Epinephrine-treated Groups Research Articles

The Effects of Nitric Oxide Synthase Inhibition on Epinephrine-Induced Arrhythmia and Myocardial Damage

We have recently reported that methylene blue (MethyB) was able to inhibit epinephrine-induced arrhythmias and cardiac muscle injury. In this study, we investigated the effect of nitric oxide synthase inhibition by NG-nitro-L-arginine methyl ester (L-NAME) on cardiac arrhythmias, and myocardial damage induced by epinephrine in rats. Whether nitric oxide inhibition would affect the antiarrhythmic and cardiac protective actions of MethyB was also examined. L-NAME (40 mg/kg), L-arginine (200 mg/kg) + L-NAME, or MethyB (100 mg/kg) + L-NAME were given intraperitoneally (i.p.). Cardiac arrhythmia was then induced with intravenous (i.v.) injection of 10 μg/kg epinephrine. Results showed that epinephrine injection caused marked bradycardia (221.0 ± 1.37 vs. 409.4 ± 3.18 beats/min), shortened QTc interval (0.096 ± 0.0093 vs. 0.177 ± 0.0008 s), increased QRS duration (0.040 ± 0.0035 vs. 0.0185 ± 0.0002 s), decreased R wave amplitude (0.176 ± 0.0051 vs. 0.21 ± 0.0009 mv), ST segment height (-0.026 ± 0.007 vs. -0.002 ± 0.0005 mv), and induced ventricular extrasystoles. L-NAME given to untreated control rats resulted in a decrease in heart rate (288.2 ± 0.88 vs. 409.4 ± 3.18 beats/min), and increased R wave amplitude (0.436 ± 0.004 vs. 0.21 ± 0.0009 mv) compared to controls. L-NAME did not cause extrasystoles in untreated control rats but significantly increased the number of extrasystoles and duration of arrhythmia in the epinephrine-treated group. The administration of L-arginine (200 mg/kg, i.p.) to epinephrine plus L-NAME-treated rats resulted in increased heart rate and markedly decreased the number of extrasystoles and duration of arrhythmia. Methylene blue given at 100 mg/kg to rats treated with epinephrine and L-NAME caused a marked increase in heart rate. It also normalized QRS duration, prevented ST segment depression, markedly suppressed ventricular extrasystoles, and decreased the duration of arrhythmia compared with either epinephrine or L-NAME plus epinephrine-treated groups. Epinephrine injection caused disorganization, and necrosis of cardiac cells, interstitial hemorrhage, and cellular infiltrations. These changes were markedly improved by treatment with either L-NAME or L-NAME/MethyB. These results suggest that (i) inhibiting nitric oxide synthase by L-NAME increases epinephrine-induced arrhythmia which is inhibited by L-arginine or MethyB; (ii) either L-NAME alone or in combination with MethyB prevented cardiac muscle injury induced by epinephrine; (iii) L-NAME did not prevent the cardiac protective and antiarrhythmic actions of MethyB.

The Efficacy of Nebulized Epinephrine in Children with Acute Asthma: A Randomized Double-blind Trial

Introduction: Countries like Bangladesh have seen an increase in the prevalence of bronchial asthma. The goal of the study was to compare the efficacy of nebulized salbutamol and nebulized epinephrine in treating children with acute asthma. Objectives: To assess the clinical improvement of acute bronchial asthma in children following nebulization with salbutamol and epinephrine. Methodology: This random, double-blind clinical trial was conducted in the paediatric department of the Mymensingh Medical College Hospital. Children of either sex with clinical features of acute exacerbation of asthma, an asthma score >5 to 11, an age range from 6 to 12 years, and the ability to measure peak expiratory flow rate (PEFR) were enrolled in this study. Outcomes were observed by measuring PEFR, respiratory rate, pulse rate, and SaO2 and also by determining asthma scores at 15, 35, 55, and 90 min after nebulization at a regular interval at 0, 20, 40, and 60 min. Differences from the base line and differences between both groups were observed. Results: A total of 56 patients with acute asthma were enrolled in this study. Among them, 27 children were in the salbutamol group, and 29 patients were in the epinephrine group. Among baseline characteristics, there was no statistically significant difference (p > 0.05) between the two groups. Asthma score and respiratory rate decreased more in the salbutamol group with time after nebulization, but no statistically significant differences existed for the follow-up at 15, 35, and 55 minutes. A statistically significant increase in asthma score and respiratory rate was seen at 90 minutes of treatment in the salbutamol group. On the other hand, percent of predicted PEFR and SpO2 increased with time in both groups, and no statistically significant differences existed except for SpO2 at 35 min of follow-up in the salbutamol group. The epinephrine-treated group had a higher incidence of side effects as compared with the salbutamol group, but there was no statistically significant difference. Conclusion: Based on this study, in the treatment of asthmatic children with a mild to moderate exacerbation, both nebulized epinephrine and nebulized salbutamol were effective when given in addition to oral steroids.

