Normal Coronary Artery Segments Research Articles

Discovering pericoronary adipose tissue differences between normal and atherosclerotic coronary segments with radiomics analysis

Abstract Introduction Pericoronary adipose tissue (PCAT) extracted from coronary CT angiography (CCTA) is a novel marker for coronary inflammation. Establishing correlation between PCAT changes and the vascular lesion itself is essential for using PCAT to monitor clinical and subclinical disease status. Past studies focused on patient-level and vessel-level PCAT differences. However, lesion-level PCAT differences beyond mean attenuation values are not well understood. Purpose To investigate the differences between PCAT adjacent to atherosclerotic plaques and PCAT adjacent to normal coronary segments using radiomics analysis. Material and Methods This study enrolled 100 consecutive patients who underwent CCTA. A total of 446 plaques were successfully annotated in 89 patients. The PCAT of these 446 plaques and also their normal segment counterparts were extracted. Following prior literature, adipose tissue was defined as voxels with attenuation ranging -190 to -30 HU. PCAT was extracted within 3 mm distance from the vessel wall, along the middle 10 mm of each plaque. The PCAT of normal coronary artery segments were extracted both proximal and distal with distance D mm to the plaque with 10 mm length. We used 3 different distances to define the normal segments (D={10, 20, 30}). PyRadiomics was used to generate radiomics features and the random forest classifier from Scikit-Learn was used to distinguish PCAT extracted adjacent to atherosclerotic plaques and PCAT adjacent to normal coronary segments. To minimize bias due to vessel diameter or shape and focus on the texture of PCAT, we included only the First Order, GLCM, GLDM, GLRLM, GLSZM and NGTDM features (total 93 features) from PyRadiomics. We used 5-fold cross validation splitted at patient-level to develop the classifier. Result The radiomics model achieved acceptable discrimination for D=30 mm (mean AUROC = 0.70), borderline discrimination for D=20 mm (mean AUROC=0.68) and D=10 mm (mean AUROC = 0.60). These results suggest a trend toward greater differences between PCAT further away from the lesion compared with PCAT adjacent to the lesion. The feature "Gray Level Size Zone Matrix (GLSZM): Low Gray Level Zone Emphasis" had the highest importance in 4 out of 5 folds in our D = 30 mm experiment. The mean value of this feature is significantly different for the PCAT adjacent to the lesions compared to PCAT extracted from the normal segments (0.152 vs 0.166, p=0.001). Conclusion We investigated the difference between PCAT adjacent to atherosclerotic plaques and PCAT adjacent to normal coronary segments using radiomics analysis. We found greater discrimination when the normal segments were extracted further away from the lesion, suggesting PCAT changes due to atherosclerosis may exist beyond the length of the plaque. Moreover, "Gray Level Size Zone Matrix (GLSZM): Low Gray Level Zone Emphasis" could serve as a novel radiomic biomarker to correlate PCAT changes to atherosclerosis.

Cardiac tamponade due to rupture of a giant coronary artery aneurysm with a coronary arteriovenous fistula: a case report

BackgroundCoronary artery aneurysm (CAA) is defined as dilatation exceeding 1.5 times the width of the normal adjacent coronary artery segments. CAA usually causes few symptoms, and rupture is rare, but can be lethal due to cardiac tamponade when it does occur.Case presentationA 79-year-old woman presented with presyncope and back pain. Emergency surgery was performed based on a diagnosis of cardiac tamponade due to either rupture of coronary arteriovenous fistula or CAA. At surgery, a rupture site was located on the wall of the giant CAA, with a diameter of 55 mm, originating from the ostium of the right coronary artery. Suture closure of the inflow and outflow of the aneurysm was performed, and the aneurysmal cavity was obliterated by multiple sutures. The patient made an uneventful recovery and was discharged from hospital on postoperative day 13.ConclusionOn the basis of this case, we propose considering rupture of a CAA as one of the causes of cardiac tamponade.

Rupture of massive coronary artery aneurysm resulting in cardiac tamponade.

