Small bowel metastasis of hepatocellular carcinoma detected by capsule endoscopy.

We report a rare case of metastasis of hepatocellular carcinoma (HCC) to the small bowel that presented as a pedunculated epithelial polyp. A 60-year-old man with liver cirrhosis type B was treated for HCC (stage IVb) at our hospital. He had been admitted for melena and anemia. Capsule endoscopy was performed in this patient with obscure gastrointestinal bleeding. It showed a polypoid lesion with bleeding in the ileum. Double-balloon endoscopy was performed. The lesion was determined to be a pedunculated polyp in the ileum. Histological examination of biopsy specimens showed tumor cells resembling HCC. We performed endoscopic mucosal resection for the lesion by double-balloon endoscopy to prevent bleeding from the tumor. The patient had no melena or anemia and his condition improved after endoscopic mucosal resection. However, he died of liver failure 2 months later.

Modulation of ventricular repolarization and R-R interval is altered in patients with globally impaired cardiac 123I-MIBG uptake.

BACKGROUND: Cardiac (123)I-metaiodobenzylguanidine (MIBG) imaging is widely used to assess cardiac sympathetic neuronal function. However, physiologic significance of impaired cardiac MIBG uptake is not fully elucidated. The purpose of the present study was to determine influences of abnormal cardiac sympathetic neuronal function on heart rate variability (HRV) and ventricular repolarization process. METHODS: Twenty-nine patients with prior myocardial infarction were divided into two groups by a heart-to-mediastinum ratio (H/M) of MIBG scintigraphy. Ten patients with globally decreased MIBG uptake (group I: H/M < 1.5), 19 patients with partially decreased MIBG uptake (group II: H/M >or= 1.5), and 17 control subjects with normal MIBG uptake (group III) were studied. Holter recording and a standard 12-lead electrocardiography were used for evaluation of HRV, QT-RR relation, and QT dispersion. RESULTS: Low, high, and total frequency components decreased in groups I and II, as compared to that of group III. The reduction of these frequency domain measures was more severe in group I than in group II, but the differences did not reach statistical significance. Circadian variation of frequency domain measures disappeared in group I. The slope of QT-RR relation was significantly greater in group I than in groups II and III. QT dispersion was also greater in group I (64 +/- 25 msec) than in group II (43 +/- 19 msec) and group III (28 +/- 9 msec). CONCLUSION: These results suggest that patients with sympathetic neuronal dysfunction inferred from globally impaired cardiac MIBG uptake have an altered modulation of ventricular repolarization process as well as decreased HRV.

The role of ANG II and endothelin-1 in exercise-induced diastolic dysfunction in heart failure.

The diastolic dysfunction present at rest in congestive heart failure (CHF) is exacerbated during exercise (Ex). Increases in circulating ANG II and endothelin-1 (ET-1) during Ex may contribute to this response. We assessed the effect of Ex on circulating plasma levels of ANG II and ET-1 and left ventricular (LV) dynamics before and after pacing-induced CHF at rest and during Ex in nine conscious, instrumented dogs. Before CHF, there were modest increases in circulating levels of ANG II (but not ET-1) during Ex. LV diastolic performance was enhanced during Ex with decreases in the time constant of LV relaxation (tau), LV end-systolic volume (V(ES)), and LV minimum pressure with a downward shift of the LV early diastolic portion of the pressure-volume (P-V) loop. This produced an increase in peak LV filling rate without an increase in mean left atrial (LA) pressure. After CHF, the resting values of ANG II and ET-1 were elevated and increased to very high levels during Ex. After CHF, mean LA pressure, tau, and LV minimum pressure were elevated at rest and increased further during Ex. Treatment with L-754,142, a potent ET-1 antagonist, or losartan, an ANG II AT(1)-receptor blocker, decreased these abnormal Ex responses in CHF more effectively than an equally vasodilatory dose of sodium nitroprusside. Combined treatment with both ANG II- and ET-1-receptor blockers was more effective than either agent alone. We conclude that in CHF, circulating ANG II and ET-1 increase to very high levels during Ex and exacerbate the diastolic dysfunction present at rest.

