The relation between atrial fibrillation wavefront characteristics and accessory pathway conduction.

Although the source-sink relationship for impulse propagation in cardiac tissues has been demonstrated in vitro, there has been no verification of this hypothesis in humans. Accordingly, eight patients undergoing surgical division of their accessory pathways were studied. A 56-channel (7 x 8) bipolar plaque electrode array was placed over the atrioventricular groove on the accessory pathway and atrial fibrillation electrically induced. 10 episodes of QRS transition from consecutively preexcited to nonpreexcited complexes were analyzed. This showed that consecutively preexcited QRS complexes were always associated with uniform large atrial wavefronts. Immediately prior to QRS transition, four general types of changes were observed: (a) premature invasion by secondary wavefronts creating local conduction block (n = 5); (b) wavefront collision leading to wavefront curvature (n = 2); (c) transition from a uniform large atrial wavefront to multiple fractionated small wavefronts (n = 1); and (d) uniform atrial wavefronts "marching" into the accessory pathway refractory period (n = 2). We conclude that local atrial wavefront characteristics are important factors influencing impulse propagation through the accessory pathway. The findings that local wavefront collision, curvature, or fractionation often precede loss of accessory pathway conduction support the notion that source-sink relationship is an important determinant of the safety factor for impulse propagation in the human heart.

Prevention of recurrent sudden cardiac arrest: role of provocative electropharmacologic testing.

This study evaluates the usefulness of serial provocative electropharmacologic testing for predicting the efficacy of prophylactic antiarrhythmic treatment regimens in patients resuscitated from sudden cardiac arrest in the absence of acute myocardial infarction. Testing was carried out in 34 consecutive patients (28 men and 6 women) who required cardiopulmonary resuscitation and direct current countershock for treatment of primary ventricular fibrillation (28 patients), ventricular tachycardia (5 patients) or excessively rapid heart rate during atrial fibrillation with preexcitation (1 patient). In 8 (24%) of the 34 patients, drug testing either was not feasible because of absence of inducible arrhythmia or was incomplete because of patient withdrawal from study; and 3 of these 8 patients had recurrent sudden cardiac arrest within 10 to 19 months. In an additional five patients, treatment regimens failed to prevent initiation of sustained ventricular tachyarrhythmias in the catheterization laboratory, and two of these five patients had cardiac arrest recurrences within 2 weeks to 25 months of follow-up. In the remaining 21 (62%) of the 34 patients, including 3 patients with preexcitation syndrome, a drug regimen or surgical treatment, or both, was found that prevented inducible life-threatening tachyarrhythmias in the laboratory. Subsequently, only 1 (5%) of these 21 patients died suddenly within a 7 to 38 month (mean +/- standard deviation, 18 +/- 8.3) follow-up period. Thus, provocative electropharmacologic testing appears to be useful in predicting response to therapy in survivors of sudden cardiac arrest.

Bromocriptine treatment of digitalis-induced ventricular tachyarrhythmias: studies in a canine model.

Ventricular tachyarrhythmias associated with digitalis toxicity are believed to be due, in part, to cardiac glycoside-mediated increased central sympathetic neural activity. Because dopaminergic receptor agonists reduce sympathetic outflow, this study assessed effectiveness of the available dopaminergic agonist, bromocriptine, in slowing or terminating ouabain-induced ventricular tachycardia in anesthetized dogs. In all experiments, ouabain was administered intravenously (20 micrograms/kg body weight bolus injection, followed by 2.5 micrograms/kg per min infusion) until the onset of stable ventricular tachycardia. Of seven untreated dogs (Group 1), ouabain-induced ventricular tachyarrhythmias resulted in ventricular fibrillation in three, while in four dogs tachycardia persisted without significant change in rate until the study was terminated. Fourteen dogs (Group 2) received bromocriptine, either 30 micrograms/kg (Group 2A) or 50 micrograms/kg (Group 2B), after the onset of ventricular tachycardia. Tachycardia slowed in all 14 dogs and terminated with resumption of sinus rhythm in 8 of the 14. In all six dogs pretreated with the peripheral dopaminergic antagonist domperidone (Group 3), bromocriptine, 50 micrograms/kg, slowed ventricular tachycardia and in three of the six, tachycardia terminated. In contrast, of five dogs pretreated with haloperidol, a central and peripheral dopaminergic receptor antagonist (Group 4), bromocriptine, 50 micrograms/kg, failed to slow ventricular tachycardia in three, and two of the three developed ventricular fibrillation. In summary, the dopaminergic receptor agonist, bromocriptine, presumably acting at central dopaminergic receptor sites, consistently slowed and in most cases reversed ouabain-induced ventricular tachycardia in a canine model.

