[EFFECT OF SEROTONIN AND VASOPRESSIN ON CORONARY CIRCULATION AND ON OXYGEN CONSUMPTION OF THE MYOCARDIUM].
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The recruitment of circulating leukocytes to atherosclerotic sites is mediated by a family of adhesion molecules. The objective of the present study was to evaluate the relationship between circulating adhesion molecule levels in the coronary circulation and the severity of coronary atherosclerosis in patients with stable coronary artery disease. The subjects were 79 patients undergoing coronary angiography. According to the severity of coronary atherosclerosis as assessed by the Gensini Score (GS) of the left coronary artery, they were classified into three groups: group C (no organic stenosis, score 0, n = 14), group M (mild organic stenosis, score 1-13, n = 39) and group S (severe organic stenosis, score > or = 14, n = 26). Blood samples were taken from the aorta (Ao) and coronary sinus (CS), and plasma levels of soluble E-selectin (sE-selectin) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured by enzyme-linked immunosorbent assay. These levels were then compared between groups. There were no significant differences in plasma sICAM-1 levels in the Ao or CS between the three groups. The difference in sICAM-1 levels between the CS and Ao (CS-Ao) also showed no significant difference. Plasma sE-selectin levels in both the Ao and CS were significantly higher in group S than in groups C and M (p < 0.05), but there were no significant differences in CS-Ao. There was a weak but significant correlation between the plasma levels of these adhesion molecules and the number of coronary risk factors present. Multivariate analysis showed that the number of coronary risk factors was the only positive predictor (p = 0.0048) of the GS; there was no association between the plasma level of either adhesion molecule and the GS. In patients with stable coronary artery disease, sICAM-1 plasma levels do not indicate the severity of coronary atherosclerosis, while sE-selectin plasma levels appear to reflect the severity of systemic rather than coronary atherosclerosis.
BACKGROUND: The relationship between vasoactive substances, including endothelin-1, nitric oxide, serotonin, angiotensin II and noradrenaline, and coronary restenosis after percutaneous transluminal coronary angioplasty (PTCA) is not clear. OBJECTIVE: To determine whether any vasoactive substance may be a marker of coronary restenosis after PTCA. METHODS: Twenty-nine patients with angina pectoris underwent elective PTCA. Three months after PTCA, coronary angiography was performed again to study the patency of the lesions. Seven patients had coronary restenosis (greater than 50% stenosis) (restenosis group) and the rest of the patients were without restenosis (patency group). Their blood samples were obtained from the coronary sinus before, immediately after and three months after PTCA. RESULTS: Endothelin-1 levels obtained immediately after PTCA (3.44+/-0.26 pg/mL) and three months after PTCA (3.57+/-0.29 pg/mL) were significantly higher than those obtained before PTCA (3.00+/-0.26 pg/mL) in the restenosis group, but not in the patency group (3.34+/-0.15 pg/mL, 3.02+/-0.17 pg/mL and 3.14+/-0.18 pg/mL, respectively). A transient decrease in nitrite/nitrate levels was observed immediately after PTCA in both groups. The serotonin levels three months after PTCA were significantly decreased in the patency group, but not in the restenosis group, and the levels of angiotensin II and noradrenaline did not change in either group throughout the study. CONCLUSIONS: Among several vasoactive substances, endothelin-1 seems to be associated with the process of coronary restenosis after PTCA. Increased endothelin-1 levels in the coronary circulation after PTCA may indicate an increased risk of coronary restenosis.
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Coronary arteriograms of 38 patients with suspected coronary artery disease (CAD) were first evaluated to decide whether or not the disease was present and, if so, whether easily recognizable collateral channels were demonstrated. In this evaluation, we found CAD in 26 of the 38 patients. Eighteen of 21 patients with severe obstructions or occlusions had functioning collateral vessels. The films were then evaluated a second and third time to determine the effects of chewable isosorbide dinitrate (ISDN) on the coronary circulation. Visual inspection of the arteriograms revealed significant increases in 1) the apparent number and diameter of collateral vessels, 2) the opacification of vessels distal to occlusions, and 3) the diameter of coronary arteries following the administration of 2.5, 5, or 10 mg chewable ISDN. Computer analysis of the arteriograms showed an average 16% increase in the diameters of specific segments of major coronary arteries following ISDN. All patients showed some degree of vasodilatation following ISDN; however, patients without CAD consistently showed more vasodilatation than patients with disease. Mean aortic blood pressure decreased an average of 10% following ISDN. These results demonstrate that the chewable form of ISDN reliably dilates the coronary arteries in patients both with and without CAD and enhances the collateral circulation to the ischemic areas in patients with CAD.
