease. METHODS AND MATERIALS: Three radiologists without knowledge of the final pathology retrospectively counted the number of microcalcifications per 0.25 cm(2) (0.5 x 0.5 cm) unit area on mammography in 57 pathologically proven non-palpable lesions including 26 cancers and 31 benign diseases. Pleomorphism of the microcalcifications, associated architectural distortion or mass or increased density and distribution of microcalcifications were also evaluated. RESULTS: The mean numbers of microcalcifications per 0.25 cm(2) were 16.4 in malignant and 16.7 in benign diseases (no statistically significant difference between the two groups). Pleomorphism of the microcalcifications, associated architectural distortion or mass or increased density were, however, important determining parameters. Clustering was more frequently observed in benign diseases. CONCLUSION: In this study, the mean number of microcalcifications per unit area is much larger than the traditional definition of 'clustering' and clustering itself is not effective in the differential diagnosis of benign and malignant breast lesions. Imaging features other than numbers of calcification per unit area are more important in assessing the significance of mammographic clustered microcalcifications.

Adult↗

PubMed2000

Expressions of human sodium iodide symporter mRNA in primary and metastatic papillary thyroid carcinomas.

The sodium iodide symporter (NIS) is a plasma membrane protein that is responsible for iodide transport into thyroid cells. To understand the regulation and expression of human NIS (hNIS) in papillary thyroid carcinomas, we evaluated the expression levels of hNIS mRNA in primary and lymph node metastatic papillary carcinoma tissues. The correlation of mRNA levels between hNIS and thyroid-specific genes, thyrotropin (TSH) receptor, and thyroglobulin (Tg), were also investigated. Twenty-three cases of papillary carcinoma and 7 pairs of primary and lymph node metastastic tissues were included in this study. We measured the expression levels of hNIS, TSH receptor, and Tg mRNAs by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and RNase protection assay (RPA). The levels of hNIS mRNA in lymph node metastatic tissues were evaluated by RT-PCR. By semiquantitative RT-PCR, 87% of papillary carcinoma (20/23) expressed hNIS mRNA, but the degrees of expression were variable and were lower than those of normal thyroid tissues. The decreased expression of hNIS mRNA in papillary carcinoma compared to normal thyroid tissue was also noticed by RPA. All 23 papillary carcinomas in this study showed the expression of TSH receptor and Tg mRNAs. The levels of TSH receptor mRNA were again lower in papillary thyroid carcinomas than in normal controls. The level of hNIS mRNA was correlated with the levels of TSH receptor (r = 0.449, p < 0.05), but not with Tg mRNA. In addition, significant correlation of mRNA level was observed between TSH receptor and Tg (r = 0.706, p < 0.01). Two of six lymph node metastatic tissues did not show hNIS mRNA even with significant hNIS expressions in papillary carcinoma tissues in thyroid. The levels of hNIS expression of the remaining four lymph node metastatic tissues were lower than those of corresponding primary tissues. Interestingly, one case showed no hNIS expression in primary tissue, but significant hNIS expression in lymph node metastatic tissue. No correlation was found in hNIS mRNA expression between primary and lymph node metastatic tissues. Our results suggest that the measurements of hNIS mRNA level in primary tissues may not predict the therapeutic response to radioactive iodine.

Adult↗

PubMed2000

Nitroprusside reverses lengthened time of contraction in stunned canine cardiac myocytes.

