The BIOSAFEPAPER project for in vitro toxicity assessments: preparation, detailed chemical characterisation and testing of extracts from paper and board samples.

Nineteen food contact papers and boards and one non-food contact board were extracted following test protocols developed within European Union funded project BIOSAFEPAPER. The extraction media were either hot or cold water, 95% ethanol or Tenax, according to the end use of the sample. The extractable dry matter content of the samples varied from 1200 to 11,800 mg/kg (0.8-35.5 mg/dm2). According to GC-MS the main substances extracted into water were pulp-derived natural products such as fatty acids, resin acids, natural wood sterols and alkanols. Substances extracted into ethanol particularly, were diisopropylnaphthalenes, alkanes and phthalic acid esters. The non-food contact board showed the greatest number and highest concentrations of GC-MS detectable compounds. The extracts were subjected to a battery of in vitro toxicity tests measuring both acute and sublethal cytotoxicity and genotoxic effects. None of the water or Tenax extracts was positive in cytotoxicity or genotoxicity assays. The ethanol extract of the non-food contact board gave a positive response in the genotoxicity assays, and all four ethanol extracts gave positive response(s) in the cytotoxicity assays to some extent. These responses could not be pinpointed to any specific compound, although there appeared a correlation between the total amount of extractables and toxicity.

Arginase activity in prostatic tissue of patients with benign prostatic hyperplasia and prostatic carcinoma.

We studied arginase activity in human prostatic tissue in 15 patients with benign hyperplasia and 27 patients with prostatic carcinoma. Arginase specific activity is greater (p less than 0.0001) in prostatic carcinomas than in hyperplastic prostates. Arginase specific activity is correlated inversely (p less than 0.0001) with the histological grade of the tumor.

Prostatic hexosaminidase activity in patients with benign prostatic hyperplasia and prostatic carcinoma.

Hexosaminidase activity in prostatic tissue has been compared in 15 patients with benign prostatic hyperplasia and 15 patients with prostatic carcinoma. The ratio of enzymatic activity for the two substrates tested (p-nitrophenyl-2-acetamido-2-deoxy-beta-D-glucopyranoside and p-nitrophenyl-2-acetamido-2-deoxy-beta-D-galactopyranoside) was not significantly different in the two groups of patients. The proportion of hexosaminidase represented by the B isozyme was not significantly different for the two groups of patients. Prostatic tissue hexosaminidase was greater (p = 0.0141) in carcinomatous prostates than in hyperplastic prostates.

5'-nucleotidase activity in prostatic carcinoma and benign prostatic hyperplasia.

In light of previous reports of alterations in 5'-nucleotidase activity in neoplastic conditions, 5'-nucleotidase activity was examined histochemically in tissue sections and quantified biochemically in extracts of human hyperplastic prostates and prostatic carcinomas obtained surgically. The 5'-nucleotidase activities per mg protein in extracts of 29 prostatic carcinomas were lower (P less than 0.0005) than in extracts from 10 samples of benign prostatic hyperplasia. The 5'-nucleotidase activity per mg protein in extracts of prostatic carcinoma from the 29 patients correlated (R = -0.369, P = 0.049) with the degree of histological differentiation; the extracts of poorly differentiated carcinomas contained low levels of 5'-nucleotidase. When age and histological differentiation (Gleason's grade) were adjusted, the enzyme activity per mg protein correlated (R = 0.242, P = 0.004) with patient survival. When all three parameters were considered together, i.e., histological grade of the tumor, 5'-nucleotidase extracted from the tumor, and age of the patient, they were found to be mutually complementary for the prediction of patient survival (R = 0.388, P = 0.0001). To our knowledge, this is the first report that prostatic epithelium expresses 5'-nucleotidase; further work will be required to define the reasons for the high levels of activity observed in prostates without cancer and for the decrease in the activity in prostatic carcinoma.

Enzyme activities in prostatic carcinoma related to Gleason grades.

