Metaproterenol Research Articles

The role of alcohol extract of cranberry in improving serum indices of experimental metaproterenol-induced heart damage in rats.

Cranberry offers numerous cardiovascular benefits. According to several studies, this fruit promotes the oxidation of low-density lipoprotein, enhances high-density lipoprotein, reduces platelet coagulation, and improves vascular activity. Albino male rats were divided into five groups (n = 5 per group). The control group received intraperitoneal administration of normal saline. The second group was injected with metaproterenol (MET) 3 days a week for 4 weeks. The third, fourth, and fifth groups were given cranberry extract in doses of 75, 100, and 150, respectively, along with heart-damaging drugs. Blood samples were collected and sent to the laboratory on the fourth weekend and 1 week after completing the injections in the fourth week (the sixth weekend) for analyzing serum factors such as cardiac creatine kinase MB, cardiac troponin I (cTnI), and aspartate aminotransferase (AST). The serum activity of the cardiac evaluation parameters in the fourth week demonstrated a highly significant correlation among the groups with respect to AST and cTnI (p < .001). Additionally, a significant relationship was observed between AST and cTnI within the target groups (p < .05). Ultimately, the findings indicated that the consumption of cranberry extract, due to its impact on heart function, could effectively modify serum indicators associated with heart damage. The utilized extract also exhibited efficacy, albeit with variable effects. Therefore, it is recommended to use cranberry extract synergistically with other chemical and herbal medications to achieve more sustained effects.

Is using metaproterenol sulfate reliable in hypertension management during the coronary artery bypass graft surgery in terms of graft patency?

INTRODUCTION: Coronary artery bypass graft (CABG) surgery that is a basic revascularization method is used commonly and hypertension appears frequently during and after CABG operations. In the treatment of hypertension, metaproterenol sulfate (MS) is one of the main agents; however, the effects of this agent on grafts are not known at an adequate level. The aim of the present study was to determine whether MS could be used safely in CABG operations by examining its effects on coronary grafts. MATERIAL AND METHODS: This cross-sectional, prospective, experimental study was conducted at a University hospital. In this study, internal thoracic artery (ITA), radial artery (RA) and saphenous vein (SV) graft materials were studied in organ bath in patients who underwent CABG surgery between 2013 and 2016. In the organ bath, 10-6 phenylephrine was added to the grafts to ensure that the ITA, RA and SV grafts contracted submaximally. Then, by adding MS with the cumulative method, the resulting relaxation results were recorded and dose-response curves were created. The p < 0.05 was considered as significant. RESULTS: A total of 30 patients were included in the study. The average age of the participants was 59.3 (45–81) years. Minimum 1 and maximum 6 grafts (2.96 in average) were taken from all patients. Relaxation response was formed in the ITA at a rate of 40.49% ± 13.52, in the RA at a rate of 28.41% ± 9.08 and in the SV at a rate of 23.87% ± 8.36 by adding MS with the cumulative method. In the statistical work that was done by comparing the relaxation values among the SV grafts, ITA and RA grafts, it was determined that the efficacy of MS in the SV grafts was significantly lower when compared with the ITA and RA grafts. CONCLUSIONS: In the present study, it was concluded that the risk of developing vasospasm was low in all three grafts when MS was used in intraoperative and postoperative periods. However, in the long-term, this made us consider that better graft patency rates might be obtained. Multicenter in-vivo studies with larger patient groups are needed to support our findings.