Potentiation of cyclosporine nephrotoxicity by nafcillin in lung transplant recipients.

The interaction between nafcillin and cyclosporine was examined in lung transplant recipients receiving cyclosporine-based immunosuppression. Nine recipients received nafcillin for one week posttransplant and 10 recipients did not receive nafcillin. Age, sex, pretransplant renal function, type of transplant procedure, use of cardiopulmonary bypass, and initial cyclosporine dose were not significantly different between groups. The degree of renal dysfunction during the early postoperative period was significantly greater in the lung recipients receiving nafcillin. Although cyclosporine doses were significantly higher in the nafcillin group, this was not reflected by differences in cyclosporine levels. No difference in survival or incidence of allograft rejection was seen--however, the incidence of viral infection was significantly higher in the patients who received nafcillin. Based on our findings the use of an alternative antibiotic for antistaphylococcal prophylaxis in transplant recipients receiving cyclosporine is recommended.

Primary diagnosis predicts prognosis of lung transplant candidates.

Optimal timing for consideration of lung transplantation remains unknown. This study examined survival in patients with end-stage lung disease awaiting transplantation. Primary disease group and relevant indicators were evaluated. Ninety-three patients who met selection criteria for lung transplantation were included in this retrospective review. Of this total, 31% underwent transplantation, 38% remain waiting, and 31% died. Results demonstrate that the six-month actuarial survival rate was 89% for Eisenmenger's syndrome, 81% for emphysema, 74% for cystic fibrosis, 60% for primary pulmonary hypertension, and 38% for interstitial lung disease. Parameters found to be significant included a higher mean right atrial pressure in primary pulmonary hypertension patients who died awaiting transplantation, and lower forced expiratory volume in one second and forced vital capacity measurements in cystic fibrosis patients who died awaiting transplantation. We conclude that primary disease significantly affects survival in candidates awaiting transplantation. Reliable indicators predictive of survival are not available. Earlier referral for consideration of lung transplantation is recommended.

Antiarrhythmic and electrophysiologic actions of bethanidine sulfate in primary ventricular fibrillation or life-threatening ventricular tachycardia.

Antiarrhythmic and electrophysiologic actions of bethanidine sulfate, a chemical analog of bretylium tosylate, were studied using programmed cardiac electrical stimulation in 14 survivors of out-of-hospital cardiac arrest unassociated with acute myocardial infarction. Before bethanidine sulfate was administered sustained ventricular tachyarrhythmias (VT) were inducible in 11 patients and reproducible nonsustained VT was induced in 3 patients. Bethanidine sulfate shortened sinus cycle length and absolute and relative ventricular refractory periods measured during sinus rhythm, but did not alter ventricular effective refractory period measured during ventricular pacing. Bethanidine sulfate prevented inducible VT in 8 patients (57%), increased the number of extrastimuli needed to induce VT in 2 patients, and was ineffective in 4 patients. In contrast, in only 1 of 26 trials with other conventional and investigational antiarrhythmic drugs in these patients was VT prevented. Orthostatic hypotension was a prominent side effect of bethanidine sulfate therapy, but could be reversed in most patients by concomitant administration of protriptyline. Five patients in whom bethanidine sulfate was effective in the laboratory have been treated chronically (400 to 600 mg 4 times daily), and all are alive at 3 to 40 months. In the remaining 9 patients, 8 were treated empirically because no drug was effective in the laboratory and 1 was treated with quinidine, which appeared to be protective during testing. Four of these 9 patients, including the patient treated with quinidine, died suddenly during follow-up. Thus, although bethanidine sulfate therapy is difficult to initiate because of orthostatic hypotensive side effects, it may be useful in treating patients at high risk of recurrent cardiac arrest.

