BACKGROUND: Non-heart-beating donors (NHBDs) have the potential to reduce the increasing numbers of patients on kidney and liver graft waiting lists. One problem observed with kidneys obtained from NHBDs is the endothelial injury seen on protocol core biopsies after implantation. We postulate that this is caused by a combination of warm ischemia, cold ischemia, and hypertonic citrate during in situ preservation (ISP) rather than hypothermic machine preservation. Our aim was to optimize ISP methods to preserve endothelial structure and function. METHODS: An animal model of ISP was used to compare the ability of eight different preservation solutions to protect mammalian vascular tissue exposed to a combination of warm and cold ischemia. Smooth muscle contractile function and endothelial dependent relaxation (nitric oxide production) were determined using an organ bath method. RESULTS: Bretchneider's HTK solution preserved the ability of endothelial tissue to relax vascular tissue in response to acetylcholine (91% relaxation vs. 17% saline control; ANOVA, P<0.001); in stark contrast, Marshall's solution performed no better than saline (15% relaxation vs. 17% saline control, P=NS). UW solution (80%) and a derivative lacking the starch colloid (70%) were comparable with HTK. Belzer-MPS (55%), Celsior (57%), and Perfadex (44%) showed a roughly equivalent level of endothelial preservation. Electron microscopy confirmed an anatomical loss of structure correlating with loss of function. CONCLUSIONS: ISP requires a large volume of fluid to be pumped at high flow rates. In this model, HTK retained a powerful ability to preserve endothelial structure and function during warm ischemia.

Adenosine↗

PubMed2004

Teaching anatomy without cadavers.

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Anatomy↗

PubMed2004

Combination antiplatelet therapy in patients with peripheral vascular bypass grafts.

Peripheral bypass graft occlusion occurs in approximately 25% of cases in the 5 years following surgery; hence, therapies directed at reducing the tendency toward thrombotic occlusion are of clinical importance. This trial was conducted to determine if the addition of clopidogrel to aspirin enhances antiplatelet therapy in patients with infrainguinal bypass grafts. A randomized placebo-controlled study was performed on 20 patients over 3 months following infrainguinal bypass surgery. In addition to their regular aspirin therapy, patients were randomized to receive either clopidogrel (group 1) or placebo (group 2) for 1 week. Platelet activation was measured ex vivo by platelet aggregometry and flow cytometry. In group 1, there was a significant reduction in spontaneous (SP), adenosine diphosphate (ADP), and arachidonic acid (AA)-induced platelet aggregation compared with group 2; SP -17% (CI -33, -0.2 p = 0.048), ADP -39%, (CI -56, -22 p = 0.001), AA -21% (CI -39, -4 p = 0.023). Flow cytometry demonstrated a significant reduction in ADP-induced platelet P-selectin expression and GPIIb/IIIa activation following treatment with clopidogrel but not with placebo. This study demonstrated that the addition of clopidogrel to aspirin reduces platelet activation measured by platelet aggregation and flow cytometry, supporting a long-term trial with clinical endpoints.

Adenosine Diphosphate↗

PubMed2004

Clopidogrel and vascular disease prevention.

In this editorial we consider some aspects of the use of clopidogrel in current clinical practice. Clopidogrel has replaced ticlopidine as an alternative to aspirin. Among the problems with the use of antiplatelet agents is aspirin intolerance. The options for these patients are discussed; these include using clopidogrel. Clopidogrel may be especially effective in patients with peripheral arterial disease. However, this impression requires confirmation in appropriately designed trials. We also consider the effect of antiplatelet agents on growth factor release by platelets and of clopidogrel on the inflammatory process. Clopidogrel is a useful, evidence-based, antiplatelet agent.

Clopidogrel↗

PubMed2004

Current management of Paget-Schroetter syndrome in the UK.

INTRODUCTION: Untreated symptomatic patients with Paget-Schroetter syndrome (PSS) can sustain chronic disability from venous obstruction, with arm swelling, pain and early exercise fatigue. This may result in significant loss of occupational productivity and quality of life. For this reason, active management is recommended in the majority of the recent literature. The objective of the this study was to assess current trends of management of PSS in the UK. METHODS: A 9-part questionnaire was sent to 90 ordinary members of the Vascular Surgical Society of Great Britain and Ireland (VSS-GBI). Names and addresses were selected by highlighting every fourth ordinary member from the UK, in the 2000 VSS-GBI handbook. Ordinary members of the VSS-GBI who were clearly radiologists were excluded. RESULTS: Of the 90 questionnaires sent, 60 were returned (66.67%). The majority of respondents used both duplex and venography (61%) as the major investigative tools though some employed duplex only (17%). Multimodality treatment (radiological and operative) was the favoured approach. Only 17% still favoured conservative management alone. Thrombolysis was the most common intervention (86.7%) usually followed by elective thoracic outlet decompression. Most favoured a delayed approach for surgery of 6-12 weeks. First rib resection was the most commonly performed operation (58%), usually by the transaxillary approach (55%). Most of the respondents were doubtful of the role of stenting in this condition and did not use it. CONCLUSIONS: There is no definite consensus on treatment of this condition in the UK. A majority tend to favour a multimodal approach. Thrombolysis is the most common form of treatment employed and first rib resection via the transaxillary approach remains the most popular surgical procedure. The lack of consensus of this potentially disabling condition highlights the need for randomised clinical trials to guide management.

Axillary Vein↗

PubMed2003

Effect of ibuprofen on cardioprotective effect of aspirin.

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Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2003

Preservation of vascular tissue under hypothermic conditions.