In an effort to identify enzymatic activities in primary prostatic carcinomas that might be complementary to histological and other clinical techniques for the prediction of prognosis, we have assayed several enzymatic activities extracted from prostatic carcinomas. We reported previously that, for each of the studied enzymes, tissues with benign prostatic hyperplasia and prostatic carcinoma showed significantly different activities. With additional patients now included and a longer interval since resection of these tumors, we have found that the histological grade (Gleason's system for grading) of the sample (prostate chip) analyzed is related to several activities extracted from the cancers including arginase (r = -0.81, p less than 0.0001), glucose-6-phosphate dehydrogenase (r = 0.72, p less than 0.0001), and the B isoenzyme of N-acetyl-beta-D-glucosaminidase (r = -0.58, p = 0.0369). Acid phosphatase (r = 0.15, p = 0.5530) and the BB isoenzyme of creatine kinase (r = -0.13, p = 0.5221) are not significantly related to histological grade. In a large series, Gleason grade is related to survival. In our series of 27 patients followed for 20 to 46 months, the Gleason grade (p = 0.22) is not related to survival, but arginase activity is related (p = 0.0392) to survival. In this small series, arginase is more valuable than the best currently proven predictor of survival, Gleason grade. Hexosaminidase B activity approaches being significantly (p = 0.0575) related to survival. Of the 11 patients whose tumors contained the lowest arginase activities, eight are dead. Of the 11 with the highest activities, only one is dead. Several of the enzyme activities in this series of 27 patients complemented each other for the prediction of Gleason grade; for example, glucose-6-phosphate dehydrogenase, arginase, and the BB isoenzyme of creatine kinase were more closely correlated (multiple correlation coefficient, r = 0.77) with the Gleason grade for all chips than was any single enzyme: arginase, r = -0.67; glucose-6-phosphate dehydrogenase, r = 0.67; creatine kinase, r = -0.16. It seems likely that enzymatic analysis may provide an approach that is qualitatively different from and complementary to histological evaluation for the prediction of prognosis in prostatic carcinoma. Verification of this hypothesis will require more patients followed over a longer period of time and will probably be facilitated by analysis of several samples from different locations in each tumor.

Heterogeneity and prognostic significance of macrophages in human colonic carcinomas.

Previously, we reported that high concentrations of eosinophils in human colonic carcinomas are associated with better prognoses, that sections taken 1 cm remote from (deep to) the margin of tumor (SRM) and sections contiguous to the margin (SCM) of tumor and adjacent uninvolved colon contain significantly different concentrations of eosinophils, and that concentrations of eosinophils in SCM and SRM are both useful and complementary for the prediction of prognosis. As a first step towards studying the ecology of the eosinophil in colonic carcinoma and with the goal of identifying other kinds of cells that might be useful for the prediction of prognosis, we counted cells in SCM and SRM that expressed histochemically demonstrable acid phosphatase, alpha-naphthylbutyrate esterase, and peroxidase. The tumors of patients with and without metastases at the time of resection of the primary tumor contained different (P = 0.0314) concentrations of cells with histochemically demonstrable alpha-naphthylbutyrate esterase in SCM but not in SRM. In contiguous 1- to 2-micron sections, morphologically macrophage-like cells with histochemically demonstrable acid phosphatase and cells with histochemically demonstrable alpha-naphthylbutyrate esterase were found to be present in different concentrations both in SCM (P less than 0.01) and in SRM (P less than 0.01); i.e., these phenotypic markers appear to identify different subpopulations of macrophages in tumors. In contrast to our previous study of human pulmonary alveolar macrophages, examination of sections stained sequentially for these phenotypic markers that are commonly used for the identification of macrophages in tumors revealed numerous cells in the same sections that expressed histochemically demonstrable acid phosphatase (red) but not alpha-naphthyl butyrate esterase (brown) and vice versa. Several of these markers promise to be useful and complementary for the prediction of prognosis.

Decrease in creatine kinase in human prostatic carcinoma compared to benign prostatic hyperplasia.