Onset of atrial fibrillation during antidromic tachycardia: association with sudden cardiac arrest and ventricular fibrillation in a patient with Wolff-Parkinson-White syndrome.

Electrophysiologic evaluation in an 18 year old youth with the Wolff-Parkinson-White syndrome who had a sudden cardiac arrest while playing racquetball revealed two types of paroxysmal reciprocating tachycardia: (1) A normal QRS tachycardia with a short ventriculoatrial (V-A) interval fulfilled the criteria for reentry within the atrioventricular (A-V) node; and (2) a wide QRS tachycardia with a QRS configuration of maximal preexcitation was demonstrated to be the result of an antidromic mechanism. During laboratory study, the wide QRS tachycardia spontaneously degenerated into atrial fibrillation. In the basal state, the shortest R-R interval between preexcited QRS complexes was 270 ms, but after infusion of isoproterenol (1.6 microgram/min intravenously), the shortest R-R interval became 180 ms. Consequently, this electrophysiologic study suggested that evolution of antidromic reciprocating tachycardia into atrial fibrillation with a rapid ventricular response during exercise-induced catecholamine release may have been the mechanism for ventricular fibrillation in this patient.

Atrial septostomy as a bridge to lung transplantation in patients with severe pulmonary hypertension.

Long waiting times for lung transplantation have limited the survival of patients with advanced pulmonary hypertension. Atrial septostomy has been used in this group of patients in an attempt to prolong survival. We evaluated the results of atrial septostomy in 12 patients using the static graded balloon dilation technique. Between December 1990 and May 1998, 10 women and 2 men (ages 13 to 56 years, mean 37 years) underwent atrial septostomy. Nine patients had primary and 3 patents had secondary pulmonary hypertension. Five patients deteriorated despite long-term intravenous prostacyclin infusions. The atrial septum was crossed with a Brockenbrough needle, followed by an 0.035-J exchange wire and progressively larger catheter balloons for atrial septal dilation, until systemic oxygen saturation decreased 5% to 10%. An atrial septal defect was successfully created in each patient. The mean right atrial pressure decreased from 23 to 18 mm Hg and the mean systemic oxygen saturation decreased from 93% to 85%. The mean cardiac index increased from 1.7 to 2.1 L/min/m2 and the mean systemic oxygen transport increased from 268 to 317 ml/min/m2. Complications occurred in 3 patients: transient hypotension during transesophageal echocardiography, a femoral pseudoaneurysm, and a femoral arteriovenous fistula. After septostomy, 6 patients had clinical improvement (resolution of ascites, edema, and no further episodes of syncope); 5 of these 6 patients underwent lung transplantation a mean of 6.1 months after septostomy. Six patients did not have clinical improvement after septostomy. Atrial septostomy improves the hemodynamic status and may be useful as a bridge to lung transplantation in selected patients with pulmonary hypertension.

Prothrombotic activation of pulmonary arterial endothelial cells in a patient with tuberculosis.

