Biomedical subjects

P Dougan

Publications and source records attributed to P Dougan.

At least 19 recordsLinked to original sources

PubMed1995

Effects of the prostacyclin analogue iloprost on patency in small arteries and veins: an experimental study in the rabbit.

Arteriotomy/intimectomy and venotomy/intimectomy were performed in the ears of 43 rabbits. Twenty were treated with iloprost given as intravenous doses of 10 micrograms/kg body weight (bw) administered shortly before reperfusion followed by hourly infusions (3 micrograms/kg b w) until 12 hrs after reperfusion. At reperfusion venous and arterial bleeding times were noted. Patency was determined at 15-min intervals until 2 hrs after reperfusion and at 1 and 2 weeks postoperatively. As controls, 23 rabbits were given a single infusion of saline. Compared to controls, iloprost significantly prolonged arterial and venous bleeding times and significantly improved patency 2 hrs after reperfusion. One and two weeks later, however, virtually all vessels were occluded. Administered in this fashion, iloprost does not improve long-term patency in highly traumatized small veins and arteries.

Animals↗

PubMed1995

The effect of dextran 40 on patency following severe trauma in small arteries and veins.

Arteriotomy/intimectomy and venotomy/intimectomy were performed in the rabbit ear. Low molecular-weight dextran (dextran 40) was infused 2 h before reperfusion and on postoperative days 1, 3 and 5 using a standard clinical protocol. Bleeding-times at reperfusion were recorded and patencies determined at intervals up to 2 weeks. Rabbits given single preoperative bolus doses of saline were used as controls. Dextran significantly prolonged bleeding-times in arteries and significantly improved early patency in both types of vessel, but the enhancements disappear by one week. Dextran 40 infusion thus has little effect on long-term patency.

Animals↗

PubMed1992

Acute thrombogenicity of collagen coating of dacron grafts: an experimental study in sheep.

The early stages of platelet accumulation in two types of sealed interposition Dacron grafts implanted in the carotid arteries of sheep have been studied. One type was externally coated with collagen (Haemaguard) while the other experimental conduit had an additional inner lining of the same substance. 32P-labelled platelets were used to assess platelet accumulation and corrections for wall absorption were calculated. The activities in both types of grafts were highest proximally and decreased towards the distal anastomosis. The increases in the doubly-sealed grafts were larger than in those that had been single sealed, presumably reflecting activation of platelets in contact with collagen at the graft-wall and bloodstream interface. In addition, a significantly larger amount of thrombus was formed in the doubly-sealed grafts 4 h after reperfusion. It is reasonable to assume that increased acute thrombogenicity due to direct collagen-blood contact on graft surfaces is unfavourable to long term patency.

Animals↗

PubMed1992

Collagen and gelatin-impregnated vascular grafts--is their thrombogenicity enhanced? An experimental study.

The early thrombogenicity of dacron vascular grafts with and without impregnation with collagen (n = 7) or gelatin (n = 7) was evaluated in a sheep carotid artery interposition model. Autologous platelets were labelled with 32P and reinjected. Flow was reduced to 25 ml/min to mimic a situation with poor run-off and the graft thrombogenicity was studied for 4 hours. The results showed no difference as regards patency, thrombus-free surface, or uptake of 32P-labelled platelets between collagen- or gelatin-impregnated grafts and their parent dacron grafts. Thus, no difference in early graft thrombogenicity could be documented.

Animals↗

PubMed1992

Prevention of microvascular thrombosis with low-dose tissue plasminogen activator.

In a blind, randomized study, two groups, each of seven rabbits, were treated with either a very low dose of human melanoma cell line-derived tissue-type plasminogen activator (t-PA) or isotonic saline. t-PA (0.067 mg/kg of body weight) was administered intraaortically, 20 percent being given as a 30-second "bolus" infusion just prior to the reperfusion of intimectomized central ear arteries and the rest as a continuous infusion during the next 2 hours. Arteriotomic bleeding times, accumulations of 32P-labeled platelets, patency, and sizes of thrombus deposits 2 hours after reperfusion were recorded. To confirm the presence of tissue plasminogen activator in plasma, fibrin-plate lysis assays of arterial plasma were performed immediately before and 1/2 hour and 2 hours after starting drug infusion. Arteriotomic bleeding times were similar in both groups. Transient "oozing" from wound edges occurred in 40 percent of rabbits treated with tissue plasminogen activator. Patency was significantly increased and thrombus deposits were smaller in the tissue plasminogen activator group. Plasma from animals treated with tissue plasminogen activator caused massive lysis of fibrin plates, whereas plasma from control animals caused little or no lysis. Platelet accumulations were very similar in both groups, indicating that occlusive thrombi mainly consisted of other elements than platelets (e.g., fibrin and red cells). Scanning electron microscopy showed normally adhering and aggregating platelets in both groups. This study shows that mild fibrinolytic stimulation with tissue plasminogen activator significantly improves patency in severely traumatized small-caliber arteries and indicates that such treatment may be one approach to prevent thrombosis at microvascular anastomotic sites.

