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Biomedical subjects

C E Jones

Publications and source records attributed to C E Jones.

At least 91 records · Page 5Linked to original sources
PubMed1991

An alpha-adrenergic coronary constriction during esophageal distention in the dog.

Previous work has shown an increase in sympathetic stimulation of the heart during chemical or mechanical irritation of visceral organs, but the involvement of the coronary circulation in such reflexes is not clear. In five preliminary experiments in anesthetized dogs, esophageal distention produced a sympathetic stimulation of the heart, as evidenced by an increase in heart rate, which was abolished by non-selective beta-adrenergic and muscarinic blockades. On the basis of these preliminary data, we further examined a sympathetic coronary constriction during acute esophageal distension in which any direct adrenergic coronary constriction was unmasked by muscarinic blockade with atropine (100 micrograms/kg, i.v.), and non-selective beta-adrenergic blockade with propranolol (1 mg/kg, i.v.). In seven dogs anesthetized with alpha-chloralose in an open-chest procedure, the esophagus was rapidly distended to a pressure of 36 +/- 2 mm Hg, which was not significantly different from the distending pressure used in the preliminary experiments. During esophageal distention, the mean circumflex blood flow decreased to 77 +/- 10% (SEM) of the predistention value. This decrease was statistically significant (p less than 0.05). There was no change in left ventricular pressure, mean arterial pressure dP/dtmax, or heart rate. Intracoronary administration of the nonselective alpha-adrenergic antagonist phentolamine completely abolished the reduction in mean circumflex coronary blood flow caused by esophageal distention in the presence of beta-adrenergic and muscarinic blockades. These results demonstrate a direct sympathetic coronary vasoconstriction elicited by esophageal distention. This vasoconstriction was due to activation of coronary alpha-adrenergic receptors.

Adrenergic alpha-Antagonists↗
PubMed1991

Systemic hypoxia activates a coronary vasoconstrictor reflex response that is blocked by prazosin.

We assessed the presence of an alpha 1-adrenoceptor-mediated coronary vasoconstrictor reflex response during acute systemic hypoxia in eight chloralose-anesthetized dogs. We avoided local vasodilator responses to myocardial and coronary hypoxia and to circulating factors by perfusing the left common coronary artery at constant pressure with normoxic blood while the dogs were ventilated with 5% O2-95% N2. Left ventricular afterload was held constant by withdrawing arterial blood during hypoxia-induced peripheral vasoconstriction. Left ventricular (LV) preload, as indicated by left atrial pressure, was unchanged. beta-adrenoceptor-mediated coronary dilation and positive chronotropic and inotropic responses to hypoxia were blocked by propranolol. Para-sympathetic-mediated coronary dilation and bradycardia were blocked by atropine. Under these conditions, systemic hypoxia caused a 19.7 +/- 2.1% decrease in left common coronary blood flow. Blockade of left coronary alpha 1-adrenoceptors with prazosin prevented coronary vasoconstriction during repeated systemic hypoxia. In four other similarly prepared dogs, repeated systemic hypoxia without alpha 1-adrenoceptor blockade reproducibly reduced left coronary blood flow 16.3 +/- 3.5 and 15.7 +/- 3.1%, respectively. The results of this investigation provide the first evidence of a coronary vasoconstrictor reflex response to systemic hypoxia. This response is mediated by alpha 1-adrenoceptors.

Adrenergic alpha-Antagonists↗
PubMed1990

Western blot identification of platelet proteins that bind normal serum immunoglobulins. Characteristics of a 95-Kd reactive protein.

