Search PubMed⌕ Search

Biomedical subjects

G D Angelini

Publications and source records attributed to G D Angelini.

At least 19 recordsLinked to original sources
PubMed2002

Myocardial injury in hypertrophic hearts of patients undergoing aortic valve surgery using cold or warm blood cardioplegia.

OBJECTIVES: Myocardial protection techniques during cardiac surgery have been largely investigated in the clinical setting of coronary revascularisation. Few studies have been carried out on patients with left ventricular hypertrophy where the choice of delivery, and temperature of cardioplegia remain controversial. This study investigates metabolic changes and myocardial injury in hypertrophic hearts of patients undergoing aortic valve surgery using antegrade cold or warm blood cardioplegia. METHODS: Thirty-five patients were prospectively randomised to intermittent antegrade cold or warm blood cardioplegia. Left ventricular biopsies were collected at 5min following institution of cardiopulmonary bypass, 30min after cross-clamping the aorta and 20min after cross-clamp removal, and used to determine metabolic changes during surgery. Metabolites (adenine nucleotides, amino acids and lactate) were measured using high pressure liquid chromatography and enzymatic techniques. Postoperative myocardial troponin I release was used as a marker of myocardial injury. RESULTS: Ischaemic arrest was associated with significant increase in lactate and alanine/glutamate ratio only in the warm blood group. During reperfusion, alanine/glutamate ratio was higher than preischaemic levels in both groups, but the extent of the increase was considerably greater in the warm blood group. Troponin I release was markedly (P<0.05, Mean+/-SD) lower at 1, 24 and 48h postoperatively in the cold compared to the warm blood group (0.51+/-0.37, 0.37+/-0.22 and 0.27+/-0.19 vs. 0.75+/-0.42, 0.73+/-0.51 and 0.54+/-0.38ng/ml for cold vs. warm group, respectively). CONCLUSIONS: Cold blood cardioplegia is associated with less ischaemic stress and myocardial injury compared to warm blood cardioplegia in patients with aortic stenosis undergoing valve replacement surgery. Both cardioplegic techniques, however, confer sub-optimal myocardial protection.

Aged↗
PubMed2001

The effect of sildenafil on corpus cavernosal smooth muscle relaxation and cyclic GMP formation in the diabetic rabbit.

Sildenafil, a type V phosphodiesterase inhibitor, enhances smooth muscle relaxation in normal human and rabbit corpus cavernosum. We investigated the in vitro effects of sildenafil on non-adrenergic, non-cholinergic and nitric oxide (NO)-mediated cavernosal smooth muscle relaxation in diabetic rabbits, since alterations in this pathway are recognised in diabetic erectile dysfunction. Diabetes mellitus was induced in male New Zealand White rabbits with alloxan. Cavernosal strips from age-matched control, 3- and 6-month diabetic animals were mounted in organ baths. Relaxation responses to electrical field stimulation (1-20 Hz) or sodium nitroprusside (10(-8)-10(-4) M) were assessed in the absence and presence of sildenafil (10(-8) and 10(-7) M). The effect of sildenafil on cGMP formation by the corpus cavernosum was also assessed following stimulation with sodium nitroprusside, A23187 and acetylcholine. Sodium nitroprusside-stimulated relaxations were significantly (P<0.03) impaired in the corpus cavernosum from both diabetic groups, (IC(50)=4.6 x 10(-6) M following 3 months of diabetes mellitus and 4.0 x 10(-6) M following 6 months of diabetes mellitus; compared to 7.5 x 10(-7) M for pooled age-matched controls). Sildenafil (10(-7) M) significantly enhanced sodium nitroprusside-stimulated relaxation in control (P<0.05) and diabetic groups (P<0.03). Electrical field stimulation-mediated relaxations of the corpus cavernosum were significantly impaired after 6-month diabetes mellitus and enhanced by sildenafil (10(-8) M). cGMP formation by the diabetic corpus cavernosum was impaired significantly, but restored towards normal by sildenafil. We suggest that the impairment of NO-mediated relaxation of the corpus cavernosum reflect, at least in part, a defect in guanylyl cyclase activity. These findings support the use of sildenafil as an effective, orally administered, treatment for diabetic erectile dysfunction.

Acetylcholine↗
PubMed2001

Age-dependent and hypoxia-related differences in myocardial protection during pediatric open heart surgery.

