Distal Coronary Segments Research Articles

Remodeling of coronary artery lesions due to Kawasaki disease: comparison of arteriographic and immunohistochemical findings.

Since the original report of Kawasaki disease in 1967 more than 150,000 cases have been reported in Japan. Although there have been no nationwide epidemics in Japan since 1987, more than 6,000 newly diagnosed cases are reported every year, and the number has been increasing year by year despite the decreasing birth rate. The etiology of the disease is still unknown. High dose intravenous gammaglobulin is currently used during the acute phase in 84% of the patients in Japan with a concomitant decrease in coronary arterial sequelae. However, 7-13% of the patients still have persistent coronary artery aneurysms after the acute stage. The aneurysms are seen mostly in the proximal coronary arteries, and are often associated with aneurysms in the distal coronary artery segments (Figure 1A, 2A). Most of the patients show a decrease in the size of aneurysms soon after the acute phase (Figure 1B). However, the aneurysms may progress to obstructive lesions even after initial regression (Figures 1C, D, 2B). Such obstructive lesions may cause sudden death or myocardial infarction. Long term follow-up of coronary artery lesions has revealed several characteristic features, including progressive localized stenosis (Figure 1D), extensive recanalizations (Figure 2D) and development of collateral arteries. Progressive increases in aneurysm size and the appearance of new aneurysms in the late phase have also been reported. The basic mechanisms of the coronary arterial remodeling in Kawasaki disease have not yet been elucidated. Only recently has immunohistochemical staining in formalin-fixed specimens become feasible. This is a major technical breakthrough since it is almost impossible to obtain fresh frozen specimens of coronary artery lesions of Kawasaki discase. In this paper, we compare immunohistochemical findings in coronary artery lesions with the corresponding coronary angiographic findings, and attempt to make inferences as to the mechanism of remodeling both in early and late phases of the disease based on the expression of vascular growth factors.

Inhibition of nitric oxide synthesis in human epicardial coronary arteries and stenoses in relation to serum lipid level

Administration of N G-monomethyl- l-arginine (LNMMA), an inhibitor of nitric oxide synthase, causes a reduction in epicardial coronary artery and stenosis diameter in patients with coronary artery disease, indicating that these diseased vessels produce nitric oxide. Elevations of low density lipoprotein cholesterol impair human endothelium-dependent relaxation. The relationship between serum lipid level and nitric oxide production by normal and atheromatous human epicardial coronary arteries in vivo is unknown. The effects of an intracoronary infusion of LNMMA (8 and 16 μmol/min) followed by intracoronary administration of 250 mcg nitroglycerin on non-stenotic proximal and distal coronary segments and coronary stenoses were studied in 11 patients with coronary artery disease and in 19 patients with ‘normal arteriograms’. Coronary luminal diameter was measured by computerized quantitative angiography. In patients with cholesterol level⩾220 mg/dl, no significant response to LNMMA was observed in the proximal segments in either those with ‘normal angiograms’ or those with coronary disease. In patients with cholesterol <220 mg/dl significant constriction ( P<0.01) was observed in the proximal segments of patients with ‘normal coronary angiograms’ at both 8 and 16 μmol doses, but occurred only at the 16 μmol/min dose ( P<0.01) in those with coronary disease. In conclusion the difference in vasomotor response to LNMMA in relation to cholesterol level is localised to the proximal coronary segments, and the response does not correlate with cholesterol or triglyceride level. This is therefore more likely to be an indirect effect of elevated cholesterol, e.g. undetected atheroma, than a direct effect on nitric oxide synthesis.

Evidence of partially preserved endothelial dilator function in diseased coronary arteries

OBJECTIVETo examine the effects of substance P (endothelium dependent vasodilator) and glyceryl trinitrate (endothelium independent vasodilator) on epicardial coronary arteries in patients with normal coronary angiograms and patients with coronary...

Do Indo-Asians have smaller coronary arteries?

There is a widespread belief that coronary arteries are smaller in Indo-Asians. The aim of the present study was to compare the size of atheroma-free proximal and distal epicardial coronary...