We have found that Western blots (WBs) of whole platelets exposed to normal autologous or homologous sera commonly have bands at 90 to 95 (95) Kd, and less often at 100 to 110, 80 to 85, 60 to 75, and 50 to 60 Kd when developed with antiglobulins. The percentages of normal sera producing a 95-Kd band with anti-immunoglobulin G (IgG), -IgA, and -IgM are 85, 50, and 30, respectively. Antiglobulin reagents alone also produce background bands on WBs that we have shown correspond to levels of platelet-associated Igs (PAIgs) or their derivatives. Titers of 95 Kd-reactive IgG in normal sera range from 10 to 1,280 (85% less than or equal to 50), and the reaction appears to be partially F(ab')2-mediated. The 95-Kd protein is internal and differs in many respects from surface glycoproteins IIIa, IV, and V of similar apparent molecular weight. In thrombocytopenic patients there was no correlation between severity of thrombocytopenia or PAIgG of platelet eluates and corresponding serum titers of 95 Kd-reactive IgG. Some WB reactions previously reported as evidence of autoimmunity may represent normal variations in reactions of Igs with internal platelet proteins. These reactions may be immunospecific or analogous to nonspecific, partially F(ab')2-dependent binding of Igs by certain bacterial proteins.

Blood Platelets↗
PubMed1990

Alpha 1-adrenergic coronary constriction during exercise and ischemia.

This paper reviews work primarily from our laboratories, examining an alpha 1-adrenergic receptor-mediated coronary constriction during exercise and myocardial ischemia in dogs. It was demonstrated that in the quiescent conscious dog, the coronary circulation is devoid of an alpha 1-coronary constriction. Furthermore, it was shown by the intracoronary injection of selective agonists that both alpha 1- and alpha 2-receptor subtypes are present in coronary vessels. However, during exercise or ischemia only the selective alpha 1-antagonist prazosin caused an increase in coronary inflow, indicating that only alpha 1-receptors were activated. During both conditions, the increase in flow caused by alpha 1-blockade was associated with an increased contractile function in subendocardium. In experiments on anesthetized dogs, it was shown that prazosin caused an equal increase in perfusion of subepicardial and subendocardial layers during stellate ganglion stimulation. However, contractile function was increased only in subendocardium. It was proposed that only in deeper muscle layers does an alpha 1-coronary constriction impose a flow-limitation on contractile function. Finally, recent results indicate that myocardial ischemia, produced either by partial coronary stenosis or by maintenance of coronary inflow at the resting level during exercise, may initiate a vicious cycle with a further increase in alpha 1-adrenergic coronary constriction. Abolition of this positive feedback mechanism may partially explain the anti-infarction effects of chronic ventricular sympathectomy, as previously observed in our laboratories.

Animals↗
PubMed1990

Augmentation of coronary flow improves myocardial function in exercise.

We compared the effects of increasing coronary blood flow (CBF) by intracoronary alpha 1-adrenergic blockade or by a direct vasodilator in six chronically instrumented dogs undergoing submaximal exercise. On different days, CBF, left ventricular pressure (LVP), regional myocardial segment length (SL), and arterial blood pressure (ABP) were measured at rest, during strenuous exercise before administration of vasodilating agents, and during exercise after administration of the vasodilating agents prazosin (0.5 mg) or adenosine (10-100 micrograms/min continuous infusion) through an indwelling circumflex artery catheter. Exercise resulted in a significant increase in CBF, which was accompanied by significant increases in maximum rate of LVP generation (dP/dtmax), percentage of SL shortening (%SL) and maximum rate of SL shortening (dL/dtmax) in both the anterior and posterior regions of the left ventricle. As compared with the exercise level alone, prazosin administration or adenosine infusion during exercise significantly increased CBF by 22 and 26%, respectively. Furthermore, these increases in CBF were followed by significant increases in both dP/dtmax and dL/dtmax over exercise levels without prazosin administration or adenosine infusion. These results suggest that myocardial contractile function may be flow-limited under conditions of submaximal exercise and that coronary vasodilation, either by alpha 1-adrenergic blockade or by a direct vasodilator, improves contractile function.

Adenosine↗
PubMed1990

Endurance training alters arterial baroreflex function in dogs.

