The effect of propranolol versus placebo on resident surgical performance.
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PURPOSE: To determine whether propranolol can decrease surgical tremor and anxiety in residents performing ocular microsurgery without impairing patient or physician safety. METHODS: In this randomized, double-masked, crossover study, 5 third-year ophthalmology residents ingested a capsule containing either propranolol, 40 mg, or placebo 1 hour prior to performing ophthalmic microsurgery. All residents were healthy men under age 30 years. Prior to commencement of the study, all participants had successfully been administered a test dose of propranolol without side effects. The study took place over a 10-week period. At the conclusion of each case, both the resident and attending surgeon observer independently completed a form grading, on a sliding scale: (1) amount of overall tremor; (2) amount of tremor during placement of the first 3 sutures after lens or nucleus extraction; (3) anticipated difficulty of the case; (4) actual difficulty with the case; and (5) anxiety (surgeon only). In addition, the type of procedure performed, complications encountered, and surgeon side effects were recorded. The data were analyzed with a 2-way analysis of variance for unbalanced data. RESULTS: A total of 73 surgical cases were performed; the surgeons were administered propranolol for 40 cases and placebo for 33. As judged by the resident surgeon, there was a highly significant effect of propranolol in decreasing anxiety (P = .0058), reducing surgical tremor overall (P < .0001), and reducing tremor while placing the first 3 sutures following lens extraction (P < .0001). There was no treatment-by-surgeon interaction for any of the measures. Complications and difficulty of the case, as judged by both the resident and attending surgeons, were not significantly different in the propranolol versus placebo groups (P > .05). There were no side effects reported or observed in any of the surgeons. CONCLUSIONS: Propranolol, 40 mg, administered 1 hour prior to surgery, significantly decreases tremor and anxiety in the surgeon without untoward effects to the surgeon and the patient. However, it is unknown whether decreased tremor and anxiety improved surgical outcome. (+info)
Ventilatory effects of 8 h of isocapnic hypoxia with and without beta-blockade in humans.
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This study investigated whether changing sympathetic activity, acting via beta-receptors, might induce the progressive ventilatory changes observed in response to prolonged hypoxia. The responses of 10 human subjects to four 8-h protocols were compared: 1) isocapnic hypoxia (end-tidal PO2 = 50 Torr) plus 80-mg doses of oral propranolol; 2) isocapnic hypoxia, as in protocol 1, with oral placebo; 3) air breathing with propranolol; and 4) air breathing with placebo. Exposures were conducted in a chamber designed to maintain end-tidal gases constant by computer control. Ventilation (VE) was measured at regular intervals throughout. Additionally, the subjects' ventilatory hypoxic sensitivity and their residual VE during hyperoxia (5 min) were assessed at 0, 4, and 8 h by using a dynamic end-tidal forcing technique. beta-Blockade did not significantly alter either the rise in VE seen during 8 h of isocapnic hypoxia or the changes observed in the acute hypoxic ventilatory response and residual VE in hyperoxia over that period. The results do not provide evidence that changes in sympathetic activity acting via beta-receptors play a role in the mediation of ventilatory changes observed during 8 h of isocapnic hypoxia. (+info)
Effects of norepinephrine and isopentenyladenosine on Na+/Ca2+ exchange currents in isolated guinea pig ventricular myocytes.
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AIM: To study the effects of norepinephrine (NE) and isopentenyladenosine (Iso) on Na+/Ca2+ exchange currents and the receptor mechanism. METHODS: The quasi-steady state current-voltage relationship from the isolated guinea pig ventricular myocytes was measured using whole-cell voltage-clamp techniques with a ramp pulse protocol. RESULTS: At potential of +50 mV, NE 0.005, 0.05, and 5 mumol.L-1 increased the Ni(2+)-sensitive current by 29% +/- 9%, 72% +/- 11%, and 124% +/- 31.4%, respectively; Iso 1.5, 150, and 1500 nmol.L-1 caused increases in the Ni(2+)-sensitive current by 2.8% +/- 2.8%, 56% +/- 13%, and 102% +/- 12%, respectively. Propranolol 10 mumol.L-1 completely inhibited the current changes induced by NE and Iso while phentolamine 50 mumol.L-1 showed no effects. CONCLUSION: NE and Iso increased the Na+/Ca2+ exchange currents via stimulation of cardiac beta-adrenoceptor. (+info)
Contribution of alpha-adrenergic and beta-adrenergic stimulation to ischemia-induced glucose transporter (GLUT) 4 and GLUT1 translocation in the isolated perfused rat heart.
