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Biomedical subjects

D C MacLeod

Publications and source records attributed to D C MacLeod.

10 recordsLinked to original sources
PubMed1994

Proliferation and extracellular matrix synthesis of smooth muscle cells cultured from human coronary atherosclerotic and restenotic lesions.

OBJECTIVES: The purpose of this study was to examine the proliferative capacity and extracellular matrix synthesis of human coronary plaque cells in vitro. BACKGROUND: Common to both primary atherosclerosis and restenosis are vascular smooth muscle cell proliferation and production of extracellular matrix proteins. The applicability to humans of experimental animal models of these processes has been questioned. METHODS: Primary atherosclerotic and restenotic lesions were excised by percutaneous directional coronary atherectomy in 93 patients. Smooth muscle cells were cultivated by an explant technique and identified by their morphology in culture, ultrastructural features under electron microscopy and immunostaining using monoclonal antibodies to smooth muscle cell alpha-actin. Proliferation in secondary culture was assessed with growth curves and the synthesis of collagen and sulfated glycosaminoglycans by the incorporation of 3H-proline and 35S-sulfate, respectively. These studies were also performed in cells derived from human umbilical artery media. RESULTS: Success rates for primary (45%) and secondary (12%) culture of coronary cells were not influenced by clinical variables or lesion category. Primary culture success was improved by the presence of organized thrombus in the plaque and in relation to increased maximal cell density of the atherectomy specimen. Restenotic cells displayed more rapid growth than did cells of primary atherosclerotic origin, which grew in a manner similar to that of umbilical artery cells. Mean calculated population-doubling times for the three cell groups were 52 h (95% confidence interval [CI] 48 to 58 h), 71 h (95% CI 62 to 83 h) and 74 h (95% CI 65 to 84 h), respectively. Restenotic and primary atherosclerotic cells did not differ in the synthesis of collagen ([mean +/- SEM] 0.034 +/- 0.004 vs. 0.033 +/- 0.004 nmol isotope.microgram protein-1, p = NS) or sulfated glycosaminoglycans (11.47 +/- 1.07 vs. 15.37 +/- 3.10 nmol isotope.microgram protein-1, p = NS), but the coronary cells synthesized significantly more collagen and sulfated glycosaminoglycans than did umbilical artery cells (0.019 +/- 0.004 and 5.43 +/- 1.00 nmol isotope.microgram protein-1, respectively, both p < 0.05). CONCLUSIONS: These data indicate that increased smooth muscle cell proliferation contributes to coronary restenosis in humans and support the concept that the extracellular matrix synthesis of adult smooth muscle cells is important to lesion formation.

Cell Division↗
PubMed1994

Effect of dietary polyunsaturated fatty acids on contraction and relaxation of rat femoral resistance arteries.

We investigated the effects of dietary polyunsaturated fatty acids (PUFA) derived from fish oil (n-3 PUFA) and plant seed oil (n-6 PUFA), in amounts relevant to human consumption, on the alpha 1-adrenoceptor-mediated contractile responses of isolated rat resistance arteries. Rats were fed semisynthetic diets, deriving 40% of total calories from fat. The control diet, which had sufficient linoleic acid to prevent essential fatty acid deficiency, had a polyunsaturated/saturated fatty acid (P/S) ratio of 0.3. The n-3 PUFA were given as a daily oral supplement of fish oil. For the n-6 PUFA diet, the proportion of linoleic acid in the diet was increased to obtain P/S ratio of 2.0. Diets were administered for 8 weeks. At the end of the feeding period, second-order branches of the femoral artery (< 300-micros diameter) were mounted in pairs in an isometric myograph, and responses to norepinephrine (NE) 3 nM-10 microM with addition of yohimbine 1 microM and timolol 1 microM were examined. Subsequently, the vessels were preconstricted with NE to 60% of their maximal response and relaxation to acetylcholine 1 nM-0.1 mM was observed. Dietary n-3 PUFA supplements led to attenuation of the contractile responses of isolated resistance arteries (p < 0.01, repeated-measures analysis of variance, ANOVA-RM) versus control. The n-6 PUFA diet did not exert this effect although there was a downward trend. Diet did not affect EC50 values for NE. Neither n-3 nor n-6 PUFA diet influenced relaxation responses. The fatty acid composition of myocardial phospholipid fractions was significantly altered by both diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1994

Predictive value of reactive hyperemic response on reperfusion on recovery of regional myocardial function after coronary angioplasty in acute myocardial infarction.