Coronary endothelial dysfunction of isolated hearts subjected to prolonged cold storage: patterns and contributing factors

Background A key role of endothelial dysfunction in the pathogenesis of early low coronary flow of heart transplants and late cardiac allograft vasculopathy indicates the importance of optimal coronary endothelial preservation during cold heart storage. We designed this study to investigate the effect of prolonged cold storage on endothelial and smooth muscle function of proximal (epicardial) and distal (intramyocardial) coronary arteries. Methods Four groups of isolated rat hearts were subjected to cold cardioplegic perfusion and immersed in storage medium at 4°C. In groups 1, 2, and 3, hearts were perfused with and stored in Celsior solution for 10, 15, and 30 hours, respectively. In group 4, hearts were perfused with Plegisol and stored in saline for 15 hours. At the end of cold heart storage, arterial segments were taken from the proximal and distal parts of the left coronary artery and mounted on an isometric wire myograph for functional studies. In fifth group, proximal and distal segments of coronary artery isolated from fresh hearts were used as controls. At the end of control measurements, these vessels were used for storage in vitro at 4°C for 15 hours in saline (group 5A) or Celsior (group 5B). Results The endothelium-dependent relaxation to acetylcholine was reduced in distal coronary arteries in group 1, and in both proximal and distal coronary artery segments in groups 2, 3, 4, and 5A. Endothelial function was significantly more impaired in both proximal and distal coronary arteries in group 4, as compared with group 2. The impairment of relaxation to acetylcholine was more pronounced following cold storage of the heart than after a similarly long storage of the isolated vessels. The endothelium-independent relaxations to isoprenaline did not differ among all groups. The basal myogenic tone was increased in distal coronary arteries in group 1, and in both proximal and distal coronary arteries in groups 2, 3, 4, and 5A. The sensitivity to the vasoconstricting action of 5-hydroxytryptamine was increased in distal coronary arteries in group 2, and in both proximal and distal coronary arteries in groups 3, 4, and 5A. Conclusions: Prolonged ischemic cold heart storage induces coronary endothelial dysfunction that is more pronounced in distal than in proximal arteries and is related to the duration of heart storage and the composition of storage medium.

Use and limitations of immediate postprocedural intracoronary Doppler blood flow measurements for predicting late result after coronary balloon angioplasty. Results of a pilot study.

Physiologic measurement of myocardial perfusion in the immediate postangioplasty period may complement the angiographic assessment of the outcome of the procedure and improve our ability to identify patients at increased risk for a suboptimal late result. Immediate in-lab identification of patients at risk for late coronary restenosis would allow the interventionalist to implement alternate interventional and/or pharmacologic strategies aimed at improving the long-term outcome of angioplasty. The present single-center pilot study was undertaken to examine prospectively the value of intracoronary Doppler flow measurements immediately postangioplasty for predicting long-term patency of the dilated coronary artery. Coronary average peak flow velocity (APV) at rest and during hyperemia (6-18 micrograms intracoronary adenosine) and coronary flow reserve in the distal coronary segment were measured in 24 consecutive patients 10-15 min after successful elective coronary angioplasty. Volume flow (Q) was calculated as APV/2 coronary cross-sectional area heart rate. Coronary arterial vessels and narrowings were measured by quantitative angiography using a geometric based method and automated edge detection. The present study reports the findings in the 16 patients undergoing conventional balloon angioplasty for whom hard endpoint angiographic data were available 4.9 +/- 1.5 months after angioplasty. A linear relation was present between angiographically measured minimal luminal dimension immediately postangioplasty and the late angiographic result of the procedure (r = 0.71, p = 0.0005). A greater acute gain during angioplasty was predictive of a larger luminal dimension at late angiographic follow-up (p = 0.006). There was no relation between the immediate postangioplasty Doppler flow measurements and the late angiographic result of the procedure. Late luminal dimension was not related to immediate postangioplasty basal or hyperemia APV, nor to immediate postangioplasty basal or hyperemic volume flow or to coronary flow reserve (all NS). In this single-center study, intracoronary blood flow and Doppler-derived coronary flow reserve immediately postpercutaneous transluminal coronary angioplasty were not predictive of long-term vessel patency or late coronary restenosis. The immediate angiographic result of angioplasty did correlate with the late result of the procedure.

