Graduated Compression Stockings as an Adjunct to Low Dose Low Molecular Weight Heparin in Venous Thromboembolism Prevention in Surgery: A Multicentre Randomised Controlled Trial.

BACKGROUND: The evidence base upon which current global venous thromboembolism (VTE) prevention recommendations have been made is not optimal. The cost of purchasing and applying graduated compression stockings (GCS) in surgical patients is considerable and has been estimated at £63.1 million per year in England alone. OBJECTIVE: The aim was to determine whether low dose low molecular weight heparin (LMWH) alone is non-inferior to a combination of GCS and low dose LMWH for the prevention of VTE. METHODS: The randomised controlled Graduated compression as an Adjunct to Pharmacoprophylaxis in Surgery (GAPS) Trial (ISRCTN 13911492) will randomise adult elective surgical patients identified as being at moderate and high risk of VTE to receive either the current "standard" combined thromboprophylactic LMWH with GCS mechanical thromboprophylaxis, or thromboprophylactic LMWH pharmacoprophylaxis alone. To show non-inferiority (3.5% non-inferiority margin) for the primary endpoint of all VTE within 90 days, 2236 patients are required. Recruitment will be from seven UK centres. Secondary outcomes include quality of life, compliance with stockings and LMWH, overall mortality, and GCS or LMWH related complications (including bleeding). Recruitment commenced in April 2016 with the seven UK centres coming "on-line" in a staggered fashion. Recruitment will be over a total of 18 months. The GAPS trial is funded by the National Institute for Health Research Health Technology Assessment in the UK (14/140/61).

Risk Factors For Stroke, Myocardial Infarction, or Death Following Carotid Endarterectomy: Results From the International Carotid Stenting Study.

OBJECTIVES: Carotid endarterectomy (CEA) is standard treatment for symptomatic carotid artery stenosis but carries a risk of stroke, myocardial infarction (MI), or death. This study investigated risk factors for these procedural complications occurring within 30 days of endarterectomy in the International Carotid Stenting Study (ICSS). METHODS: Patients with recently symptomatic carotid stenosis >50% were randomly allocated to endarterectomy or stenting. Analysis is reported of patients in ICSS assigned to endarterectomy and limited to those in whom CEA was initiated. The occurrence of stroke, MI, or death within 30 days of the procedure was reported by investigators and adjudicated. Demographic and technical risk factors for these complications were analysed sequentially in a binomial regression analysis and subsequently in a multivariable model. RESULTS: Eight-hundred and twenty-one patients were included in the analysis. The risk of stroke, MI, or death within 30 days of CEA was 4.0%. The risk was higher in female patients (risk ratio [RR] 1.98, 95% CI 1.02-3.87, p = .05) and with increasing baseline diastolic blood pressure (dBP) (RR 1.30 per +10 mmHg, 95% CI 1.02-1.66, p = .04). Mean baseline dBP, obtained at the time of randomization in the trial, was 78 mmHg (SD 13 mmHg). In a multivariable model, only dBP remained a significant predictor. The risk was not related to the type of surgical reconstruction, anaesthetic technique, or perioperative medication regimen. Patients undergoing CEA stayed a median of 4 days before discharge, and 21.2% of events occurred on or after the day of discharge. CONCLUSIONS: Increasing diastolic blood pressure was the only independent risk factor for stroke, MI, or death following CEA. Cautious attention to blood pressure control following symptoms attributable to carotid stenosis could reduce the risks associated with subsequent CEA.

Systematic review of the efficacy of cilostazol, naftidrofuryl oxalate and pentoxifylline for the treatment of intermittent claudication.