BACKGROUND: Preservation of vascular tissue plays a crucial role in the success of organ transplantation. We investigated and compared the performance of 4 preservation solutions at preserving vascular tissue over 24, 48, and 72 h under hypothermic conditions. MATERIALS AND METHODS: Rat aortic segments were stored in University of Wisconsin (UW), Modified University of Wisconsin (mUW), EuroCollins (EC), and Bretschneider Histidine-tryptophan-ketoglutarate (HTK) solutions at 4 degrees C for 24, 48, and 72 h. Functional assessment was performed by measuring smooth muscle cell contraction and endothelium-dependent relaxation after stimulation with phenylephrine and acetylcholine, respectively, in an organ bath. RESULTS: UW and EC solutions were superior to the other solutions for endothelial cell preservation and were not statistically different from each other at any time (P < 0.05). Smooth muscle cell (i.e., contractile) preservation was best achieved with UW solution for up to 72 h. HTK appeared to function well at 24 h, but at 48 and 72 h, there was a major decline in contractile response and relaxation. CONCLUSION: UW solution appears to be superior for the preservation of the functional integrity of vascular tissue stored under hypothermic conditions up to 72 h.

Animals↗

PubMed2003

Influence of platelet count and activity on thromboelastography parameters.

It has been suggested that thromboelastography TEG) can help in limiting or directing the appropriate use of blood products during surgery. However, the contribution of platelets to the TEG profile has not been studied in detail. Blood was taken from eight healthy subjects and eight patients with peripheral arterial disease (PAD). Immunomagnetic separation was achieved by the addition of Dynabeads labeled with a CD41 murine antibody (to the GPIIb/IIIa receptor) to achieve 90-100% depletion of platelets from blood. This was then titrated with whole blood to achieve platelet counts of approximately 0, 25 and 50% of the original count to compare with whole blood using TEG. Platelet function was also assessed by spontaneous platelet aggregometry (SPA) at baseline and at the 50% dilution. SPA, maximum amplitude (MA) and K time were significantly different in PAD patients compared to controls (P < 0.05). In both controls and PAD patients there was a strong linear correlation between Log10 [platelet count] and MA (r = 0.97 for controls, r = 0.89 for PAD) and K time (r = -0.86 for controls, r = -0.68 for PAD). Correlation between Log10 [platelet count] and R time was poor in both groups. The MA and K TEG parameters may be most useful for assessing platelet transfusion requirements.

Aged↗

PubMed2003

Value of thromboelastography in the assessment of platelet function.

Thromboelastography (TEG) is a useful measure of coagulation. Modified TEG (that is with the addition of a GP IIb/IIIa receptor antagonist) has been used to assess the contribution of the fibrinogen-platelet interaction to TEG parameters (in particular the maximum amplitude, MA). Modified TEG was compared with other investigations of platelet function to assess its sensitivity in both normal subjects and in patients with peripheral arterial disease (PAD), a condition associated with activated platelets. Blood was collected from eight healthy subjects and 12 PAD patients. Platelet function was measured by TEG, flow cytometry (using PAC-1, P-selectin, GP IIIa and GP Ib murine antibodies) and platelet aggregometry (spontaneous and ADP-induced) in the presence and absence of tirofiban (a GP IIb/IIIa receptor antagonist). TEG showed a statistically significant reduction in MA with tirofiban at 0.4 mg/L and an increase in k (kinetic time; which indicates how fast clot strength is increasing once clotting starts) at 0.2 and 0.4 mg/L of tirofiban in both healthy subjects and PAD patients. Flow cytometry showed a significant decrease in the PAC-1 binding index (at 0.2 mg/L). This finding was compatible with the significant reductions found in spontaneous and ADP-induced platelet aggregation. However, aggregometry and flow cytometry were more sensitive indicators of platelet inhibition than the TEG parameters. TEG does not provide a comprehensive or sensitive reflection of impaired platelet function. If TEG is used as an index of severely impaired platelet function, we recommend that the k parameter should be used as well as MA. TEG should be supplemented by other methods of platelet function assessment wherever possible.

Adenosine Diphosphate↗

PubMed2003

Current practice in the use of antiplatelet agents in the peri-operative period by UK vascular surgeons.

BACKGROUND: There currently appears to be no firm consensus with regards to the use of antiplatelet agents during the peri-operative period in vascular surgical practice. METHODS: A nine-part questionnaire relating to peri-operative antiplatelet use was sent to 137 ordinary members of the Vascular Surgical Society of Great Britain and Ireland (VSS-GBI). RESULTS: Of the 137 questionnaires sent, 90 were returned (66%). For patients undergoing infra-inguinal bypass, carotid endarterectomy and varicose vein surgery, over 90% of vascular surgeons continue antiplatelet agents peri-operatively; however, in the case of aortic aneurysm repair, this figure is lower (77%). Three of the respondents stated that they would stop clopidogrel, but not aspirin, prior to surgery because of concerns over increased operative bleeding. In patients starting routine heparin prophylaxis against thrombosis, most surgeons opted to continue antiplatelet therapy (82%), although in patients requiring therapeutic heparin treatment, opinions were almost equally split. Most vascular surgeons (93%) would to start an alternative antiplatelet agent if a patient was intolerant of aspirin for gastrointestinal reasons. CONCLUSIONS: Although the benefits of antiplatelet drugs in the long-term reduction of vascular events is established, evidence supporting their use in the peri-operative period is scarce. The general consensus of opinion from this survey suggests that most vascular surgeons do not stop antiplatelet drugs pre-operatively.

Aortic Aneurysm, Abdominal↗