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Biomedical subjects

B F Buxton

Publications and source records attributed to B F Buxton.

At least 19 recordsLinked to original sources

Induction of Ca2+ signaling and possible exocytosis in endothelial cells by a stable leukocyte-derived factor.

Previous studies have shown that polymorphonuclear leukocytes (PMNs) release a stable factor that inhibits endothelium-dependent relaxation. In the present studies, the effects of the factor on Ca2+ signaling and on ultrastructure of endothelial cells were investigated. In the cultured endothelial cells, the PMN-derived factor induced an increase in [Ca2+]i in a pattern of oscillations. The frequency of the Ca2+ oscillations was less than 3 spikes/10 minutes. Removal of extracellular Ca2+ by perfusion with Ca(2+)-free Krebs' solution abolished the spikes. The results of electron microscopy showed that this factor induced an increase in vesicle formation on the luminal surface of the rat aortic endothelium. The increased vesicle formation may represent exocytosis. The structure of the smooth muscle cells was not changed. In conclusion, the PMN-derived factor induces a Ca2+ influx and In conclusion, the PMN-derived factor induces a Ca2+ influx and possible exocytosis, suggesting that the factor may have other biological functions besides the inhibition of the vascular relaxation.

Animals

Vascular responses to vasopressin antagonists in man and rat.

1. The effects of the non-peptide arginine vasopressin V1 receptor antagonist (OPC-21268) and the non-peptide V2 receptor antagonist (OPC-31260) on vasopressin-induced contraction of human internal mammary arteries and rat mesenteric resistance arteries were investigated. 2. In human internal mammary arteries, the non-peptide V1 receptor antagonist, OPC-21268, failed to antagonize vasopressin-induced contraction at low concentrations and potentiated the contraction at higher concentrations (300 nmol/l, P < 0.05). A peptide selective V1 receptor antagonist ([d(CH2)5, sarcosine7]arginine vasopressin) potently inhibited the vasopressin-induced contraction, indicating the presence of functionally constrictor V1 receptors in human internal mammary arteries. Both peptide (desGly-NH29[d(CH2)5, D-Ile2, Ile4]arginine vasopressin) and non-peptide 'selective' V2 receptor antagonists (OPC-31260, 3 mumol/l) significantly antagonized vasopressin-induced contraction (P < 0.01), indicating partial V1 receptor antagonist activity. 3. The vasopressin-induced contraction in human internal mammary arteries was reversed by high concentrations of the non-peptide V2 receptor antagonist, OPC-31260, but not by the non-peptide V1 receptor antagonist, OPC-21268. 4. The effects of OPC-21268 and OPC-31260 were specific to vascular vasopressin receptors as neither compound influenced endothelin- or noradrenaline-induced contraction in human internal mammary arteries. 5. In rat mesenteric resistance arteries, both OPC-21268 (10 nmol/l) and OPC-31260 (1 mumol/l) antagonized vasopressin-induced contraction (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Tolerance to glyceryl trinitrate in isolated human internal mammary arteries.

The purpose of this study was to examine the vascular reactivity of segments of internal mammary artery removed from patients undergoing coronary artery bypass operations. Responses to relaxant and contractile agents were compared in arteries removed from patients who had or had not been treated with glyceryl trinitrate after admission to the hospital until operation. Segments of mammary artery were removed from 13 patients who underwent coronary artery bypass grafting. Endothelium-containing rings of artery, 3 to 5 mm long, were suspended in physiologic saline solution in 20 ml organ baths. Responses to the endothelium-dependent relaxant acetylcholine and the endothelium-independent relaxants glyceryl trinitrate and sodium nitroprusside were compared. In addition, contractile responses to phenylephrine and 9,11-dideoxy-9 alpha,11 alpha-methanoepoxy prostaglandin F2 alpha (U46619) were examined. Glyceryl trinitrate-induced relaxation was significantly impaired in mammary artery segments from patients treated with that nitrate before operation; the responses to acetylcholine and sodium nitroprusside were not affected. Previous treatment with glyceryl trinitrate also reduced the contractile responses to both phenylephrine and U46619. These studies indicate that treatment of patients with glyceryl trinitrate before operation induces significant tolerance to this agent in the mammary artery; however, there was no evidence of cross tolerance to sodium nitroprusside or the endothelium-dependent vasodilator acetylcholine. Glyceryl trinitrate may therefore not always be effective in dilating mammary artery grafts and sodium nitroprusside may be a more effective dilator of the internal mammary artery in patients who have been treated with glyceryl trinitrate before operation.

