PubMed Health⌕ Search

Biomedical subjects

A H Chester

Publications and source records attributed to A H Chester.

At least 55 records · Page 3Linked to original sources
PubMed1996

Inducible nitric oxide synthase is present within human atherosclerotic lesions and promotes the formation and activity of peroxynitrite.

Inflammatory cytokines associated with atherosclerosis may be capable of stimulating the synthesis and activity of inducible nitric oxide synthase (iNOS), which could further influence the pathologic features associated with the disease. Although there is a certain amount of indirect evidence to support the presence of iNOS in atherosclerosis, there has been no definitive study to confirm this. This study has assessed the localization of iNOS within human normal and atherosclerotic vessels by immunocytochemistry, Western blotting, and in situ hybridization. Further, activity of NO synthase has been assessed by detection of nitrotyrosine, which is a marker indicative of the formation and activity of the nitric oxide-derived oxidant, peroxynitrite. In Western blots of crude homogenates of atherosclerotic aorta, the iNOS antiserum reacted with a band of approximately 130 kd (the known molecular weight for iNOS), but no such band was seen in normal aorta. Immunostaining and in situ hybridization confirmed the presence of iNOS in atherosclerotic vessels, in which it was specifically localized to (CD68-positive) macrophages, foam cells, and the vascular smooth muscle. The antiserum to nitrotyrosine reacted with a wide range of protein bands (approximately 180 to 30 kd) in Western blots of atherosclerotic aorta. The distribution of immunostaining for nitrotyrosine was virtually identical to that seen for iNOS and was present in macrophages, foam cells, and the vascular smooth muscle. In conclusion, these studies have demonstrated that stimulated expression of iNOS is associated with atherosclerosis and that the activity of this enzyme under such conditions preferentially promotes the formation and activity of peroxynitrite. This may be important in the pathology of atherosclerosis, which contributes to lipid peroxidation and to vascular damage.

Adult↗
PubMed1995

Oestrogen relaxes human epicardial coronary arteries through non-endothelium-dependent mechanisms.

BACKGROUND: Oestrogen-replacement therapy is associated with a reduced incidence of cardiovascular disease. The acute administration of oestrogen improves myocardial ischemia in women with coronary heart disease. In this study we investigated the relaxing effect of oestradiol-17 beta on human coronary arteries in vitro and determined the role of endothelial modulation in this relaxation by using isolated human coronary arteries. METHODS: Atherosclerosis-free epicardial arteries from men and women were removed from patients undergoing heart or combined heart and lung transplantation. The arteries were cut into ring segments and placed into organ baths containing Tyrode's solution. Changes in isometric tension were measured. The relaxing response to oestradiol-17 beta (10(-10) - 10(-5) mol/l) was investigated and the effects of endothelium, NGmonomethyl-L-arginine and indomethacin on the response of oestradiol-17 beta were assessed. RESULTS: Oestradiol-17 beta (10(-10) - 10(-5) mol/l) induced significant relaxation in coronary arteries pre-contracted with the thromboxane A2 analog (U46619; 3 x 10(-8) mol/l). Relaxation was significantly greater in coronary arteries from female patients. No significant differences were observed between arteries with or without endothelium nor after nitric oxide synthase or cyclo-oxygenase inhibition. These results indicate that oestradiol-17 beta induces human coronary artery relaxation via an endothelium-independent mechanism in vitro. The sex of the patients significantly affects sensitivity of the coronary arterial rings to oestrogen. CONCLUSION: Oestradiol-17 beta-induced coronary relaxation may play an important role in regulation of coronary tone, and may partly explain why oestrogen improves myocardial ischemia in women and why it protects postmenopausal women from the risk of developing coronary heart disease.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1995

L-arginine reverses low coronary reflow and enhances postischaemic recovery of cardiac mechanical function.

