Low Doses Of Epinephrine Research Articles

495 STANFORD TYPE-A ACUTE AORTIC DISSECTION: A LIFE-THREATENING EMERGENCY

Abstract Stanford type A acute aortic dissection is a life-threatening cardiological emergency which occurs when an intimal tear in the ascending aorta creates a false lumen within the media refilled by pulsatile blood flow. Some investigators report the immediate mortality to be as high as 40%. Both congenital and acquired conditions can be the cause of an instability of the aortic wall that can lead to dissection. Diagnosis, which requires a high level of suspicion, is usually made with aortic angio-CT. The case we present involves a 62-years old man with a history of hypertension, parossistic atrial fibrillation and familiarity for type B aortic dissection. He called 911 complaining of sudden onset dorsal pain that then irradiated anteriorly to the chest and upwardly to the neck, associated with profuse sweating. An EKG performed at patient's home showed ST elevation in V1 meaningful of right ventricle infarction. Arrived at the Emergency Ward of our hospital arterial pressure was 80/50 mmHg with an HR of 44 bpm. Rapidly, because of the suspect of aortic dissection, an angio-TC was performed showing a type A aortic dissection starting from Valsalva sinuses and extending till common right iliac artery and external left iliac artery including left subclavian artery ostium. The left renal artery originated from false lumen, but patient had a so-called horseshoe kidney. For this reason, the patient was transferred immediately to the cardiac surgery room with indication for Bentall procedure (aortic valve plus ascending aorta replacement with home-made valved Dacron tubular prosthesis), aortic arch repair with supra-aortic vessels debranching and reimplantation and saphenous graft on right coronary artery. During surgery was evident that intimal tear was located immediately after left common carotid artery and right coronary sinus was involved in the dissection thus explaining why right ventricle free wall was visibly hypokinetic. Surgery went without complication and patient entered ICU with circulation supported by a low dose of epinephrine and norepinephrine; respiratory weaning took place in day 1 post-operation. The following days patient developed circumferential pericardial effusion which needed percutaneous subxiphoid drainage despite not being hemodynamically relevant. Echocardiography before discharge showed aortic valve prosthesis and ascending aorta prosthesis well positioned, bi-ventricular normal dimensions and function and organized residual pericardial effusion with fibrin strands. Stanford type A is the most common type of aortic dissection and requires immediate surgical treatment. The Bentall procedure is considered the gold standard for patients needing ascending aorta plus aortic valve replacement. Even though mortality rates remain high for Stanford type A acute aortic dissection, this case shows how is possible to survive from such a life-threatening condition if a prompt and correct diagnosis is made and thanks to flawless surgical operation.

Assessment of postoperative risk factors for EEG abnormalities in routine clinical management after paediatric cardiopulmonary bypass.

The postoperative risk factors for electroencephalogram(EEG) abnormalities after paediatric cardiopulmonary bypass (CPB) remain to be identified. We investigated the characteristics of EEG abnormalities and risk factors in routine clinical management post-CPB. EEG and cerebral oxygen saturation (ScO2) were monitored in 96 patients (aged 3 days, 37 months, median 5 months) for 72 h post-CPB. Clinical measurements included 4-hourly arterial and central venous pressure, arterial blood gases, doses of inotropic and vasoactive drugs, daily C-reactive protein (CRP) and NT-proB-type Natriuretic Peptide (NT-proBNP). Demographics, STAT categories and outcomes (duration of mechanical ventilation,CICU stay) were recorded. Un. Seizures occurred in 20 patients (20.8%) beginning at 0-48 hand lasting 10 min-31 h; background abnormalities occurred in 67 (69.8%) beginning at 0-8 h and lasting 4-48 h. Patients with EEG abnormalities had worse outcomes. In univariable regression, seizures positively correlated with STAT categories, CPB time, temperature, blood pressure, central venous pressure, NT-proBNP, CRP, lactate and epinephrine, negatively with ScO2 and PaCO2 (P < 0.001 for lactate and epinephrine, P < 0.1 for the remaining). The degree of background abnormalities positively correlated with STAT categories, CPB time, operative time, central venous pressure, milrinone, negatively with blood pressure (P = 0.0003-0.087); it negatively correlated with lower dose of epinephrine (P < 0.001) and positively with higher dose (P = 0.03l). In multivariable regression, seizures positively correlated with epinephrine, lactate and temperature; the background abnormality correlations remain significant except for milrinone and operative time (P < 0.001 for epinephrine, P < 0.05 for the remaining). Numerous perioperative risk factors are associated with EEG abnormalities post-CPB. The most significant and consistent risk factor is epinephrine.

Vasopressor and Inotrope Therapy in Cardiac Critical Care.