We tested the hypothesis that stunning reduces the function of isolated canine ventricular myocytes and that nitroprusside (NP) reverses this effect. After stunning (15 min occlusion, 45 min reperfusion), isolated myocytes were prepared from control (circumflex artery) and stunned (left anterior descending) regions of the hearts of seven dogs. The myocytes were examined at baseline and with NP (10(-6,-5,-4) M) for oxygen consumption (MVO2, nl O2/min/10(5) cells), cyclic guanosine monophosphate (cyclic GMP; fmol/10(5) cells), and cell contraction. Basal MVO2 was not significantly different between control and stunned myocytes (888 +/- 108 vs. 716 +/- 94). NP caused a dose dependent decrease in MVo2 (control, 262 +/-51; stunned, 287 +/- 59, NP 10(-4) M). Basal cyclic GMP levels were comparable between control and stunned myocytes (117 +/-28 vs. 124 +/- 18). NP produced a similar dose-dependent increase in cyclic GMP in control and stunned myocytes. Baseline cell shortening (%) was similar in control vs. stunned myocytes (12.1 +/- 1.2 vs. 11.0 +/- 0.9). NP reduced shortening (6.9 +/- 0.3 vs. 7.3 +/- 0.5, NP 10(-4) M). There was no baseline difference in maximal rate of shortening (microm/s) between control and stunned myocytes (164 +/- 14, 157 +/- 20). With NP, a decrease in the maximal rate of shortening was seen in both groups (128 +/- 12, 139 +/- 21, NP 10(-4) M). The time of contraction (s) was significantly longer in stunned (0.20 +/- 0.03) versus control (0.13 +/- 0.01). NP significantly lengthened the time of contraction in controls in a dose-dependent manner (0.33 +/-0.05, NP 10(-4) M). In stunned myocytes, however, low-dose NP (10(-6) M) caused a decrease in the time of contraction (0.15 +/-0.03). High-dose NP (10(-4) M) did not significantly lengthen time of contraction in stunned cells (0.23 +/- 0.02). The time of relaxation followed a similar pattern. We conclude that part of the effect of NP in low doses in stunned myocardium is to reduce the lengthened time of contraction and relaxation characteristic of stunning.

Animals↗

PubMed2000

Association of estrogen receptor-alpha genotypes with body mass index in normal healthy postmenopausal Caucasian women.

Several lines of evidence suggest the importance of the estrogen receptor (ER) in determining body mass index (BMI). Our purpose was to investigate whether genetic polymorphisms at the restriction enzyme PvuII site of the ER-alpha gene locus are associated with BMI variation. Data on BMI, age, and ER-alpha genotypes were obtained from 108 healthy midwestern U.S. postmenopausal Caucasian women. The study subjects were unrelated and aged 65 yr and over (mean age +/- SD, 73.4 +/- 5.1 yr), with an average BMI of 25.25 (SD, 4.04). The ER-alpha genotypes were obtained by PCR followed by restriction enzyme PvuII digestion. We found that in our study subjects the ER-alpha genotypes are significantly associated with BMI (by ANOVA, P = 0.04), explaining about 6.2% of the BMI variation in our study sample. The allelic effects of this locus on BMI are approximately additive. In our sample, individuals of the PP and Pp genotypes have, respectively, 11.4% and 4.8% higher BMI than individuals of the pp genotype. There is a significant ER-alpha genotype by age interaction, so that in our sample PP individuals tend to gain weight with age, whereas Pp and pp individuals tend to lose weight with age. Therefore, the ER-alpha polymorphisms are associated with BMI variation in healthy postmenopausal Caucasian women aged 65 yr and over. Our result is consistent with some recent findings suggesting the potential effects of the ER on BMI. The importance of the ER-alpha genotypes in other populations and other age groups needs to be demonstrated. Although the results of the ER-alpha genotype by age interaction are obtained here from cross-sectional data, direct confirmation may come from longitudinal studies in which individuals are measured multiple times over several years. The importance of the ER-alpha genotypes on BMI should be confirmed by further studies using methods robust to the potential problem of population substructuring that may confound the conclusions of population association studies.

Aged↗

PubMed2000

[The measurement of temperature with Raman scattering spectra of polycrystal (SrNO3)2].

We have developed a new method for the determination of temperature with Raman scattering spectra. The strontium nitrate was chosen as an experiment substance. It has two bands of Raman scattering, and their wavenumbers are 738 and 1,057 cm-1 in 600-1,700 cm-1. We have obtained the intensities of their Stokes and Anti-Stokes scattering, then we have got two temperatures of strontium nitrate according to the formula. The result from the 738 cm-1 scattering band has larger error than that from the 1,057 cm-1. This may account for the noise of the photocounter. This no touch method is fit to measure the temperature of the molecular.

