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Biomedical subjects

G J Grega

Publications and source records attributed to G J Grega.

At least 37 records · Page 2Linked to original sources
PubMed1982

Effect of norepinephrine on lymph flow and edema formation in the canine forelimb.

In the present study we sought evidence for the hypothesis that norepinephrine (NE) can cause constriction of lymph vessels in the canine forelimb perfused at constant flow. Mechanical venous compression (small-vein pressure approximately equal to 45 mmHg), intra-arterial infusion of histamine (16 micrograms base/min), and intra-arterial infusion of NE (16 micrograms base/min) caused the limbs to gain weight at similar rates due to edema formation; the first two maneuvers caused a sustained increase in skin lymph flow, but the increase in lymph flow with NE was only transient. Similar changes were seen during infusion of NE at 1 and 2 micrograms/min, and studies with radioactive microspheres indicated that NE increased capillary blood flow. When venous pressure was elevated and held constant at 45 mmHg. NE (4 micrograms base/min ia) antagonized and phentolamine (400 micrograms/min ia) potentiated the increase in skin lymph flow. Finally, NE (16 micrograms base/min ia) caused a reduction in histamine (16 micrograms base/min)-elevated skin lymph flow, despite the fact that capillary pressure was greatly increased due to active venous constriction. We conclude that intra-arterial infusion of norepinephrine in the dog forelimb perfused at constant flow causes constriction of lymphatic trunk vessels in skin, resulting in increased resistance to the flow of lymph.

Animals↗
PubMed1982

Pharmacological modification of the edema produced by combined infusions of prostaglandin E1 and bradykinin in canine forelimbs.

In dogs anesthetized with pentobarbital, 60 min local i.a. infusions of prostaglandin E1 (4 micrograms/min) together with bradykinin (10 micrograms base/min) into forelimbs perfused at a constant pump controlled flow rate produced decreases in perfusion pressure and very marked increases in lymph flow, lymph total protein concentration, total protein transport and weight (266 g). Pretreatment with indomethacin did not significantly reduce the very marked increases in these parameters produced by the combined prostaglandin E1-bradykinin infusions. Treatment with diphenhydramine completely prevented the increases in lymph flow, lymph total protein concentration, total protein transport, weight and vasodilation produced by infusions of histamine, but not those produced by infusions of prostaglandin E1 or bradykinin. Pretreatment with methylprednisolone prevented the increases in lymph flow, lymph total protein concentration, total protein transport and weight produced by infusions of prostaglandin E1, but not those produced by infusions of high doses of histamine or bradykinin. Treatment with either methylprednisolone or diphenhydramine significantly reduced the very marked increases in these parameters produced by combined infusions of prostaglandin E1 and bradykinin to levels produced by infusions of bradykinin alone. Vasopressin or isoproterenol treatment essentially prevented the very marked increases in lymph flow, lymph total protein concentration, total protein transport and weight produced by combined infusions of prostaglandin E1 and bradykinin. These data suggest that the potentiation of the bradykinin edema formation produced by prostaglandin E1 results from an endogenous release of histamine and that treatment with vasopressin or isoproterenol essentially prevents the development of edema produced by combined infusions of these autacoids. Moreover, the potentiation is not dependent on the vasodilator action of prostaglandin E1 as it may be demonstrated under constant controlled flow conditions.

Alprostadil↗
PubMed1981

Interactions among inflammatory mediators on edema formation in the canine forelimb.