OBJECTIVE: To evaluate the effect of L-arginine, the physiological substrate of nitric oxide (NO), upon coronary flow (CF) and mechanical function during reperfusion following cardioplegic arrest. METHODS: Two groups of isolated rat hearts were subjected to cardioplegic arrest for 4 h at 4 degrees C. In group 1 (n = 10) cardioplegic arrest was followed by 4 consecutive periods of reperfusion with Krebs buffer (control), Krebs plus L-lysine (1 mmol/1), Krebs plus L-arginine (1 mmol/1) and Krebs plus L-NGmonomethylarginine (L-NMMA), a specific inhibitor of NO synthesis, (0.5 mmol/1). In group 2, hearts (n = 8) were perfused by Krebs, then L-NMMA, during both pre- and postischaemic periods. In group 3, hearts (n = 8) were perfused by Krebs, then L-arginine (1, 2 and 4 mmol/1). In group 4 (n = 5), NO released into the perfusate was measured before ischaemia and during reperfusion. RESULTS: In group 1, L-arginine enhanced the postischaemic CF (ml/min +/- s.e.m.) from 15.0 +/- 0.4 to 17.2 +/-0.4. This was reduced by L-NMMA to 11.3 +/- 0.3. Postischaemic cardiac output (% of preischaemic value +/- s.e.m.) was increased from 55.8 +/- 2.4 to 80.1 +/- 2.5 by L-arginine and dropped to 54.3 +/- 2.3 with L-NMMA. In group 2, the pre- and postischaemic loss of coronary flow (CF) by L-NMMA was 51% and 31% respectively. In group 3, L-arginine did not modify CF. In group 4 the preischaemic level of NO (in nmol/ml/min) in the coronary effluent, measured by chemiluminescence, was 14.84 +/- 0.83 and dropped significantly (P < 0.05) to levels ranging from 3.80 +/- 0.56 to 4.75 +/- 0.51 during the postischaemic period. CONCLUSION: Exogenous administration of L-arginine improves low coronary reflow and postischaemic mechanical function.

Animals↗
PubMed1994

Effect of mode of application of papaverine on the contractile response of the internal mammary artery.

A study was performed to investigate the duration of action of papaverine applied either intraluminally or in a combined intraluminal and extraluminal fashion in vitro, and how the reactivity of the internal mammary artery (IMA) to a range of vasoconstrictors is affected. Segments of IMA exposed to only intraluminal papaverine (10(-4) mol/l) for 15 min recovered their contractile response to 90 mmol/l potassium chloride to pretreatment levels within 2 h. In contrast, combined intraluminal and extraluminal administration of papaverine resulted in a significant depression of the contractile response to 90 mmol/l potassium chloride (P < 0.001), which persisted for at least 5 h. Responses to 5-hydroxytryptamine, noradrenaline, the thromboxane mimetic U46619, histamine and dopamine were not significantly different between control tissues and those that had received intraluminal papaverine. The duration of action of papaverine is affected by its route of delivery and there are no significant short-term effects on the contractile mechanisms in the arterial wall after intraluminal administration.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1994

Endothelial function and vasodilator profile of the inferior epigastric artery.

In the inferior epigastric artery, endothelium-dependent relaxations in response to substance P, histamine, and acetylcholine were present. These were greater than reported values in saphenous veins but less than the documented responses in internal mammary and gastroepiploic arteries. Endothelium-independent stimulation with nifedipine, papaverine, sodium nitroprusside, and glyceryl trinitrate induced relaxations that also were reduced compared with established arterial conduits. These findings appear to justify the clinical use of the inferior epigastric artery as a coronary bypass graft with monitoring of its long-term results and possibly perioperative pharmacologic manipulations.

Abdominal Muscles↗
PubMed1994

Preferential vasoconstriction to cysteinyl leukotrienes in the human saphenous vein compared with the internal mammary artery. Implications for graft performance.