Allopurinol enhances the contractile response to dobutamine and exercise in dogs with pacing-induced heart failure.

BACKGROUND: Superoxide (O(2)(-)) generated by enhanced xanthine oxidase (XO) activity may contribute to the increased myocardial oxidative stress in heart failure (CHF). Because blocking XO with allopurinol augments myofilament Ca(2+) sensitivity in reperfusion injury and CHF, we hypothesized that it may improve adrenergic inotropic responsiveness in CHF. METHODS AND RESULTS: We studied the effect of allopurinol on the contractile response to dobutamine and exercise in 7 chronically instrumented conscious dogs before and after producing CHF by rapid pacing. Left ventricular (LV) contractile performance was measured by the slopes of the LV end-systolic pressure-volume relation (E(ES)) and stroke work-end-diastolic volume relation (M(SW)). Before CHF, allopurinol produced no change in LV contractile performance and did not alter the response to dobutamine or exercise. After CHF, allopurinol produced significant (P:<0.05) increases in E(ES) (5.0+/-0.6 versus 3.3+/-0.6 mm Hg/mL) and M(SW). Dobutamine and allopurinol produced greater increases in E(ES) (5.4+/-0.6 versus 7.4+/-0.6 mm Hg/mL) and M(SW) (60.1+/-7.4 versus 73.7+/-4.4 mm Hg) than did dobutamine alone. After allopurinol, dP/dt(max), stroke volume, and M(SW) were higher during CHF exercise. LV diastolic pressures were lower during CHF exercise after allopurinol. CONCLUSIONS: Allopurinol has no discernable effects on LV contractile function or adrenergic responsiveness in normal, conscious animals. In pacing-induced CHF, however, allopurinol improves LV systolic function at rest and during adrenergic stimulation and exercise.

Exercise-induced negative U waves in precordial leads as a marker of viable myocardium in patients with recent anterior myocardial infarction.

Patients with recent anterior myocardial infarction and a significant stenosis in the left anterior descending coronary artery were divided into two groups according to the presence (Group A, n=24) or absence (Group B, n=77) of negative U waves in the precordial leads during exercise stress test to compare the coronary arteriographic findings. Both total occlusion of the left anterior descending coronary artery (79% vs. 31%, P<0.01)) and good (index=2, 3) collateral circulation to the territory of this artery (92% vs. 36%, P<0.01) were observed more often in group A than in group B. In order to determine whether detection of exercise-induced negative U waves in precordial leads can predict the presence of viable myocardium, the 56 patients (20 of group A and 36 of group B) with total or subtotal occlusion of the left anterior descending coronary artery were studied further. The coronary arteriographic and exercise 201Tl scintigraphic findings were compared between the groups. Good collateral circulation to the territory of this artery was observed significantly (P<0.05) more often in group A (100%) than in group B (61%). Patients with multivessel disease were significantly (P<0.05) more prevalent in group A (70%) than in group B (33%). The incidence of a significant partial redistribution in the anteroseptal area in the 20Tl images 4 h after exercise was significantly (P<0.01) higher in group A (85%) than in group B (39%). In 29 patients with anterior Q-wave myocardial infarction and exercise-induced ST elevation in precordial leads, a significant 201Tl redistribution in the anteroseptal area was observed in 8 (80%) of 10 patients of group A in contrast to only 4 (21%, P<0.05) of 19 in group B. In the diagnosis of the viability associated with 201Tl redistribution in the anteroseptal area by the finding of exercise-induced negative U waves, the sensitivity was 67% and the specificity was 88% in these patients. We conclude that exercise-induced negative U waves in precordial leads are a convenient and specific marker for the presence of viable myocardium in patients with recent anterior myocardial infarction.