Animals↗

PubMed1991

Importance of fibrinolysis in limiting thrombus formation following severe microarterial trauma: an experimental study in the rabbit.

In a blind randomized study, two groups of six rabbits were treated with either the fibrinolytic inhibitor tranexamic acid, 14 mg/kg bw, or isotonic saline solution (control group) given intraaortically as single bolus injections 5 min prior to arteriotomy and intimectomy of central ear arteries. Arteriotomic bleeding times, accumulations of 32P-labeled platelets, patency, and sizes of thrombus deposits 2 hr after reperfusion were recorded. Fixed vessels were observed by scanning electron microscopy. Bleeding times were similar in the two groups. The patency rate in the tranexamic acid group was 2/12, i.e., a significant reduction (P less than 0.05) from 7/12 in the control group. Thrombus deposits in occluded vessels contained large amounts of fibrin and red cells. Platelet accumulations in occluded vessels were significantly lower in the tranexamic acid group than in the control group, which indicates that the ratio of fibrin to platelets was increased in thrombi formed during antifibrinolytic treatment. This study has demonstrated the importance of normal fibrinolytic capacity in limiting thrombus formation following microarterial trauma. It is suggested that the use of antifibrinolytic agents in microvascular surgery should be restricted.

Animals↗

PubMed1991

Studies of the antithrombotic effects of dextran 40 following microarterial trauma.

The effects of dextran 40 on platelet function and thrombus formation have been studied in vivo in arteries of the rabbit ear. Intra-aortic infusions of 32P-labelled platelets were followed by infusions of 1.7 g dextran 40 in 17 ml saline/kg b w. Treated and untreated groups were studied using as trauma either end-to-end anastomosis or arteriotomy (7 mm)/intimectomy (5 mm). After restoring blood flow, bleeding times at the sites of anastomosis and arteriotomy/intimectomy were recorded. Accumulations of labelled platelets were followed in vivo for 2 hours, after which patencies were determined and amounts of red thrombotic material evaluated. In a separate series of measurements, haematocrit levels after dextran infusion were studied. Nearly all vessels in the end-to-end anastomosis groups were patent. In the arteriotomy/intimectomy groups, there was a significant increase in patency following dextran infusion. Dextran infusion did not alter platelet accumulation following end-to-end anastomosis, but following arteriotomy/intimectomy median values were somewhat reduced. Its antithrombotic effects must therefore arise mainly at stages of thrombus formation subsequent to platelet deposition.

Anastomosis, Surgical↗

PubMed1991

Adverse effects of topical prostacyclin application in microvascular surgery: an experimental study.

The efficacy of topical prostacyclin as an antithrombotic agent was tested in a model of microvascular trauma. Preliminary measurements were made to determine a suitable dosage. Twenty-seven central arteries of rabbit ears were then prepared and 32P-labelled platelets infused intraaortically. Arteriotomy (7 mm) was followed by intimectomy (5 mm). Fifteen vessels in a control group were irrigated with Ringer's lactate and 12 vessels in an experimental group were treated with prostacyclin (10 ng/ml) in normal saline. Bleeding times at the sites of arteriotomy intimectomy, in vivo accumulations of isotope-labelled platelets, amounts of red thrombotic material, and patency were recorded. Patency was lower following prostacyclin treatment (1/12 as against 5/15) but not significantly so, and there were no statistically significant differences in other parameters. Prostacyclin treatment decreased vessel wall tone, interfering with blood-flow and promoting thrombus formation.

Administration, Topical↗

PubMed1991

Effect of low and ultra low oral doses of acetylsalicylic acid in microvascular surgery. An experimental study in the rabbit.

About 10 h after administering acetylsalicylic acid (ASA) orally in doses of 4 mg and 20 micrograms/kg b.w., the central arteries of rabbit ears were subjected to severe vascular trauma (arteriotomy/intimectomy). Bleeding times from the trauma regions at reperfusion were measured and the activities from accumulating 32P-labelled homologous platelets recorded until 2 h after reperfusion when patencies were determined. In other studies, the effects of ASA on ex vivo platelet aggregation (aggregometry), thromboxane production, euglobulin clot lysis time and bleeding time following arterial puncture were investigated. Relative to controls, the following parameters were changed: patency was increased, as were the bleeding times following arterial puncture and thromboxane production was reduced. The median values of platelet accumulation were lower, but the changes were not statistically significant. Aggregometry showed decreased rates of platelet aggregability following treatment with ASA 4 mg/kg.