Patients admitted to the cardiac intensive care unit (CICU) are often in shock and require hemodynamic support. Identifying and addressing the pathophysiology mechanisms operating in an individual patient is crucial to achieving a successful outcome, while initiating circulatory support therapy to restore adequate tissue perfusion. Vasopressors and inotropes are the cornerstone of supportive medical therapy for shock, in addition to fluid resuscitation when indicated. Timely initiation of optimal vasopressor and inotrope therapy is essential for patients with shock, with the ultimate goals of restoring effective tissue perfusion in order to normalize cellular metabolism. Use of vasoactive agents for hemodynamic support of patients with shock should take both arterial pressure and tissue perfusion into account when choosing therapeutic interventions. For most patients with shock, including cardiogenic or septic shock, norepinephrine (NE) is an appropriate choice as a first-line vasopressor titrated to achieve an adequate arterial pressure due to a lower risk of adverse events than other catecholamine vasopressors. If tissue and organ perfusion remain inadequate, an inotrope such as dobutamine may be added to increase cardiac output to a sufficient level that meets tissue demand. Low doses of epinephrine or dopamine may be used for inotropic support, but high doses of these drugs carry an excessive risk of adverse events when used for vasopressor support and should be avoided. When NE alone is inadequate to achieve an adequate arterial pressure, addition of a noncatecholamine vasopressor such as vasopressin or angiotensin-II is reasonable, in addition to rescue therapies that may improve vasopressor responsiveness. In this review, we discuss the pharmacology and evidence-based use of vasopressor and inotrope drugs in critically ill patients, with a focus on the CICU population.

Resuscitative effect of aortic balloon occlusion on traumatic cardiac arrest in swine

Objective To investigate the resuscitation effect of aortic balloon occlusion (ABO) on the traumatic cardiac arrest (TCA) in swine. Methods Twenty-seven male domestic swine weighing (32.7±3.8)kg were utilized. After 40% of estimated blood volume was removed within 20 minutes, the animals were subjected to 5 minutes of untreated ventricular fibrillation and then 5 minutes of cardiopulmonary resuscitation. Additionally, fluid resuscitation was initiated coincident with the beginning of cardiopulmonary resuscitation. The animals were randomly divided into model group (n=12) and ABO group (n=15). Once cardiopulmonary resuscitation was implemented, aortic balloon was concurrently inflated to stop the blood flow of descending thoracic aorta at the level of the diaphragm in the ABO group. In the model group, aortic balloon was placed in the same position without inflation. During cardiopulmonary resuscitation, the changes of coronary perfusion pressure (CPP), forehead's regional cerebral oxygen saturation (rSO2) and pressure of end-tidal CO2 (PETCO2) were continuously monitored, and the rate of return of spontaneous circulation (ROSC), duration of cardiopulmonary resuscitation, number of shocks and dose of epinephrine were recorded. At 5 minutes after successful resuscitation, the levels of arterial blood gas, lactate and jugular venous blood oxygen saturation (SjvO2) were measured. Results Compared with the model group, the values of CPP, rSO2 and PETCO2 during cardiopulmonary resuscitation were significantly increased in the ABO group [CPP: (33.5±5.6)mmHg vs. (23.1±5.2)mmHg at 1 minute, (35.3±6.0)mmHg vs. (26.8±7.4)mmHg at 2 minutes, (36.3±6.3)mmHg vs. (28.2±6.3)mmHg at 3 minutes, (40.1±7.1)mmHg vs. (30.5±6.2)mmHg at 4 minutes, (38.1±7.5)mmHg vs. (29.8±5.3)mmHg at 5 minutes; rSO2: (45.4±5.2)% vs. (39.2±5.1)% at 1 minute, (47.2±3.6)% vs. (42.0±6.4)% at 2 minutes, (47.7±3.0)% vs. (41.5±5.4)% at 3 minutes, (47.0±2.5)% vs. (42.1±5.9)% at 4 minutes, (47.1±2.0)% vs. (41.5±7.4)% at 5 minutes; PETCO2: (17.0±3.5)mmHg vs. (12.7±4.2)mmHg at 1 minute, (18.5±3.7)mmHg vs. (14.5±2.7)mmHg at 2 minutes, (20.7±5.3)mmHg vs. (15.5±3.2)mmHg at 3 minutes, (18.7±4.5)mmHg vs. (14.9±3.5)mmHg at 4 minutes, (18.2±3.2)mmHg vs. (14.5±4.2)mmHg at 5 minutes] (all P<0.05). The rate of ROSC was significantly higher in the ABO group than in the model group[100%(15/15) vs. 75%(9/12)] (P<0.05). Additionally, shorter duration of cardiopulmonary resuscitation, less number of shocks and lower doses of epinephrine were observed in the ABO group when compared with the model group[duration of cardiopulmonary resuscitation: 5(5, 5)minutes vs. 5(5, 12.5)minutes, number of shocks: 1(1, 1)times vs. 1(1, 4)times, dose of epinephrine: 0.62(0.62, 0.74)mg vs. 0.64(0.59, 2.59)mg] (all P<0.05). At 5 minutes after resuscitation, the level of arterial lactate was significantly decreased and the value of SjvO2 was significantly increased in the ABO group compared with the model group[Lactate: (9.6±0.8)mmol/L vs. (10.8±1.4)mmol/L; SjvO2: (50.0±8.6)% vs. (37.9±16.3)%] (both P<0.05). Conclusions In a swine model of TCA, ABO can increase cardiac and cerebral perfusion during cardiopulmonary resuscitation and improve the efficacy of cardiopulmonary resuscitation. It might provide a novel and effective method for the resuscitation of TCA in the clinical setting. Key words: Heart arrest; Cardiopulmonary resuscitation; Aortic balloon occlusion

