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Biomedical subjects

A J Bryan

Publications and source records attributed to A J Bryan.

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

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

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

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↗
PubMed1999

Patient-prosthesis mismatch is negligible with modern small-size aortic valve prostheses.

BACKGROUND: Concern has been raised about residual significant gradients when small aortic prostheses are used, particularly in patients with large body surface areas. We studied the performance of six types of small aortic prostheses using dobutamine stress echocardiography. METHODS: Sixty-three patients (mean age, 67 +/- 7 years) who had undergone aortic valve replacement 17 +/- 6 months previously were studied. Two bileaflet mechanical prostheses (St. Jude Medical and CarboMedics: sizes, 19 mm and 21 mm) and two biological prostheses (Medtronic Intact and St. Jude BioImplant: size, 21 mm) were evaluated. A graded infusion of dobutamine was given and Doppler studies of valve performance were carried out. RESULTS: All prostheses except one biological valve had acceptable hemodynamic performance under stress. Using regression modeling, gradient at rest was the only variable found to predict gradient under stress (p < 0.001). Moreover, the most important predictor of gradient at rest was valve design, which accounted for 72% of the variance (p < 0.001). This relationship was independent of valve size (19 mm or 21 mm) or material (ie, mechanical or biological). Body surface area accounted for 4% of the variance in gradient only. CONCLUSIONS: The main predictor of transprosthetic gradient is the inherent characteristics of each particular prosthesis, with relatively insignificant contribution from variations in body surface area. Patient-prosthesis mismatch is not a problem of clinical significance when certain modern valve prostheses are used.

Aged↗
PubMed1999

Influence of normothermic systemic perfusion temperature on cold myocardial protection during coronary artery bypass surgery.

OBJECTIVE: To determine the effect of normothermic systemic perfusion on myocardial injury when using cold cardioplegic techniques in patients undergoing coronary artery bypass surgery. METHOD: Sixty six patients with stable angina pectoris were prospectively randomized into three groups according to cardiopulmonary bypass temperature: hypothermia (28 degrees C, n = 22), moderate hypothermia (32 degrees C, n = 22) and normothermia (37 degrees C, n = 22). All patients received cold antegrade crystalloid cardioplegia and topical cooling with saline at 4 degrees C. Serum samples were collected for troponin T and I estimation preoperatively, 4 hours after removal of the aortic cross clamp, and 12, 24, 36 and 48 hours postoperatively. In addition, serial electrocardiographic studies were undertaken on days 1, 3 and 5. RESULTS: Patients were similar with regard to preoperative and intraoperative characteristics Four patients showed ECG changes typical of perioperative myocardial infarction but remained clinically well (28 degrees C, one; 32 degrees C, one; 37 degrees C, two). In the remaining 62 patients, serum troponin T increased significantly from a mean baseline value of 0.02 ng/ml to 1.5+/-0.9 ng/ml 4 hours after removal of the aortic cross-clamp (P<0.0001). Similarly, troponin I increased from 0.06 ng/ml to 0.63+/-0.47 ng/ml 12 hours after reperfusion (P<0.0001). Serum concentrations of both markers subsequently declined with time but remained higher than preoperative values at 48 hours. There were no differences between the three groups with respect to peak and cumulative serum troponin release. Normothermic cardiopulmonary bypass did not compromise the efficacy of cold myocardial protection when assessed by serum troponin concentrations in low risk patients undergoing coronary revascularization.

Aged↗
PubMed1999

Beating versus arrested heart revascularization: evaluation of myocardial function in a prospective randomized study.