Prostaglandin E1, 4 microgram/min, infused locally intra-arterially (ia) for 60 minutes into forelimbs perfused at constant pump controlled inflow produced decreases in perfusion pressure, increases in lymph total protein concentration (approximately equal to g/100 ml), and small increases in weight (23 g) owing to edema formation. Histamine, 16 microgram base/min, or bradykinin, 10 microgram base/min, infused locally ia for 60 minutes produced large increases in lymph flow, lymph total protein concentration, total protein transport, and weight (70 g and 130 g, respectively). However, the local ia infusion of prostaglandin E1, 4 microgram/min, together with histamine, 16 microgram base/min, or bradykinin, 10 microgram base/min, produced weight increases of 180 g and 236 g, respectively, and the rate of weight gain during the combination infusions greatly exceeded that produced by infusions of histamine or bradykinin alone. Moreover, the increases in lymph flow and in total protein transport far exceeded those produced by infusions of prostaglandin E1 and histamine or bradykinin alone or additively. The edema produced by the local ia infusion of prostaglandin E1, 4 microgram/min, together with bradykinin, 10 microgram base/min, was even more more marked in naturally perfused forelimbs. Similarly, the local ia infusion of histamine, 4 microgram base/min, or bradykinin, 0.8 microgram base/min, for 60 minutes into forelimbs perfused at constant inflow produced increases in lymph flow, lymph total protein concentration, total protein transport, and weight (38 g and 14 g, respectively). In contrast, histamine, 4 microgram base/min, and bradykinin, 0.8 microgram base/min, infused together locally ia for 60 minutes produced increases in weight of 118 g. The increase in lymph flow and total protein transport was considerably more marked during the combined infusions than during the infusions of histamine or bradykinin alone or additively.

Animals↗
PubMed1980

Effects of intravenously infused histamine on canine forelimb transvascular protein efflux following adrenergic receptor blockade.

The intravenous infusion of high doses of histamine (400 micrograms base/min) produced only small increases in weight (approximately equal to +30 g) and lymph total protein concentration (+ 0.9 g/100 ml) in canine forelimbs perfused at constant inflow. The weight gain was associated with profound decreases in aortic pressure (112 to 30 mm Hg) and in forelimb perfusion pressure (105 to 75 mm Hg) and marked increases in forelimb skin small-vein pressure (from 12 to 25 mm Hg). After treatment with phentolamine, the intravenous infusion of these doses of histamine under the same conditions produced marked decreases in forelimb perfusion pressure (120 to 60 mm Hg) and failed to increase forelimb skin small-vein pressure, yet still produced only minimal increases in weight (+ 12 g) and lymph total protein concentration (+ 0.8 g/100 ml). Following treatment with both phentolamine and propranolol, the intravenous infusion of histamine caused very marked increases in forelimb weight (approximately equal to +75 g) and lymph total protein concentration (+ 2.9 g/100 ml). These marked increases in forelimb weight and lymph formation were associated with profound decreases in perfusion pressure (112 to 60 mm Hg) but no change in skin small-vein pressure relative to control. These same increases in weight and lymph total protein concentration were observed after treatment with propranolol alone. Thus, treatment with propranolol markedly increased net fluid filtration and protein efflux during intravenous infusions of massive doses of histamine, idicating that this edemogenic agent causes an endogenous release of catecholamines which tend to antagonize the direct actions of histamine on the microvascular membrane via stimulation of beta-adrenergic receptors.

Adrenergic beta-Antagonists↗
PubMed1979

Morphological and physiological correlation of bradykinin-induced macromolecular efflux.

Bradykinin applied topically for 4 min produced marked dose-related increases in the number of fluorescent dextran (mol wt 145,000) vascular leakage sites exclusively from small postcapillary venules--evidence for an increase in macromolecular permeability. The increase in macromolecular permeability was short-lived, making repeated applications possible. The number of bradykinin-induced venular fluorescent dextran leakage sites could be greatly reduced by the simultaneous topical application of isoproterenol, and this antagonism of the increase in macromolecular permeability could be prevented by pretreatment with propranolol. The topical application of papaverine failed to antagonize the increase in the number of venular leakage sites of fluorescent dextran by bradykinin. A continuous 90-min superfusion of bradykinin elicited an initial marked increase in the number of fluorescent dextran venular leakage sites, which then waned after 20-30 min, returning to near control despite the continued superfusion with bradykinin. In canine forelimbs the bradykinin-induced increase in protein efflux, total protein transport, and lymph flow also peaked in approximately 30 min and then waned markedly despite continued local intra-arterial infusions of this agent for prolonged periods. The morphological data from the cheek pouch agrees well with the physiological data from the forelimb, suggesting that an increase in protein efflux in the canine forelimb could be readily explained by an increase in the number of large pores.