Coronary artery aneurysm is a fairly uncommon clinical entity, which is defined by a characteristic dilatation that exceeds 1.5 times the width of normal adjacent coronary artery segments. In the present report, we describe a case of rupture of a massive coronary artery aneurysm. A man in his 40s was found dead in his bed. The pericardial cavity contained 270mL of blood with 428.2g of coagulation. Two true aneurysms of the right coronary artery were identified. A proximal aneurysm, adjacent to the right auricle, had ruptured on the right. A distal unruptured aneurysm was identified 5.1cm distal to the proximal ruptured aneurysm. Atherosclerosis of the coronary arteries and aorta was severe. The heart weighed 799.1g and showed concentric ventricular hypertrophy, myocardial thinning, and patchy fibrosis. Histological analysis showed that both aneurysms were purely atherosclerotic true aneurysms without considerable inflammation. The cause of death was determined as cardiac tamponade due to rupture of a giant coronary atherosclerotic aneurysm.

EComment. Coronary artery dilatation: ectasia or aneurysm

We read with great interest the paper by Singh et al [1]. They described surgical treatment including proximal ligation and plication of the aneurysm with coronary artery bypass grafting in a series of 4 cases of coronary artery aneurysm (CAA) from a single centre. We would like to congratulate the authors for bringing such a rare entity to our attention. We would also like to add a short comment on this topic. Coronary artery dilatation is an exceptional and frequently unrecognized incidental finding in patients with coronary artery disease [2]. At present there is no uniform definition of this pathology. Coronary artery ectasia (CAE) and CAA are characterized by an abnormal dilatation of the coronary artery. They are used interchangeably for the condition. CAE may be classified into four types on basis of the extent of coronary artery involvement: Type I - diffuse ectasia of two or three vessels; Type II - diffuse ectasia in one vessel and localised disease (ie, aneurysm) in another; Type III - diffuse ectasia in one vessel only, and; Type IV - localised or segmental involvement (CAA) only [3]. This classification may have prognostic implications, with the worst outcomes in types I and II [2]. CAA may be classified in three different ways on the basis of the composition of the vessel wall (true aneurysms or pseudoaneurysms), the morphologic structure (saccular or fusiform aneurysms), and size (e.g., large or giant aneurysms) [2]. The various factors contributing to CAA formation include atherosclerosis, congenital malformations, Kawasaki disease, percutaneous coronary interventions, inflammatory arterial diseases (polyarteritis nodosa, systemic lupus erythematosus, Takayasu's arteritis), infectious causes (endocarditis, syphilis, candidosis, Lyme borreliosis), chest traumas, vasculitis (eg, Behcet disease), connective tissue disorders (Marfan's syndrome, Ehlers Danlos syndrome, scleroderma), primary cardiac lymphoma and primary hyperaldosteronism [2]. CAE is used to describe diffuse dilatation (>1.5 times the normal diameter) of the coronary arteries that involves 50% or more of the length of the vessel. However, CAA is defined as a localized dilatation that exceeds the diameter of normal adjacent coronary artery segments, or the diameter of the patient's largest coronary vessel by 1.5 times. Herein, coronary artery involment is less than 50% of the total length of the vessel [2]. A giant aneurysm is defined as one where the maximal vessel diameter exceeds 20 mm in adults or 8 mm in children. In adults, the reported diameter of giant CAAs varies from 50 to 150 mm. Giant CAAs are rare, with a reported prevalence of 0.02% [4]. Potential complications include rupture (subsequent cardiac tamponade), thrombosis, embolization, dissection, mechanical obstruction, and erosion into surrounding structures. In these patients, surgery should be considered as a means to avoid complications [5]. Conflict of interest: none declared

Acute Myocardial Infarction Secondary to Catecholamine Release Owing to Cocaine Abuse and Pheochromocytoma Crisis

Most pheochromocytomas are not suspected clinically while a high percentage of them are curable with surgery. We present the case of an adult cocaine-addicted male patient with an underlying pheochromocytoma and repeated myocardial infarctions. Computed tomography showed a left round adrenal mass, also high 24-hour urine levels of catecholamines and metanephrines were detected from urinalysis. The patient was given alpha and beta blockers, moreover a laparoscopic left adrenalectomy was performed. Cocaine can block the reuptake of noradrenaline, leading to increasing its concentration and consequently its effects as well, and induce local or diffuse coronary vasoconstriction in normal coronary artery segments per se, cocaine can also trigger pheochromocytoma crisis, and therefore, cardiac complications such as myocardial infarction due to these additive effects are intended to occur. For this reason, in the presence of typical clinical manifestations of pheochromocytoma, such as sustained or paroxysmal hypertension, headache, sweating, tachycardia and abdominal pain, probable association of this tumor in patients with cocaine abuse and associated cardiac complications must be ruled out.