BACKGROUND: Platelet aggregation with the release of their vasoactive mediators is an important factor contributing to the patency of coronary bypass grafts. However, the role of leukocyte-derived mediators on graft performance is unclear. Leukotrienes (LTs) are proinflammatory mediators released from a variety of leukocytes that possess both vasoactive and mitogenic properties. We have therefore compared the effects of the cysteinyl LTs (C4, D4, and E4) on the human saphenous vein (SV) and human internal mammary artery (IMA). METHODS AND RESULTS: Human SVs from 43 patients (mean age, 58 years) and IMAs from 33 patients (mean age, 57 years) were obtained from individuals undergoing coronary artery bypass surgery for coronary artery disease. The samples were set up in organ baths to record changes in vessel wall tension. In undistended SVs the cysteinyl LTs elicited concentration-dependent contractions. The Emax for LTE4 (4.23 +/- 1.0 mN; n = 6) was significantly less than that observed with either LTC4 (25.7 +/- 4.01 mN; n = 7; P < .001) or LTD4 (26.19 +/- 3.16 mN; n = 7; P < .001). In addition, the LTD4 receptor antagonist ICI 198615 (30 nmol/L) significantly inhibited the LTD4 concentration-response curve but not the LTC4 responses. Furthermore, treatment of the SV with acivicin (0.05 mmol/L), a gamma-glutamyl transpeptidase inhibitor, caused a significant rightward displacement of the LTC4 concentration-response curve. In contrast, LTC4 and LTD4 produced a response in IMAs from only 3 of 29 patients. LTC4 and LTD4 produced small contractions, of which the maximum responses were 3.28 +/- 1.92 mN (n = 5) and 3.12 +/- 1.38 mN (n = 5). LTE4 produced no responses in the IMA. Experiments in which the SV was pretreated with L-NG-monomethyl-L-arginine (L-NMMA; 10(-4) mol/L) or indomethacin (10(-5) mol/L) or was denuded of endothelium had no significant effect on the Emax values for LTE4. Also, the IMA remained unresponsive to cysteinyl leukotrienes after treatment with L-NMMA or indomethacin or endothelium removal. In vitro autoradiography localized specific [3H]-LTC4 and [3H]-LTD4 binding sites (putative receptors) to the smooth muscle cells of both SV and IMA, with greater binding to the SV. CONCLUSIONS: Our data show that there is a preferential contraction to LTs in SV compared with IMA. This difference in smooth muscle cell reactivity to the cysteinyl LTs suggests that endogenous LT production from circulating or infiltrating leukocytes may be an important factor contributing to graft function.

Adult↗
PubMed1994

Effect of surgical preparation and arterialization on vasomotion of human saphenous vein.

To gain an insight into venous physiologic adaptation to arterialization, this study examined the effects of thromboxane, 5-hydroxytryptamine, endothelin, leukotriene C4, and norepinephrine on isolated segments of native and distended human saphenous vein, short-term (up to 1 year) grafts, and long-term (1 to 10 year) grafts. The mean maximum constrictor responses, expressed as percentage of maximum potassium depolarization, were as follows: thromboxane analog U46619: native vein 147.0% +/- 10.5%, distended vein 251.2% +/- 29.1%, short-term graft 174.6% +/- 33.8%, long-term graft 220.9% +/- 21.7%; 5-hydroxytryptamine: native vein 115.6% +/- 6.1%, distended vein 129.9% +/- 13.3%, short-term graft 80.0% +/- 15.0%, long-term graft 95.1% +/- 12.1%; endothelin-1: native vein 126.5% +/- 22.1%, distended vein 138.1% +/- 24.7%, short-term graft 120.7% +/- 43.3%, long-term graft 171.4% +/- 26.0%; leukotriene C4: native vein 49.9% +/- 8.7%, distended vein 78.9% +/- 11.8%, short-term graft 90.8% +/- 39.1%, long-term graft 7.4% +/- 5.0%; and norepinephrine: native vein 127.0% +/- 9.3%, distended vein 155.0% +/- 17.8%, short-term graft 61.6% +/- 11.3%, long-term graft 80.1% +/- 7.7%. The vasoconstriction elicited by each agonist, in absolute terms (in millinewtons), diminished with age of graft. We conclude that surgical treatment of saphenous vein immediately renders it more responsive to U46619, norepinephrine, and leukotriene C4. An agonist-specific profile of response was evident up to 10 years after operation, which may affect myocardial blood supply when luminal bore is diminished by vein graft disease.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

Action of vasoactive intestinal peptide and distribution of its binding sites in vessels used for coronary artery bypass grafts.