Facile synthesis of layer-by-layer decorated graphene oxide based magnetic nanocomposites for β-agonists/dyes adsorption removal and bacterial inactivation in wastewater

The escaped β-agonists and dyes during conventional wastewater treatment processes pose a non-negligible threat to humans and environment. In this study, a novel method based on the thiol modified chitosan magnetic graphene oxide nanocomposite (Fe3O4@SiO2/GO/CS/MPTS) was reported for the effective removal of β-agonists and dyes as well as the disinfection of microorganisms in complex wastewater. The surface and textural properties of the nanocomposites were characterized through Fourier transform infrared spectrums (FT-IR), scanning electron micrographs (SEM), X-ray photoelectron spectra (XPS), vibrating sample magnetometry (VSM) and zeta-potential measurements analysis. And the influence of several parameters (pH, contact time, pollutants concentration and adsorbent dose) on the adsorptive performances of nanoparticles was carefully estimated by the batch adsorption studies. According to Langmuir isotherm, the maximum adsorption capacities of Fe3O4@SiO2/GO/CS/MPTS were 215.52, 263.85, 184.16, 558.66 and 613.50 mg g−1 for dopamine (DA), clenbuterol (CLE), orciprenaline (ORC), methylene blue (MB) and crystal violet (CV), respectively. The data of the adsorption kinetic and adsorption isotherm fitted well with pseudo-second order kinetic and Langmuir isotherm models, which indicating the existence of chemical adsorption and monolayer adsorption process. The adsorption mechanisms of β-agonists and dyes were ascribe to electrostatic interaction, π–π interaction and cation− π interaction. Moreover, the nanocomposite could be reused for four cycles for β-agonists and five cycles for dyes with minor loss of adsorption capacity. In addition to its excellent adsorption capacity, the as-prepared nanocomposite exhibited the highest antibacterial activity of 88.94% and 100% against E. coli and S. aureus at the nanomaterial concentration of 75 μg mL−1, as compared to GO showing 31.67% and 26.87% antibacterial activity for E. coli and S. aureus, respectively. Predictably, this magnetic nanomaterial with high adsorption efficiency and excellent antibacterial activity provided a potential method for the removal of pollutants and inactivation of bacterial in wastewater.

Evaluation of microRNAs − 208 and 133a/b as differential biomarkers of acute cardiac and skeletal muscle toxicity in rats

Conventional circulating biomarkers of cardiac and skeletal muscle (SKM) toxicity lack specificity and/or have a short half-life. MicroRNAs (miRNAs) are currently being assessed as biomarkers of tissue injury based on their long half-life in blood and selective expression in certain tissues. To assess the utility of miRNAs as biomarkers of cardiac and SKM injury, male Sprague–Dawley rats received a single dose of isoproterenol (ISO); metaproterenol (MET); allylamine (AAM); mitoxantrone (MIT); acetaminophen (APAP) or vehicle. Blood and tissues were collected from rats in each group at 4, 24 and 48h. ISO, MET, and AAM induced cardiac and SKM lesions and APAP induced liver specific lesions. There was no evidence of tissue injury with MIT by histopathology. Serum levels of candidate miRNAs were compared to conventional serum biomarkers of SKM/cardiac toxicity. Increases in heart specific miR-208 only occurred in rats with cardiac lesions alone and were increased for a longer duration than cardiac troponin and FABP3 (cardiac biomarkers). ISO, MET and AAM induced increases in MyL3 and skeletal muscle troponin (sTnl) (SKM biomarkers). MIT induced large increases in sTnl indicative of SKM toxicity, but sTnl levels were also increased in APAP-treated rats that lacked SKM toxicity. Serum levels of miR-133a/b (enriched in cardiac and SKM) increased following ISO, MET, AAM and MIT treatments but were absent in APAP-treated rats. Our results suggest that miR-133a/b are sensitive and specific markers of SKM and cardiac toxicity and that miR-208 used in combination with miR-133a/b can be used to differentiate cardiac from SKM toxicity.

Long-term effects of metaproterenol in asthmatic children.

Oral metaproterenol was administered daily for 3 months to asthmatic children. The study was designed to determine whether chronic tolerance developed to this drug. Initial and final crossovers on the first 2 and the last 2 days of the investigation to a test dose of metaproterenol and placebo failed to show tolerance as indicated by improvement in lung volumes and dynamic mechanics of breathing after metaproterenol. Forced expiratory volume in 1 sec was the test most consistent in demonstrating bronchodilation; the action of metaproterenol. Forced expiratory volume in 1 sec was the test most consistent in demonstrating bronchodilation; the action of metaproterenol appeared to last at least 5 hours as measured by this test. T of distribution of ventilation, e.g., single- and multiple-breath nitrogen washout tests, were not consistently altered by metaproterenol. These tests did not appear to be sufficiently sensitive to detect improvement even when airway resistance decreased and forced expiratory volume in 1 sec increased toward the normal range.