Heterogeneous cardiac sympathetic innervation in heart failure after myocardial infarction of rats.

We examined cardiac neuronal function and beta-receptor with a dual-tracer method of [(131)I]meta-iodobenzylguanidine (MIBG) and [(125)I]iodocyanopindolol (ICYP) in rat heart failure after myocardial infarction (MI). In rats with MI, left ventricular (LV) systolic function decreased, and LV dimension and right ventricular (RV) mass increased gradually. MIBG accumulations of the noninfarcted LV (remote region) and RV decreased by 15% at 1 wk compared with sham-operated rats, and these accumulations were restored by 71% and 56%, respectively, at 24 wk compared with age-matched sham rats despite sustained depletion of myocardial norepinephrine contents in these regions. ICYP accumulation of the remote region and of the RV did not decrease at any stages. Myocardial MIBG distribution was heterogeneous at 1 wk when it was lower in the peri-infarcted region than in the remote region, associated with reduced ICYP accumulation in the peri-infarcted region. The heterogeneous distribution of both isotopes disappeared at 12 wk. Thus cardiac sympathetic neuronal alteration was coupled with downregulation of beta-receptors in rat heart failure after MI. The abnormal adrenergic signaling occurred heterogeneously in terms of ventricular distribution and time course after MI.

Time-varying spectral analysis of heart rate and left ventricular pressure variability during balloon coronary occlusion in humans: a sympathoexicitatory response to myocardial ischemia.

OBJECTIVES: We assessed time-varying spectral components of heart rate and left ventricular (LV) pressure variability during coronary angioplasty to elucidate dynamic autonomic responses to transient myocardial ischemia. BACKGROUND: Sympathoexcitatory reflexes elicited by acute coronary occlusion are rarely addressed in the clinical settings because of a lack of technique to monitor transient changes in sympathetic activation. METHODS: RR interval and LV pressure and volume were serially recorded in 14 patients with effort angina during balloon coronary angioplasty. Wavelet analysis was applied for determination of nonstationary spectral components of RR interval and LV peak pressure variability. RESULTS: The wavelet analysis revealed that coronary occlusion provoked low-frequency (LF) fluctuations of RR interval (seven patients) and LV peak pressure (six patients) at 0.06 +/- 0.01 Hz, but not in the remaining patients. Following the balloon inflation, the LF component of RR interval began to increase after the onset of myocardial ischemia, peaked at about 80 s, and then declined in the late phase of inflation. Consequently, the ratio of low to high frequency component rose to be significantly greater in the LF augmentation group than in the no LF augmentation group in the middle phase of coronary occlusion. The patients with no LF augmentation had little evidence of myocardial ischemia as reflected by changes in ST segment and LV systolic function during coronary occlusion. CONCLUSIONS: The wavelet analysis of RR interval and LV pressure variability clearly showed a dynamic profile of spectral components in response to transient coronary artery occlusion. The resultant regional myocardial ischemia elicited a profound sympathoexcitatory response followed by a gradual suppression. This method provides a useful tool to gain a new insight into the nonstationary autonomic influence on the cardiovascular system.

Modulation of left ventricular diastolic distensibility by collateral flow recruitment during balloon coronary occlusion.

