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Biomedical subjects

A Owen

Publications and source records attributed to A Owen.

At least 19 recordsLinked to original sources
PubMed1994

Aprotinin does not decrease early graft patency after coronary artery bypass grafting despite reducing postoperative bleeding and use of donated blood.

Forty-five male patients with planned coronary artery bypass operation were randomized in a double blind fashion to receive either 6 million kallikrein inactivator units of aprotinin (high-dose group), 2 million kallikrein inactivator units of aprotinin (low-dose group), or placebo (control group). Postoperative bleeding was significantly decreased in both aprotinin groups in comparison to that in the control group (590 ml [290 to 1800 ml] high-dose group and 650 ml [280 to 1900 ml] low-dose group versus 920 ml (350 to 2700 ml) control group, p < 0.001). There was no difference between the two aprotinin groups. The need for postoperative blood transfusion was significantly lower in the aprotinin groups (1.46 [0 to 4] blood units high-dose group and 1.65 [0 to 5] blood units low-dose group versus 2.43 [0 to 7] blood units control group, p < 0.05). All patients underwent coronary angiography between the seventh and twelfth postoperative day. No difference was found among the three groups in patency of vein grafts-93.8% in the high-dose group, 94.5% in the low-dose groups, and 93.3% in the control group. Therefore, aprotinin significantly reduced postoperative bleeding and transfusion requirement after coronary artery bypass grafting without influencing early graft patency.

Aprotinin↗
PubMed1992

Physiological features of pericardial constriction in the absence of pericardial disease.

To sustain a clinical diagnosis of constriction it is classically held that the fibrous pericardium must be thickened and adherent to the surface of the heart. A case is presented in which leukaemic infiltration of the fat overlying the myocardium resulted in the physiological features of constriction, although all layers of the pericardium itself were normal. Constriction is thus a physiological diagnosis; it may develop in the absence of the classical anatomical findings.

Aged↗
PubMed1992

Aprotinin decreases release of 6-keto-prostaglandin F1 alpha and increases release of thromboxane B2 in cultured human umbilical vein endothelial cells.

Use of the proteinase inhibitor aprotinin significantly improves hemostasis and reduces bleeding after operations in which extracorporeal circulation is used. The mechanism of action, however, has been only partially clarified. In this work we investigated whether aprotinin influenced the production and release of the eicosanoids prostacyclin, measured as the stable metabolite 6-keto-prostaglandin F1 alpha, and thromboxane A2, measured as the stable metabolite thromboxane B2, from endothelial cells. Human umbilical vein endothelial cells were incubated with different concentrations of aprotinin (5.5, 20, 55, and 100 mumol/L). The levels of 6-keto-prostaglandin F1 alpha and thromboxane B2 were measured at baseline and after thrombin stimulation. A concentration-dependent effect of aprotinin on 6-keto-prostaglandin F1 alpha synthesis was demonstrated. After incubation with 100 mumol/L of aprotinin, a 90% reduction in 6-keto-prostaglandin F1 alpha production was seen (31.69 versus 307.44 picograms per million cells; p less than 0.001). Conversely, thromboxane B2 production showed a 345% increase after incubation with aprotinin (287.80 versus 83.82 picograms per million cells; p less than 0.0001). Since 6-keto-prostaglandin F1 alpha inhibits and thromboxane B2 strongly enhances platelet aggregation, it appears that one mechanism of the clinically observed effectiveness of aprotinin lies in the altered ratio of 6-keto-prostaglandin F1 alpha: thromboxane B2 in endothelial cells, which leads to enhanced platelet aggregation and improved vessel sealing.

6-Ketoprostaglandin F1 alpha↗
PubMed1992

Aprotinin increases release of von Willebrand factor in cultured human umbilical vein endothelial cells.

Through the perioperative administration of the proteinase inhibitor aprotinin, hemostasis can be improved and postoperative bleeding reduced after cardiac operations. The mechanism of action has been only partially clarified. The goal of our study was to investigate the influence of aprotinin on the synthesis of von Willebrand factor (vWF) in human endothelial cells. Human umbilical vein endothelial cells (HUVEC) were cultivated in vitro and incubated with different aprotinin concentrations (55, 100, and 215 mol/L). With all investigated aprotinin concentrations, there was an increase in vWF synthesis compared with basal secretion (p less than 0.001). When the HUVEC were preincubated with aprotinin and stimulated with thrombin, there was a further significant increase in vWF synthesis. HUVEC that, were first incubated with aprotinin and then stimulated with thrombin demonstrated a significant increase in vWF synthesis compared with basal secretion in nonincubated cells (p less than 0.0001). Also, compared with the cells that had received thrombin stimulation alone, the combination of aprotinin incubation and thrombin stimulation led to a significantly higher vWF concentration (p less than 0.05). Because vWF is necessary for the interaction with platelet factor glycoprotein Ib and platelet adhesion, the demonstrated increase in vWF synthesis could be one of the mechanisms of action of aprotinin leading to its blood-sparing effect.

Aprotinin↗
PubMed1992

Effects of coronary artery bypass grafting on global and regional myocardial function. An intraoperative echocardiographic assessment.