In an attempt to establish the possible role of vasoactive intestinal peptide (VIP) in the regulation of vasomotor tone of coronary artery bypass grafts, this study examined the action of this peptide and the distribution of [125I]VIP binding sites in isolated human gastroepiploic artery (GEA), internal mammary artery (IMA) and saphenous vein. VIP (10(-10)-3 x 10(-7) M) elicited concentration-dependent relaxations in ring segments that were preconstricted with the thromboxane analog U46619. The maximal response was mean +/- SEM 79 +/- 4%, 52 +/- 8% and 23 +/- 3% of glyceryl trinitrate (3 x 10(-5) M)-induced maximal smooth muscle relaxation in the GEA, IMA and saphenous vein, respectively. Both receptor-binding and competition studies indicated that there was a higher density of [125I]VIP binding to smooth muscle cells of the GEA and IMA than to the saphenous vein. Total binding, at 50pM [125I]VIP, was 604 +/- 89, 381 +/- 64 and 87 +/- 12 amol/mg wet weight in the GEA, IMA and saphenous vein, respectively. Dense binding of [125I]VIP was associated with the tunica media in all the vessels studied. There was also binding to perivascular regions with no obvious binding to endothelial cells. These data demonstrate that arterial grafts, particularly the GEA, are more sensitive to the relaxant effect of VIP and this may possibly be due to a higher receptor density.

Adult↗
PubMed1993

Vasoconstrictor profile of the inferior epigastric artery.

The inferior epigastric artery is a putative arterial bypass graft. The receptor mechanisms that control vascular tone are thought to play a role in the performance of bypass conduits. We have compared the vascular reactivity of the inferior epigastric artery with that of the internal mammary artery. Segments from a total of 15 inferior epigastric and 12 internal mammary arteries were examined for their response to increasing concentrations of noradrenaline, 5-hydroxytryptamine, dopamine, histamine, endothelin-1, or the thromboxane analogue U46619. The responsiveness of the smooth muscle was significantly greater in the inferior epigastric artery (p < 0.05) as judged by contractions elicited by 90 mmol/L potassium chloride. However, although the response of the inferior epigastric artery tended to be greater, this significant enhancement of smooth muscle function was not paralleled by the maximal responses of noradrenaline, 5-hydroxytryptamine, dopamine, histamine, or endothelin-1. However, the tension generated in response to U46619 did differ significantly, with maximal responses in the inferior epigastric and internal mammary arteries of 59.2 +/- 8.3 mN and 35.0 +/- 3.6 mN, respectively. When receptor function was compared by expressing the response as a percentage of that of 90 mmol/L potassium chloride, it was revealed that noradrenaline was capable of inducing significantly greater relative contractions in the internal mammary artery (114.8% +/- 20.5%) as compared with the inferior epigastric artery (49.9% +/- 19.1%); the potency of this constrictor was sixfold greater in the internal mammary artery.(ABSTRACT TRUNCATED AT 250 WORDS)

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

Effect of peri-operative storage solution on the vascular reactivity of the human saphenous vein.

The performance of the saphenous vein as a bypass conduit in myocardial revascularisation may, in part, be determined by its vascular reactivity. The present study investigates whether the choice of peri-operative storage solution influences the response of this vessel to a range of vasoconstrictors and vasodilators. Saphenous vein ring segments (210) were obtained from 24 patients undergoing coronary artery bypass surgery, and following a 1 h incubation in either (1) heparinised blood, (2) heparinised saline, (3) 199-TC solution, (4) St. Thomas' cardioplegic solution or (5) plasma-lyte solution, rings of vein were set up as organ bath preparations. The relative magnitude of control constrictor response was: noradrenaline = 5-hydroxytryptamine > or = dopamine > histamine > acetylcholine. There was a significantly different (P < 0.05) enhanced response to noradrenaline and 5-hydroxytryptamine in segments stored in heparinised saline compared to 199-TC; similarly, dopamine and noradrenaline responses were significantly potentiated (P < 0.05) following storage in heparinised saline compared to cardioplegia. Storage in plasma-lyte enhanced the response significantly storage in heparinised saline compared to cardioplegia. Storage in plasma-lyte enhanced the response significantly (P < 0.05) to acetylcholine alone. None of the solutions had a significant effect on the potency (EC50) of the constrictors. Relaxations of pre-constricted segments were recorded to acetylcholine and sodium nitroprusside, but there was no difference in efficacy or potency in these responses following storage in the different solutions. This study demonstrates that the choice of peri-operative storage solution may influence the vascular reactivity of the human saphenous vein.