BACKGROUND: Current cardioplegic protection techniques used in pediatric cardiac surgery do not take into consideration age and cyanotic differences. The aim of the present work was to address this question by monitoring clinical outcome, myocardial metabolism, and reperfusion injury in pediatric patients protected by cold-crystalloid cardioplegia. METHODS AND RESULTS: Fifty-eight patients (31 children and 27 infants) with or without hypoxic stress (cyanosis) undergoing open heart surgery with cold-crystalloid cardioplegia were included in the study. Clinical outcome measures assessed included inotropic and ventilatory support, intensive care, and hospital stay. Ischemia-induced changes in metabolism (adenine nucleotides, purines, lactate, and amino acids) were determined in ventricular biopsies collected at the beginning and end of ischemic time (cross-clamp time). Reperfusion injury was assessed by measuring postoperative serial release of troponin I. Evidence was observed of ischemic stress during cardioplegic arrest in children and infants as shown by significant changes in cellular metabolites. Compared with infants, children had significantly less reperfusion injury and better clinical outcome, and these factors were related to duration of ischemic time. Cyanosis did not influence outcome in infants, but cyanotic children showed worse reperfusion injury and clinical outcome than acyanotic children. CONCLUSIONS: Extent of myocardial protection with cold-crystalloid cardioplegia in pediatric open heart surgery is dependent on age and degree of cyanosis.

Age Factors↗
PubMed2001

Thapsigargin inhibits angiogenesis in the rat isolated aorta: studies on the role of intracellular calcium pools.

OBJECTIVE: Since the role of Ca2+ in angiogenesis is not fully understood, we investigated the effect of thapsigargin (TG: depletes intracellular Ca2+ pools) and other Ca2+ modulators [ionomycin, calcium ionophore A23187 and dibutyrylhydroquinone (DBHQ)] on in vitro angiogenesis by rat aortic rings. METHODS: Aortae from Sprague-Dawley rats were cut into 2-mm rings, embedded in a fibrin clot and cultured for 15 days in serum-free medium containing drugs and the microvessels counted. Rings were also pre-treated with TG and Ca2+ modulators for 1 h prior to embedding and culture. Viability was examined by the measurement of lactic acid dehydrogenase release. Rings were also treated with hydrocortisone and lavendustin A (a tyrosine kinase inhibitor), as positive controls. The effect of TG on the proliferation and migration of human umbilical artery endothelial cells (HUVECs) was studied in parallel. RESULTS: TG significantly inhibited microvessel formation and HUVEC proliferation and migration in a dose-dependent manner, all at <10 nmol/l, without affecting viability. In contrast, ionomycin, A23187 and DBHQ were cytotoxic at inhibitory concentrations. Continual exposure to hydrocortisone and lavendusin A also inhibited angiogenesis without affecting viability. CONCLUSION: Since low concentrations of TG deplete intracellular Ca2+ stores, it is concluded that these pools play a central role in mediating angiogenesis.

Analysis of Variance↗
PubMed2001

Clinical and angiographic outcome of different surgical strategies of bilateral internal mammary artery grafting.

Long-term survival, relief of angina, and prevention of myocardial infarction after coronary revascularization are related to the preoperative status of the patient, progression of coronary artery atherosclerosis, and the patency of the conduits used. The increased use of the internal mammary artery for coronary grafting depends upon the accumulation of data on superior late patency compared with venous conduits. These data have supported the simultaneous use of both left and right internal mammary arteries with reported improved late survival. However, controversy still surrounds the clinical and angiographic outcomes of some of the surgical strategies of bilateral internal mammary artery grafting. This review examines a range of surgical strategies of bilateral internal mammary artery grafting and their mid- and long-term clinical and angiographic outcomes. From the available data, careful preoperative selection of patients is paramount. Clinical and angiographic outcome of bilateral internal mammary grafting is superior to single internal mammary grafting with supplemental vein grafts when pedicled, sequential, or free aorto-coronary internal mammary artery is used. Further studies are needed to evaluate the midterm and long-term clinical and angiographic outcomes of complex strategies such as Y or T procedures.

Coronary Angiography↗
PubMed2001

Off-pump coronary operations can be safely taught to cardiothoracic trainees.