Crystallization↗

PubMed1999

Estimating genetic influence on disease from population-based case-control data: application to cancers of the breast and ovary.

We describe genetic mixture models and goodness-of-fit statistics for evaluating the joint effects of genetic and environmental factors on the risk of chronic diseases. We focus particularly on situations wherein the gene(s) of interest play roles in several diseases, and death due to one disease can censor the occurrence of others. We use the methods to investigate the risks of cancers of the breast and ovary associated with germline mutations of BRCA1, using data pooled from three population-based U.S. case-control studies of ovarian cancer. We evaluate the goodness-of-fit of the genetic models by comparing the predicted numbers of diseased mother-daughter and sister-sister pairs to the numbers observed. We also use simulations to examine the performance of estimates obtained from such complex mixture models, and the contribution of control families to the precision of parameter estimates.

Adolescent↗

PubMed1999

Carcinoembryonic antigen gene and carcinoembryonic antigen expression in the liver metastasis of colorectal carcinoma.

The presence of the carcinoembryonic antigen (CEA) gene and CEA expression in the liver was tested to identify their possible roles in the liver metastasis of colorectal carcinoma. The CEA gene in the liver was identified by amplifying the CEA-specific N-terminal domain exon with digoxigenin-dUTP labeling in 16 colorectal carcinomas with liver metastases. Next, CEA expression was tested by immunostaining using the anti-CEA monoclonal antibody (T84.66, ATCC). Liver tissues from 13 stomach cancer patients and 12 colorectal cancer patients without liver metastasis were also tested as control groups. Three grades (<25%, 25-50%, and 50%< or =) were given according to the proportion of positive cells. The CEA gene was amplified in the metastatic tumor cells of the liver (2.6 +/- 0.2, mean grade +/- SEM) and their surrounding hepatocytes (1.5 +/- 0.2) in all cases. CEA expression was found in all metastatic tumor cells and 14 cases of the surrounding hepatocytes. Among the control groups, the CEA gene of the hepatocytes was found in 9 cases each of the colorectal and the stomach cancers that did not exhibit CEA expression. The level of serum CEA was related with the numbers and volume of liver metastases, but not with CEA expression in tumor cells and surrounding hepatocytes. The CEA gene in the metastatic tumor cells, not in the hepatocytes, was closely associated with CEA expression in the surrounding hepatocytes (p<0.01). Although the precise mechanism of CEA gene regulation in hepatocytes remains to be proven, the CEA gene in the metastatic tumor of the liver seems to affect CEA expression in the surrounding hepatocytes facilitating liver metastasis in colorectal carcinoma.

Carcinoembryonic Antigen↗

PubMed1999

In vitro and in vivo studies of 1H NMR visibility to detect deoxyhemoglobin and deoxymyoglobin signals in myocardium.

1H nuclear magnetic resonance (NMR) spectroscopy can be used noninvasively to detect the proximal histidyl N delta proton signals of deoxymyoglobin in the myocardium. However, the quantification of deoxymyoglobin is based on the assumption that the deoxymyoglobin signal detected is not contaminated by the deoxyhemoglobin signals contributed from the blood. The purpose of this study was to conduct in vitro and in vivo 1H NMR studies to examine the in vivo NMR visibility of deoxyhemoglobin in the myocardium. The results demonstrate that the NMR visibility of alpha and beta subunits of deoxyhemoglobin is sensitive to the pulse width for spin excitation because of short T2 relaxation times, and they are not NMR visible in the canine myocardium in vivo at 4.7 T when a 0.5-1.0 msec long Gaussian excitation pulse is used. Therefore, the resonance peak detected at approximately 72 ppm (relative to the water resonance) in the ischemic canine myocardium in vivo is dominated by deoxymyoglobin.

Animals↗

PubMed1999

The association of bone mineral density with vitamin D receptor gene polymorphisms.

