Absence of myocardial dysfunction during stress in patients with syndrome X.

Stress two-dimensional echocardiographic studies were performed in 18 patients with angina, a positive exercise test and normal findings on coronary angiography (syndrome X). Rest and immediate posttreadmill exercise two-dimensional echocardiograms were performed with a digitized cine loop and side by side visual analysis in all patients. In 16 of these patients, right atrial pacing up to 160 beats/min was also performed and percent systolic wall thickening was calculated at five equally spaced segments around the left ventricle, each corresponding to an anterior, lateral and inferior wall and the posterior and the anterior ventricular septum. Measurements of percent systolic wall thickening were established in 10 age- and gender-matched normal persons for comparison. ST segment depression occurred in all patients during exercise and persisted for 42.1 s (range 18 to 75) into the recovery period. Immediate postexercise echocardiography was started within 20.1 +/- 5.4 s and completed in 54.1 +/- 11.3 s. No patient had regional wall motion abnormalities seen on two-dimensional imaging of any myocardial segment. Thirteen patients (72%) reported reproduction of their usual chest pain, which led to termination of the test. During rapid right atrial pacing, nine patients (56%) developed ST segment depression that was associated with angina in seven. In all 16 patients, percent systolic wall thickening increased over values at rest in each myocardial segment. Percent systolic wall thickening averaged 47.1 +/- 6.1% at rest and increased to 74 +/- 8% during right atrial pacing (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular hypercontractility and ST segment depression in patients with syndrome X.

OBJECTIVES: This study was designed to assess the relation between rest left ventricular function and exercise capacity in patients with syndrome X. BACKGROUND: Clinical observation has suggested that some patients with syndrome X have a high rest left ventricular ejection fraction. In this study we determined the relation between left ventricular ejection fraction and exercise capacity and the electrocardiographic (ECG) changes that develop on exercise. METHODS: The pattern of left ventricular function, exercise capacity and 24-h ambulatory ECG monitoring were studied in 37 patients (9 men, 28 women; mean age 52 +/- 7 years) with syndrome X (angina with normal coronary arteries and a positive exercise test result). All patients had normal findings on echocardiogram and rest ECG. All treatment was discontinued for > or = 48 h. Left ventricular ejection fraction was determined by computerized analysis of the left ventricular angiogram. In patients with syndrome X, exercise duration and heart rate were measured at 1-mm ST segment depression and at peak exercise. RESULTS: Left ventricular hypercontractility (ejection fraction > or = 80%) was observed in 12 patients (32%) (group 1), whereas 25 patients (68%) had normal left ventricular contraction (group 2). The time to 1-mm ST depression on exercise testing was significantly earlier in group 1 than in group 2 (5.13 +/- 1.03 vs. 10.76 +/- 0.63 min, respectively, p < 0.001). The magnitude of the ST segment depression at peak exercise was significantly greater in group 1 than in group 2 (2.03 +/- 0.2 vs. 1.33 +/- 0.05 mm, respectively, p < 0.001). The mean time for ST segment depression to normalize was significantly greater in group 1 than in group 2 (4.76 +/- 0.78 vs. 3.16 +/- 0.39 min, respectively, p < 0.05). Linear regression analysis of all patients with syndrome X showed a significant correlation between exercise duration and ejection fraction (r = 0.55, p < 0.001). The mean circadian variation of heart rate and episodes of ST segment depression on 24-h ambulatory ECG monitoring were similar in the two groups of patients. CONCLUSIONS: These findings indicate that approximately one third of patients with chest pain, normal coronary angiograms and a positive exercise test have left ventricular hypercontractility, and this is associated with the development of ST segment depression at a lower heart rate and work load and a longer time to normalization of ST segment depression after exercise.

Response of the pulmonary circulation to acetylcholine, calcitonin gene-related peptide, substance P and oral nicardipine in patients with primary pulmonary hypertension.