Activation of endothelial cells occurs in response to numerous physiological stimuli and results in the concerted expression of endothelial cell proteins that change the nonthrombogenic intimal surface of a vessel into a thrombogenic surface, with the subsequent development of local thrombosis. For example, both type 1 plasminogen activator inhibitor and tissue factor expression are mediated by endothelial cell stimulation in vitro; however, in contrast to type 1 plasminogen activator inhibitor, it has been difficult to detect tissue factor associated with endothelial cells in vivo. This case study describes the presence of both type 1 plasminogen activator inhibitor and tissue factor antigen associated with pulmonary arterial endothelial cells of a patient exhibiting a mycobacterial infection. The disease was associated with chronic hemoptysis and characterized by extensive tissue destruction and local thrombosis within the pulmonary artery. The data show that conditions occur in vivo in which local thrombosis is associated with increased levels of type 1 plasminogen activator inhibitor and tissue factor.

Surgical management of congenital obstruction of the left main coronary artery with supravalvular aortic stenosis.

OBJECTIVE: Stenosis of the left main coronary artery is a recognized complicating feature of supravalvular aortic stenosis. We have retrospectively identified three anatomic subtypes of left main coronary obstruction in patients with supravalvular aortic stenosis, each necessitating a distinct surgical approach. METHODS: From 1991 to 1998, 9 patients underwent surgical repair of supravalvular aortic stenosis and left main coronary stenosis. Five patients (group 1) had obstruction from near-circumferential thickening of the left main ostium, 2 patients (group 2) had restricted coronary flow due to fusion of an aortic valve leaflet to the supravalvular ridge, and 2 patients (group 3) had diffuse narrowing of the left main coronary artery. Group 1 patients were treated with patch aortoplasty encompassing the left main ostium and supravalvular aortic stenosis. Group 2 patients were treated with excision of the fused leaflet from the aortic wall and patch aortoplasty. Group 3 patients were treated with bypass grafting and aortoplasty. RESULTS: Surgical strategy was determined by coronary angiography and intraoperative assessment of coronary anatomy. There was 1 early death. All surviving patients underwent echocardiography with or without postoperative catheterization. The mean postoperative supravalvular gradient for 7 patients was 8 mm Hg (range 2-15 mm Hg). One patient required reoperation for a residual aortic gradient as a result of aortic arch involvement. No evidence of left main coronary artery stenosis was seen in groups 1 and 2; bypass grafts were patent in group 3 patients at a mean follow-up of 54.8 months. CONCLUSION: Three subtypes of left main coronary stenosis with supravalvular aortic stenosis are described. Each anatomic type mandates an individual surgical approach. Favorable surgical outcomes are achievable with each category.

Experience and results with 150 pulmonary thromboendarterectomy operations over a 29-month period.

A program to alleviate chronic, major vessel thromboembolic pulmonary hypertension by pulmonary thromboendarterectomy was initiated at this institution in 1970. Multiple evolutionary changes in the diagnostic evaluation, surgical approach, and postoperative management have been implemented over the series of 323 thromboendarterectomies performed through March 1992. A sequence of five surgeons at the University of California at San Diego have performed these procedures, with the last 150 having been performed by one surgeon. We report here the changes in surgical approach developed over the last 150 cases and the results obtained. The operation involves a median sternotomy incision, the institution of cardiopulmonary bypass, and deep hypothermia with circulatory arrest periods. Incisions are made in both pulmonary arteries into the lower lobe branches. Pulmonary thromboendarterectomy is always bilateral, with removal of both organized thrombus and an endarterectomy plane from all involved vessels. The right atrium is routinely explored for atrial septal defects. Current techniques appear to allow more thorough revascularization and shorter circulatory arrest times. The surgical mortality of 8.7% over this span is below that previously reported from this and other institutions. Among survivors, the hemodynamic and functional results have been excellent. Surgically correctable chronic thromboembolic pulmonary hypertension likely remains underdiagnosed. The diagnostic, surgical, and postoperative management evolution provided by the coordinated team involved at this institution has established that pulmonary thromboendarterectomy can be performed with an acceptable risk and good hemodynamic and symptomatic results.