Computational aided-molecular imprinted polymer design for solid phase extraction of metaproterenol from plasma and determination by voltammetry using modified carbon nanotube electrode.

A molecular imprinted polymer (MIP) was computationally designed and synthesized for the selective extraction of metaproterenol (MTP), from human plasma. In this regards semi empirical MP3 and mechanical quantum (DFT) calculations were used to find a suitable functional monomers. On the basis of computational and experimental results, acrylic acid (AA) and DMSO:MeOH (90:10 %V/V) were found to be the best choices of functional monomer and polymerization solvents, respectively. This polymer was then used as a selective sorbent to develop a molecularly imprinted solid-phase extraction (MISPE) procedure followed by differential pulse voltammetry by using modified carbon nanotube electrode. The analysis was performed in phosphate buffer, pH 7.0. Peak currents were measured at +0.67 V versus Ag/AgCl. The linear calibration range was 0.026-8.0 μg mL(-1) with a limit of detection 0.01 μg mL(-1). The relative standard deviation at 0.5 μg mL(-1) was 4.76% (n=5). The mean recoveries of 5 μg mL(-1) MTP from plasma was 92.2% (n=5). The data of MISPE-DPV were compared with the MISPE-HPLC-UV. Although, the MISPE-DPV was more sensitive but both techniques have similar accuracy and precision.

Effects of an Agonist of β2 Adrenoreceptors on Reactions of Pyramidal Neurons of Area CA1 of the Rat Hippocampus Modified Due to Blocking of GABAA Receptors

On acute slices of the rat brain, we studied, using extracellular recording of orthodromic field dischargers (OFDs), the effects of an agonist of β2 adrenoreceptors, metaproterenol (MPT), and a blocker of GABAA receptors, bicuculline; OFDs were evoked by electrical stimulation of Schaffer collaterals. Isolated application of MPT resulted in some (insignificant) trend toward increase in the intensity of OFDs of pyramidal neurons. Applications of bicuculline induced the appearance of additional spikes (two or even three) in the OFD composition. Upon simultaneous application of MPT and bicuculline, the effect of the latter was preserved and, in some cases, even noticeably enhanced. It is concluded that the agonist of β2 adrenoreceptors MPT does not counteract the events switched on after blocking of GABAA receptors and, probably, even facilitates the corresponding effects.

A spectroscopic and molecular modeling studies of the inclusion complexes of orciprenaline and terbutaline drugs with native and modified cyclodextrins

The inclusion complexation behavior of orciprenaline (ORC) and terbutaline (TER) with α-CD, β-CD, HP-α-CD and HP-β-CD are examined by absorption, fluorescence, life time and molecular modeling methods. ORC and TER forms 1:1 (CD/drug) inclusion complexes in lower CD concentrations and 1:2 (CD/drug) inclusion complexes with higher CD concentrations. The inclusion of both drugs with HP-CDs was stronger than that of native CDs. Both drugs exhibit dual emission (excimer) in the CD solution, whereas in water single emission is seen. The hydrogen bonding and van der Waals interaction between the drugs and the CD plays an important role in the inclusion complexes. Computational results show the side chain of the drugs encapsulated in the CD cavity. The molecular modeling results by PM3 were in good agreement with the experimental results.