OBJECTIVES: The goals of this study were to elucidate the scaffolding effect of blood-filled coronary vasculature and to determine the functional role of recruited collateral flow in modulating left ventricular (LV) distensibility during balloon coronary occlusion (BCO). BACKGROUND: Although LV distensibility is an important factor affecting acute dilation after myocardial infarction, the response of LV diastolic pressure-volume (P-V) relations to coronary occlusion is inconsistent in humans. METHODS: Micromanometer and conductance derived LV P-V loops were serially obtained from 16 patients undergoing percutaneous transluminal coronary angioplasty. Coronary collateral flow recruitment was angiographically evaluated by contralateral and ipsilateral contrast injection during BCO. RESULTS: In the group with poor collateral flow (grades 0-I; n = 8), BCO resulted in a downward and rightward shift of the diastolic P-V relations, where end-diastolic volume (EDV) increased by 13% (p < 0.05) without appreciable change in end-diastolic pressure (EDP; 18 +/- 6 to 18 +/- 8 mm Hg). In contrast, BCO in the group with good collateral flow (grades II-III; n = 8) shifted the diastolic P-V relations upward to the right with a concomitant increase in minimal pressure (min-P; 6 +/- 4 to 10 +/- 5 mm Hg, p < 0.05), EDP (15 +/- 7 to 21 +/- 9 mm Hg, p < 0.05) and EDV (+/- 10%, p < 0.05). Reactive hyperemia after balloon deflation caused a rapid and parallel upward shift of the diastolic P-V relations with a marked increase in min-P and EDP, especially in the group with poor collateral flow, before any improvement in LV contraction or relaxation abnormalities. CONCLUSIONS: Grades of coronary filling, either retrograde or anterograde, abruptly modulate LV distensibility through the rapid scaffolding effect of coronary vascular turgor.

Consumption of vitamin E in coronary circulation in patients with variant angina.

OBJECTIVES: The plasma status of vitamin E has been suggested to be linked to the activity of coronary artery spasm. This study was designed to determine whether vitamin E is actually consumed in the coronary circulation in patients with active variant angina having repetitive spasm-induced transient myocardial ischemia and reperfusion. METHODS: Blood samples were obtained simultaneously from the aortic root, coronary sinus and right atrium in 12 patients with variant angina due to spasm of the left coronary artery, nine patients with stable effort angina and nine control subjects. Plasma vitamin E (alpha- and gamma-tocopherol) concentrations were determined by use of high-performance liquid chromatography and plasma lipid peroxides were measured as thiobarbituric acid-reactive substances (TBARS). RESULTS: At baseline, both plasma alpha- (p < 0.01) and gamma- (p < 0.05) tocopherol levels were significantly lower in the coronary sinus (5.50 +/- 0.50 and 0.55 +/- 0.07 mg/l, mean +/- SEM) than in the aortic root (6.63 +/- 0.57 and 0.63 +/- 0.08 mg/l) and also in the right atrium (6.44 +/- 0.61 and 0.63 +/- 0.09 mg/l) in the variant angina group. The TBARS level was significantly (p < 0.05) higher in the coronary sinus than in the aortic in this group. In contrast, these levels were not significantly different between the samples from the coronary sinus and the aortic root or the right atrium in the control group and also in the stable effort angina group. The coronary sinus-aortic difference in plasma vitamin E levels in the variant angina group was not significantly altered after left coronary artery spasm induced by intracoronary injection of acetylcholine. Also, the plasma vitamin E levels in the aortic root, coronary sinus and right atrium all remained unchanged in the stable effort angina group after pacing-induced angina and in the control group after intracoronary administration of acetylcholine. CONCLUSIONS: Transcardiac reduction in plasma vitamin E concentrations concomitant with lipid peroxide formation was demonstrated in patients with active variant angina, suggesting actual consumption of this major endogenous antioxidant. Oxidative stress and vitamin E exhaustion may be involved in the pathogenesis of coronary artery spasm.

Dual-tracer assessment of coupling between cardiac sympathetic neuronal function and downregulation of beta-receptors during development of hypertensive heart failure of rats.