Administration, Oral↗

PubMed1990

Time of low-dose acetylsalicylic acid administration influences in vivo platelet function and thrombus formation following arteriotomy and intimectomy; an experimental study in small arteries of rabbits.

To investigate if low-dose acetylsalicylic acid (ASA), 4 mg/kg b.w., infused peroperatively or 10 hours preoperatively has antithrombotic effects, the central arteries of rabbit ears were prepared and 32P-labeled platelets injected. Arteriotomy and intimectomy were performed and blood flow was restored. Bleeding times at the sites of arteriotomy/intimectomy, in vivo accumulations of isotope-labeled platelets, amounts of red thrombotic material, and patency were recorded. Bleeding times following arterial puncture and the effect of ASA on thromboxane production were studied separately. Ten hours after ASA administration, bleeding times were shortened at the sites of arteriotomy/intimectomy but were prolonged following arterial puncture. Platelet accumulations were lower in patent vessels in this group than in an untreated control group. Peroperative ASA treatment increased but treatment 10 hours prior to blood flow restoration did not significantly affect the number of occlusions. Thromboxane production in ASA-treated rabbits is largely inhibited even 14 hours after administration.

Animals↗

PubMed1990

Does dextran 40 reduce early graft thrombogenicity? An experimental investigation on patency and platelet deposition on prosthetic graft materials in sheep.

The mechanism by which dextran 40 reduces early graft thrombogenicity has not been fully elucidated. Dextran improves haemaodynamics, reduces platelet aggregation, alters fibrin formation and enhances thrombus lysis. In this experimental investigation on sheep using a low flow model, the thrombogenicity of various grafts was studied when either a dextran or saline infusion was given. Bilateral carotid interposition grafts with expanded polytetrafluorethylene (ePTFE) on one side and dacron on the other (random allocation) were inserted in 12 sheep. The sheep were randomly divided into two groups, one given a dextran infusion and the other saline. A tendency for improved graft patency was seen in the dextran 40 treated animals (P less than 0.05 at 3 h). However, platelet accumulation did not differ markedly between the dextran 40 and saline treated groups. On the other hand there was a clear reduction of platelet accumulation on ePTFE grafts compared to dacron grafts (P less than 0.01). A large part of the radioactivity measured from the dacron graft was located within the graft wall. Further studies to clarify the mechanism of action of dextran are needed.

Animals↗

PubMed1990

Hydroxyethyl starch increases patency and reduces thrombus formation following arteriotomy/intimectomy in small arteries: an experimental study in the rabbit.

Twenty-four arteries of rabbit ears, divided into two groups of 12 vessels each, were prepared and 32P-labelled platelets were infused. Arteriotomy/intimectomy was performed after 1 hr and in vivo platelet accumulation recorded for 2 hr. Group A comprised untreated control animals and group B was treated with 1 g hydroxyethyl starch (HES), MW 450,000 in 17 ml saline/kg b.w. (Plasma-steril). Vessel bleeding-times were normal, patency was improved, and intraluminal thrombotic material was reduced after HES treatment. Initial in vivo platelet accumulation was rapid and reached similar levels in both groups. However, the platelet accumulation curves decreased more frequently following HES than in the control group. HES does not prevent platelet accumulation at trauma sites, but reduces the sizes of the thrombi formed and may enhance disaggregation/fibrinolysis.

Animals↗

PubMed1990

Washout of vessels with heparin does not improve patency following severe microarterial trauma: an experimental study.

The antithrombotic effect of heparin used as a wash-out solution in small arteries has been evaluated following severe vessel trauma (arteriotomy/intimectomy). Twenty-three central arteries of rabbit ears were prepared and platelets labeled with phosphorus-32 injected intraaortically. The arteries were positioned in double vascular clamps and opened by arteriotomy, and intimectomy was performed. After reestablishing blood flow, arteriotomic bleeding times, platelet accumulation in vivo, patency, and the amounts of intraluminal red thrombotic material were recorded. The rabbits were divided into two groups. In group A (12 vessels) the vessel interior was flushed with 2 ml of saline or Ringer's lactate solution. Group B (11 vessels) was similar except that the vessels were flushed with 2 ml of heparin, 100 IU/ml, in Ringer's lactate solution. In the control group (A) the bleeding time was 5 +/- 2 min, while in group B bleeding was so profuse that extra sutures had to be used in 6 of the vessels. Although significantly fewer platelets accumulated in heparin-treated animals, the patency frequencies and amounts of thrombotic material observed in both groups were similar. The final volume of thrombus formed is thus not always proportional to the degree of platelet accumulation. Washout of small traumatized arteries with heparin is thus not beneficial.

