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Biomedical subjects

W H Barry

Publications and source records attributed to W H Barry.

At least 109 records · Page 6Linked to original sources
PubMed1984

Contrast agents for cardiac angiography: effects of a nonionic agent vs. a standard ionic agent.

The effects on cardiac hemodynamics and serum parameters of a standard contrast agent (sodium methylglucamine diatrizoate [Renografin 76]) were compared with the effects of a new nonionic agent (iohexol) in a double-blind study in 51 patients undergoing coronary angiography and left ventriculography. No significant alteration in measured blood parameters occurred with either contrast agent. Hemodynamic changes occurred with both, but were significantly greater with the standard Renografin than with the low-osmolality, nonionic iohexol. After left ventriculography, heart rate increased and peripheral arterial pressure fell with both agents, but less with iohexol. Following coronary artery injections, heart rate and arterial pressure decreased with both agents, but the changes were more marked and occurred earlier with the standard contrast material. It is concluded that iohexol causes less alteration in cardiac function than does the agent currently most widely used. Nonionic contrast material is likely to improve the safety of coronary angiography, particularly in those patients at greatest risk.

Angiography↗
PubMed1984

Myocardial metabolic inhibition and membrane potential, contraction, and potassium uptake.

Interruption of synthesis of ATP during hypoxia or ischemia can produce membrane depolarization that may be related to inhibition of Na+-K+-ATPase. To examine this hypothesis, the effects of exposure of cultured chick embryo ventricular cells to 1 mM cyanide (CN), to 20 mM 2-deoxy-D-glucose (2-DG), to CN + 2-DG, and to ouabain (10(-3) M) on contraction, membrane potential, and 42K uptake were determined. CN produced moderate membrane depolarization and electromechanical uncoupling within 2 min. 2-DG caused marked membrane depolarization with a transient negative inotropic effect. Exposure to CN + 2-DG produced marked depolarization (-38 mV) and mechanical arrest of the cells in a relaxed state. Ouabain produced marked depolarization (-39 mV) and contracture of the cells. Uptake of 42K was inhibited by 10(-3) M ouabain within seconds. However, CN + 2-DG produced no inhibition of 42K uptake within the first 2 min of exposure, and inhibition of the Na pump by CN + 2-DG required 30 min to develop fully. Exposure to CN alone produced no inhibition of 42K uptake, whereas moderate inhibition was produced by 2-DG alone even when substrate for oxidative phosphorylation was provided. We conclude that the acute effects of inhibition of glycolysis and oxidative phosphorylation on membrane potential and contraction in these cells are not due to inhibition of the Na pump and that during partial metabolic inhibition active univalent cation transport in these cells is relatively dependent on ATP derived from glycolysis, whereas contraction is more dependent on ATP supplied by oxidative phosphorylation.

Animals↗
PubMed1984

An array of microelectrodes to stimulate and record from cardiac cells in culture.

An array of extracellular microelectrodes containing 25 recording and 6 stimulating electrodes was fabricated using microelectronics technology. Ventricular myocardial cells from 8- to 10-day chick embryos were cultured on the surface of the microelectrode array. Extracellular potentials were recorded simultaneously from multiple sites. Simultaneous recordings of extracellular and transmembrane potentials were made from single sites. Extracellular potentials were also recorded simultaneously with cell motion from single sites. Cells were paced by means of electrical stimuli applied via the stimulating electrodes. Conduction velocity in a strip of cells varied linearly as a function of temperature from 0.21 m/s at 26 degrees C to 0.38 m/s at 36.5 degrees C.

Animals↗
PubMed1984

Effects of growth in low potassium medium or ouabain on membrane Na,K-ATPase, cation transport, and contractility in cultured chick heart cells.

