Effect of angioplasty and grafting on porcine vascular nerves: a potential neurotropic role for endothelin-1.
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Angioplasty, Balloon, Coronary↗
Biomedical subjects
G D Angelini
Publications and source records attributed to G D Angelini.
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↗
Activation of matrix-degrading metalloproteinases by mast cell proteases in atherosclerotic plaques.
Recent studies suggest that mast cell-derived neutral proteases can activate matrix-degrading metalloproteinases (MMPs). We have investigated the role of the mast cell proteases tryptase and chymase in the activation of MMPs in human carotid endarterectomy specimens (atherosclerotic, n=32) and postmortem carotid arteries (control, n=17). In vitro degranulation of mast cells in atherosclerotic carotid arteries by compound 48/80 caused a significant increase in MMP activity. Addition of the nonselective tryptase inhibitor antipain, the specific trypsinlike protease inhibitor 4-amidinophenylmethanesulfonyl fluoride, and the chymase inhibitor chymostatin reduced this increase in MMP activity by 30+/-6%, 23+/-6%, and 9+/-2%, respectively. Immunocytochemistry identified significantly higher numbers of tryptase-containing cells (mast cells) and cells expressing MMP-1 and MMP-3 in the "shoulder" regions of atherosclerotic artery lesions compared with the tunica media of control arteries. Dual immunocytochemistry showed collocation of MMP-1 and MMP-3 with mast cells in the shoulder regions. Degranulation was observed in 78+/-5% (mean+/-SEM) of mast cells in this area, whereas nonactivated mast cells were observed in all other areas. In situ zymography revealed caseinolytic and gelatinolytic activity in these areas. In conclusion, in vitro mast cell degranulation, which releases mast cell proteases, in carotid arteries increases MMP activity. Furthermore, elevated MMP-1 and MMP-3 expression is collocated with increased numbers of degranulated mast cells and with greater MMP activity in the shoulder regions of atherosclerotic plaques. Activation of MMPs by mast cell-derived proteases may be an important mechanism in atherosclerotic plaque destabilization.
Aged↗
Biomaterials and cardiovascular devices.
In the field of cardiovascular surgery there is presently a lack of biomaterials possessing essential characteristics of the native tissue or organ which is to be replaced. This paper describes various biomaterials that have been introduced into the circulatory system and the complex reactions that subsequently occur. The risk of infection is also discussed as well as prevention and treatment regimes that can be used. Examples of future biomaterial development are outlined in an attempt to achieve biocompatibility.
Blood Substitutes↗
Left ventricular volume reduction for end-stage heart failure: intrapapillary or extrapapillary resection, mitral valve repair or replacement?
We report on two patients with end-stage dilated cardiomyopathy and functional mitral valve insufficiency who underwent left ventricular volume reduction. Intrapapillary resection and correction of the mitral valve regurgitation produced inadequate reduction of the ventricular cavity and resulted in inability to wean the patients from cardiopulmonary bypass. Following extension of the resection to include the papillary muscles and mitral valve replacement, there was a significant improvement in cardiac function. Both patients survived surgery; subsequent echocardiography provided evidence of improved myocardial function and NYHA functional class.
Aged↗
Differential alterations of prostacyclin, cyclic AMP and cyclic GMP formation in the corpus cavernosum of the diabetic rabbit.
OBJECTIVE: To investigate the effect of alloxan-induced diabetes mellitus (DM, a major risk factor for erectile dysfunction and associated with impaired endothelial function) on the formation of nitric oxide (NO), prostacyclin (PGI2), cGMP and cAMP in the corpus cavernosum of rabbits. MATERIALS AND METHODS: Rabbits were rendered diabetic (hyperglycaemic, nonketotic) with alloxan; after 3 and 6 months, the penises were excised and the corpus cavernosum processed for the study of PGI2, NO, cAMP and cGMP formation, using a range of stimulators and radioimmunoassays. RESULTS: PGI2 formation in response to acetylcholine and phorbol ester, but not arachidonate, and cGMP formation in response to A23187 (NO-release dependent), was significantly diminished in diabetic rabbit corpus cavernosum compared with controls at both 3 and 6 months after the induction of DM. cAMP formation in response to forskolin and prostaglandin E1 was reduced after 6 but not 3 months, although nitroprusside-stimulated cGMP (activates guanylyl cyclase directly) was unaffected in cavernosal tissue from diabetic rabbits. CONCLUSIONS: These results show that the formation of NO and PGI2, and adenylyl cyclase activity but not guanylyl cyclase, are impaired in the corpus cavernosum of diabetic rabbits. As NO and PGI2 are produced by the endothelium, these studies consolidate the view that endothelial dysfunction is a major contributor to erectile dysfunction in diabetes mellitus.