Coronary vasospasm during a regadenoson stress test

A 43 year-old male was referred for pharmacological stress testing in 2010 in the setting of increasing dyspnea on exertion and atypical chest pain. He had been diagnosed with hypertrophic cardiomyopathy following a ventricular fibrillation arrest in 2004. At that time, he underwent a negative evaluation for coronary atherosclerosis and intracardiac defibrillator implantation, and had done well since. Upon regadenoson injection (0.4 mg over 10 s) he became tachycardic, diaphoretic, and complained of severe chest tightness. His ECG showed exaggeration of baseline abnormalities, non-specific for ischemia (Figs. 1, 2). He was given aminophylline (150 mg intravenous) with resolution of his symptoms. Myocardial imaging revealed a moderate to large-sized reversible defect involving the anteroseptal, anterior, and inferolateral walls, as well as stress-associated left ventricular dilation (Fig. 3). Subsequent coronary angiography was negative for significant coronary artery disease or anatomical coronary anomalies (Fig. 4). Adenosine and its analogs provoke coronary vasodilation via activation of A2A type adenosine receptors, and are useful as pharmacological stress agents by exploiting flow-reserve differences between normal and atherosclerotic coronary artery segments [1]. However, coronary vasospasm is a well-known occurrence of adenosine administration, and milder side effects are frequently encountered, likely related to the activation of non-A2A type receptors [2].

Traditional Risk Factors Are Predictive on Segmental Localization of Coronary Artery Disease

The aim of this study was to investigate the relationship between established risk factors and segmental localization of coronary artery disease. A total of 2760 patients who underwent coronary angiography were enrolled into the study. Coronary angiographic segmental evaluation was performed according to the scheme of American Heart Association. Patients were classified into 2 groups (group 1: normal coronary artery segments, group 2: coronary artery segments with coronary artery disease). Smoking was highly related with left main coronary artery disease (odds ratio = 7.5; P = .005). Diabetes mellitus and male sex increased the risk of atherosclerosis in all coronary vasculature (odds ratio = 2.7-2.2; P < .001-P < .001). Hypertension was correlated with distal coronary artery (odds ratio = 1.4; P < .001) and family history with distal circumflex lesions (odds ratio = 4.5; P = .005) High triglyceride levels were associated with right coronary artery lesions (odds ratio = 1.00; P =.03). The effect of advanced age was small (odds ratio = 1.08; P < .001). Risk factors may be predictive for segmental localization.

Atherosclerosis in angiographically “normal” coronary artery reference segments: An intravascular ultrasound study with clinical correlations

Objectives.This study evaluated the magnitude, patterns and clinical correlates of atherosclerosis in angiographically “normal” reference segments in patients undergoing transcatheter therapy for symptomatic coronary artery disease.Background. Pathologic studies indicate that the extent of coronary atherosclerosis is underestimated by visual analysis of angiographically normal coronary artery segments. Intravascular ultrasound allows detailed, high quality cross-sectional imaging of the coronary arteries in vivo.Methods. Intravascular ultrasound was used to study angiographically normal coronary artery reference segments in 884 patients evaluated for transcatheter therapy for symptomatic native coronary artery disease. The reference segment was the most visually normal intravascular ultrasound cross section within 10 mm proximal to the target lesion but distal to any major side branch. Results are presented as mean value ± 1 SD.Results. Only 60 (6.8%) of 884 angiographically normal reference segments were normal by intravascular ultrasound. Reference segment percent cross-sectional narrowing measured 51 ± 13% and correlated poorly with the target lesion percent cross-sectional narrowing (r = 0.166, p < 0.0001). Reference segments contained less calcific and dense fibrotic plaque and proportionately more soft plaque elements. Independent predictors of reference segment percent cross-sectional narrowing were male gender, patient age, diabetes mellitus, hypercholesterolemia and presence of multivessel disease. Independent predictors of reference segment calcification were patient age and serum creatinine levels. Reference segment percent cross-sectional narrowing in 723 patients undergoing transcatheter therapy was similar to that in patients studied for diagnostic purposes; however, reference segment arc of calcium was greater in treated patients (43 ± 81 vs. 25 ± 57, p = 0.015). Reference segment disease was not an independent predictor of subsequent angiographic restenosis or clinical events within 12 months of follow-up.Conclusions. Atherosclerosis is ubiquitous in angiographically normal coronary artery reference segments. Reference segment disease parallels the severity of target lesion disease and is associated with many of the conventional risk factors for coronary artery disease. Because of its sensitivity in detecting atherosclerosis in angiographically normal reference segments, intravascular ultrasound should enhance the study of risk factors for atherosclerosis and the results of therapies to control disease progression.