A recent meta-analysis of 16 publications suggested that bone mineral density (BMD) is not associated with vitamin D receptor (VDR) gene polymorphism (VDRGP) at the 0.05 significance level when a study with genotyping mistakes is excluded. We wished to determine whether 'positive' findings supporting the BMD-VDRGP association may be explained by chance, and what factors affect the outcomes of these studies. Seventy-five articles and abstracts on the association of VDRGP with BMD and related skeletal phenotypes published before January 1997 were identified. Twenty-three of 67 (34.3%) studies on spinal BMD and 22 of 51 (43.1%) on femoral neck BMD had found a BMD-VDRGP association at p < 0.05, significantly (p = 7 x 10(-14) for spinal BMD, p = 9 x 10(-16) for hip BMD) higher than the expected 5% false positive rate under the null hypothesis of 'no association'. 'Positive' results were more frequently observed in studies on females before the menopause than those on females after the menopause (p < 0.02) or on male and female subjects combined (p < 0.05) when skeletal phenotypes at any bone sites were considered. The 'positive rate' among studies was also influenced by the age range of subjects studied and by the inclusion of subjects with osteoporosis. It is concluded that: (1) BMD is associated with VDRGP with high levels of confidence and (2) non-genetic factors and genetic heterogeneity interfere with the detection of the effects of VDRGP on bone phenotypes.

Age Factors↗

PubMed1999

Association of bone dimensions with a parathyroid hormone gene polymorphism in women.

We have recently shown that bone radiogrammetric dimensions are associated with vitamin D receptor gene polymorphism. Since parathyroid hormone (PTH) plays a central role in maintaining calcium homeostasis and in bone remodeling, we investigated whether bone radiogrammetric dimensions are associated with a PTH gene polymorphism in 91 healthy Caucasian women, who were premenopausal at entry into the study. These women had assessments of bone by radiogrammetry every five years for a median period of 20 years (range 4-27). DNA was extracted from white blood cells. A segment of the PTH gene with a polymorphism at a BstBI restriction site was amplified by polymerase chain reaction. Diameter, cortical thickness and cross-sectional area at standard sites of the metacarpals, radius and femur were measured with radiogrammetry. Higher metacarpal diameter and cross-sectional cortical area, and a slower decrease in radial cortical area with age, were associated with the absence of the BstBI restriction site of the PTH gene. PTH gene polymorphism accounts for about 7-9% of the total variances of bone dimensional variables. These findings suggest that the dimensions of long bones are influenced by allelic variations in the PTH gene or in genes nearby.

Adult↗

PubMed1999

Association of VDR and estrogen receptor genotypes with bone mass in postmenopausal Caucasian women: different conclusions with different analyses and the implications.

Much work has been done on the association between vitamin D receptor (VDR) genotypes and bone mineral density (BMD). Despite considerable effort, the results are inconsistent. While the VDR association remains unresolved, studies have expanded to other candidate genes (i.e., estrogen receptor (ER) genotypes), also yielding inconsistent results. A few studies have suggested that interaction effects between VDR and ER genotypes significantly affect BMD. We assessed associations of BMD with VDR BsmI genotypes, and ER XbaI and PvuII polymorphisms (denoted as ERX and ERP respectively) with spine, femoral neck, distal radius BMD, and with total body bone mineral content (tbBMC) in 108 US Mid-western postmenopausal Caucasian women. We statistically controlled for confounding factors such as height, weight, etc., in the analysis. No significant association was detected for ER genotypes with spine and radius BMD, or for VDR genotypes with femoral neck and radius BMD and tbBMC. No significant interaction between VDR and ER genotypes was detected in our sample. However, the VDR genotypes are significantly (p = 0.004) associated with approximately 5.8% spine BMD variation. Both ERX and ERP genotypes are significantly (p = 0.02) associated with approximately 3.5% femoral neck BMD variation. ERX genotypes are significantly (p = 0.03) associated with approximately 2.4% tbBMC variation. However, if the data were analyzed by simple ANOVA as in some previous studies, without adjusting statistically for confounding factors, all the significant results we found here would have gone undetected. Our findings suggest that: (1) VDR and ER genotypes may have different effects on BMD at different sites and on tbBMC; and (2) if significant factors influencing bone are not appropriately controlled, true significant associations can easily be missed. These findings may offer a partial explanation for some of the earlier inconsistent results of association studies on BMD with VDR and ER genotypes.