BACKGROUND: A systematic review and network meta-analysis was undertaken to consider the evidence for the efficacy and tolerability of placebo, cilostazol, naftidrofuryl oxalate and pentoxifylline in patients with intermittent claudication due to peripheral arterial disease (PAD). METHODS: MEDLINE, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Conference Proceedings, BIOSIS, National Research Register and MetaRegister databases were searched. Eligible studies were randomized controlled trials (RCTs) and published systematic reviews of patients with intermittent claudication due to PAD and whose symptoms persisted despite a period of conservative management. Study selection was conducted by one reviewer with involvement from a clinician. Data were extracted by one reviewer with no blinding to authors or journal, and checked by a second reviewer. Outcome measures were maximum walking distance (MWD) and pain-free walking distance (PFWD). RESULTS: The review identified 1876 citations; 26 RCTs met the inclusion criteria for the systematic review. Eleven trials provided data relevant for the meta-analysis. Naftidrofuryl oxalate was ranked first for both MWD and PFWD (probability of 0·947 and 0·987, respectively, of being the best treatment) followed by cilostazol and pentoxifylline. For naftidrofuryl oxalate, cilostazol and pentoxifylline, MWD increased by 60 (95 per cent credible interval 20 to 114) per cent, 25 (11 to 40) per cent and 11 (-1 to 24) per cent respectively relative to placebo, and PFWD increased by 49, 13 and 9 per cent. CONCLUSION: Naftidrofuryl oxalate and cilostazol are both effective treatments for claudication; naftidrofuryl oxalate is likely to be the most effective, with minimal serious adverse events.

The management of venous thromboembolic diseases and the role of thrombophilia testing: summary of NICE Guideline CG144.

Venous thromboembolic disease (VTE) is a common presentation in acute medicine and ensuring fast, accurate diagnosis and appropriate management is important. Getting it right not only reduces mortality but can also reduce the long-term complications associated with the disease such as post-thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension.

Prevalence and predictors of persistent health status impairment in patients referred to a vascular clinic with intermittent claudication.

BACKGROUND: The goal of treatment for lower extremity peripheral artery disease is often to improve health status. Factors associated with failure to improve are unknown. METHODS: Health status was assessed with the Peripheral Artery Questionnaire (PAQ) at baseline and 2 years in 344 patients referred to vascular clinics. Improvement was defined as an increase of ≥5 points on the PAQ Summary Score. Multivariable logistic regression identified patient and treatment characteristics associated with impaired baseline health status, and predictors of no improvement (<5 points). RESULTS: Older age, bilateral symptoms, female sex and prior revascularization were associated with impaired baseline health status. At 2 years 36% reported unimproved health status. Factors associated with no improvement were older age (Odds Ratio 1.67/decade, CI 1.28, 2.19), better baseline health status (OR 1.40/10-points, CI 1.24, 1.59), beta blocker use (OR 2.53, CI 1.37, 4.68), prior stroke (OR 4.12, CI 1.33, 12.77) and bilateral claudication (OR 1.79, CI 1.07, 2.99). SUMMARY: Older patients, women, and those with bilateral symptoms or prior revascularization have worse health status at vascular referral. Over 1/3 of patients' health status did not improve over 2 years; older patients and those with bilateral or milder symptoms, prior stroke or using beta blockers were less likely to improve.

Clinical experience of a new NPWT system in diabetic foot ulcers and post-amputation wounds.

OBJECTIVE: The primary aim of this pilot observational study was to assess the reduction in wound depth and area achieved with a new negative pressure wound therapy (NPWT) system in diabetic patients with foot ulcers and post-amputation wounds. Secondary aims were to assess pain levels, extent of exudate removal, and ease of use of the system for both the patient and care giver. METHOD: Patients in both acute and home care settings were enrolled into this 4-week study. Dressings were changed three times per week. Wound area and depth, exudate removal and pain severity were evaluated at each dressing change. At the final visit, the investigators and patients were surveyed with respect to equipment and dressings used in the study. RESULTS: Sixteen patients were enrolled into the study. Data relating to 14 patients with a variety of post-amputation wounds were included in the intention-to-treat (ITT) analysis. The post-amputation wounds showed a general trend for a reduction in the median wound surface area between baseline (22.9cm2; range 0.5-55) and the final visit (15.3cm2; range 2.4-63.5). This equates to a median change (calculated from the percentage change in wound area for each patient individually) of -41% (range -82% to +15%). There was also a general trend in reduction in the median depth between baseline (17mm; range 0-35) to final visit (5mm; range 0-35). One patient presented with a foot ulcer that demonstrated a 50% reduction in depth from baseline to the final assessment. The device effectively managed wound exudate and most patients reported low pain levels during therapy. Ease of use of the system was rated very highly by investigators and patients. CONCLUSION: This pilot study indicates that the use of the new NPWT system can be expected to have a positive effect on the healing of post-amputation wounds and foot ulcers in patients with diabetes. The findings demonstrate that the system is easy to use, effectively controls exudate and minimises pain and inconvenience for patients being treated with NPWT. DECLARATION OF INTEREST: This study was sponsored by Mölnlycke Heath Care (Gothenburg, Sweden) and Medela AG (Baar, Switzerland). The authors have no other conflicts of interest that are directly relevant to the content of this manuscript.