Change in magnesium concentration in erythrocytes in fish under stress

At present, the role of erythrocyte magnesium in the respiratory processes of fish (and other animals) under conditions of stress load is not known. This article presents the results of research on change in the concentration of magnesium in erythrocytes under the action of stressors of different quality and quantity for bream (Abramis brama L.), silver crucian carp (Carassius auratus gabelio Bloch) and tench, (Tinca tinca L.) in Rybinsk Reservoir. The concentration of magnesium ions was analyzed on an atomic absorption spectrometer AAS-1 manufactured by Carl Zeiss (Germany) in the absorption regime in an air-acetylene flame. For the first time, the dependence of the change in magnesium concentration in erythrocytes on the intensity of the stress load of different nature on the example of fishes was revealed. Weak and moderate strength effects (low doses of epinephrine, norepinephrine, small changes in water temperature, saline injection, prick into the abdominal cavity, short-term removal of fish from the water, short-term keeping of fish in a limited volume of water) increased the concentration of magnesium in erythrocytes up to 2.5 times. At the same time, an increase in the affinity of hemoglobin for oxygen and a decrease in oxygen consumption were observed. However, strong stressors such as catching, transporting fish to the laboratory (representing complex effects of hypoxia, limited water volume, mechanical effects, etc.), as well as a sharp and large change in water temperature, high doses of adrenaline reduced the concentration of magnesium in erythrocytes 3 times. At the same time, the hemoglobin affinity for oxygen decreased and oxygen absorption increased. However, before the death of fish (from exhaustion), with a low level of magnesium in erythrocytes the affinity of hemoglobin for oxygen increased and the intensity of gas exchange decreased. The research conducted allow us to consider the change in the concentration of magnesium ions in erythrocytes – which are positive modulators of the affinity of hemoglobin for oxygen – in fish exposed to stress as one of the mechanisms for reducing the gas exchange intensity for weak and medium short-term stress effects and increasing it for strong short-term ones. Especially important is the role of erythrocyte magnesium as a molecular mechanism for reducing oxygen uptake and, consequently, increasing anabolism and, thus, increasing the growth and development of animals under the action of mild, short-term stressors, i.e. with eustress. In addition, the concentration of magnesium in erythrocytes can serve as an indicator of the state of fish. A high level of this cation in erythrocytes (1.5–2.0 times higher and more than normal) is characteristic for strong, healthy animals in a state of eustress or physiological stress, and extremely low values of this indicator (1.5–2.0 and more times below the norm) are an indicator of reversible or permanent ill-being (distress or pathological stress). Weakened, exhausted animals are not capable of a response to eustress or physiological stress. The possible causes of low magnesium concentrations in human erythrocytes are discussed.

Advanced Atrio-Ventricular Blocks in a Foal Undergoing Surgical Bladder Repair: First Step to Cardiac Arrest?

A 3-day-old Swiss Warmblood colt was diagnosed with uroabdomen after urinary bladder rupture. The foal had classical electrolyte abnormalities (hyponatremia, hypochloremia and hyperkalemia) on presentation. The foal was supported prior to surgery with intravenous fluids and the electrolyte abnormalities were treated with physiologic saline, glucose and insulin. Urine could not be drained from the abdomen prior to surgery because the omentum was continuously occluding the drainage cannula and due to progressive abdominal distension, it was decided to pursue surgery without further correction of electrolyte abnormalities. After induction of anaesthesia, signs of hypoxemia were present. Controlled mandatory ventilation using a pressure-controlled ventilation mode with positive end-expiratory pressure was initiated. Urine was drained from the abdomen by free flow. Atrio-ventricular (AV) blocks unresponsive to intravenous antimuscarinic drugs developed. After low dose of epinephrine and cardiac massage, sinus rhythm was restored. Surgery was completed successfully and the foal recovered from anaesthesia. The postoperative period was uneventful and the foal was discharged from the hospital three days later. Based on a clinical case, the purpose of the manuscript is to provide the clinician with potential causes, prevention and treatment of this already known but rarely observed dysrhythmia which could lead to fatal consequences. Definitions of cardiac arrest and asystole are reappraised. We discuss the fact that advanced AV-blocks should be treated as a cardiovascular emergency with advanced life support. The early recognition of advanced AV blocks is the first step to reduce perioperative mortality and morbidity of foal suffering from uroabdomen.