Many previous studies have shown that a proportion of patients with carcinoma of the prostate have increased activity of the creatine kinase (E.C. 2.7.3.2) isoenzyme designated BB in sera from their peripheral blood. We have analyzed tissues from prostatic hyperplasia of 22 patients and from prostatic carcinoma of 23 additional patients. Prostatic carcinomas contain less (p less than 0.001) creatine kinase activity (units/g) than do prostates with benign prostatic hyperplasia. The facts that (a) histochemical studies that we performed confirmed the observation reported previously by others that creatine kinase activity is found primarily in the epithelial elements of hyperplastic prostates and prostatic carcinomas, (b) the carcinomas that we examined had, on the average, a somewhat larger epithelial component than the hyperplastic prostates that we examined, and (c) prostate cancer was found to contain less creatine kinase activity than hyperplastic prostates suggest that the epithelial cells in prostate cancers contain less creatine kinase activity per cell than do those from hyperplastic prostates. The BB form of creatine kinase accounts for 98% of the activity in prostatic carcinoma and in prostates without cancer. Creatine kinase has been discussed as a possible marker for prostatic carcinoma, and we had hoped that it might be useful for the assay of tumor burden. Our data suggest that, if creatine kinase is to be useful in the monitoring of tumor burden, it will be useful only in the contexts of particular patients studied longitudinally since the creatine kinase activity varies enormously among different prostatic carcinomas.

Large-capacity separation of malignant cells and lymphocytes from the Furth mast cell tumor in a reorienting zonal rotor.

The Furth murine mastocytoma was adapted to the ascitic form and separated into fractions enriched with respect to lymphocytes and malignant cells by velocity sedimentation in the SZ-14 reorienting zonal rotor or in the isokinetic gradient. Lymphocytes were more highly purified (p less than 0.01) in the isokinetic gradient than in the zonal rotor, i.e., lymphocytes comprised 99.1% of the nucleated cells in the purest fraction from the isokinetic gradient and 80.1% of the nucleated cells in the purest fraction from the zonal rotor. Neoplastic mast cells were similarly purified by the two methods; they comprised 67.7 and 78.5% of the nucleated cells in the purest fractions from the isokinetic gradient and zonal rotor, respectively. Up to 160 million tumor cells can be purified in a single step with the reorienting zonal rotor, whereas 30 to 40 million cells per gradient approach the limit of the isokinetic gradient. After centrifugation in the zonal rotor, recovery was 85.6 +/- 12% (S.D.) of the cells layered over the gradient; and the separated tumor cells retained their ability to form tumors when transplanted into mice. The separation of large numbers of lymphocytes and malignant cells from the same tumor in the SZ-14 rotor should aid in the biochemical and immunological characterization of cancer.

Correlation of stromal cells by morphometric analysis with metastatic behavior of human colonic carcinoma.

The cellular compositions of the inflammatory infiltrates in human colonic carcinoma in well-defined compartments have not been quantified previously. Morphometric analysis of this tissue revealed several relationships between the concentrations of different kinds of cells that may be an important first approach to understanding the nature of the host reaction in different groups of patients. Primary tumors without metastases differ from those with metastases in that those without metastases contain higher concentrations of plasma cells (P = 0.0019) and eosinophils (P = 0.0098) in sections taken at a location remote from the margin (tissue located greater than 1 cm from the margin) and increased concentrations of eosinophils (P = 0.0224) in sections of tumor contiguous to the margin (tissue 0-4.5 mm from the margin). In sections contiguous to the margin, the concentration of plasma cells is related to the concentrations of lymphocytes (R = 0.55, P = 0.0014), eosinophils (R = 0.46, P = 0.0085), fibroblasts (R = 0.47, P = 0.0075), and neutrophils (R = 0.63, P = 0.0001). In sections remote from the margin, the concentration of plasma cells is related to the concentration of lymphocytes (R = 0.36, P = 0.0442), eosinophils (R = 0.36, P = 0.0457), mast cells (R = 0.38, P = 0.0375), and neutrophils (R = 0.38, P = 0.0371).

Fenton's reagent for the rapid and efficient isolation of microplastics from wastewater.

Fenton's reagent was used to isolate microplastics from organic-rich wastewater. The catalytic reaction did not affect microplastic chemistry or size, enabling its use as a pre-treatment method for focal plane array-based micro-FT-IR imaging. Compared with previously described microplastic treatment methods, Fenton's reagent offers a considerable reduction in sample preparation times.

Adrenal androgen excess in women: lack of a role for 17-hydroxylase and 17,20-lyase dysregulation.