Absorptiometry, Photon↗

PubMed1999

Myocardial oxygenation at high workstates in hearts with left ventricular hypertrophy.

BACKGROUND: High cardiac workloads produced by catecholamine infusion result in loss of myocardial phosphocreatine (PCr) and accumulation of inorganic phosphate (Pi) which are more prominent in heart with left ventricular hypertrophy (LVH) than in normal hearts. Since ischemia can cause changes in phosphorylated compounds similar to those during catecholamine stimulation, this study tested the hypothesis that the exaggerated depletion of PCr and accumulation of Pi during high workloads in LVH is the result of impaired myocyte oxygenation. METHODS AND RESULTS: 31P- and 1H-NMR spectroscopy were used to determine myocardial high energy phosphate levels and myoglobin desaturation, respectively, in eight normal dogs and nine dogs with LVH produced by ascending aortic banding. The mean LV weight/body weight ratio was approximately twice normal in the LVH group. Infusion of dobutamine (15 and 30 micrograms/kg/min), and dobutamine + dopamine (each 20 micrograms/kg/min) caused progressive similar increases in the heart rate x systolic LV pressure product to a maximum of 57.4 +/- 3.3 x 10(3) in normal and 63.9 +/- 2.7 x 10(3) in LVH animals, while myocardial oxygen consumption increased from 0.09 +/- 0.01 to 0.24 +/- 0.04 in normals and from 0.10 +/- 0.02 to 0.25 +/- 0.03 ml/min/g in LVH. PCr/ATP ratios during basal conditions were lower in LVH hearts (1.73 +/- 0.10, 1.61 +/- 0.09 and 1.51 +/- 0.09 in subepicardium, midwall and subendocardium, respectively) as compared with normals (2.24 +/- 0.09, 2.01 +/- 0.08 and 1.89 +/- 0.07; each p < 0.01 normal vs. LVH). Catecholamine infusions caused dose-related decreases in PCr/ATP and appearance of Pi which was more marked in LVH than in normal hearts. 1H-NMR spectroscopy did not detect deoxymyoglobin in either normal or LVH hearts even during the highest workloads. In contrast, occlusion of the anterior descending coronary artery resulted in a large deoxymyoglobin signal. CONCLUSIONS: Increases of cardiac work produced by catecholamine stimulation resulted in greater decreases of PCr and greater increases of Pi in hypertrophied than in normal hearts. These abnormalities were not the result of inadequate intracellular oxygen availability and consequently cannot be ascribed to demand ischemia.

Adenosine Triphosphate↗

PubMed1999

Gross type-matched study of clinicopathologic features of advanced gastric carcinoma with replication error.

Sporadic gastric carcinomas with replication error (RER) have been described and have distinct clinicopathological features, such as: older age group, predominant antral location, elevated gross type, near-diploidy, expanding pattern (Ming's classification), intestinal type, low desmoplastic response, and less frequent lymph node metastasis. Previous study revealed that replication error-positive (RER+) advanced gastric carcinomas (AGC) had a preponderance of Borrmann type 2. Regardless of RER status, AGC of Borrmann type 2 usually exhibit expanding pattern (Ming's classification), intestinal type, and low desmoplastic reaction. Therefore, to better characterize the clinicopathological features of RER+ gastric carcinomas, gross type-matched analysis would be necessary. We analyzed 53 cases of Borrmann type 2 AGC for RER status using polymerase chain reaction analysis of eight microsatellite loci and compared the clinicopathological features between RER+ and RER-negative (RER-) tumors. Sixteen (30.2%) out of 53 cases were RER+ phenotype which had a significant association with female sex, older age, expanding pattern, small and uniform nuclei, and low DNA index (P < 0.05). However, RER status was not significantly associated with histological differentiation, histological type (Lauren's classification), desmoplastic response, intratumoral lymphoid infiltration, and tumor location. Most of the previously known clinicopathological features of RER+ AGC were related to Borrmann type 2, except for female sex, older age, expanding pattern, and low DNA index.