Importance of Nitric Oxide in the Coronary Artery at Rest and During Pacing in Humans

Objectives. The purpose of this study was to investigate the role of endothelium-dependent vascular regulation in the human coronary circulation during rest and hyperemic states.Background. Evidence of the role of nitric oxide (NO) during metabolic demand is not consistent in animal and human coronary circulation.Methods. NG-Monomethyl-l-arginine (l-NMMA), a specific inhibitor of NO synthesis, was infused into the left anterior descending coronary artery at rest and during rapid atrial pacing in 18 subjects—9 with normal coronary arteries (control) and 9 with atherosclerotic coronary arteries. The diameter of the epicardial coronary artery was measured by quantitative coronary angiography. Vasodilation of the coronary microcirculation was assessed using an intracoronary Doppler FloWire.Results. Infusion of 25 μmol/min of l-NMMA reduced the diameter of the proximal and distal epicardial coronary artery segments by 8 ± 2% (mean ± SE) and 11 ± 2%, respectively (p < 0.05) in the control subjects. The coronary blood flow (CBF) decreased by 33 ± 13% during l-NMMA infusion. l-NMMA caused similar changes in the diameter of the distal epicardial segment and the CBF in patients with coronary artery disease. The proximal vessel diameter did not change significantly during infusion of l-NMMA. During pacing, infusion of l-NMMA caused the same changes in vessel diameter as before pacing in both groups, but did not affect CBF.Conclusions. Our findings indicate that NO synthesis maintains basal vasomotor tone in both conduit and resistance vessels in the normal human coronary circulation. Although NO release was impaired in the large epicardial coronary arteries in patients with atherosclerosis, NO still regulated vascular tone in the small epicardial coronary arteries and arterioles. Our results suggest that vasodilation in arterioles during increased myocardial oxygen demand is mediated by metabolic or myogenic mechanisms, or both, rather than by endothelium-dependent production of NO.(J Am Coll Cardiol 1997;29:85–92)>

Variable coronary vasomotor responses to acetylcholine in patients with normal coronary arteriograms: evidence for localised endothelial dysfunction.

The vasomotor responses of the epicardial coronary arteries to acetylcholine were examined in patients with normal coronary arteries and chest pain. Quantitative angiography was used to measure minimum lumen diameter of proximal and distal coronary artery segments at baseline, during intracoronary infusion of acetylcholine (10(-7) - 10(-3) mol/l), and following an intracoronary bolus (2 mg) of isosorbide dinitrate. Coronary arteriograms were obtained in 15 patients (mean (SEM) age 48 (10) years) with normal coronary arteries and chest pain. In response to the low concentrations of acetylcholine (10(-7) - 10(-6) mol/1) 20 (61%) distal and 11 (41%) proximal segments showed dilatation (group 1), whereas 13 (39%) distal segments and 14 (52%) proximal segments showed constriction (group 2) (P < 0.05 v group 1). In group 1, the maximum dilatation induced by acetylcholine in the proximal and distal segments was 7.83 (1.19)% and 11.6 (2.2)% respectively. In group 2, the maximum constriction at higher concentration was 16.55 (3.3)% and 33.11 (11.63)% in the proximal and distal segments respectively. The two different patterns of the vasomotor response coexisted in eight (53%) of the 15 patients. Intracoronary isosorbide dinitrate caused a greater increase in the coronary luminal diameter of distal segments than in proximal segments in group 1 (25.63 (5.16)% v 12.43 (3.48)%, P < 0.01) but not in group 2 (12.65 (2.53)% v 10.82 (3.33)%. Constriction and dilatation may occur in proximal and distal coronary artery segments, suggesting local areas of endothelial dysfunction, in response to acetylcholine in patients with chest pain and angiographically normal coronary arteries.

Coronary segmental responses to acetylcholine in patients with hypercholesterolemia.