Emergency Percutaneous Coronary Intervention in Post-Cardiac Arrest Patients Without ST-Segment ElevationPattern: Insights From the PROCAT II Registry.

In a large cohort of out-of-hospital cardiac arrest (OHCA) patients without ST-segment elevation (STE), the study assessed the relationship between the use of an early invasive strategy and patient outcome. Emergent coronary angiogram (CAG) and reperfusion are currently a standard of care in patients resuscitated from an OHCA with ST-segment elevation (STE). However, using a similar invasive strategy is still debated in patients without STE. In the absence of an obvious extracardiac cause, for many years our practice has had to perform an emergent CAG in all OHCA patients (STE and no STE) at admission, followed by percutaneous coronary intervention (PCI) when required. All patients' characteristics are prospectively collected in the PROCAT (Parisian Registry Out-of-Hospital Cardiac Arrest) database. Focusing on non-STE patients and using logistical regression, we investigated the association between early PCI and favorable outcome (cerebral performance category 1 to 2 at discharge) and we searched predictive factors for PCI requirement. During the study period (2004 to 2013), we investigated 958 OHCA patients with an emergent CAG. Amongthem 695 of 958 (73%), mostly male (76%), and average 60 years of age had no evidence of STE on the post-resuscitation electrocardiography. A PCI was deemed necessary in 199 of 695 (29%). A favorable outcome was observed in 87 of 200 (43%) in patients with PCI compared with 164 of 495 (33%) in patients without PCI (p= 0.02). After adjustment, PCI was associated with a better outcome (adjusted odds ratio: 1.80 [95% confidence interval: 1.09 to 2.97]; p= 0.02). The other predictive factors of favorable outcome were a shorter resuscitation length (<20 min), an initial shockable rhythm, and a lower dose of epinephrine during resuscitation (p< 0.001). An initial shockable rhythm (adjusted odds ratio: 2.83 [95% confidence interval: 1.84 to 4.36]; p< 0.001) was the sole independent indicator for PCIrequirement. A culprit coronary lesion requiring PCI was found in nearly one-third of OHCA patients without STE. Inthese patients, emergent PCI was associated with a nearly 2-fold increase in the rate of favorable outcome. These findings support the use of an invasive strategy in these patients, particularly in those resuscitated from a shockable rhythm.

497

Introduction: Although randomized controlled trials have explored the use of epinephrine for out-of-hospital cardiac arrest patients, there remains a lack of research on the benefit and proper dose of epinephrine for in-hospital cardiac arrest patients. Past research has indicated that epinephrine might increase return of spontaneous circulation (ROSC), but has not been shown to significantly improve long-term outcomes. Further, it has been linked to post-resuscitation myocardial dysfunction and reduced cerebral microcirculation, which might be a contributing factor to anoxic brain injury. Therefore, conservative use of epinephrine for in-hospital cardiac arrest patients might increase the survival rate. Methods: I conducted a retrospective chart review to see whether the use of epinephrine affects 24 hour survival after in-hospital cardiac arrest. Clinical, demographic, and treatment data were collected and analyzed for 85 in-hospital cardiac arrest patients. Of these 85 patients, 70 had a non-VF cardiac arrest due to pulseless electrical activity (PEA) or asystole. The non-VF arrest group was divided into three groups: short-duration arrest group (defined by downtime of less than 10 minutes), intermediate-duration arrest group (defined by downtime of 10 to 20 minutes), and long-duration arrest group (defined by downtime of more than 20 minutes). Results: In the non-VF arrest group, 60 percent of patients (42/70) survived 24 hours after cardiopulmonary resuscitation (CPR) initiation. 76 percent of patients (32/42) who survived 24 hours received a low dose of epinephrine (0mg -2mg) as compared to 21 percent (6/28) in the non-survivor group (p–value= 0.0029). In the intermediate-duration arrest group, 71 percent of patients (10/14) who survived 24 hours received a low dose of epinephrine (0mg-2mg) as compared to 10 percent (1/10) in the non-survivor group (p–value=0.0045). In the long-duration arrest group, 50 percent of patients (5/10) who survived 24 hours received a low dose of epinephrine (0mg-2mg) as compared to 19 percent (3/16) in the non-survivor group (p–value=0.1892). Further, 63 percent of patients (15/24) who survived 24 hours in prolonged cardiac arrest (defined by downtime of more than 10 minutes) received a low dose of epinephrine as compared to 15 percent (4/26) in the non-survivor group (p–value=0.0011). Conclusions: The results suggest that the conservative use of epinephrine might be beneficial for in-hospital cardiac arrest patients due to PEA or asystole. Further studies are needed to verify this intriguing preliminary data with more subjects.