Coronary vasoconstriction induced by mental stress (simulated public speaking)

The present study demonstrates that potent mental stress, such as that produced in response to the simulated public speaking task, results in an increase in heart rate and blood pressure, and vasoconstriction of normal coronary artery segments in patients with and without angiographically demonstrable coronary artery disease.

Patterns of coronary artery stenosis vasomotion

Patterns of constriction and dilatation of angiographically normal coronary artery segments and coronary stenoses, in response to vasoactive stimuli, remain speculative. We compared the vasomotor response of angiographically normal and stenotic coronary segments and assessed the effects of stenosis location and morphology on coronary stenosis vasomotion in 52 patients with chronic stable angina (40 men and 12 women) who underwent intracoronary ergonovine or isosorbide dinitrate administration or both. Changes in coronary diameter in response to nitrate and ergonovine were assessed by computed arteriography. The "predicted" change in stenosis diameter was calculated according to the "geometric theory" (based on the vasomotor response of angiographically normal segments adjacent to the lesion and on stenosis severity). Coronary diameter was assessed at baseline and after nitrate administration in 58 stenoses (34 concentric and 24 eccentric), of which 40 were located proximally and 18 distally, and also after ergonovine administration (23 stenoses: 14 proximal and 9 distal, 14 concentric and 9 eccentric). Significant (> or = 10% lumen diameter change) vasoconstriction was observed after ergonovine administration in 14 of the 23 stenoses (61%), and significant vasodilation was noted after nitrate administration in 29 of 58 stenoses (50%). A larger proportion of distal (89%) and eccentric (89%) compared with proximal (43%) and concentric (43%) stenoses showed a greater than 10% vasoconstriction after ergonovine administration (P < 0.05). Vasodilatation after nitrate administration was also observed in a larger proportion of distal (78%) and eccentric (67%) than in proximal (38%) and concentric (38%) stenoses (P < 0.05). On average, the "observed" changes in coronary diameter in response to nitrate and ergonovine administration were of significantly less magnitude than those "predicted" by the geometric theory in both proximal and distal stenoses and in concentric and eccentric stenoses. In only 17% of stenoses were observed and predicted vasoconstriction similar. Our results suggest that in patients with chronic stable angina, calculations based on the "geometric theory" cannot predict the actual vasomotor response of a stenosis. Factors other than severity, such as baseline coronary tone, stenosis location, and stenosis morphology, appear to modulate stenosis vasomotion in vivo.

Relationship of blood cholesterol and apoprotein B levels to angiographically defined coronary artery disease in young males.

