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Biomedical subjects

D L Packer

Publications and source records attributed to D L Packer.

At least 55 records · Page 3Linked to original sources
PubMed1994

Voltage dependence of beta-adrenergic modulation of conduction in the canine Purkinje fiber.

Although recent voltage-clamp and microelectrode studies have demonstrated beta-adrenergic modulation of Na+ current (INa) the modulation of conduction by catecholamines and the voltage dependence of that process have not been elucidated. To determine whether voltage-dependent modulation of conduction occurs in the presence of a beta-adrenergic agonist, the effect of 1 mumol/L isoproterenol on impulse propagation in canine Purkinje fibers was examined by using a dual-microelectrode technique. At physiological membrane potentials ([K+]o 5.4 mmol/L), isoproterenol increased squared conduction velocity [theta 2, 0.39 +/- 0.25 (m/s)2 (mean +/- SD)] from 3.46 +/- 0.86 to 3.85 +/- 0.98 (m/s)2 (P < .011), an 11% change, without altering the maximum first derivative of the upslope of phase 0 of the action potential (Vmax, 641 +/- 50 versus 657 +/- 47 V/s, P = NS). At transmembrane potential of -65 mV, produced by 12 mmol/L [K+]o titration, theta 2 declined 79% to 0.73 +/- 0.44 (m/s)2 as Vmax decreased 85% to 95 +/- 43 V/s (P < .02). The addition of isoproterenol further decreased theta 2 to 0.49 +/- 0.33 (m/s)2 (P = .02) in parallel with a further decline in Vmax to 51 +/- 25 V/s (P < .05). Isoproterenol produced a 3-mV hyperpolarizing shift of apparent Na+ channel availability curves generated from both theta 2 and Vmax, used as indexes of the fast inward INa, without changing the slopes of the relation. The relation between normalized theta 2 and Vmax over a range of depolarized potentials was linear and was not appreciably altered by isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1994

Direct quantification of apparent binding indices from quinidine-induced in vivo conduction delay in canine myocardium.

To characterize quantitatively the quinidine (QUIN)-induced conduction delay (CD) in vivo, canine ventricular activation times were examined with an epicardial mapping technique. A high-resolution index of normalized (N) QUIN CD, derived from all 56 recording sites, was used to quantify QUIN effect. Repetitive stimulation elicited monoexponential increases in CD(N), the rates of which were a linear function of interpulse recovery interval, tr. Steady-state CD(N) was also linearly related to an exponential function of tr and drug uptake rates. The frequency-dependent properties of QUIN in 14 dogs were characterized by apparent binding and unbinding rates of ka = 7.1 +/- 3.5 x 10(6) M-1 s-1, la = 81 +/- 51 s-1 for activated, and kr = 12.6 +/- 11.3 x 10(3) M-1 s-1, lr = 0.51 +/- 0.26 s-1 for resting states. ka and la were similar to values previously derived in canine Purkinje fibers. Drug unbinding at resting potentials was faster in vivo than previously observed in vitro. The time constant of recovery from QUIN block extracted from the interpulse recovery rate was also identical to that determined from post-mature stimulus diastolic scanning. As predicted by the two-state model, similar binding rates were also derived from declining CD(N) elicited by step decreases in heart rate. These findings represent a complete quantitative description of use-dependent QUIN CD in vivo and provide a firm foundation for characterizing antiarrhythmic drug action under physiologic and pathologic conditions.

Action Potentials↗
PubMed1993

A population study of the natural history of Wolff-Parkinson-White syndrome in Olmsted County, Minnesota, 1953-1989.