Blood Pressure Reduction Induced by Low Dose of Epinephrine via Different Routes in Rats

Epinephrine was recently shown to induce a hypotension episode. Activation of β₂-adrenoceptors with smooth muscle relaxation may be the underlying mechanism. This study investigated the effects of ICI 118551, a β₂-adrenoceptors antagonist, on epinephrine-induced blood pressure reduction via different administration routes in rats. A total of 144 Sprague Dawley rats were equally randomized into 3 groups (intranasal, intravenous, and intra-arterial administration), each with 4 subgroups: saline + saline, ICI 118551 + saline, saline + epinephrine, and ICI 118551 + epinephrine. All rats were anesthetized while spontaneously breathing. Epinephrine was administered at doses of 5 μg/kg via nose, 0.25 μg/kg via femoral vein, and 0.1 μg/kg via aorta. Mean arterial pressure and heart rate were monitored. Mean arterial pressure decreased in all 3 saline + epinephrine subgroups after administration (P < 0.05), whereas it did not in other subgroups. Heart rate had no significant change in all subgroups. Epinephrine-induced blood pressure reduction can be prevented by ICI 118551 in rats, suggesting that the activation of β₂-adrenoceptors contributes to blood pressure reduction.

Effects of Adding Epinephrine to Arthroscopic Irrigation Fluid on Cultured Chondrocyte Survival In Vitro

This study evaluates the effect of low doses of epinephrine contained in common arthroscopic irrigation solutions on viability of in vitro human articular chondrocytes during short-term exposure. Isolated cultured human chondrocytes were treated with culture medium, normal saline solution, 1:300,000 epinephrine solution (equivalent to 10 mL of 1:1,000 epinephrine added to a 3-L saline solution bag), or 1:3,000,000 epinephrine solution (equivalent to 1 mL of 1:1,000 epinephrine added to a 3-L saline solution bag) for 1 hour (N = 84). Twenty-four hours after treatment, chondrocyte viability was measured. Statistical analysis was performed with an analysis of variance with Bonferroni post-test. Chondrocyte viability was significantly better when exposed to normal saline solution alone versus high-dose 1:300,000 epinephrine (87.9% ± 5.4% v 74.6% ± 9.4%, P < .05). Exposure to low-dose 1:3,000,000 epinephrine had significantly better survival versus high-dose 1:300,000 epinephrine (85.0% ± 8.3% v 74.6% ± 9.4%, P < .05). There was no difference in viability after exposure to low-dose 1:3,000,000 epinephrine versus normal saline solution (85.0% ± 8.3% v 87.9% ± 5.4%, P > .05). In vitro, normal saline solution and low-dose 1:3,000,000 epinephrine are significantly less toxic than high-dose 1:300,000 epinephrine to cultured human articular chondrocytes. This in vitro study suggests that arthroscopic irrigation fluid containing 1:3,000,000 epinephrine is less chondrotoxic than solutions containing 1:300,000 epinephrine. Surgeons may wish to use the least amount of epinephrine required for adequate visual clarity during surgery. This study does not establish a contraindication to the use of higher doses of epinephrine.

Abrupt Termination of an Ethanol Regimen Provokes Ventricular Arrhythmia and Enhances Susceptibility to the Arrhythmogenic Effects of Epinephrine in Rats