Coronary heart disease is mainly caused by the effects of obstruction to blood flow in the coronary arteries from discrete mural lesions that encroach into the lumen and usually occur in arteries that are involved by atherosclerosis. Even though the level of certain lipoproteins is indisputably related to the degree of this atherosclerotic involvement of the coronary arteries, the question of whether lipoproteins are also associated with the obstructive lesions remains uncertain. This study addressed the question in 53 males (age, 44.6 +/- 4.9 y) with premature coronary heart disease and angiographically proven coronary artery disease. The cholesterol, triglyceride, high-density lipoprotein, apoprotein B, and apoprotein A-I levels were compared by linear correlation to semiquantitative angiographic measures of coronary artery disease severity (coronary stenosis score and mean coronary stenosis score), the extent of mural involvement (coronary atheromatous score and mean coronary atheromatous score), and also the number of normal coronary artery segments, an alternative severity score (Jenkins), and left ventricular function score. Age, past and present cholesterol, low-density lipoprotein cholesterol, and apoprotein B levels correlated directly with the extent of disease (r = 0.27, 0.46, 0.29, 0.26, 0.35, respectively, P < 0.05 with coronary atheromatous score; r = 0.29, 0.44, 0.33, 0.30, 0.35, respectively, P < 0.05 with mean coronary atheromatous score). Age and New York Heart Association angina functional class correlated directly with disease severity (r = 0.25, 0.31, respectively, P < 0.05 with coronary stenosis score; r = 0.25, 0.34, respectively, P < 0.05 with mean coronary stenosis score). There was an inverse association between age, past and present cholesterol, low-density lipoprotein cholesterol, and apoprotein B levels with the number of normal segments (r = -0.23, -0.46, -0.38, -0.35, -0.39, respectively, P < 0.05). Multiple regression analysis was undertaken with lipoproteins and age as independent variables and angiographic scores as dependent variables; the apoprotein B level was the most predictive of the extent of coronary artery disease (P < 0.02) and inversely predicted the number of normal segments (P < 0.002). Of those variables entered into the regression model, only age was independently predictive of the severity of angiographic coronary artery disease. Apoprotein B levels are not predictive of coronary artery disease severity but do predict independently the extent of involvement of coronary atherosclerosis defined angiographically.

Increased production of thromboxane A 2 by coronary arteries after thrombolysis

The coronary artery produces large amounts of prostacyclin (PGl 2) and a small amount of thromboxane A 2 (TXA 2); this high PGl 2 TXA 2 ratio contributes to the antithrombotic properties of the coronary artery. This study was designed to determine whether this ratio changes after coronary artery thrombosis and thrombolysis and accounts for coronary artery reocclusion. Anesthetized dogs ( N = 12) were subjected to electrically induced coronary artery thrombosis and tissue plasminogen activator-induced thrombolysis. Thrombolysis was achieved in 11 dogs, and the coronary artery reoccluded in five of these dogs after the initial reperfusion. Spontaneous and ionophore A23, 187-stimulated PGl 2 and TXA 2 synthesis in normal circumflex and ischemic-reperfused left anterior descending coronary artery segments was measured by radioimmunoassay of thromboxane B 2 and 6-keto-prostaglandin F 1α, respectively. Production of TXA 2 was 413% to 656% greater in left anterior descending segments (from the region of thrombosis and sites proximal and distal to the thrombus) compared with normal circumflex segments ( p < 0.001). Production of PGl 2 was also increased but only by 46% to 80% in the left anterior descending segments compared with normal circumflex segments ( p < 0.05). TXA 2 production was greater in coronary artery segments that reoccluded compared with segments that stayed open ( p < 0.02). Scanning electron microscopy revealed platelet deposition in thrombosed left anterior descending segments but not in segments proximal or distal to the thrombus site, indicating that the vascular wall per se may be a source of increased production of TXA 2. In other experiments, normal coronary artery segments were exposed to thrombin and showed enhanced production of TXA 2, suggesting a role for thrombin in the increased production of TXA 2 in thrombosed-reperfused coronary arteries. In conclusion, increased TXA 2 production by coronary arteries after reperfusion may induce platelet aggregation and vasospasm and contribute to reocclusion after thrombolysis.