Acetylcholine

Haematological effects of reinfused mediastinal blood after cardiac surgery.

OBJECTIVE: To explore the risk of inducing a coagulation defect in cardiac surgery patients by the reinfusion of mediastinal blood. DESIGN: Ten patients who underwent coronary artery surgery were prospectively studied for the haematological effects of reinfusion of blood drained from the chest drain tubes after the operation by a Sorenson autologous transfusion system. SETTING: Surgery was performed at a private hospital and patient selection was made at the time of reinfusion. PATIENTS: Nine patients had primary coronary artery surgery and one had a reoperation. MAIN OUTCOME MEASURES: Blood samples were taken from the patients before reinfusion, one hour after reinfusion, and 24 hours later as well as from the collected blood. Measurements were made of the haemoglobin content, white cell and platelet counts, fibrinogen and fibrinogen degradation products, D-dimer, antithrombin III and plasma haemoglobin content. Estimations were also made of the prothrombin time, the thrombin clotting time and the activated partial thromboplastin time. The hypothesis to be tested by this study was that the reinfusion of mediastinal blood after the operation did not cause any significant disturbance of the patient's blood clotting profile. RESULTS: An average of 535 mL (range, 400-950 mL) was reinfused after a period of three hours drainage (range, 45 minutes to 5 hours). While the initial patient samples contained a raised plasma haemoglobin level (0.19 g/L) significantly related to the cardiopulmonary bypass time (P less than 0.001), these were free of fibrinogen degradation products except for a sample from one patient who had a reoperation. The blood drained by the Sorenson system was lower in haemoglobin content (7.7 g/dL), and had a significant content of fibrinogen degradation products (147 mg/L) and D-dimer (6.4 mg/L) together with reduced clotting factors when compared with the patients' blood. After reinfusion, the patient sample showed evidence of altered coagulation with mildly increased clotting times (activated partial thromboplastin time 57 s, thrombin clotting time 123 s), the extent of which was related to the volume reinfused (P less than 0.001), but 24 hours later, these effects had all disappeared. All samples were sterile in aerobic and anaerobic culture media. CONCLUSION: We conclude that the Sorenson system of retrieval of mediastinal blood after cardiac surgery provides a safe and simple method of blood conservation provided that the volume of reinfusion is not excessive.

Blood Coagulation

Coexistence and localization of beta 1- and beta 2-adrenoceptors in the human heart.

Quantitative autoradiography was used to determine the location and density of beta 1- and beta 2-adrenoceptors in the right atrium (RA), left ventricular free wall (LVFW), right ventricular free wall (RVFW), interventricular septum (IVS), right atrium from an area near the atrioventricular node (RAAV) and cardiac nerves (N) taken from a patient with end-stage cardiac failure. The densities of beta-adrenoceptors detected by the non-selective beta-adrenoceptor antagonist radioligand (-)-[125I] cyanopindolol (50pM) were 4.93 (N), 10.6 (RVFW), 12.2 (RA), 12.4 (IVS), 15.8 (LVFW) and 18.7 fmol (mg protein)-1 (RAAV). The proportion of beta 2-adrenoceptors ranged from 19.5% (RAAV) to 95% (N). RA taken from patients with ischaemic heart disease had a higher density of beta-adrenoceptors (29.3 fmol (mg protein)-1). The results suggest that both beta 1- and beta 2-adrenoceptors are down-regulated in patients with end-stage cardiac failure. Positive inotropic responses were established to (-)-isoprenaline, RO363 (beta 1-selective), procaterol (beta 2-selective) and dopexamine in the absence or presence of the antagonist CGP 20712A (beta 1-selective) or ICI 118,551 (beta 2-selective) in electrically driven human right atrial appendage strips. RO363 and procaterol were nearly full agonists in this preparation and produced their responses through activation of beta 1- or beta 2-adrenoceptors, while dopexamine was a partial agonist which produced its inotropic responses through activation of both receptor subtypes. These studies demonstrate the presence and location of beta 1- and beta 2-adrenoceptors in the human heart.