The Registry of the International Society for Heart and Lung Transplantation: eighth official report--1991.

Less than 25 years since the first human-human heart transplantation, the worldwide experience exceeds 16,000 heart and 1600 lung transplantations from more than 200 centers. Excellent results in heart transplantation have been achieved in a wide variety of patients. During the past few years, lung transplantation has come of age. The specific indications for each technique continue to evolve. Although much progress has been made, it is hoped that future developments in immunosuppression will solve the problems of chronic rejection and decrease the risk of infections. On behalf of the Society, we would like to take this opportunity to sincerely thank each of the participants throughout the world who took the time and care to submit their data to the Registry. Through this compilation of the world's experience, the state of the art in thoracic transplantation may be shared with the transplant community. The extensive Registry data base will permit risk assessment of thoracic transplant recipients while avoiding the problems associated with small sample sizes. Each participant's continued diligence in providing follow-up reports on all recipients is essential for an accurate evaluation of the long-term prognosis of heart and lung transplantation.

Techniques for bronchial anastomosis.

BACKGROUND: Many techniques have been described to optimize the construction of the bronchial anastomosis in lung transplantation. Over the past 60 months we have performed 86 bronchial anastomoses in 70 patients receiving single lung or bilateral single lung transplants. METHODS: No anastomosis was wrapped and no attempt was made at revascularization of bronchial arteries. A continuous nonabsorbable suturing technique was used in all cases. Standard triple-drug immunotherapy with cyclosporine, azathioprine, and prednisone (starting at day 7) was used for each patient. RESULTS: There were no anastomotic leaks, and seven stenoses were identified in five patients (7%). All complications were managed conservatively with stenting, and there were no related deaths. Mean time to stent placement was 109 days. One patient had bilateral stents placed prophylactically during an episode of severe infection for questionable anastomotic viability but without evidence of airway necrosis or obstruction. This patient died of infection at 16 days. Another patient died with stents in place at 71 days. In the four remaining patients, all stents have been removed after a mean of 310 days. These patients were followed up with serial bronchoscopy and were without evidence of recurrent obstruction at 2, 34, 35, and 36 months. Six of seven stenoses occurred in patients with cystic fibrosis. In each patient where stenosis developed the anastomosis was telescoped. Since abandoning the telescoping technique in the remaining 50 anastomoses (14 in patients with cystic fibrosis), no dehiscence or stenosis was encountered. CONCLUSIONS: These data suggest that elaborate techniques aimed at construction of the bronchial anastomosis are not necessary. Moreover, attempts at telescoping may be detrimental. Patients with cystic fibrosis may be a population at higher risk for anastomotic complications. Airway complications can be managed conservatively with good results and little risk to the patient.

Lung transplantation without the use of antilymphocyte antibody preparations.

Survival, infection, and rejection rates and functional data are reported in 35 lung recipients treated with triple-drug immunosuppression without antilymphocytic antibody therapy. Early mortality (less than 60 days) was 6%. Thirty recipients (86%) are alive, with a mean follow-up period of 16 months (range, 1 to 36 months). Actuarial survival was 91% at 1 year and 83% at 2 years. Thirty-seven infections occurred in 24 patients. Actuarial freedom from infection was 61% at 3 months and 27% at 1 year. Only one patient died of infection (aspergillosis). Thirty-six episodes of acute rejection were treated in 23 patients. Time to first rejection was 14 +/- 7.8 days. Actuarial freedom from acute rejection was 36% at 2 months. Significant functional improvement was evident in all operative survivors. Pulmonary function and exercise performance data in patients without bronchiolitis obliterans remain stable 1 year after transplantation. We conclude that the use of triple-drug immunosuppression without antilymphocytic antibody preparations in lung transplantation provides effective immunosuppression with a low risk of serious infectious complications.

Volume reduction surgery in the native lung after single lung transplantation for emphysema.