We investigated coronary segmental response to intracoronary acetylcholine (ACh) in 19 patients with hypercholesterolemia and 18 patients with normal cholesterol levels. All patients had atypical and chest pain and angiographically normal coronary arteries. After baseline angiography, ACh (3 and 30 micrograms/min) was infused into the left coronary artery, followed by infusion of nitroglycerin. Percent changes in diameter of the proximal, middle, and distal segments of the left coronary arteries were measured by quantitative angiography. In the normocholesterolemic group, 3 micrograms/min of ACh produced significant coronary vasodilation in the distal segments (+8.2 +/- 2.6%, p < 0.005), while 30 micrograms/min did not cause any changes. In the hypercholesterolemic group, 30 micrograms/min of ACh caused significant coronary vasoconstriction in the middle and distal segments (-7.2 +/- 1.9% and -6.2 +/- 1.9%, p < 0.001 and p < 0.01, respectively), while 3 micrograms/min caused no changes. In each group, vasodilator responses to nitroglycerin in the middle and distal segments were significantly greater than those in the proximal segments (p < 0.001). Our results suggest that impaired endothelial function may be evaluated more effectively in the distal coronary segments in patients in the early stage of epicardial coronary atherosclerosis attributable to hypercholesterolemia.

814-1 Variations of Segmental Endothelium Dependent and Endothelium Independent Vasomotor Tone in the Long Term Follow Up After Cardiac Transplantation (Qualitative Changes in Endothelial Function)

To assess segmental vasoconstrictor and dilator responses in patients after cardiac transplantation (CT) without obvious angiographic disease we infused the endothelium dependent vasodilator acetylcholine (ACH) and the endothelium independent vasodilator SIN-1 sequentially into the left coronary artery. ACH infusions always preceded SIN-1 infusions. Responses of 156 nonstenotic coronary segments (LAD and CX) were investigated in 26 patients (P). Group 1: l0 P 11.3 ± 3 months after CT. Group 2: 16 P 52 ± 11 months after CT. Five different responses to ACH followed by SIN-1 were observed: A) dilation followed by no change (fully preserved endothelium dependent function). B) dilation followed by further dilation. C) no change followed by dilation. D) constriction followed by dilation (defective endogenous NO-release and intact vascular smooth muscle function). EI constriction followed by constriction (defective endogenous NO-release and defective vascular smooth muscle function). Different segmental reaction types in both groups.Empty Cellproximal LADdistal LADGroup 1:20% A, 20% B. 30% C. 30% D50% C. 50% DGroup 2:19% C. 69% 0.12% E12% C. 81% D.7% E (1) In only 20% of patients 1 year after CT the endothelium dependent vasodilation is completely preserved. In 40% of the patients 1 year after CT the endothelium shows segmental heterogeneity in response to ACH [absence of endothelium dependent vasodilation (type A and B) in the distal segment]. (2) In the long term course after CT more than 80% of P have defective endothelial function in proximal and distal segments [absence of endothelium dependent vasodilation (type A and B) in the proximal and distal segment]. Moreover approximately 10% have defective vascular smooth muscle function. Functional assessment of endothelial integrity in P after CT shows time dependent qualitative differences between proXimal and distal coronary segments

Effects of ketanserin on epicardial coronary arteries after coronary angioplasty in patients with stable angina

Previous studies have demonstrated the development of vasoconstriction immediately after percutaneous coronary angioplasty (PTCA), distal to the dilated stenosis, presumably resulting from endothelial injury. We have investigated the role of 5-HT2 receptors in mediating vasomotor changes in proximal and distal coronary segments and coronary stenoses, immediately after successful PTCA in patients with chronic stable angina. We compared the effects of the intracoronary infusion of 1 mg ketanserin (5-HT2 receptor antagonist) on proximal and distal coronary arterial segments immediately after PTCA in both vessels subjected to PTCA and control vessels. Coronary diameters, before and after angioplasty and after ketanserin administration, of proximal and distal segments and coronary stenoses were measured by computerized quantitative coronary angiography (CAAS system) in 12 patients (10 male, two female; mean age 54 +/- 6 years) with stable angina subjected to PTCA. After coronary angioplasty, vasoconstriction was observed in the segment distal to the dilated stenosis but not in the distal segments of control vessels (-0.12 +/- 0.04 and -0.02 +/- 0.02 mm respectively; P < 0.05). After ketanserin infusion significant dilatation was found in the distal segments of both PTCA vessels and control vessels, but the dilatation was greater in the PTCA vessels (P < 0.05). No significant changes were found in the proximal segments of either PTCA or control vessels, or at the PTCA site. In conclusion, the vasoconstriction distal to the site of PTCA is mediated, at least in part, via 5-HT2 receptors.