Safety and Efficacy of Intravesical Epinephrine Instillation in Patients with Intractable Lower Urinary Tract Hematuria – A Novel Approach

To treat intractable hematuria with intravesical instillation of epinephrine. Sixty patients were treated with intravesical instillation of epinephrine at Mackay Memorial Hospital. The control group was composed of 60 patients who were treated with standard-of-care cystoscopic electrocautery fulguration. Under general anesthesia, epinephrine-treated group were injected with 150 mL of diluted epinephrine (1:10,000) through cystoscopy, followed by bladder irrigation with 1:100,000-diluted epinephrine at the ward. Successful hemostasis was defined as hematuria resolution within 1 month post-treatment without additional invasive procedures. In the 60 patients who underwent intravesical instillation of epinephrine, radiation cystitis was the most common etiology (65.0%). Fifty-two patients (86.7%) required no additional therapy within 1 month after one course of intravesical epinephrine instillation treatment compared with 28 patients (46.7%) in the electrocautery fulguration-control group (P <.001). We observed a significant decrease in both the median length of hospitalization (P=.049) and the need for additional invasive procedures (P <.001) in the epinephrine group. In addition, cardiopulmonary monitoring of mean blood pressure, mean heart rate, and mean respiratory rate demonstrated no significant differences after epinephrine treatment. In this study, intravesical instillation of epinephrine was an innovative method of hemostasis for intractable lower urinary tract hematuria with a success rate of 86.7%, compared to 46.7% in the control group, and significantly reduced the number of additional procedures required and the length of hospitalization. It was well-tolerated by all patients, and was a safe and effective treatment modality for intractable hematuria or bladder hemorrhage.

Epinephrine promotes development potential of vitrified mouse oocytes.

Cryopreserved oocytes show low developmental ability. To understand the mechanism underlying their development impairment, study was designed to determine the effect of epinephrine on the in vitro developmental competence of vitrified mouse oocytes. Mature oocytes were vitrified using Open Pulled Straw (OPS) method. The vitrified oocytes were warmed and introduced into M2 medium which contains epinephrine at different concentrations (10(-2), 10(-4), 10(-6), 10(-8) mol L(-1) in an incubator for 1 h. Then the survival rate of the oocytes was evaluated and the subsequent development of oocytes was assessed through in vitro Fertilization (IVF). Furthermore, the levels of intracellular ROS, GSH and the concentration of ATP were determined among 10(-4) mol L(-1) epinephrine-treated group, vitrification group and fresh group. Results showed that vitrified oocytes treated with 10(-4)) mol L(-1) epinephrine had significant higher rates of cleavage (66.4 vs.45.2%) and blastocyst (47.2 vs. 34.7%) than no epinephrine treated group, as well as more blastocyst cells (54.5 vs. 36.8) and lower ratio of apoptotic cells (5.9 vs. 21.5%; p < 0.05). Further experiment found that 10(-4) mol L(-1) epinephrine treatment could significantly reduce intracellular ROS level and enhance cytoplasmic ATP concentration (p < 0.05), but there was no different in GSH level compared to vitrification group. In conclusion, epinephrine could promote vitrified oocytes cryosurvival and their subsequent development ability, which maybe related with the changes of intracellular ROS level and ATP content.