The natural history of emphysema suggests that progression of disease in the native lung may contribute to late deterioration in respiratory function after single lung transplantation. In this report, we describe our experience with unilateral volume reduction surgery in three single lung transplant recipients with emphysema. Each patient had had a late decline in lung function with a recurrence of symptoms. Chest radiographs demonstrated hyperinflation of the native lungs with encroachment on the grafts. Serial pulmonary function testing documented progressive reduction in expiratory flows with increases in residual volumes. Exercise testing confirmed severe intolerance to maximal exercise. Unilateral volume reduction surgery was undertaken at 36, 39, and 55 months after transplantation without incident. Radiographs obtained after the procedures demonstrated restoration of normal diaphragmatic contour, decreased aeration of the native lungs, and improved inflation of the allografts. Exercise testing at 3 months documented a mean improvement in maximal oxygen consumption of 35%. Expiratory flows improved by a mean of 60%. Quantitative ventilation and perfusion scans, however, were essentially unchanged. This experience suggests that unilateral volume reduction surgery may be considered as an alternative strategy in single lung transplant recipients with emphysema who exhibit clinically significant functional deterioration. Differentiation of the adverse effects of hyperinflation of the native lung from other potential causes of late deterioration might not be necessary but may be predictive of the degree of functional improvement after volume reduction. The relief of thoracic overdistention seems to play a primary role in the improvement pulmonary function.

Outpatient inhaled nitric oxide in a patient with idiopathic pulmonary fibrosis: a bridge to lung transplantation.

Inhaled nitric oxide (INO) has been shown to improve oxygenation and decrease intrapulmonary shunt and pulmonary hypertension in various lung diseases. In this study we report a patient with end-stage idiopathic pulmonary fibrosis and pulmonary hypertension who received INO after coronary artery bypass surgery, with significant improvement in arterial oxygenation and pulmonary arterial pressure. Using a pulsing delivery system, the patient continued to receive outpatient INO for 30 months while waiting for lung transplantation. Exercise study and two-dimensional echocardiogram, after 3 months of inhaled NO, demonstrated continued benefits of INO for improvement of arterial oxygenation, pulmonary arterial pressure and exercise tolerance.

Recovery of adenine nucleotide levels after global myocardial ischemia in dogs.

Loss of myocardial adenosine triphosphate (ATP) during ischemia can result in decreased cardiac function. Postischemic ATP levels remain low, and the reason for this is poorly understood. Previous attempts to enhance ATP recovery after ischemia have been only partially successful. To determine the long-term dynamics of ATP recovery and evaluate the effect of providing ATP precursors, we devised a method of obtaining sequential ventricular biopsies in dogs after 20 minutes of normothermic global ischemia on cardiopulmonary bypass. Our kinetic data show adenine (A) is metabolically favored over adenosine to regenerate ATP levels when adequate ribose (R) is present to produce phosphoribosylpyrophosphate. Therefore A (20 mM) plus R (80 mM) or saline (NS) was infused (1.0 ml X min-1) into the right atrium of dogs for 48 hours after ischemia. During A infusion myocardial tissue A was 0.19 +/- 0.07 nmol X mg-1, arterial A was 18.3 +/- 1.3 microM, coronary sinus A was 11.0 +/- 1.6 microM, and extraction of A by the myocardium was 38% +/- 10%. We found that while the decrease in ATP levels during ischemia was at least 50% in both groups, the postischemic ATP recovery rate in A/R dogs was more than eightfold greater than de novo synthesis (2.8 +/- 0.59 versus 0.34 +/- 0.06 nmoles X mg-1 X day). ATP levels in NS dogs were only 54% +/- 8% of preischemic values by 48 hours and required 9.9 +/- 1.4 days for full recovery. Recovery in A/R dogs required 1.2 +/- 0.2 days. Our results reveal that ATP recovery after a significant ischemic insult is slow, precursor availability is an important limiting factor in ATP recovery, and recovery time can be greatly shortened with precursor infusion even when started after the ischemic insult.

