Endothelin receptors in the human coronary artery, ventricle and atrium - A quantitative autoradiographic analysis

In the present experiments we investigated endothelin (ET) receptors in the human coronary artery, and in ventricular and atrial muscle using quantitative receptor autoradiography. Displacement of [125I]Sf6b (Sarafotoxin S6b) (30 pM)- and [125I]ET-1 (30 pM)-labeled binding sites was studied using ET-1, the ETA receptor selective ligand BQ-123 (cyclo[D-Asp-L-Pro-D Val-L-Leu-D-Trp-]), and the ETB receptor selective ligand [Ala1,3,11,15]ET-1. Specific binding was more dense in atrium and coronary artery (relative optical density (r.o.d.): 0.14±0.01 and 0.16±0.01, respectively) than in ventricular muscle (r.o.d.: 0.10±0.01). In the coronary artery, binding was especially dense in the media. ET-1 displaced [125I]ET-1 and [125I]Sf6b monophasically in atrium, ventricle and coronary artery. [Ala1,3,11,15]ET 1 and BQ-123 displaced [125I]ET-1 and [125I]Sf6b-labeled sites biphasically in the ventricle and in the atrium. In the human coronary artery, [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I]ET-1-labeled sites monophasically (pIC50): ET-1 (9.72±0.12) > BQ-123 (6.84±0.08) > [Ala1,3,11,15]ET-1 (6.40±0.12). In contrast, [Ala1,3,11,15]ET-1 and BQ-123 displaced [125I] Sf6b-labeled coronary artery sites biphasically (high affinity pIC50: BQ-123, 9.03±0.25;[Ala1,3,11,15]ET-1, 8.40±0.14; low affinity pIC50: BQ-123, 7.24±0.14; [Ala1,3,11,15]ET-1, 6.99±0.09). These data indicate that both [125I]ET-1 and [125I] Sf6b-labeled ETA and ETB binding sites in human ventricular and atrial muscle. In the human coronary artery, both radioligands labeled ETA binding sites, but [125I] Sf6b also labeled a non-ETA, non-ETB binding site with relatively high affinity for both BQ-123 and [Ala1,3,11,15] ET-1

Chronic aspirin treatment affects collagen deposition in non-infarcted myocardium during remodeling after coronary artery ligation in the rat

Low-dose aspirin (acetylsalicylic acid; ASA), inhibiting platelet thromboxane production in favor of endothelium formation of prostaglandins, is successfully used as primary or secondary prophylaxis against myocardial infarction. Although prognosis may be improved, effects of long-term ASA treatment on wound healing and cardiac remodeling are not well understood. The aim of the present study was to mimic the clinical situation by inducing myocardial infarction in low-dose ASA (25 mg/kg/day, i.p.) pretreated rats, and to determine effects on plasma eicosanoid levels, cardiac hypertrophy and collagen deposition, and left ventricular function during continued ASA treatment. The effects of this dose were verified to selectively inhibit platelet thromboxane production, and lower plasma levels of thromboxane, but did not affect plasma levels of prostacyclin and prostaglandin E2during the acute inflammatory stage following myocardial infarction. As measured by heart dry weight/body weight, cardiac hypertrophy was not affected by ASA treatment. However, interstitial fibrosis in the spared myocardium as well as perivascular fibrosis, associated with infarction-induced cardiac remodeling, were affected by ASA treatment. Replacement fibrosis in the infarct itself, considered as representing wound healing, was not significantly influenced by ASA treatment. Wall thinning following infarction was not aggravated, nor did treatment influence left ventricular cavity diameter in a relaxed state. Results fromin vitroleft ventricular function measurements showed no effects on left ventricular peak velocity of contraction or relaxation after ASA treatment. In conclusion, although low-dose ASA may not be expected to have anti-inflammatory action, it did influence post-infarct cardiac remodeling by affecting interstitial and perivascular fibrosis. ASA treatment did not have effects onin vitroleft ventricular dysfunction

Collagen content and distribution in the normal and transplanted human heart: A postmortem quantitative light microscopic analysis

Endomyocardial biopsies in heart transplant patients offer the opportunity to study the myocardial interstitium in the context of myocardial function. For that purpose endomyocardial biopsies should reliably reflect the composition of the entire myocardium. We determined whether the collagen content in the subendocardial region of the right side of the interventricular septum (site of right ventricular endomyocardial biopsy), in 16 normal and 30 transplanted human hearts, is representative for the entire myocardium. Moreover we determined whether or not the mean collagen content of the myocardium is altered along with the posttransplantation survival time and which factors might contribute to the development of interstitial myocardial fibrosis. Transmural sections of the right and left ventricular free wall and interventricular septum were stained with Sirius red, which specifically stains collagen fibers. Collagen in the subendocardial region and central parts of the myocardium was quantified using a digital image analyzer. In normal hearts the mean collagen content of the subendocardial region of the right side of the interventricular septum (site of right ventricular endomyocardial biopsy) correlates well with the mean collagen content of the right ventricular wall and the center of the interventricular septum, but it does not reliably reflect the mean collagen content of the left ventricular free wall. In transplanted hearts the collagen content at the site of right ventricular endomyocardial biopsy correlates highly with the mean collagen content of the entire myocardium. In transplanted hearts the increase in collagen content is a result mainly of an increase in collagen of the left ventricular free wall. We conclude that in heart transplant patients, right ventricular endomyocardial biopsies have potential value in the analysis of the causes of left ventricular dysfunction. In transplanted human hearts, the posttransplantation survival time correlates positively with the collagen content, and this is attributable mainly to an increase in the collagen of the left ventricular free wall

Directional atherectomy: combining basic research and intervention

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Analysis of VNTR loci amplified by the polymerase chain reaction for investigating the origin of intimal smoth muscle cells in a coronary artery lesion developing after heart transplantation in man

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Histologic characteristics of tissue excised during directional coronary atherectomy in stable and unstable angina pectoris

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