BACKGROUND: Off-pump coronary artery bypass (OPCAB) operations are evolving rapidly and becoming established in many cardiothoracic centers. For the technique to be widely applicable, teaching methods must be developed for surgical trainees. Early and midterm clinical outcomes of OPCAB performed at our institution by trainees as first operators under supervision were compared to those obtained in patients operated on by consultants. METHODS: Analysis was undertaken on data prospectively inserted in the Patient Analysis & Tracking System. Of the 559 OPCAB operations performed between January 1997 and May 2000, 124 (22%) were carried out by a supervised trainee and 435 (78%) by a consultant. RESULTS: There was no difference in age, sex, angina class, New York Heart Association functional class, or operative priority and extent of coronary artery disease in the two groups. More patients operated on by consultants had a history of congestive heart failure requiring medical therapy, significantly lower ejection fraction, and higher Parsonnet score compared with patients operated on by trainees. Early and midterm clinical results, in terms of morbidity and mortality, were similar in patients operated on by trainees or by consultants. CONCLUSIONS: Our data show no differences in early and midterm clinical outcome for patients undergoing OPCAB operations performed either by consultants or by trainees under supervision. The improvements in exposure and stabilization techniques, as well as the use of intracoronary shunts, have made it possible and safe to teach trainees off-pump multivessel coronary artery revascularization.

Aged↗
PubMed2001

Hemodynamic performance of the 21-mm Sorin Bicarbon mechanical aortic prostheses using dobutamine Doppler echocardiography.

BACKGROUND: Small-sized mechanical aortic prostheses are commonly associated with generation of high transvalvular gradients, particularly in patients with large body surface area, and can result in patient-prosthesis mismatch. This study evaluates the hemodynamic performance of 21-mm Sorin Bicarbon bileaflet mechanical prostheses using dobutamine stress echocardiography. METHODS: Fourteen patients (7 women; mean age, 63+/-8 years) who had undergone aortic valve replacement with a 21-mm Sorin Bicarbon bileaflet mechanical prosthesis 32.4+/-5.1 months previously were studied. After a resting Doppler echocardiogram, a dobutamine infusion was started at a rate of 5 microg x kg(-1) x min(-1) and increased to 30 microg x kg(-1) x min(-1) at 15-minute intervals. Pulsed- and continuous-wave Doppler echocardiographic studies were performed at rest and at the end of each increment of dobutamine. Both peak and mean velocity and pressure gradient across the prostheses were measured, and effective orifice area, discharge coefficient, and performance index were calculated. RESULTS: Dobutamine stress increased heart rate and cardiac output by 83% and 81%, respectively (both p < 0.0001), and mean transvalvular gradient increased from 15.6+/-5.5 mm Hg at rest to 35.4+/-11.9 mm Hg at maximum stress (p < 0.0001). Although the indexed effective orifice area was significantly lower in patients with a larger body surface area, this was not associated with any significant pressure gradient. The performance index of this valve was unchanged throughout the study. Regression analyses demonstrated that the mean transvalvular gradient at maximum stress was independent of all variables except resting gradient (p = 0.05). Body surface area had no association with the changes in cardiac output, transvalvular gradient at maximum stress, and effective orifice area. CONCLUSIONS: These data show that the 21-mm Sorin Bicarbon bileaflet mechanical prosthesis offers an excellent hemodynamic performance with full utilization of its available orifice when implanted in the aortic position. The lack of significant transvalvular gradient in patients with a larger body surface area suggests that patient-prosthesis mismatch is highly unlikely when this prosthesis is used.

Adult↗
PubMed2001

Coronary revascularization with or without cardiopulmonary bypass in patients with preoperative nondialysis-dependent renal insufficiency.

BACKGROUND: Preoperative renal insufficiency is a predictor of acute renal failure in patients undergoing conventional coronary artery bypass grafting. Off-pump coronary artery bypass operations have been shown to reduce renal dysfunction in patients with normal renal function, but the effect of this technique in patients with preoperative nondialysis-dependent renal insufficiency is unknown. METHODS: From June 1996 to December 1999, data of 3,250 consecutive patients undergoing coronary artery bypass grafting were prospectively entered into the Patient Analysis & Tracking Systems (PATS, Dendrite Clinical Systems, London, UK). Two hundred and fifty-three patients with preoperative serum creatinine more than 150 micromol/L were identified (202 patients on-pump, 51 patients off-pump), and clinical outcomes were analyzed. Serum creatinine and urea, in-hospital mortality, and morbidity were compared between groups. The association of perioperative factors with acute renal failure was investigated by multiple logistic regression analysis. RESULTS: Preoperative characteristics were similar between the groups. Mean number of grafts was 2.9 +/- 0.8 and 2.3 +/- 0.8 in the on-pump and off-pump groups, respectively (p < 0.0001). Comparison between groups showed a significantly higher incidence of stroke, inotropic requirement, blood loss, and transfusion of red packed cell and platelets in the on-pump group (all p < 0.05). Postoperative serum creatinine and urea were higher in the on-pump group with a significant difference at 12 hours postoperatively (p < 0.05). Logistic regression analysis identified cardiopulmonary bypass, serum creatinine level 60 hours postoperatively, inotropic requirement, need for intraaortic balloon pump, transfusion of red packed cell, and hours of ventilation as predictors of postoperative acute renal failure. CONCLUSIONS: This study suggests that off-pump coronary artery bypass operations reduce in-hospital morbidity and the likelihood of acute renal failure in patients with preoperative nondialysis-dependent renal insufficiency undergoing myocardial revascularization.

