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Biomedical subjects

G D Angelini

Publications and source records attributed to G D Angelini.

At least 127 records · Page 7Linked to original sources
PubMed1997

Cardiac troponin T and troponin I release during coronary artery surgery using cold crystalloid and cold blood cardioplegia.

OBJECTIVE: To evaluate and compare myocardial protection using cold crystalloid and blood cardioplegia by measuring release of cardiac Troponin T and Troponin I during coronary artery surgery. METHODS: Forty two patients undergoing myocardial revascularization were prospectively randomised into two groups in whom myocardial protection was achieved with either antegrade cold (4 degrees C) crystalloid (CCP) (n = 21) St. Thomas' I cardioplegic solution. Serial venous blood samples were collected for measurement of cardiac Troponin T and Troponin I, prior to induction of anesthesia and at 4, 12, 24 and 48 h after removal of the aortic cross clamp. RESULTS: There were no hospital deaths in the two groups and one patient in each group suffered a perioperative myocardial infarction. Rising levels of Troponin T and Troponin I were found in all patients. Serum concentrations increased as early as 4 h after removal of the aortic cross clamp, and reached a peak at 12 h postoperatively in both groups. These levels subsequently declined, but remained higher than preoperative values at 48 h. There were no differences between the two groups with respect to serum Troponin T and I release at 4, 12, 24 and 48 h, area under the respective curves, and peak Troponin T and I release. Serum Troponin levels were significantly higher in patients with unstable angina and in two patients who suffered a perioperative myocardial infarction. CONCLUSION: Serum release of cardiac Troponin T and Troponin I is significantly raised in low risk patients undergoing myocardial revascularization. This release is similar when either cold crystalloid or cold blood cardioplegia are used. This may imply that both methods offer identical protection to the myocardium in a low risk group of patients.

Aged↗
PubMed1997

The influence of surgical preparation on cyclic nucleotide synthesis in an organ culture of human saphenous vein.

OBJECTIVES: To investigate adenosine cyclic 3'5' monophosphate (cAMP) and guanosine cyclic 3'5' monophosphate (cGMP) synthesis in freshly isolated and surgically prepared human saphenous vein before and after culture. SETTING: Bristol Heart Institute, Bristol, U.K. METHODS: Freshly isolated and surgically prepared human saphenous vein was obtained from patients undergoing coronary artery bypass graft surgery. cAMP and cGMP synthesis, was assessed by radioimmunoassay in response to specific simulators in segments of saphenous veins after collection and following 14 days culture. RESULTS: Immediately after collection there was a significant reduction in the synthesis of cAMP (forskolin and prostaglandin E1-stimulated) and cGMP (sodium nitroprusside-stimulated) in surgically prepared compared to freshly isolated saphenous veins. In contrast, following 14 days in culture, cAMP and cGMP synthesis was significantly elevated in surgically prepared compared to freshly isolated saphenous veins. CONCLUSIONS: These data indicate that surgical preparation results in a marked reduction in cyclic nucleotide synthesis in saphenous vein which may be relevant to the pathophysiology of early vein graft failure. The normalisation of both cAMP and cGMP synthesis in surgically prepared veins following 14 days culture indicates that cyclic nucleotide synthesising capacity may not be a major determinant of neointima formation in this experimental model.

Acetylcholine↗
PubMed1997

Vein quality influences neointimal hyperplasia in an organ culture model of human saphenous vein.

OBJECTIVES: The severity of pre-existing pathological changes in human saphenous vein (HSV) correlates with the development of vein graft stenosis and graft patency. The aim of this study was to investigate the influence of pre-existing intimal hyperplasia on development of the neointima in vitro, using an organ culture model. MATERIALS AND METHODS: Segments of HSV were harvested during coronary artery bypass surgery. Histology was performed on part of the vein; the remainder was maintained in culture. Pre-existing intimal thickness (PIT) in HSV from day 0 and neointimal thickness (NIT) in cultured HSV were measured using computerised image analysis on histological sections. Day 0 and 14 veins were compared with respect to intimal hyperplasia. RESULTS: Twelve pairs of veins were examined. A mean tissue ATP of 297 nmoles/g wet weight for cultured. HSV confirmed cell viability. Mean PIT was 180 microns (CI: 86-274) and mean NIT was 60 microns (CI: 48-72), with a significant correlation between them using the Spearman Rank test (Rs = 0.72; p = 0.008). CONCLUSIONS: Pre-existing vein quality as measured by PIT correlates with the development of neointimal hyperplasia in culture, adding further support to clinical evidence that poor vein quality predisposes to vein graft stenosis due to an inherent susceptibility to intimal hyperplasia.