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The intracellular signaling mechanism of the ischemia-stimulated glucose transporter (GLUT) translocation in the heart is not yet characterized. It has been suggested that catecholamines released during ischemia may be involved in this pathway. The purpose of this study was to evaluate the contribution of alpha-adrenoceptors and beta-adrenoceptors to ischemia-mediated GLUT4 and GLUT1 translocation in the isolated, Langendorff-perfused rat heart. Additionally, GLUT translocation was studied in response to catecholamine stimulation with phenylephrine (Phy) and isoproterenol (Iso). The results were compared with myocardial uptake of glucose analogue [18F]fluorodeoxyglucose (FDG). Subcellular analysis of GLUT4 and GLUT1 protein on plasma membrane vesicles (PM) and intracellular membrane vesicles (IM) using membrane preparation and immunoblotting revealed that alpha- and beta-receptor agonists stimulated GLUT4 translocation from IM to PM (2.5-fold for Phy and 2.1-fold for Iso, P<0.05 versus control), which was completely inhibited by phentolamine (Phe) and propranolol (Pro), respectively. Plasmalemmal GLUT1 moderately rose after Iso exposure, and this was prevented by Pro. In contrast, ischemia-stimulated GLUT4 translocation (2.2-fold, P<0.05 versus control) was only inhibited by alpha-adrenergic antagonist Phe but not by beta-adrenergic antagonist Pro. Similarly, Phe but not Pro inhibited ischemia-stimulated GLUT1 translocation. GLUT data were confirmed by FDG uptake monitored using bismuth germanate detectors. The catecholamine-stimulated FDG uptake (6.9-fold for Phy and 8.9-fold for Iso) was significantly inhibited by Phe and Pro; however, only Phe but not Pro significantly reduced the ischemia-induced 2.5-fold increase in FDG uptake (P<0.05 versus ischemia). This study suggests that alpha-adrenoceptor stimulation may play a role in the ischemia-mediated increase in glucose transporter trafficking leading to the stimulation of FDG uptake in the isolated, perfused rat heart, whereas beta-adrenergic activation does not participate in this signaling pathway. (+info)
Neuropeptide Y is a prejunctional inhibitor of vagal but not sympathetic inotropic responses in guinea-pig isolated left atria.
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1. The effects of NPY and related peptides were examined on basal contractile force and nerve-mediated inotropic responses to electrical field stimulation of the guinea-pig isolated left atrium. 2. Electrical field stimulus (EFS)-inotropic response curves were constructed by applying 1-64 trains of four field pulses (200 Hz, 0.1 ms duration, 100 V) across isolated left atria (paced at 4 Hz, 2 ms, 1-4 V) within the atrial refractory period. Curves were constructed in presence of vehicle, propranolol (1 microM) or atropine (1 microM) to determine appropriate stimulus conditions. 3. The effects of PYY (1-10,000 nM), NPY (0.01-10 microM), N-Ac-[Leu28,31]NPY(24-36) (N-A[L]NPY(24-36); 0.01-10 microM) and clonidine (0.1-1000 nM) were examined on the positive and negative inotropic responses to EFS (eight trains, four pulses per refractory period). 4. NPY-related peptides had no effect on basal force of contraction nor on the inotropic concentration-response curves to bethanechol or isoprenaline. All three peptides inhibited vagally-mediated negative inotropic responses; rank order of potency PYY>NPY> or =N-A[L]NPY(24-36) was consistent with an action at prejunctional Y2-receptors. Clonidine concentration-dependently inhibited sympathetic inotropic responses. However, PYY, NPY and N-A[L]NPY(24-36) failed to mediate any significant inhibition of the positive inotropic response to EFS. 5. These data demonstrate that NPY is an effective inhibitor of vagal but not sympathetically-mediated inotropic responses in the guinea-pig isolated left atria. This may suggest that endogenously co-released NPY is important in mediating cross talk between efferent components of the autonomic nervous system modulating cardiac contractility, acting overall to sustain positive inotropic responses. (+info)
Characterization of chloride currents and their noradrenergic modulation in rat taste receptor cells.
