EDTA sample contamination is common and often undetected, putting patients at unnecessary risk of harm.

BACKGROUND: Potassium ethylenediaminetetraacetic acid (EDTA) is a sample tube anticoagulant used for many laboratory analyses. Gross potassium EDTA contamination of blood samples is easily recognised by marked hyperkalaemia and hypocalcaemia. However, subtle contamination is a relatively common, often unrecognised erroneous cause of spurious hyperkalaemia. Potassium EDTA contamination may also cause hypomagnesaemia and hypozincaemia. There are, however, no data on the prevalence of EDTA contamination as a cause of hypocalcaemia, hypomagnesaemia and hypozincaemia. METHODS: Following a recent service evaluation, we measure EDTA in serum samples from patients with unexplained hyperkalaemia (serum potassium > 6.0 mmol/l). In addition, over a 1-month period EDTA concentrations were measured in hypocalcaemic (serum adjusted calcium < 2.0 mmol/l), hypomagnesaemic (serum magnesium < 0.7 mmol/l) and hypozincaemic (serum zinc < 11 micromol/l) serum samples. RESULTS: Ethylenediaminetetraacetic acid contamination was detected in 31 samples, nine of which were detected by our routine screening programme. The remaining 22 samples represented 14.3% (19/133) of hypocalcaemic samples, 4.8% (5/104) of hypomagnesaemic samples and 1.4% (2/139) of hypozincaemic samples. A total of 25/31 (80.6%) of patients were re-bled, of which 23/25 (92%) results normalised. CONCLUSIONS: Factitious hyperkalaemia, hypocalcaemia and hypomagnesaemia caused by potassium EDTA contamination in our studies are relatively common, and if unrecognised may adversely affect patient care and waste scarce healthcare resources. Correct order of draw of blood samples, improved education and routine laboratory screening of EDTA are necessary to prevent and identify EDTA contamination.

Common supraventricular tachycardias: mechanisms and management.

Supraventricular tachycardias (SVTs) are common. Reentry is the most common of the underlying mechanisms. The most frequently observed narrow QRS complex SVTs are atrioventricular nodal reentrant tachycardia and atrioventricular reentrant tachycardia using an accessory pathway. All reentrant tachycardias share certain characteristics that distinguish them from automatic or triggered tachycardias. These characteristics include unidirectional block, delayed conduction, and recovery of excitability within an intact circuit. The characteristics of the reentrant circuit and the physiology of the pathways can be used to define treatments that may be efficacious and/or may have potential risk. Differentiation of SVTs is possible with careful application of monitoring, history taking, and electrophysiologic interventions such as programmed stimulation.

Cost of managing anemia with and without prophylactic epoetin alfa therapy in breast cancer patients receiving combination chemotherapy.

The cost of managing anemia with prophylactic epoetin alfa therapy versus blood transfusions in breast cancer patients receiving combination chemotherapy was studied. A retrospective study of anemia in breast cancer patients treated with four cycles of cyclophosphamide and doxorubicin with fluorouracil (CAF) or without fluorouracil (CA) was conducted. For each cycle of chemotherapy, patients were assessed for fatigue, subsequent blood transfusions administered, and potential response to and adverse effects of blood transfusions. Transfusions were given at the prescriber's discretion rather than in accordance with standard guidelines. The lowest hemoglobin concentration and hematocrit of each patient per cycle were reported. Data on these patients, along with data from published studies of prophylactic use of epoetin alfa, were used in a decision analysis of the costs associated with using epoetin alfa versus red blood cell transfusions to manage anemia. The charts of 50 patients were reviewed. In the study group, the percentage of patients with anemia and the frequency of fatigue rose with each chemotherapy cycle. In general, blood transfusions were not used. The cost of using epoetin alfa prophylactically for all four cycles was estimated at $6483 per patient for the literature-based group versus $169 for the study group. The cost of managing anemia in breast cancer patients was substantially lower when blood transfusions were used than when epoetin alfa was given prophylactically throughout four cycles of therapy with CAF or CA; the absence of standard guidelines for transfusion might have exaggerated the difference in costs.