Comparison of norepinephrine-dobutamine to epinephrine for hemodynamics, lactate metabolism, and organ function variables in cardiogenic shock. A prospective, randomized pilot study*

There is no study that has compared, in a randomized manner, which vasopressor is most suitable in optimizing both systemic and regional hemodynamics in cardiogenic shock patients. Hence, the present study was designed to compare epinephrine and norepinephrine-dobutamine in dopamine-resistant cardiogenic shock. Open, randomized interventional human study. Medical intensive care unit in a university hospital. Thirty patients with a cardiac index of <2.2 L/min/m and a mean arterial pressure of <60 mm Hg resistant to combined dopamine-dobutamine treatment and signs of shock. Patients were not included in cases of cardiogenic shock secondary to acute ischemic events such as myocardial infarction. Noninclusion criteria also included immediate indication of mechanical assistance. Patients were randomized to receive an infusion of either norepinephrine-dobutamine or epinephrine titrated to obtain a mean arterial pressure of between 65 and 70 mm Hg with a stable or increased cardiac index. Both regimens increased cardiac index and oxygen-derived parameters in a similar manner. Patients in the norepinephrine-dobutamine group demonstrated heart rates lower (p<.05) than those in the epinephrine group. Epinephrine infusion was associated with new arrhythmias in three patients. When compared to baseline values, after 6 hrs, epinephrine infusion was associated with an increase in lactate level (p<.01), whereas this level decreased in the norepinephrine-dobutamine group. Tonometered PCO2 gap, a surrogate for splanchnic perfusion adequacy, increased in the epinephrine-treated group (p<.01) while decreasing in the norepinephrine group (p<.01). Diuresis increased in both groups but significantly more so in the norepinephrine-dobutamine group, whereas plasma creatinine decreased in both groups. When considering global hemodynamic effects, epinephrine is as effective as norepinephrine-dobutamine. Nevertheless, epinephrine is associated with a transient lactic acidosis, higher heart rate and arrhythmia, and inadequate gastric mucosa perfusion. Thus, the combination norepinephrine-dobutamine appears to be a more reliable and safer strategy.

Hemodynamic effects of an intravenous bolus of epinephrine in healthy rats: A randomized, open-label, controlled pilot study

Background: IV epinephrine is widely used in the treatment of shock to increase blood pressure (BP). However, whether it may also induce hypotension remains unknown. Objective: The aim of this randomized, open-label, controlled pilot study was to observe hemodynamic changes after an IV bolus of epinephrine in healthy rats. Methods: Healthy male Sprague-Dawley rats were randomized to 1 of 5 groups to receive IV epinephrine in doses of 0.5 μg/kg (group 1); 1 μg/kg (group 2); 2 μg/kg (group 3); 4 μg/kg (group 4); or 8 μg/kg (group 5). A sixth group received placebo (0.3 mL of normal saline) and served as the control. BP was monitored continuously. Mean arterial pressure (MAP) and heart rate (HR) were recorded at 0, 5, 15, and 30 seconds and 1, 2, 3, 4, 6, 8, 10, 12, 14, 16, 18, and 20 minutes after administration. The highest mean (SD) systolic BP (SBP) and the lowest mean (SD) diastolic BP (DBP) during this period were also recorded. Hypertension and hypotension were defined as BP increased or decreased > 10% from baseline. Results: Forty-two Sprague-Dawley rats were included in the study. The initial hypertension occurred at ~18 seconds in all epinephrine-treated groups (all, P < 0.01), and the subsequent hypotension occurred at mean (SD) 1.3 (0.5), 2.2 (0.4), 3.0 (0.6), and 3.4 (1.1) minutes in groups 2, 3, 4, and 5, respectively (all, P < 0.01). The highest mean (SD) SBP and the lowest mean (SD) DBP in groups 1, 2, 3, 4, 5, and the control group were 184 (12)/78 (11), 208 (14)/78 (10), 219 (18)/69 (14), 232 (17)/55 (11), 243 (16)/56 (15), and 148 (12)/91 (7) mm Hg, respectively, compared with baseline. HR decreased significantly at 15 seconds in groups 2 and 3, and at 5, 15, and 30 seconds in groups 4 and 5 (all, P < 0.01). One rat in group 4 and 1 rat in group 5 died due to treatment-related cerebral hemorrhage. The control group had no significant hemodynamic changes from baseline. Compared with the control group, MAP increased significantly at 5, 15, and 30 seconds and 1 minute in the epinephrine-treated groups and decreased significantly at 2, 3, and 4 minutes in group 3 and at 2, 3, 4, and 6 minutes in groups 4 and 5 (all, P < 0.05). Conclusions: An IV bolus of epinephrine > 1 μg/kg was associated with biphasic changes in BP, including initial hypertension and subsequent hypotension, in these healthy rats. Future blinded and larger studies using lower doses are needed.