Animals

Reactivity of human isolated internal mammary artery to constrictor and dilator agents. Implications for treatment of internal mammary artery spasm.

Perioperative spasm of the internal mammary artery (IMA) may occur after coronary artery bypass surgery. To establish the most appropriate dilator agent, we tested the reactivity of ring segments of human IMA in organ baths to various constrictor and dilator agents. We found that the thromboxane mimetic U46619 was the most potent IMA constrictor agent, followed by norepinephrine, serotonin, phenylephrine, and potassium chloride (K+). In K+- or U46619-precontracted IMA, glyceryl trinitrate and papaverine caused full relaxation. In K+-precontracted arteries, nifedipine, verapamil, and diltiazem caused full relaxation, but nifedipine was 15-fold more potent than the other calcium antagonists. In contrast, pretreatment of vessels with glyceryl trinitrate failed to alter subsequent contraction to U46619 or K+ while nifedipine pretreatment abolished subsequent contraction to K+ and reduced sensitivity of the IMA to U46619. We conclude that perioperative IMA spasm could be treated with the rapid-onset, nonspecific, vasodilator glyceryl trinitrate, but for prophylaxis of IMA spasm, calcium antagonists or specific receptor antagonists should be tested in the clinical setting.

Dose-Response Relationship, Drug

Blood-conservation techniques for coronary-artery bypass surgery at a private hospital.

The utilization of homologous blood and blood products was recorded in 100 consecutive patients who underwent primary coronary-artery bypass surgery. Nine patients underwent saphenous-vein grafts only, 55 patients underwent a single internal-mammary-artery graft that was supplemented by vein grafts and 36 patients underwent bilateral internal-mammary-artery grafts and vein grafts. All patients underwent normovolaemic haemodilution, and autologous blood was collected before bypass surgery. Residual blood was collected from the cardiopulmonary bypass machine and was washed and concentrated in a cell processor, and blood also was scavenged postoperatively from the mediastinal drainage tubes as methods to conserve blood. The mean (+/- SD) utilization of homologous blood was 1.3 +/- 1.5 units with 0.2 +/- 0.7 units of fresh-frozen plasma being used, and 0.8 +/- 2.1 units of platelets being used. The utilization of homologous blood was not different among the three different methods of coronary-artery bypass surgery, but patients who underwent bilateral internal-mammary-artery grafts suffered a greater postoperative loss of blood than did those patients who underwent saphenous-vein grafts or single internal-mammary-artery grafts. A comparison of patients who were taking aspirin or a non-steroidal anti-inflammatory drug preoperatively with those patients who were not showed no difference in the utilization of homologous blood but a statistically-significant difference was found in the loss of blood postoperatively.

Adult

Autoradiographic localization and function of beta-adrenoceptors on the human internal mammary artery and saphenous vein.

1. Receptor autoradiography with (-)-[125I]-cyanopindolol (CYP) was used to study the distribution of beta 1- and beta 2-adrenoceptor subtypes in the human internal mammary artery and saphenous vein. 2. Images from X-ray film and nuclear emulsion coated coverslips, exposed to [125I]-CYP labelled sections, showed a high density of beta 2-adrenoceptors localized to the endothelium of the internal mammary artery and fewer beta 2-adrenoceptors on the smooth muscle. 3. The function of beta-adrenoceptors in ring preparations of the internal mammary artery was investigated in organ bath studies. (-)-Isoprenaline produced concentration-dependent relaxation of phenylephrine contracted rings. The potency and maximal effects of (-)-isoprenaline were not influenced by the presence of the endothelium. 4. Images of [125I]-CYP binding to the saphenous vein, from X-ray film and nuclear emulsion coated coverslips, showed localization of beta 2-adrenoceptors to the outer smooth muscle and not to the endothelium. 5. Relaxation of mammary artery and saphenous vein to (-)-isoprenaline is mediated via beta 2-adrenoceptors located on the smooth muscle. Endothelial beta 2-adrenoceptors, although present on the internal mammary artery, mediate other functions.

