Histological patterns of atherosclerotic plaques in unstable angina patients vary according to clinical presentation.

BACKGROUND: Unstable angina is a heterogeneous clinical syndrome. The diverse clinical presentations of unstable angina may reflect different pathogenic mechanisms within the plaque. OBJECTIVE: To investigate the cellular constituents of culprit coronary atheromatous plaques in patients with stable angina pectoris and patients with diverse clinical presentations of unstable angina. METHODS: 48 patients who underwent coronary atherectomy for management of ischaemic heart disease: 23 had stable angina and 25 had unstable angina. Of the latter, 11 patients were classified as Braunwald's IIB and 14 as Braunwald's IIIB unstable angina. The presence of thrombus, cholesterol clefts, and smooth muscle cell proliferation was assessed in atherectomy samples using standard histological techniques. Monoclonal antibodies were used to identify smooth muscle cells and macrophages within atherosclerotic plaque fragments. RESULTS: Fresh thrombus was more frequently found in patients with Braunwald's IIIB unstable angina (64%) than in patients with stable angina (22%) or IIB unstable angina (27%) (p < 0.0006). A pattern of smooth muscle cell proliferation ("accelerated progression pattern") was observed which was also associated with coronary thrombus. This pattern was present in 30% of patients with stable angina, 64% of patients with IIIB unstable angina, and in all patients (100%) with IIB unstable angina. Atherosclerotic plaques with thrombus, cholesterol clefts, and macrophages were more common in patients with unstable angina than in stable angina patients. CONCLUSION: The presence of a specific smooth muscle cell proliferation (accelerated progression) pattern in patients with unstable angina, particularly in those with Braunwald's IIB unstable angina, suggests that episodic plaque disruption and subsequent healing may be an important mechanism underlying angina symptoms in these patients.

Short-term anti-ischemic effect of 17beta-estradiol in postmenopausal women with coronary artery disease.

BACKGROUND: Short-term administration of 17beta-estradiol improves effort-induced myocardial ischemia in female patients with coronary artery disease. 17Beta-estradiol also has direct and indirect coronary vascular smooth muscle relaxing properties. The aim of the present study was to evaluate the effect of short-term administration of 17beta-estradiol on pacing-induced myocardial ischemia by means of continuous monitoring of coronary sinus pH in 16 postmenopausal female patients with coronary artery disease. METHODS AND RESULTS: Patients underwent incremental atrial pacing starting at a rate of 100 bpm and increments of 20 bpm every 2 minutes up to 160 bpm before and 20 minutes after either 17beta-estradiol (1 mg sublingual, 9 patients) or placebo (sublingual, 7 patients). The time to the onset of myocardial ischemia during pacing was significantly increased by 17beta-estradiol (mean+/-SD, 254+/-36 versus 298+/-23 seconds; P<.02) but not by placebo (262+/-45 versus 256+/-34 seconds; P=NS) The pH shift was significantly reduced by 17beta-estradiol but not by placebo at every step of the pacing protocol. The maximum pH shift at peak pacing was significantly reduced by the administration of 17beta-estradiol by 0.022 pH units (95% CI, 0.001, 0.043; P<.04) but not by sublingual placebo (-0.002 pH units; 95% CI, -0.0073, 0.0021; P=NS). The maximum pH shift at maximum comparable pacing was also reduced by 17beta-estradiol by 0.015 pH units (95% CI, 0.012, 0.017; P<.001) but not by placebo (-0.0022 pH units; 95% CI, -0.006, 0.0015; P=NS). CONCLUSIONS: 17Beta-estradiol reduces the degree of pacing-induced myocardial ischemia in postmenopausal patients with coronary artery disease. The reduction of pacing-induced coronary sinus pH shift is consistent with an anti-ischemic effect of the hormone and is not due to preconditioning, as evidenced by the absence of improvement after placebo.

Effect of acute administration of estradiol 17 beta on aortic blood flow in menopausal women.

Acute administration of estradiol 17beta increases aortic blood flow velocity in menopausal women. This suggests that the effect of the ovarian hormone on cardiac dynamics is mainly dependent on a reduction in peripheral vascular resistances.

Failure to demonstrate myocardial ischaemia in patients with angina and normal coronary arteries. Evaluation by continuous coronary sinus pH monitoring and lactate metabolism.

BACKGROUND: Whether myocardial ischaemia is the mechanism underlying chest pain in patients with angina and normal coronary arteriograms is controversial. We sought to detect the presence of transient myocardial ischaemia using continuous monitoring of coronary sinus blood pH during atrial pacing. METHODS AND RESULTS: We studied 14 patients (eight women, six men, mean age 51 +/- 3 years) with typical exertional angina and normal coronary arteriograms and nine patients with coronary artery disease (two men, seven women, mean age 61 +/- 7 years). Of the 14 patients with normal coronary arteries, eight had a reduced coronary blood flow reserve (< 2.5-fold increase), 11 had an ischaemic-appearing response to exercise testing, six had reversible perfusion detects on exercise thallium scans and one had resting left bundle branch block. All patients underwent continuous pH monitoring of coronary sinus blood at rest and during incremental atrial pacing (up to 160 bpm). Coronary sinus oxygen saturation and myocardial lactate extraction ratio were also evaluated at rest and at peak pacing. Eleven patients with angina and normal coronary arteries and eight with coronary artery disease had angina during pacing. Both patients with angina and normal coronary arteries (n = 13) and patients with coronary artery disease (n = 9) showed a fall in coronary sinus pH (-0.02 +/- 0.02 vs -0.11 +/- 0.03 pH units, respectively, P < 0.01). Coronary sinus oxygen saturation expressed as a percentage dropped by 19 +/- 6% in patients with coronary artery disease and by 6 +/- 2% in patients with angina and normal coronary arteriograms (P < 0.05). Myocardial lactate extraction ratio decreased from 33 +/- 6% to -1.4 +/- 4% in patients with coronary artery disease and from 23 +/- 8% to 20 +/- 8% in those with angina and normal coronary arteriograms. Three patients with angina and normal coronary arteries had a drop in coronary sinus pH > 0.02 pH units (-0.043 +/- 0.006 pH units) and in coronary sinus oxygen saturation > 8% (16 +/- 3%) consistent with myocardial ischaemia. CONCLUSION: Despite severe chest pain and reduced coronary flow reserve after pacing, most patients with angina and normal coronary arteriograms do not show metabolic evidence of myocardial ischaemia.

