Alexander H. Kulier

Subcutaneous recombinant human erythropoietin and autologous blood donation before coronary artery bypass surgery

Conventional therapies with recombinant human erythropoietin (rHuEPO) to sustain preoperative autologous blood collection entail high doses of the drug at short intervals. To evaluate the efficacy of a single weekly dose of rHuEPO for autologous blood collection, we randomly assigned 24 male patients scheduled for coronary artery bypass surgery to receive 400 IU/kg rHuEPO subcutaneously once a week or iron only. Patients were examined weekly and a total of up to 4 units of autologous blood were obtained if the hemoglobin level exceeded 12 g/dL. Patients receiving rHuEPO had consistently higher hemoglobin values than those receiving iron only (P < 0.001). Consequently, more autologous red cells were obtained from this group (776 +/- 49 mL vs 682 +/- 91 mL; P < 0.05). One patient receiving rHuEPO and eight in the control group required homologous blood at surgery (P < 0.01). These results suggest that 400 IU/kg rHuEPO administered subcutaneously once a week efficiently stimulates erythropoiesis and compensates the hemoglobin decrease after autologous blood donation.

Effects of desflurane, sevoflurane and halothane on postinfarction spontaneous dysrhythmias in dogs

Background: Although desflurane (DES) and sevoflurane (SEV) have desirable features for use in patients with coronary artery disease, their effects on ventricular dysrhythmias following infarction are less known. We therefore examined the effects of DES and SEV upon spontaneous postinfarction ventricular dysrhythmias in dogs, and compared those effects to the well‐established antidysrhythmic effects of halothane (HAL) in this model.

The Response of Anesthetic Agent Monitors to Trifluoromethane Warns of the Presence of Carbon Monoxide from Anesthetic Breakdown

Objective. Trifluoromethane and CO are produced simultaneously duringthe breakdown of isoflurane and desflurane by dry CO2absorbents. Trifluoromethane interferes with anesthetic agent monitoring, andthe interference can be used as a marker to indicate anesthetic breakdown withCO production. This study tests representative types of gas monitors todetermine their ability to provide a clinically useful warning of COproduction in circle breathing systems. Methods. Isoflurane anddesflurane were reacted with dry Baralyme® at 45 °C. Standardizedsamples of breakdown products were created from mixtures of reacted andunreacted gases to simulate the partial degrees of reaction which might resultduring clinical episodes of anesthetic breakdown using 1% or 2% isoflurane and 6% or 12% desflurane. These mixtures were measured by the monitors tested, andthe indication of the wrong agent or a mixture of agents due to the presenceof trifluoromethane was recorded and related to the CO concentration in thegas mixtures. Results. When presented with trifluoromethane fromanesthetic breakdown, monochromatic infrared monitors displayedinappropriately large amounts of isoflurane or desflurane. Agent identifyinginfrared and Raman scattering monitors varied in their sensitivity totrifluoromethane. Mass spectrometers measuring enflurane at mass to charge= 69 were most sensitive to trifluoromethane. Conclusions. Monochromaticinfrared monitors were unable to indicate anesthetic breakdown viainterference by trifluoromethane, but did indicate falsely elevated anestheticconcentrations. Agent identifying infrared and Raman monitors provided warningof desflurane breakdown via the interference of trifluoromethane by displayingthe wrong agent or mixed agents, but may not be sensitive enough to warn ofisoflurane breakdown. Some mass spectrometers provided the most sensitivewarnings to anesthetic breakdown via trifluoromethane, but additional dataprocessing by some patient monitor units reduced their overall effectiveness.

Epinephrine dysrhythmogenicity is not enhanced by subtoxic bupivacaine in dogs.

Since bupivacaine and epinephrine may both precipitate dysrhythmias, circulating bupivacaine during regional anesthesia could potentiate dysrhythmogenic effects of epinephrine.We therefore examined whether bupivacaine alters the dysrhythmogenicity of subsequent administration of epinephrine in conscious, healthy dogs and in anesthetized dogs with myocardial infarction. Forty-one conscious dogs received 10 micro gram centered dot kg-1 centered dot min-1 epinephrine. Seventeen animals responded with ventricular tachycardia (VT) within 3 min. After 3 h, these responders randomly received 1 or 2 mg/kg bupivacaine or saline over 5 min, followed by 10 micro gram centered dot kg-1 centered dot min-1 epinephrine. In the bupivacaine groups, epinephrine caused fewer prodysrhythmic effects than without bupivacaine. VT appeared in fewer dogs and at a later time, and there were more sinoatrial beats and less ectopies. Epinephrine shortened QT less after bupivacaine than in control animals. One day after experimental myocardial infarction, six additional halothane-anesthetized dogs received 4 micro gram centered dot kg-1 centered dot min-1 epinephrine until VT appeared. After 45 min, 1 mg/kg bupivacaine was injected over 5 min, again followed by 4 micro gram centered dot kg-1 centered dot min-1 epinephrine. In these dogs, the prodysrhythmic response to epinephrine was also mitigated by preceding bupivacaine. Bupivacaine antagonizes epinephrine dysrhythmogenicity in conscious dogs susceptible to VT and in anesthetized dogs with spontaneous postinfarct dysrhythmias. There is no evidence that systemic subtoxic bupivacaine administration enhances the dysrhythmogenicity of subsequent epinephrine. (Anesth Analg 1996;83:62-7)