Effect of an Agonist of β2 Adrenoreceptors on Inhibition in the Rat Hippocampal CA1 Area Induced by Activation of GABAB Receptors

In experiments on rat brain slices using extracellular recording, we studied the effects of an agonist of β2 adrenoreceptors, metaproterenol (MPT), on reactions of pyramidal neurons of the hippocampal CA1 area induced by activation of GABAB receptors. Isolated application of an agonist of GABAB receptors, baclofen (10 μM), resulted in intense inhibition (by 50% or more during the 1st min of action) of orthodromic field discharges (OFDs) in the pyramidal layer of the above-mentioned area of the hippocampus; the discharges were evoked by electrical stimulation of Schaffer collaterals. On the 3rd to 4th min, OFDs were suppressed nearly completely. After washing out from baclofen, the parameters of the evoked responses never completely restored to the initial level. In all cases, simultaneous application of 150 μM MPT and 10 μM baclofen prevented full manifestation of the inhibitory effect of the latter agent on OFDs of pyramidal neurons. The amplitude of evoked responses decreased, but the relative intensity of inhibition under these conditions during 2-min-long application was significantly lower than that upon isolated action of baclofen. The recovery of the amplitude of evoked responses in the course of washing out under conditions of parallel action of MPT was more rapid and, in some cases, complete. Therefore, our experiments showed that GABAB-ergic inhibitory transmission in the rat hippocampal CA1 area in vitro can be suppressed significantly by the β2 adrenoreceptor agonist.

β2 Adrenoreceptor-Mediated Noradrenergic Effect on GABA-ergic Transmission in the CA1 Zone of the Rat Hippocampus in vitro

Using extracellular recording of evoked potentials, we examined the effect of an agonist of β 2 adrenoreceptors, metaproterenol (MPT), on GABA-ergic transmission in the CA1 zone of slices of the rat hippocampus. Isolated application of GABA evoked in these slices rapid reversible suppression of orthodromic population discharges recorded from the pyramidal layer of the above hippocampal zone after electrical stimulation of Schaffer collaterals in the radial layer. In most cases (13 of 19 preparations), combined application of GABA and MPT interfered with the development of the inhibitory GABA effect. In the case of the action of both of the above agents, the amplitude and duration of evoked responses decreased, but these changes were significantly weaker than those observed upon isolated GABA application. Our experiments showed that the noradrenergic system is capable of modulating GABA-ergic inhibition via β 2 adrenoreceptors and, in such a way, is probably involved in regulation of the inhibition level in the hippocampus. Noradrenaline-induced effects on inhibitory neuronal networks in the hippocampus, similarly to those exerted by several other cerebral neurotransmitter systems, underlie the involvement of the noradrenergic cerebral system in a few physiological processes (emotions, attention, and memory) and are related to some pathological states (Alzheimer’s disease, schizophrenia, epilepsy, etc.).

Influence of β-Adrenergic Agonist (Metaproterenol) and Lysine on Growth, Carcass Quality in Broiler Chickens

An investigation was made to find out the importance of $ adnergenic and lysine on carcass characteristics and blood metabolite of 648 broiler chickens from 2142 days of age. Effect of metaproterenol (a $2adrenergic agonist) and lysine were assessed by mixing them in feed at 0.0, 0.25, 0.50 and 1.00 ppm metaproterenol sulfate and 100%, 115% and 130% of NRC recommended lysine in a 4×3 factorial arrangement of treatments. Chickens were reared under normal condition to 3 week of ages and then randomly allocated to treatments. Each treatment contained 3 pens with 18 birds/pen. Body weight gains (BWG), feed conversion ratio (FCR) abdominal fat pat (AFP) breast weight (BW) were measured. Result indicate that during 4 and 5 week of study using metaproterenol (0.5 ppm ), compare to control group, th th improved BWG (5.1%), carcass efficiency (3.4%) and breast weight (2.2%), breast and thigh muscle protein and depressed abdominal fat (P<0.05). Increasing lysine levels lead to significant increase in body weight gain, carcass weight, carcass efficiency, breast muscle weight (P<0.5), but it has no effect on feed intake, feed conversion ratio, blood metabolites. Data from this experiment suggested that both adding 0.5 ppm $adrenergic agonist metaproterenol sulphate significantly improved birds performance and their carcass quality and the most efficient lysine level for broiler chickens was proved to be 115% NRC recommended.