Growth of cultured cells in low potassium medium has been shown to result in an increase in the number of Na,K-ATPase sites. This phenomenon and its physiological and pharmacological consequences were examined in spontaneously beating monolayers of cultured chick heart cells. Growth of cells in 1 mM extracellular potassium, 2 microM ouabain, or 1 microM veratridine for 48 hours caused 60%, 40%, or 20% increases, respectively, in the total number of specific ouabain binding sites measurable in intact cells. Acute exposure of control cells grown in 4 mM to 1 mM extracellular potassium caused elevation of steady state [Na+]i by 37%, while 1 microM veratridine exposure increased [Na+]i by 12%. After 48 hours of growth in 1 mM extracellular potassium, intracellular sodium concentrations declined to near-control levels. In cells grown in low extracellular potassium and then equilibrated with 4 mM potassium for 30 minutes, the positive inotropic effects of 1 mM extracellular potassium and 0.3 microM isoproterenol, expressed as a percent of contractile response to 3.6 mM calcium, were 40 +/- 6% and 37 +/- 5% (means +/- SEM), respectively, in low potassium-grown cells, compared with 63 +/- 8% and 35 +/- 4% in control cells. Growth of cells in low potassium shifted the concentration-effect curve for ouabain to the right. The rapid component of calcium uptake in zero extracellular sodium was significantly lower in low potassium-grown cells than in control cells after equilibration in 1 mM extracellular potassium for 30 minutes. These findings demonstrate that prolonged exposure of cultured heart cells to 1 mM extracellular potassium or ouabain causes induction of additional functional sarcolemmal sodium pump sites. The increased levels of intracellular sodium caused by these interventions appear to be an important determinant of sodium pump site density. The reduced contractile response of cells grown in 1 mM extracellular potassium and ouabain (but not isoproterenol) supports the view that elevated intracellular sodium due to Na,K-ATPase inhibition mediates the positive inotropic response to low extracellular potassium and ouabain, probably via augmented transsarcolemmal sodium-calcium exchange. In addition, our results support a mechanism of inotropic action of digitalis glycosides based on inhibition of the sodium pump rather than altered calcium binding properties of sarcolemmal sites due to cardiac glycoside binding to Na,K-ATPase.

Animals↗
PubMed1984

Kinetics of ouabain binding and changes in cellular sodium content, 42K+ transport and contractile state during ouabain exposure in cultured chick heart cells.

To define further the mechanism of positive inotropic action of cardiac glycosides, the temporal relationships among ouabain binding, sodium pump inhibition and positive inotropy were examined using cultured chick embryo ventricular cells. In K+-free medium, specific [3H]ouabain binding to intact cells followed pseudo first-order kinetics with saturation of binding sites occurring at 1 microM ouabain. The KD values calculated from the association and dissociation rate constants were 1.4 and 4.9 X 10(-7) M, respectively, in K+-free and 4 mM K+ medium. The Scatchard plot of binding in K+-free medium was linear, consistent with the presence of a single class of binding sites (KD = 1.3 X 10(-7) M). In 4 mM K+, 0.1 microM ouabain occupied 10% of the total binding sites and failed to produce an inotropic effect, inhibit 42K+ uptake or alter [Na+]i. Exposure of cells to 1 microM ouabain caused a significant increase in contractile state after 30 sec, reaching a plateau after 7 min with 50 +/- 6% augmentation of the amplitude of cell motion; the 42K+ uptake rate was concurrently inhibited by 36% accompanied by a 35% increase in [Na+]i and occupation of 38% of total ouabain binding sites. The initial rate of 42K+ uptake in cells loaded with Na+ by incubation in K+-free medium was 4 times greater than that observed without Na+ loading. These results indicate that more than 10% of sodium pump sites must be inhibited to produce an appreciable change in the rate of monovalent cation transport, [Na+]i or contractile state, due to the reserve capacity of uninhibited sodium pumps.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Phasic pressure gradients across coronary and renal artery stenoses in humans.

Fluid-filled catheter-transducer systems have been developed for assessment of phasic pressure gradients across arterial stenoses. The two catheters we have employed are 3 French and 2 French in diameter. After the catheters are flushed with carbon dioxide and filled with degassed saline solution to remove microbubbles of air, the catheters are attached to a low-volume displacement transducer. The frequency response of both catheter-transducer systems is adequate to record phasic arterial pressures. The catheters are very flexible and radioopaque, and the ability to monitor phasic pressure continuously at the tip during passage across a stenosis enhances safety of their use. The catheters have been employed successfully to measure phasic pressure gradients across 36 coronary and five renal artery stenoses. Maximal pressure gradients were observed in early diastole for coronary stenoses and in systole for renal artery stenoses, consistent with known differences in phasic flow patterns in these vascular beds. The pressure gradients in patients with coronary stenoses could be markedly increased by injection of contrast medium (Renograffin 76). Relatively poor correlation was observed between the resting pressure gradients and the angiographically defined degree of coronary stenoses.