Some investigators have suggested that "dysregulation" of cytochrome P450c17 alpha may result in the exaggerated secretion of ovarian androgens in hyperandrogenism. Although the majority of hyperandrogenic (HA) patients demonstrate an ovarian source for their androgens, approximately 50% also display adrenocortical hyperactivity and adrenal androgen excess. To determine whether 17-hydroxylase (17-OH) and/or 17,20-lyase dysregulation is responsible for the adrenocortical abnormalities noted in many HA patients, we studied 92 consecutive women with hirsutism and/or HA oligomenorrhea; 26 healthy eumenorrheic nonhirsute women served as controls. The basal levels of total and free testosterone (T), sex hormone-binding globulin, and dehydroepiandrosterone sulfate were measured, and pregnenolone, 17-hydroxypregnenolone, progesterone, 17-hydroxyprogesterone, dehydroepiandrosterone, and androstenedione were measured 0 and 60 min after the acute iv administration of ACTH-(1-24). Controls and HA patients did not differ in mean age or body mass, but HA women had higher basal T, free T, dehydroepiandrosterone sulfate, androstenedione, and LH/FSH and lower sex hormone-binding globulin levels. The mean estimated basal 17-OH activity was higher among HA patients than in controls. Although 52 HA patients demonstrated solely an exaggerated basal delta 5-17-OH activity estimate, few HA patients had an exaggerated estimate for either basal delta 4-17-OH or ACTH-stimulated 17-OH activity. No HA patient demonstrated an exaggerated 17,20-lyase basal activity, whereas 14 demonstrated an exaggerated delta 4-17,20-lyase ACTH-stimulated activity only. There was no association between these estimates of 17-OH and 17,20-lyase activities and the circulating adrenal androgen levels in HA women. Importantly, none of the patients demonstrated an increase in the basal activities of both 17-OH and 17,20-lyase, and only 4 patients demonstrated an exaggerated ACTH-stimulated activity of both 17-OH and 17,20-lyase. In conclusion, the steroidogenic profile observed in this population of HA women before and after ACTH-(1-24) stimulation is not consistent with dysregulation of cytochrome P450c17 alpha and probably represents a generalized alteration of adrenocortical control or biosynthesis.

On the origin of the elevated 17-hydroxyprogesterone levels after adrenal stimulation in hyperandrogenism.

Hyperandrogenic women appear to demonstrate an exaggerated 17-hydroxyprogesterone (17-HP) response to adrenal stimulation which is not due to the marked 21-hydroxylase deficiency of late-onset adrenal hyperplasia (LOAH). Furthermore, in hyperandrogenism the ovary also appears to secrete excessive amounts of 17-HP. It is not clear to what extent the elevated 17-HP levels after ACTH stimulation are due to extraadrenal production of the steroid. This investigation was undertaken to assess the adrenal contribution to the elevated 17-HP levels after ACTH stimulation observed in non-LOAH hyperandrogenism. One hundred and sixty consecutive unselected women with hirsutism and/or hyperandrogenic oligomenorrhea formed the clinical population. Excluded were 4 women with LOAH and all patients with hyperprolactinemia. For the purpose of investigating the relationship between adrenal response and clinical symptoms, hyperandrogenic patients were divided into 3 subgroups: hirsute only (n = 23), hirsute oligomenorrheic (n = 84), and oligomenorrheic only (n = 24). Subclassification for an additional 29 patients (18%) with hyperandrogenemia was not possible, since their symptomatology was not clearly stated in the record. However, these individuals were included in the patient group as a whole. Controls consisted of 21 healthy, regularly menstruating, nonhirsute female volunteers. Both patients and controls underwent acute adrenal stimulation with 1 mg ACTH-(1-24), and serum was obtained before and 30 min after ACTH administration. Hyperandrogenic patients had higher mean basal total testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHS), 17-HP, and LH/FSH levels, but not cortisol (F), compared to normal subjects (P less than 0.02). Oligomenorrheic only women had higher mean A and progesterone (P) levels than other hyperandrogenic patients (P less than 0.02). No correlation was noted between body mass index (BMI) and the levels of DHS, P, or A, while a weak positive association was noted between the BMI and the mean T (r = 0.31; P less than 0.002) and a weak negative correlation between the mean F and BMI (r = -0.21; P less than 0.05). The mean 17-HP level 30 min after ACTH administration (17-HP30) was significantly higher in hyperandrogenic women than in normal subjects whether analyzed in separate subgroups or together and was due to the higher basal 17-HP levels. Basal 17-HP correlated with the circulating levels of T, A, and P, steroids largely of ovarian origin. Alternatively, the net increment in 17-HP from 0-30 min after ACTH (delta 17-HP30) was not significantly higher in hyperandrogenic women than normal subjects and did not correlate with the basal levels of T, A, and P. Neither the basal level of 17-HP nor its response to ACTH correlated with circulating DHS levels.(ABSTRACT TRUNCATED AT 400 WORDS)

Leuprolide and estrogen versus oral contraceptive pills for the treatment of hirsutism: a prospective randomized study.