Graft Occlusion, Vascular↗
PubMed1997

Effect of copper on nitric oxide synthase and guanylyl cyclase activity in the rat isolated aorta.

1. The potential role of copper (Cu2+) in modulating the activity of nitric oxide synthase (NOS) and guanylyl cyclase (GC) was investigated by use of diethyldithiocarbamic acid (DEDCA), a high affinity Cu2+ chelator. 2. DEDCA 100 microM inhibited sodium nitroprusside (SNP; 0.005-10 microM)-evoked relaxation of rat isolated aortic rings precontracted with 3 microM phenylephrine (PE). A lower concentration of DEDCA (10 microM) did not significantly attenuate SNP-evoked responses but did inhibit relaxation to the endothelium-dependent dilator, A23187 (0.01-10 microM). 3. The presence of 100 microM Cu2+, but not 100 microM Fe2+, alone enhanced A23187- and SNP-evoked relaxation of aortae precontracted with PE. 4. The inhibitory effect of DEDCA on SNP- and A23187-induced relaxation was reversed by equimolar concentrations of Cu2+ but not Fe2+, indicating that DEDCA does not act via removal of haem-iron from the NOS and GC complexes. 5. Superoxide dismutase (30 mu ml-1) was without effect on the inhibition of DEDCA relaxation induced by either SNP or A23187 in aortae precontracted with PE. 6. When assessed by radioimmunoassay, DEDCA inhibited SNP- and A23187-stimulated cyclic GMP formation with IC50 values of 0.5 microM and 50 microM, respectively. 7. These data demonstrate that Cu2+ plays a role in controlling NOS and GC activity in the rat aorta.

Animals↗
PubMed1997

Effects of sildenafil, a type-5 cGMP phosphodiesterase inhibitor, and papaverine on cyclic GMP and cyclic AMP levels in the rabbit corpus cavernosum in vitro.

OBJECTIVE: To investigate further the mechanisms of action of sildenafil, a highly selective and potent inhibitor of type 5 cGMP phosphodiesterase (PDE5) that has proved effective in the treatment of erectile dysfunction, by assessing its effect on the in vitro formation of cGMP and cAMP in the corpus cavernosum of the rabbit. MATERIALS AND METHODS: Male New Zealand White rabbits (2.5 kg) were killed and their penises rapidly excised, cut into segments and pooled. Penile segments were then incubated with various concentrations of sildenafil or papaverine. The formation of cGMP was stimulated with increasing concentrations of sodium nitroprusside (SNP) and the cGMP and cAMP concentrations measured by radioimmunoassay. Responses were compared to those obtained with papaverine, which is used therapeutically as an erectogen. RESULTS: In the presence or absence of SNP, sildenafil increased cGMP concentrations in rabbit penile tissue with increasing dose; the increase was greatest (about 28-fold) when cGMP was stimulated with SNP (up to 10 mumol/L). At all stimulatory concentrations of SNP, the effective concentrations for 50% stimulation (EC50) of sildenafil were 430-520 nmol/L. Concentrations of cAMP were unaltered by sildenafil. Papaverine enhanced cGMP formation in response to SNP, but at much higher concentrations than did sildenafil (> or = 10 mumol/L). CONCLUSIONS: Sildenafil specifically increases cGMP levels in rabbit corpora cavernosa; the increase is greater in the presence of SNP indicating that, in vivo, sildenafil may enhance erection by the augmentation of nitric oxide-mediated relaxation pathways. The erectogenic effect of sildenafil is mediated by a specific enhancement of cGMP accumulation in the corpus cavernosum, consistent with the known activity of sildenafil as a potent and highly selective inhibitor of cGMP-specific PDE.