Effects of two beta-adrenergic agonists on adipose tissue, plasma hormones and metabolites of Moghani ewes

The effects of different levels of dietary terbutaline (T) and metaproterenol (MP) on adipocyte size, plasma hormones and metabolites in Moghani ewes (a native fat-tailed breed) were examined. MP and T were administered at 0, 5 (low dose), 10 (middle dose) and 20 (high dose) mg/kgDM in a concentrate diet. Plasma concentrations of insulin, T 4, triglyceride, cholesterol, high and low density of lipoprotein (HDL and LDL) were measured on days 60 and 90 of fattening period. Adipose tissue samples of fat-tail were taken after slaughtering the animals. Both beta agonists decreased the diameter of fat-tail adipocyte ( P < 0.01). Plasma concentration of insulin was decreased in ewes receiving low dose of MP on days 60 and 90, likewise middle dose of T, low and high doses of MP on day 90 decreased plasma insulin ( P < 0.05). T 4 plasma concentration was increased on day 60 by middle dose of both beta agonists ( P < 0.05), but this effect was not observed on day 90. Treatment of ewes with low and high doses of T and high dose of MP decreased the plasma concentration of triglycerides on day 90 ( P < 0.05). Three levels of MP decreased cholesterol plasma concentration on day 60 ( P < 0.05). This effect was not statistically different on day 90. Low dose of MP decreased plasma HDL on days 60 and 90, likewise middle dose of T and middle and high doses of MP decreased plasma HDL on day 90 ( P < 0.05). Three levels of T and MP on day 60, and low dose of MP on day 90 decreased plasma LDL ( P < 0.05). It is concluded that the measured repartitioning effects of T and MP were within the range of effects observed for thin-tailed sheep and other animals, but their effects on size of fat-tail adipocyte are particularly seen in Moghani ewes.

Catecholaminergic control of NK cell cytolytic activity regulatory factors in the spleen

We examined the effects of norepinephrine (NE), isoproterenol (ISO) and metaproterenol (MP) on natural killer (NK) cell cytolytic activity and on the protein and mRNA levels of the regulatory factors perforin and granzyme B and interferon-γ (IFN-γ) in splenocytes. NE, the β-adrenergic agonist ISO, and the β2-selective-agonist MP all inhibited the protein and mRNA levels of perforin, granzyme B and mRNA levels of IFN-γ. NE inhibited NK cell cytolytic activity as well. Furthermore, MP inhibition of granzyme B mRNA was blocked by the β-antagonist nadolol. These data suggest that NE and β-adrenergic agonists may inhibit NK cell cytolytic activity by regulating the production of perforin, granzyme B, and IFN-γ in splenocytes.

Bronchodilator responses to metaproterenol sulfate among subjects with spinal cord injury.

A previous study using spirometric methods demonstrated that 42% of subjects with tetraplegia experienced significant bronchodilation following inhalation of metaproterenol sulfate (MS). Comparative studies involving subjects with paraplegia were not performed and none has been performed in this population using body plethysmography, a more sensitive method used to assess airway responsiveness. Stable subjects with tetraplegia (n = 5) or paraplegia (n = 5) underwent spirometry and determination of specific airway conductance (sGaw) by body plethysmography at baseline and 30 minutes after nebulization of MS (0.3 mL of a 5% solution). Among subjects with tetraplegia, inhaled MS resulted in significant increases in spirometric indices and sGaw. Among subjects with paraplegia, only sGaw increased significantly, although this increase was considerably less than that seen in subjects with tetraplegia. Our findings indicate that subjects with tetraplegia exhibit greater bronchodilation in response to inhaled MS than do subjects with paraplegia and that sGaw measurements may confer greater sensitivity for assessing bronchodilator responsiveness in tetraplegia.