OBJECTIVE: Conventional coronary artery bypass grafting (CABG) is both safe and effective. Nevertheless, the use of cardiopulmonary bypass (CPB) and cardioplegic arrest are associated with several adverse effects. Over the last 2 years there has been a revival of interest in performing CABG on the beating heart. In this prospective randomized study we evaluated the efficacy and safety of on and off pump coronary revascularization on myocardial function. METHODS: Eighty patients (65 males, mean age 61+/-9.7 years) undergoing first time CABG were prospectively randomized to: (i) conventional revascularization with CPB at normothermia and cardioplegic arrest with intermittent warm blood cardioplegia (on pump) or (ii) beating heart revascularization (off pump). Troponin I (Tn I) release was serially measured as a specific marker of myocardial damage. Haemodynamic measurements as well as inotropic requirement, incidence of arrhythmia and postoperative myocardial infarction were also recorded. RESULTS: There were no significant differences between the two groups in terms of age, sex, extent of disease, left ventricular function and number of grafts. There were no deaths or intraoperative myocardial infarctions in either group. Tn I release was constantly lower in the off pump group and this was significant at 1, 4, 12 and 24 h postoperatively. Furthermore, in this group there was a significantly reduced incidence of arrhythmias. Inotropic requirements were less in the off pump group but this did not reach statistical significance. CONCLUSION: These results suggest that off pump coronary revascularization is a safe and effective strategy for myocardial revascularization. Myocardial injury as assessed by Tn I release is also reduced when compared with conventional coronary revascularization with CPB and cardioplegic arrest.

Aged↗
PubMed1999

Intraoperative localisation and management of coronary artery fistula using transesophageal echocardiography.

Coronary artery fistula is a rare congenital malformation that can be complicated by intracardiac shunts, endocarditis, myocardial infarction, coronary aneurysm and sudden death. Clinical symptomatology depends upon the underlying anatomy and the size of the fistulous connection between the left or right side of the heart. We report the successful management of a giant right coronary artery with fistulization into the right atrium. Intraoperative transesophageal echocardiography with colour flow Doppler was used for precise location of the fistulous communication, selective demonstration of vessels feeding the fistula and documentation of abolition of fistulous flow all without the need for cardiopulmonary bypass. Furthermore the effect of shunt occlusion on regional wall motion was documented which facilitated the successful ligation of the fistula.

Adult↗
PubMed1999

The effects of cardiopulmonary bypass temperature on inflammatory response following cardiopulmonary bypass.

OBJECTIVES: The inflammatory response to cardiopulmonary bypass is believed to play an important role in end organ dysfunction after open heart surgery and may be more profound after normothermic systemic perfusion. The aim of the present study was to investigate the effects of cardiopulmonary bypass temperature on the production of markers of inflammatory activity after coronary artery surgery. METHODS: Forty-five low risk patients undergoing elective coronary artery surgery were prospectively randomized into three groups: hypothermia (28 degrees C, n = 15), moderate hypothermia (32 degrees C, n = 15), and normothermia (37 degrees C, n = 15). All patients received cold antegrade crystalloid cardioplegia and topical myocardial cooling with saline at 4 degrees C. Serum samples were collected for the estimation of neutrophil elastase, interleukin 8, C3d, and IgG under ice preoperatively, 5 min after heparinisation, 30 min following start of CPB, at the end of CPB, 5 min after protamine administration, and 4, 12 and 24 h postoperatively. RESULTS: Patients were similar with regard to preoperative and intraoperative characteristics (age, sex, severity of symptoms, number of grafts performed, aortic cross clamp time, cardiopulmonary bypass time). Neutrophil elastase concentration increased markedly as early as 30 min after the onset of cardiopulmonary bypass and peaked 5 min after protamine administration. Levels were not significantly different between the three groups. A similar finding was apparent for C3d release. Interleukin 8 concentrations also demonstrated a considerable increase related to cardiopulmonary bypass in all groups, but there was a significantly more rapid decline in interleukin 8 concentrations in the normothermic group in the postoperative period. Eluted IgG fraction showed a much earlier peak concentration than the other markers, occurring within 30 min of the start of cardiopulmonary bypass. Levels reached a plateau, before declining soon after the end of bypass and remained higher than preoperative values at 24 h. There was no difference between the three groups. The cumulative release of all markers was calculated from the concentration-time curves, and was not statistically different between groups. CONCLUSION: Normothermic systemic perfusion was not shown to produce a more profound inflammatory response compared to hypothermic and moderately hypothermic cardiopulmonary bypass.

Aged↗
PubMed1998

Metabolic differences between hearts of patients with aortic valve disease and hearts of patients with ischaemic disease.

The hypertrophic hearts of patients with aortic valve disease are likely to have metabolic demands different from hearts with ischaemic disease. In this study we measured the myocardial concentration of ATP, ADP, lactate and 16 different amino acids in left ventricular biopsies collected from patients with aortic valve disease and from patients with ischaemic heart disease. Compared to hearts with ischaemic disease, hypertrophic hearts had significantly higher concentrations of ATP, but lower concentrations of lactate, branched-chain amino acids and alanine. These differences have important implications for energy metabolism and protein turnover in the two pathologies.