Acetates↗
PubMed1993

Enhanced excretion of urinary leukotriene E4 in coronary artery disease and after coronary artery bypass surgery.

BACKGROUND: Excretion of leukotriene (LT) E4, the major urinary metabolite of cysteinyl leukotrienes in humans, is increased in patients with unstable angina and myocardial infarction, suggesting that cysteinyl leukotrienes are released into the circulation during episodes of myocardial ischaemia. Furthermore, leukotrienes are known to induce potent vasoconstrictive effects in human atherosclerotic coronary arteries and the saphenous vein. Accordingly, we measured urinary excretion of LTE4 in patients with stable coronary artery disease both before and after coronary artery bypass surgery, and in age-matched healthy controls, to study the relation between the systemic synthesis of cysteinyl leukotrienes and stable coronary artery disease, as well as the possible changes after bypass surgery. METHODS: LTE4 was isolated from urine samples by solid-phase extraction, purified by reverse-phase high-performance liquid chromatography, and subsequently quantified by radioimmunoassay. RESULTS: In patients with coronary artery disease, preoperative urinary LTE4 levels were normally distributed on a log10 scale, with a genometric mean of 115 pmol/mmol creatinine (95% confidence interval 67-196) compared with 63.0 pmol/mmol creatinine (95% confidence interval 47.9-82.7) in healthy subjects (P < 0.05). Urinary LTE4 levels increased further in patients after coronary artery bypass surgery with levels peaking on the second day after surgery (266.2 pmol/mmol creatinine, 95% confidence interval 167.2-423.9) at significantly higher than preoperative levels (P < 0.02), and then decreasing by day 3. CONCLUSIONS: Levels of cysteinyl leukotrienes are raised in coronary artery disease patients both before and after coronary artery bypass surgery. As these mediators are capable of inducing potent vasoconstrictive effects on atherosclerotic coronary arteries and the saphenous vein, our results could have important clinical and possibly therapeutic implications.

Adult↗
PubMed1993

Different responses of the human gastroepiploic and internal mammary arteries to vasoactive peptides.

Peptidergic influences have been implicated in the control of tone in human arteries. We have examined the response of human gastroepiploic arteries (GEA) and internal mammary arteries (IMA) to three vasoactive peptides in vitro. Vasoactive intestinal peptide (VIP, 10(-11) to 3 x 10(-7) M) elicited relaxations in the GEA and IMA [maximum generated response (Emax) 74.6 +/- 9.4 and 56.5 +/- 7.7%, respectively] that were significantly reduced after removal of endothelium. NG-monomethyl-L-arginine (L-NMMA) and indomethacin partially inhibited the response of the GEA to VIP (P < 0.05). In the IMA, VIP-induced relaxation was significantly attenuated by L-NMMA but not indomethacin. Bombesin (10(-10) to 3 x 10(-6) M) produced endothelium-dependent relaxation selectively in the GEA, which was only inhibited by indomethacin (Emax reduced from 59.0 +/- 10.0 to 12.8 +/- 4.9%, P < 0.001). Bombesin elicited a weak endothelium-independent constriction in the IMA, giving 12.7 +/- 1.2% of the response to 90 mM KCl. Gastrin (10(-10) to 3 x 10(-7) M) had no effect on IMA segments but induced a relaxation of 40.0 +/- 3.2% in the GEA via a direct action on the smooth muscle. It is concluded that human GEA and IMA exhibit heterogenous responses to VIP, bombesin, and gastrin that may have important physiological and clinical implications.