BACKGROUND: Virtually all natural history studies of Wolff-Parkinson-White (WPW) syndrome have been case series and, as such, have been constrained by referral biases, skewed age and sex distributions, or brief follow-up periods. The purpose of our study was to examine the natural history, the development of arrhythmias, and the incidence of sudden death in an entire cohort of pediatric and adult WPW patients from a community-based local population. METHODS AND RESULTS: We identified 113 residents of Olmsted County, Minnesota, during the period 1953-1989 using the centralized records-linkage system provided by the Mayo Clinic and the Rochester Epidemiology Program Project. Medical records and ECGs were reviewed to confirm the diagnosis and to establish pathway location by ECG criteria. Follow-up, via record review and telephone interview, was complete in 95% of subjects through 1990. The incidence of newly diagnosed cases was approximately four per 100,000 per year. Preexcitation was not present on the initial ECG of 22% of the cohort. Approximately 50% of the population was asymptomatic at diagnosis, with 30% subsequently having symptoms related to arrhythmia at follow-up. Two sudden cardiac deaths (SCD) occurred over 1,338 patient-years of follow-up, yielding an overall SCD rate of 0.0015 (95% confidence interval, 0.0002-0.0054) per patient-year. No SCD occurred in patients asymptomatic at diagnosis. CONCLUSIONS: The incidence of sudden death in a local community-based population is low and suggests that electrophysiological testing should not be performed routinely in asymptomatic patients with WPW syndrome. Nevertheless, young, asymptomatic patients, particularly those < 40 years old, should return for medical follow-up should symptoms develop.

Adolescent↗
PubMed1992

New observations on atrial fibrillation before and after surgical treatment in patients with the Wolff-Parkinson-White syndrome.

The records of 342 patients who received surgical treatment for the Wolff-Parkinson-White syndrome between 1968 and 1986 were reviewed to evaluate the characteristics of atrial fibrillation. The patients were classified into two groups according to the presence (n = 166) or absence (n = 176) of documented episodes of atrial fibrillation preoperatively. The mean follow-up duration was 6 years (range 2 to 20). As compared with reports based on smaller patient groups and shorter follow-up, the study revealed several new findings. 1) During follow-up, nine patients in the atrial fibrillation group developed recurrent atrial fibrillation after a successful operation; five of these nine patients did not have associated heart disease. 2) All three patients with a history of atrial fibrillation and an accessory pathway conducting in the anterograde direction only had a successful surgical procedure and no postoperative atrial fibrillation. 3) The cycle length of atrioventricular (AV) reciprocating tachycardia was significantly shorter in the atrial fibrillation group (304 +/- 42 ms, mean +/- SD) than in the no-atrial fibrillation group (321 +/- 54 ms, p less than 0.005), and the cycle length of AV reciprocating tachycardia that degenerated into atrial fibrillation (289 +/- 26 ms) was shorter than that for the AV reciprocating tachycardia without subsequent atrial fibrillation (316 +/- 51 ms, p less than 0.005). 4) Sustained atrial fibrillation was induced in 30% of patients without a history of atrial fibrillation. 5) Atrial fibrillation occurred in four patients with an accessory pathway that conducted only in the retrograde direction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Physiological substrate for antidromic reciprocating tachycardia. Prerequisite characteristics of the accessory pathway and atrioventricular conduction system.