Endothelium-dependent vasodilation of the pulmonary vascular bed was investigated in five patients with primary pulmonary hypertension. Three endothelium-dependent vasodilators (acetylcholine, calcitonin gene-related peptide and substance P [in two patients]) were infused sequentially into the right atrium, followed by nicardipine given orally during full hemodynamic monitoring. Acetylcholine, calcitonin gene-related peptide and substance P had no effect on pulmonary artery pressure, total pulmonary vascular resistance or cardiac output, although calcitonin gene-related peptide significantly decreased systemic arterial systolic pressure from 132 +/- 34 to 113 +/- 33 mm Hg. In contrast, oral nicardipine decreased total pulmonary vascular resistance from 23 +/- 12 to 13 +/- 8 U, with a concomitant increase in cardiac output from 3.1 +/- 1 to 4.7 +/- 2 liters.min-1 and decrease in systemic vascular resistance from 30 +/- 9 to 13 +/- 4 U. Thus, despite the presence of a reversible component in these five patients with primary pulmonary hypertension, pulmonary vascular resistance did not decrease in response to the infused endothelium-dependent vasodilator agents, indicating that endothelium-dependent vasodilation is impaired in these patients.

Basal and flow-mediated nitric oxide production by atheromatous coronary arteries.

OBJECTIVES: This study assessed the effects of inhibition of nitric oxide synthesis on epicardial human coronary arteries and on coronary flow velocity during baseline conditions and during atrial pacing. BACKGROUND: Epicardial coronary artery dilation occurs in response to an increase in heart rate. It is not known whether the dilation of both angiographically normal and diseased epicardial coronary arteries during atrial pacing is nitric oxide dependent in humans. METHODS: The effects of an intracoronary infusion (4 mumol/min for 8 min) of NG-monomethyl-L-arginine (LNMMA), an inhibitor of nitric oxide synthesis, was studied in 16 patients with coronary artery disease and in 6 patients with normal coronary arteriograms. In all patients atrial pacing was performed during normal saline and during LNMMA infusion. the lumen diameter of epicardial coronary arteries was assessed by quantitative angiography, and changes in blood flow velocity were measured with a Doppler catheter. RESULTS: During saline infusion a significant increase in the lumen diameter of the proximal (p < 0.05) and distal (p < 0.01) segments of both normal and diseased arteries occurred during atrial pacing. No significant lumen diameter changes occurred in either group when atrial pacing was performed during LNMMA infusion. Stenosis diameter decreased during LNMMA infusion but did not change with atrial pacing either during saline infusion or during LNMMA infusion. The mean percent change in coronary blood flow with atrial pacing was less (p < 0.05) during LNMMA infusion than during saline infusion in both groups. CONCLUSIONS: These findings confirm that epicardial coronary artery dilation induced by pacing is nitric oxide dependent. Nitric oxide production contributes to the vasomotor tone of coronary resistance vessels. Nitric oxide is produced at the site of atheromatous stenosis but is unaffected by pacing.

Delayed recovery of coronary resistive vessel function after coronary angioplasty.