Pharmacokinetic interaction between ondansetron and cyclophosphamide during high-dose chemotherapy for breast cancer.

PURPOSE: Both ondansetron and cyclophosphamide are thought to be metabolized by hepatic microsomal processes. The purpose of this study was to evaluate the potential pharmacokinetic interactions between ondansetron and high-dose alkylating agent chemotherapy. METHODS: A total of 54 breast cancer patients receiving high-dose cyclophosphamide, cisplatin and carmustine were treated prospectively in four sequential cohorts. Cohorts I and II received continuous infusions of both ondansetron and prochlorperazine, and cohorts III and IV received a continuous infusion of ondansetron alone at the same doses. All patients received lorazepam every 4 h. A group of 75 matched historical controls had received a continuous infusion of prochlorperazine with lorazepam. Pharmacokinetic monitoring of each drug used in the high-dose chemotherapy regimen was conducted. RESULTS: Median AUCs of cyclophosphamide in patients receiving ondansetron (73.6 mg/ml x min) were lower than those of the control patients (88.3 mg/ml x min, n = 75, P = 0.0004), but the median cisplatin AUC was approximately 10% higher and no difference in the disposition of carmustine was demonstrated. Patients treated with ondansetron displayed a higher frequency of headaches than the controls. The frequency of achieving complete emetic control was greater in the ondansetron + prochlorperazine groups compared to the ondansetron alone groups and was greater in both these groups than in the prochlorperazine alone group on the first day of therapy only. CONCLUSION: Ondansetron altered the systemic exposure to cyclophosphamide when these agents were administered concomitantly. Ondansetron did not substantially improve overall emetic control when used alone but may improve control in combination with prochlorperazine. Future randomized studies are needed to delineate the effect of ondansetron on the disposition of the active cyclophosphamide metabolites so that clinical implications can be addressed.

Reduced mortality following bone marrow transplantation for breast cancer with the addition of peripheral blood progenitor cells is due to a marked reduction in veno-occlusive disease of the liver.

Clinical trials involving breast cancer in the Duke University Bone Marrow Transplant Program were evaluated to assess the association between type of hematopoietic support and treatment-related morbidity/mortality. Case histories of patients treated with high-dose chemotherapy and hematopoietic rescue on three separate protocols between 1986 and 1994 were reviewed. This included 307 patients with stage IV disease and 85 patients with high-risk (10 or more positive axillary lymph nodes) stage II or III disease. One hundred and twenty-eight of these patients were rescued with autologous bone marrow (BM) alone and 264 additionally received autologous peripheral blood progenitor cells (PBPC). The 100 day transplant-related mortality rate in those patients who received BM alone was 20.3%, with an overall mortality rate due to the high-dose chemotherapy procedure of 24.2%. The PBPC-treated group experienced a 100 day transplant-related mortality of only 6.1% and an overall trans-plant- related mortality of 10.2%. Sixteen of 31 deaths were attributed to veno-occlusive disease (VOD) in the group that received BM alone compared to only one VOD-related death in the PBPC group. These data demonstrate a marked improvement in transplant-related mortality which is related to the use of PBPC. This effect has been almost entirely due to a reduction in mortality from hepatic veno-occlusive disease.

Evaluation of symptom distress in a bone marrow transplant outpatient environment.