Doppler color flow mapping of epicardial coronary arteries: Initial observations

Objectives. We addressed the hypothesis that blood flow could be imaged by Doppler color flow mapping of the coronary arteries and characteristic patterns described in normal and diseased vessels.Background. Echocardiographic imaging of the epicardial coronary arteries has been suggested as a useful adjunct to their intraoperative evaluation. Addition of Doppler color flow mapping could potentially enhance this evaluation by displaying the flow disturbance produced by anatomic lesions whose physiologic significance may otherwise be uncertain. In experimental models, such displays could also potentially provide insights into the pathophysiology of coronary blood flow and stenosis.Methods. Epicardial coronary arteries were examined with a high resolution 7-MHz linear phased-array transducer both in vivo and in vitro. 1) The coronary arteries were studied in the beating hearts of 10 open chest dogs in which experimental stenoses were also created; the maximal extent of the arterial tree in which flow could be seen in the most ideal setting was also examined in four additional excised perfused canine hearts. 2) Six excised human coronary arteries were perfused in a pulsatile manner to determine whether abnormal flow patterns could be prospectively identified and subsequently correlated with pathologic evidence of stenosis.Results. All normal coronary artery segments studied showed homogeneous flow without evidence of flow disturbance. In the excised heart, flow could be visualized to the distal extent of the epicardial vessels; in the open chest model, visualization of the proximal 5 to 6 cm was comparable, although surrounding structures limited access to the terminal portions of the vessels. The stenotic lesions created in the canine hearts (n = 9) showed recognizable alterations in the flow pattern: localized aliasing, proximal blood flow acceleration, distal flow disturbance and recirculatory flow. In the excised human arteries, these features identified 12 lesions, all of which corresponded to areas of ≥50% lumen narrowing by pathologic examination.Conclusion. Blood flow in the epicardial coronary arteries can be imaged by Doppler color flow mapping and characteristic flow patterns described in normal and diseased vessels.

Histological and angiographic effects of a pulsed holmium:YAG laser in normal and atherosclerotic human coronary arteries and aorta.

The aims were (1) To determine the histological and angiographic effects of holmium:YAG laser energy delivered through clinical multifibre laser catheters on fresh cadaveric coronary arteries; and (2) to relate the placement of optical fibres in the catheter to patterns of tissue ablation in cadaveric aorta. Eight fresh cadaveric hearts and segments of aorta were used. Hearts were mounted on a new pressure perfusion device. The laser catheter was delivered over a guidewire in the lumen until it met an area of resistance. The coronary artery lumen was perfused at approximately 100 mm Hg mean pressure. These arterial areas were identified on angiography, marked, and then exposed to laser energy in the range 600-3000 mJ.mm-2. Normal and atherosclerotic areas of fresh cadaveric aortic strips were exposed to increasing laser energies using either constant or increasing fluence. Coronary arteries were pressure perfused with formalin for 18-24 h at 100 mm Hg mean pressure, and aortic strips were immersed in 5% formalin. Light and scanning electron microscopy studies were carried out. There were no perforations or dissections by angiography in the fresh coronary arteries. One of 15 normal coronary artery segments and 10 of 16 of the pressure perfused, fixed, atherosclerotic coronary artery segments showed thermal changes associated with atherosclerotic plaque ablation. In aortic tissue, thermal effects extended 0 to 0.6 mm lateral to the ablated crater. Acoustic effects were seen only in the aortic strips after ablation at fluences > 1000 mJ.mm-2. The "dead spaces" around the optical fibres in the catheter resulted in significant amounts of coagulated tissue fragments remaining in the crater. Holmium:YAG laser energy delivered through multifibre catheters ablated atherosclerotic tissue in coronary arteries with minimal damage to the normal walls. The cadaveric coronary artery perfusion apparatus is useful for assessing catheter delivery and mobility and the effects of laser energy on the coaxially orientated normal and atherosclerotic coronary arterial wall.

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)

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.

Pathological basis of failure of concurrent glyceryl trinitrate therapy to improve efficacy of tissue type plasminogen activator in coronary thrombosis