Adolescent↗
PubMed1983

Potentiation of coronary vasoconstriction by beta-adrenergic blockade in patients with coronary artery disease.

Although beta-adrenergic blocking agents reduce myocardial oxygen consumption and symptoms of myocardial ischemia in patients with coronary artery disease (CAD), propranolol has been reported to exacerbate coronary artery spasm in some patients with variant angina. To determine whether increased coronary vasomotor tone can be induced by beta-adrenergic blockade, we measured the changes in coronary vascular resistance (CVR) during cold pressor testing (CPT) in 15 patients, nine with severe CAD and six with normal left coronary anatomy, before and after i.v. propranolol (0.1 mg/kg). Coronary blood flow was measured by coronary sinus thermodilution. CVR was calculated as mean arterial pressure divided by coronary sinus blood flow. Heart rate was maintained constant at a paced subanginal rate of 95 +/- 5 beats/min. Before propranolol, CPT induced significant increases in coronary vascular resistance in patients with CAD (15.0 +/- 2.2%, p less than 0.02), but no increase in CVR in the normal patients. After propranolol, the CVR change during CPT was augmented for patients with CAD (29 +/- 6%, p less than 0.01) and for the normal population (9 +/- 5%, NS). The potentiated increase in CVR occurred without significant changes in resting CVR or in the magnitude of the hypertensive response to CPT. We conclude that beta-adrenergic blockade with propranolol can potentiate coronary artery vasoconstriction in some patients with CAD, possibly mediated by unopposed alpha-adrenergic vasomotor tone. These changes may be important in patients in whom intense adrenergic stimulation may increase coronary artery tone and adversely influence the balance between myocardial oxygen supply and demand.

Adrenergic beta-Antagonists↗
PubMed1983

Potentiation of the cardiovascular effects of nitroglycerin by N-acetylcysteine.

The biochemical basis of the mechanism of vasodilatation by nitroglycerin (NTG) has not been previously investigated in man. However, evidence from in vitro studies suggests that NTG induces activation of guanylate cyclase via a series of enzymatic reactions that are modulated by the availability of sulfhydryl groups. Cysteine appears to be particularly effective in potentiating guanylate cyclase activation by NTG. To determine whether hemodynamic responsiveness to NTG in man might be modulated by sulfhydryl availability, concentration-response curves for effects of intravenously infused NTG on mean arterial pressure (MAP) and mean pulmonary capillary wedge pressure (PCW) were obtained in 10 patients undergoing cardiac catheterization for investigation of chest pain. NTG infusion was repeated 10 min after the intravenous infusion of 100 mg/kg of the cysteine source N-acetylcysteine (NAC). NAC induced no significant hemodynamic effect, but after NAC infusion there was a significant reduction both in the NTG infusion rate associated with a 10% fall from control values in MAP (25.8 +/- 8.3 to 9.3 +/- 2.7 micrograms/min; p less than .01) and in the infusion rate inducing a 30% reduction in PCW (13.6 +/- 4.6 to 4.2 +/- 1.6 micrograms/min; p less than .02). In a control group of five patients who received no NAC, there was no significant change in responsiveness to NTG between infusions. It is concluded that NAC potentiates the vasodilator effects of NTG in man. This suggests that sulfhydryl availability and/or redox state may be determinants of in vivo responsiveness to NTG.

Acetylcysteine↗
PubMed1983

Relationship of binding of a calcium channel blocker to inhibition of contraction in intact cultured embryonic chick ventricular cells.