OBJECTIVE: To measure patient perceptions of autologous bone marrow transplantation (ABMT)-associated symptoms in the outpatient setting, assess the efficacy of the established antiemetic protocol, evaluate patient satisfaction, and report patient medication compliance. DESIGN: A prospective, descriptive study of patients with breast cancer who were enrolled in an outpatient ABMT program. SETTING: Duke University Autologous Bone Marrow Transplantation Program. METHODS: Patient perceptions of 12 symptoms were measured by the Symptom Distress Scale (SDS) on the day of admission to the hospital, the day of discharge to the outpatient clinic, after bone marrow reinfusion, and before patient release from the clinic. The number of retching and vomiting episodes was recorded by each patient daily. Patient satisfaction was determined by a standardized personal interview conducted prior to discharge. Patient compliance was assessed by a review of patient medication documentation. RESULTS: Twenty-eight patients were enrolled over 5 months. The median SDS scores for each symptom evaluated revealed that anorexia, nausea, fatigue, insomnia, and bowel problems were the most distressing symptoms patients experienced in the outpatient ABMT program. Scores for pain, negative outlook, cough, diminished concentration, and change in appearance indicated only mild distress associated with these variables. The total number of vomiting episodes ranged from 1 to 33 total episodes per patient per outpatient stay. The percentage of patients experiencing a complete antiemetic response ranged from 24% to 48% over the 4 days after chemotherapy but steadily improved thereafter to a peak of 90% 1 week later. Patient satisfaction results showed that patients preferred being out of the hospital and reported their anxiety controlled although most had some problems with the outpatient clinic or medications required. CONCLUSIONS: Loss of appetite, fatigue, and insomnia have been identified as symptoms that are frequently present during the course of the outpatient ABMT program. Mild, intermittent nausea persists in the outpatient setting for up to 9 days after bone marrow transplant despite continuous combination antiemetic therapy. Patient interviews confirmed the belief that patients enjoy being out of the hospital. Medication compliance is more than 90% in this structured outpatient setting.

The pharmacologic effects of recombinant, human colony-stimulating factors and their modulation by theophylline.

STUDY OBJECTIVES: To investigate the effect of colony-stimulating factors (CSFs) on drug metabolism using theophylline as a substrate (phase I), and to evaluate the influence of theophylline on endogenous serum cytokine concentrations (phase II). DESIGN: Open-label, prospective study. SETTING: The bone marrow transplant unit of a tertiary university teaching hospital. PATIENTS: Thirty-seven women with breast cancer (28 phase I, 9 phase II). INTERVENTIONS: Patients received aminophylline 0.58 mg/kg either as a 30-minute intravenous infusion before receiving recombinant CSFs or after several days of CSF therapy, just before high-dose chemotherapy (phase I) or as a continuous intravenous infusion after bone marrow transplantation (phase II). MEASUREMENTS AND MAIN RESULTS: Clearance of theophylline was significantly higher after CSF administration (0.76 vs 0.99 ml/min/kg, p = 0.019). Continuous infusion of aminophylline resulted in elevations of serum macrophage-CSF and interleukin 6. CONCLUSIONS: Administration of CSFs before autologous bone marrow transplantation for priming progenitor cells may alter drug metabolism. Studies should be conducted to evaluate the potential effects of CSFs on the disposition of chemotherapeutic agents.

Peripheral blood progenitor cell transplantation for breast cancer: pharmacoeconomic considerations.

The recent observation that mobilized peripheral blood progenitor cells (PBPCs) can be used as a source of hematopoietic support has had a major effect on the cost and morbidity associated with bone marrow transplantation in patients with breast cancer. The pharmacoeconomic impact of this new technology is especially evident when secondary costs are analyzed. We see a reduction in hospital stay, decreased use of resources such as platelet transfusions and antibiotics, and long-term quality life-years gained for those patients benefiting from this therapy. Experienced transplant centers have found that the direct cost of high-dose chemotherapy using filgrastim and PBPC support is reduced as much as 50% to the patient or their insurance company. Pharmacists will play a key role in optimizing the benefits of PBPC transplantation, particularly because this therapy is moving to the outpatient arena. This article will review the pharmacoeconomic impact of PBPC transplantation primarily in terms of secondary cost measures and quality of life and discuss the limited direct cost data available and the impact of this therapy on pharmacy practice.

Randomized, double-blind comparison of a prochlorperazine-based versus a metoclopramide-based antiemetic regimen in patients undergoing autologous bone marrow transplantation.