Adenocarcinoma, Mucinous↗

PubMed1999

Fentanyl pharmacokinetics in hemorrhagic shock: a porcine model.

BACKGROUND: It is common clinical practice to administer reduced doses of opioid to patients suffering from hemorrhagic shock to minimize adverse hemodynamic consequences and to prevent prolonged opioid effect However, the scientific foundation supporting this practice is not well established. The aim of this study was to test the hypothesis that hemorrhagic shock alters both the distribution and clearance of opioids using fentanyl in a porcine isobaric hemorrhage model. METHODS: Eighteen pigs were randomized to shock or control groups. The animals in the shock group were subjected to hemorrhage using an isobaric method. Pigs in both groups received fentanyl (50 microg/kg) intravenously over 5 min. Frequent arterial blood samples were obtained for radioimmunoassay. Each animal's pharmacokinetic parameters were estimated by fitting a three-compartment model to the concentration versus time data Nonlinear mixed-effects population pharmacokinetic models examining the influence of mean arterial pressure and cardiac index were also constructed. Clinical simulations using the final population model were performed. RESULTS: The shock cohort reached substantially higher fentanyl concentrations. The shock group's central clearance and central- and second-compartment distribution volumes were significantly reduced. The most useful population model scaled all pharmacokinetic parameters to mean arterial pressure. The simulations illustrated that hemorrhagic shock results in higher fentanyl concentrations for any given dosage scheme. CONCLUSION: The essential finding of the study is that fentanyl pharmacokinetics are substantially altered by hemorrhagic shock. The reduced opioid requirement commonly observed during hemorrhagic shock is at least partially attributable to pharmacokinetic mechanisms.

Analgesics, Opioid↗

PubMed1999

Cyclic GMP protein kinase mediates negative metabolic and functional effects of cyclic GMP in control and hypertrophied rabbit cardiac myocytes.

We tested the hypothesis that in isolated cardiac myocytes, the negative metabolic and functional effects of cyclic guanosine monophosphate (GMP) are mediated by cyclic GMP protein kinase activity, and that these effects are altered in renal hypertensive (one-kidney, one-clip, 1K1C) cardiac hypertrophic rabbits. By using isolated cardiac myocytes from control and 1K1C rabbits, oxygen consumption (Mvo2; O2 nl/ min/10(5) cells), cyclic GMP (fmol/10(5) cells), and cell shortening (percentage) data were collected (a) at baseline; (b) with cyclic GMP protein kinase inhibitors KT5823 (10(-6) M) or Rp8-pCPT-cGMP (5 x 10(-6) M); (c) with the cyclic GMP phosphodiesterase inhibitor zaprinast (10(-6), 10(-4) M); and (d) with zaprinast (10(-6), 10(-4) M) and protein kinase inhibitors. Basal levels of cyclic GMP were similar in control versus 1K1C myocytes (62 +/- 10 vs. 66 +/- 17 pmol/10(5) myocytes). Zaprinast produced a dose-dependent increase in cyclic GMP in both control and 1K1C myocytes. The addition of KT5823 did not significantly affect cyclic GMP levels. Zaprinast significantly and dose dependently decreased Mvo2, and KT5823 partially restored it in control and 1K1C. Zaprinast also significantly decreased percentage shortening, and KT5823 partially restored it in control. Similar results were obtained with Rp-8pCPT-cGMP, although neither inhibitor was effective without zaprinast. The hypertrophied myocytes demonstrated comparable responses to all agents. These data suggest that the cyclic GMP protein kinase activity was not significant under basal conditions; however, the importance of cyclic GMP protein kinase in control and 1K1C myocytes was significant under conditions of increased intracellular cyclic GMP.

Alkaloids↗

PubMed1999

Myocardial creatine kinase kinetics in hearts with postinfarction left ventricular remodeling.