BACKGROUND: Although the anatomic "substrate" for the occurrence of antidromic reciprocating tachycardia (ART) has been previously examined, the underlying physiological substrate for this unusual arrhythmia in patients with the Wolff-Parkinson-White syndrome has not been thoroughly characterized. METHODS AND RESULTS: The electrophysiological properties of the accessory pathway and normal ventriculoatrial conduction system in 30 patients with ART and a single accessory pathway were compared with those observed in a control group of 36 patients without this arrhythmia to elucidate the critical physiological substrate essential for the development and maintenance of ART. Inducible ART had a mean cycle length of 286 +/- 31 msec. The average retrograde ventriculoatrial conduction system effective refractory period in ART patients was significantly less than that in the control group (244 +/- 32 versus 291 +/- 46 msec, p = 0.0002). All of the ART patients showed retrograde conduction over the normal conduction system at cycle lengths of less than or equal to 360 msec; 23 had 1:1 conduction to less than or equal to 300 msec, and 16 showed 1:1 propagation at cycle lengths of less than or equal to 260 msec. The shortest cycle length accompanied by 1:1 retrograde propagation over the normal conduction system in patients with ART was also significantly less than that observed in the control group (274 +/- 39 versus 347 +/- 73 msec, p less than 0.001). The accessory pathway anterograde ERP in ART patients with 1:1 retrograde conduction over the normal ventriculoatrial conduction system at cycle lengths of less than or equal to 360 was significantly less than that seen in comparable control patients (247 +/- 23 versus 284 +/- 56 msec, p = 0.001), and the accessory pathway location was significantly further from the atrioventricular node in 21 patients with ART undergoing surgery than that in 22 operated control patients (3.8 +/- 0.8 versus 2.9 +/- 0.8 mapping units, p = 0.0025) who also had retrograde ventriculoatrial conduction to cycle lengths of less than or equal to 360 msec. No significant differences in anterograde atrioventricular conduction system properties, retrograde accessory pathway refractoriness, or shortest ventricular pacing cycle lengths maintaining 1:1 conduction via the accessory pathway were observed between groups. CONCLUSIONS: This quantitative characterization of the properties of conduction and refractoriness of both the accessory pathway and ventriculoatrial conduction system and the relation between these characteristics and the accessory pathway location in ART patients provides additional insight into the prerequisites for the initiation and maintenance of this rhythm disturbance.

Adult↗
PubMed1990

Surgical treatment of automatic atrial tachycardias.

From 1979 to 1989, 18 patients were seen in the Electrophysiology Service, Duke University Medical Center, with automatic atrial tachycardia. There were 8 male and 10 female patients with a mean age of 28.1 +/- 2.9 years. Electrophysiological mapping localized automatic foci to right atrial sites (14 patients) and left atrial sites (4 patients). Depending on origin of the focus, patients were further diagnosed as having either chronic ectopic atrial tachycardia or inappropriate sinus tachycardia. Of the 15 patients with chronic ectopic atrial tachycardia, 6 responded to medical treatment; in 9, the tachycardia was not adequately controlled. Six of them were referred for surgical intervention. All 3 patients with inappropriate sinus tachycardia underwent operative therapy. In the surgical group of patients with chronic ectopic atrial tachycardia, all 6 had a tachycardia-induced cardiomyopathy with ejection fractions ranging from 14% to 27% (mean ejection fraction, 21% +/- 2.7%). Surgical techniques used (alone or in combination) included an isolation procedure in 1 patient, cryoablation in 4 patients, and excision of atrial appendages or portions of atrial free walls in 7. Normal sinus rhythm developed in all surgical patients except 1 patient who had intractable congestive heart failure preoperatively and died of this condition and stroke. The overall success rates for medical and surgical therapy were 33.3% and 88.9%, respectively (p less than 0.01). Long-term follow-up was possible for 7 (87.5%) of 8 patients 3 to 7 years after operation. All patients with chronic ectopic atrial tachycardia were cured, but only 1 of 3 patients with inappropriate sinus tachycardia was in sinus rhythm.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Occurrence of atrial fibrillation in patients with paroxysmal supraventricular tachycardia due to atrioventricular nodal reentry.

The occurrence of atrial fibrillation in patients with paroxysmal supraventricular tachycardia (PSVT) has been well documented when PSVT is secondary to atrioventricular reentry, but not when PSVT is secondary to atrioventricular nodal reentry (AVNRT). Seventeen patients with AVNRT were followed using transtelephonic electrocardiogram monitoring to document symptomatic tachycardias. The median length of telephone monitor surveillance was 357 days. Fifteen of 17 patients transmitted electrocardiograms that showed PSVT. Three of 17 patients (18%) transmitted electrocardiograms that showed atrial fibrillation. A transition from PSVT into atrial fibrillation was not recorded, but all three did have PSVT recorded on other days of follow-up. We report the occurrence of atrial fibrillation in patients with AVNRT and that its incidence is higher than expected for the general population.