BACKGROUND: The objective of the study was to determine the coronary vasodilatory reserve in reperfused myocardium in patients with acute myocardial infarction and its relation to regional myocardial function. METHODS AND RESULTS: The study population consisted of 22 patients with acute myocardial infarction who underwent successful coronary angioplasty. The vasodilatory reserve in the reperfused myocardium was assessed quantitatively using computer-assisted digital subtraction cine-angiography immediately after angioplasty and at follow-up angiography before hospital discharge. Myocardial contrast medium appearance time and density were determined before and after pharmacological hyperemia induced by an intracoronary injection of 12.5 mg papaverine. Global and regional left ventricular functions were determined from contrast angiography. After papaverine, the mean contrast medium appearance time decreased significantly from 3.5 +/- 0.7 to 2.7 +/- 0.7 cardiac cycles (P < .000005) immediately after successful coronary angioplasty and from 3.8 +/- 0.7 to 2.7 +/- 0.9 cardiac cycles (P < .000005) at angiography before hospital discharge. The mean contrast medium density increased significantly from 48.7 +/- 13.8 to 61.0 +/- 19.0 pixels (P < .003) and from 49.6 +/- 19.7 to 80.3 +/- 29.6 pixels (P < .000005), respectively. As a consequence, the calculated coronary flow reserve increased significantly from 1.8 +/- 0.7 to 2.6 +/- 1.0 (P < .0008). The global ejection fraction increased significantly from 52 +/- 12% to 58 +/- 14% (P < .03), primarily because of a significant improvement in the regional myocardial function of the infarct zone from 20.8 +/- 9.0% to 26.0 +/- 10.5% (P < .001). Coronary flow reserve correlated well with regional myocardial function both during the acute phase (R = .79, P < .002) and at follow-up angiography (R = .82, P < .000004). Interestingly, coronary flow reserve measurement on reperfusion, immediately after angioplasty, correlated significantly with regional myocardial function at follow-up angiography (R = .81, P < .00003). CONCLUSIONS: The results indicate that there is a pharmacologically inducible vasodilatory reserve in reperfused ischemic myocardium after successful coronary angioplasty in patients with acute myocardial infarction and that this is increased at 10-day follow-up angiography. More important, the degree of reactive hyperemic response on reperfusion has a predictive value regarding the ultimate degree of recovery of regional myocardial function. Quantitative assessment of reperfusion may be useful in investigating the role of coronary reperfusion and salvage of myocardial function.

Angiography, Digital Subtraction↗
PubMed1993

Interventional techniques for the management of coronary artery lesions: an update.

Coronary balloon angioplasty has become standard treatment for ischemic coronary artery disease. Major limitations of angioplasty are the inferior results obtained with unfavorable lesions, the occurrence of abrupt occlusion responsible for in-hospital mortality and morbidity, and the high restenosis rate at 6 months. New techniques for stents, laser, and atherectomy have been developed to overcome these limitations. Until now, although the initial results are encouraging, these new techniques have not as yet shown to be clearly superior to balloon angioplasty. However, due to the limitations of balloon angioplasty, further development of new techniques should be stimulated so that nonsurgical treatment of coronary artery disease will become safer, more effective, and applicable to a wider spectrum of coronary artery disease.

Angioplasty, Balloon, Coronary↗
PubMed1993

Clinical and histological determinants of smooth-muscle cell outgrowth in cultured atherectomy specimens: importance of thrombus organization.

BACKGROUND: Coronary atherectomy provides a unique opportunity to obtain plaque tissue from a wide variety of clinical syndromes. We investigated the relation between the clinical status and histopathological substrate of tissue retrieved during directional coronary atherectomy and the proliferative and migratory potential of smooth-muscle cells judged from successful outgrowth during cell culture. METHODS: After directional coronary atherectomy, tissue samples were examined macroscopically, divided into two equal pieces, and separately subjected to cell culture and histopathological study. Cell culture was performed using an explant technique. In-vitro smooth-muscle cell outgrowth was related to clinical and histological variables. RESULTS: Atherosclerotic tissue was obtained from 98 consecutive atherectomy procedures. Histological examination revealed a broad spectrum of appearances, ranging from complex atheroma containing dense fibrous tissue, calcium deposits, macrophages, and necrotic debris to neointimal proliferation and organized thrombi. Smooth-muscle cell outgrowth was observed in 43 of the 98 samples (44%). Although not affected by any of the clinical variables, cell outgrowth was influenced by histological variables, in particular the presence of organizing thrombi. Outgrowth was successful in eight out of 10 samples with thrombus (80%) and in only 35 out of 88 (40%) without (P = 0.03). CONCLUSION: The presence of organizing thrombi in the retrieved tissue facilitates smooth-muscle cell outgrowth and suggests an enhanced proliferative and migratory potential. These findings may be relevant to the understanding of neointimal proliferation in coronary syndromes where mural thrombosis is likely to occur.

Angina Pectoris↗
PubMed1992

Coronary vasodilatory action of elgodipine in coronary artery disease.

The effects of intravenous elgodipine, a new second-generation dihydropyridine calcium antagonist, on hemodynamics and coronary artery diameter were investigated in 15 patients undergoing cardiac catheterization for suspected coronary artery disease. Despite a significant decrease in systemic blood pressure, elgodipine infused at a rate of 1.5 micrograms/kg/min over a period of 10 minutes did not affect heart rate and left ventricular end-diastolic pressure. The contractile responses during isovolumic contraction showed a slight but significant increase in maximum velocity (56 +/- 10 to 60 +/- 10 seconds-1; p less than 0.005), whereas the time constant of early relaxation was shortened from 49 +/- 11 to 44 +/- 9 ms (p less than 0.05). Coronary sinus and great cardiac vein flow increased significantly by 15 and 26%, respectively. As mean aortic pressure decreased, a significant decrease in coronary sinus (-27%) and great cardiac vein (-28%) resistance was observed, while the calculated myocardial oxygen consumption remained unchanged. In all, 69 coronary segments (including 13 stenotic segments) were analyzed quantitatively using computer-assisted quantitative coronary angiography. A significant increase in mean coronary artery diameter (2.27 +/- 0.53 to 2.48 +/- 0.53 mm; p less than 0.000001), as well as in obstruction diameter, (1.08 +/- 0.29 to 1.36 +/- 0.32 mm; p less than 0.02), was observed. The results demonstrate that elgodipine, in the route and dose described, induces significant vasodilatation of both coronary resistance and epicardial conductance vessels, without adverse effects on heart rate, myocardial oxygen demand and contractile indexes.

Adult↗