OBJECTIVES: The aim of this study was to use Doppler catheterization and sequential dynamic positron emission tomography (PET) to investigate the role and time course of abnormal coronary resistive vessel function in the impairment of the coronary vasodilator response (maximal/basal coronary blood flow) after successful coronary angioplasty. BACKGROUND: The coronary vasodilator response may be impaired immediately after coronary angioplasty, despite successful dilation of a flow-limiting stenosis. METHODS: Twelve men (mean age 52 +/- 10 years) with single-vessel coronary artery disease and normal left ventricular function were studied. The coronary vasodilator response to intravenous dipyridamole (0.5 mg.kg-1 over 4 min) was determined from intracoronary Doppler measurement of coronary flow velocity, before and after successful angioplasty. Basal and maximal myocardial blood flow in the angioplasty region and a normal region were determined in nine patients wtih positron emission tomography with H2(15)0 at 1 day (PET1), 7 days (PET2) and 3 months (PET3) after angioplasty. RESULTS: The coronary vasodilator response, measured by Doppler catheterization, was similar before and immediately after angioplasty, 1.63 +/- 0.41 and 1.62 +/- 0.55, respectively (p = NS). After angioplasty, in seven of nine patients without restenosis, basal myocardial blood flow at PET1, PET2 and PET3 was 0.98 +/- 0.16, 0.94 +/- 0.09 and 0.99 +/- 0.13 ml.min-1 x g-1, respectively, in the remote region and 1.19 +/- 0.23 (p < 0.01 vs. remote region), 1.17 +/- 0.19 (p < 0.01 vs. remote region) and 1.10 +/- 0.08 ml.min-1 x g-1 (p = NS vs. remote region), respectively, in the angioplasty region. Myocardial blood flow after dipyridamole at PET1, PET2 and PET3 was 3.04 +/- 0.68, 3.00 +/- 0.71 and 3.00 +/- 0.60 ml.min-1 x g-1, respectively, in the remote region and 2.11 +/- 0.80 (p < 0.01 vs. remote region), 2.28 +/- 0.73 (p = NS vs. remote region) and 3.06 +/- 0.86 ml.min-1 x g-1 (p = NS vs. remote region), respectively, in the angioplasty region. The coronary vasodilator response at PET1, PET2 and PET3 was 3.15 +/- 0.85, 3.18 +/- 0.68 and 3.08 +/- 0.75, respectively, in the remote region and 1.80 +/- 0.68 (p < 0.01 vs. remote region), 1.94 +/- 0.49 (p < 0.01 vs. remote region) and 2.77 +/- 0.74 (p = NS vs. remote region), respectively, in the angioplasty region. CONCLUSIONS: After successful angioplasty, basal myocardial blood flow is increased for > or = 7 days in the angioplasty region, with a reduction in the dipyridamole-induced increase in maximal myocardial blood flow for > or = 24 h after the procedure. Thus, the coronary vasodilator response is impaired for > or = 7 days after angioplasty, indicating that there is abnormal resistive vessel function in the coronary vascular bed distal to a coronary artery stenosis that persists for 7 days to 3 months.

Diffuse reduction of myocardial beta-adrenoceptors in hypertrophic cardiomyopathy: a study with positron emission tomography.

OBJECTIVES: This study was conducted to determine the myocardial beta-adrenoceptor density as a marker of sympathetic function in patients with hypertrophic cardiomyopathy and normal control subjects. BACKGROUND: Although some cases of hypertrophic cardiomyopathy are familial with an autosomal dominant pattern of inheritance, there remains a substantial proportion of cases in which neither a family history nor genetic abnormalities can be demonstrated. Additional abnormalities, both genetic and acquired, may be important in the phenotypic expression of this condition. Clinical features of the disease and metabolic studies suggest an increased activity of the sympathetic nervous system. METHODS: Eleven patients with hypertrophic cardiomyopathy, none of whom had previously received beta-blocking drugs, and eight normal control subjects underwent positron emission tomography to evaluate regional left ventricular beta-adrenoceptor density and myocardial blood flow using carbon-11-labeled CGP 12177 and oxygen-15-labeled water as tracers. Plasma catecholamines were also measured. RESULTS: Mean (+/- SD) myocardial beta-adrenoceptor density was significantly less in the hypertrophic cardiomyopathy group than in the control group (7.70 +/- 1.86 vs. 11.50 +/- 2.18 pmol/g tissue, p < 0.001). Myocardial blood flow was similar in both groups (0.91 +/- 0.22 vs. 0.91 +/- 0.21 ml/min per g, p = NS). The distribution of beta-adrenoceptor density was uniform throughout the left ventricle in both groups. In the hypertrophic cardiomyopathy group, there was no correlation between regional wall thickness and myocardial beta-adrenoceptor density. There were no significant differences in either plasma norepinephrine or epinephrine concentrations between the two groups. CONCLUSIONS: There is a diffuse reduction in myocardial beta-adrenoceptor density in patients with hypertrophic cardiomyopathy in the absence of significantly elevated circulating catecholamine concentrations. This most likely reflects downregulation of myocardial beta-adrenoceptors secondary to increased myocardial concentrations of norepinephrine and is consistent with the hypothesis that cardiac sympathetic drive is increased in this condition.