Atrial Fibrillation↗
PubMed1990

Nonpharmacologic treatment of the Wolff-Parkinson-White syndrome and other supraventricular tachycardias.

Nonpharmacologic treatment using surgery or intracardiac catheter ablation can be used for several forms of supraventricular tachycardia. Surgery is highly successful in preventing recurrent tachyarrhythmias in patients with the Wolff-Parkinson-White syndrome and can be recommended as first-line treatment in several situations. Catheter ablation of the atrioventricular conduction system combined with an implanted ventricular pacemaker can offer substantial relief to selected patients with drug-refractory atrial fibrillation. Technical advances in catheter ablation will undoubtedly lead to more widespread use of this form of therapy in supraventricular tachycardia.

Cardiac Catheterization↗
PubMed1989

Utility of introducing ventricular premature complexes during reciprocating tachycardia in specifying the location of left free wall accessory pathways.

The usefulness of the response to single and double ventricular premature complexes (VPCs) introduced during reciprocating tachycardia (RT) in predicting the location of a left free wall accessory pathway was studied in 55 patients with the Wolff-Parkinson-White syndrome. One VPC introduced from the right ventricle into narrow QRS RT when the His bundle was refractory resulted in retrograde atrial preexcitation in 25 of 55 (45%) patients, while 30 (55%) showed no preexcitation. Double VPCs produced retrograde atrial preexcitation in 9 of 26 patients not responding to a single VPC. No difference in RT cycle length, AH, HV or ventriculoatrial intervals was found between those patients who did or did not show retrograde atrial preexcitation. The response to single and double VPCs during RT was related to the location of the AP. The average distance of the AP from the crux determined by intraoperative epicardial mapping in the 41 patients who underwent surgery was 2.7 +/- 0.7 mapping units (left posterolateral region) in patients showing retrograde atrial preexcitation with a single VPC, 3.6 +/- 0.7 units (at the lateral left ventricular margin) in those responding to double VPCs and 4.3 +/- 0.8 units (beyond the LV margin) in those showing no response. Left bundle--branch block (LBBB) aberrancy during RT resulted in an average 60 +/- 14 ms prolongation of the ventriculoatrial interval in 40 patients, including 5 in whom LBBB was seen only after procainamide infusion. VPCs introduced into LBBB RT resulted in significant retrograde atrial preexcitation in 6 additional patients in whom no response during normal QRS RT was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Bundle-Branch Block↗
PubMed1989

Characterization of concentration- and use-dependent effects of quinidine from conduction delay and declining conduction velocity in canine Purkinje fibers.

The dynamic response of squared conduction velocity, theta 2, to repetitive stimulation in canine Purkinje fibers with quinidine was studied using a double-microelectrode technique. With stimulation, a frequency-dependent monoexponential increase in conduction delay (CD) and a decline in theta 2 were observed. The exponential rates and changes in steady-state CD and theta 2 were frequency- and concentration-dependent. The overall drug uptake rates describing blockade and the interpulse recovery interval were linearly related and steady-state values of theta 2 were linearly related to an exponential function of the stimulus intervals. Based on first-order binding, the frequency- and concentration-dependent properties of quinidine were characterized by the apparent binding and unbinding rates of 14.2 +/- 5.7 X 10(6) mol-1.s-1 and 63 +/- 12 s-1 for activated and 14.8 +/- 1.0 X 10(2) mol-1.s-1 and 0.16 +/- 0.03 s-1 for resting states. The recovery time constant extracted from the pulse train interpulse interval was 5.8 +/- 1.5 s compared with 5.1 +/- 0.6 s determined from a posttrain test pulse protocol. This study demonstrates that the kinetics of drug action can be derived from measures of impulse propagation. This provides a basis for characterizing frequency-dependent properties of antiarrhythmic agents in vivo and suggests the plausibility of a quantitative assessment of drug binding and recovery rates in man.