Effect of induced hypercholesterolemia in rabbits on functional responses of isolated large proximal and small distal coronary arteries.

We studied the effects of hypercholesterolemia on the vascular responses of proximal and distal parts of the rabbit coronary circulation in two consecutive studies. For 12 weeks, New Zealand White rabbits were fed a control diet or a diet with 1% cholesterol dissolved in either 3% coconut oil (study A) or ether (study B). Isolated proximal epicardial and distal intramyocardial coronary arteries from control and hypercholesterolemic rabbits were mounted for isometric tension recording in a double myograph. In study A for hypercholesterolemic rabbits (n = 12), the maximal relaxation and sensitivity to acetylcholine (ACh) were significantly decreased in proximal coronary segments contracted with 30 mmol/l potassium solution compared with segments from control rabbits (n = 13). The only change observed in distal coronary segments was a slight decrease in relaxation in response to low ACh concentrations (10(-8) and 3 x 10(-8) mol/l). However, in study B for proximal coronary and distal coronary segments from hypercholesterolemic rabbits (n = 13), the area under the ACh relaxation curve was increased compared with that of control rabbits (n = 12). Other parameters that were similarly affected in studies A and B include the following: 1) proximal coronary segments from hypercholesterolemic rabbits were more sensitive to sodium nitroprusside (SNP) than were those from control rabbits, but this was not true for distal coronary segments; 2) endothelial removal from arterial segments of control rabbits induced a significant increase in sensitivity and maximal relaxation to SNP of proximal coronary and distal coronary arteries; 3) in segments from hypercholesterolemic rabbits, the absence of endothelium did not alter the response of proximal coronary segments to SNP but did augment the relaxation of distal coronary segments to SNP; 4) the maximal response to 5-hydroxytryptamine in proximal coronary arteries from hypercholesterolemic rabbits was increased compared with those from control rabbits, whereas such changes were not observed in distal coronary arteries; and 5) histological examination showed the presence of atheromatous plaques in proximal coronary but not in distal coronary segments from treated animals. In conclusion, the present investigation demonstrates that induced hypercholesterolemia alters both the structure and function of proximal parts of the coronary circulation. In distal coronary arteries of hypercholesterolemic rabbits, the only change observed was an impaired endothelium-dependent cholinergic relaxation, but even this change appeared to be dependent on the manner in which cholesterol was added to the diet, although parallel studies are required to confirm this.

Epicardial coronary artery tone and reactivity in patients with normal coronary arteriograms and reduced coronary flow reserve (syndrome X)

The vasomotor response of proximal and distal angiographically normal coronary artery segments was studied in 12 patients with syndrome X, 17 age- and gender-matched patients with chronic stable angina and 10 control subjects with atypical chest pain and a normal coronary arteriogram. Ergonovine (300 micrograms by intravenous injection) and isosorbide dinitrate (1 mg by intracoronary injection) were administered to all patients. Computerized coronary artery diameter measurement (angiographically normal segments only) was carried out before and after the administration of ergonovine and nitrate. Baseline intraluminal diameters (mean +/- SEM) of proximal and distal coronary segments were not significantly different in control subjects and patients with syndrome X or coronary artery disease (proximal 2.88 +/- 0.19, 3.01 +/- 0.13 and 2.86 +/- 0.13 mm; distal 1.57 +/- 0.09, 1.70 +/- 0.10 and 1.61 +/- 0.06 mm, respectively). With ergonovine, proximal segments constricted by 10 +/- 2%, 7 +/- 2% and 11 +/- 3% and distal segments by 12 +/- 3%, 14 +/- 3% and 14 +/- 2% in control subjects and patients with syndrome X or coronary artery disease, respectively (p = NS). With isosorbide dinitrate, proximal coronary segments dilated by 11 +/- 2%, 10 +/- 2% and 8 +/- 2% (p = NS) and distal segments by 15 +/- 2%, 11 +/- 3% and 13 +/- 2% (p = NS) in control subjects and patients with syndrome X or coronary artery disease, respectively. Within groups, constriction in response to ergonovine and dilation in response to nitrate were not significantly different in proximal and distal segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Reactivity of proximal and distal angiographically normal and stenotic coronary segments in chronic stable angina pectoris