Inhibition by barium and glibenclamide of the net loss of 86Rb+ from rabbit myocardium during hypoxia.

STUDY OBJECTIVE: The aim was to determine the effects of barium ions and glibenclamide on the hypoxia induced K+ efflux from rabbit myocardium. DESIGN: Experiments were performed on the isolated interventricular septum of the rabbit perfused with a physiological solution through the septal artery. The stimulation rate was 90 beats.min-1 and the temperature 32 degrees C. The flux of 86Rb+ was used as a surrogate of K+ fluxes. EXPERIMENTAL MATERIAL: Septa were obtained from adult male New Zealand white rabbits. MEASUREMENTS AND MAIN RESULTS: The uptake of 86Rb+ by the septum could be fitted to a single exponential curve with a rate constant of 0.024(SEM 0.001) min-1 (n = 14). Washout experiments were performed in which septa were labelled with 86Rb+ and then perfused with unlabelled solution for 60 min. The rate constants for the efflux of 86Rb+ were similar and were 0.022(0.001) min-1 (n = 13) for radioactivity in the tissue and 0.029(0.001) min-1 (n = 13) for radioactivity in the effluent. These rate constants were similar to those reported previously for 42K+. Septa were labelled for 150 to 180 min with 86Rb+ and then perfused with a hypoxic substrate free solution for 15 min followed by reoxygenation. The net loss of 86Rb+ was calculated to be equivalent to 4.00(0.20) mmol.kg-1 wet tissue of K+ (n = 8) and in washout experiments (n = 6) this loss was shown to be due to increased efflux. Ba2+, 0.1 mM and 1.0 mM, added at the onset of hypoxia decreased net tissue loss of 86Rb+ by 64(6)% (n = 5) and 97(1)% (n = 6) respectively (both p less than 0.01). Glibenclamide (0.1 mM) decreased tissue net loss by 52(3)% (n = 6, p less than 0.01). CONCLUSIONS: Part of hypoxia induced net K+ loss in this preparation can be attributed to activation of ATP sensitive K+ channels but other mechanisms are also involved.

Potassium efflux from the myocardium during hypoxia: role of lactate ions.

To determine the role of lactate in the causation of potassium efflux during hypoxia, the effect of lactate ions on the uptake and efflux of 42potassium was studied in the isolated arterially perfused interventricular septum of the rabbit. Septa were equilibrated with lactate (50 mmol.litre-1) under isosmotic conditions before switching to a perfusate containing the inert and impermeant anion isethionate (50 mmol.litre-1). A reduction in tissue 42potassium content was detected, which could only partly be accounted for by increased efflux. During hypoxic substrate free perfusion potassium loss was due to an increased efflux with no evidence of altered influx. The extrusion of accumulating anions, such as lactate ions, from the myocardium is one mechanism for the early potassium loss during hypoxia.

Altered resistive vessel function after coronary angioplasty is not due to reduced production of nitric oxide.