Animals↗
PubMed1997

Changes in myocardial concentration of glutamate and aspartate during coronary artery surgery.

Myocardial ischemic arrest, using a cold crystalloid cardioplegic solution, decreases intracellular concentrations of glutamate (from 6.2 +/- 0.5 to 4.5 +/- 0.45 micromol/g wet weight, n = 19, P < 0.05) and ATP (from 3.0 +/- 0.4 to 1.9 +/- 0.3 micromol/g wet weight, n = 9, P < 0.05) but not aspartate. After 20 min of normothermic reperfusion, the fall in glutamate and ATP was maintained (4.5 +/- 0.52 and 2.0 +/- 0.2 micromol/g wet weight, respectively), and there was a fall in aspartate (from 1.32 +/- 0.12 to 0.9 +/- 0.1 micromol/g wet weight). Myocardial arrest with cold blood cardioplegic solution did not cause a significant fall in tissue ATP, glutamate, or aspartate. However, after reperfusion all three fell significantly. With the exception of a fall in tissue valine during ischemia with cold crystalloid cardioplegic solution and a rise in alanine during ischemia with cold blood cardioplegic solution, there were no significant changes in tissue alanine, valine, leucine, or isoleucine during ischemia or after reperfusion using crystalloid or blood cardioplegic solutions. This work documents the changes in the intracellular concentrations of important metabolites in the hearts of patients undergoing coronary artery surgery using different myocardial protection techniques.

Adenosine Triphosphate↗
PubMed1997

Short-term exposure to thapsigargin inhibits neointima formation in human saphenous vein.

Vascular smooth muscle cell (VSMC) migration and proliferation are involved in the intimal thickening responsible for late vein graft failure. In addition to growth and chemotactic factors, VSMCs require expression of matrix-degrading enzymes, e.g., metalloproteinases (MMP), to relieve the antiproliferative and antimigratory constraints of the extra-cellular matrix. Thapsigargin irreversibly inhibits Ca(2+)-ATPase, eliciting an increase in intracellular Ca2- and depletion of the intracellular calcium pools that are thought to be involved in the control of VSMC migration, VSMC proliferation, and MMP activity. We therefore studied the effect of thapsigargin on VSMC migration, VSMC proliferation, and MMP expression in human saphenous vein organ cultures. Vein segments were cultured for 14 days, and VSMC proliferation and migration were determined by autoradiography. Cell death was assessed using in situ end-labeling and lactate dehydrogenase release. Using Western blotting, we examined MMP-2 and MMP-9 and tissue inhibitor of metalloproteinases (TIMP)-1 and TIMP-2 expression. Exposure to thapsigargin at 10 nmol/L for 60 minutes before culture significantly inhibited neointimal thickening (60%, P < .05), intimal and medial VSMC proliferation (32%, P < .05 and 37%, P < .05, respectively), and VSMC migration (36%, P < .05). Thapsigargin at 10 nmol/L did not significantly increase cell death or MMP-2, MMP-9, TIMP-1, and TIMP-2 expression. These results suggest that blockade of Ca(2+)-ATPase by thapsigargin inhibits VSMC migration and proliferation involved in neointimal formation without affecting MMP-2 and MMP-9 expression. Because short-term exposure to thapsigargin was sufficient to inhibit neointima formation, this drug may prove useful in the treatment of intimal thickening after arterial bypass graft surgery.

Apoptosis↗
PubMed1997

Hemodynamics of St. Jude Medical prostheses in the small aortic root: in vivo studies using dobutamine Doppler echocardiography.