To assess whether vasoreactivity of significant coronary stenosis (>5O% intraluminal diameter reduction) and that of angiographically normal coronary segments differs in proximal and distal locations, S3 patients (40 men, 13 women, mean ± standard deviation age SS ± 11 years) with chronic stable angina and angiographically documented coronary artery disease were studied. While abstaining from antianginal therapy, all 53 patients underwent coronary arteriography before and after 1 mg of intracoronary isosorbide dinitrate and 21 of the S3 also before and after 20 to 30 μg intracoronary ergonovine. Computerized quantitative angiography was used to assess changes in the intraluminal diameter of 126 normal coronary segments (63 proximal, 63 distal) and 43 significant coronary stenoses. Nitrates dilated proximal normal coronary segments by 7.4 ± 1.2% and distal normal coronary segments by IS ± 1.7% (p < 0.01). Significant proximal coronary stenoses dilated by 11 ± 2.S% and distal stenoses by 23 ± 2.8% (p < 0.01) after nitrates. Ergonovine reduced the diameter of proximal normal coronary segments by 9.3 ± 1.7% and that of normal distal segments by 15.5 ± 1.4% (p < 0.01). Proximal stenoses constricted by 11 ± 2.2% and distal stenoses by 18.4 ± 2.8% (p = 0.06). Analysis of segments showed that nitrates dilated 19 of 63 (30%) proximal normal segments (by ≥ 10%), 31 of 63 (49%) distal (p <O.O5) and 21 of 43 (49%) stenoses. Ergonovine constricted (by ≥10%) IS of 37 (41%) proximal normal segments, 27 of 37 (73%) distal (p < 0.01) and 13 of 22 (5g9%) significant stenoses. These findings indicate that distal normal coronary segments have greater reactivity to nitrates and to ergonovine than proximal segments. Stenosis reactivity parallels that of angiographically normal segments.

Comparison of epicardial coronary artery tone and reactivity in Prinzmetal's variant angina and chronic stable angina pectoris

It has been suggested that a generalized coronary vasomotion disorder is present in variant angina and that evaluation of baseline coronary artery tone may be useful for predicting the occurrence of coronary artery spasm. The vasomotor response of angiographically normal proximal and distal coronary artery segments was studied in 9 patients with atypical chest pain and normal coronary arteriograms (control group), 13 patients with active variant angina and 41 patients with chronic stable angina. Ergonovine (intravenous, 100 to 300 μg, or intracoronary, 8 to 20 μg, was administered to all 22 patients in the control and variant angina groups and to 11 of the 41 patients with chronic stable angina. All patients also received intracoronary isosorbide dinitrate (1 to 2 mg).Computerized coronary artery diameter measurement of angiographically normal segments was carried out before and after ergonovine and nitrate administration. Mean baseline intraluminal diameter of proximal and distal coronary segments was not significantly different in control patients and those with variant angina (nonspastic segments only) or coronary artery disease (proximal 2.89 ± 0.15, 2.83 ± 0.14 and 2.82 ± 0.09 mm; distal 1.60 ± 0.08, 1.63 ± 0.07 and 1.62 ± 0.06 mm, respectively). After ergonovine, proximal segments constricted by 10 ± 2%, 15 ± 3% and 11 ± 4% and distal segments by 11 ± 3%, 11 ± 2% and 14 ± 3% in control, variant angina and coronary artery disease groups, respectively (p = NS). After isosorbide dinitrate, proximal coronary segments dilated by 13 ± 2%, 11 ± 3% and 8 ± 2% (p = NS) and distal segments by 13 ± 3%, 14 ± 4% and 15 ± 2% (p = NS) in control, variant angina and coronary artery disease groups, respectively.The results of this study indicate that rest baseline coronary tone and the vasomotor response of angiographically normal coronary artery segments to ergonovine and isosorbide dinitrate are similar in patients with noncardiac chest pain, Prinzmetal's variant angina and coronary artery disease. Evaluation of basal coronary artery diameter, therefore, is not useful for predicting the occurrence or location of coronary spasm.