BACKGROUND: Heart failure is associated with activation of the sympathetic nervous system and downregulation of beta-receptors. However, the coupling between cardiac sympathetic neuronal function and the beta-receptor during the development of hypertensive heart failure is not clear. METHODS AND RESULTS: We determined cardiac neuronal function and beta-receptors with a dual-tracer method of [131I]metaiodobenzylguanidine (MIBG) and 125I-cyanopindolol (ICYP) in Dahl salt-sensitive (DS) and salt-resistant (DR) rats. The rats were fed an 8% NaCl diet after the age of 6 weeks. Blood pressure was raised to >200 mm Hg at 12 weeks in DS rats and remained elevated until 18 weeks, but only slightly in DR rats. Left ventricular (LV) function of DS rats was preserved at 12 weeks but deteriorated at 18 weeks. Despite a 56% reduction of cardiac norepinephrine (NE) content at 12 weeks in DS rats, neither MIBG nor ICYP uptake in DS rats was different from that of DR rats. At 18 weeks, both MIBG and ICYP uptakes decreased, by 52% and 39%, respectively, in association with 71% reduction of cardiac NE, in DS rats. MIBG uptake of the LV was homogeneous at 6 weeks but was lower in the LV endocardial regions at 18 weeks in DS rats. CONCLUSIONS: The present results indicate that cardiac sympathetic neuronal function is relatively preserved at the compensated, hypertrophic stage of DS rats but deteriorates in association with beta-receptor downregulation at the failing stage. The cardiac neuronal dysfunction occurs heterogeneously. A combination of scintigraphic portrayal of beta-receptors with MIBG should provide valuable information regarding sympathetic nerve signaling in living hearts.

Alterations of autonomic nervous activity preceding nocturnal variant angina: sympathetic augmentation with parasympathetic impairment.

BACKGROUND: Autonomic nervous discharge has been implicated in the pathogenesis of coronary artery spasm. METHODS: Cardiac autonomic nervous activities were evaluated from the power of the low-frequency and the high-frequency spectral components of heart rate variability with Holter monitoring in 18 patients with nocturnal variant angina. Samples during the first 512 seconds of each 10-minute period from 60 minutes before to immediately before an anginal attack occurring during the night or at dawn (2:00 to 7:00 AM) were analyzed by fast Fourier transformation. RESULTS: The R-R interval during the 10- to 0-minute period was significantly shorter than those during the other 10-minute periods. The coefficient of variance of the high-frequency component (0.15 to 0.40 Hz) (CVHF) from the 10- to 0-minute period was not significantly different from the other 10-minute periods. However, both the coefficient of variance of the low-frequency component (0.04 to 0.15 Hz) (CVLF) and the ratio of CVLF and CVHF (CVLF/CVHF) were significantly greater during the 10- to 0-minute period than those during the 30- to 20-minute period, respectively. A significant nighttime fluctuation in the spectral components of heart rate variability with a peak in the CVHF and a nadir in both the CVLF and CVLF/CVHF observed in the control group was blunted in the patients during the attack-free periods while they were medicated with calcium entry blockers. CONCLUSION: Sympathovagal imbalance, sympathetic activation without parasympathetic augmentation, enhanced in the early morning may play an important role in the genesis of coronary artery spasm in patients with nocturnal variant angina.

Soluble E-selectin, ICAM-1 and VCAM-1 levels in systemic and coronary circulation in patients with variant angina.

OBJECTIVE: The purpose of this study was to assess whether the plasma levels of soluble adhesion molecules including E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are elevated in patients with variant angina and whether they are released in the coronary circulation. METHODS: Antecubital venous plasma samples were collected from 33 patients with variant angina, 22 patients with stable effort angina and 20 control subjects. Samples were also collected from the aortic root (AO) and the coronary sinus (CS) in 18 patients with variant angina before and after left coronary spasm induced by intracoronary injection of acetylcholine. The soluble adhesion molecules were assayed by enzyme immunoassay. RESULTS: Antecubital venous plasma soluble E-selectin (P < .05), ICAM-1 (P < .01) and VCAM-1 (NS) levels were higher in the variant angina group than in the control group, respectively. The plasma soluble ICAM-1 level was also higher (P < .01) in the variant angina group than in the stable effort angina group. In the variant angina group, both soluble ICAM-1 (P < .05) and VCAM-1 (P < .01) levels were significantly lower in CS than AO at baseline. In contrast, after the spasm the plasma soluble ICAM-1 level was (P < .05) higher in CS than AO and the CS-AO differences of soluble ICAM-1 (P < .05) and VCAM-1 (P < .05) increased as compared with the baseline, respectively. These values were remained unchanged in the stable effort angina group after rapid atrial pacing and in the control group after administration of acetylcholine. CONCLUSIONS: Circulating plasma levels of both soluble E-selectin and ICAM-1 were elevated in patients with variant angina, indicating an association of an inflammatory reaction with coronary spasm. Both soluble ICAM-1 and VCAM-1 appeared to be trapped in the coronary circulation at baseline and released into the coronary circulation following coronary spasm and reperfusion in the patients.