BACKGROUND: Highly emetogenic combination alkylator therapy is routinely used in autologous bone marrow transplantation for treatment of eligible patients with solid tumors. Antiemetic therapy remains less than optimal in this setting. METHODS: One hundred twenty-six patients with cancer receiving high dose cisplatin, cyclophosphamide, and carmustine with autologous bone marrow support were randomized to receive one of four double-blinded antiemetic regimens: 4-day continuous infusion prochlorperazine (6 mg/m2 intravenous [i.v.] loading dose followed by 1.5 mg/m2/hour) or metoclopramide (80 mg/m2 iv loading dose followed by 20 mg/m2/hr) each with either dronabinol 5 mg/m2 or placebo capsules for two doses before carmustine on the last day of chemotherapy. All subjects received scheduled lorazepam and diphenhydramine throughout the 4-day study period. Efficacy was measured by the Emetic Process Rating Scale and the Rhodes Index of Nausea and Vomiting (INV) Form 2. RESULTS: One hundred six patients completed the study and were fully evaluable. The median number of emetic episodes on the metoclopramide study arm were: 1 (0-7, day -6), 1 (0-6, day -5), 2 (0-9, day -4), and 2 (0-10, with dronabinol day -3) or 2 (0-7, no dronabinol day -3) and on the prochlorperazine study arm were: 4 (0-12, day -6), 0 (0-8, day -5), 0 (0-12, day -4) and 2.5 (0-9, with dronabinol day -3) or 2 (0-12, no dronabinol day -3). Metoclopramide was significantly better on the first day of therapy (day -6, P < .002) and prochlorperazine was significantly better on the third day of therapy (day -4, P < 0.002). There was no significant difference among any of the four arms on the last day of chemotherapy (day -3), or when the median number of emetic episodes over the total study period were compared. The patients' assessment of nausea, vomiting, and retching on the INV Form 2 was consistent with the observer ratings. Toxicities requiring dose reduction or discontinuation of antiemetic drugs included diarrhea, cardiac arrhythmias, sedation, anxiety, and akathisia. CONCLUSIONS: Both metoclopramide and prochlorperazine in combination with lorazepam and diphenhydramine offer good control of nausea and vomiting although the sedation and low risk for cardiac toxicity limit the regimen to an inpatient setting with close monitoring. No regimen was clearly superior during the entire treatment period but prochlorperazine offered more consistent control after the first day.

Disposition of recombinant human granulocyte-macrophage colony-stimulating factor in patients receiving high-dose chemotherapy and autologous bone marrow support.

Recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) produces dose-related therapeutic and toxic effects; however, relationships between its pharmacokinetics and pharmacodynamics have not been extensively evaluated. The following studies were undertaken to investigate patterns in the disposition of rHuGM-CSF administered after high-dose chemotherapy (cyclophosphamide, cisplatin, carmustine) and autologous bone marrow support. Continuous 14 or 21 day intravenous infusions or daily 4-hour infusions were studied at doses of 1.2 to 19.2 micrograms/kg/d. GM-CSF was measured by an enzyme-linked immunosorbent assay from serum and urine samples collected throughout drug administration. Pharmacokinetic parameters were determined by compartmental (4-hour infusions) or noncompartmental methods (continuous infusions). GM-CSF was rapidly eliminated from the serum. Average systemic exposure increased with dose, although wide interpatient variability was evident. Approximately one half of the patients receiving continuous infusions demonstrated increasing GM-CSF clearance that corresponded to the appearance of white blood cells in the periphery. Conversely, clearance decreased in those experiencing renal dysfunction during the infusion. The percentage of a GM-CSF dose found in 24-hour urine collections was substantially reduced in the latter group. A subset of patients who developed renal dysfunction also experienced significant hypotension. Rapidly increasing serum GM-CSF concentrations corresponded to the hypotensive episodes. GM-CSF serum concentration monitoring may be useful for evaluation of therapeutic and toxic effects in patients receiving high-dose chemotherapy with autologous bone marrow support.