BACKGROUND AND AIMS OF THE STUDY: The well known correlation between prosthetic valve orifice area and transvalvular pressure drop has raised concerns about the presence of significant residual gradients when only a small-sized prosthesis can be implanted, particularly in patients with a large body surface area. The aim of this study was to study the hemodynamic performance of small-size St. Jude Medical aortic prostheses using dobutamine echocardiography. METHODS: Fifteen patients (14 females, one male, of mean age 67 years) who had undergone aortic valve replacement with size 19 mm St. Jude Medical prostheses at a mean of 19 +/- 8 (SD) months previously were studied. Dobutamine infusion was started at a rate of 5 micrograms/kg/min and increased to 10 and subsequently to 20 micrograms/kg/min at 15-min intervals. Pulsed and continuous-wave Doppler studies were performed at rest and at the end of each stage. Effective orifice area (EOA) and mean gradient across each prosthesis were calculated, and cardiac output (CO) was determined by Doppler measurement of flow in the left ventricular outflow tract. RESULTS: Dobutamine-stress increased heart rate and cardiac output by 57% and 86% respectively (both p < 0.0005), and mean transvalvular gradient increased from 22.0 +/- 4.9 mmHg at rest to 41.9 +/- 9 mmHg at maximum stress (p < 0.0001). Regression modeling analyses demonstrated that maximum stress gradient was independent of all variables except resting gradient (p = 0.0068). Body surface areas had no effect on the changes in cardiac output, effective orifice area or transprosthetic gradient at maximum stress. CONCLUSIONS: These data demonstrate that the size 19 mm St. Jude Medical prosthesis exhibits favorable hemodynamic performance. Transvalvular gradients remained within a clinically acceptable range, both at rest and under stress conditions. Moreover, in the patient population studied, overall hemodynamic performance indicates that with St. Jude Medical aortic valves, patient-prosthesis mismatch is unlikely to be a problem of clinical importance.

Adult↗
PubMed1996

Experimental models of accelerated atherosclerosis syndromes.

The processes of angioplasty restenosis, vein graft failure, and transplant atherosclerosis, collectively termed 'syndromes of accelerated atherosclerosis', have been the focus of significant clinical and experimental research. Limitations of clinical studies have forced emphasis onto experimental animal models for the purpose of determining pathophysiology and evaluation of potential therapeutic strategies. However, the apparent failure of many in vivo animal models to predict interventional outcome in humans has raised doubt over their suitability as models of these pathophysiological states. Similar criticism has befallen the use of in vitro techniques for elucidating pathophysiology of the cellular elements. An awareness of the shortcomings of the various experimental models in use would therefore seem prerequisite both to a more critical evaluation of data generated from their use, and to the development of truly effective therapeutic strategies for humans.

Animals↗
PubMed1996

Influence of external stent size on early medial and neointimal thickening in a pig model of saphenous vein bypass grafting.

BACKGROUND: Late saphenous vein graft failure results from intimal and medial thickening due to migration and proliferation of vascular smooth muscle cells and superimposed atheroma. These changes may represent an adaptation by the vein to its insertion into the arterial system. Using a porcine model of arteriovenous bypass grafting, we recently demonstrated that supporting the graft with a nonrestrictive external Dacron velour stent significantly reduced intimal hyperplasia and total wall thickness. In the present study, we investigated the influence of different external stent sizes on graft wall dimensions and cell proliferation. METHODS AND RESULTS: Three stent sizes were tested: mildly restrictive, nonrestrictive, and oversized (5, 6, and 8 mm in diameter, respectively). Four weeks after grafting, total wall thickness was decreased 40% by 5-mm stents (P = .02), 66% by 6-mm stents (P = .0004), and 81% by 8-mm stents (P = .02 versus unstented grafts). Neointimal thickness was reduced almost 62% by 6-mm and 72% by 8-mm stents (both P = .01) but not by 5-mm stents. As a result, the encroachment of the intima into the lumen was reduced approximately 70% by 6- or 8-mm stents (P = .02 and P = .01 versus unstented grafts, respectively). Both neointimal and medial cell proliferation were significantly reduced by all three stents compared with unstented grafts. CONCLUSIONS: External stenting of saphenous vein bypass grafts reduces early intimal and medial hyperplasia. Oversized stents give equally profound suppression of intimal thickening, obviating the need for precise size matching with the graft and greatly simplifying the surgical procedure.

Animals↗
PubMed1996

Effects of cardiopulmonary bypass temperature on pulmonary gas exchange after coronary artery operations.

