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Biomedical subjects

F J Haddy

Publications and source records attributed to F J Haddy.

At least 91 records · Page 5Linked to original sources

Vascular sodium-potassium pump activity in various models of experimental hypertension.

1. Ouabain-sensitive 86Rb uptake was used to assess sodium-potassium pump activity in vascular smooth muscle of animals with various types of experimental hypertension. 2. The findings suggest that pump activity is suppressed in the non-genetic low renin, presumably volume-expanded forms of hypertension. 3. By contrast, pump suppression does not appear to be involved in spontaneously hypertensive rats or in salt-induced hypertension in Dahl's salt-sensitive rats. In these genetic models the primary defect may be increased cell membrane permeability.

Animals↗

Cardiovascular effects of vanadate in the dog.

We have investigated the cardiovascular actions of vanadate, a naturally occurring Na+-K+-ATPase inhibitor, in six series of pentobarbitalized dogs. In three of the series, isomotic sodium vanadate was infused intravenously at progressively faster rates while arterial pressure and other parameters were measured. In two other series, the solution was infused directly into the coronary artery with coronary flow held constant during measurement of perfusion pressure, left ventricular contractile force (LVCF), and dP/dt. In one series, the agent was infused into the brachial artery with brachial artery flow held constant, and small and large vessel resistances in skin and muscle were calculated. Intravenous infusion increased arterial pressure and reduced cardiac output, the latter resulting from both decreased heart rate and stroke volume. LVCF fell. Total peripheral, pulmonary, coronary, and renal resistances rose. Coronary and renal flows fell, and the latter was associated with reduced urine flow. Intracoronary infusion raised coronary resistance, but had little effect on heart rate, LVCF, and dP/dt. Intrabrachial infusion raisedthe resistance to flow through all components of the forelimb vascular bed. Thus, in the dog, vanadate activates vascular smooth muscle, but has little effect on cardiac muscle. In the latter respect, its action differs from that of ouabain.

Animals↗

Evidence from bioassay studies indicating a role for adenosine in cardiac ischemic and hypoxic dilation in the dog.

Previous studies using bioassay demonstrated the presence of a vasoactive substance or substances in coronary sinus blood during myocardial reactive hyperemia which had, on bioassay, characteristics of adenosine and/or AMP. In the present studies, specific blockers were applied to an improved bioassay system to define more precisely the nature of the substance or substances and to determine whether it also appears during local cardiac hypoxia. In the anesthetized dog, coronary sinus blood was bioassayed in an isolated autologous kidney during reactive and hypoxic dilation. During reactive dilation, the bioassay kidney responded with a large resistance increase which was blocked by theophylline and adenosine deaminase and converted to a decrease by adenosine autoblockade. The same was true for hypoxic dilation, except in this instance, only adenosine deaminase reduced the response (40%). Theophylline and adenosine autoblockade eliminated responses of the bioassay organ to both exogenous adenosine and exogenous AMP, but adenosine deaminase was specific for adenosine. These results confirm that one or more vasoactive substances appear in sinus blood in vasoactive quantities during cardiac reactive dilation, and that the peak concentration correlates roughly with the peak flow. In addition, they show that this also is the case for hypoxic dilation. More importantly, they demonstrate that the substance almost certainly is adenosine in the case of reactive dilation, and that increased adenosine levels also are present during hypoxic dilation, but in addition, suggest that AMP sometimes appears in coronary sinus blood during severe cardiac hypoxia in the dog heart.

Adenosine↗

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↗

Release of adenosine, inosine and hypoxanthine from the isolated guinea pig heart during hypoxia, flow-autoregulation and reactive hyperemia.

In an attempt to test the hypothesis whether adenosine is involved in the regulation of coronary flow adenosine, inosine and hypoxanthine were measured in the effluent perfusate and in the tissue of isolated guinea pig hearts under various experimental conditions. In addition, the release of 14C-adenosine, 14C-inosine and 14C-hypoxanthine was determined after prelabeling cardiac adenine nucleotides with 14C-adenine. The decrease in coronary resistance induced by hypoxic perfusion (30% and 20% in the gas phase) and during autoregulation was associated with a considerable increase in the release of adenosine and hypoxanthine. Under both conditions the concentrations of adenosine in the effluent perfusate were clearly within the coronary vasodilating range of exogenously administered adenosine. The tissue content of adenosine also increased significantly when the perfusion pressure was reduced. The release of 14C-adenosine closely paralleled the changes in coronary resistance during hypoxic perfusion, autoregulation and during reactive hyperemia. The specific activity of adenosine in the effluent perfusate, however, decreased substantially upon reduction of the oxygen supply to the heart, indicating that the release of 14C-adenosine does not provide an absolute measure of total adenosine release by the heart. Our data indicate that the greater part of the adaptive changes of vascular resistance during hypoxia and autoregulation can be attributed to adenosine which is formed at an enhanced rate under these conditions. However, other factors might be involved as well.

Adenosine↗

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↗

An extracorporeal shunt for the measurement of coronary flow in the closed-chest dog.

An extracorporeal shunt circuit interposed between the left carotid artery and the left coronary ostium employs an electromagnetic flowmeter to measure coronary blood flow in the closed-chest anesthetized dog. Flow may be measured with the animal's arterial pressure as the driving force; introduction of a roller pump, or a roller pump and a negative feedback pressure controller allows for constant flow or constant pressure modes. During occlusion of the circuit or cessation of pump flow, retrograde coronary blood flow can be collected for measurement. The construction of the circuit is relatively simple and inexpensive, using common laboratory materials and a commercially available electromagnetic flowmeter and probe.

Animals↗

The effects of thoracotomy on coronary blood flow in the dog.

A velocity-sensitive catheter-tip flowmeter was used to measure left coronary arterial blood flow prior to, during, and following left lateral thoracotomy in the artificially ventilated dog anesthetized with sodium pentobarbital. Thoracotomy was performed with (six dogs) and without (10 dogs) the addition of an increased expiratory airway resistance. Opening the chest without the increased airway resistance had no effect on coronary blood flow, despite a fall in arterial pressure, because coronary vascular resistance decreased. This was associated with a fall in arterial PO2. Thoracotomy with the airway resistance in place caused a transient slight fall in coronary flow owing to decreased arterial pressure and increased coronary resistance. All changes disappeared by the twelfth minute. Arterial PO2 was unaffected. Under the conditions of this experiment, thoracotomy had surprisingly little effect on coronary blood flow.

Airway Resistance↗