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Biomedical subjects

J D Gallagher

Publications and source records attributed to J D Gallagher.

At least 37 records · Page 2Linked to original sources

The electrophysiologic effects of amiodarone and halothane on canine Purkinje fibers.

Amiodarone may cause serious complications in patients receiving general anesthetics. Potentially adverse electrophysiologic interactions between amiodarone and halothane were studied with the use of standard microelectrode techniques to record intracellular action potentials (APs) from excised canine Purkinje fibers. A second dog (support dog) was anesthetized and a femoral arteriovenous bypass circuit created in which arterial blood from the support dog superfused the Purkinje fiber in a tissue bath. The applicability of this model was established by first comparing the AP effects of halothane during blood perfusion with those in Tyrode's solution. Halothane reduced AP duration (APD; P less than 0.05) during Tyrode's solution superfusion and blood cross-perfusion. After the blood perfusion-Purkinje fiber model was validated, the interaction between halothane and amiodarone was studied using Purkinje fibers from dogs chronically treated with oral amiodarone, superfused with blood from chronically amiodarone-treated support dogs. Amiodarone reduced resting membrane potential and prolonged APD. Depression of AP amplitude and reduction of the maximum rate of increase of phase 0 of the AP (Vmax) by halothane (both P less than 0.05) suggested risk of conduction defects if halothane is administered to patients receiving chronic amiodarone therapy.

Action Potentials↗

The effects of halothane on ventricular tachycardia in intact dogs.

Halothane has either proarrhythmic or antiarrhythmic effects in a variety of clinical circumstances. This investigation tested the hypothesis that halothane would display different effects on ventricular tachycardia (VT) produced by different electrophysiologic mechanisms in intact dogs. Four models of VT produced by abnormal automaticity, reentry, delayed-afterdepolarization-induced triggered activity, and early-afterdepolarization-induced triggered automaticity (groups 1-4, respectively) were studied. In groups 1 and 2, the left anterior descending coronary artery (LAD) was ligated. In group 1 (n = 5), 24 h after LAD ligation and infarction, all dogs demonstrated incessant VT with 94.7 +/- 2.3% of beats of ventricular origin. This ectopy presumably was due to abnormal automaticity. Halothane reduced the frequency of ventricular ectopy until at 2% halothane only 34.8 +/- 15% of beats were of ventricular origin. One week after LAD ligation, programmed stimulation produced nonstimulated extrasystoles of presumably reentrant origin in six dogs. In three, halothane 1% abolished extrasystoles while increasing the ventricular refractory period by 23 +/- 3.8% (P less than 0.05). In the three other dogs, halothane had no effect (two dogs) or worsened the severity of VT (one dog), while the refractory period increased by 7.7% (P greater than 0.05). In group 3 dogs, ouabain was infused until VT secondary to triggered activity occurred. Halothane restored sinus rhythm in 4 of 5 dogs. Overall the percentage of sinus beats increased from 11.1 +/- 2.8 to 97.4 +/- 2.6% when halothane 2% was added during ouabain toxicity. Cesium chloride infusion increased the QT interval and produced complex VT in 5 dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Halothane antagonizes ouabain toxicity in isolated canine Purkinje fibers.

Standard intracellular microelectrode techniques were used to study the effects of halothane on ouabain-induced delayed after depolarizations (DAD) in canine Purkinje fibers. Free running Purkinje fibers were superfused with 2 X 10(-7)M ouabain in Krebs-Henseleit buffer for 30-50 min until DAD appeared. Purkinje fibers were then paced for 20 beats at cycle lengths between 1,000 ms and 200 ms, and the amplitude of the DAD and coupling interval between the DAD and last paced beat were determined. Halothane (0.5, 1, and 2%) was then administered and measurements repeated. Halothane produced dose-related decreases in DAD amplitude without changing DAD coupling interval. The ability of calcium to antagonize the effects of halothane was evaluated by doubling buffer calcium concentration to 5 mM in the presence of halothane 2%. Doubling buffer calcium concentration to 5 mM antagonized the reduction of DAD amplitude caused by halothane. In several preparations, dysrhythmias occurred during ouabain superfusion. Halothane reversibly terminated these arrhythmias. Halothane antagonizes DAD and dysrhythmias induced in vitro by ouabain toxicity. This effect, in part, may account for the apparent effectiveness of halothane against ouabain-induced dysrhythmias in vivo.