BACKGROUND: The coronary vasodilator reserve with dipyridamole may be impaired immediately after successful angioplasty due to reduced endothelial production or release of nitric oxide. As the vasodilator response to exogenous nitrates is enhanced by endothelium removal or inhibition of nitric oxide synthesis, an increased vasodilator response to nitrovasodilators, such as nitroprusside, should occur. METHODS: The coronary vasodilator reserve (maximal/basel coronary blood flow) with intravenous dipyridamole (0.56 mg/min for 4 min) was measured by Doppler catheterization before and after angioplasty in 10 patients with single-vessel coronary disease. At peak dipyridamole effect, incremental doses of nitroprusside (4-50 micrograms/min) were given intracoronary until systolic blood pressure fell by > or = 5 mmHg. RESULTS: Before angioplasty, the coronary blood flow increased from 19.7 +/- 6.1 (mean +/- s.d.) at basal to 30.1 +/- 11.9 ml/min at the peak dipyridamole effect (P < 0.01), giving a coronary vasodilator reserve of 1.62 +/- 0.39 (range 1.20 - 1.96). After angioplasty, the coronary blood flow increased from 32.4 +/- 13.2 at basal to 53.4 +/- 23.3 ml/min at the peak dipyridamole effect (P < 0.01), giving a coronary vasodilator reserve of 1.77 +/- 0.64 (range 1.7-2.42). Sodium nitroprusside had no additional effect on coronary flow (49.5 +/- 20.4 and 52.2 +/- 18.0 ml/min) before and after a fall in systolic blood pressure, respectively. CONCLUSIONS: The vasodilator response to dipyridamole was markedly impaired immediately after successful angioplasty, and was not augmented by intracoronary nitroprusside. Thus, a reduced production or release of nitric oxide in the coronary circulation does not seem to be responsible for the impaired vasodilator response after angioplasty.

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 micromol/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> or = 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 micromol doses, but occurred only at the 16 micromol/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.

Inhibition of nitric oxide synthesis during the cold pressor test in patients with coronary artery disease.

The effects of a cold pressor test during intracoronary infusions of L-NMMA and normal saline were studied in patients with chronic stable angina and in patients with normal coronary arteriograms. The cold pressor test during saline infusion caused significant dilation of proximal and distal segments in patients with normal coronary arteriograms, and this dilation was abolished by L-NMMA infusion; in patients with coronary disease the cold pressor test during saline caused constriction of the stenoses and distal segments and this constriction was augmented by L-NMMA infusion.

Effects of changing the availability of the substrate for nitric oxide synthase by L-arginine administration on coronary vasomotor tone in angina patients with angiographically narrowed and in patients with normal coronary arteries.

We assessed the effects of intracoronary administration of substance P, LNMMA, L-arginine, and nitroglycerin in patients with normal coronary angiograms and in patients with coronary artery disease. LNMMA constricted (p <0.01) and both substance P and nitroglycerin dilated normal and diseased proximal and distal segments and stenoses (p <0.01). L-Arginine reversed the effect of LNMMA in all segments and caused greater dilation of the diseased arteries, including stenoses (p <0.05), indicating that there is a relative deficiency of L-arginine in diseased coronary arteries.

Vasomotor responses of coronary stenoses to acetylcholine and their relation to serum lipid levels in stable angina pectoris.

The effects of acetylcholine administration on coronary stenoses in relation to serum lipids level were evaluated in 18 patients (15 men, 3 women) with coronary artery disease and stable angina. Intracoronary acetylcholine was infused in concentrations 10(-7), 10(-6), 10(-5) M, followed by intracoronary bolus administration of isosorbide dinitrate. Computerized angiography was used to assess the changes in the diameter of stenoses and of proximal and distal segments. During acetylcholine infusion, at concentrations between 10(-7) to 10(-5) M, there was a significant (p <0.01) dose-dependent constriction of proximal and distal segments and of stenoses reversed by isosorbide dinitrate. There was no correlation between the serum total cholesterol level and the responses of proximal and distal segments to acetylcholine or nitrate. A correlation (p <0.05) was found between the serum total cholesterol level and the response of stenoses to acetylcholine, but there was no correlation with the response to isosorbide dinitrate. In conclusion, in patients with stable angina current serum total cholesterol level correlates with the vasomotor response of coronary stenoses to intracoronary acetylcholine. These findings are consistent with a direct effect of cholesterol, increasing basal coronary vasomotor tone and increasing the stimulated vasoconstrictor response of stenoses.

Left ventricular function and coronary artery disease progression early after coronary bypass grafting.