Epinephrine promotes hemostasis in rats with cyclophosphamide-induced hemorrhagic cystitis

Objectives To evaluate the hypothesis that intravesical instillation of epinephrine would attenuate bladder hemorrhage in a rat model of cyclophosphamide (CYP)-induced hemorrhagic cystitis. Methods Female Sprague-Dawley rats were divided into seven treatment groups: positive control (CYP, 150 mg/kg), negative control (epinephrine, 10 μg/mL), intravesical instillation of normal saline (vehicle) and epinephrine (2.5, 5, and 10 μg/mL), and intraperitoneal administration of mesna (50 mg/kg). Rats were killed on days 1, 2, and 3, and the urinary bladders were removed, weighed, and evaluated by gross and histologic analysis. Vesical vascular permeability was determined by wet bladder weight and Evan’s blue dye absorbance. Results Cyclophosphamide administration induced severe hemorrhagic cystitis with marked edema, hemorrhage, and inflammation. All three epinephrine-treated groups had marked attenuation of hemorrhagic cystitis compared with the positive and negative control and mesna-treated groups. Epinephrine was also associated with significant inhibition of tissue edema, indicating decreased vesical vascular permeability. Conclusions In this rat model of CYP-induced hemorrhagic cystitis, intravesical instillation of epinephrine inhibited edema, hemorrhage, and inflammation.

Maintenance of liver graft viability in the state of brain death. Synergistic effects of vasopressin and epinephrine on hepatic energy metabolism in brain-dead dogs.

The influence of vasopressin and epinephrine on hepatic energy metabolism in the state of brain death was assessed by measuring arterial ketone body ratio (AKBR) and hepatic energy charge (EC) in brain-dead dogs. Mean arterial blood pressure (MABP) was significantly decreased from 125.5 +/- 5.5 to 53.4 +/- 1.7 mmHg after complete brain death (P less than 0.01). In the control group AKBR and EC were maintained at near the normal values thereafter, despite marked hypotension. Combined administration of vasopressin and epinephrine sustained AKBR normally and improved MABP above 90 mmHg (P less than 0.01). EC was also maintained within the normal range at 5 hr after initiation of administration of the drugs. By contrast, vasopressin or epinephrine alone maintained AKBR and EC at near the normal values, but improved MABP just slightly to around 60 mmHg (P less than 0.01). As for the volume control, the urinary output was significantly smaller in the vasopressin and epinephrine-treated group than in the control group (P less than 0.05). It is suggested that combined administration of vasopressin and epinephrine has a synergistic effect in improving the hemodynamics and maintenance of the energy status of the liver. This regimen is recommended as a good one for maintaining potential liver donors in the state of brain death.

The Effects of Methoxamine and Epinephrine on Survival and Regional Distribution of Cardiac Output in Dogs with Prolonged Ventricular Fibrillation

This study compares the effects of methoxamine, a pure alpha 1-agonist, and epinephrine on cerebral and myocardial blood flow, central hemodynamics, and survival in a randomized placebo-controlled fashion during prolonged ventricular fibrillation (VF) in a canine model. Twenty-four anesthetized and ventilated adult mongrel dogs were instrumented for regional blood flow determinations using radio-labeled microspheres. The dogs were randomized to receive either 20 mg of methoxamine as a single intravenous bolus or repeated boluses of 0.02 mg/kg of epinephrine, 0.2 mg/kg of epinephrine, or normal saline solution placebo beginning at three minutes following induction of VF and initiation of closed chest cardiac massage (CCCM). Organ blood flow measurements were determined during normal sinus rhythm and after five and 20 minutes of VF. All six dogs receiving methoxamine were successfully resuscitated in contrast to only one in each of the epinephrine-treated groups and none of the dogs receiving placebo (p less than .01). Although epinephrine was associated with significantly higher blood pressures than placebo during cardiopulmonary resuscitation (CPR), blood pressures achieved with methoxamine were significantly higher than those observed in the other three treatment groups (p less than .001). Cerebral blood flow was significantly higher with both methoxamine and high-dose epinephrine (p less than .05). Mean left and right ventricular myocardial flows were highest with methoxamine but this did not achieve statistical significance. In contrast, organ flows measured in the animals receiving the lowest dose of epinephrine were not significantly higher than those associated with placebo. Cardiac output after 20 minutes of CPR was significantly lower with high-dose epinephrine than with methoxamine or placebo (p less than .05). Our results suggest that methoxamine significantly improves regional cerebral blood flow and survival during CPR and although high-dose epinephrine is associated with comparable improvements in regional cerebral blood flow, this treatment is associated with deterioration in central hemodynamics during prolonged VF and does not enhance survival.