Adenosine Diphosphate↗
PubMed1998

Warm blood cardioplegia reduces the fall in the intracellular concentration of taurine in the ischaemic/reperfused heart of patients undergoing aortic valve surgery.

The effect of cold and warm intermittent antegrade blood cardioplegia, on the intracellular concentration of taurine in the ischaemic/reperfused heart of patients undergoing aortic valve surgery, was investigated. Intracellular taurine was measured in ventricular biopsies taken before institution of cardiopulmonary bypass, at the end of 30 min of ischaemic arrest and 20 min after reperfusion. There was no significant change in the intracellular concentration of taurine in ventricular biopsies taken after the period of myocardial ischaemia in the two groups of patients (from 10.1 +/- 1.0 to 9.6 +/- 0.9 mumol/g wet weight for cold and from 9.3 +/- 1.3 to 10.0 +/- 1.3 mumol/g wet weight for warm cardioplegia, respectively). Upon reperfusion however, there was a fall in taurine in both groups but was only significant (P < 0.05) in the group receiving cold blood cardioplegia (6.9 +/- 0.8 mumol/g wet weight after cold blood cardioplegia versus 8.0 +/- 0.8 mumol/g wet weight following warm blood cardioplegia). Like taurine, there were no significant changes in the intracellular concentration of ATP after ischaemia in the two groups of patients (from 3.2 +/- 0.32 to 2.95 +/- 0.43 mumol/g wet weight for cold and from 2.75 +/- 0.17 to 2.62 +/- 0.21 mumol/g wet weight for warm cardioplegia, respectively). However upon reperfusion there was a significant fall in ATP in both groups with the extent of the fall being less in the group receiving warm cardioplegia (1.79 +/- 0.19 mumol/g wet weight for cold and 1.98 +/- 0.27 mumol/g wet weight for warm cardioplegia, respectively). This work shows that reperfusion following ischaemic arrest with warm cardioplegia reduces the fall in tissue taurine seen after arrest with cold cardioplegia. Accumulation of intracellular sodium provoked by hypothermia and a fall in ATP, may be responsible for the fall in taurine by way of activating the sodium/taurine symport to efflux taurine.

Adenosine Triphosphate↗
PubMed1998

Distribution of endothelin-1 (ET) receptors (ET(A) and ET(B)) and immunoreactive ET-1 in porcine saphenous vein-carotid artery interposition grafts.

Proliferation of vascular smooth muscle cells (VSMC) is a principal event in neointima formation in saphenous vein-coronary artery bypass grafts. Since endothelin-1 (ET-1) promotes VSMC replication and ET-1 receptor antagonists inhibit neointima formation in arterial injury models, it is reasonable to propose that ET-1 may be involved in neointima formation in vein grafts. However, it is not known what alterations of ET-1 and its receptors (if any) occur in vein grafts. The objective of this study, therefore, was to investigate the distribution of ET-1 and ET-1 receptor subtypes (ET(A) and ET(B)) in porcine vein grafts. Unilateral interposition saphenous vein grafting was performed by end to end anastomosis after excision of a segment of carotid artery in Landrace pigs. One month after surgery, vein grafts, ungrafted saphenous veins and carotid arteries were excised, ET-1 immunoreactivity identified by immunocytochemistry and ET(A) and ET(B) receptor subtypes studied using autoradiography. In vein grafts, there was a greater density of ET(A) compared to ET(B) receptors in both the tunica media and neointima. ET(A) binding in the tunica media of ungrafted saphenous vein was greater than that in the carotid artery or vein grafts, but greater in the vein graft compared to the carotid artery. Immunoreactive ET-1 was located in endothelial cells and throughout the neointima of the vein graft. Dense ET-1 binding (to both ET(A) and ET(B) receptors) was also associated with microvessels in the adventitia within the graft. In vein grafts, there was strong ET(B) binding to neutrophils which were present in high numbers at the subendothelium and within the adventitia. It is concluded ET(A) receptors may play a role in vein graft thickening at the medial and neointimal VSMC level, whereas ET(B) receptors may play a role in microangiogenesis. The higher levels of ET(A) receptors in the tunica media of ungrafted saphenous vein relative to the carotid artery and vein graft may also render this conduit susceptible to neointima formation. These data indicate that studies on the effect of ET receptor antagonists on the pathobiology of vein graft disease is warranted.