Pathologists examining victims of sudden unexpected death encounter alcoholics more often than expected; alcohol may play a role in sudden arrhythmic death. Here we determine whether a pattern of alcohol consumption, chronic ethanol intake, and withdrawal increases the incidence of malignant ventricular arrhythmia and modulates susceptibility to the arrhythmogenic potential of sympathetic stimulation from an epinephrine test in rats. Male Wistar rats were treated with a continuous ethanol liquid diet for 7 weeks, and then subjected to 1-day withdrawal or 21-day abstinence. Ventricular ectopy was evaluated by 24-hour electrocardiographic telemetry recording; whole-body sympathetic activation, cardiac sympathovagal balance, and susceptibility to ventricular arrhythmia induced by sympathetic stimulation were evaluated based on blood noradrenalin metabolite concentrations, heart rate variability, and a 3-step epinephrine test. Ventricular arrhythmia and related death were observed only in rats at 1 day of withdrawal, but not in nonalcoholic, continuous ethanol intake or 21-day abstinence rats. One-day withdrawal after a 7-week continuous ethanol regimen elevated circulating noradrenalin metabolite levels and induced cardiac sympathovagal imbalance. Deaths related to the epinephrine test and ventricular arrhythmia induced by low doses of epinephrine were observed only in 1-day withdrawal rats. However, all anomalies were normalized by 21-day abstinence. Abrupt termination of a 7-week continuous ethanol regimen is sufficient to enhance the whole-body sympathetic activation and cardiac sympathovagal imbalance that contribute to ventricular arrhythmia and sudden death in alcoholic rats. Those providing medical care for alcoholics, including in cases of legal imprisonment, should be aware of the possibility of enhanced susceptibility to sudden arrhythmic death due to the abrupt termination of a chronic ethanol regimen.

Dose response of dexamethasone for the enhanced ocular hypotensive response to epinephrine in rabbits with prior dexamethasone treatment.

We have previously shown that administration of epinephrine to the rabbit eye with dexamethasone pretreatment resulted in a significant decrease in intraocular pressure (IOP), compared to the use of epinephrine alone. Furthermore, this decrease in IOP is dose-dependent on epinephrine with the largest response of decrease of IOP occurring at the lower doses of epinephrine. We now extend this study to determine whether the decrease in IOP is dose-dependent on dexamethasone. Rabbit eyes were pretreated with five applications of topical dexamethasone or saline, administered at fifteen-minute intervals. Eyes were then treated with 0.005% epinephrine (0.01% epinephrine bitartrate). IOP was monitored for the next four hours. Different groups of rabbits received varying concentrations of dexamethasone base, from 0.0004% to 0.07% (dexamethasone phosphate), and a dose response curve was obtained. When compared to eyes treated with epinephrine alone, eyes pretreated with dexamethasone showed a significantly greater decrease in pressure at free base dexamethasone concentrations of 0.07%, 0.007% and 0.0007%, with the greatest difference at the 0.007% concentration (mean = 6.8 mm Hg). Similarly, the duration taken for the IOP to return to baseline levels was prolonged in the groups receiving dexamethasone pretreatment. The synergism between dexamethasone and epinephrine in lowering IOP may be a useful alternative in the treatment of ocular hypertension and glaucoma especially using a combination of a low dose of epinephrine with a low dose of dexamethasone.

Modulation of honey bee thermoregulation by adrenergic compounds.

The effects of adrenergic compounds on the thermoregulation of resting honey bees were investigated using a non-traumatizing approach. Bees fed ad lib were treated orally and kept at an ambient temperature of 22 degrees C; the surface thoracic temperature was monitored by infrared thermography. Bees were treated with the adrenergic agonists epinephrine and ephedrine, and with the beta-blocking agent alprenolol. Low doses of adrenergic agonists had no significant effect on thermogenesis, but high doses caused a hypothermia. Alprenolol triggered a dose-dependent hypothermia that was reversed by low doses of epinephrine and ephedrine. Results are discussed with reference to the metabolic and neural adrenergic pathways that may be involved in bee thermoregulation.

Effects of Subanesthetic Concentrations of Isoflurane and Their Interactions with Epinephrine on Acquisition and Retention of the Rabbit Nictitating Membrane Response

Evidence concerning the concentrations of volatile anesthetics that prevent learning and recall is limited. Epinephrine is believed to enable learning during anesthesia. We investigated the effects of isoflurane and its interaction with epinephrine on learning and subsequent retention of the rabbit's classically conditioned nictitating membrane response. In experiment 1, a tone (conditioned stimulus, CS) preceded paraorbital shock (unconditioned stimulus, US) during 60-min daily sessions of 60 presentations of these paired stimuli for 6 days of acquisition training under 0, 0.4%, or 0.8% isoflurane (n = 8, 13, and 9, respectively). Responses were recorded as conditioned responses (CRs) if they occurred during the CS and before the onset of the US. After 1 day of rest, the animals were given 3 days of extinction consisting of 60 presentations of CS-alone and without isoflurane to assess the retention of CRs from acquisition training. In experiment 2, epinephrine in a dose of 0, 0.01, or 0.1 mg/kg was injected subcutaneously in rabbits receiving 0.4% isoflurane. Two types of epinephrine were used, a sustained release form and epinephrine hydrochloride. Acquisition and retention were tested in the same way as in experiment 1. No isoflurane or epinephrine was used during retention testing. Learning was significantly suppressed during 0.4% isoflurane (approximately equal to 0.2 MAC) treatment and eliminated during 0.8% (approximately equal to 0.4 MAC). Information learned during administration of 0.4% isoflurane was not retained (P < 0.05). Although the low doses of epinephrine improved learning during the last day of the acquisition phase (P < 0.05), there were no differences between the treatment groups on any of the remaining acquisition or extinction days. There was no learning during treatment with 0.8% concentration. Even a 0.4% concentration, which allowed some learning, abolished CRs in extinction, perhaps because of state-dependent retrieval. Epinephrine did not alter substantially the rates of CR acquisition or resistance to extinction.