The present study was designed to determine whether 12 wk of daily exercise alter autonomic neural control of the heart during baroreflex stimulation in healthy dogs. We studied 16 untrained and 12 endurance-trained anesthetized dogs which were instrumented to measure arterial blood pressure (AP), carotid sinus baroreceptor pressure (CBP), electrocardiogram (ECG), heart rate (HR), and R-R interval (RR). The arterial baroreflex was studied during hypertension caused by i.v. bolus infusion of phenylephrine, hypotension caused by i.v. bolus infusion of nitroprusside, and bilateral carotid occlusion (BCO) in which carotid sinus pressure was reduced to 41 +/- 2 mm Hg (mean +/- SEM). Arterial baroreflex sensitivity, which was assessed by determining the change in heart interval (i.e., change in RR) per unit change in systolic AP (delta RR/delta AP), was significantly lower during the hypertensive challenge in the trained dogs compared to the untrained dogs (2.2 +/- 0.3 vs 6.8 +/- 1.5 ms.mm Hg-1, respectively). Similarly, the delta RR/delta AP was substantially lower during the hypotensive challenge in trained dogs vs the untrained dogs (1.2 +/- 0.3 vs 1.8 +/- 0.4 ms.mm Hg-1, respectively). In addition, the HR response to the BCO was significantly less in trained dogs (22 +/- 2 bpm) vs untrained dogs (32 +/- 5 bpm). The open-loop gain (Go), which was used to quantitate the effectiveness of the carotid baroreflex to increase mean systemic AP during BCO, was similar in both untrained and trained dogs (2.9 +/- 0.6 and 2.4 +/- 0.5, respectively). These data indicate that, while endurance training significantly reduces the HR component of the arterial baroreflex, the arterial pressure response apparently is not altered.

Animals↗
PubMed1989

Carotid eversion endarterectomy revisited.

Carotid eversion endarterectomy appears to be a safe and anatomically acceptable alternative to the standard carotid bifurcation endarterectomy, as evidenced by the absence of permanent neurologic morbidity and mortality in 98 operations. Preliminary clinical, angiographic, and noninvasive laboratory parameters suggest that there is a significant reduction of both residual technical defects and early recurrent stenosis. Specifically, no perioperative thrombosis or early restenosis was encountered in the 98 endarterectomies. Furthermore, only two technical defects have been noted, and one of these occurred in one patient who required a longitudinal arteriotomy and attendant suture line when the common carotid artery was transected too proximally and the eversion maneuver could not be accomplished. Serial long-term clinical and noninvasive laboratory follow-up evaluation, in addition to indicated postoperative angiography, will continue in an effort to assess the durability of a technical approach to carotid endarterectomy that may minimize residual defects and early restenosis.

Adult↗
PubMed1989

Anion channel blockers cause apparent inhibition of exocytosis by reacting with agonist or secretory product, not with cell.

Agents that act as anion channel blockers (ACBs) and do not permeate cells appear to inhibit exocytosis in platelets, parathyroid cells, and neutrophils. Based in large part on these observations, anion influx through plasma membrane channels has been considered a factor controlling cellular secretion, but there have been no direct anion influx measurements in cells or granules to support this concept. We have found that ACBs inhibit only thrombin-induced platelet secretion, not secretion induced by ADP, collagen, or A23187. ACBs inhibit thrombin esterolytic activity, binding of thrombin to platelets, and thrombin-stimulated platelet production of malondialdehyde in proportion to the degree of inhibition of thrombin-induced platelet secretion. Thus inhibition of platelet secretion by ACBs is due to inactivation of the stimulatory agonist, thrombin, and not to interference with cellular secretion per se. We have also found that previously reported inhibition of secretion of parathyroid cells and neutrophils by ACBs can be explained by the ability of ACBs to interfere with detection of the cellular secretory products that were measured to assess exocytosis. Our measurements of parathyroid hormone and beta-glucuronidase in the presence of ACBs were reduced to the same degree as the reported reduction in apparent cellular secretion produced by these agents. We conclude that plasma membrane anion channels of the type that can be blocked by ACBs such as 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, 4-acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic acid, suramin, and probenecid do not participate in cellular secretory processes. Whether other types of anion channels exist that are not affected by these ACBs and whether there are mechanisms of anion flux during secretion not dependent on channels remain open questions.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1989

On the proluminal movement of 3H-androgens across the rat epididymal epithelium.