Animals↗
PubMed1978

Effects of isoprenaline and cooling on histamine induced changes of capillary permeability in the rat hindquarter vascular bed.

Histamine infused intra-arterially into artificially perfused, maximally dilated rat hindquarters markedly increased fluid filtration and CFC but had essentially no effect on the diffusion capacity to small molecules. Isoprenaline largely prevented the increase in fluid filtration and CFC if infused prior to the start of the histamine infusion and, if infused after the start of the histamine infusion, promptly reduced fluid filtration and CFC to near control levels. Additionally, it was noted that severe cooling of the perfusate also largely prevented the marked increase in fluid filtration and CFC by histamine. This antagonism of histamine induced increases in macromolecular permeability represents a direct action of isoprenaline on the microvascular membrane which effectively counteracts that of histamine. The data also suggest that the large pores created by histamine are different from the large pore through which macromolecules normally transverse the microvascular membrane, and that catecholamines may exert a regulatory function in the control of microvascular permeability to macromolecules in pathophysiological states associated with massive histamine release.

Animals↗
PubMed1978

Antagonism of histamine edema formation by catecholamines.

Histamine (4 microgram base/min) infused into the brachial artery for 60 min greatly increases skin lymph flow and lymph protein concentration in forelimbs perfused either naturally or at constant inflow. In contrast, the simultaneous intrabrachial infusion of histamine and norepinephrine (4 microgram base/min of each) or histamine and isoproterenol (4 microgram base/min and 3 microgram/min, respectively) for 60 min failed to alter lymph protein concentration in forelimbs perfused either naturally or at constant inflow. The edema in forelimbs naturally perfused by histamine (4 microgram base/min) infused into the brachial artery for 60 min was also greatly reduced by the simultaneous histamine-catecholamine infusions. Phentolamine (in concentrations that antagonize the vascular actions of norepinephrine) failed to prevent the antagonism of histamine protein efflux by norepinephrine. Hence, it must be concluded that catecholamines antagonize the protein efflux by locally infused histamine, independent of alpha-adrenergic receptor activity.

Animals↗
PubMed1978

Effects of locally and systemically infused bradykinin on transvascular fluid and protein transfer in the canine forelimb.

Local intra-arterial infusions of bradykinin into canine forelimbs perfused either naturally or at constant inflow markedly increase skin lymph protein concentration promoting edema formation. However, prolonged systemic infusions of this agent either intravenously or into the left ventricular chamber, in blood concentrations calculated to exceed those that produce massive protein and fluid efflux on local administration, causes only minimal increases in lymph protein concentration, and in naturally perfused forelimbs promotes extravascular fluid reabsorption rather than net fluid filtration. Local infusions of bradykinin fail to alter aortic pressure whereas systemic infusions produce a profound but transient decrease in this variable. Moreover, the local intra-arterial infusion of bradykinin into forelimbs perfused at constant inflow fails to increase skin lymph protein concentration after 60 minutes of systemic hypotension. In contrast to bradykinin alone, the simultaneous infusion of bradykinin and norepinephrine or bradykinin and isoproterenol fails to increase skin lymph protein concentration. The antagonism of the bradykinin protein efflux by both norepinephrine and isoproterenol can be prevented by prior treatment with propranolol. These data suggest that the liberation of catecholamines may account, in part, for the minimal increases in forelimb protein efflux during systemic infusions of bradykinin relative to that produced by local intra-arterial infusions of this agent.

Animals↗
PubMed1977

Effects of systemically infused histamine on transvascular fluid and protein transfer.