Animals↗

A comparison of the electrophysiologic effects of acute and chronic amiodarone administration on canine Purkinje fibers.

The electrophysiologic effects of acutely and chronically administered amiodarone on canine Purkinje fibers were assessed using microelectrode techniques to record intracellular action potentials. Chronically treated dogs received amiodarone for 3 weeks (serum levels, 0.91 +/- 0.09 microgram/ml or 1.42 X 10(-6) M). Acute studies were performed using fibers from untreated dogs superfused for 1 h with 5 X 10(-5) M amiodarone (32 micrograms/ml) in Tyrode's solution (KCl = 4 mM). Acute superfusion shortened the action potential duration to 50 and 90% repolarization by 41 and 8%, respectively (p less than 0.01), and decreased Vmax of phase 0 from 418 +/- 20 to 309 +/- 23 V/s (p less than 0.01) (paced cycle length of 500 ms). Prominent use-dependent depression of Vmax was noted. Acute exposure of fibers from untreated dogs to blood from dogs chronically treated with amiodarone using the blood cross-perfusion technique decreased the action potential duration to 50% repolarization and Vmax, similar to acute exposure in Tyrode's solution. Blood cross-perfusion was used to study fibers from treated dogs superfused with blood from another amiodarone-treated dog. Chronic amiodarone prolonged the action potential duration to 90% repolarization by 13% (p less than 0.02) and did not change Vmax when compared to control studies using fibers obtained from untreated dogs superfused with blood from untreated dogs. Thus, the effects of acutely superfused amiodarone on action potentials of canine Purkinje fibers differ from the effects of chronically administered amiodarone.

Action Potentials↗

Determination of the pulmonary capillary wedge position in patients with giant left atrial V waves.

Thirteen patients with giant left atrial V waves during preoperative cardiac catheterization were admitted into the study group. While awake and breathing spontaneously, simultaneous recordings of electrocardiographic leads II and V5, radial arterial traces, and pulmonary arterial or pulmonary capillary wedge traces were obtained. Measurements were made on four consecutive cardiac cycles in the unwedged and wedged positions for the following intervals: Q wave to the radial arterial upstroke (220 +/- 20 milliseconds) and peak (360 +/- 10 milliseconds), Q wave to the pulmonary arterial upstroke (170 +/- 20 milliseconds) and peak (350 +/- 20 milliseconds), Q wave to the V wave upstroke (280 +/- 20 milliseconds) and peak (570 +/- 20 milliseconds), and QT interval (420 +/- 20 milliseconds). These findings indicate that the radial arterial and pulmonary arterial upstrokes and peaks occur nearly simultaneously. Upon wedging, the V wave upstroke occurs significantly later in the cardiac cycle (P less than .05) compared with the pulmonary arterial upstroke, and the V wave peak occurs significantly later compared with both the pulmonary arterial and the radial arterial peak (P less than .05). A rapid, simple beat-to-beat method for differentiating pulmonary arterial from pulmonary capillary wedge positions in the presence of giant left atrial V waves is the superimposition of the pulmonary arterial trace on the radial arterial trace. When a wedge position is attained, there is an immediate rightward shift in the upstroke and peak of the pulmonary arterial pressure trace, which can be easily identified by observing the relationship between the pulmonary arterial and systemic arterial traces.

Adult↗

Chronotropic response of an activity detecting pacemaker compared with the normal sinus node.

We compared the rate responsiveness of an activity-detecting multiprogrammable, single chamber pacemaker (Medtronic Activitrax) to rate responsiveness of the normal sinus node. This pacemaker changes its basic pacing rate in response to physical activity. The rate responsiveness is programmable by selecting one of three activity thresholds, and one of 10 rate response settings. The study included a group of six normal volunteers and 12 patients implanted with Activitrax to examine the similarity of the pacemaker rate to normal sinus rhythm during acceleration and deceleration. The pacemaker was set to Activity mode, at a basic rate of 60 bpm. In volunteers, the device was externally secured on the chest wall and tested at two programmed settings. When programmed at a high threshold of activity and high rate response in volunteers, there was no significant difference in maximum normal sinus rates and pacemaker rates during arm waving, jumping in place, and walking during stress testing. At a medium activity threshold, the only significant difference occurred during submaximal stress testing, when the maximum sinus rate achieved was 141 +/- 19 bpm and the maximum pacing rate was 105 +/- 8 bpm (p less than .02). The pacemaker behaved in a similar manner in patients, successfully simulating the typical fast acceleration and slow deceleration of a normal sinus node in exercise testing. There was no difference in pacer response when implanted in abdominal or infraclavicular locations. The implanted units have functioned normally over a follow-up period of nine to 22 months. Activitrax can be programmed to achieve physiologic pacing rates in response to normal daily activities with appropriate programming.