Combined aspirin and cilostazol treatment is associated with reduced platelet aggregation and prevention of exercise-induced platelet activation.

BACKGROUND: Cilostazol has proven efficacy in increasing walking distance in claudicants, but it has not been demonstrated to be more effective than placebo in secondary cardiovascular prevention. The direct effect of exercise on platelet function remains less well defined. We have investigated the effect of combination treatment with aspirin and cilostazol on platelet activity in claudicants subjected to repeated treadmill exercise. METHODS: Nineteen claudicants completed a double-blind, randomised, controlled, cross-over trial. Each subject received a 2-week course of aspirin (75mg) and placebo and aspirin and cilostazol (100mg twice daily). Following each 2-week treatment period, patients participated in a standardised treadmill test (3.2kmh(-1), 10 degrees incline) walking to maximal claudication distance. The exercise was repeated thrice in total, and blood was sampled before and after exercise. Platelet activation was measured using free platelet counting aggregation, flow cytometry for surface markers of platelet activation and soluble P-selectin assay. RESULTS: Compared to aspirin and placebo, combination treatment with aspirin and cilostazol was associated with reduced arachidonic-acid-induced platelet aggregation (p<0.01, Wilcoxon signed-rank test). Aspirin and placebo treatment were associated with elevated P-selectin expression, platelet-monocyte aggregation and reduced CD42b expression (p<0.05, Wilcoxon signed-rank test) post-exercise. No difference was seen in spontaneous platelet aggregation whilst soluble P-selectin was reduced post-exercise with combination treatment with aspirin and cilostazol (p<0.05, Wilcoxon signed-rank test). CONCLUSIONS: Combination treatment with aspirin and cilostazol results in suppression of platelet activation and reduces the effect of exercise on platelets. The benefit seen may be a result of cilostazol enhancing the inhibitory effect of aspirin on the cyclo-oxygenase pathway.

Combined intermittent pneumatic leg compression and pharmacological prophylaxis for prevention of venous thrombo-embolism in high-risk patients.

BACKGROUND: It has been suggested that combined modalities (methods of treatment) are more effective than single modalities in preventing venous thrombo-embolism (defined as deep vein thrombosis and pulmonary embolism, or both) in high-risk patients. OBJECTIVES: To assess the efficacy of intermittent pneumatic leg compression combined with pharmacological prophylaxis versus single modalities in preventing venous thrombo-embolism in high-risk patients. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases (PVD) Group searched the reference lists of their Specialised Register (last searched 17 July 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) (last searched The Cochrane Library 2008, issue 3) for relevant articles to identify additional trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) or controlled clinical trials (CCTs) of combined intermittent pneumatic leg compression and pharmacological interventions used to prevent venous thrombo-embolism in high-risk patients. DATA COLLECTION AND ANALYSIS: Data extraction was undertaken independently by two review authors using data extraction sheets.

Increased platelet-monocyte aggregation in male claudicants with the Pl(A1/A2) polymorphism of Gp IIb/IIIa.

OBJECTIVES: To investigate the relationship between the Pl(A1/A2) polymorphism and platelet activation and aggregation in patients with Peripheral Arterial Disease (PAD). DESIGN: A prospective single-centre cohort study. METHODS: 45 patients with PAD on aspirin 75mg were recruited and phenotyped/genotyped for the Gp IIb/IIIa Pl(A1/A2) polymorphism. Platelet-Monocyte Aggregation (PMAs) was evaluated using flow-cytometry. RESULTS: The formation of PMAs in the Pl(A2) group was higher but not statistically significant (p=0.17). However, when males were analysed separately, the formation of PMAs was significantly higher in the Pl(A2) group (p=0.0192). No difference was seen in the females. CONCLUSIONS: In this study we show that the Pl(A1/A2) polymorphism primarily affects the aggregation of platelets to monocytes in males. The effect is not observed in females and understanding the mechanism behind this may help elucidate the way the polymorphism alters platelet function in the presence of aspirin.