The effects of a Chinese herb formula, anti-cancer number one (ACNO), on NK cell activity and tumor metastasis in rats

The effects of anti-cancer number one (ACNO), a 19-herb Chinese formula used to treat cancer patients, were studied in F344 rats. In the first study, the number and activity of circulating NK cells were evaluated following 18 days of oral consumption of 0.1, 0.5, or 2 g/kg/day. The second study assessed the effect of ACNO on resistance to metastasis of the MADB106 tumor line, a syngeneic mammary adenocarcinoma that metastasizes only to the lungs and is highly sensitive to NK activity (NKA) in vivo. Resistance to metastasis was assessed under baseline conditions and following the administration of a β-adrenergic agonist, metaproterenol (MP). MP was used to simulate sympathetic response to stressful conditions, and was previously shown to suppress resistance to MADB106 metastasis. The results of the first study indicated a dose-dependent increase in NKA per ml of blood and per NK cell, with no significant changes in blood concentration of NK cells. In the second study, whereas MP caused a 4.5-fold increase in the number of metastases in untreated rats, only a 2.3-fold increase occurred in rats treated with ACNO. No significant improvement in baseline levels of resistance to metastasis was observed. These findings indicate the importance of studying ACNO under stressful conditions in patients with potentially metastasizing tumors. This may prove particularly important during the perioperative period, spanning from the detection of the primary tumor to postoperative treatment. During this critical period, psychological and physiological stress responses are known to cause massive immunosuppression, which was suggested to promote metastatic development.

Timing within the oestrous cycle modulates adrenergic suppression of NK activity and resistance to metastasis: possible clinical implications.

Clinical observations suggest that the rate of metastatic development and long-term mortality following surgery in breast cancer patients is influenced by the menstrual phase during which surgery is conducted. The menstrual cycle is known to modulate various physiological responses and medical conditions that involve adrenergic mechanisms (e.g., asthma). Natural killer activity (NKA), an immune function controlling metastasis, is suppressed following surgery, and in vitro by adrenaline. We therefore hypothesize that the clinical observation may be partly attributable to surgery-induced adrenergic suppression of NK-dependent resistance to metastasis, a suppression that depends on menstrual phase during surgery. To test this hypothesis in rats, 140 F344 females at different phases of their oestrous cycle were injected with a β-adrenergic agonist, metaproterenol (MP) (0.4 or 0.8 mg kg–1, s.c.), or with vehicle, before i.v. inoculation with MADB106 tumour cells. This syngeneic mammary adenocarcinoma line metastasizes only to the lungs, and is highly sensitive to NKA. In a second experiment, the suppression of NKA by MP was studied in vitro in blood drawn at different phases of the oestrous cycle (n = 36). Finally, the effects of stress on the number and activity of NK cells were assessed along the oestrous cycle (n = 71). The findings indicate that the suppressive effects of MP on resistance to metastasis and on NKA, are significantly greater during the oestrous phase characterized by high oestradiol levels (D3/proestrus/oestrus). Similarly, NKA per cell was suppressed by stress only during this phase. In untreated animals, in which inadvertent stress was minimized, no effects of the oestrous cycle on NKA or on resistance to metastasis were evident. These findings indicate that the oestrous cycle modulates adrenergic suppression of NKA and of resistance to metastasis. The relevance of these findings to the above clinical observation, as well as that of our related findings in women from a parallel study, is discussed. © 2000 Cancer Research Campaign http://www.bjcancer.com

Effects of a β2-Agonist on Airway Hyperreactivity in Subjects With Cervical Spinal Cord Injury