Abdomen↗

Simultaneous appearance of endocardial late potentials and ability to induce sustained ventricular tachycardia after procainamide administration.

We describe a patient in whom procainamide induced the appearance of late potentials during intraoperative sinus rhythm electrogram mapping. Only nonsustained ventricular tachycardia (VT) could be induced while off all antiarrhythmic drugs. After administration of the procainamide, programmed stimulation induced sustained VT coincident with the appearance of late potentials during sinus rhythm. The late potential was recorded from the same site, during normal sinus rhythm, where mid to late diastolic activation during VT was recorded, and where cryotermination occurred during cryomapping. We hypothesize that procainamide slowed conduction, manifested as prolongation or appearance of late potentials in sinus rhythm, and facilitated induction of sustained reentrant ventricular tachycardia.

Adult↗

Prophylactic nitroglycerin infusions during coronary artery bypass surgery.

The effects of prophylactic infusion of 1 microgram X kg-1 X min-1 nitroglycerin (NTG) on the incidence of ischemia, hypertension, hypotension and perioperative myocardial infarction were studied in 81 patients during coronary artery bypass grafting (CABG). Forty-one patients (Group 1) received NTG and 40 patients (Group 2) received placebo. All patients received fentanyl for anesthesia and pancuronium. Mean arterial pressure (MAP), pulmonary capillary wedge pressure (PCWP), heart rate (HR), and cardiac output (CO) were measured before and after induction of anesthesia, after intubation, before and after chest incision, after sternotomy, after the pericardium was opened, and during normothermic cardiopulmonary bypass. Myocardial ischemia and infarction were diagnosed from the ECG, hypertension was defined as a 20% increase in MAP, and hypotension was defined as a 20% decrease in MAP compared with preinduction values. No significant differences between Groups 1 and 2 in HR, PCWP, or CO were seen. MAP was significantly lower in Group 1 than Group 2 (P less than 0.05) before chest incision, but increased to levels equal to Group 2 after sternotomy. Hypertension occurred in 32 Group 2 patients and 25 Group 1 patients (0.05 less than P less than 0.1). Group 1 patients had 0.95 +/- 0.14 episodes per patient of hypertension, while Group 2 patients had 2.10 +/- 0.31 episodes (P less than 0.05). Hypotension occurred in 20 Group 1 patients but only six Group 2 patients (P less than 0.05). There was no difference in the incidence of ischemia. In Group 1, nine patients (22%) had ECG changes of ischemia, while 12 patients in Group 2 (30%) had ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗

Electrophysiologic effects of halothane and quinidine on canine Purkinje fibers: evidence for a synergistic interaction.

The authors studied possible interactions between halothane and quinidine on the action potentials of canine Purkinje fibers superfused with Tyrode's solution. Using standard microelectrode techniques and a physiologic pacing rate (2 Hz), halothane in concentrations from 0.5% to 2% decreased the action potential duration to 50% repolarization (ADP50). Total ADP (APD100), in contrast, increased after 1% and 2% halothane. Resting membrane potential (RMP) and action potential amplitude (APamp) increased after 0.5% halothane, but returned to control with higher halothane levels. Conduction time (CT) increased at each halothane level. Pacing at faster (3 Hz) or slower (1 Hz) rates did not markedly alter the effects of halothane. Quinidine 1 X 10(-5)M decreased the phase O upstroke (Vmax) and prolonged APD100 and CT. When halothane was added, RMP and APamp decreased, Vmax decreased further, and APD100 and CT were markedly prolonged. This resulted in conduction block or inexcitability, especially at faster pacing rates (3 Hz). Synergistic interactions between halothane and quinidine were found on RMP, APamp, APD100, and CT. Effects on Vmax, APD50, and action potential duration to 90% repolarization (APD90) were additive. It is concluded that quinidine and halothane act synergistically to decrease action potential amplitude, lower RMP, and prolong conduction. Severe depression of conduction often progressed to conduction block or inexcitability when halothane, 2%, was administered during superfusion with therapeutic concentrations of quinidine.

