Large Epicardial Coronary Arteries Research Articles

Alpha adrenergic receptor activity of epicardial coronary artery in the anesthetized dog.

The epicardial coronary artery plays an important role not only as a conduit artery but also as a locus of coronary spasm. Accordingly, diameter change of the large epicardial coronary artery of the in situ canine heart was continuously measured by ultrasonic dimension gauge technique and the effects of alpha adrenergic stimulation on the caliber were studied. After the intravenous administration of phenylephrine the aortic pressure increased by 28 mmHg, however, the left circumflex coronary artery diameter decreased by 3.4% (p less than 0.01). Norepinephrine and sciatic nerve stimulation after propranolol (1 mg/kg) induced coronary vasoconstriction by 1.3 (p less than 0.025) and 2.5% (p less than 0.05) against the obvious increases of aortic pressure by 16 and 19 mmHg, respectively. Thus alpha adrenergic stimulation, in situ in dogs, was shown to directly constrict the large epicardial coronary artery.

Hyperreactivity of coronary arterial smooth muscles in response to ergonovine from rabbits with hereditary hyperlipidemia.

This study was undertaken to examine the response to ergonovine, an agent used to provoke spastic constriction of large epicardial coronary arteries, to elucidate the responsible underlying mechanism, and to determine the impact of endogenous hyperlipidemia on contractile properties of isolated vessels from different beds. The isolated arteries from both control and Watanabe hereditary hyperlipidemic rabbits (WHHL rabbits) were suspended for recording isometric force in oxygenated Krebs buffer and exposed to agonists and antagonists. In atherosclerotic aortas from WHHL rabbits, the concentration-response relations for ergonovine and serotonin exhibited a marked leftward shift with significantly depressed constrictor threshold concentration and lowered one-half maximally effective concentration values. In coronary arteries with no atherosclerotic lesions detectable macroscopically from WHHL rabbits, the concentration-response relations showed a leftward shift for ergonovine but not serotonin. Coronary contraction evoked by ergonovine was remarkably inhibited by 0.1 microM cyproheptadine and 0.3 microM methysergide, serotonergic antagonists, in both groups. alpha-Adrenergic blockade with 0.1 microM prazosin was effective in inhibiting ergonovine-induced contraction of aortas from control rabbits, but not that of atherosclerotic ones. The constrictor response to ergonovine of atherosclerotic aortas was inhibited by cyproheptadine. The responsiveness to ergonovine of both carotid and femoral arteries from WHHL rabbits with no sclerotic lesions, which was suppressed by prazosin was not different from that of control rabbits. In contrast, the concentration-response relations for phenylephrine in the four different types of arteries did not differ appreciably between the two groups, and the constrictor responses to 20 mM KCl were virtually identical. Thus, aortas and coronary arteries exposed to endogenous hyperlipidemia appear to be hyperreactive to ergonovine mediated by a serotonergic mechanism.

Regulation of large coronary arteries by increases in myocardial metabolic demands in conscious dogs.

In order to assess the effects of increasing myocardial metabolic demand on the large epicardial coronary arteries, we measured left circumflex coronary artery diameter (ultrasonic transit time technique) and blood flow in conscious dogs with chronically implanted transducers. Myocardial oxygen consumption was increased by pacing-induced tachycardia and aortic constriction, and monitored by multiplying left circumflex coronary arterial blood flow by coronary arterio-venous oxygen content difference. Increase of heart rate by 90 beats/min caused myocardial oxygen consumption to increase by 34 +/- 4.3% (1 SEM); coronary blood flow at constant arterial pressure to increase by 32 +/- 6.8%; and coronary diameter to increase by 0.07 +/- 0.01 mm, P less than 0.01. Aortic constriction, producing a 53 +/- 5.1% increase of left ventricular systolic pressure, caused myocardial oxygen consumption to increase by 49 +/- 7.2%, coronary blood flow to increase by 50 +/- 6.0%, and coronary diameter to increase 0.03 mm, P less than 0.01. The increases in coronary artery diameter were gradual, not immediate, in onset and not altered by beta-adrenergic blockade. Thus, increased myocardial metabolic demand dilates large epicardial coronary arteries, but with a slower response time than the rapid dilation of the smaller resistance vessels.

Magnitude of dilatation of large and small coronary arteries of nitroglycerin.

Vasodilatory responses of segments of large epicardial left coronary artery (CA), small intramyocardial CAs (0.3-1.0 mm), coronary stenoses and CAs filled by collaterals were determined in 34 patients. Measurements were made before and after nitroglycerin (0.4 mg, sublingual) by means of quantitative magnification coronary angiography using photospot film and a calibrated 6-power viewing device. The left main CA, proximal, middle and distal anterior descending and circumflex segments, and small CAs showed dilatation that varied in magnitude. When magnitude of dilatation was compared with control diameter of the vessel and its location, control diameter proved to be the significant independent variable. CAs with the smallest control diameter showed the greatest magnitude of vasodilatation. CA branches filled by collaterals had vasodilatation similar in magnitude to that of CAs of comparable control diameter. Although coronary stenoses dilated, the magnitude of dilatation was less than that observed in nonstenosed arterial segments of similar control diameter. When areas of stenosis were excluded, however, results were similar regardless of whether the patient had CA disease. These data indicate that a principal determinant of the CA vasodilatory response to nitroglycerin is the size of the artery before nitroglycerin.