The aim was to examine the effect of glyceryl trinitrate, a potent coronary vasodilator, on the thrombolytic effects of tissue type plasminogen inhibitor (t-PA) in dogs with coronary thrombosis. The thrombus was formed by delivery of anodal direct current into the left anterior descending coronary artery. Fourteen dogs were randomly given t-PA alone (0.75 mg.kg-1 over 20 min) or t-PA with glyceryl trinitrate (125 micrograms.min-1 for 40 min). In four other dogs, glyceryl trinitrate was given after t-PA induced thrombolysis. Its effect on t-PA induced thrombolysis, in terms of reperfusion rate, time to thrombolysis, peak coronary blood flow, and reocclusion rate, was quantitated. Peripheral blood platelet counts and whole blood platelet aggregation were measured in all dogs. The thrombosed left anterior descending artery and normal circumflex coronary artery segments were examined by scanning electron microscopy at the end of the experiment. The reperfusion rate in the t-PA plus glyceryl trinitrate (t-PA + GTN) group was 57% (4/7 dogs) and with t-PA alone, 71% (5/7 dogs). The time to thrombolysis in the t-PA + GTN group was greater than with t-PA alone, at 30(SD 10) v 18(7) min, p less than 0.02, and the duration of reperfusion much shorter, at 11(17) v 48(15) min, p less than 0.02. Peak coronary blood flow in the t-PA + GTN group following reperfusion was less compared with t-PA alone, at 36(52) v 53(18) ml.min-1, p less than 0.02. Reocclusion rates in the two groups were similar. Peripheral blood platelet counts decreased during thrombus formation in all dogs; this decrease stabilised when t-PA was given alone but not when it was given with glyceryl trinitrate [mean platelet count at the end of t-PA infusion 7.23(1.68) and 4.78(3.00) X 10(8).ml-1 respectively, p less than 0.02], suggesting continued sequestration of platelets in the intracoronary thrombus in the latter group. Whole blood platelet aggregation decreased significantly with t-PA alone, but less so with t-PA + GTN [magnitude of platelet aggregation 0.23(0.57) and 5.67(6.23) ohms, respectively, p less than 0.02], suggesting lower plasma concentrations of t-PA when given with glyceryl trinitrate. Glyceryl trinitrate given after thrombolysis induced by t-PA failed to sustain reperfusion. Scanning electron microscopy of occluded left anterior descending artery showed extensive endothelial injury and a thrombus composed of platelet--red blood cells--fibrin mesh. The reperfused left anterior descending artery showed extensive endothelial injury and residual thrombus consisting mostly of fibrin and red blood cells with some platelets. Glyceryl trinitrate given concurrently with t-PA or after t-PA induced thrombolysis does not modify the thrombolytic potential of t-PA. The potentially "detrimental" effects of glyceryl trinitrate may be due to increase in hepatic blood flow and subsequent enhanced catabolism of t-PA. Lack of any significant effect of therapeutic dosage of glyceryl trinitrate on platelet--fibrin rich thrombus may explain the absence of a salutary action of this agent. Dynamic coronary vasoconstriction does not play an important role in coronary reocclusion after initial thrombolysis.

Calcium — a Neglected Key Factor in Arteriosclerosis. The Pathogenetic Role of Arterial Calcium Overload and Its Prevention by Calcium Antagonists

Using specific calcium antagonists as experimental tools, both the physiological messenger and current carrying function of calcium ions as well as their pathogenetic potencies could be elucidated. Notably, excess intracellular calcium signalling and intra- and extracellular calcium overload turned out to be pathogenetic principles of general importance. In this context, progressive calcium overload of arteriosclerotic vascular walls and the antiarteriosclerotic effects of calcium antagonists, deserve particular interest. In fact, with the help of calcium antagonists, arterial calcium overload as decisive component of various types of experimental arteriosclerosis became accessible to a direct therapeutic intervention. According to their responsiveness to calcium antagonists, two pathophysiologically different types of experimental coronary plaques could be characterized: (1) The calcium type, i.e. coronary calcinosis of vitamin D3-intoxicated rats highly sensitive to calcium antagonist treatment, (2) the cholesterol type, represented by coronary atheromata of cholesterol-intoxicated rabbits; this primary coronary cholesterol accumulation could not be inhibited by calcium antagonists. The formation of conventional human coronary artery plaques is characterized from the very early lesion onwards by a progressive local uptake of calcium, finally leading to lethal consequences. Conversely, the analysis of the mural cholesterol does not allow to discriminate arteriosclerotic from normal coronary artery segments. Thereby, conventional human coronary plaques typically represent a calcium-dominated type of human arteriosclerosis and differ widely from plaques produced in cholesterol-fed rabbits. The results indicate the decisive pathophysiological role of calcium and calcium overload in both calcium-dominated types of experimental arteriosclerosis and conventional human coronary artery plaques. Moreover, the antiarteriosclerotic effects of calcium antagonists are demonstrated to be based--in various types of experimental arteriosclerosis--on the inhibition of intra- and extracellular calcium overload of arterial walls evoked by various risk factors (vitamin D3 intoxication, hypertension, nicotine, diabetes).