Aerosolized ipratropium bromide or orally administered baclofen or oxybutynin chloride (Ditropan) block methacholine-associated airway hyperreactivity in subjects with chronic cervical spinal cord injury (SCI), whereas these agents do not inhibit airway hyperreactivity associated with the inhalation of histamine. The present study was performed to determine whether pretreatment with a beta2-agonist attenuates airway hyperresponsiveness in these subjects. Subjects with chronic cervical SCI previously demonstrating airway hyperreactivity were challenged with methacholine (n = 9) or histamine (n = 16) alone and, on a separate day, 25 min following inhalation of nebulized metaproterenol sulfate. Inhalation of the beta2-agonist was associated with an increase in provocative concentration causing a 20% decrease in FEV1 (PC20) values (geometric mean) from 1.01+/-2.76 to 20.54+/-6.24 mg/mL for methacholine and from 2.29+/-2.26 to 19.82+/-5.93 mg/mL for histamine. No correlation was found between specific PC20 values for individual subjects and percentage improvement in FEV1 (liter) following inhalation of metaproterenol sulfate and between PC20 values and baseline FEV1 percent. These data, combined with findings that patients with chronic high cervical SCI experience increased breathlessness following exposure to exogenous agents, suggest that long-term prophylactic beta2-agonist therapy may reduce respiratory symptoms associated with airway hyperreactivity in these patients.

Patients with stable chronic obstructive pulmonary disease can safely undergo intravenous dipyridamole thallium-201 imaging

Background Patients with chronic obstructive pulmonary disease are usually excluded from intravenous dipyridamole thallium-201 testing. We developed a nurse-administered protocol to screen and pretreat patients so they could be safely tested.Methods and Results We prospectively screened patients referred for intravenous dipyridamole thallium testing and retrospectively reviewed a comparison group of patients who had undergone intravenous dipyridamole testing before our bronchospasm protocol. We studied 492 consecutive patients referred for intravenous dipyridamole thallium testing, separating those with complete data (n = 451) into two groups: group A (n = 72), patients assessed to be at risk for intravenous dipyridamole-induced bronchospasm who received our bronchospasm treatment protocol; and group B (n = 379), patients assessed to be free of risk, who did not receive our bronchospasm protocol. Group C (n = 89) was a retrospective comparison group of patients who had undergone intravenous dipyridamole testing before initiation of the protocol. Patients were considered at risk for an adverse event if any of the following were present: peak flow ≤400 ml at the time of the test (spirometry by nurse) that increased to >400 ml after bronchodilator treatment, wheezing audible with stethoscope, history of chronic obstructive pulmonary disease or asthma or dyspnea on exertion at less than four blocks, or resting respiratory rate >18 breaths/min. The test was considered contraindicated if resting oxygen saturation was <85%, respiratory rate ≥36 breaths/min, or peak flow measured by peak flowmeter <400 ml after bronchodilator inhalant (albuterol or metaproterenol sulfate by spacer) at a dose of up to six puffs. One minute after injections of thallium-201, patients at risk were given 50 mg aminophylline by slow intravenous injection. We looked for major and minor adverse effects and divided them into three categories: (1) minor events (transient headache, abdominal discomfort, or nausea), wheezing (audible by stethoscope but without marked respiratory distress), (2) marked events (severe bronchospasm or severe ischemia defined as wheezing audible with or without stethoscope, respiratory rate >20 breaths/min or increased by 10 from pretest evaluation, oxygen desaturation to <90%, hypoventilation [reduced respiratory rate with decreased mental status], respiratory arrest, chest pain, horizontal ST-segment depression ≥1 mm on the electrocardiogram in any lead, symptomatic hypotension), or (3) other intravenous dipyridamole-induced side effects (persistent headache, dizziness, flushing, nausea, dyspnea, and ischemic chest pain) or anginal equivalent. The protocol properly identified patients with impaired pulmonary function. There was no difference in the frequency of adverse marked events among groups A, B, or C (1% vs 4% vs 2%, p = 0.25). Patients in group A had more minor side effects than those in group B (53% vs 35%, p = 0.004). Specifically, patients in group A were more likely to wheeze (39% vs 1%, p = <0.001), but wheezing in group A was self-limited or responded to treatment as described in the protocol. The prevalence of positive thallium-201 scans in group A (44%) compared with group C (49%) was not different (p = 0.15).Conclusions A nurse-administered risk assessment and pretreatment protocol (1) properly identified patients with impaired pulmonary function, (2) permitted completion of intravenous dipyridamole testing in patients at risk for bronchospasm without an increased incidence of marked adverse events, and (3) did not appear to influence the interpretation of the thallium test. (Am Heart J 1998;136:307-13.)