Action Potentials↗
PubMed1988

Procainamide infusion test: inability to identify patients with Wolff-Parkinson-White syndrome who are potentially at risk of sudden death.

Persistence of preexcitation in sinus rhythm with procainamide infusion has been reported to occur in patients with a short anterograde accessory pathway effective refractory period (AERPAP) and this test has been proposed as a reliable noninvasive method to identify patients with the Wolff-Parkinson-White syndrome who are at risk of sudden death. However, sudden death correlates best with a shortest preexcited RR interval during atrial fibrillation (SRRPE) of 260 msec or less. We infused 10 to 12 mg/kg procainamide to 56 patients to determine whether persistence or loss of preexcitation in sinus rhythm identified patients with SRRPEs of 260 or less or greater than 260 msec, respectively. Atrial fibrillation was induced in 53 patients. Of these, 32 patients had persistence of preexcitation with procainamide infusion and SRRPE in this group of patients was shorter than that in patients in whom preexcitation was lost (194 +/- 44 vs 235 +/- 55 msec, p less than .05). However, preexcitation persisted after procainamide infusion in only 31 of 46 (67%) patients with SRRPEs of 260 msec or less. Furthermore, 15 of 21 patients who lost preexcitation had SRRPEs of 260 msec or less and two of these patients had a history of ventricular fibrillation. The correlation between AERPAP and SRRPE was studied in a separate group of 79 patients with single accessory pathways. There was a significant (p less than .001) but poor (r = .58) correlation between these two variables. Thus, the procainamide test regarding accessory pathway refractoriness often cannot be extrapolated to SRRPE.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Fibrillation↗
PubMed1988

Hemodynamic effects of nifedipine in a canine model of acid aspiration.

A solution of ethyl alcohol, polyethylglycol, and distilled water that did (n = 5) or did not (n = 5) contain 250 micrograms/kg of the calcium channel blocker, nifedipine, was infused into the right atrium in 10 healthy mongrel dogs. Hydrochloric acid (pH = 1.8), 2 ml/kg, was then instilled into both lungs of all dogs via the tracheal tube. Hemodynamic data were collected before and 10 minutes after nifedipine was infused and 10, 45, 90 and 180 minutes after acid was instilled into the lungs. Gas exchange, including PaO2 and venous admixture, did not differ between the two groups. However, after aspiration, oxygen delivery significantly improved in the dogs given nifedipine compared to oxygen delivery in those not treated with nifedipine. We conclude that, despite significant decreases in PaO2 and venous admixture, nifedipine can restore oxygen delivery back to normal levels.

Animals↗
PubMed1987

Beta-blocker therapy for the Wolff-Parkinson-White syndrome.

Two types of arrhythmias are associated with the Wolff-Parkinson-White syndrome: those in which the accessory pathway is a required part of the reentrant circuit, e.g., orthodromic atrioventricular reciprocating tachycardia, and those that conduct over the accessory pathway but do not require its activation for maintenance of tachycardia, e.g., atrial flutter/fibrillation. Increased sympathetic tone shortens the refractoriness of atrial and ventricular tissue; however, conduction in the atrium and ventricle is not considered the limiting factor for maintenance of atrioventricular reciprocating tachycardia or conduction over the accessory pathway in atrial arrhythmias. Intravenous beta-adrenergic blockers given to patients in the resting state have a minimal to moderate effect in depressing atrioventricular nodal conduction, but have little or no effect on accessory pathway refractoriness or conduction in most patients. In patients presenting with atrioventricular reentry, intravenous administration of beta-adrenergic blocking drugs often is not effective to terminate tachycardia. However, long-term oral therapy with these agents may be beneficial, especially in patients in whom enhanced sympathetic tone is responsible for the initiation or maintenance of tachycardia.

Adrenergic beta-Antagonists↗
PubMed1987

Frequency, diagnosis and clinical characteristics of patients with multiple accessory atrioventricular pathways.