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Taste receptor cells contain a heterogeneous array of voltage-dependent ion conductances that are essential components for the transduction of gustatory stimuli. Although mechanistic roles have been proposed for several cationic conductances, the understanding of anionic currents is rudimentary. This study characterizes biophysical and pharmacological properties of chloride currents in rat posterior taste cells using whole cell patch-clamp recording technique. Taste cells express a heterogeneous array of chloride currents that displayed strong outward rectification, contained both calcium-dependent and calcium-independent components, and achieved a maximal conductance of almost 1 nS. Reversal potentials altered predictably with changes in chloride concentration. Currents were sensitive to inhibition by the chloride channel pharmacological agents DIDS, SITS, and niflumic acid but were insensitive to 9-AC. Adrenergic enhancement of chloride currents, present in other cell types, was tested on taste cells with the beta-adrenergic agonist isoproterenol (ISP). ISP enhanced the outwardly rectifying portion of the chloride current. This enhancement was calcium dependent and was blocked by the beta-adrenergic antagonist propranolol. Collectively these observations suggest that chloride currents may participate not only in usually ascribed functions such as stabilization of the membrane potential and volume regulation but additionally play active modulatory roles in the transduction of gustatory stimuli. (+info)
Analysis of heart rate variability during head-up tilt testing in a patient with idiopathic postural orthostatic tachycardia syndrome (POTS).
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A 16-year-old boy was diagnosed with idiopathic postural orthostatic tachycardia syndrome (POTS) during head-up tilt testing. During a passive tilt, the patient's heart rate (HR) increased by 30 beats/min within 5 min. After 25 min of tilting, his HR further increased to 133 beats/min and he began to complain of lightheadedness and weakness without hypotension. Power spectral analysis of HR variability during the tilt test revealed that the ratio of low and high frequency powers increased with the onset of orthostatic intolerance. Propranolol (10mg every morning) dramatically alleviated his clinical symptoms, and he has been asymptomatic with gaining weight after discontinuing his crowded train commuting. (+info)
Nitric oxide donors can increase heart rate independent of autonomic activation.
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Administration of nitric oxide (NO) donors in vivo is accompanied by a baroreflex-mediated increase in heart rate (HR). In vitro, however, NO donors can increase HR directly by stimulating a pathway that involves NO, cGMP, and the hyperpolarization-activated current (I(f)). The aim of this study was to assess the functional significance of this pathway in vivo by testing whether NO donors can increase HR in the anesthetized rabbit independent of the autonomic nervous system. New Zealand White rabbits were vagotomized, cardiac sympathectomized, and treated with propranolol (0.3 mg/kg iv). The NO donor molsidomine (0.2 mg/kg iv) caused a progressive increase (Delta) in HR (DeltaHR, 14 +/- 3 beats/min; P < 0.01). This effect was significantly reduced by the I(f) blocker ZD-7288 (0.2 mg/kg iv; DeltaHR, 2 +/- 3 beats/min; P = not significant). Similar results were seen with sodium nitroprusside. The positive chronotropic effect of sodium nitroprusside (50 microM) was confirmed in the isolated working rabbit heart preparation (DeltaHR, 17 +/- 3 beats/min; P < 0.01). In conclusion, NO donors exert a small, but significant, positive chronotropic effect in vivo that is independent of the autonomic nervous system. These results are also consistent with data in sinoatrial node cells that show that NO donors increase HR by stimulating I(f). (+info)