Alloxan↗
Left ventricular volume reduction surgery.
Left ventricular volume reduction has recently been introduced as a surgical treatment for end stage dilated cardiomyopathy. This operation involves the resection of a slice of viable left ventricular myocardium in order to reduce the wall tension imposed upon the contracting heart chamber. Early results are encouraging, but clinical evaluation on a larger scale is required. In the present article, we describe the indications, surgical principles and results of left ventricular volume reduction surgery with reference to our group's experience.
Animals↗
Towards the prevention of vein graft failure.
Improved outcome after coronary bypass surgery over the last decade has been attributed largely to the increasing use of arterial conduits and their superior patency rates over that of saphenous vein grafts. In spite of this trend, autologous saphenous vein has remained an important and convenient conduit for a variety of operative scenarios, and is still used for more than 70% of grafts. As a result, vein graft failure continues to represent a significant clinical and economic burden upon the health care service. Between 15 to 30% of saphenous vein grafts occlude within the first year of surgery, increasing to over 50% after 10 years. By this time, more than 10% of patients will require further intervention to alleviate symptoms arising from occluded grafts and progression of native disease. Graft occlusion arises either from early thrombosis or the later onset of 'vein graft disease' and subsequent atherosclerotic changes.
Animals↗
Staged minimally invasive direct coronary artery bypass and percutaneous angioplasty for multivessel coronary artery disease.
OBJECTIVE: Minimally invasive direct coronary artery bypass (MIDCAB) using the left internal mammary artery (IMA) to the left anterior descending (LAD) coronary artery can be performed with low operative risk. MIDCAB can be combined with percutaneous transluminal coronary angioplasty (PTCA) to treat patients with multivessel disease. We report here our experience with staged MIDCAB and PTCA in the management of a selected group of patients. METHODS AND RESULTS: 11 patients (9 males, mean age 64.6+/-8.7 years) with multivessel coronary artery disease received left IMA grafts to the LAD using the MIDCAB approach. There were no postoperative morbidity or mortality. All patients were extubated within 4 h of leaving the operating room with a mean ITU stay of 12.8 h. All patients but two underwent coronary angioplasty during the same hospital admission, 3.8+/-1.3 days after the MIDCAB procedure. Angiography confirmed IMA grafts patency in all patients, and complete revascularisation by PTCA of other coronary arteries was possible in all patients but one. Mean hospital stay was 5.9 days, and all patients remain free of angina at a mean follow-up period of 11.4 months. CONCLUSIONS: Staged MIDCAB and angioplasty is an experimental approach for the management of selected patients with multi-vessel coronary artery disease. Further experience is needed to clarify patient selection and the long-term outcome of this approach.
Aged↗
It is right to publicise recent advances in the media.
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Cardiac Surgical Procedures↗
Left-ventricular-volume reduction for end-stage heart failure.
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Aged↗
Effect of ischaemia and reperfusion on the intracellular concentration of taurine and glutamine in the hearts of patients undergoing coronary artery surgery.