Facilitation of a distributed shuttlebox conditioning with post-training epinephrine in rats

Forty-two male Wistar rats were trained in a two-way active avoidance task during 5 consecutive days (10 trails/session). Immediately after each training session animals were given an injection, ip, of 0.1 mg/kg (EPI 0.1 group) or 0.05 mg/kg (EPI 0.05 group) of epinephrine, or vehicle (Vehicle group). Long-term retention was tested 20 days after the last acquisition session. Our results showed that the lower dose of epinephrine (0.05 mg/kg) led to a significant improvement of acquisition, compared with both the Vehicle and the EPI 0.1 group. On the long-term retention session the level of avoidances in both EPI 0.05 and Vehicle groups was similar to that achieved on the last acquisition session, although differences between groups failed to reach statistical significance. Concerning the EPI 0.1 group, a significant increase in the number of avoidances was observed between the last acquisition session and the long-term retention session. This later result might suggest that the higher dose of epinephrine would need a longer period to manifest its effectiveness. We conclude that the facilitatory effects of epinephrine are dose-dependent, and that under a distributed paradigm epinephrine modulates memory consolidation processes leading to an improvement of the magnitude of learning rather than merely speeding up learning.

Adverse effects of epinephrine in patients with advanced left ventricular dysfunction: analysis of ventriculo-arterial coupling

We examined the response of ventriculo-arterial coupling to epinephrine in 19 patients with normal left ventricular function and with left ventricular dysfunction of various degrees using a conductance catheter. They were divided into three groups: group I, seven patients without left ventricular wall motion abnormality; group II, six patients with ejection fraction of 45–60%; group III, six patients with ejection fraction of 28–40%. Changes in the slope of the end-systolic pressure-volume relationship (end-systolic elastance), the effective arterial elastance, the ratio of effective arterial elastance to end-systolic elastance and the ventricular work efficiency during administration of two different doses of epinephrine (0.05 and 0.1 μg/kg/min) were compared among the three groups. At baseline there were no significant differences among the three groups in the ratio of effective arterial elastance to end-systolic elastance, or ventricular work efficiency. At the lower dose of epinephrine, the mean ratio of effective arterial elastance to end-systolic elastance decreased and the mean ventricular work efficiency increased in any groups. At the higher dose of epinephrine the mean ratio of effective arterial elastance to end-systolic elastance further decreased and the mean ventricular work efficiency further increased in groups I and II. However, the mean ratio of effective arterial elastance to end-systolic elastance did not decrease but the mean ventricular work efficiency even decreased in group III. Thus, in patients with advanced left ventricular dysfunction, even a high dose of epinephrine does not modulate the ventriculo-arterial coupling to increase ventricular work efficiency.

エピネフリンと抗癌剤の腫よう内投与による抗腫よう効果の増強

Modifing effect of epinephrine injected intratumorously (i.t) on the effect of anti-cancer drugs injected i.t was studied using Lewis lung carcinoma. Intratumoral injection of epinephrine (0.05 ml/tumor, 1.4 mg/kg) had no effect on tumor growth delay nor development of metastases. Intratumoral injection of epinephrine (0.028∼1.4 mg/kg) before intratumoral injection of anti-cancer drugs prolonged growth delay, as 2∼3 times in DWA2214R, (-)-(R)-2-aminomethylpyrrolidine (1, 1-cyclobutanedicarboxylato) platinum (II) monohydrate, and as 1.3∼1.4 times in peplomycin or mitomycin C as each drug alone, respectively. Low dose of epinephrine (0.014 mg/kg) enhanced the effect of DWA2114R as well as high dose. However, epinephrine reduced the effect of SMANCS, a derivative of neocarcinostatin conjugated with copolymer of styrene and meleic acid. The mechanism of enhancement effect was discussed. It was considered that epinephrine was useful in intratumoral injection of some drugs.