Adolescent↗
PubMed1993

Interaction between thromboxane A2 and 5-hydroxytryptamine receptor subtypes in human coronary arteries.

BACKGROUND: Platelets release two powerful vasoconstrictors--thromboxane A2 (TXA2) and 5-hydroxytryptamine (5-HT). Animal studies have suggested that these two substances may act in a synergistic fashion to stimulate platelet activity and smooth muscle vasoconstriction. METHODS AND RESULTS: To assess the interaction between TXA2 and 5-HT at the individual 5-HT receptor subtypes reported to mediate contraction, the effect of the amine was determined in the presence of differing concentrations of the thromboxane mimetic U46619. A total of 168 vessel segments were removed from 20 recipient hearts of patients undergoing cardiac transplantation. Segments were set up in isolated organ baths and tested for their response to 5-HT in the presence of an EC10, EC30, or EC50 concentration of U46619 (n = 4). A synergistic response was only seen in a small number of the segments tested under these conditions. However, in the presence of ketanserin (10(-6) M) to block 5-HT2 receptors, there was a significant increase in the response to 10(-6) M 5-HT in the presence of both the EC30 (p < 0.025) and EC50 (p < 0.05) concentrations of U46619 (n = 4). The potentiation of non-5-HT2 receptor mediated responses to 5-HT, in the presence of U46619 (EC30), could be prevented by 10(-7) M methiothepin, a nonselective 5-HT1-like/5-HT2 receptor antagonist. CONCLUSIONS: These data indicate that TXA2 receptor activation can increase the response of 5-HT mediated by 5-HT1-like receptors in human coronary arteries. 5-HT1-like receptors have been shown to mediate the contractile effect of 5-HT in patients with variant and chronic stable angina. Thus, platelet contents may act together at specific receptor subtypes in the induction of myocardial ischemia.

Adult↗
PubMed1993

Influence of atherosclerosis on the vascular reactivity of isolated human epicardial coronary arteries to leukotriene C4.

Leukotrienes, lipid mediators derived from arachidonic acid by the 5-lipoxygenase pathway, have been implicated in a variety of myocardial ischemic events including myocardial infarction and coronary spasm. We have examined the comparative effects of leukotriene C4 in isolated human non-atherosclerotic and atherosclerotic coronary arteries to gain an insight into the role of leukotrienes in coronary heart disease. Human coronary arteries, obtained from recipient hearts at the time of cardiac transplantation, were cut into rings and examined in an isolated organ bath. In atherosclerotic arteries leukotriene C4 (1nM-100nM) produced a maximal contractile response of 54.9 +/- 7.98% KCI (n = 7) and the mean EC50 value was 11.1nM (95% confidence interval: 9.4-13.0). The leukotriene receptor antagonist ICI-198,615 (3 x 10(-8)M) produced an approximate 50-fold rightward shift of the leukotriene C4 dose-response curve (n = 5). In contrast, non-atherosclerotic arteries were either non-responsive (n = 5) or only weakly responsive (n = 2) to leukotriene C4 (1nM-100nM), producing an average maximum response of 3.65 +/- 3.05% KCI (n = 7; p < 0.01 atherosclerotic vs non-atherosclerotic). In the presence of indomethacin and in vessels denuded of endothelium, non-atherosclerotic arteries remained unresponsive to leukotriene C4 (n = 3). In addition, leukotriene C4 did not relax preconstricted vessels (n = 7). In vitro autoradiography showed specific [3H]-leukotriene C4 binding to smooth muscle in both non-atherosclerotic and atherosclerotic arteries, with no evidence of endothelium-dependent binding.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Comparison of cyclic GMP in human internal mammary artery and saphenous vein: implications for coronary artery bypass graft patency.