Cilostazol for peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) affects 4% to 12% of people aged 55 to 70 years and 20% of people over 70 years. The most common complaint is intermittent claudication (IC) characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age-matched controls, people with IC have a three- to six-fold increase in cardiovascular mortality. Symptoms of IC, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise program. Antiplatelet treatment is beneficial in patients with IC for the reduction of vascular events but has not been shown to influence claudication distance. OBJECTIVES: To determine the effect of cilostazol on improving walking distance and in reducing vascular mortality and cardiovascular events in patients with stable IC. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group searched their specialised register (last searched August 2007) and the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2007). We searched MEDLINE (1966 to November 2005), EMBASE (1980 to November 2005), several more specialised databases, and reference lists of articles. SELECTION CRITERIA: Double-blind, randomised controlled trials of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable IC or patients undergoing vascular surgical intervention for PAD. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for selection and all three authors independently extracted data. MAIN RESULTS: Seven randomised controlled trials comparing cilostazol with placebo were included. The weighted mean difference (WMD) for the initial claudication distance (ICD) was improved following treatment with cilostazol 100 mg twice daily (WMD 31.1 m; 95% confidence interval (CI): 21.3 to 40.9 m) and 50 mg twice daily (WMD 41.3 m; 95% CI: -7.1 to 89.7 m) compared with placebo. Participants receiving cilostazol 150 mg twice daily had an increased ICD (WMD 15.7 m; 95% CI: -9.6 to 41.0 m) compared with those receiving placebo. One study also included a comparison with pentoxifylline. In this study, participants receiving cilostazol had significant improvement in ICD compared with placebo. There was no increase in major adverse events including cardiovascular events or mortality in patients receiving cilostazol compared with placebo. AUTHORS' CONCLUSIONS: Patients with IC should receive secondary prevention for cardiovascular disease. Cilostazol has been shown to be of benefit in improving walking distance in people with IC. There are no data on whether it results in a reduction of adverse cardiovascular events.

Assessment of oxygenation and perfusion in the tongue and oral mucosa by visible spectrophotometry and laser Doppler flowmetry in healthy subjects.

UNLABELLED: Use of Visible Light Spectrophotometry (VLS) and Laser Doppler Flowmetry (LDF) is currently being studied by the authors to assess the viability of tissue margins in colon resection and to assess mucosal oxygenation in the colon. Thus, as a preliminary study it was necessary to evaluate whether there is any systematic inter-probe variability of the measurements by VLS and LDF. The oral mucosa was used as a model. METHODS: SO2 with VLS (Whitland Research RM200) and blood flow with LDF (Moor Instruments DRT4) were measured at 10 sites each on the tongue and oral mucosa of 10 healthy volunteers at 0, 6 and 24 hours using 3 different probes for VLS and 2 probes for LDF. RESULTS: The results showed that the SO2 measurements by VLS using the different probes on the tongue and mucosa were significantly correlated (P < 0.05). SO2 values at 6 hours were significantly higher than at 0 and 24 hours (P < 0.05) in all but one case. SO2 measurements were not correlated with LDF. LDF measurements by the 2 probes were correlated significantly (P < 0.05) but the standard deviations were very large. CONCLUSIONS: SO2 measurements on the oral mucosa are reproducible. Due to the large variations in LDF, VLS is likely to be the more clinically useful tool for identifying mucosal ischaemia.

Cryoplasty for peripheral vascular disease.