Histamine (4-64 microgram base/min) infused into the brachial artery clearly promotes edema formation in forelimbs perfused at natural flow. In contrast, intravenously administered histamine, even in blood concentrations exceeding those achieved by local infusion, not only fails to promote edema formation, but rather causes net extravascular fluid reabsorption. In this study, high concentrations of histamine were infused into the left ventricular chamber to bypass the pulmonary circuit. Histamine (400-800 microgram base/min) infused into the left ventricle of the heart for 90 min produced marked hypotension and only very slight increases in forelimb skin lymph flow and lymph protein concentration and failed to produce visible signs of edema. Thus the differential actions of local and intravenous histamine on lymph flow, protein efflux, and fluid fluxes cannot be explained by uptake or destruction of histamine in the lung during intravenous infusions of this agent. It seems more likely that they result from different actions on microvascular pressure, surface area, and/or permeability to plasma proteins. Prior hypotension produced either by acetylcholine, systemically infused histamine, or arterial hemorrhage almost completely prevents the increase in skin lymph flow and lymph protein concentration by histamine infused locally into the brachial artery, even in forelimbs perfused at constant flow.

Animals↗
PubMed1977

Evidence for a centrally mediated hypotensive effect of Escherichia coli endotoxin in the anesthetized dog.

The centrally mediated cardiovascular effects of Escherichia coli endotoxin were studied utilizing a neurally intact vascularly isolated head-trunk preparation in the anesthetized dog. The vascularly isolated head was perfused at constant flow with arterial blood supplied by a donor animal. Spectrophotometric examination of the donor and recipient trunk blood after administration of Evan's blue dye indicated that there was no blood exchanged between the head and trunk of the recipient dog. The responses to various physiological maneuvers and denervations indicated that the central nervous system and all afferents and efferents involved in the control of the cardiovascular system were functioning normally. The infusion of purified E. coli endotoxin into the arterial perfusion circuit to the head, either before or after bilateral denervation of the carotid sinus-body complexes, resulted in marked hypotension within 30 minutes in the trunk of the recipient dog. These findings indicate that purified E. coli endotoxin is capable of eliciting marked centrally mediated hypotensive responses. The time course of these responses suggests that the centrally mediated hypotensive effects of endotoxin do not participate in the initial precipitous fall in blood pressure seen after systemic administration of endotoxin, but rather that they may contribute significantly to the maintenance of the hypotension.

Animals↗
PubMed1975

Effects of ischemia on forelimb weight and lymph protein concentration.

The aim of this study was to determine if edema develops in the canine forelimb after relief of prolonged ischemia. Two hours of ischemia was induced either by interrupting brachial artery inflow in collateral-free innervated, naturally and constantly perfused preparations or by applying a pressure cuff in intact preparations. Changes in extravascular fluid volume were inferred from changes in limb weight. Relief of ischemia produced a transient 1.7% increase in weight in the collateral-free, naturally perfused preparation but had no effect on weight in the collateral-free, constantly perfused or intact preparations. Skin lymph flow failed to change significantly and total lymph protein concentration increased only slightly. Thus, relief of 2 hr of ischemia does not produce marked edema or a large increase in microvascular permeability to plasma proteins in the dog forelimb.

Albumins↗
PubMed1975

Pressure-dependent factors in edema formation in canine forelimbs.

Acetycholine (10 mug/min) infused intra-arterially for 30 minutes into naturally perfused forelimbs increased forelimb weight 23 g. largely due to edema formation. The weight gain was associated with markedly elevated skin and skeletal muscle blood flows and small vein pressures, suggesting that the edema was attributable, in part, to a rise in microvascular pressures. Mechanically increasing venous pressure and blood flow to similar levels for 30 minutes in pump-perfused forelimbs produced a weight gain of 27 g. The rate of weight gain for the acetylcholine and mechanical alterations was nearly identical. Acetylcholine and mechanical alterations both increased forelimb lymph flow rate but failed to increase lymph total protein concentration significantly. These studies indicate that in the dog forelimb elevated microvascular pressures result in edema formation by increasing the transcapillary hydrostatic pressure gradient without producing an important decrease in the transcapillary colloid osmotic pressure gradient. Increased pressure is not associated with a large increase in microvascular permeability to plasma proteins as is seen with the administration of high doses of histamine and bradykinin.

Acetylcholine↗