3H-Androgens in rat epididymal interstitium have previously been shown to move into the epididymal lumen against a concentration gradient. This is true especially in the caput epididymidis. The present investigation used the technique of in vivo epididymal perifusion and tubule micropuncture to demonstrate that the proluminal movement of 3H-androgens is subject to competitive inhibition (unlabeled testosterone in the perifusion fluid at 10 times and 100 times the concentration of 3H-testosterone significantly reduced proluminal movement of isotope) and is not energy-dependent (1 mM 2,4-dinitrophenol in perifusion fluid did not reduce the proluminal movement of isotope). Additionally, dry-mount autoradiography demonstrated high intraluminal concentrations of isotope relative to interstitial concentrations after caput tubule incubation in 3H-dihydrotestosterone (3H-DHT), and showed that the high intraluminal concentrations of isotope were not dependent on the presence of spermatozoa, i.e. proluminal movement of 3H-androgens was not due to binding to intraluminal spermatozoa. Isolation of caput epididymidal sperm on filters followed by 3H-DHT binding experiments also failed to demonstrate the presence of specific binding of this androgen to spermatozoa. Finally, it was confirmed that electrophoresed epididymal lumen fluid contains a single 3H-DHT binding peak that is at its highest concentration in the caput epididymal fluid. These data are consistent with the conclusion that intraluminal androgen-binding protein is an important factor in transepithelial androgen movement.

Androgens↗
PubMed1989

Thromboresistant polymers: a new approach.

Selected antithrombotic agents were found to impart improved thromboresistance to polysilicone tubes when covalently bound to such tubes in pilot studies. Bonding was accomplished by radiation grafting of epoxypropyl acrylate monomer on the polysilicone, followed by reaction of the hydroxyl groups of the antithrombotic agents with the epoxy groups on the grafted monomer chains. The bound antithrombotic agents may act by chelating or complexing calcium ions, which are known to perform several functions in blood coagulation.

Acrylates↗
PubMed1989

Benzodiazepines identified by capillary gas chromatography-mass spectrometry, with specific ion screening used to detect benzophenone derivatives.

We developed algorithms for confirmation and identification of benzodiazepines and their metabolites, initially detected in urine samples by enzyme-multiplied immunoassay (EMIT). These algorithms are based on the pattern of benzophenone derivatives of benzodiazepines obtained by gas chromatography-mass spectrometry (GC-MS) with use of a modified specific ion selection mode. Benzophenone derivatives were produced by acid hydrolysis of urine samples containing benzodiazepines and (or) their metabolites. We present mass spectra of the newer benzodiazepines--alprazolam, midazolam, and triazolam--and we determined the detection limit (0.2 mg/L) for these drugs as measured with the EMIT d.a.u. benzodiazepine assay and the ETS instrument (both from Syva Co.). We conclude that these algorithms are useful mostly in forensic toxicology in which unequivocal identification of benzodiazepines is the desired goal.

Alprazolam↗
PubMed1988

Endothelial cell adhesion to vascular prosthetic surfaces.