Acute Kidney Injury↗
PubMed2001

Macro-porosity is necessary for the reduction of neointimal and medial thickening by external stenting of porcine saphenous vein bypass grafts.

BACKGROUND: placing external non-restrictive macro-porous stents around porcine vein grafts prevents neointima formation and medial thickening in both the short and long term. Whether the porosity of the stent material influences this effect, however, has not been determined. Therefore, the effect on neointimal and medial thickening of external macro-porous (polyester) and micro-porous (polytetrafluorethylene) stents of equal diameter were compared. The effect on expression of platelet-derived growth factor (PDGF), a potent mediator of vascular smooth muscle cell migration and proliferation and its receptors was also investigated. METHODS AND RESULTS: saphenous vein-carotid artery interposition grafting was performed in Landrace pigs with external placement of 8 mm diameter macro- and micro-porous stents contralaterally. One month after surgery, graft wall dimensions, PDGF and PDGF receptor expression and cell proliferation using proliferating cell nuclear antigen (PCNA) were measured on histological sections. Macro-porous stents significantly reduced neointimal and medial thickening compared with micro-porous stents (0.1+/-0.02 vs. 0.25+/-0.03 mm, P<0.002, and 0.10+/-0.02 vs. 0.17+/-0.02 mm, P<0.014, respectively). Macro-porous stents significantly reduced the percentage of cells expressing PDGF and PCNA, compared with micro-porous stents (36+/-9 vs. 80+/-7, P < 0.002, and 11+/-3 vs. 21+/-2, P < 0.02, respectively). The percentage of cells expressing PDGF receptors was similar with both the stent types. Adventitial microvessel formation occurred across macro-porous stents but was markedly suppressed by micro-porous stents. CONCLUSIONS: porosity is crucial to the efficacy of external stents in reducing neointima formation in porcine vein grafts. Decreases in PDGF expression and cell proliferation accompany the reduction in neointima formation. In addition, macro-porous stents allow adventitial microvessels to connect with the vasculature outside the stent, thereby potentially improving oxygenation. Although external stenting is highly effective in reducing neointima formation after vein grafting, the properties of the stent material necessary for this effect have not been defined. This study establishes that macro-porosity is one essential feature required to reduce PDGF expression cell proliferation and neointima formation.

Animals↗
PubMed2001

Haemodynamic changes during beating heart coronary surgery with the 'Bristol Technique'.

OBJECTIVES: Optimal exposure and stabilization of the target coronary vessel is essential to allow the construction of a precise coronary anastomosis during off pump coronary surgery. However, this might be achieved at the expense of significant haemodynamic deterioration, particularly while grafting the circumflex and the posterior descending coronary arteries. The present study was designed to assess the haemodynamic changes with the beating heart positioned for grafting the three main coronaries. METHODS: Twenty-nine consecutive patients (21 male, mean age 62.6+/-7.1 years) undergoing off pump coronary surgery were enrolled in the study. Three different surgical settings of exposure and stabilization were used according to the site of anastomosis: left anterior descending (LAD - set-up 1; n=29), posterior descending (PDA - set-up 2; n=15), and circumflex (Cx - set-up 3; n=21) coronary arteries. Haemodynamic measurements were recorded before any cardiac manipulation (baseline) in set-ups 1, 2 and 3, and immediately after the completion of each distal anastomosis with the heart returned to its anatomical position. RESULTS: There were no marked changes in heart rate (HR) and systemic mean arterial pressure during the construction of the anastomoses for any of the three surgical settings. Set-up 1 (LAD) showed a decrease of 15.5% in stroke volume (SV) and an increase of 9% in pulmonary capillary wedge pressure (PCWP) compared to baseline (both P<0.05), with all the other haemodynamic parameters remaining unchanged. Set-up 2 (PDA) showed a marked decrease in SV and cardiac index (CI), and an increase in central venous pressure (CVP) when compared to baseline (all P<0.05). The most extensive changes were observed in set-up 3 (Cx) with a considerable reduction in SV and CI, and an increase in CVP, PCWP, pulmonary arterial pressure, and systemic vascular resistance index (all P<0.05). These haemodynamic changes were transient and totally recovered after the heart was returned to its anatomical position. CONCLUSIONS: Exposure and stabilization of the three main coronary arteries during beating heart surgery does not produce any appreciable change in systemic blood pressure and HR. The haemodynamic deterioration observed during the construction of the circumflex and posterior descending coronary arteries distal anastomoses is transient and well tolerated with no adverse clinical events.