Multiple Agents Potentiate α1-Adrenoceptor–induced Conduction Depression in Canine Cardiac Purkinje Fibers

Background Halothane more so than isoflurane potentiates an &agr;1-adrenoceptor (&agr;1-AR)-mediated action of epinephrine that abnormally slows conduction in Purkinje fibers and may facilitate reentrant arrhythmias. This adverse drug interaction was further evaluated by examining conduction responses to epinephrine in combination with thiopental and propofol, which “sensitize” or reduce the dose of epinephrine required to induce arrhythmias in the heart, and with etomidate, which does not, and responses to epinephrine with verapamil, lidocaine, and l-palmitoyl carnitine, a potential ischemic metabolite. Methods Action potentials and conduction times were measured in vitro using two microelectrodes in groups of canine Purkinje fibers stimulated at 150 pulses/min. Conduction was evaluated each minute after exposure to 5 &mgr;m epinephrine (or phenylephrine) alone or with the test drugs. Changes in the rate of phase 0 depolarization (Vmax) and the electrotonic spread of intracellular current were measured during exposure to epinephrine with octanol to evaluate the role of inhibition of active and passive (intercellular coupling) membrane properties in the transient depression of conduction velocity. Results Lidocaine (20 &mgr;m) and octanol (0.2 mm) potentiated &agr;1-AR–induced conduction depression like halothane (0.4 mm), with maximum depression at 3–5 min of agonist exposure, no decrease of Vmax, and little accentuation at a rapid (250 vs. 150 pulses/min) stimulation rate. Thiopental (95 &mgr;m), propofol (50 &mgr;m), and verapamil (2 &mgr;m) similarly potentiated epinephrine responses, whereas etomidate (10 &mgr;m) did not. Between groups, the decrease of velocity induced by epinephrine in the presence of (10 &mgr;m) l-palmitoyl carnitine (−18%) was significantly greater than that resulting from epinephrine alone (−6%; 0.05 ≤P ≤ 0.10). Current injection experiments were consistent with marked transient inhibition of cell-to-cell coupling correlating with &agr;1-AR conduction depression in fibers exposed to octanol. Conclusions Anesthetic “sensitization” to the arrhythmogenic effects of catecholamines may be a special case of a more general phenomenon by which not only some anesthetics and antiarrhythmic drugs but also possible ischemic fatty acid metabolites potentiate conduction depression due to acute &agr;1-AR–mediated cell-to-cell uncoupling.

Sympathetic and mesenteric venous responses to baroreceptor or chemoreceptor stimulation during epidural anesthesia in rabbits.

Background Baroreceptor and chemoreceptor reflexes maintain homeostasis through mechanisms that involve sympathetic activation. Because sympathetic control of the mesenteric veins plays a central role in hemodynamic responses to stress, the effects of epidural blockade on reflex responses to hypoxia and bilateral carotid occlusion (BCO) were examined by monitoring direct measures of splanchnic sympathetic neural traffic and mesenteric venous capacitance. Methods Rabbits were studied during alpha-chloralose anesthesia and mechanical ventilation. Sympathetic efferent nerve activity to the mesenteric vessels was measured by surgically placed electrodes, and mesenteric venous diameter was measured by videomicroscopy. Heart rate and mean arterial pressure were monitored by intraarterial cannulation. Intraluminal venous pressure was monitored by a servo-null micropressure technique. Responses were recorded during repeated administration of three different stresses, FI O2 = 0% for 40 s, FI O2 = 11% for 2.5 min, and BCO for 60 s. Animals received either thoracolumbar epidural blockade (0.4 ml/kg lidocaine 1.5%; n = 7) or 15 mg/kg intramuscular lidocaine (n = 7). Results Hypoxia and BCO produced sympathetic stimulation and active constriction of mesenteric veins. Epidural anesthesia accentuated the mean arterial pressure decrease from FI O2 of 0%, caused the 11% response to FI O2 to become depressor instead of pressor, and decreased the pressor effect BCO. Sympathetic efferent nerve activity and venous diameter responses to hypoxia and BCO were attenuated or eliminated. Conclusions The hemodynamic effects of hypoxia result from a combination of direct depression and reflex activation. Thoracolumbar epidural anesthesia in rabbits impairs compensatory reflexes invoked by chemoreceptor stimulation and eliminates response to baroreceptor stimulation. Loss of splanchnic control of mesenteric capacitance contributes to the inhibition of the hemodynamic response to hypoxia or BCO during epidural anesthesia in rabbits.