Action Potentials↗

Halothane metabolism in acyanotic and cyanotic patients undergoing open heart surgery.

The metabolism of halothane was examined in patients with acyanotic and cyanotic congenital heart disease undergoing open heart surgery. Statistically significant (P less than 0.05) pre-surgical differences between acyanotic and cyanotic groups included pH (7.46 +/- 0.02 vs 7.36 +/- 0.02), PaO2 (277 +/- 58 vs 51 +/- 3 torr), O2 saturation (97 +/- 1 vs 74 +/- 4%), and hematocrit (45 +/- 3 vs 58 +/- 2%). Serum fluoride levels were significantly greater in cyanotic than in acyanotic groups 2-4 hours after initial exposure to halothane. Both groups had significant intragroup increases in serum levels of fluoride, bromide, and trifluoroacetic acid. Significant increases in serum levels of lactate dehydrogenase, creatinine phosphokinase, and glutamic oxaloacetate transaminase were observed in both groups, whereas, the cyanotic patients had additional significant increases in blood urea nitrogen and direct bilirubin. The cyanotic group also had higher total and direct serum bilirubin levels than the acyanotic group. Therefore, patients with cyanotic congenital heart disease had greater reductive metabolism of halothane than acyanotics. However, cyanotic and acyanotic patients had essentially similar postoperative derangements in hepatic and renal function.

Cardiopulmonary Bypass↗

Comparison of radial and femoral arterial blood pressures in children after cardiopulmonary bypass.

We compared radial and femoral arterial blood pressures in 29 patients, ranging in age from 1.25 to 17 years, during and after cardiopulmonary bypass for repair of congenital heart disease. Radial mean arterial pressure (MAP) was more than 10% lower than femoral MAP in 17 patients (58%), and in 7 of these patients (24%) radial MAP was more than 20% lower than femoral MAP. In 27 of 29 patients (93%) systolic radial pressure was 10% lower than systolic femoral pressure, and in 20 of these (69%) it was more than 20% lower. The ratio of radial to femoral pressure correlated with MAP (i.e., lower MAP produced greater differences), and the ratio of systolic radial to systolic femoral pressure inversely correlated with systemic vascular resistance index. We found no correlation between femoral-minus-radial pressure difference and postoperative course. These data demonstrate that radial arterial pressure may be misleadingly low in children undergoing operation for correction of congenital cardiac defects.

Adolescent↗

Aspiration during induction of anaesthesia in patients with colon interposition.

The risk of aspiration during induction of anaesthesia in patients with oesophageal disease is not well defined, and controversy exists with respect to patients who have undergone pharyngeal-gastric colon interposition. Excellent gastrooesophageal competence has been documented in many of these patients, and propulsive peristalsis has been demonstrated in interposed colonic segments, suggesting that aspiration risk is low. This report, however, describes recent anaesthetic experiences in two patients with colon interpositions and shows that these patients may have markedly redundant interposed segments that retain food or other particulate residue and, thus, present a significant risk of particulate aspiration. Awake intubation may be the best approach to avoid aspiration in these patients.

Adult↗

Effect of hypothermic cardiopulmonary bypass on nitroprusside metabolism.

At a rectal temperature of 25 degrees C, six patients undergoing hypothermic cardiopulmonary bypass received intravenous infusions of sodium nitroprusside (SNP) at a rate of 7.3 +/- 1.7 micrograms/kg/min for 20 minutes. Total SNP dose per patient was 11.0 +/- 1.1 mg. Blood samples for serum cyanide (CN-), red blood cell cyanide (RBC CN-), and thiocyanate (SCN-) determinations were drawn immediately before SNP infusion. These determinations were repeated at the end of the infusion, at the start of rewarming, and at a rectal temperature greater than 34 degrees C and 1, 4 (five subjects), and 24 hours (three subjects) thereafter. Extracorporeal blood flow was held constant at 2.4 L/min/m2 and mean arterial pressure was maintained between 50 to 100 mm Hg with phenylephrine (3.62 +/- 0.75 mg) during SNP infusion and trimethaphan (37.8 +/- 15.6 mg) after the end of the infusion. There was a significant increase in RBC CN- after the SNP infusion that lasted until the subjects were rewarmed. One subject developed a peak RBC CN- level of 0.8 microgram/ml. Plasma CN- levels changed little throughout and SCN- levels were elevated only after rewarming. The nonenzymatic release of free CN- from SNP was not inhibited by hypothermia, while the enzymatic detoxification of CN- to SCN- may have been delayed.