Epinephrine and Norepinephrine in Cardiopulmonary Resuscitation: Effects on Myocardial Oxygen Delivery and Consumption

Norepinephrine, an alpha 1,2-beta 1,2-adrenergic agonist, seems to be an alternative to epinephrine, an alpha 1,2-beta 1,2-agonist, for restoration of spontaneous circulation in VF. We therefore studied the effect of epinephrine and norepinephrine on MDO2 and MVO2 using OCCM after five minutes of cardiopulmonary arrest in 21 pigs. After OCCM of three minutes, seven animals each received placebo (controls) or epinephrine (45 micrograms/kg) or norepinephrine (45 micrograms/kg). All drugs were given blindly. At 90 seconds after epinephrine or norepinephrine, mean arterial blood pressure was significantly higher than in the control group. Prior to cardiac arrest, MBF, measured with radioactive microspheres, was 193 +/- 30 ml/min/100 g. During CPR but before drug administration, MBF was 51 +/- 23 in the control group, 71 +/- 10 in the group with epinephrine, and 74 +/- 11 ml/min/100 g in the group with norepinephrine. At 90 seconds after epinephrine, MBF increased to 126 +/- 18 and after norepinephrine to 107 +/- 30 ml/min/100 g (p less than 0.05). Compared to OCCM alone, MDO2 increased from 9.6 +/- 1.7 to 17.1 +/- 3.2 ml/min/100 g after epinephrine and from 9.4 +/- 1.8 to 13.6 +/- 4.2 ml/min/100 g after norepinephrine (p less than 0.05). There was an increase in MVO2 from 4.0 +/- 1.5 to 9.4 +/- 3.0 ml/min/100 g after epinephrine (p less than 0.05), whereas MVO2 increased only from 4.2 +/- 0.8 to 5.1 +/- 2.0 ml/min/100 g after norepinephrine. Because epinephrine led to a greater increase in MVO2 than norepinephrine, the myocardial oxygen ER remained unchanged. The oxygen requirements of the fibrillating heart seemed to be increased via beta 2-adrenergic stimulation. In both the control and epinephrine-treated groups, only three of the seven animals could be successfully resuscitated, whereas all of the animals in the group with norepinephrine survived the 15-minute period of observation. In this model, norepinephrine, in contrast to epinephrine, improves the balance between MDO2 and MVO2 and eases restoration of spontaneous circulation.

Mechanisms of release of atrial natriuretic factor. II. Effect of chronic administration of α- and β-adrenergic and cholinergic agonists on plasma and atrial ANF in the rat

The effect that chronic subcutaneous infusion of α- and β-adrenergic and cholinergic agonists on plasma and atrial ANF was investigated. Isoproterenol, a β-adrenergic agonist, and carbachol, a cholinergic agonist produced a 3-fold increase in plasma ANF levels which were constant until the end of the infusion period. An increased natriuresis was observed in the same groups which was positively correlated with plasma ANF. No differences were observed in atrial content of ANF between the experimental groups. A sharp post-surgery decline in plasma ANF was observed in control, phenylephrine and epinephrine-treated groups which was maintained during the observation period of five days. This suggests that the rise in plasma ANF induced by isoproterenol and carbachol may be secondary to hemodynamic changes and not to direct receptor stimulation, and may play a role in the observed natriuresis. It is also suggested that the depression of plasma ANF may contribute to the well known post-surgery sodium retention.

Effects of epinephrine on metabolism of glucose of normal dogs.

Following the intravenous administration of a tracer dose of C14 glucose, nonradioactive glucose was infused in normal, anesthetized dogs over a 2-hour period with and without the concomitant administration of epinephrine. Blood samples were obtained from the portal vein, hepatic vein, femoral artery and femoral vein at various periods after the start of the infusion. The blood glucose concentration was higher in the epinephrine-treated animals than in the controls and blood glucose radioactivity remained at consistently higher levels in the former group. Blood glucose specific activity, however, dropped faster and attained lower values in the controls. Blood lactate levels were higher in the epinephrine-treated animals. The individual and cumulative specific activities of expired CO2 were appreciably lower in the epinephrine-treated group. The results are interpreted as demonstrating a dual effect of epinephrine; decrease in glucose uptake by tissues and an increase in lactate entry into the blood.