The administration of long-acting GnRH analogs (GnRH-a) results in gonadotropin and androgen suppression in hyperandrogenic women. Nonetheless, no randomized studies are available comparing GnRH-a with currently used treatments for hirsutism. We have hypothesized that the greater degrees of androgen suppression achieved with GnRH-a therapy could result in a more rapid improvement in hirsutism compared to oral contraceptive (OCP) administration. To test this hypothesis, we studied 17 hirsute women before and during 6 months of randomized treatment with 1) leuprolide depot (3.75 mg/month) plus conjugated estrogen (0.625 mg/day) and medroxyprogesterone acetate (10 mg; days 1-12; n = 9; leuprolide+ERT), or 2) an OCP containing ethynodiol diacetate (1 mg) and ethinyl estradiol (35 micrograms; n = 8). LH, FSH, estradiol, dehydroepiandrosterone sulfate, androstenedione (A4), sex steroid-binding globulin, and total and free testosterone (T) were measured at weeks 0, 2, 4, 8, 12, and 28. At 0 and 28 weeks of treatment, hirsutism was evaluated subjectively by patient self-evaluation and by the Ferriman-Gallwey score, and objectively by determination of facial hair density, outer hair shaft diameter, and growth rate, determined both photographically and in plucked hairs. In the leuprolide+ERT, but not OCP, groups, there was a significant decrease in the circulating LH and FSH levels. In both groups, T and A4 decreased with treatment, although the decrease in A4 levels did not reach significance in OCP-treated women. The circulating sex steroid-binding globulin level increased in both treatment groups, but the changes in the OCP-treated women was greater. Consequently, although the calculated percent free T decreased significantly in both treatment groups, the decrease was greater in the OCP-treated women. The dehydroepiandrosterone sulfate level did not change with either therapy. A significant percent decrease in the Ferriman-Gallwey score was noted in the leuprolide+ERT, but not OCP, patients, and by self-evaluation, seven (78%) and five (55%) of leuprolide+ERT patients, compared to two (25%) and two (25%) OCP-treated women, noted an improvement in hair growth and texture, respectively. No significant difference in mean facial hair density or outer hair diameter was noted with either therapy. Patients treated with leuprolide+ERT demonstrated a decrease in the actual hair growth rate, using the photographic method, or percent decrease in growth rate, using plucked hair. In conclusion, treatment with leuprolide plus cyclic estrogen/progestin appears to provide a more rapid, and possibly greater, improvement in hirsutism, compared to a standard OCP regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Vitamin fluctuations in the blood of female baboons in relation to normal menstrual cycles, treatments with Lo-Ovral or Depo-Provera and a selected vitamin supplement.

Both endogenous and exogenous sex steriods may induce changes in plasma vitamin levels by altering availability, transport, binding, or use of vitamins. This study investigated some of those mechanisms by observing in a primate model (baboon), the blood levels of carotene, folate, vitamins A, B12, and C, and the status of vitamin B6, riboflavin, and thiamin. The latter three vitamins were studied by determining their relationship to asparate aminotransferase, glutathione reductase, and thiamin transketolase, respectively. The vitamin screen was obtained throughout normal menstrual cycles in 10 baboons and weekly for 55 wk in five baboons receiving Lo-Ovral and in four baboons receiving Provera. During the last 16 wk of hormonal treatment, all baboons received a vitamin supplement containing pyridoxine, riboflavin, and thiamin. Only carotene (p less than 0.0001), vitamin A (p less than 0.05), glutathione reductase (p less than 0.05), and thiamin transketolase (p less than 0.05) levels fluctuated significantly during normal menstrual cycles. Long-term treatment with Lo-Ovral and Provera resulted in numerous changes but there were very few differences between the two hormone treatments. Compared to control levels, vitamin C was elevated during treatment while all three enzyme activities were lowered. Vitamin supplementation raised asparate aminotransferase and glutathione reductase activity and the levels of folic acid, vitamin A, and carotene. This study demonstrates that interactions between hormones and vitamins and among vitamins themselves, are complex but it is likely that the treatments used here caused no physiologically significant vitamin alterations.