Vitamin E deficiency in variant angina.

BACKGROUND: Oxidative modification of LDL has been suggested to increase coronary vasoreactivity to agonists. A deficiency of vitamin E, a major antioxidant, may be related to the occurrence of coronary artery spasm. METHODS AND RESULTS: Vitamin E levels were determined with the use of high-performance liquid chromatography in normolipidemic subjects, including 29 patients with active variant angina (group 1), 13 patients with inactive stage of variant angina without anginal attacks during the past 6 months (group 2), 32 patients with a significant (>75%) organic coronary stenosis and stable effort angina (group 3), and 30 patients without coronary artery disease (group 4). Total lipid levels in blood were calculated as total cholesterol plus triglyceride levels. The plasma alpha-tocopherol levels as well as alpha-tocopherol/lipids were significantly lower in group 1 than in groups 2 through 4. Also, the plasma gamma-tocopherol levels were significantly lower in group 1 than in groups 2 through 4. The vitamin E levels were not significantly different between group 1 patients with and those without a significant organic stenosis. In group 1, both alpha- and gamma-tocopherol levels were significantly elevated after a > or = 6-month angina-free period. The alpha-tocopherol levels in the LDL fraction were significantly lower in group 1 than in group 4. Plasma alpha-tocopherol levels were significantly correlated with those in the LDL fractions. In 6 patients of group 1 still having anginal attacks while receiving calcium channel blockers, the addition of vitamin E acetate (300 mg/d) significantly elevated plasma alpha-tocopherol levels and inhibited the occurrence of angina. CONCLUSIONS: Plasma vitamin E levels were significantly lower in patients with active variant angina than in subjects without coronary spasm, suggesting an association between vitamin E deficiency and coronary artery spasm.

Effective and safe dose of intracoronary nicorandil in man.

Nicorandil is a hybrid of a nitrate and a potassium channel opener, and has a potent vasodilatory effect on coronary arteries. The effects of intracoronary injection of nicorandil on coronary circulation were examined in 12 adult patients with angiographically normal or near-normal left coronary arteries to determine the optimal dose of this agent. The intracoronary injection of nicorandil (up to 1 mg over 1 min) dilated left coronary artery segments in a dose-dependent manner, with no significant effects on systemic hemodynamic parameters. The percent increase in the epicardial coronary artery diameter with 1 mg nicorandil (31 +/- 5%, mean +/- SEM) was not significantly different from that with 0.3 mg sublingual nitroglycerin (39 +/- 5%). Coronary sinus venous oxygen saturation increased immediately after the intracoronary injection of 1 mg nicorandil, and then returned to the baseline level within 3 min. Neither arrhythmias nor conduction disturbances were observed. These results indicate that dilatation of the epicardial coronary artery was achieved with intracoronary nicorandil in a dose-dependent manner (up to 1 mg over 1 min) without any adverse effects in man, and the dilatory effect on coronary resistance vessels was of short duration.

Comparative effects of early and late reperfusion of the infarct-related coronary artery and collateral circulation which develops after infarction on left ventricular size and function.