Primary pulmonary artery sarcoma: a report of six cases.

Pulmonary artery tumors are rare and a frequently overlooked cause of pulmonary artery occlusion. The presentation is one of progressive pulmonary dysfunction and right ventricular failure. The diagnosis seldom is made preoperatively. We report 6 cases of primary sarcoma of the pulmonary artery identified at operation, which were treated surgically. Resection with or without adjuvant therapy currently offers the only chance for survival. Emphasis must be placed on earlier identification of these tumors.

Surgical management of ventricular tachycardia.

BACKGROUND: Ventricular tachyarrhythmias are the leading cause of death from coronary artery disease. A small percentage of these arrhythmias originate in chronically ischemic myocardium, rather than acutely ischemic myocardium, and can be refractory to medical management. Epicardial mapping and focal cryoablation of foci demonstrating early activation may provide definitive therapy when pharmacologic management fails. We report a series of 42 consecutive patients with refractory ventricular tachycardia (VT) who were treated with open epicardial mapping and focal cryoablation after pharmacologic management failed. METHODS: We retrospectively reviewed the records of patients who underwent surgical treatment of malignant VT. For patients not recently seen in the clinic, we conducted telephone interviews. At the time of operation, epicardial mapping was performed to locate foci of early electrical activation. These foci were then cryoablated, using 2-minute applications of liquid nitrogen-cooled probes. All patients underwent postoperative electrophysiologic studies to test for inducible VT. RESULTS: Of these 42 patients, 34 (81%) were male, 8 (19%) female. Average age was 62.9 +/- 10.6 years; ejection fraction, 0.20 (range, 0.04 to 0.50); and number of foci ablated, 2.1 +/- 1.1 (range, 1 to 6). At the time of cryoablation, all patients underwent additional procedures, including aneurysmectomy, coronary artery bypass, or valve replacement. The 30-day operative mortality was 9.5% (4 of 42). Of the 38 survivors, 36 (94.7%) were clinically free of VT; the remaining 2 had spontaneous or inducible VT. CONCLUSIONS: Open cryoablation of foci propagating VT appears to be safe and effective. It may be the most definitive treatment for malignant VT.

Cellular electrophysiologic effects of dexamethasone sodium phosphate: implications for cardiac stimulation with steroid-eluting electrodes.

Impregnation of implantable cardiac pacemaker electrodes with dexamethasone sodium phosphate dexamethasone) has been associated with reduced energy requirements for both atrial and ventricular stimulation. To determine whether cardiac cellular electrophysiologic effects of dexamethasone could in part account for lower stimulation thresholds, conventional microelectrode recording and stimulation techniques were used to assess both the immediate (acute) effects of dexamethasone (10(-6) and 10(-4) M) in superfused isolated rabbit right atrial and right ventricular preparations, and chronic effects in rabbit right ventricular tissue following 2 weeks of either daily parenteral dexamethasone (5 mg/kg, plasma concentration approximately 1 to 5 x 10(-5) M) or saline placebo injections. In acute superfusion studies, dexamethasone resulted in a concentration dependent prolongation of spontaneous right atrial cycle length, but did not significantly affect right atrial transmembrane action potential characteristics or refractoriness. However, acute dexamethasone superfusion tended to increase right ventricular resting membrane potential and diminish stimulation threshold. On the other hand, compared to findings in saline-injected control rabbits, chronic dexamethasone injection had little effect on right ventricular stimulation threshold transmembrane action potential characteristics, or right ventricular refractoriness. Thus, the acute direct electrophysiologic effects of high-dose dexamethasone are compatible with the early reduction of cardiac stimulation thresholds associated with dexamethasone impregnated pacing electrodes. On the other hand, electrophysiologic findings in the presence of chronic dexamethasone exposure do not fully account for long-term reduction of stimulation energy requirements.