Selective transcatheter ablation of the fast and slow pathways using radiofrequency energy in patients with atrioventricular nodal reentrant tachycardia.

BACKGROUND: The safety and efficacy of selective fast versus slow pathway ablation using radiofrequency energy and a transcatheter technique in patients with atrioventricular nodal reentrant tachycardia (AVNRT) were evaluated. METHODS AND RESULTS: Forty-nine consecutive patients with symptomatic AVNRT were included. There were 37 women and 12 men (mean age, 43 +/- 20 years). The first 16 patients underwent a fast pathway ablation with radiofrequency current applied in the anterior/superior aspect of the tricuspid annulus. The remaining 33 patients initially had their slow pathway targeted at the posterior/inferior aspect of the right interatrial septum. The fast pathway was successfully ablated in the initial 16 patients and in three additional patients after an unsuccessful slow pathway ablation. A mean of 10 +/- 8 radiofrequency pulses were delivered; the last (successful) pulse was at a power of 24 +/- 7 W for a duration of 22 +/- 15 seconds. Four of these 19 patients developed complete atrioventricular (AV) block. In the remaining 15 patients, the post-ablation atrio-His intervals prolonged from 89 +/- 30 to 138 +/- 43 msec (p less than 0.001), whereas the shortest 1:1 AV conduction and effective refractory period of the AV node remained unchanged. Ten patients lost their ventriculoatrial (VA) conduction, and the other five had a significant prolongation of the shortest cycle length of 1:1 VA conduction (280 +/- 35 versus 468 +/- 30 msec, p less than 0.0001). Slow pathway ablation was attempted initially in 33 patients and in another two who developed uncommon AVNRT after successful fast pathway ablation. Of these 35 patients, 32 had no AVNRT inducible after 6 +/- 4 radiofrequency pulses with the last (successful) pulse given at a power of 36 +/- 12 W for a duration of 35 +/- 15 seconds. After successful slow pathway ablation, the shortest cycle length of 1:1 AV conduction prolonged from 295 +/- 44 to 332 +/- 66 msec (p less than 0.0005), the AV nodal effective refractory period increased from 232 +/- 36 to 281 +/- 61 msec (p less than 0.0001), and the atrio-His interval as well as the shortest cycle length of 1:1 VA conduction remained unchanged. No patients developed AV block. Among the last 33 patients who underwent a slow pathway ablation as the initial attempt and a fast pathway ablation only when the former failed, 32 (97%) had successful AVNRT abolition with intact AV conduction. During a mean follow-up of 6.5 +/- 3.0 months, none of the 49 patients had recurrent tachycardia. Forty patients had repeat electrophysiological studies 4-8 weeks after their successful ablation, and AVNRT could not be induced in 39 patients. CONCLUSIONS: These data suggest that both fast and slow pathways can be selectively ablated for control of AVNRT: Slow pathway ablation, however, by obviating the risk of AV block, appears to be safer and should be considered as the first approach.

Unexplained syncope evaluated by electrophysiologic studies and head-up tilt testing.

OBJECTIVE: To determine the clinical characteristics of subgroups of patients with unexplained syncope having electrophysiologic studies and head-up tilt testing and to assess the efficacy of various therapies. DESIGN: Retrospective study. SETTING: Inpatient services of a tertiary referral center. PATIENTS: Eighty-six consecutively referred patients with unexplained syncope. MEASUREMENTS: All patients had electrophysiologic examinations. Patients with negative results subsequently had head-up tilt testing. MAIN RESULTS: Twenty-nine (34%) patients (group 1) had abnormal electrophysiologic results, with sustained monomorphic ventricular tachycardia induced in 72%. Thirty-four (40%) patients (group 2) had syncope provoked by head-up tilt testing. The cause of syncope remained unexplained in 23 (26%) patients (group 3). Structural heart disease was present in 76%, 6%, and 30% of groups 1, 2, and 3, respectively. In group 1, pharmacologic or nonpharmacologic therapy was recommended based on electrophysiologic evaluation. All group 2 patients had negative results on head-up tilt testing while receiving oral beta blockers (27 patients) or disopyramide (7 patients). Group 3 patients did not receive any specific therapy. During a median follow-up period of 18.5 months, syncope recurred in 9 (10%) patients. CONCLUSIONS: The combination of electrophysiologic evaluation and head-up tilt testing can identify the underlying cause of syncope in as many as 74% of patients presenting with unexplained syncope. Therapeutic strategies formulated according to the results of these diagnostic tests appear to prevent syncope effectively in most patients.