5-Hydroxytryptamine does not release endothelium-derived relaxing factor in rat isolated coronary arteries

Removal of the endothelium from isolated rat proximal and distal coronary artery segments shifted the 5-HT concentration-response curve to the left without affecting, the maximal contractile response. 5-HT had no relaxing effect in 10 −5 M prostaglandin F 2α-precontracted vessels with an intact endothelium in the presence of 10 −5 M ketanserin. The spontaneous myogenic tone increased in both proximal and distal coronary artery segments after the endothelium had been removed. Indomethacin (10 −5 M) reduced the response of the proximal coronary artery segments to 5-HT by 35% but indomethacin had no effect on the 5-HT concentration-response curve of the distal coronary artery segments. Indomethacin relaxed precontracted (40 mM potassium) proximal coronary artery segments independently of the presence of the endothelium, suggesting a non-specific relaxing effect of indomethacin in these arteries. It is concluded that rat coronary artery endothelium is unresponsive to 5-HT because it lacks 5-HT 1 receptors. The increased 5-HT sensitivity and spontaneous myogenic tone of endothelium-denuded rat coronary arteries is probably due to the elimination of the relaxing stimulus mediated by spontaneously released endothelium-derived relaxing factor.

Coronary stenosis dilation by low dose intravenous nitroglycerin

In a randomized double-blind study, 40 patients with coronary heart disease received either 0.025 mg nitroglycerin or placebo intravenously. Before and 2-3 min after injection, the aortic and left ventricular pressures were recorded and coronary angiography was performed. Mean heart rate, systolic and diastolic aortic pressure, left ventricular filling pressure and the pre- and poststenotic coronary artery diameters, as well as the diameters of representative distal coronary artery segments showed no significant changes. Coronary artery stenosis diameters remained unchanged after placebo (1.01 +/- 0.5 to 1.13 +/- 0.49 mm; n.s.) but increased significantly after nitroglycerin from 1.15 +/- 0.68 to 1.32 +/- 0.73 mm (P less than 0.01). Since it has been demonstrated, on the other hand, that the same dose of nitroglycerin reveals antianginal activity, it can be hypothesized from these results that dilatation of coronary stenoses plays an important role in the antianginal action of nitroglycerin. Strong haemodynamic effects do not appear to be a prerequisite of the beneficial effects of nitroglycerin.

Spontaneous coronary artery spasm in variant angina is caused by a local hyperreactivity to a generalized constrictor stimulus

To assess whether spontaneous coronary artery spasm in patients with variant angina results from local coronary hyperreactivity to a generalized constrictor stimulus or from a stimulus generated only at the site of the hyperreactive segment, the behavior of spastic and nonspastic coronary segments was studied in six patients with variant angina in whom focal coronary spasm developed spontaneously during cardiac catheterization. None of the patients had critical (> 50% luminal diameter reduction) organic coronary stenoses. Coronary diameters were measured by computerized quantitative arteriography during control, spontaneous spasm and ergonovine-induced spasm and after intracoronary nitrates were given.During spontaneous spasm, the luminal diameter of spastic and both proximal and distal nonspastic coronary segments was significantly reduced from control values, 64.2%, 13.2% and 14.8%, respectively. Average diameter reduction of unrelated arteries was 12.3%. Ergonovine, which was also administered to four patients, provoked focal spasm at the same site as spontaneous spasm. During intravenous ergonovine, luminal diameter of spastic segments was reduced by 91.5%, that of nonspastic proximal segments by 17.8% and that of nonspastic distal segments by 11.5%. Luminal diameter of unrelated arteries during ergonovine-induced spasm was reduced by 17.7%. Constriction of spastic segments was greater during ergonovine-induced spasm (p < 0.05), whereas the extent of diameter reduction of nonspastic segments was not significantly different during spontaneous spasm and ergonovine-induced spasm. Intracoronary isosorbide dinitrate dilated spastic and nonspastic coronary segments to a similar extent from control (20.7%, 18% and 16.5%, respectively; p = NS).This study demonstrates that spontaneous focal coronary spasm in variant angina results from a local exaggerated coronary constrictor response to a generalized stimulus that produces only mild constriction in other coronary segments.

