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Biomedical subjects

M W Gorman

Publications and source records attributed to M W Gorman.

26 records · Page 2Linked to original sources
PubMed1986

Endothelial cell uptake of adenosine in canine skeletal muscle.

The vascularly isolated muscles in the hindlimbs of five dogs were perfused with an oxygenated physiological salt solution. The extractions of adenosine and of a nontransported analogue of adenosine, 9-beta-D-arabinofuranosyl hypoxanthine (AraH), were determined by the single-pass indicator-dilution technique. A bolus containing [125I]albumin (reference tracer), [14C]adenosine, and [3H]AraH was injected into the artery while samples of venous effluent were collected over the next minute. This injection was repeated with dipyridamole (10(-5) M) in the perfusate. Early extractions of AraH (EAra) and adenosine (EAdo) under control conditions were 48 +/- 4 and 80 +/- 4%, respectively. In the presence of dipyridamole, EAra was unchanged (47 +/- 5) while EAdo decreased to 45 +/- 7%. Since early extraction reflects primarily the barrier posed by endothelial cells, these results demonstrate significant endothelial uptake of adenosine. Analysis of these data using a mathematical model of blood-tissue exchange indicates that, under the conditions of these experiments, at least 78% of the adenosine taken up by skeletal muscle entered endothelial cells.

Adenosine↗
PubMed1986

Aminophylline and interstitial adenosine during sustained exercise hyperemia.

We tested the hypothesis that an increase in interstitial fluid (ISF) adenosine concentration contributes to vasodilation of high oxidative skeletal muscle during sustained free-flow exercise. Canine calf muscles were stimulated at 3 Hz for 10 min before and after the infusion of the adenosine receptor antagonist aminophylline (10 mg/kg). The vasodilation that occurred during aminophylline infusion was allowed to decay before the postaminophylline exercise period was begun. This dose of aminophylline shifted the response to infused adenosine 20-fold during rest and reduced the response to a standard dose by 90% during exercise. Aminophylline had no significant effect on blood flow or on O2 consumption at rest or during exercise. Adenosine release (venous minus arterial plasma concentration times plasma flow) increased during 3-Hz exercise both before and after aminophylline infusion, but venous plasma adenosine concentration did not increase in either case. We developed a mathematical model of adenosine movement between ISF and plasma to help us judge whether to use adenosine release or venous concentration as an index of ISF adenosine and decided that venous concentration should be used. We conclude that aminophylline has no effect on sustained 3-Hz exercise hyperemia because under these conditions ISF adenosine concentration does not increase.

Adenosine↗
PubMed1986

Adenosine release into venous plasma during free flow exercise.

We measured adenosine release into venous plasma as an index of interstitial adenosine concentration during free flow exercise hyperemia. Isolated, blood-perfused dog calf muscles were stimulated at 6 Hz for 10 min at free flow. Plasma samples were collected before, during, and after the exercise period for analysis of plasma adenosine concentration [( ADO]) by HPLC. Adenosine release (Rado) was calculated as plasma flow times venous-arterial [ADO] difference. Rado (nmole/min/100 g) went from -0.1 +/- 0.1 at rest to 6.6 +/- 4.6 during 6-Hz exercise. Isoproterenol infusion, which caused an increase in blood flow equivalent to 6-Hz exercise, did not result in increased Rado. Infusion of the 5'-nucleotidase inhibitor, alpha, beta, methylene adenosine 5'-diphosphate (AOPCP) did not prevent the increase in Rado during exercise. These results support the hypothesis that interstitial adenosine concentration increases during sustained free flow twitch exercise and that this results in increased release of adenosine into venous plasma.

Adenosine↗
PubMed1985

Progressive vasomotor changes in ischaemic myocardium.

Under certain conditions, a progressive increase in vascular resistance occurs within ischaemic myocardium during the first three hours after coronary artery stenosis. Measurements of vasodilator reserve in the ischaemic region demonstrated that this is at least partly due to an increase in vascular smooth muscle tone. Two hypotheses were suggested as an explanation: release of vasoconstrictors within the ischaemic area, or a decreasing release of vasodilators. Potential coronary constrictors considered included norepinephrine, PGF2 alpha, thromboxane A2, and high K+. Each of these substances was eliminated as the source of the vasoconstriction by pharmacological studies on ischaemic canine hearts. Measurement of adenosine release from isolated guinea pig hearts provided support for the possibility that the vasoconstriction results from a decreasing release of metabolic vasodilators. Throughout the period of ischaemia, both blood flow and myocardial function were far below the levels that could have been achieved in the presence of the stenosis. We conclude that during moderate ischaemia, myocardial function and blood flow are linked in a positive feedback cycle which promotes reduced ventricular function and coronary blood flow.

Adenosine↗
PubMed1985

Capillary transport of adenosine.

We tested the hypothesis that capillary exchange of adenosine is influenced by the ability of endothelial cells (ECs) to take up adenosine. Triple-indicator diffusion experiments were performed by injecting [14C]adenosine, [3H]9-beta-D-arabinofuranosylhypoxanthine ( [3H]araH), and radioiodinated serum albumin (RISA) into the arterial perfusate of isolated nonworking guinea pig hearts. Tracer appearance in venous effluent was observed over time. The early extraction of [14C]adenosine was much higher than that of [3H]araH. Extracted [3H]araH returned to the vascular space, but [14C]adenosine did not. Quantitative analysis of the curves by using a mathematical model indicates that approximately half of the extracted adenosine enters ECs and is metabolized. The remainder enters the interstitium and is taken up by myocytes, ECs, or other cells and is metabolized. We conclude that uptake of adenosine by ECs represents a significant influence on the capillary exchange of adenosine.

Adenosine↗
PubMed1985

Modeling of transendothelial transport.

Capillary-tissue exchange of inert hydrophilic solutes in the heart occurs through aqueous channels, the clefts between endothelial cells (ECs). For adenosine (and other vasoactive agents and substrates), there is also transport across the plasmalemma of the ECs. The multiple-indicator dilution technique comparing tracer adenosine flux with that of 9-beta-D-arabinofuranosylhypoxanthine (an analog that is not transported by the nucleoside carrier) can be used to estimate the conductance of the facilitated transport mechanism, which is equivalent to a permeability-surface area product. Analysis by using a model of exchanges among capillary, EC, interstitium, and myocardial cells suggests that the abluminal surface of the ECs is also highly permeable to adenosine. The inference is that ECs may be an important component of a system for adenosine exchange and regulation in the heart.

Adenosine↗
PubMed1980

Nitroglycerin causes vasodilatation within ischaemic myocardium.

Vasodilators such as nitroglycerin have been reported to increase collateral blood flow to ischaemic myocardium. One proposed mechanism of action is dilatation of collateral vessels. The purpose of this study was to determine whether dilatation of vessels within the ischaemic area also contributes to the increase in flow. The left anterior descending coronary artery (LAD) was ligated in chloralose-anaesthetised dogs. Peripheral LAD pressure (PLAD) was measured distal to the occlusion. Myocardial blood flows were measured with 15 micrometers radioactive microspheres. Ischaemic bed vascular resistance was calculated as PLAD/LAD flow. After 1 h of ischaemia, nitroglycerin (2.3 micrograms . kg-1 . min-1) decreased ischaemic bed resistance by 10% when infused into the LAD, by 16% when infused into the circumflex coronary artery, and by 15% when infused via the right atrium. However, adenosine infusion (2 micrograms . kg-1 . min-1) into the LAD did not decrease ischaemic bed resistance. We conclude that nitroglycerin increases collateral flow in part by dilating large coronary arteries within an acutely ischaemic area.

Adenosine↗