BACKGROUND: In the UK, symptomatic peripheral arterial disease (PAD) occurs in 5 to 7% of people over the age of 55 years. Cryoplasty offers a new approach by combining the dilation force of balloon angioplasty with the delivery of cold thermal energy to the vessel wall. Cryoplasty is thought to provoke apoptosis rather than necrosis in the arterial smooth muscle cells and thus has the theoretical advantage of reduced myointimal hyperplasia in long-term patency. As it is an emerging therapy, safety and efficacy questions remain. This systematic review evaluates the treatment and provide focus for further research in the field. OBJECTIVES: To assess the efficacy of, and complications associated with, cryoplasty for maintaining patency in the iliac or infrainguinal arteries. SEARCH STRATEGY: We searched the Specialized Register of the Cochrane Peripheral Vascular Diseases Group (inception to August 2007), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library 2007, Issue 3, along with MEDLINE (1966 to August 2007) and EMBASE (1980 to August 2007). SELECTION CRITERIA: Trials in which patients with peripheral arterial disease (PAD) of the iliac or infrainguinal arteries were randomised to cryoplasty with or without another procedure versus a procedure without cryoplasty. This includes trials where all patients receive angioplasty and the randomisation is for cryoplasty versus none. DATA COLLECTION AND ANALYSIS: Studies identified for potential inclusion were independently assessed for inclusion by at least two authors, with excluded trials arbitrated by the third author. As no randomised controlled trials of cryoplasty were found, no statistical analyses were performed. MAIN RESULTS: No randomised controlled trials of cryoplasty were identified. AUTHORS' CONCLUSIONS: The benefit of cryoplasty over conventional angioplasty has not been established as no randomised controlled trials exist to properly evaluate this method. Technical success and primary patency rates seen in the prospective series are encouraging and may suggest a future role for cryoplasty in the treatment of PAD, but cannot be reliably interpreted due to the nature of the studies.

Cilostazol for peripheral arterial disease.

BACKGROUND: Peripheral arterial disease (PAD) affects 4% to 12% of people aged 55 to 70 years and 20% of people over 70 years. The most common complaint is intermittent claudication (IC) characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age-matched controls, people with IC have a three- to six-fold increase in cardiovascular mortality. Symptoms of IC, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise program. Antiplatelet treatment is beneficial in patients with IC for the reduction of vascular events but has not been shown to influence claudication distance. OBJECTIVES: To determine the effect of cilostazol on improving walking distance and in reducing vascular mortality and cardiovascular events in patients with stable IC. SEARCH STRATEGY: The Cochrane Peripheral Vascular Diseases Group searched their specialised register (last searched August 2006) and the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 3, 2006). We searched MEDLINE (1966 to November 2005), EMBASE (1980 to November 2005), several more specialised databases, and reference lists of articles. SELECTION CRITERIA: Double-blind, randomised controlled trials of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable IC or patients undergoing vascular surgical intervention for PAD. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trials for selection and all three authors independently extracted data. MAIN RESULTS: Eight randomised controlled trials comparing cilostazol with placebo were included. The weighted mean difference (WMD) for the initial claudication distance (ICD) was improved following treatment with cilostazol 100 mg twice daily (WMD 31.1; 95% confidence interval (CI): 21.4 to 40.9) and 50 mg twice daily (WMD 41.3; 95% CI: -7.1 to 89.7) compared with placebo. Participants receiving cilostazol 150 mg twice daily had an increased ICD (WMD 15.7; 95% CI: -9.6 to 41.0) compared with those receiving placebo. One study also included a comparison with pentoxifylline. In this study, participants receiving cilostazol had significant improvement in ICD compared with placebo. There was no increase in major adverse events including cardiovascular events or mortality in patients receiving cilostazol compared with placebo. AUTHORS' CONCLUSIONS: Patients with IC should receive secondary prevention for cardiovascular disease. Cilostazol has been shown to be of benefit in improving walking distance in people with IC. There are no data on whether it results in a reduction of adverse cardiovascular events.

Prediction of surgical site infections after major surgery using visible and near-infrared spectroscopy.