Improving the long term patency of small diameter prosthetic grafts remains an important but elusive objective in vascular surgery. In pursuit of a non-thrombogenic surface, we have cultured human-adult endothelial cells, examined their adhesive properties and their ability to colonize the inner surface of a Dacron graft. To examine cell adhesion, endothelial cells were labelled with 111In-oxine and inoculated onto prosthetic wells previously prepared with either cold insoluble globulin (CIG), 1% gelatin, alginate or left untreated as a control. At 100 min, mean percentage adhesion to CIG and gelatin precoated wells was 86.0 +/- 9.9% (+/- SD) and 81.6 +/- 2.9% respectively, whereas alginate at 57.5 +/- 7.5% and the control well at 48.3 +/- 9.9% showed significantly less adhesion. Further experiments examined the adhesion of Indiumoxine labelled endothelial cells to Dacron graft (2 cm X 6 mm ID) placed in an in vitro arterial circuit. An immediate loss of approximately 20% of the cells occurred within the first 30 s, whereafter, a stable population were adherent to the graft material. By 102 min, 73.4 +/- 1.8% of cells remained attached when exposed to tissue culture medium, but only 64.1 +/- 6.9% after exposure to blood. Cultured human adult endothelial cells adhere most effectively to prosthetic surfaces precoated with CIG or gelatin, and remain attached following exposure to shear forces.

Alginates↗
PubMed1988

Developmental determinants of recovery after relief of partial ureteral obstruction.

Although obstructive nephropathy is a major cause of renal insufficiency at all ages, the functional consequences of relief of obstruction on the developing kidney are poorly understood. To evaluate recovery from chronic partial ureteral obstruction (CPUO) in the neonatal period, the left ureter of guinea pigs was constricted within the first 48 hours of life, and the obstruction was relieved 10 days later. At three and eight weeks of age, intraureteral pressure, number of perfused glomeruli (NPG), renal blood flow (RBF), and glomerular filtration rate (GFR) were measured. These animals were compared with sham-operated and unrelieved groups. Two additional groups underwent CPUO at five weeks of age, with persistent obstruction or relief in 10 days, and were also studied at eight weeks. In all animals, intraureteral pressure increased during ipsilateral ureteral obstruction and normalized following its release. Recovery of RBF and GFR after relief of ipsilateral CPUO in the newborns was only partial at eight weeks, with no renal growth or increase in NPG from three to eight weeks of age. In contrast, recovery of RBF in the adult was complete 10 days after relief of obstruction, with significant increase in GFR, and no decrease in renal mass or NPG. We conclude that if delayed, relief of CPUO in the neonate may not restore renal growth and functional maturation which have been impaired by CPUO.

Age Factors↗
PubMed1988

Adenosine deaminase attenuates canine coronary vasodilatation during regional non-ischaemic myocardial hypoxia.

To test the hypothesis that adenosine contributes to the coronary hyperaemia produced by regional non-ischaemic myocardial hypoxia coronary blood flow and myocardial oxygen extraction and consumption were continuously monitored in 21 anaesthetised open chest dogs under the following conditions: control 1--postinstrumentation, steady state control; hypoxia 1--3-5 min of regional (LAD) hypoxaemia (partial pressure of oxygen, PO2, 21.4(2.0) mmHg (3.1(0.2) kPa), coronary arterial oxygen content, CaO2, 3.9(0.4) ml.100 ml-1 (39(4) ml.litre-1): control 2--repeat steady state control; and hypoxia 2--3-5 min repeat regional hypoxaemia (PO2 18.9(2.4) mmHg (2.5(0.3) kPa); CaO2 3.6(0.6) ml.100 ml-1 (36(6) ml.litre-1) blood). Left anterior descending artery perfusion pressure was held constant for all conditions. Control 2 and hypoxia 2 were performed in the presence of locally infused adenosine deaminase (n = 16) or saline vehicle (n = 5). The 16 dogs given adenosine deaminase were further subdivided into those perfused with blood deoxygenated by a donor canine lung (group 1, n = 11) and those perfused with blood from a paediatric oxygenator (group 2, n = 5). Systemic haemodynamics, heart rate, and coronary arterial PO2 and O2 contents were similar during the two control periods and during the two exposures to hypoxia in all three groups. Left anterior descending artery blood flow increased by approximately 400% (p less than 0.05) in all three groups during the first exposure to hypoxia. Myocardial oxygen consumption was unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗
PubMed1988

Adenosine deaminase attenuates norepinephrine-induced coronary functional hyperemia.