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The pathophysiology of coronary circulation and its effects on myocardial oxygen supply in angina are discussed and reviewed in relation to the haemodynamic effects of nitrates, with special reference to the action of nitrates on coronary circulation.
We investigated changes in blood coagulation in the coronary circulation after percutaneous transluminal coronary angioplasty (PTCA) and its clinical significance. We examined 43 patients with ischemic heart disease who underwent elective PTCA of isolated stenotic lesions in the left coronary artery. Ten patients underwent PTCA alone, 15 received percutaneous transluminal rotational atherectomy (PTRA) and 18 stent implantation. Blood samples were drawn from the coronary sinus before and immediately after PTCA, as well as 4 and 24 h later. Plasma levels of tissue factor (TF), thrombin-antithrombin III complex (TAT) and prothrombin fragment 1+2 (F 1+2) were measured by enzyme-linked immunosorbent assay. Follow-up coronary angiography was performed 6 months after PTCA. Minimal luminal diameter was assessed by quantitative coronary angiography to evaluate late loss index. TF, TAT and F 1+2 levels in the coronary sinus blood showed significant increases 24 h after PTCA. A significant positive correlation was found between changes in TF levels 24 h after PTCA and late loss index 6 months after the procedure. TF levels in the coronary sinus blood were significantly higher in patients with late restenosis than in those without restenosis. These results suggest that TF expression in the coronary circulation after PTCA is a prognostic factor for late restenosis.
Pseudoaneurysms in the coronary circulation are an uncommon occurrence that can develop spontaneously in the setting of atherosclerosis or can develop after catheter-based coronary interventions. The natural history, clinical outcome, and optimal therapy for pseudoaneurysms in the coronary circulation are not clearly established. Recent advances in the techniques and technologies used for endovascular treatment of intracranial aneurysms may be applicable to the management of coronary aneurysms and pseudoaneurysms. We present a case of spontaneous coronary pseudoaneurysm formation after paclitaxel drug-eluting stent implantation and a case of pseudoaneurysm formation in a saphenous vein graft that were both successfully treated with stent-assisted detachable coil embolization.
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Many clinical studies have evaluated the inflammatory response (mainly interleukin [IL]-6 and C-reactive protein [CRP]) after percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD). The aim of this study was to verify the source of possible elevation of IL-6 and CRP after PCI using coronary sinus sampling. We studied 87 subjects who underwent coronary angiography for diagnostic, therapeutic, or follow-up purposes. Blood samples were taken by the PCI team during the catheterization study from the coronary sinus. We measured coronary IL-6 levels by sandwich enzyme-linked immunosorbent assay, and high-sensitivity CRP levels were measured by latex immunonephelometry. The subjects were then classified according to their coronary angiographic findings into non-CAD (no evidence of significant organic CAD), mild CAD (1 vessel narrowed), and severe CAD (>or=2 vessels narrowed) groups. PCI (including stent deployment) was performed in 16 patients with CAD. The mean coronary IL-6 value was higher in the severe than in the mild CAD group (3.67 +/- 2.48 vs 2.3 +/- 1.15 pg/ml, p = 0.027). The mean coronary IL-6 value was higher in the subjects who underwent PCI than in those who did not (2.9 +/- 1.23 vs 1.87 +/- 0.9 pg/ml, p = 0.037), and the same was found regarding CRP (1.244 +/- 0.72 vs 0.498 +/- 0.51 mg/L, p = 0.032). The coronary IL-6 values correlated positively with the coronary CRP values (r = 0.374, p = 0.017). In conclusion, the increase in coronary IL-6 and CRP levels after PCI in patients with CAD might be attributed to their release from the coronary atheroma secondary to the direct mechanical effect applied on the atheroma itself by balloon inflation and stent deployment.