Final results of an investigation into whether oxygen saturation of tissues (StO2, measured by spectrophotometry) could predict surgical site infections (SSI) after major abdominal surgery are presented. StO2 was measured on the arm and wound site pre-operatively and then at 12, 24 and 48 hours post-operatively. A Whitland Research RM200 was employed as the visible lightguide spectrophotometer. StO2 measurements using this machine were designated SSO2 (skin SO2). A Hutchinson Inspectra Model 325 was used for the near infrared spectroscopy (NIS) measurements. StO2 measurements using this machine were designated MSO2 (muscle SO2). Of 59 patients (38 males, 21 females), 42 healed uneventfully and 17 developed SSI. The overall infection rate was 28.8%. No significant differences were seen in wound SSO2 between outcome groups at any stage. At 12 hours there was a significant difference between the two groups with respect to mean wound MSO2 (A = 58.3 +/- 21.6%, B = 42.2 +/- 16.6%, p = 0.005, 95% confidence interval = 5.26, 26.98). A receiver operating characteristic curve showed that when a wound MSO2 of 53% was chosen as the threshold to classify potential infection a sensitivity of 71% and a specificity 73% (chi-squared test, p = 0.002) was achieved. The use of the near-infrared spectrophotometry as a tool to predict wound infections should be further evaluated and advocated.

A prospective patient observational study of the role of hyperhomocysteinemia in restenosis in patients undergoing infrainguinal angioplasty or bypass procedures.

AIM: The aim of this study was to examine the correlation between elevated plasma homocysteine (HCy) and restenosis/occlusion in patients undergoing infrainguinal angioplasty or bypass grafting. METHODS: Fifty-three patients presenting to the Northern Vascular Unit were sequentially recruited to the study and prospectively followed up for 12 months post-infrainguinal angioplasty or bypass surgery. Plasma HCy was measured preprocedure and at least 3 months postprocedure using the Abbott IMx system. Hyperhomocysteinemia (HHCy) was taken at a level >15 microM/L. All patients were serially duplex scanned at 6 weeks, and 3, 6, 9 and 12 months. Kaplan-Meier analysis was performed to assess the restenosis/occlusion rate in patients with HHCy versus controls. Analysis of correlation between risk factors for restenosis/occlusion was performed using the Pearson correlation coefficient. In addition, logistic regression analysis was performed. RESULTS: Forty-eight percent of procedures was performed in patients with HHCy. There were 18 graft stenoses/occlusions, and 13 restenoses/occlusions postangioplasty. HHCy did not correlate with an increased risk of restenosis/occlusion (P=0.79). There was a significant correlation between HCy, age, folate and cholesterol levels. Logistic regression analysis revealed no factors that correlated with failure of therapeutic intervention. CONCLUSIONS: This study does not support the hypothesis that HHCy is associated with an increased risk of restenosis after vascular intervention.

The effect of cold storage of rat thoracic aortic rings in organ preservation solutions--a study of receptor-linked vascular prostacyclin synthesis.

An important aspect of organ preservation is the maintenance of intrinsic dilator and antithrombotic mechanisms of blood vessels. Blood vessels synthesize prostacyclin (PGI2), a potent vasodilator and inhibitor of platelet adhesion and aggregation. PGI2 synthesis is controlled by complex mechanisms including adrenoceptor-linked calcium influx and protein kinase C. Since organ preservation solutions may influence these mechanisms, we investigated the effect on in vitro PGI2 synthesis of cold storage of rat aortic rings in lactobionate-raffinose solution (LRS) and hypertonic citrate kidney preservation solution (KPS) on in vitro PGI2 synthesis. Acute incubation of aortic tissue in both preservation solutions at 37 degrees C (compared with minimal essential medium) completely inhibited PGI2 synthesis when stimulated with noradrenaline (NA), phorbol ester (a protein kinase C activator), NaF (a G protein activator), or A23187. Following storage of aortic rings at 4 degrees C (for up to 72 hr) in LRS and KPS, subsequent washing and incubation in MEM, PGI2 synthesis was initially markedly enhanced in response to NA when compared with tissues stored in MEM. These enhanced responses disappeared, and PGI2 synthesis returned to normal following 1 hr incubation of tissues in MEM at 37 degrees C. These data demonstrate that cold storage in preservation fluids exerts minimal deleterious effects, not only on PGI2 synthesis, but possibly on other key processes (calcium homeostasis, protein kinase C activity) in blood vessels.