OBJECTIVE: The aim was to examine the capacity of the human saphenous vein (native and surgically prepared) and the internal mammary artery to generate cyclic GMP, the second messenger that mediates smooth muscle relaxation following production of nitric oxide. METHODS: 209 vessel segments were used from 22 patients undergoing coronary revascularisation. Isolated vessel segments were stimulated with a range of endothelium dependent and endothelium independent agonists and flash frozen for radioimmunoassay for cyclic GMP. RESULTS: Control/basal levels of cyclic GMP were significantly higher in the internal mammary artery than either native or distended saphenous vein. Endothelium dependent agonist stimulation with acetylcholine, bradykinin, or substance P induced significant increases in cyclic GMP in internal mammary artery and native saphenous vein, whereas distended veins showed non-significant changes in response to agonist stimulation. Endothelium removal abolished agonist stimulated increases in cyclic GMP. Glyceryl trinitrate and sodium nitroprusside elicited significant further increases in cyclic GMP in native vein and internal mammary artery. All values obtained were significantly greater in arterial than in venous tissue. CONCLUSION: Differences in basal and stimulated cyclic GMP activity in arteries and veins have been shown. This could represent an additional protective mechanism against constrictor influences in arterial bypass grafts, which may explain their documented better long term performance.

Acetylcholine↗
PubMed1992

Ischaemic endothelial dysfunction after single or multidose cardioplegia.

The effect of ischaemia, either alone or after a single or multidose infusion of St Thomas' Hospital cardioplegia solution (ST), on endothelial function was studied by examining its influence on 5-Hydroxytryptamine- (5-HT-) and nitroglycerine- (GTN-) induced coronary vasodilation in the isolated rat heart. Eighty rat hearts were perfused on a modified Langendorff preparation. Thirty minutes of unprotected ischaemia (N = 16) abolished the vasodilatory response to 5-HT but maintained the response to GTN (expressed as % of the control value 5-HT, pre 45.0 +/- 3.5, post 2.3 +/- 3.2, GTN, pre 42.3 +/- 4.4, post 39.8 +/- 4.0). The increase in coronary flow induced by either agent was unaltered following 30 or 60 min of ischaemia protected by a single dose of ST (N = 16 in each). Ninety minutes of ischaemia preceded by a single infusion of ST (N = 16) markedly reduced the 5-HT response but maintained the vasodilation induced by GTN (5-HT, pre 37 +/- 2.6, post 6.9 +/- 2.6, GTN, pre 40.1 +/- 2.5, post 37 +/- 2.8). During 90 min of ischaemia, infusion of an additional dose of ST after 45 min (N = 8) or two extra doses every 30 min (N = 8) maintained the 5-HT-induced increase in coronary flow (pre 39.5 +/- 3.9, post 36.4 +/- 3.5). It can be concluded that coronary vascular endothelium is more susceptible to ischaemic damage when compared with vascular smooth muscle. This results in early loss of endothelium-dependent vasodilation. Multidose infusion of St Thomas' Hospital cardioplegia solution is superior to a single infusion in protecting endothelial function following prolonged cardiac ischaemia.

Animals↗
PubMed1992

Effect of endothelin on normal and diseased human coronary arteries.

We have examined the action of endothelin on healthy and diseased human epicardial coronary arteries to assess its possible role in coronary vascular disorders such as vasospasm and atherosclerosis. Endothelin (10(-10) mol l-1-10(-7) mol l-1) produced dose-dependent contractions in both normal and diseased vessels. The level of constriction was significantly greatly in healthy vessels at 10(-8) mol l-1 endothelin. A greater response was recorded in smaller, more distal vessel segments, irrespective of the pathology of the tissue. Endothelium denudation of disease-free segments had no significant effect on the response to endothelin. In the presence of a threshold dose of endothelin (10(-9) mol l-1), there was no measurable increase in the tension generated by potassium chloride, the thromboxane-mimetic U46619, noradrenaline and histamine. However, the response to 5-HT showed a large increase in arteries from four patients (440-147%) but slight or no increase in arteries from another three patients. We conclude that the interaction with other vasoconstrictor substances is a possible mechanism whereby endothelin may be involved in coronary artery vasospasm. In addition, endothelin may also be involved in the regulation of vascular tone of the small vessels of the heart.

Adult↗