Multiple accessory atrioventricular (AV) pathways were documented in 52 of 388 patients (13%) who underwent detailed electrophysiologic evaluation. Multiple AV pathways were identified during intraoperative mapping or electrophysiologic study by different patterns of ventricular preexcitation during atrial fibrillation, flutter or atrial pacing with different delta-wave morphologic and ventricular activation patterns; different sites of atrial activation during right ventricular pacing or orthodromic reciprocating tachycardia; or preexcited reciprocating tachycardia using a second pathway as the retrograde limb of the tachycardia. A logistic model was used to determine which clinical, electrocardiographic and electrophysiologic variables were associated with multiple AV pathways. Right free-wall and posteroseptal accessory AV pathways were more common in patients with multiple AV pathways and were frequently associated. Multivariate logistic regression identified Ebstein's anomaly, and a history of preexcited reciprocating tachycardia as significant variables (p less than 0.0001). Pathway location was not subjected to statistical analysis because of confounding variables.

Adolescent↗
PubMed1987

Ligand binding to transiently accessible sites: mechanisms for varying apparent binding rates.

Many biological processes are characterized by models where ligand has continuous access to binding sites. Use-dependent processes such as ion channel blockade appear to represent a class of processes where binding site access is transient and is dependent on channel conformation (state). (Alternatively, the existence of a proper conformation for binding might be transient.) We assume binding takes place only with a site that is accessible or in a bindable conformation. For ion channels, channel conformation responds to local chemical or electrical stimulation. The stimulus amplitude determines the mixture of channels with accessible and inaccessible sites. When conformation equilibrium is achieved rapidly in relation to ligand binding, then ligand binding can be considered the result of an apparent binding rate determined by the true binding rate as modified by the fraction of accessible sites. With repetitive stimulation, the continuous access model can be extended to a setting where apparent binding rates repetitively switch in response to the stimulus induced variation in mixture of site states. The resulting theoretical description provides a means for relating equilibrium binding parameters with those obtained under conditions of repetitive stimulation. In particular: (1) binding is piecewise exponential; (2) the envelope of binding measured at each pulse in a train varies exponentially with an apparent rate linearly dependent on the mixture specific rates; and (3) the steady state degree of binding site saturation is linearly dependent on the mixture specific equilibria.

Animals↗
PubMed1987

Value of the 12-lead electrocardiogram in discriminating atrioventricular nodal reciprocating tachycardia from circus movement atrioventricular tachycardia utilizing a retrograde accessory pathway.

The value of the 12-lead electrocardiogram for distinguishing atrioventricular (AV) nodal reciprocating tachycardia from circus movement AV tachycardia utilizing a retrograde accessory pathway was studied in 100 patients with narrow QRS complex tachycardia. Intracardiac electrograms showed AV nodal reciprocating tachycardia in 40 patients and circus movement AV tachycardia in 60. The 12-lead electrocardiograms recorded during tachycardia were randomly sorted and reviewed by 4 experienced cardiac electrophysiologists who were blinded to the diagnosis associated with each tracing, the relative proportion of each arrhythmia and the hypotheses to be tested. Each reviewer was asked to indicate the location of the P wave relative to the QRS complex, electrical axis of the P wave in the frontal and horizontal planes and presence or absence of QRS alternation, and to interpret the most likely mechanism. The performance of published electrocardiographic criteria to differentiate AV nodal reciprocating tachycardia from circus movement AV tachycardia was evaluated. The overall accuracy of the reviewers' interpretations was 75%, similar to the accuracy of the predefined criteria when applied by these observers (71% correct, difference not significant). Interobserver agreement of reviewer interpretations was 76% and the intraobserver agreement was 78%. Features associated with circus movement AV tachycardia by univariable analysis were P waves after the QRS complex, faster tachycardia rates and QRS alternation. Multivariable analysis showed that only the location of the P wave relative to the QRS complex was independently associated with the mechanism of tachycardia (p = 0.002). QRS alternation was found by multivariate analysis to be associated with the rate but not the mechanism of the tachycardia.

Diagnosis, Differential↗