This study assesses the effects of early and late reperfusion of the infarct-related coronary artery and collateral circulation developed after infarction on left ventricular morphology and function in 22 patients with a first acute anterior myocardial infarction and without long-standing preinfarction angina. The patients were categorized into 4 groups: group A-5 patients with successful reperfusion within 6 h after the onset of infarction: group B-6 patients with late patency of the infarct-related coronary artery; group C-6 patients without recanalization of the infarct-related coronary artery who had good collateral circulation (collateral index (CI) = 2 or 3); and group D-5 patients without recanalization who had either poor or no collateral circulation (CI = 0 or 1). The left ventricular size and function were evaluated by means of contrast left ventriculography during the chronic stage of infarction. The left ventricular global and regional functions were preserved better (p < 0.05) in group A than in the other three groups. Although there was no difference in regional wall motion of the infarct area among groups B, C and D, the ejection fraction was greater (p < 0.05) and the percentage perimetric circumference was smaller (p < 0.05) in groups B and C than in group D. Among the 4 groups, the left ventricular end-diastolic volume index tended to be greater in group D. Thus, these results suggest that blood supply to the infarct area is essential for the preservation of left ventricular size and function regardless of the timing and route.

Effects of intracoronary administration of nitroglycerin on contralateral intracoronary acetylcholine test results.

This study examined the question of whether intracoronary administration of nitroglycerin modifies contralateral intracoronary acetylcholine test results. Acetylcholine was injected separately into both left and right coronary arteries in 63 patients with coronary spastic angina. Acetylcholine (20 and 50 micrograms) was injected first into the coronary artery responsible for the documented regional ischemia during spontaneous or induced attacks, and then into the other coronary artery. Coronary spasm was defined as severe transient coronary artery vasoconstriction with chest pain and/or electrocardiographic ischemic ST-segment deviation. Spasm was induced in either coronary artery in 60 patients (95%) and in both coronary arteries in 23 patients (37%). The frequency of induced spasm was 67% (42 of 63) in the coronary artery first challenged by acetylcholine. The coronary artery spasm subsided with the intracoronary injection of nitroglycerin (250-750 micrograms) in 19 patients. In the second challenge of intracoronary acetylcholine injection into the contralateral coronary artery, coronary spasm was induced in 29 (66%) of 44 patients. This was done without intracoronary administration of nitroglycerin in the first challenge and in 12 (63%) of 19 patients who had been given intracoronary nitroglycerin. The sensitivity for spasm induced by intracoronary acetylcholine appeared to be unaffected by nitroglycerin. Coronary spasm with ST-segment elevation by intracoronary acetylcholine in the second challenge was significantly less frequent in the patients receiving intracoronary acetylcholine in the second challenge was significantly less frequent in the patients receiving intracoronary nitroglycerin (first: 89%, second: 26%, p < 0.05) as well as in those not receiving intracoronary nitroglycerin for the spasm in the first challenge (first: 52%, second: 13%, p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of intracoronary injection of acetylcholine on coronary collateral circulation.

To clarify the effect of intracoronary injection of acetylcholine on coronary collateral circulation, acetylcholine (20 and 50 micrograms) was injected directly into the donor artery of 5 patients with rest angina who had angiographically demonstrable collateral channels. Coronary spasm was defined as severe vasoconstriction (> or = 90% of luminal diameter) with chest pain and/or ischemic ST-segment changes. The intracoronary injection of acetylcholine induced spasm in all the 5 patients. The site of spasm was collateral vessels in 3, and the recipient coronary artery in 2 of the 5 patients. The spasm resolved spontaneously without administration of nitroglycerin. The contralateral intracoronary injection of acetylcholine also induced diffuse coronary spasm in 4 patients. These findings indicate that collateral vessels and recipient coronary arteries of the collateral circulation are susceptible to acetylcholine. Impaired relaxation and vasospastic responses to acetylcholine presumably due to endothelial dysfunction in the collateral and recipient coronary vessels may explain, at least in part, myocardial ischemia in patients with a well-developed collateral circulation.