Vasoactive intestinal polypeptide, a neurotransmitter peptide detected in animal and human hearts, has been found in nerves of coronary arteries. To determine the amount and distribution of vasoactive intestinal polypeptide in the large coronary vessels and its possible participation in coronary vasoregulation, two groups of animals were studied. In the first group, 11 anesthetized dogs were sacrificed to collect three (1 cm) segments along the circumflex and left anterior descending coronary arteries. These segments represented proximal (I), middle (II) and distal (III) portions of the two arteries. Concentrations (ng/g) of vasoactive intestinal polypeptide-like immunoreactive substance were determined by radioimmunoassay. Vasoactive intestinal polypeptide-like immunoreactivity was present in the left anterior descending (I = 7.28 +/- 1.65, II = 3.74 +/- 0.57, III = 2.29 +/- 0.53) and circumflex (I = 4.16 +/- 1.52, II = 4.58 +/- 1.13, III = 4.00 +/- 0.81) coronary arteries. The difference in vasoactive intestinal polypeptide-like immunoreactivity among epicardial segments of the anterior descending artery was significant, but there was no significant difference among segments of the circumflex coronary artery. In the second group (eight closed chest anesthetized dogs), the effects of vasoactive intestinal polypeptide intracoronary infusion on epicardial coronary constriction were examined at rest and with the artery constricted by serotonin. Left anterior descending (segments I, II and III) artery responses (% area change) to vasoactive intestinal polypeptide and vasoactive intestinal polypeptide plus serotonin were examined using quantitative coronary angiography. Vasoactive intestinal polypeptide infusion resulted in significant vasodilation in all the segments (I, II and III) of the left anterior descending artery.(ABSTRACT TRUNCATED AT 250 WORDS)
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BACKGROUND: Tissue factor pathway inhibitor (TFPI) is the endogenous inhibitor of the extrinsic coagulation pathway; however, its involvement during thrombus formation in patients with acute coronary syndromes (ACS) is still unknown. METHODS AND RESULTS: Transcardiac (aorta/coronary sinus) free and total TFPI (free + lipoprotein-bound form) levels, as well as TFPI/factor Xa (FXa) complex levels, were measured in plasma samples obtained from patients with acute myocardial infarction undergoing primary PTCA and patients with unstable angina undergoing urgent PTCA. Patients with stable angina undergoing elective PTCA served as controls. In addition, prothrombin fragment 1+2 and fibrinopeptide A plasma levels were measured. Samples were collected at baseline, after PTCA, and after stent deployment. In patients with ACS, both total and free TFPI plasma levels in the coronary sinus were significantly lower than the corresponding levels measured in the aorta at any time point of the study; conversely, a significant increase in TFPI/FXa complex plasma levels was observed in the coronary sinus as compared with the aorta. In contrast, in patients with stable angina, no differences were observed in TFPI and TFPI/FXa levels at baseline in the coronary sinus as compared with the aorta. CONCLUSIONS: TFPI is involved in the process of thrombus formation in vivo in patients with ACS, which suggests a potential role for TFPI in modulating coronary thrombosis.
BACKGROUND: Estrogen reverses acetylcholine-induced coronary vasoconstriction via the possible facilitation of endothelium-derived NO. Estrogen also affects endothelium-derived constrictor factors. We therefore investigated the effects of 17beta-estradiol on coronary vasomotor responses to substance P (SP), and coronary sinus endothelin-1 and NO metabolite levels in postmenopausal women with coronary heart disease. METHODS AND RESULTS: We studied 20 women; 14 received estrogen (mean age 65+/-2 years) and 6 served as ethanol control subjects (age 63+/-3 years). Intracoronary infusions of papaverine (8 mg) and SP were administered before and 20 minutes after 50 pg/min 17beta-estradiol or 0.2 microL/min control. Coronary blood flow was calculated from the diameter, as measured with quantitative coronary angiography, and flow velocity, as measured with intracoronary Doppler. Coronary sinus plasma endothelin-1 and nitrite/nitrate (NO(2)/NO(3)) were measured at baseline, at peak velocity response to each infusion, and every 5 minutes during the estradiol infusion. Endothelin-1 levels were decreased after 20 minutes of estradiol (1.12+/-0.18 versus 0.86+/-0.17 pmol/L baseline2 versus estradiol, P:=0.05). Endothelin-1 levels to SP decreased after 17beta-estradiol (1.29+/-0. 18 versus 1.04+/-0.15 and 1.3+/-0.16 versus 0.99+/-0.17 pmol/L for before versus after estradiol, 10 and 25 pmol/min SP; both P:<0.05). NO(2)/NO(3) levels did not change. There was no change in vasomotor responses to estradiol alone or to papaverine or SP before versus after estradiol. CONCLUSIONS: Short-term intracoronary 17beta-estradiol administration decreases coronary endothelin-1 levels. There was no enhancement of vasomotor responses to SP after the administration of estrogen, suggesting that the effects of estrogen on coronary acetylcholine responses may be a specific and not a generalized effect on coronary vasoreactivity.
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