Coronary excimer laser angioplasty: Reduced complications and indium-111 platelet accumulation compared with thermal laser angioplasty

The relative safety and thrombogenicity of pulsed excimer and thermal laser angioplasty systems were compared in 20 normal coronary artery segments in a total of seven pigs. Using similar over the wire catheter systems and laser delivery periods of 3 to 5 s, thermal laser angioplasty was achieved with a 1.3 mm metal probe heated with 10 W of continuous argon laser energy and excimer laser angioplasty was performed with a 4.5F excimer laser catheter consisting of 13 concentrically arranged 200 μm fiber optics delivering 35 to 40 mJ/mm2of xenon chloride (308 nm) excimer laser irradiation at a repetition rate of 25 to 30 Hz and a pulse duration of 120 ns.On angtography, the incidence of vessel perforation (1 in 10 versus 3 in 10) and abrupt vessel closure (0 in 10 versus 2 in 10) was less with excimer compared with thermal laser angioplasty. Macroscopically, there was a greater incidence of mural and occlusive thrombus formation after thermal laser than after pulsed excimer laser angioplasty. Histologic examination confirmed that this thrombogenicity was associated with greater charring and coagulation necrosis of the media.Quantitative indium-111-labeled platelet deposition was significantly increased after thermal laser angioplasty (median 87.2 × 106/cm length) compared with excimer-treated (0.4 × 106/cm length) or control (1.2 × 106/cm length) segments (p < 0.001). Thus, excimer laser angioplasty was found to result in fewer complications and, as a consequence, less thrombosis and platelet accumulation than did thermal laser angioplasty.

Impaired coronary vasodilator reserve in the immediate postcoronary angioplasty period: Analysis of coronary artery flow velocity indexes and regional cardiac venous efflux

The ratio of peak hyperemic/basal mean coronary flow velocity, an index of coronary vasodilator reserve, immediately after coronary angioplasty normalizes in <50% of patients. To evaluate other indexes of coronary vasodilator capacity, both intracoronary arterial velocity and cardiac venous efflux were measured at rest and during vasodilator-induced coronary hyperemia (intracoronary nitroglycerin and papaverine) before and after angioplasty in 27 patients; 17 patients had measurements of intracoronary velocity alone and 10 had thermodilution measurements of great cardiac vein flow. Coronary flow velocity responses were also measured in 6 angiographically normal segments in patients undergoing angioplasty and in 10 normal left coronary artery segments in patients with normal coronary arteries or isolated right coronary artery disease.Despite significant angiographic (72 ± 12 to 23 ± 11% diameter narrowing) and hemodynamic (49 ± 12 to 19 ± 12 mm Hg aortocoronary gradient) improvement, coronary vasodilator reserve ratios for both arterial velocity and venous flow after angioplasty were only minimally affected. Angioplasty did not significantly increase rest coronary vein flow or artery flow velocities, but did result in significantly higher papaverine responses after angioplasty. Mean and phasic coronary velocity, diastolic coronary flow velocity integral and measured great cardiac vein flow ratios were significantly lower when compared with those in 16 angiographically normal coronary artery segments.These data indicate that maximal hyperemic coronary flow velocity is increased after angioplasty, but the reserve ratios, calculated by any of several flow velocity indexes, remain minimally improved. Angiographic correlations (percent coronary diameter, absolute diameter or crosssectional area) with variables of coronary blood flow or velocity suggest that no single variable is useful in assessing angioplasty results. However, postangioplasty arterial mean velocity and diastolic flow velocity integral are nearly normalized in most patients, whereas relative changes remain attenuated. These findings are important in studies assessing coronary vasomotor responses in patients with atherosclerotic coronary disease, especially after angioplasty.