Coronary Artery Spasm*

Variant angina with ST elevation indicates transmural myocardial ischaemia and is due to spasm of a large epicardial coronary artery. Spasm occurs in arteries with varying degrees of fixed obstruction, giving rise to different clinical profiles of variant angina. However, coronary angiography is required to differentiate between those with minor coronary disease, and those with significant (greater than 70%) obstruction. In patients with minor coronary disease or normal arteries, beta-blockers are contraindicated, and treatment with calcium antagonist vasodilators should be commenced after documentation of spontaneous or ergonovine induced spasm. Patients with significant fixed coronary obstructions require bypass grafting if technically feasible. The role of coronary spasm is not confined to variant angina, as it causes angina at rest with ST depression, and may also cause myocardial infarction and sudden death.

Myocardial blood flow in coronary artery disease: Studies at rest and during stress with inert gas washout techniques

HIS article will review techniques using inert gases that have been utilized to measure average left ventricular and regional myocardial blood flow in man. The development of these techniques has been spurred primarily by the desire to evaluate clinically the disturbances of myocardial blood flow that occur in patients with coronary artery disease. Coronary atherosclerosis is a focal process that affects primarily large epicardial coronary arteries and their major branches and to a lesser extent the smaller intramyocardial vessels.‘,’ Discrete coronary lesions produce alterations in myocardial blood flow both in different regions of the heart (i.e., spatial heterogeneity of blood flow) and also in different layers of the ventricular wall (i.e., transmural heterogeneity of blood flow). In turn, these blood flow alterations in the myocardium may impair cardiac performance. Both global and segmental abnormalities of ventricular contraction are associated with coronary artery disease.” When the blood flow to a region of the myocardium is insufficient to meet the metabolic requirements of the working heart muscle for oxygen, &hernia develops and may produce angina pectoris, myocardial infarction, and/or local abnormalities of cardiac metabolism and function. Coronary arteriography is commonly used to visualize the extent and distribution of coronary artery obstructions. It is a necessary prerequisite to consideration of surgical therapy for angina, infarction, or ventricular failure.+ However, coronary arteriography does not reveal to what degree myocardial blood flow has been compromised by the obstructing lesion. It cannot reveal the presence of small vessel disease (i.e., abnormal vessels < 200~ in diameter) nor the extent

Human coronary artery size during life. A cinearteriographic study.

The diameters of large epicardial coronary arteries were measured by quantitative cinearteriography in 99 patients. Average coronary size was larger than normal in patients with lesions associated with left ventricular hypertrophy and∕or dilation. The size of the coronary arteries supplying the left ventricle was normal in patients with pure mitral stenosis and in those with the “floppy mitral valve syndrome” (when mitral regurgitation was slight or absent). The left coronary artery was larger than the right coronary artery in 83% of cases. Measurement of coronary artery size is a simple and useful extension of coronary arteriography.

Size of the Major Epicardial Coronary Arteries at Necropsy

Measurements at necropsy on 401 men indicate that variations in the original, presclerotic size of large epicardial coronary arteries may play a significant role in vulnerability to myocardial infarction and suggest that angiographic measurements of these vessels during life might detect susceptible individuals. Infarcts are seldom found in hearts with large coronary arteries (more than 7 sq cm external surface area per 100 gm heart weight) but are common when these arteries are small (less than 6 sq cm/100 gm). They are, in fact, seven times as frequent in the latter groups as in the former. Unlike large elastic arteries, the coronaries do not enlarge with advancing age. They increase only slightly in size in hypertrophied hearts and do not shrink in size in atrophic ones.

SPONTANEOUS CORONARY ARTERIOSCLEROSIS IN REPEATEDLY BRED MALE AND FEMALE RATS.

Repeatedly bred male and female rats of several strains develop arteriosclerosis spontaneously, irrespective of diet. The severity of the lesions differs between male and female breeders. The morphology and pathogenesis of these lesions have been found to be the same in all of the strains examined. Once the process of arteriosclerosis has been initiated within the abdominal aorta, the subendocardial and medium-sized myocardial coronary arteries also show degenerative changes. The large epicardial coronary arteries become arteriosclerotic only when the process of arteriosclerosis has become severe and generally distributed throughout the aorta. The smaller subendocardial lesions are characterized by occlusive swelling of medial muscle cells and by the presence of vacuoles. These vacuoles react negatively to lipid stains but stain positively for mucopolysaccharide. The myocardial arteries show endothelial hyperplasia, elastosis and accumulations of mucopolysaccharides, especially in the region of fragmented elastic elements. The mucopolysaccharide-rich endothelial cushions eventually become fibrosed. The epicardial arteries show intense accumulations of calcium-mucopolysaccharide complexes. These arteries become greatly distended and can be detected grossly because of their size and tortuosity. Acute and chronic myocardial infarct-like lesions are found but these cannot be associated with specific coronary thrombi or arteriosclerotic lesions. Valvular scarring, calcification of the papillary muscles and disappearance of myocardial mast cells has been correlated with advancing arteriosclerosis. The relation between the intensity of coronary arteriosclerosis and the frequency of breeding, the sex of the animal, and the strain indicates that the pathogenesis of this disease in breeder rats is probably governed by hormonal factors, e.g., sex and adrenal steroids, as well as by genetic factors.