The Effects of the New Antiarrhythmic E 047/1 on Postoperative Ischemia-Induced Arrhythmias in Dogs

UNLABELLED Perioperative malignant ventricular tachyarrhythmias pose an imminent clinical danger by potentially precipitating myocardial ischemia and severely compromising hemodynamics. Thus, immediate and effective therapy is required, which is not always provided by currently recommended IV drug regimens, indicating a need for more effective drugs. We examined antiarrhythmic effects of the new benzofurane compound E 047/1 on spontaneous ventricular tachyarrhythmia in a conscious dog model. One day after experimental myocardial infarction, 40 dogs exhibiting tachyarrhythmia randomly received (bolus plus 1-h infusion) E 047/1 6 mg/kg plus 6 mg x kg(-1) x h(-1), lidocaine 1 mg/kg plus 4.8 mg x kg(-1) x h(-1), flecainide 1 mg/kg plus 0.05 mg x kg(-1) x h(-1), amiodarone 10 mg/kg plus 1.8 mg x kg(-1) x h(-1), or bretylium 10 mg/kg plus 20 mg x kg(-1) x h(-1). Electrocardiogram was evaluated for number of premature ventricular contractions (PVC), normally conducted beats originating from the sinoatrial node, and episodes of ventricular tachycardia. Immediately after the bolus, E 047/1 reduced PVCs by 46% and increased sinoatrial beats from 4 to 61 bpm. The ratio of PVCs to total beats decreased from 98% to 58%. Amiodarone and flecainide exhibited antiarrhythmic effects with delayed onset. Lidocaine did not suppress PVCs significantly, and bretylium was proarrhythmic. The antiarrhythmic E 047/1 has desirable features, suppressing ischemia-induced ventricular tachyarrhythmia quickly and efficiently, and may be a useful addition to current therapeutic regimens. IMPLICATIONS Life-threatening arrhythmias of the heart after myocardial infarction or ischemia may be treated quickly and efficiently by the new drug E 047/1.

Effect of thoracic epidural anesthesia on spontaneous postinfarction ventricular dysrhythmia in awake dogs.

Background and Objectives. Sympathetic neural activity contributes to the genesis of ventricular ectopic activity, particularly in the setting of myocardial ischemia and infarction, so thoracic epidural anesthesia should diminish ventricular ectopy by blocking sympathetic innervation of the heart. However, the possible antidysrhythmic effect of epidural anesthesia has been studied only in the presence of general anesthesia. We therefore examined changes in spontaneous postinfarction ventricular dysrhythmia during thoracic epidural anesthesia in awake dogs. Methods. A survivable myocardial infarction was created by two‐stage ligation of the left anterior descending coronary artery. The following day, multifocal idioventricular tachycardia was the predominant cardiac rhythm. Lidocaine was administered either by thoracic epidural catheter to achieve block of at least the first five thoracic segments or intravenously as a control for direct effects, without concurrent general anesthesia or sedation. Electrocardiographic recordings were analyzed for the number of ventricular ectopic and sinoatrial depolarizations. Results. Epidural and intravenous administration both produced plasma lidocaine concentrations of about 2 mg/mL. There was no change in rhythm following intravenous lidocaine. During epidural anesthesia, total ectopic beats per minute decreased from 167 ± 8 to 135 ± 14 (mean ±SE, P < .05), and the dysrhythmic ratio (ventricular beats/total beats) decreased from 0.93 ± 0.03 to 0.81 ± 0.08 (P < .05). However, ventricular tachydysrhythmia remained the predominant rhythm. Conclusions. Epidural block modestly reduces spontaneous ventricular dysrhythmia in a perioperative setting in dogs following a large myocardial infarction. These findings do not support the choice of thoracic epidural anesthesia for the purpose of preventing or decreasing severe ventricular dysrhythmia.

Preoperative Prostaglandin E1 Therapy in a Patient with Atrial Septal Defect and Predominant Right-to-Left Shunting

A trial septal defects (ASD) are frequently diagnosed in adult patients (l-3), and surgical closure remains the therapy of choice (4, 5). However, the treatment of patients older than 50 years with excessively increased pulmonary artery pressure (PAP) and ASD is still controversial (6). When reversed shunting (right to left atrium) is found, surgical closure of the ASD may lead to postoperative right heart failure due to pulmonary hypertension, and it is not considered a therapeutic choice (7,8). Recently, prostaglandin E, @‘GE,) has been successfully introduced in the therapeutic management of heart transplantations (9), congenital heart disease (lo), and patients with primary pulmonary hypertension. PGE, markedly reduces PAP and pulmonary vascular resistance (PVR) due to a long-lasting vasodilatory effect (9). However, a beneficial effect of PGE, in patients with reversed shunting before ASD surgery has not yet been investigated. We present a patient with a secundum ASD, markedly increased PAP, and predominant right-to-left shunting in whom PGE, was used in conjunction with diuresis and inotropic drugs to stabilize hemodynamic function before surgical closure.