Anastomosis, Surgical↗
PubMed2001

Prevention of spinal cord ischaemia during descending thoracic and thoracoabdominal aortic surgery.

Surgery of the descending and thoracoabdominal aorta has been associated with post-operative paraparesis or paraplegia. Different strategies, which can be operative or non-operative, have been developed to minimise the incidence of neurological complications after aortic surgery. This review serves to summarise the current practice of spinal cord protection during surgery of the descending thoracoabdominal aortic surgery. The pathophysiology of spinal cord ischaemia will also be explained. The incidence of spinal cord ischaemia and subsequent neurological complications was associated with (1) the duration and severity of ischaemia, (2) failure to establish spinal cord supply and (3) reperfusion injury. The blood supply of the spinal cord has been extensively studied and the significance of the artery of Adamkiewicz (ASA) being recognised. This helps us to understand the pathophysiology of spinal cord ischaemia during descending and thoracoabdominal aortic operation. Techniques of monitoring of spinal cord function using evoked potential have been developed. Preoperative identification of ASA facilitates the identification of critical intercostal vessels for reimplantation, resulting in re-establishment of spinal cord blood flow. Different surgical techniques have been developed to reduce the duration of ischaemia and this includes the latest transluminal techniques. Severity of ischaemia can be minimised by the use of CSF drainage, hypothermia, partial bypass and the use of adjunctive pharmacological therapy. Reperfusion injury can be reduced with the use of anti-oxidant therapy. The aetiology of neurological complications after descending and thoracoabdominal aortic surgery has been well described and attempts have been made to minimise this incidence based on our knowledge of the pathophysiology of spinal cord ischaemia. However, our understanding of the development and prevention of these complications require further investigation in the clinical setting before surgery on descending and thoracoabdominal aorta to be performed with negligible occurrence of these disabling neurological problems.

Angiography↗
PubMed2001

Off-pump coronary artery bypass surgery for critical left main stem disease: safety, efficacy and outcome.

OBJECTIVES: To determine whether patients with critical left main stem (LMS) coronary artery disease can undergo off-pump coronary artery bypass (OPCAB) surgery safely and successfully. METHODS: From May 1996 to March 2000 data for patients with critical (> or =50%) LMS stenosis who underwent conventional coronary artery bypass surgery with cardiopulmonary bypass (CCAB) or without (OPCAB) were collected prospectively using the Patient Analysis & Tracking System. A reusable pressure stabilizer, intra-coronary shunts and a single posterior pericardial stitch exposure technique were used in all OPCAB cases. Non-randomized, retrospective data analysis included demographic and preoperative risk factors, operative details, clinical outcome and early follow-up. RESULTS: During the study period 387 patients with LMS stenosis underwent surgery (OPCAB n=75, CCAB n=312). Groups were similar in terms of preoperative and intraoperative variables although CCAB patients received significantly more grafts per patient (3.1+/-0.73 vs. 2.6+/-0.76, P< or =0.001). Mortality was similar in both groups (OPCAB 1.3% vs. CCAB 2.6%). OPCAB patients when compared to CCAB patients had a lower requirement for postoperative inotropes (12.0% vs. 38.1%, P=0.0001), temporary postoperative pacing (2.7% vs. 10.1%, P=0.02), and blood product transfusion (6.7% vs. 31.4%, P<0.0001), a lower incidence of postoperative chest infection (0% vs. 6.7%, P=0.02) and a slightly reduced postoperative length of stay (7.9+/-5.46 vs. 8.3+/-5.11 days, P=0.01). At 24 months follow-up, CCAB and OPCAB actuarial survival was 94.1+/-1.7% and 97.7+/-2.3%, respectively. CONCLUSIONS: OPCAB surgery is safe and effective in patients with critical LMS disease.

Aged↗
PubMed2001

Wild-type p53 gene transfer inhibits neointima formation in human saphenous vein by modulation of smooth muscle cell migration and induction of apoptosis.