Enhanced evaluation of treadmill tests by means of scoring based on multivariate analysis and its clinical application: a study of 608 patients.

Six hundred eight patients being evaluated for chest pain who did not have valvular disease, cardiomyopathy, left ventricular hypertrophy or bundle branch block, and were not receiving digitalis, had treadmill tests and coronary angiograms. In 351, various exercise variables were correlated by multivariate analysis to coronary artery disease (CAD). In men, significant variables were: (1) maximal heart rate achieved less than 80% of maximal predicted heart rate (Mx PHR), (2) ST-T change greater than or equal to 1 mm, (3) age greater than or equal to 55 years and (4) treadmill time (TT) less than 8 minutes. These variables rated diagnostic scores of 9, 6, 5, and 3, respectively. A score of greater than or equal to 7 was considered diagnostic of CAD. In a test group of 192 men in which ST-T change was compared with treadmill score, sensitivity was 65 versus 85%, specificity 79 versus 74% and accuracy 69 versus 83%. In women, maximal heart rate less than 90% of Mx PHR and TT of less than 6 minutes were significant, with an accuracy of 75%. Moreover, 89% of incomplete tests and 70% of tests in patients with previous myocardial infarction were also correctly diagnosed. This method allows convenient use of significant exercise variables for clinical purposes with improved results.

Comparison of primary angioplasty versus thrombolytic therapy for acute myocardial infarction. Alabama Registry of Myocardial Ischemia Investigators.

To determine the relative merits of primary percutaneous transluminal coronary angioplasty (PTCA) and intravenous thrombolytic therapy for acute myocardial infarction, 12 tertiary care hospitals entered patients who had > or = 30 minutes of chest pain and were admitted to a cardiac intensive care unit within 12 hours of symptom onset into a prospective registry. Of 1,170 such patients, 118 (10%) underwent primary PTCA and 230 (19%) received intravenous thrombolytic therapy within 6 hours of registry hospital admission (144 at the registry hospital and 86 prior to arrival at the registry hospital). Baseline demographic characteristics of PTCA and thrombolytic subgroups were remarkably similar. The interval from initial evaluation at the registry hospital to treatment was shorter with intravenous thrombolytic therapy than with primary PTCA (64 vs 104 minutes, p < 0.001), as was the interval from pain onset to treatment (184 vs 252 minutes, p < 0.001). Among the 230 thrombolytic patients, coronary arteriography and PTCA were performed within the first 24 hours in 44% and 18%, respectively, and during the entire hospitalization in 90% and 49%, respectively. During hospitalization, blood was transfused in 16% of the 230 thrombolytic patients versus 5.9% of the 118 PTCA patients (p < 0.001). Otherwise, adverse events during the initial hospitalization were similar in PTCA and thrombolytic groups. Survival at 1-year follow-up was 88% in the PTCA group and 91% in the thrombolytic group (p = NS), and survival free of reinfarction was 85% and 88%, respectively (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Inferior and superior vena caval blood flows during cross-clamping of the thoracic aorta in pigs.

Changes in blood flow through the inferior and superior venae cavae during cross-clamping of the thoracic aorta just above the diaphragm were studied in 28 miniature pigs anesthetized with enflurane titrated to maintain systemic arterial blood pressure close to normal values. Surgical preparation included sternotomy with subsequent placement of a noncannulating electromagnetic probe around the ascending aorta and a cannulating electromagnetic probe in the transected inferior vena cava. Superior vena caval flow was calculated as the difference between aortic flow and inferior vena caval flow. Clamping of the thoracic aorta alone (n = 10) was accompanied by severe arterial hypertension, a dramatic decrease in inferior vena caval flow, and an increase in superior vena caval flow, which resulted in a moderate increase in aortic flow. Simultaneous clamping of the thoracic aorta and inferior vena cava (n = 13) was accompanied by no significant change in arterial pressure or superior vena caval flow. The oxygen content in mixed venous blood significantly (p less than 0.05) increased from 9.5 +/- 1.1 to 13.4 +/- 1.8 ml.dl-1 in animals undergoing clamping of the thoracic aorta only, but did not change significantly in animals subjected to simultaneous clamping of the aorta and inferior vena cava. The study demonstrates a substantial increase in superior vena caval flow during cross-clamping of the thoracic aorta. Further studies elucidating the mechanism of the observed changes are required.