Animals↗

PubMed1990

Low dose ASA (4 mg/kg) peroperatively does not prevent in vivo platelet accumulation at microarterial anastomotic sites. An experimental study in the rabbit.

Twenty microarterial end-to-end anastomoses were performed on the central arteries of the ears in 12 rabbits divided into two groups: Group A (10 anastomoses) served as control and Group B (10 anastomoses) was treated with 4 mg ASA per kg b.w. given as a single intraaortical dose 5 min prior to infusion of 32P-labelled platelets. Two hours later blood-flow was reestablished after end-to-end anastomoses. Anastomotic bleeding-times, qualitative and quantitative differences in platelet accumulation and patency were registered. In addition, platelet aggregability and thromboxane production were studied in 3 rabbits. The bleeding-times (median and quartiles) in group A were 3(+0)-2 min and in group B 3(+2)-0 min. In vivo accumulation of 32P-labelled platelets was somewhat increased initially (p less than 0.05) in the ASA group. Poor patency was registered in two vessels, one in each group, all other vessels having good patency. Aspirin peroperatively in low doses (4 mg/kg) did not markedly affect bleeding-times or patency rates in microarterial anastomoses, but platelet accumulation in vivo was initially increased. The radioactivity values decreased with time in all aspirin cases but only in 50% of the control group vessels, suggesting efficient platelet disaggregation/fibrinolysis. This might favour the view that PGI2 production in the endothelium recovers more rapidly than the pro-aggregatory mechanisms affected by ASA. ASA-treatment led to almost complete inhibition of thromboxane production for at least four hours, but, despite this, a moderate decrease in platelet aggregability occurred only when collagen was used as stimulant.

Anastomosis, Surgical↗

PubMed1988

A comparison of the behaviour of autologous and homologous platelets in microporous polyurethane grafts. An experimental study in sheep.

In experimental studies in sheep the behaviour of autologous and homologous platelets in microporous polyurethane grafts was compared at a flow rate of 25 ml/min. The grafts were interposed to replace segments of resected carotid arteries. The deposition of 32P-labelled platelets on the graft wall was recorded, as were graft patency, thrombus weight and thrombus-free surface. Compared to autologous platelets, homologous platelets accumulated over longer periods of time and in greater numbers, leading to deposition of larger amounts of thrombus material and reduced patency.

Animals↗

PubMed1987

Acute thrombogenicity of a compliant polyurethane urea graft compared with polytetrafluoroethylene: an experimental study in sheep.

The acute thrombogenicity of a new polyurethane urea graft has been compared with polytetrafluoroethylene (PTFE) grafts using labelled homologous platelets in the carotid arteries of sheep in a low-flow model. There was no difference in patency. Thrombus weight and thrombus free surface were the same in both types of graft after 4 h. The accumulation of homologous 32P platelets was measured at the 2 anastomoses and at a midgraft position. At no point was there any statistically significant difference between the 2 grafts, but the activity was always somewhat higher in the polyurethane grafts. Although more compliant, in this study polyurethane urea grafts behaved much like PTFE ones.

Animals↗

PubMed1987

Effects of different graft preparation techniques on the acute thrombogenicity of autologous vein grafts. An experimental study in sheep.

The effects of different techniques of preparing autologous vein grafts on acute thrombogenicity have been studied in a sheep model. Storing grafts at room temperature or rinsing with different solutions seemed to be of minor importance, whereas distending them to a pressure of 400 mm Hg significantly reduced patency and increased platelet accumulation and thrombus formation.

Animals↗

PubMed1986

Effect of dextran 70 and saline on thrombus formation following arteriotomy and intimectomy in small arteries.

Twenty-four arteries of rabbit ears, divided into three groups of eight, were prepared and 32P-platelets injected. Arteriotomy (7 mm) and intimectomy (5 mm) were performed and in vivo platelet accumulation followed for 2 hours. Group A comprised untreated control animals, group B was treated with 17 ml saline/kg bw, and group C with 1 g dextran and 17 ml saline/kg bw (Macrodex). Significant differences in platelet accumulation were observed only between the control and Macrodex groups at 105 and 120 minutes. In the control and saline groups four of eight vessels showed poor or no patency. All Macrodex vessels showed good patency. Control and saline vessels had large amounts of red thrombotic material, except for three saline cases with small amounts. After Macrodex treatment five of eight vessels were apparently clean, while the other three showed only small amounts of red thrombotic material. Dextran seems not to influence platelet function but rather to inhibit fibrin stabilization and probably increases fibrinolysis. Vascular patency was only endangered by the formation of solid fibrin-containing red thrombi.

Animals↗