BACKGROUND: Pulmonary dysfunction is one aspect of the postoperative morbidity associated with cardiopulmonary bypass. Normothermic systemic perfusion can result in shorter intubation times, which have been attributed to improved pulmonary gas exchange, but the influence of perfusion temperature on pulmonary gas exchange itself is not known. METHODS: Pulmonary gas exchange was assessed using alveolar-arterial oxygen pressure gradients in 45 patients undergoing routine coronary revascularization who were randomized to undergo cardiopulmonary bypass at 28 degrees C, 32 degrees C, or 37 degrees C. This was part of a more comprehensive study of the effects of temperature on bodily systems. The gradients were estimated preoperatively with the patients breathing air, again over a period between 2 and 4 hours postoperatively during mechanical ventilation with three different oxygen concentrations (30%, 40%, and 60%), and again 1 hour after extubation while breathing the same three oxygen concentrations. RESULTS: Preoperative alveolar-arterial oxygen pressure gradients on air were 24.4 +/- 8.2 mm Hg (mean +/- standard deviation) (28 degrees C), 24.5 +/- 20.4 mm Hg (32 degrees C), and 20.5 +/- 9.5 mm Hg (37 degrees C). Postoperatively, during ventilation and after rewarming, the gradients increased with the increase in inspired oxygen fraction concentrations (30% to 60%) from 67.1 +/- 12.0 mm Hg to 193.1 +/- 30.5 mm Hg (28 degrees C), from 76.4 +/- 20.6 mm Hg to 246.7 +/- 47.7 mm Hg (32 degrees C), and from 79.0 +/- 18.0 mm Hg to 222.9 +/- 40.5 mm Hg (37 degrees C), respectively. A similar pattern was noted 1 hour after extubation, when the gradients increased from 72.4 +/- 12.5 mm Hg to 256.6 +/- 26.5 mm Hg (28 degrees C), from 75.7 +/- 13.9 mm Hg to 252.7 +/- 38.3 mm Hg (32 degrees C), and from 69.1 +/- 19.3 mm Hg to 253.1 +/- 33.0 mm Hg (37 degrees C). There were no significant differences in alveolar-arterial oxygen pressure gradient between the three groups during ventilation or after extubation. CONCLUSIONS: Cardiopulmonary bypass perfusion temperature does not influence alveolar-arterial oxygen pressure gradients in the first 12 hours after routine coronary artery bypass grafting in patients with uncompromised pulmonary and left ventricular function.

Carbon Dioxide↗
PubMed1996

Reduced prostacyclin and increased leukotriene B4 synthesis in porcine venous-arterial grafts.

BACKGROUND: Migration and proliferation of vascular smooth muscle cells in the intima and superimposed atheroma are the main changes underlying late failure of saphenous vein bypass grafts. There is evidence that these events are partly modulated by complex interactions between inhibitors of vascular smooth muscle cell proliferation, such as prostacyclin (PGI2), and mitogens, such as leukotriene B4 (LTB4). Because the relative balance between these eicosanoids may play a role in vein graft failure, the synthesis of PGI2 and LTB4 was measured in porcine saphenous vein-carotid artery grafts 4 weeks after implantation and compared with ungrafted vein and common carotid artery from the same animal. METHODS: Vessels were cut into 2-mm squares and preincubated in Dulbecco's minimum essential medium for 4 hours at 37 degrees C. Tissues were then further incubated with Dulbecco's minimum essential medium containing a range of concentrations of noradrenaline, arachidonate, and calcium ionophore A23187. Release of PGI2 and LTB4 into the supernatant was then assessed by radioimmunoassay. RESULTS: In response to all stimulators, PGI2 release was markedly diminished in vein grafts compared with ungrafted saphenous veins and carotid arteries. The patterns of responses were similar in each vessel type. In contrast, LTB4 release was significantly enhanced in vein grafts compared to ungrafted saphenous veins and carotid arteries. CONCLUSIONS: These data indicate that there is a down-regulation of cyclooxygenase or PGI2 synthase in porcine vein grafts, which may constitute a further phenotypic change that would augment the hyperplastic process. Local increases in LTB4 synthesis in the vein graft, which indicates an induction of lipoxygenase and LTB4 synthase enzymes (and possibly reflects release from leukocytes which have infiltrated the graft), may contribute to increased intimal proliferation by direct promitogenic effects on smooth muscle cells.

Animals↗