Aged↗

Hemodynamic and anesthetic effects of sufentanil as the sole anesthetic for pediatric cardiovascular surgery.

The efficacy, safety, and hemodynamic response to 5 micrograms/kg, 10 micrograms/kg, or 20 micrograms/kg of sufentanil and 0.1 mg/kg pancuronium was evaluated in children between 4 and 12 years of age scheduled for open heart surgery. Systolic time intervals, 2-D echocardiograms, systolic blood pressures (SBP), diastolic blood pressures (DBP), and heart rates (HR) were recorded before and after induction of anesthesia. Significant changes 10 min following induction of anesthesia but before intubation included increases in SBP in the 5 micrograms/kg group (P less than 0.01) and in the ratio of preejection period to left ventricular ejection time in the 20 micrograms/kg group (P less than 0.05). Instances of myoclonic jerking and coughing episodes were observed in all three study groups. Following intubation there were significant (P less than 0.05) increases in SBP in all groups, in DBP in the 5 micrograms/kg group, and in HR in the 5 micrograms/kg and 10 micrograms/kg groups. Smaller increases in SBP, DBP, and HR were seen in all groups after skin incision and sternotomy. Mean plasma catecholamine levels showed nonsignificant increases following periods of intraoperative stimulation with wide patient variations. Recovery of responsiveness to command occurred in all groups within one hour from the end of surgery but extubation was impeded by shallow periodic breathing and hypercapnea. The authors conclude that for children undergoing open heart surgery use of sufentanil as a sole anesthetic in bolus form did not provide a reliable depth of anesthesia with any of the induction doses studied.

Anesthesia, Intravenous↗

Effects of advanced age on extravascular lung water accumulation during coronary artery bypass surgery.

Pulmonary extravascular thermal volume (ETVL) accumulation during aortocoronary bypass grafting (CABG) was compared between nine patients (group 1) aged 49 +/- 2 (SEM) yr and nine patients (group 2) aged 65 +/- 1.2 yr, using the thermal-dye technique. Before extracorporeal bypass (ECB), ETVL was significantly correlated with age and mean ETVL was significantly lower in group 1 (3.93 +/- 0.48 ml/kg body weight) than group 2 (5.93 +/- 0.38 ml/kg). During ECB, ETVL rose to 5.15 +/- 0.65 ml/kg in group 1 (p less than .05) and to 6.38 +/- 0.56 ml/kg in group 2. By the next morning, ETVL had returned to pre-ECB levels. Post-ECB, cardiac index decreased in group 1 and colloid osmotic pressure decreased in both groups, but all values returned to pre-ECB levels by the next morning. Although PaO2 had decreased and pulmonary shunt fraction had increased by this time, changes in these variables did not correlate with changes in ETVL. During ECB, ETVL increased transiently but returned to pre-ECB levels by the next morning.

Aged↗

Cryothermal mapping of recurrent ventricular tachycardia in man.

Intraoperative reversible cryothermal mapping of recurrent ventricular tachycardia was performed in seven patients with left ventricular aneurysms with use of a 0 degrees C ice probe. A single, reproducible cryotermination site was found in each patient. The cryotermination site was uniformly located in an area where local electrograms obtained during ventricular tachycardia showed electrical activation during the diastolic portion of the surface electrocardiogram, and was different than the site of activation coincident with the onset of the QRS complex on the surface electrocardiogram (earliest reactivation site or ERS) by 4.5 +/- 2.7 cm (mean +/- SD) in five of seven patients. Sinus rhythm late potentials were recorded at the cryotermination site in five of six patients and from the ERS in one. In five patients, extensive subendocardial resection including both the ERS and cryotermination sites was performed. In two patients only the cryotermination site was excised. In six survivors, including one in whom only the cryotermination site was excised, ventricular tachycardia could not be induced 2 weeks after surgery and has not recurred during the follow-up period of 7 to 17 months (12 +/- 4.5 months, mean +/- SD). Reversible cryothermal mapping may provide additional important information not obtained by standard electrogram mapping of ventricular tachycardia that may help guide surgical therapy of recurrent ventricular tachycardia.

Cold Temperature↗