To investigate the effects of coronary artery disease progression on left ventricular function in patients who suffer angina early after coronary artery bypass grafting, we studied the progression of coronary stenoses, the occurrence of graft occlusions, and measured left ventricular ejection fraction (regional and global) in 34 consecutive patients who underwent repeat angiography 25.2 +/- 3.5 (standard error of the mean) months postoperatively, from a total population of 550 patients who underwent bypass grafting. Resting left ventricular function and stenosis severity were assessed using a computerized, quantitative analysis system. Coronary stenosis progression was defined as an increase in the percentage of the stenotic occlusion by 30% or more, any increase in lesion severity that resulted in total coronary artery occlusion, or the occurrence of a new stenosis that occluded the artery by 50% or more. Group 1 comprised 21 patients with all grafts patent and group 2 comprised 13 patients with one or more grafts occluded (20 of 34 grafts). Coronary artery disease progressed in all patients in group 1, and this involved 22 of 54 (41%) grafted vessels and 3 of 15 (20%) nongrafted vessels (p < 0.05). Coronary artery disease progressed in 11 patients in group 2, involving 15 of 32 (47%) grafted vessels and 1 of 6 (17%) nongrafted vessels (p < 0.01). An increased collateral circulation was observed in both groups. The left ventricular ejection fraction remained unchanged in both groups (group 1, 0.60 +/- 0.03 versus 0.62 +/- 0.03; group 2, 0.62 +/- 0.05 versus 0.62 +/- 0.04 before and after bypass, respectively; p = not significant) and there was no difference between the groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac troponin T does not increase after electrical cardioversion for atrial fibrillation or atrial flutter.

OBJECTIVE: To determine whether cardiac troponin T increases after electrical cardioversion in patients with atrial fibrillation or atrial flutter. DESIGN: Serum creatine kinase (CK), creatine kinase-MB (CKMB), and cardiac troponin T were measured before, 24 hours, and 48 hours after cardioversion in 15 patients with atrial fibrillation or atrial flutter. RESULTS: 12 of the 15 patients (80%) were successfully cardioverted to sinus rhythm. The median number of shocks was three (range one to six), the median cumulative energy 710 J (50 to 1430 J), and the median peak energy 300 J (50 to 360 J). Total CK increased from a baseline median concentration of 92 (45 to 259) to 1324 (96 to 6660) U/l at 24 hours and 1529 (120 to 4774) U/l at 48 hours after cardioversion. There was a small increase in CKMB but the ratio of CKMB to CK did not increase. There was no increase in cardiac troponin T in any patient. CONCLUSIONS: Following electrical cardioversion of atrial fibrillation or atrial flutter, cardiac troponin T remains unchanged despite a large rise in total CK, indicating that the CK is derived from skeletal muscle and that myocardial injury does not occur. If cardiac troponin T is increased after cardioversion for atrial arrhythmias then other causes of myocardial damage should be sought.

Impairment of the myocardial vasomotor response to cold pressor stress in collateral dependent myocardium.

OBJECTIVE: To study the vasomotor response (cold pressor/basal flow) in myocardium perfused entirely by collaterals, using the reflex sympathetic stimulation of cold pressor stress. DESIGN: Regional myocardial blood flow was measured in collateral dependent and in remote myocardium using positron emission tomography with 15O water at basal and at cold pressor stress. Regional ischaemia was measured with 18F-fluorodeoxyglucose (FDG). PATIENTS: Nine patients (mean (SD) age 53 (6) years) with an occluded coronary artery supplied entirely by collaterals from other angiographically normal arteries. RESULTS: In remote myocardium, basal and cold pressor flow were 0.99 (0.26) and 1.46 (0.60) ml/min/g (P < 0.05), respectively, a myocardial vasomotor response of 1.46 (0.45). In collateral dependent myocardium, basal and cold pressor flow were 0.91 (0.20) and 0.87 (0.35) ml/min/g, respectively (the latter value, P < 0.05 v remote region), a myocardial vasomotor response of 0.97 (0.43) (P < 0.05 v remote region). The myocardial vascular resistance (mean arterial pressure/flow) during cold pressor was higher in the collateral dependent than in remote myocardium, at 147.0 (61.1) and 85.6 (32.3) mm Hg.min.g/ml (P < 0.05), respectively, but with no relative increase in FDG uptake. CONCLUSIONS: In contrast to the decrease in myocardial resistance in remote myocardium with cold pressor, an increase was observed in collateral dependent myocardium suggesting a vasoconstrictor response in resistive vessels, without demonstrable myocardial ischaemia.