Effect of recombinant human granulocyte-macrophage colony-stimulating factor on hematopoietic reconstitution after high-dose chemotherapy and autologous bone marrow transplantation.

Recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF) has been reported to increase the leukocyte count in subhuman primates subjected to total-body irradiation and in patients with the acquired immunodeficiency syndrome. We administered this substance to 19 patients with breast cancer or melanoma treated with high-dose combination chemotherapy and autologous bone marrow support. Groups of three or four patients were treated with 2.0, 4.0, 8.0, 16.0, or 32.0 micrograms per kilogram of body weight per day of glycosylated rHuGM-CSF by continuous intravenous infusion for 14 days, beginning three hours after bone marrow infusion. Total leukocyte and granulocyte recovery was accelerated in these patients as compared with 24 historical controls matched for age, diagnosis, and treatment. Leukocyte counts (mean +/- SD) obtained 14 days after transplantation were 1511 +/- 1003 per microliter in patients given 2 to 8 micrograms per kilogram per day, 2575 +/- 2304 in those given 16 micrograms, and 3120 +/- 1744 in those given 32 micrograms, as compared with 863 +/- 645 per microliter in the controls. No consistent effect on platelet counts was noted. Toxic effects were generally mild and not clearly dose-related in patients given 2 to 16 micrograms per kilogram per day. Edema, weight gain, or myalgias occurred in all patients given 32 micrograms per kilogram; marked weight gain, generalized edema, pleural effusions, and hypotension developed in two patients, one of whom also had acute renal failure. Our results indicate that rHuGM-CSF can accelerate myeloid recovery after high-dose chemotherapy and autologous bone marrow transplantation, over a range of doses that can be tolerated. In this setting the ability to increase the dose is limited by the development of myalgias and fluid retention.

Normal electrophysiologic responses of the human heart.

A thorough understanding of physiologic behavior of the human conduction system is essential to define the abnormalities. This article deals with normal responses of the cardiac conduction system to both antegrade and retrograde direction. Responses to electrical as well as mechanical stimulation are discussed.

Antineoplastic activity of a series of boron analogues of alpha-amino acids.

A series of amine cyanoboranes, amine carboxyboranes, and boron analogues of alpha-amino acids have been investigated for antineoplastic activity against the growth of Ehrlich ascites cells. Additional studies demonstrated that the boron analogues inhibited DNA and RNA synthesis at 300 microM. The suppression of DNA synthesis of Ehrlich ascites cells correlated with the reduction of DNA polymerase, 5-phosphoribosyl-1-pyrophosphate amidotransferase, and dihydrofolate reductase activities afforded by the boron compounds. These derivatives did not suppress protein synthesis, thymidylate synthetase, or thymidine monophosphate kinase activities as previously reported for some boron antineoplastic agents.

Antitumor agents 68: effects of a series of helenalin derivatives on P-388 lymphocytic leukemia nucleic acid and protein synthesis.

A series of analogues related to helenalin demonstrated moderate capability for inhibiting the growth of murine P-388 lymphocytic leukemia cells in vivo and in vitro. The growth inhibition correlated with suppression of both DNA and protein synthesis in P-388 cells. The inhibition of protein synthesis occurred at a relatively low concentration and appeared to occur at the level of initiation. The suppression of DNA synthesis in P-388 cells correlated positively with inhibition of inosine 5'-monophosphate dehydrogenase activity. Although nuclear and alpha DNA polymerase activities were suppressed by certain analogues, the inhibition of the polymerases did not correlate positively with DNA synthesis inhibition and, furthermore, the magnitude of suppression of DNA polymerase activity did not appear to be sufficient to account for the observed suppression of DNA synthesis in P-388 cells.