Variant angina pectoris. Role of coronary spasm in the development of fixed coronary obstructions.

BACKGROUND: It has been suggested that recurring coronary artery spasm may lead to the development of fixed atherosclerotic coronary obstructions. METHODS AND RESULTS: We studied 10 patients with typical Prinzmetal's variant angina in whom the disease remained active for years and in whom occlusive coronary spasm occurred reproducibly at the same arterial site during repeat coronary arteriography (25 +/- 12 months after initial angiography). At initial evaluation, four patients had significant (greater than or equal to 50% fixed coronary diameter reduction) one-vessel coronary artery disease, and six had nonsignificant disease. Spasm developed at stenotic sites (20-65% diameter reduction) in nine patients and at an angiographically normal site in one patient. Progression of coronary disease was assessed in 62 segments: 10 spastic (of which nine were stenotic) and 52 nonspastic (eight stenotic and 44 angiographically normal), using computerized arteriography. Mean diameters (millimeters) of spastic segments, nonspastic stenoses, and angiographically normal nonspastic segments were not significantly different at first and second arteriograms (1.52 +/- 0.14 versus 1.43 +/- 0.21, 1.32 +/- 0.17 versus 1.12 +/- 0.23, and 2.40 +/- 0.12 versus 2.42 +/- 0.12, respectively). Stenosis progression (from 65% diameter reduction to total occlusion) occurred in one patient at a spastic site and in two at nonspastic sites (from 34% to 65% and from 84% to 100%). Complicated stenoses suggestive of plaque fissuring were not observed during the study. CONCLUSIONS: In patients with chronic Prinzmetal's variant angina without myocardial infarction, stenosis progression was not frequently observed at spastic sites despite the recurrence of focal coronary spasm over relatively long periods of time.

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)

Usefulness of high-frequency analysis of signal-averaged surface electrocardiograms in acute myocardial infarction before and after coronary thrombolysis for assessing coronary reperfusion.

The incidence of late potentials on the signal-averaged electrocardiogram before and after coronary thrombolysis was studied in 54 patients with an acute myocardial infarction of less than or equal to 5 hours' duration and with an angiographically documented total occlusion of the infarct-related coronary artery on admission. A significant (p = 0.038) 50% relative reduction in the incidence of late potentials was observed in the group of 35 patients who underwent reperfusion: from 16 of 35 (46%) before to 8 of 35 (23%) at 120 minutes after the start of thrombolytic treatment. No significant reduction was seen in the 19 patients in whom thrombolysis was unsuccessful: from 8 of 19 (42%) before to 7 of 19 (37%) afterward. Despite successful recanalization, late potentials persisted or newly developed after thrombolytic therapy in 8 of 54 patients (15%). It is concluded that successful thrombolysis reduces the incidence of late potentials on the signal-averaged electrocardiogram but that the sensitivity and specificity of this finding are not high enough to allow reliable monitoring of coronary reperfusion at the bedside.

[Late potentials in patients with myocardial infarction subjected to coronary thrombolysis]. / Comportamento dos potenciais tardios em portadores de infarto do miocárdio submetidos à trombólise coronária.

PURPOSE: Analyse the behavior of the late potentials (LP) in patients submitted to thrombolysis with success. MATERIAL AND METHODS: Thirty-five patients with acute myocardial infarction, 32 (91.4%) male with ages varying from 33 to 68 (mean 52.6). Thrombolysis was obtained during cinecoronarography with intravenous infusion "in bolus" of doses of 50 mg, 60 mg and 70 mg of rt-PA, with a new bolus of 30 mg at 60 minutes after the procedure. A new angiographic study was performed 12-48 hours late. The high resolution ECG was taken with the ART system model 1200 EPX, before, after and 72 hours later. The presence of electrical activity in the last 40 ms of the QRS complex with less than 20 mu volts in amplitude and more than 35 ms in duration characterized the LP. RESULTS: LP was observed in 16 (46%) patients during the phase of arterial occlusion. LP was recorded only in 23% after recanalization and in 26% when the infarcted related artery (IRA) remain opened. The reduction in the LP was 43.5%. Only one patient with LP had threatening arrhythmia. CONCLUSION: In patients with demonstrated thrombotic occlusion of the IRA, the recanalization diminished the incidence of LP in 43.5% of the patients. Further studies are necessary to achieve the exact clinical importance of these findings.