Responses to norepinephrine (NE) before and after treatment with adenosine deaminase (ADA) were examined in anesthetized dogs. In four dogs repeatable changes in coronary blood flow, myocardial oxygen extraction and consumption, left ventricular +dP/dtmax, and heart rate (HR) were demonstrated during two successive intracoronary infusions of 0.13 micrograms.kg-1.min-1 NE. In eight dogs, the NE-induced hyperemia was decreased from +150 to +67%, the change in myocardial oxygen consumption (MVo2) was attenuated from +177 to +101% by ADA, and the increase in HR was reduced from +28 to +16%. In six dogs, the increase in HR caused by NE before ADA was maintained after ADA by atrial pacing. The NE-induced hyperemia and the increase in MVo2 were again decreased by ADA. Similar results were observed in 12 other dogs with hearts paced at a constant, elevated rate during control as well as during both infusions of NE. In all groups, the O2 extraction response to increased MVo2 increased and the flow response decreased after ADA. In six dogs nitroprusside was infused during NE after ADA. When coronary flow was restored to the same level observed before deaminase, MVo2 was not diminished. These results support a role for adenosine in the coronary functional hyperemia accompanying NE activation of the canine myocardium.

Adenosine↗
PubMed1988

Coronary and cardiac responses to exercise after chronic ventricular sympathectomy.

This study examined the effects of chronic surgical ventricular sympathectomy on the relationships between left ventricular mechanical performance, coronary blood flow, and exercise workload in sham-operated control dogs and dogs which had been ventricular sympathectomized 8 wk earlier. During exercise, left ventricular global contractile state was less in sympathectomized ventricles than in control ventricles, as indicated by reduced systolic pressure and maximal rate of pressure generation. Regional contractile shortening was not different. Heart rate was significantly elevated in sympathectomized ventricles. Therefore, peak systolic pressure-heart rate product and tension-time index were not different in sympathectomized ventricles compared to control ventricles. However, at each level of exercise, mean coronary flow in sympathectomized ventricles was reduced by about 50% compared to control values. The slopes of coronary flow on pressure-rate product and tension-time index were also reduced. No difference in left ventricular oxygen extraction between control and sympathectomized hearts were observed. Thus, chronic ventricular sympathectomy altered the relationships between coronary flow and oxygen consumption, on the one hand, and ventricular oxygen-dependent performance and whole-body exercise level, on the other hand.

Animals↗
PubMed1988

Comparative effects of alpha-1 and alpha-2 adrenoceptors in modulation of coronary flow during exercise.

During submaximal exercise, an alpha adrenergic vasoconstriction that opposes metabolic dilation exists in the coronary circulation. Fifteen dogs were given i.c. injections of prazosin (0.5 mg) or yohimbine (0.7 mg) to determine the participation of alpha 1 and alpha 2 adrenoceptors in the vasoconstriction during exercise. All dogs were chronically instrumented to measure left circumflex blood flow, heart rate, regional left ventricular function and global left ventricular function. The experimental protocol consisted of a graded exercise regimen during which, at the highest level of exercise an alpha antagonist was given i.c. Exercise significantly increased heart rate, left ventricular pressure, dP/dt, systolic shortening and rate of shortening, and coronary blood flow. After the prazosin injection there was an increase in circumflex blood flow (25 +/- 3%) as well as regional (38 +/- 6%) and global (20 +/- 3%) contractile function. However, there was no change in circumflex blood flow or myocardial function after yohimbine. These data indicate that during exercise the sympathetic constrictor tone in the coronary circulation is mediated primarily by alpha 1 adrenoceptors, with little or no involvement from alpha 2 adrenoceptors.

Adrenergic alpha-Antagonists↗