Hypolipidemic activity of tetrakis-mu-(trimethylamine-boranecarboxylato)-bis(trimethylamin e- carboxyborane)-dicopper(II) in rodents and its effect on lipid metabolism.

A binuclear copper(II) complex was shown to have potent hypolipidemic activity in rats and mice at low doses, i.e., 2.5-10 mg/kg/d. The agent moderately lowered liver ATP-dependent citrate lyase, acetyl CoA synthetase, and phosphatidate phosphohydrolase activities in vivo. The appetite of the animal was reduced by drug treatment, and orally administered cholesterol absorption from the intestine was markedly lowered. Higher lipid levels were found in the chyme and the feces, indicating accelerated excretion of lipids by the drug, probably via the biliary route. Organs, e.g., liver and small intestine, as well as serum lipoprotein levels, demonstrated lower lipid content after drug administration. Thus, this chemical class of agents may have potential as a hypolipidemic agent in humans.

An electrocardiographic--electrophysiologic correlation of aberrant ventricular conduction in man.

Surface electrocardiographic (ECG) features of aberrant ventricular conduction (VAb) were correlated with His bundle electrograms (HBE) in 16 patients to assess the usefulness and limitations of ECG in the diagnosis of VAb. VAb was studied in these patients using the technique of atrial premature stimulation (A2) during paced atrial cycle lengths (A1). VAb in the form of right bundle branch block (RBBB) was noted in 12/16 patients, left (L) BBB in 7/16, whereas 3/16 showed R as well as LBBB following A2. The longest atrial coupling (A1A2) intervals resulting in VAb approximated 50% of the basic cycle length (BCL) and VAb was frequently abolished at closer A1A2 intervals due to excessive AV nodal delays. While the PR interval preceding an aberrant QRS complex always exceeded the PR of the prior CL, the two major components of the PR [i.e. AV node and His Purkinje system (HPS)] showed different and unpredictable degrees of delays. In comparison to the beats of BCL, during VAb the AV nodal delays amounted to a maximum of a twofold increase, whereas a greater than fourfold increase was noted in the HPS in some instances. The constant finding of PR prolongation and frequent conduction delay in the HPS (HV prolongation) associated with VAb suggested that the appearance of an unexpectedly shortened PR interval, though not usually considered in the differentiation of VAb from premature ventricular beats, may prove extremely useful; yet the often utilized R-R interval relationship poorly reflects the H-H interval relationship (which determines VAb) and therefore may be frequently unreliable.

Atrioventricular sequential pacing: differential effect on retrograde conduction related to level of impulse collision.

Patients with DDD pacemakers who have intact retrograde conduction are known to be at risk of developing ventricular and "endless loop" tachycardia. To address this problem, a pacing protocol was designed in which V2A2 conduction was assessed in 16 patients during ventricular pacing alone (standard method) and during paced atrioventricular (AV) sequential drive (AV sequential method); the results were then compared. In eight of 16 patients who had intact retrograde conduction with both methods (group 1), the V2A2 intervals were significantly shorter (by 60 to 340 msec) with the AV sequential method. In the remaining eight patients, who demonstrated V2A2 block with the standard method, no V2A2 block occurred with the AV sequential method. In this study, two sets of AV intervals were programmed to produce collision of the two impulses (atrial and ventricular), either in the AV node or the His-Purkinje system (HPS). The site of V2A2 facilitation was related to the site of impulse collision. These results can be explained by earlier excitation by the atrial impulse (of AV node and/or HPS) during AV sequential pacing. However, in some cases it was evident that antegrade propagation of the atrial impulse was responsible for subsequent facilitation. The data suggest that assessment of retrograde conduction in candidates for DDD pacemakers can be made most accurately by the AV sequential method.