This study examined whether alterations in myocardial creatine kinase (CK) kinetics and high-energy phosphate (HEP) levels occur in postinfarction left ventricular remodeling (LVR). Myocardial HEP and CK kinetics were examined in 19 pigs 6 wk after myocardial infarction was produced by left circumflex coronary artery ligation, and the results were compared with those from 9 normal pigs. Blood flow (microspheres), oxygen consumption (MVO2), HEP levels [31P magnetic resonance spectroscopy (MRS)], and CK kinetics (31P MRS) were measured in myocardium remote from the infarct under basal conditions and during dobutamine infusion (20 micrograms. kg-1. min-1 iv). Six of the pigs with LVR had overt congestive heart failure (CHF) at the time of study. Under basal conditions, creatine phosphate (CrP)-to-ATP ratios were lower in all transmural layers of hearts with CHF and in the subendocardium of LVR hearts than in normal hearts (P < 0.05). Myocardial ATP (biopsy) was significantly decreased in hearts with CHF. The CK forward rate constant was lower (P < 0.05) in the CHF group (0.21 +/- 0.03 s-1) than in LVR (0.38 +/- 0.04 s-1) or normal groups (0.41 +/- 0.03 s-1); CK forward flux rates in CHF, LVR, and normal groups were 6.4 +/- 2.3, 14.3 +/- 2.1, and 20.3 +/- 2.4 micromol. g-1. s-1, respectively (P < 0.05, CHF vs. LVR and LVR vs. normal). Dobutamine caused doubling of the rate-pressure product in the LVR and normal groups, whereas CHF hearts failed to respond to dobutamine. CK flux rates did not change during dobutamine in any group. The ratios of CK flux to ATP synthesis (from MVO2) under baseline conditions were 10.9 +/- 1.2, 8. 03 +/- 0.9, and 3.86 +/- 0.5 for normal, LVR, and CHF hearts, respectively (each P < 0.05); during dobutamine, this ratio decreased to 3.73 +/- 0.5, 2.58 +/- 0.4, and 2.78 +/- 0.5, respectively (P = not significant among groups). These data demonstrate that CK flux rates are decreased in hearts with postinfarction LVR, but this change does not limit the response to dobutamine. In hearts with end-stage CHF, the changes in HEP and CK flux are more marked. These changes could contribute to the decreased responsiveness of these hearts to dobutamine.

Animals↗

PubMed1999

Transmural metabolic heterogeneity at high cardiac work states.

This study compared the transmural distribution of high-energy phosphate (HEP) depletion during oxidative stress induced by pacing- and dobutamine-induced tachycardia in myocardium perfused by a flow-limiting coronary stenosis. Myocardial blood flow (MBF) was measured with radioactive microspheres. Creatine phosphate (CrP), ATP, and P(i) were measured with transmurally localized (31)P NMR spectroscopy. In normal dogs a hydraulic occluder was used to produce a left anterior descending coronary artery stenosis, which maintained constant flow measured with a Doppler probe. Tachycardia was induced by rapid pacing (200 beats/min, n = 11) or by dobutamine infusion (20 micrograms . kg(-1). min(-1) iv, n = 13) to produce a similar heart rate. In the presence of stenosis, pacing and dobutamine caused similar reductions of subendocardial (Endo)-to-subepicardial (Epi) MBF ratios (0.66 +/- 0.06 vs. 0.63 +/- 0.08, respectively). Stenosis plus pacing caused a decrease of the CrP-to-ATP ratio (CrP/ATP) in Endo from 2.00 +/- 0.07 to 1.65 +/- 0. 08 (P < 0.05) with no significant change in Epi. Stenosis plus dobutamine caused HEP changes across the left ventricular wall, which were most marked in the outer myocardial layer (Epi CrP/ATP decreased from 2.33 +/- 0.11 to 1.67 +/- 0.12; Endo CrP/ATP decreased from 1.99 +/- 0.09 to 1.64 +/- 0.12). Thus HEP changes during oxidative stress that are produced by pacing parallel the pattern of hypoperfusion and are most severe in the subendocardium. In contrast, in response to inotropic stimulation, the transmural metabolic changes did not correspond to the pattern of the hypoperfusion.

Animals↗