Cardiovascular Effects of Low-dose Epinephrine Infusions in Relation to the Extent of Preoperative β-Adrenoceptor Blockade

The relationship between the extent of preoperative beta-adrenoceptor blockade and the hemodynamic properties of epinephrine was investigated in patients scheduled for elective myocardial revascularization during the immediate preoperative period under steady-state hemodynamic and anesthetic conditions. Twenty patients had been treated with beta-adrenoceptor blocking drugs for at least 3 weeks before the study; 11 unblocked patients served as control group. The extent of clinical beta-adrenoceptor blockade was quantified using the isoproterenol sensitivity test. The dose of isoproterenol required to increase heart rate by 25 beats per min was defined as the chronotropic dose 25 (CD25), representing the degree of beta-adrenoceptor blockade. Geometric mean CD25 per 70 kg was 3.0 micrograms in the control group and 21.8 micrograms in the patients receiving beta-adrenoceptor blocking drugs. The authors found a significant inverse relationship between CD25 values and changes in cardiac index in response to three epinephrine infusion rates (0.01, 0.02, and 0.04 micrograms.kg-1.min-1), the correlation coefficients being -0.71, -0.81, and -0.86, respectively. Compared to unblocked patients, almost no change, or even a decrease, of the cardiac index was observed at greater degrees of clinical beta-adrenoceptor blockade, particularly in patients receiving nonselective blockers. Moreover, there was a significant linear correlation (r = 0.76-0.86) between CD25 values and the effects of epinephrine on systemic vascular resistance index (SVRI); i.e., SVRI significantly decreased in control patients but markedly increased in patients with high degrees of preoperative beta-adrenoceptor blockade. This unmasked vasoconstrictive response to low doses of epinephrine was observed despite the fact that the majority of our patients had received cardioselective adrenergic blocking drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Decrease in repetitive extrasystole threshold during epinephrine infusion is enhanced in conscious dogs with perinephritic hypertension

Hypertension is associated with myocardial hypertrophy as well as increased adrenergic responsiveness, both of which can predispose to malignant ventricular arrhythmias. This study was designed to test the effects of subpressor doses of epinephrine (0.15 and 0.3 μg/kg/min × 30 min) on vulnerability to ventricular arrhythmia in normotensive and perinephritic hypertensive dogs. Two groups of 6 dogs each were chronically instrumented with aortic catheters to measure mean arterial pressure and bipolar pacing catheters in the apex of the right ventricle to measure repetitive extrasystole threshold, an index of vulnerability to ventricular fibrillation. In the normotensive dogs, the low dose of epinephrine (0.15 μg/kg/min IV) had no significant effects on mean arterial pressure, heart rate or repetitive extrasystole threshold. However, in the hypertensive dogs, the same dose caused a significant 39% increase in heart rate ( p<0.05) and 41% decrease in repetitive extrasystole threshold ( p<0.05). These findings suggest that electrophysiological vulnerability of the myocardium caused by epinephrine infusion is enhanced in the hypertensive animal.

Modulation of memory by post-training epinephrine: involvement of cholinergic mechanisms.

Extensive evidence indicates that memory storage can be modulated by peripheral epinephrine as well as by drugs affecting the muscarinic cholinergic system. Low doses of epinephrine (Epi) facilitate memory while high doses induce amnesia. Retention is enhanced by post-training administration of cholinergic muscarinic agonists and impaired by antagonists. The present experiments examined the interaction of peripheral Epi and cholinergic drugs in memory modulation. Male CFW mice (60 days old) were trained on an inhibitory avoidance response (IA) or a Y-maze discrimination response (YMD), injected (IP) immediately post-training and tested 24 h later. In the Y-maze task, retention was assessed by discrimination reversal training. Findings obtained in the two tasks were comparable. Epi (IA: 3.0 micrograms/kg; YMD: 30.0 micrograms/kg) potentiated the memory-enhancing effect of low doses of oxotremorine (Otm) (IA: 16; YMD: 5.0 micrograms/kg) and physostigmine (Phy) (6.8 and 22.0 micrograms/kg for both IA and YMD). The memory-facilitating effect of Otm (50.0 micrograms/kg) was not blocked by an amnestic dose of Epi (IAT: 0.3 mg/kg; YMD: 1.0 mg/kg). Retention was not affected when these amnestic doses of Epi were administered together with a memory-facilitating dose of Phy (68.0 micrograms/kg). In contrast, atropine (IA: 10.0 mg/kg; YMD: 3.0 mg/kg) completely blocked the facilitatory effect of Epi (IA: 10.0 micrograms/kg; YMD: 300 micrograms/kg). These findings indicate that, when administered in low doses, Epi interacts with Otm and Phy. However, cholinergic drugs can block both the memory-enhancing and the memory-impairing effects of Epi. The findings suggest that Epi may modulate memory through cholinergic systems.