Taurine and glutamine are the most abundant intracellular free amino acids in mammalian hearts where changes in their intracellular concentrations are likely to influence a number of cellular activities. In this study we investigated the effects of ischaemia and reperfusion on the intracellular concentrations of taurine and glutamine in the hearts of patients undergoing coronary artery bypass surgery using cold crystalloid or cold blood cardioplegic solutions. Ischaemic arrest (30 min), using cold crystalloid cardioplegic solution (n = 19), decreased the intracellular concentrations (micromol/g wet weight) of taurine (from 9.8 +/- 0.8 to 7.7 +/- 0.7, P < 0.05) and glutamine (8.7 +/- 0.5 to 7.2 +/- 0.6). After 20 min of normothermic reperfusion the fall in taurine and glutamine was maintained (7.5 +/- 0.5 and 7.4 +/- 0.7 for taurine and glutamine respectively). Myocardial ischaemic arrest with cold blood cardioplegic solution (n = 16) did not cause a significant fall in tissue taurine or glutamine. However, on reperfusion there was a marked fall in the intracellular concentrations of taurine (9.4 +/- 0.5 to 6.5 +/- 0.7) and glutamine (8.0 +/- 0.7 to 5.8 +/- 0.4). The fall in amino acids was associated with a fall in ATP and a rise in tissue lactate. This work demonstrates that irrespective of the cardioplegic solution used to arrest the heart, there is a marked fall in tissue taurine and glutamine which may influence the extent of recovery following surgery. The fall in taurine is largely due to efflux whereas changes in glutamine are due to both transport and metabolism. Ischaemia, hypothermia and changes in the transmembrane concentration gradients are the likely factors responsible for the changes in tissue amino acids.
Adenosine Triphosphate↗
Nitric oxide synthase and adenylyl and guanylyl cyclase activity in porcine interposition vein grafts.
BACKGROUND: A high proportion of autologous saphenous vein grafts occlude as the result of intimal thickening. Blood vessels synthesize substances that may inhibit such intimal thickening. These include cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which are stimulated by prostacyclin and nitric oxide, respectively. The prostacyclin-cAMP and nitric oxide-cGMP axes were therefore investigated in porcine vein grafts. METHODS: Saphenous vein-carotid artery interposition graft procedures were carried out in pigs. One month after the operation, ungrafted saphenous veins, vein grafts, and carotid arteries were excised, the formation of cAMP and cGMP was assessed by radioimmunoassay, and the nitric oxide synthase content was determined by autoradiography. RESULTS: The formation of cAMP and nitroprusside-stimulated cGMP was significantly diminished in vein grafts compared with ungrafted saphenous veins and carotid arteries. Calimycin-stimulated cGMP synthesis (nitric oxide release dependent) and the endothelial nitric oxide synthase content (autoradiography) were significantly elevated in vein grafts compared with ungrafted saphenous veins but were significantly less than those in carotid arteries. CONCLUSIONS: Adenylyl and guanylyl cyclase activity are down-regulated in vein grafts, which may contribute to the development of intimal and medial thickening. Nitric oxide release and endothelial nitric oxide synthase content are up-regulated in vein grafts, which is indicative of an adaptation to the arterial conditions of shear stress and pulsatile pressure.
Adaptation, Physiological↗
Biochemical markers of myocardial injury during cardiac operations.
The evaluation of myocardial damage in relation to cardiac operation from a clinical and a research perspective is of great importance, particularly for the evaluation of different cardioprotective strategies. Although measurements of serum biochemical markers have often been used, their value has been limited by their lack of sensitivity and specificity in the presence of skeletal muscle damage. A newer range of markers are now available that may reliably indicate both perioperative myocardial infarction, as well as more subtle degrees of subclinical myocyte injury. In this review, the application of biochemical markers for clinical and research purposes during cardiac operation is considered.
Biomarkers↗
Dynamic evaluation of the 21-mm Medtronic Intact aortic bioprosthesis by dobutamine echocardiography.
BACKGROUND: High residual transvalvular gradients have been reported with the use of small Medtronic Intact aortic valve prostheses. The aim of this study was to evaluate the hemodynamic performance of 21-mm prostheses using dobutamine Doppler echocardiography. METHODS: Ten patients (7 women; mean age, 79 years) who had undergone aortic valve replacement with 21-mm Medtronic Intact prostheses 19.1 +/- 9.9 (standard deviation) months previously were studied. Dobutamine infusion was started at a rate of 5 microg x kg(-1) x min(-1) and increased to 10 and 20 microg x kg(-1) x min(-1) at 15-minute intervals. Pulsed and continuous-wave Doppler studies were performed at rest and at the end of each stage. Effective orifice area, performance index, and discharge coefficient of each valve were calculated, and peak and mean velocity and pressure drop across the prostheses were measured. Cardiac output was determined by Doppler measurement of flow in the left ventricular outflow tract. RESULTS: Dobutamine stress increased heart rate and cardiac output by 68% and 65%, respectively (both p < 0.005), and mean transvalvular gradient increased from 19.1 +/- 5.1 mm Hg at rest to 33.2 +/- 7.7 mm Hg at maximum stress (p < 0.0001). Regression analyses demonstrated that maximum-stress gradient was independent of all variables except resting gradients (p < 0.004). Body surface area had no effect on the changes in cardiac output, effective orifice area, or transprosthetic gradient at maximum stress. CONCLUSIONS: These data show that the 21-mm Medtronic Intact aortic prosthesis exhibits acceptable hemodynamic performance. Transvalvular gradients remained within a clinically acceptable range, both at rest and at maximum stress. Moreover, overall hemodynamic performance suggests that patient-prosthesis mismatch is unlikely to be a problem of clinical importance when this prosthesis is used.