Aged

Characterization and autoradiographic localization of beta-adrenoceptor subtypes in human cardiac tissues.

1 Receptor autoradiography using (-)-[125I]-cyanopindolol (CYP) was used to study the distribution of beta-adrenoceptor subtypes in human right atrial appendage, left atrial free wall, left ventricular papillary muscle and pericardium. 2 The binding of (-)-[125I]-CYP to slide-mounted tissue sections of human right atrial appendage was time-dependent (K1 = 4.11 +/- 1.01 X 10(8) M-1 min-1, K-1 = 1.47 +/- 0.25 X 10(-3) min-1, n = 3), saturable (42.02 +/- 2.96 pM, n = 4) and stereoselective with respect to the optical isomers of propranolol (pKD (-):8.97 +/- 0.02, (+):6.88 +/- 0.06, n = 3). 3 The proportions of beta-adrenoceptor subtypes were determined in slide-mounted tissue sections using the antagonists CGP 20712A (beta 1-selective) and ICI 118,551 (beta 2-selective). In right atrial appendage and left ventricular papillary muscle 40% (34-45%) of the beta-adrenoceptors were of the beta 2-subtype. 4 Images from X-ray film and nuclear emulsion coated coverslips exposed to (-)-[125I]-CYP-labelled sections showed an even distribution of beta-adrenoceptor subtypes over the myocardium of the right atrial appendage, left ventricular papillary muscle and left atrial free wall. Sections of pericardium exhibited predominantly beta 2-adrenoceptors. beta 2-Adrenoceptors were localized to the intimal surface of coronary arteries. 5 The selective beta 1-adrenoceptor agonist RO363 and beta 2-selective agonist procaterol produced concentration-dependent inotropic responses in right atrial appendage strips. Responses to RO363 were antagonized by CGP 20712A (pKB = 9.29) suggesting an interaction with beta 1-adrenoceptors. Responses to procaterol were antagonized by ICI 118,551 (pKB = 9.06) suggesting an interaction at beta 2-adrenoceptors. 6 The finding that a significant proportion of human myocardial adrenoceptors are of the beta 2-subtype has important clinical implications for the involvement of these receptors in the control of heart rate and force, and the autoradiographic evidence suggests other roles in the coronary vasculature and pericardium.

Adolescent

Aortoduodenal fistula.

A primary aortoduodenal fistula is usually associated with an atherosclerotic aortic aneurysm, and a secondary fistula with a leaking anastomotic aortic suture line. Two examples of each are reported. The typical features of a primary fistula are haematemesis or melaena, pain, and a pulsatile abdominal mass; the features of a secondary fistula are haematemesis and melaena with a past history of aortic resection. The initial haemorrhage is rarely fatal: a lag period allows urgent laparotomy. The fistula is diagnosed by dissection of the fourth part of the duodenum from the aorta. The treatment is closure of the duodenum, and resection of an aneurysm if present. Reconstruction is by a graft anastomosed to the aorta proximal to the fistula, if the area is clean, or by an extra anatomical bypass, if the area is heavily contaminated.

Aged

Ruptured abdominal aortic aneurysms presenting to a general hospital.

Fifty-six patients with a ruptured abdominal aortic aneurysm presented to an acute general hospital over six years from 1968 to 1973. Twelve patients died before operation, while 19 of 44 patients (43%) survived replacement of the aneurysm with a Dacron graft. Patients aged under 70 years and not shocked on admission to hospital had the best chance of survival. It is suggested that survival rates can be significantly raised only by a decrease in the time between the onset of symptoms and an operation. A correct diagnosis may be made more often if it is remembered that the classical clinical triad of pain, shock and an abdominal mass is seen is less than half of the cases presenting to hospital.

Age Factors

Secretin and cholecystokin-pancreozymin in combination in the inhibition of gastric acid secretion.

Both secretin, and the single substance which possesses both cholecystokinin and pancreozymin activity, have been shown to inhibit gastric acid secretory responses. Since potentiation may occur between pairs of stimulants of gastric secretion, the effects of combining secretin and cholecystokinin/pancreozymin have been studied in Heidenhain pouches stimulated by continuous intravenous pentagastrin. Evidence suggesting potentiation between these two inhibitor agents is presented.

Animals