In Vivo β-Adrenergic Stimulation Suppresses Natural Killer Activity and Compromises Resistance to Tumor Metastasis in Rats

AbstractThe sympathetic nervous system has been implicated in mediating stress-induced alterations in NK cell activity, particularly through stimulation of β-adrenergic receptors. However, because catecholamines induce time-dependent alterations in the distribution of NK cells, the impact of β-adrenergic stimulation on individual NK cell cytotoxicity is not clear, nor are its implications regarding host resistance to metastatic spread. To address these issues, we used the β-adrenergic agonist, metaproterenol (MP), in F344 rats. The number of blood NK cells doubled within 10 min of MP administration and returned to baseline levels within 1 h. By this time, MP suppressed blood NK activity in a dose-dependent manner. Two β-adrenergic antagonists, propranolol, which crosses the blood-brain barrier, and nadolol, which does not, blocked this suppression. Corresponding findings were obtained using an NK-sensitive tumor model, the MADB106. MP caused an up to 10 times increase in the number of tumor cells retained in the lungs 1 day after inoculation and a similar rise in the number of consequent lung metastases detected 3 wk later. These effects were dose dependent and nadolol reversible. NK cells appear to play a central role in mediating the tumor-enhancing effects of MP because their selective depletion nearly abolished this effect. Overall, our findings suggest that independent of the transitory increase in numbers of blood NK cells, in vivo β-adrenergic stimulation suppresses NK activity in the rat. This suppression is induced peripherally and can compromise host resistance to NK-sensitive tumors. Homologies to studies in humans and clinical relevance are discussed.

Interpretation of Positive Results of a Methacholine Inhalation Challenge and 1 Week of Inhaled Bronchodilator Use in Diagnosing and Treating Cough-Variant Asthma

In diagnosing cough due to asthma, methacholine chloride inhalation challenge (MIC) interpreted in a traditional fashion has been shown to have positive predictive values from 60% to 82%. To determine whether any features of positive results of an MIC or the results of a 1-week trial of inhaled beta-agonist therapy were helpful in predicting when the cough was due to asthma. The study design was a prospective, randomized, double-blind, placebo-controlled, crossover format performed in adult, nonsmoking subjects, who were referred for diagnosis and treatment of chronic cough. The subjects had no other respiratory complaints or medical conditions for which they were taking medications, the results of baseline spirometry and chest roentgenograms were normal, and the results of MIC were positive. After obtaining baseline data, including MICs on 2 separate days, objective cough counting, and self-assessment of cough severity using a visual analog scale, subjects were randomized to receive 2 inhalations (1.3 mg) of metaproterenol sulfate or placebo by metered dose inhaler attached to a spacer device every 4 hours while awake. At 1 week, data identical to baseline were collected, and subjects received the other metered dose inhaler for 7 days. At 1 week, data identical to baseline were collected. After completion of the protocol, subjects were followed up in the clinic to observe the final response of the cough to specific therapy. Based on the disappearance of the cough with specific therapy, the cough was due to asthma in 9 of 15 subjects and nonasthma in 6 of 15 subjects. Baseline data were similar between groups. With respect to MICs, there were no significant differences between groups in the cumulative dose of methacholine that provoked a 20% decrease in forced expiratory volume in 1 second from the postsaline baseline value (PD20 values), slopes of dose-response curves, and maximal-response plateaus. Cough severity significantly improved after 1 week of metaproterenol use compared with the severity of the cough at baseline (P = .03) and with placebo (P = .02) only in subjects with asthma. No matter how the results are analyzed, positive MIC results, without observing response to therapy, are only consistent with asthma as the cause of the cough. The results are only diagnostic of asthma when they are followed by a favorable response to asthma therapy. After 1 week of inhaled beta-agonist, only the cough due to cough-variant asthma is significantly better.