Patency of autologous human saphenous vein coronary artery bypass grafts (CABG) is compromised by intimal thickening and superimposed atherosclerosis, caused by migration of vascular smooth muscle cells (SMC) to the intima where they proliferate. Here, using adenoviral transfer, we have targeted SMCs using wild-type p53 (wt p53) overexpression. Initial in vitro analyses demonstrated that wt p53 overexpression had no effect on SMC proliferation but promoted apoptosis, which was inhibited by co-expression of bcl2 or crmA. Wt p53 inhibited SMC invasion through reconstituted matrices, a phenotype not affected by bcl2 or crmA. Overexpression of wt p53 in human saphenous vein before organ culture significantly induced apoptosis (P < 0.01, Student's t test) without affecting proliferation rates either in the media or in the intima. SMC migration was, however, significantly reduced by wt p53 (P < 0.01, Student's t test). Intimal thickening and the number of neointimal cells were reduced by 89% and 73%, respectively, after 14 days (P < 0.01 and P < 0.001, respectively, Student's t test). This study demonstrates that overexpression of wt p53 promotes apoptosis and inhibits migration of SMC leading to reduced intimal thickening. This maybe a useful approach for increasing patency rates in CABG procedures in the clinic.

Adenoviridae↗
PubMed2001

Reduced postoperative blood loss and transfusion requirement after beating-heart coronary operations: a prospective randomized study.

OBJECTIVE: Coronary artery bypass grafting on the beating heart through median sternotomy is a relatively new treatment, which allows multiple revascularization without the use of cardiopulmonary bypass. A prospective randomized study was designed to investigate the effect of coronary bypass with or without cardiopulmonary bypass on postoperative blood loss and transfusion requirement. METHODS: Two hundred patients with coronary artery disease were prospectively randomized to (1) on-pump treatment with conventional cardiopulmonary bypass and cardioplegic arrest and (2) off-pump treatment on the beating heart. Postoperative blood loss identified as total chest tube drainage, transfusion requirement, and related costs together with hematologic indices and clotting profiles were analyzed. RESULTS: There was no difference between the groups with respect to preoperative and intraoperative patient variables. The mean ratio of postoperative blood loss and 95% confidence interval between groups was 1.64 and 1.39 to 1.94, respectively, suggesting on average a postoperative blood loss 1.6 times higher in the on-pump group compared with the off-pump group. Seventy-seven patients in the off-pump group required no blood transfusion compared with only 48 in the on-pump group (P <.01). Furthermore, less than 5% of patients in the on-pump group required fresh frozen plasma and platelet transfusion compared with 30% and 25%, respectively, in the on-pump group (both P <.05). Mean transfusion cost per patient was higher in the on-pump compared with that in the off-pump group ($184.8 +/- $35.2 vs $21.47 +/- $6.9, P <.01). CONCLUSIONS: Coronary artery bypass grafting on the beating heart is associated with a significant reduction in postoperative blood loss, transfusion requirement, and transfusion-related cost when compared with conventional revascularization with cardiopulmonary bypass and cardioplegic arrest.

Blood Transfusion↗
PubMed2001

Injury induces dedifferentiation of smooth muscle cells and increased matrix-degrading metalloproteinase activity in human saphenous vein.

Long-term patency of human saphenous vein bypass grafts is low because of intimal thickening and superimposed atherosclerosis. Matrix-degrading metalloproteinases (MMPs) and changes in vascular smooth muscle cell (VSMC) phenotype are thought to be essential for the VSMC migration that contributes to intimal thickening. We examined VSMC phenotype and MMP activity in saphenous veins obtained before and after surgical manipulation. Surgical preparation of the veins significantly increased pro-MMP-1 expression by 2-fold and significantly reduced tissue inhibitor of MMPs (TIMP)-2 expression, whereas MMP-3 and TIMP-1 were unaffected. Furthermore, caseinolytic and gelatinolytic activities measured by in situ zymography were dramatically elevated by injury. The expression of desmin and smoothelin was significantly decreased by injury, whereas vimentin expression was significantly increased. In addition, these changes in phenotype and MMP activity were localized to a subpopulation of VSMCs, the circumferential medial VSMCs. Our data show that surgical preparative injury induces phenotypic modulation of a subpopulation of medial VSMCs to a synthetic phenotype and increases MMP activity. This may favor matrix degradation, VSMC migration, and the subsequent intimal thickening that leads to graft failure.

Caseins↗