Aged↗
Prevention of vein graft failure: potential applications for gene therapy.
The use of gene therapy in the clinical setting is believed to be a realistic option for the future. Many clinical trials are underway for treatment of disorders as diverse as cancer, peripheral vascular disease, and numerous monogenic disease. However, gene therapy for vein graft failure may be more distant due to the highly complex, multifactorial aetiology of the disease. Although many of the cellular mechanisms involved in vein graft failure have been reported, important barriers still need to be overcome before gene therapy could become a clinical reality. Further understanding of the molecular mechanisms involved in graft failure will lead to the identification of appropriate therapeutic genes. Moreover, limitations in the current delivery systems need to be overcome to allow efficient, safe delivery and expression of transgenes for the required length of time in vivo. However, currently available gene delivery vectors are extremely useful tools to help in our understanding of vein graft failure. In this review, we address the issues surrounding gene therapy with particular emphasis on its future potential to ameliorate long term vein graft occlusion.
Gene Transfer Techniques↗
Neuropsychologic outcome after normothermic cardiopulmonary bypass.
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Cardiopulmonary Bypass↗
Influence of normothermic systemic perfusion during coronary artery bypass operations: a randomized prospective study.
OBJECTIVES: Normothermic cardiopulmonary bypass has been proposed as a more physiologic technique than hypothermic bypass for the maintenance of the body during cardiac surgery. The aims of this study were to investigate the effects of systemic perfusion temperature on clinical outcome after coronary revascularization. METHODS: Three hundred patients (mean age 60 +/- 9 years, 88% male) were prospectively randomized into three groups: hypothermia (28 degrees C, n = 100), moderate hypothermia (32 degrees C, n = 100), and normothermia (37 degrees C, n = 100). All patients received cold antegrade St. Thomas' Hospital crystalloid cardioplegic solution, and patients in the normothermic group were actively rewarmed during cardiopulmonary bypass (nasopharyngeal temperature 37 degrees C). RESULTS: No differences were found between groups with respect to mortality (1%), intraaortic balloon pump use, perioperative infarction rates, focal neurologic deficits (1%), intubation time, intensive care unit stay, and postoperative hospital stay. Further stepwise regression analysis identified age and intensive care unit stay as important predictors of the variability in postoperative stay (both R2 = 0.114; p < 0.001), whereas perfusion temperature remained a nonsignificant explanator. Normothermic perfusion necessitated larger doses of phenylephrine to maintain arterial pressure above 50 mm Hg during cardiopulmonary bypass (p < 0.0001 vs 28 degrees C, p < 0.01 vs 32 degrees C) but less requirement for electrical defibrillation during reperfusion (p < 0.05 vs 32 degrees C, p < 0.01 vs 28 degrees C). Total chest drainage was not different between groups, but patients undergoing normothermic cardiopulmonary bypass required less transfusion of blood (p < 0.05 vs 28 degrees C and 32 degrees C) and platelets (p < 0.04 vs 32 degrees C, p < 0.001 vs 28 degrees C) in the postoperative period. CONCLUSIONS: Cardiopulmonary bypass temperature did not influence early clinical outcome after routine coronary artery bypass operations. Normothermic systemic perfusion was associated with an increased requirement for vasoconstrictors and reduced requirements for electrical defibrillation and transfusion of blood products.
Bicarbonates↗