The immediate effect of coronary artery bypass grafting on global and regional myocardial function was studied by means of epicardial two-dimensional echocardiography during operations in 20 patients. Echocardiograms were recorded before cardiopulmonary bypass and 5 and 30 minutes after bypass. Global left ventricular function was expressed as percent short-axis area change and regional function as percent fractional area change. Segments were classified according to their baseline function as normal (percent fractional area change greater than 40%), moderately hypokinetic (percent fractional area change 21% to 40%), or severely dysfunctional (percent fractional area change less than 20%). Percent short-axis area change was significantly reduced immediately after cardiopulmonary bypass (from 42.0% +/- 4.6% to 34.9% +/- 3.0%, p less than 0.05) but had returned to baseline 30 minutes after bypass (42.6% +/- 4.0%). Similarly, function of normal and moderately hypokinetic segments decreased significantly immediately after cardiopulmonary bypass (normal segments: percent fractional area change 56% +/- 0.9% before bypass to 42.3% +/- 1.5% after bypass, p less than 0.0001; moderately hypokinetic segments: 31.0% +/- 0.9% to 25.1% +/- 1.4%, p less than 0.002). Both normal and moderately hypokinetic areas regained baseline function by 30 minutes after bypass (normal segments: 53.4% +/- 1.6%; moderately hypokinetic segments: 35.4% +/- 2.0%). In contrast, severely dysfunctional segments were found to be significantly improved immediately after bypass (14.7% +/- 0.9% before bypass to 27.7% +/- 2.1% after bypass, p less than 0.0001). This improvement was maintained 30 minutes after bypass (22.8% +/- 1.5%, p less than 0.001). We conclude that coronary revascularization exhibits an immediate beneficial effect on chronically underperfused myocardium having severely depressed baseline function. However, in normal and moderately hypokinetic areas, the depressant effects of global ischemia and reperfusion prevail in the immediate postbypass period, leading to a global depression of cardiac function.

Angina Pectoris↗
PubMed1991

Immediate effects of mammary artery revascularization versus saphenous vein on global and regional myocardial function: an intraoperative echocardiographic assessment.

The immediate effect of coronary artery bypass surgery on global and regional myocardial function using the internal mammary artery (IMA) versus saphenous vein (SV) was studied intraoperatively using transesophageal echocardiography (TEE). Thirty-two patients received an IMA and 10 patients only SV. Transesophageal echocardiography was recorded before thoracotomy, 5 minutes after the end of cardiopulmonary bypass (CPB) and after chest closure. Global and regional left ventricular function were expressed as a percent of the short axis area change (%SAAC) and a percent of the fractional area change (%FAC), respectively. Segments were classified according to their baseline function as normal, %FAC greater than 40%, or dysfunctional, %FAC less than 40%. Only normal segments were considered in this study. No significant change in %SAAC in either group was observed in this study. Internal mammary artery revascularized segments showed a significant decrease in %FAC from 57 +/- 1 before thoractomy to 53 +/- 2 5 minutes after CPB, whereas SV segments showed a significant improvement in %FAC from 56 +/- 1 to 61 +/- 1. Applying strict criteria derived from intraobserver and cycle-to-cycle variability, 17% of IMA segments had deteriorated by more than 36% whereas only 4% of SV segments showed such deterioration. Conversely, 17% of SV segments showed an increase in %FAC by more than 36% and only 3% of IMA segments improved similarily. The observed changes were of short duration and had largely resolved by chest closure.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

A single myocardial stretch or decreased systolic fiber shortening stimulates the expression of heat shock protein 70 in the isolated, erythrocyte-perfused rabbit heart.

The regulation of heat shock protein 70 (HSP 70) expression was examined in the isolated, red blood cell-perfused rabbit heart by Northern and Western blot analysis. In the isovolumic (balloon in left ventricle), isolated perfused heart, HSP 70 mRNA was increased threefold after 30 min and sevenfold at 2 and 4 h compared to normal, nonperfused hearts. To further elucidate the etiology of the increase in HSP 70 mRNA, the effects of decreased systolic shortening (isovolumic heart) and of a single ventricular stretch were examined. Perfusion without the application of a stretch or the presence of a balloon resulted in no increase in HSP 70 mRNA; while a single stretch resulted in a threefold increase in HSP 70 mRNA. These changes were accompanied by an increase in HSP 70 protein by Western blot analysis. To elucidate the signalling mechanism mediating the increase in HSP 70, hearts were perfused with H7, a protein kinase C inhibitor. H7 did not prevent the induction of HSP 70. These results indicate that initiation of expression of myocardial HSP 70 can be stimulated by a single myocardial stretch or by prevention of systolic shortening. These mechanisms may contribute to the rapid expression of HSP 70 after coronary occlusion when dyskinesis, reduced systolic shortening, and increased diastolic segment length all occur.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

Stimulus-secretion coupling of arginine-induced insulin release. Effect of 2-aminoisobutyric acid upon ornithine decarboxylase activity and insulin secretion.

Recent studies have revealed that, in rat pancreatic islets, exogenous L-arginine or L-ornithine are converted to putrescine, spermidine and spermine. The possible role of polyamine generation in the secretory response of the B-cell to the cationic amino acids was investigated in islets either preincubated for 90 min with 2-aminoisobutyric acid (AIB; 10 mM) or removed from rats injected intraperitoneally with AIB (2.4 mmol) 210 min before sacrifice. Although AIB failed to exert any direct effect upon the secretory response of the islets to either L-arginine or L-ornithine, preincubation of the islets with AIB increased both the activity of ornithine decarboxylase and, to a modest extent, the insulinotropic action of L-arginine and L-ornithine. Likewise, after treatment with AIB in vivo, the activity of ornithine decarboxylase increased tenfold or more in kidney, liver, pancreas, parotid gland and islet homogenates. The secretory response to D-glucose was little affected in islets removed from AIB-treated rats, but the insulinotropic action of L-arginine and L-ornithine were slightly increased. These findings suggest that the de novo generation of polyamines only plays a restricted role in the secretory response of islet cells to L-arginine and L-ornithine.

Amino Acids↗