To study the mechanism of action of calcium channel-blocking drugs in intact, functioning myocardial tissue under physiological conditions, we related the inhibition of contraction of spontaneously beating monolayers of cultured chick embryo ventricular cells to studies of binding of four calcium channel-blocking drugs to the same preparation under the same physiological conditions. Nitrendipine produced a concentration-dependent decrease in amplitude of contraction (IC50 = 23 nM) as determined by a computer-assisted optical-video system. Studies using [3H]nitrendipine and equilibrium-binding techniques revealed a high affinity binding site in ventricular homogenates (KD = 0.15 nM) and on intact cultured heart cells (KD = 0.26 nM, Bmax = 51 fmol/mg of protein). These dissociation constants are similar to those reported by other workers for ventricular homogenates, but 100-fold lower than the IC50 for the negative inotropic effect in intact cells. Computer analysis of displacement of [3H]nitrendipine by unlabeled nitrendipine yielded a slope factor of 0.76 and identified an additional low affinity binding site for nitrendipine with KD = 19 nM, in good agreement with the IC50 for inhibition of contraction. Verapamil partially interacted with nitrendipine binding, whereas diltiazem showed no interaction. We conclude that, in intact myocardial cells, there are two classes of binding sites for nitrendipine; interaction of dihydropyridines with the low affinity site appears to mediate their effects on contractile function.

Animals↗
PubMed1982

Hypoxia, calcium fluxes, and inotropic state: studies in cultured heart cells.

Methods have been developed for the study of cellular mechanisms underlying a variety of physiologic and pathophysiologic phenomena using cultured chick embryo heart cells. These spontaneously beating monolayer preparations lack appreciable diffusion barriers, and interstitial space components can be defined and controlled conveniently. These properties facilitate the measurement of transmembrane fluxes and cellular contents of sodium, potassium, and calcium. Concomitantly, methods have been developed to measure the contractile state as reflected in the amplitude and velocity of movement of individual myocytes in the culture. Experiments are described in which the contractile responses of cultured heart cells to graded hypoxia demonstrated a critical PO2 level around 12 mm Hg, below which progressive impairment of contractile function occurred. In preparations with iodoacetate-induced glycolytic blockade, enhanced sensitivity to hypoxia occurred. Although experiments are described, demonstrating the applicability of this model system to the study of problems including the mechanism of cardiac glycoside-induced increases in inotropic state and the definition of calcium flux pathways important in excitation-contraction coupling.

Animals↗
PubMed1982

Mechanisms of transmembrane calcium movement in cultured chick embryo ventricular cells.

1. Uptake of calcium was studied in spontaneously contracting monolayers of cultured chick embryo ventricular cells. Ca exchange could be separated into two components: a rapid phase with a rate constant of 3.91/min, accounting for 1.6 nmol/mg protein; and a slower phase with a rate constant of 0.069/min, accounting for 2.7 nmol/mg protein.2. Negatively inotropic concentrations of the slow Ca channel blocker verapamil inhibited the rapid phase of Ca uptake partially, with a maximum inhibition of 30-40% observed at concentrations of verapamil which completely inhibited contraction.3. The component of Ca uptake not inhibited by verapamil could be stimulated up to 25-fold by elevation of intracellular Na concentration and reduction of extracellular Na concentration, and thus appeared to represent at least in part Ca uptake via Na-Ca exchange.4. Ca uptake by cultured cells could be almost completely inhibited by exposure to LaCl(3), 1 mmol/l, within 5 s. This same concentration of La completely inhibited contraction within 5 s.5. During efflux of (45)Ca from cells, exposure to La (1 mmol/l) slightly inhibited efflux initially with more marked inhibition of Ca influx after 3 min of La exposure. There was no evidence for a component of superficial La-displaceable Ca, and thus the rapid phase of Ca uptake probably is due to an intracellular rapidly exchanging Ca pool. Efflux of Ca from this rapidly exchanging intracellular Ca pool was not significantly altered by exposure to Na-free choline chloride solutions.6. We conclude that rapid Ca uptake in these cultured myocardial cells is due primarily to Ca influx via the slow Ca channel and via Na-Ca exchange. In the presence of physiological [Ca(2+)](i), efflux of Ca from this intracellular Ca pool does not appear to be due to Na-Ca exchange.