The Effect of Cigarette Smoking on the Pattern of Coronary Atherosclerosis: A Case-Control Study

Cigarette smoking is a risk factor for development of coronary atherosclerosis. We examined the relationship between smoking and the anatomic location of coronary artery stenosis in 8,705 patients undergoing cardiac catheterization for suspected coronary artery disease (CAD). The smoking history of patients with CAD (greater than or equal to 70 percent stenosis) was compared with that of control subjects (0 percent stenosis) for each of nine anatomic locations (proximal, middle, and distal segments of right [RCA], anterior descending [LAD], and circumflex arteries [LCX]), using a case-control method. The odds ratio (OR) estimate of relative risk of CAD for smokers relative to nonsmokers was 2.8, with a 95 percent confidence interval (CI) of 2.5 to 3.1. Relative risk was greater for RCA stenosis (OR = 5.8; CI = 4.6-7.2) than for LCX (OR = 3.5; CI = 2.7-4.5) or LAD (OR = 2.1; CI = 1.8-2.4) lesions when comparing smokers with nonsmokers. After control for age, gender, history of diabetes mellitus, and serum cholesterol level, the adjusted relative risk for an RCA lesion (Mantel-Haenszel odds ratio [MOR] = 4.9) was significantly elevated (p less than 0.05) compared with the LAD (MOR = 1.9) but not with the LCX (MOR = 3.1). The relative risks of CAD were the same (p greater than 0.05) for the proximal, middle, and distal coronary segments. Thus, smoking increased the risk of all coronary lesions but did so more for the RCA than for other vessels, suggesting a spatial pattern to the increased risk produced by smoking.

Active and passive changes in coronary diameter after vasodilation with SIN-1, the active metabolite of molsidomine

The vasodilating effects of intracoronary injections of 0.4 mg of SIN-1, the active metabolite of molsidomine, on epicardial coronary arteries and coronary stenoses were evaluated in 14 patients with coronary artery disease in a double-blind, randomized fashion vs placebo. Nine additional patients with well defined coronary stenoses received 0.4 mg of SIN-1 as well. Diameter changes of nonstenotic coronary arteries in proximal, medial, and distal coronary segments as well as changes of the residual luminal diameters within coronary stenoses were determined before (K), immediately after (M1), and 10 minutes after (M2) intracoronary administration of SIN-1. Aortic pressures and heart rate were monitored continuously. After administration of SIN-1, the diameters of nonstenotic coronary arteries increased in proximal segments by 9.4% (M1) and 11.7% (M2), in medial segments by 17.9% (M1) and 17.6% (M2), and in distal segments by 25.6% (M1) and 28.8% (M2). Within coronary stenoses the residual luminal diameters showed mean increases of 31.5% (M1) and 48.3% (M2). Placebo administration did not alter coronary diameters significantly. Aortic pressure and heart rate did not change after administration of SIN-1 or placebo. SIN-1 effectively dilates nonstenotic and stenotic coronary segments, as do nitrates and calcium channel blockers. By intracoronary injections, the direct effects on coronary vessels can be evaluated without interference with systemic effects. The increase in the residual luminal diameters within dynamic coronary stenoses after administration of SIN-1 is probably an important antianginal mechanism also for molsidomine.