Anastomosis, Surgical↗
PubMed1998

Warm blood hyperkalaemic reperfusion ('hot shot') prevents myocardial substrate derangement in patients undergoing coronary artery bypass surgery.

OBJECTIVE: A significant metabolic derangement occurs in the ischaemic-reperfused heart of patients undergoing coronary artery bypass surgery using cold blood cardioplegia. The aim of the present study was to investigate whether this effect could be reversed by complementing cold blood cardioplegia with a short terminal exposure of warm blood hyperkalaemic cardioplegia ('hot shot'). METHODS: Thirty-five patients undergoing primary elective coronary revascularisation were randomized to one of two different techniques of myocardial protection. In the cold blood group (n = 17) myocardial protection was induced using antegrade hyperkalaemic cold blood cardioplegic solution. In the hot shot group (n = 18) this was supplemented with a short exposure to hyperkalaemic warm blood cardioplegia prior to removal of the cross clamp. Intracellular substrates (ATP and amino acids) were measured in left ventricular biopsies collected 5 min after institution of cardiopulmonary bypass, after 30 min of ischaemic arrest and 20 min after reperfusion. RESULTS: Biopsies taken at the end of the period of myocardial ischaemia, when compared to control, did not show any significant change in the intracellular concentration of ATP (from 2.71 +/- 0.32 to 2.43 +/- 0.37 micromol g wet for cold blood group and from 2.6 +/- 0.3 to 2.5 +/- 0.34 micromol/g wet weight for hot shot group) or total free intracellular amino acids pool (from 33.0 +/- 1.4 to 30.0 +/- 1.4 micromol/g wet weight for cold blood group and from 34.0 +/- 1.4 to 34.5 +/- 2.3 micromol/g wet weight for hot shot group). Upon reperfusion, however, there was a significant fall in ATP (23.7 +/- 1.6 micromol/g wet weight amino acids, P < 0.05) and in amino acids (1.53 +/- 0.24 micromol/g wet weight, P < 0.05) in the group receiving only cold blood cardioplegia but not in the hot shot group (2.27 +/- 0.27 micromol/g wet weight ATP and 30.5 +/- 1.6 micromol/g wet weight amino acids). CONCLUSIONS: The data suggest that warm blood hyperkalaemic reperfusion hot shot prevents myocardial metabolic derangement seen during coronary artery surgery.

Adenosine Triphosphate↗
PubMed1998

The end of the cold era: from intermittent cold to intermittent warm blood cardioplegia.

BACKGROUND: A major reduction in the energy demand of the myocardium results from the electromechanical arrest, and cooling contributes to a lesser degree to this reduction. It is from this assumption that strategies of myocardial protection, utilizing warm blood cardioplegic induction, followed by cold cardioplegia with terminal warm reperfusion before removal of the aortic cross clamp, became established as optimal myocardial protection. Continuous normothermic perfusion 'closed the loop' by avoiding myocardial ischemia and linking warm induction and terminal reperfusion. A series of laboratory and clinical data confirmed the benefits of warm heart surgery on myocardial function and metabolism. The disadvantages of continuous warm blood cardioplegia including disturbance of the operative field, led surgeons to administer warm hyperkalaemic blood intermittently as a new cardioplegic strategy. METHODS: This review examines the laboratory and clinical data with reference to the intermittent warm blood cardioplegia, to establish its experimental basis and place in clinical practice. CONCLUSIONS: Experimental observation and clinical application have established intermittent warm blood cardioplegia as a practical, effective and cheap myocardial protection technique, particularly with reference to coronary artery surgery.

Animals↗
PubMed1998

Intermittent antegrade hyperkalaemic warm blood cardioplegia supplemented with magnesium prevents myocardial substrate derangement in patients undergoing coronary artery bypass surgery.