Animals↗
PubMed1982

Desensitization to the inotropic effect of isoproterenol in cultured ventricular cells.

To determine whether monoalyers of cultured chick embryo ventricular cells would show tachyphylaxis to chronotropic and inotropic effects of a beta adrenergic agonist, spontaneously contracting monolayers of primary cell cultures were studied using a phase-contrast microscope-video motion detector system that permitted quantitation of the chronotropic and inotropic state. The monoalyers were chronotropically unresponsive to isoproterenol between 10(-9) to 10(-6) M and chronotropically unresponsive to a 6-fold increase in perfusate calcium concentration. However, the cells were very inotropically responsive to calcium and to isoproterenol. Expressing the isoproterenol inotropic response as a percentage of response to 3.6 mM Ca, the response to 10(-6) M isoproterenol was 79 +/- 4% of the Ca response and the EC50 for isoproterenol was 3 x 10(-9) M. The monolayers rapidly developed dose-dependent desensitization to the inotropic effect of isoproterenol; after a 30-min exposure to 1 x 10(-6) M isoproterenol, the inotropic response was 40 +/- 5% of the initial response; desensitization was long-lasting and could be prevented by propranolol. Response to calcium remained unchanged after exposure to 10(-6) M isoproterenol. Thus, the cultured cell preparation shows rapid, sustained, beta receptor specific desensitization to the inotropic effects of a catecholamine.

Animals↗
PubMed1982

Lack of interaction between digoxin and quinidine in cultured heart cells.

Previous investigations have raised the possibility that the digoxin-quinidine interaction is associated with a reduction in the positive inotropic effect of digoxin due to displacement of digoxin from cardiac as well as skeletal muscle. To circumvent some of the complexities presented by intact animal models, this interaction was investigated in cultured chick embryo ventricular cells. Quinidine, even at relatively high concentrations (10(-4)--2 x 10(-3) M), did not significantly affect positive inotropic effects of digoxin and did not protect against cellular contracture induced by toxic digoxin concentrations, despite preincubation of cells with quinidine for 60 min. The effects of digoxin on monovalent cation transport, as judged by active uptake of the K analog 86Rb, were also not altered by 10(-4) M to 2 x 10(-3) M quinidine. These data suggest that quinidine does not displace digoxin from Na, K adenosine triphosphatase binding sites in this preparation. Although these data must be extrapolated to the intact animal with caution, our findings suggest that changes digoxin clearance are more likely of primary importance in the digoxin-quinidine interaction, and indicate that the approximately 2-fold increase in serum digoxin concentration observed after addition of quinidine would be expected to have direct effects on myocardial cells comparable with those seen with increased digoxin concentration in the absence of quinidine.

Animals↗
PubMed1981

Coronary vasoconstrictor effect of indomethacin in patients with coronary-artery disease.

Prostaglandins may be important regulators of coronary blood flow. To investigate this possibility, we studied the effect of blockade of prostaglandin synthesis by indomethacin in nine patients with coronary-artery disease. Coronary-sinus blood flow (determined with the thermodilution technique) was recorded, together with mean arterial blood pressure and the myocardial arteriovenous oxygen difference from simultaneously obtained arterial and coronary-sinus blood samples, before and 20 minutes after an intravenous dose of indomethacin (0.5 mg per kilogram of body weight). There were significant increases (P less than 0.05) in mean arterial pressure (from 99 +/- 4 to 118 +/- 5 mm Hg [+/- S.E.M.]), coronary vascular resistance (+73 per cent), and myocardial arteriovenous oxygen difference (from 107 +/- 5 to 138 +/- 4 ml per liter) after indomethacin, but coronary blood flow fell significantly, from 181 +/- 29 to 111 +/- 14 ml per minute (P less than 0.05). Thus, despite an increase in myocardial oxygen demand, coronary blood flow fell and coronary vascular resistance increased. This coronary vasoconstrictor effect may have been due to blockade of vasodilatory prostaglandin synthesis or to a direct drug effect. Whatever the mechanism, indomethacin should be used with caution in patients with severe coronary-artery disease.

Blood Pressure↗