Hemodynamics and oxygen uptake below and above aortic occlusion during crossclamping of the thoracic aorta and sodium nitroprusside infusion.

The effects of controlled vasodilation on blood flow and oxygen consumption above and below the aortic occlusion during crossclamping of the thoracic aorta were examined in 16 mongrel dogs anesthetized with halothane. Blood flow in the inferior vena cava was measured with an electromagnetic cannulating flow probe, and cardiac output was measured by thermodilution. The animals were divided into two groups. In the control group the thoracic aorta was crossclamped at the diaphragmatic level for 30 minutes. In the sodium nitroprusside group the aorta was also crossclamped for 30 minutes, but an infusion of sodium nitroprusside was initiated after 10 minutes of occlusion to decrease systemic blood pressure. Measurements were made before and at 10, 20, and 30 minutes after aortic crossclamping, and at 10 minutes after aortic unclamping. Crossclamping of the thoracic aorta was associated with marked decreases in blood flow and oxygen consumption in organs and tissues below the aortic occlusion in both groups. Above the occlusion, blood flow increased but oxygen uptake decreased. Sodium nitroprusside increased cardiac output and blood flow above the aortic occlusion even more than crossclamping alone while it decreased blood flow and oxygen consumption below the crossclamp.

Effects of crossclamping the descending aorta on the high-energy phosphates of myocardium and skeletal muscle. A phosphorus 31-nuclear magnetic resonance study.

The study was designed to test the hypothesis that a moderate decrease in upper body oxygen consumption observed during crossclamping of the thoracic aorta represents tissue hypoxia (possibly as a result of microcirculatory disorders) and results in adenosine triphosphate homeostasis disturbances. We averaged phosphorus 31-nuclear magnetic resonance spectroscopy measurements for 10 minutes with the use of a surface coil on the left ventricle and on the deltoid muscle during a 1-hour period before aortic crossclamping, during aortic crossclamping, and after aortic unclamping. Skeletal muscle creatine phosphate levels decreased 3.1% (p < 0.01), whereas the ratio of creatine phosphate to adenosine triphosphate decreased 2.2% (p < 0.05); glycolytic intermediates increased 70% (p < 0.01) and intracellular inorganic phosphate decreased 9% (p < 0.01). Myocardial creatine phosphate decreased 15% (p < 0.01), whereas the ratio of creatine phosphate to adenosine triphosphate decreased 5.3% (p < 0.01); glycolytic intermediates did not change, but intracellular inorganic phosphate almost doubled (p < 0.05). These data suggest that observations of reduced upper body oxygen consumption after aortic crossclamping are consistent with the effects of skeletal muscle hypoxia. Changes in myocardial metabolites may result from transient ischemia caused by the increased wall stress.

Suture techniques for atrioventricular valves: experimental study.

Repair of the complete atrioventricular canal defect is still complicated by dehiscence of sutured atrioventricular valves. An in vitro study of initial suture line strength during tensile loading was made using canine pericardial leaflets. Type of "non-pledgetted" stitch was not related to suture line strength. Closer spacing of non-pledgetted stitches (1 mm versus 2 mm) increased strength 29% (p less than 0.05). Pledgets increased strength 25% (p = 0.004). Greater depth (3 mm versus 1.5 mm) increased strength 32% (p less than 0.0001) in both pledgetted and non-pledgetted stitches. Larger suture size (4-0 versus 6-0) increased strength minimally. An in vivo study was performed to determine if the positive effect of pledgets on initial stitch strength would persist in a functioning mitral valve during healing. Four incisions were made at the base of the anterior mitral leaflet in dogs and were closed with one horizontal mattress stitch, with or without pledgets. After 1 to 7 days, none of the 16 pledget-supported stitches had disrupted whereas nine of the 16 stitches without pledgets had torn out of the leaflet (p = 0.001). Tensile testing indicated use of pledgets resulted in stronger stitches (p = 0.0005). Results indicate that in the repair of the complete atrioventricular canal defect, pledget-supported sutures should be used. If non-pledgetted stitches are necessary, bites should be deep and closely spaced.