OBJECTIVE: The influence of the addition of magnesium on myocardial protection with intermittent antegrade warm blood hyperkalaemic cardioplegia in patients undergoing coronary artery surgery was investigated and compared with intermittent antegrade warm blood hyperkalaemic cardioplegia only. METHODS: Twenty-three patients undergoing primary elective coronary revascularization were randomized to one of two different techniques of myocardial protection. In the first group, myocardial protection was induced using intermittent antegrade warm blood hyperkalaemic cardioplegia. In the second group, the same technique was used except that magnesium was added to the cardioplegia. Intracellular substrates (ATP, lactate and amino acids) were measured in left ventricular biopsies collected 5 min after institution of cardiopulmonary bypass, after 30 min of ischaemic arrest and 20 min after reperfusion. RESULTS: There were no significant changes in the intracellular concentration of ATP or free amino acid pool in biopsies taken at the end of the period of myocardial ischaemia. However, the addition of magnesium prevented the significant increase in the intracellular concentration of lactate seen with intermittent antegrade warm blood hyperkalaemic cardioplegia. Upon reperfusion there was a significant fall in ATP and amino acid concentration when the technique of intermittent antegrade warm blood hyperkalaemic cardioplegia was used but not when magnesium was added to the cardioplegia. CONCLUSIONS: This work shows that intermittent antegrade warm blood hyperkalaemic cardioplegia supplemented with magnesium prevents substrate derangement early after reperfusion.

Adenosine Triphosphate↗
PubMed1998

External stenting reduces long-term medial and neointimal thickening and platelet derived growth factor expression in a pig model of arteriovenous bypass grafting.

Bypass of stenotic coronary arteries with autologous saphenous vein is an established treatment for ischemic heart disease. However, its long-term clinical success is limited. Late vein graft failure is the result of medial and intimal thickening consequent upon medial vascular smooth muscle cell migration, proliferation and extracellular matrix deposition, followed later by superimposed atherosclerosis. These changes directly compromise graft blood flow and provoke thrombosis. Vein graft wall thickening may represent an adaptation imposed by arterial hemodynamic factors, and these factors have been shown to promote vascular smooth muscle cell migration and proliferation through activation of key mediators including platelet-derived growth factor (PDGF). Many pharmacological interventions aimed at preventing these long-term changes have proven unsuccessful in clinical evaluation. We recently demonstrated in a pig saphenous vein graft model that application of an external polyester stent to the outside of carotid interposition vein grafts reduced intimal hyperplasia and total wall thickness 1 month after implantation. However, it is not known whether the benefits of the stent are maintained in the longer term or what mechanisms underlie its effect. The present study therefore compared morphological changes and PDGF expression in stented grafts and contralateral unstented grafts in the same pigs, 6 months after graft implantation. Reduced medial thickening, neointima formation, and cell proliferation were sustained in externally stented grafts, and these effects were associated with a significant reduction in PDGF expression.

Animals↗
PubMed1998

Endothelin-1 and endothelin receptors in porcine saphenous vein-carotid artery grafts.

The regional distribution of endothelin-1 (ET-1) and its receptor subtypes (ETA and ETB) in porcine saphenous vein into carotid artery interposition grafts was studied 1 month after surgery and compared to ungrafted saphenous vein and carotid artery. ET-1 immunoreactivity was identified by immunohistochemistry and ET receptor subtypes were studied using in vitro autoradiography. In vein grafts, there was a higher density of ETA compared to ETB receptor binding in both the tunica media and the neointima. ETA binding to the tunica media of ungrafted saphenous vein was greater than that in the carotid artery or vein grafts, but greater in the vein graft compared to the carotid artery. Immunoreactive ET-1 was located in endothelial cells and throughout the neointima of the vein graft. Dense ETA and ETB binding was also associated with adventitial microvessels in the graft, and ETB binding was also identified to neutrophils, which accumulated at the subendothelium and within the adventitia. ETA receptors may play a role in vein graft thickening at the medial and neointimal vascular smooth-muscle cell level, whereas ETB receptors may play a role in microangiogenesis. The high levels of ETA receptors in the tunica media of ungrafted saphenous vein, relative to the carotid artery and vein graft, may also render this conduit susceptible to neointimal formation. These data indicate that studies of the effect of ET receptor antagonists on the pathobiology of vein graft disease are warranted.

Animals↗