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

OBJECTIVE: The vasomotor responses of the epicardial coronary arteries to acetylcholine were examined in patients with normal coronary arteries and chest pain. DESIGN: 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. PATIENTS: Coronary arteriograms were obtained in 15 patients (mean (SEM) age 48 (10) years) with normal coronary arteries and chest pain. MAIN RESULTS: 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)%. CONCLUSIONS: 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.

Effects of L- and D-arginine on the basal tone of human diseased coronary arteries and their responses to substance P.

OBJECTIVE: To assess the effects of substance P administration alone and in combination with L- and D-arginine in patients with normal angiograms and in patients with coronary artery disease. DESIGN: Intracoronary infusions of (a) normal saline, (b) the receptor mediated nitric oxide stimulant substance P (5.6 and 27.8 pmol/min) before and after L- or D-arginine (50 and 150 micromol/min), and (c) glyceryl trinitrate (250 microg bolus) were given to 17 patients with coronary artery disease and stable angina, and to six patients with normal angiograms. The diameter of angiographically normal proximal and distal segments and coronary stenoses were measured by computerised quantitative angiography. RESULTS: L-arginine administration was associated with significant dilatation of stenoses (p < 0.01) of proximal segments of both "normal" (p < 0.05) and diseased (p < 0.01) arteries, and of distal segments of diseased arteries (p < 0.01). No significant changes were associated with D-arginine administration. Dose dependent dilatation of all segments including stenoses, was observed with substance P both before and after L-arginine infusion (p < 0.01). The magnitude of dilatation of stenoses and all segments of both "normal" and diseased coronaries was greater after L-arginine (p < 0.05) but not D-arginine and substance P infusion, than it was after saline and substance P infusion. Administration of D- or L-arginine did not change the magnitude of substance P induced dilatation. CONCLUSIONS: Diseased and "normal" coronary arteries dilated in response to substance P and L-arginine but were unaffected by D-arginine infusion. The magnitude of the response to substance P was not increased by L-arginine administration, indicating that it is not critically dependent on the availability of substrate for nitric oxide synthase.

Platelet and Thrombin Activity Following Cardiac Catheterization Despite Treatment with Aspirin.

Thromboembolic complications are reported to occur in up to 0.5-2% of left cardiac catheterizations and angiographies. Activation of the hemostatic system may contribute to their onset. To prevent platelet and thrombin activity during catheterization, aspirin or systemic heparin are often used in addition to heparinized flush solutions. We investigated whether aspirin alone can prevent platelet and thrombin activity induced by catheterization in ten consecutive patients (nine males, mean 50 +/- 8 years) undergoing elective left cardiac catheterization after at least 5 days of oral aspirin (75-300 mg/d). Anticoagulant drugs were not given. Peripheral venous samples were drawn before, immediately after (time 0), and at 15, 60, and 180 minutes after the procedure for measurement of thrombin-antithrombin (TAT), prothrombin fragment 1.2 (F 1.2), fibrinopeptide A (FPA), and beta-thromboglobulin (beta-TG). TAT, F1.2, and FPA increased significantly at time 0 compared with both before and 180 minutes after the procedure (P < 0.04); beta-TG values were higher at time 0 compared with 180 minutes later (P = 0.01). TAT levels were related to those of FPA (r = 0.66; P = 0.0003), F1.2 (r = 0.35; P = 0.01), and beta-TG (r = 0.37; p = 0.04). Thus, routine left cardiac catheterization is associated with transient, systematically detectable, activation of coagulation and platelets, despite aspirin therapy. Newer antiplatelet agents may be more effective in preventing hemostatic activation induced by catheterization.