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Biomedical subjects

W M Smith

Publications and source records attributed to W M Smith.

At least 145 records · Page 8Linked to original sources

Intravenous amiodarone bolus versus oral quinidine for atrial flutter and fibrillation after cardiac operations.

The safety and efficacy of amiodarone and quinidine in reverting atrial tachyarrhythmias after cardiac operations were compared in a randomized cross-over trial. Patients with sustained atrial fibrillation or flutter for more than 2 hours' duration, stable hemodynamic status, and prior digoxin therapy were randomized to receive either intravenous amiodarone, 5 mg/kg over 20 minutes (41 patients), or oral quinidine, 400 mg immediately and 400 mg in 4 hours (39 patients), with cross-over at 8 hours if reversion was not achieved. Thirty-six patients had a coronary artery operation, 35 a valvular operation, five had both, and there were four miscellaneous cases. There was a male:female ratio of 1.5:1 and a mean age of 58 years (range 23 to 75 years). Preoperative atrial fibrillation or flutter was present in nine patients, and four patients had an ejection fraction less than 40%. Twenty-five of 39 patients (64%) given quinidine first reverted to sinus rhythm, compared with 17 of 41 patients (41%) given amiodarone first (2p = 0.04). Side-effects occurred in 18 patients given quinidine and five patients given amiodarone (2p = 0.01). Two patients, both given quinidine, were withdrawn from the study. There was no correlation, with either drug, between serum levels and clinical efficacy. Multivariate analysis identified longer times from arrhythmia to treatment, preoperative atrial fibrillation, mitral valve operations, and concomitant propranolol therapy as factors predictive of failure to revert to sinus rhythm. Oral quinidine was more effective than intravenous amiodarone in reverting postoperative atrial fibrillation and flutter but caused more side-effects.

Administration, Oral↗

Comparison of the internal defibrillation thresholds for monophasic and double and single capacitor biphasic waveforms.

Implantable cardiac defibrillators are now an accepted form of therapy for patients with life-threatening ventricular arrhythmias that cannot be controlled by antiarrhythmic drugs. These devices could be made even more acceptable if they were smaller, had increased longevity and the surgical procedure for implantation was less invasive. Reducing the energy requirements for internal defibrillation with use of a nonthoracotomy system would make all of these goals achievable. Monophasic and double and single capacitor biphasic waveforms were compared in 14 anesthetized dogs (25.5 +/- 2.2 kg) with use of a nonthoracotomy lead system that has previously been shown to distribute the delivered voltage throughout the heart more equally. Cathodal catheter electrodes were placed in the right ventricular apex and outflow tract. The anodal electrode was a large cutaneous R2 patch placed over the left side of the chest. The mean energy requirement for defibrillation when a single capacitor biphasic waveform was used was significantly less (6.4 +/- 2.6 J) than that for either the double capacitor biphasic or the monophasic waveform (18.0 +/- 8.0 and 17.4 +/- 8.0 J, respectively) of the same duration. Unexpectedly, the leading edge voltage for the phase I of the single capacitor biphasic waveform was significantly less (266 +/- 51 V) than that for either the double capacitor biphasic or the monophasic waveform (336 +/- 76 and 427 +/- 117 V, respectively). In conclusion, in large dogs, defibrillation is possible at low energy levels with a single capacitor biphasic waveform.

Animals↗

Catheter ablation of the atrioventricular junction in patients with refractory atrial arrhythmias.

Twelve patients with refractory symptomatic atrial arrhythmias were evaluated for closed chest ablation and permanent pacemaker implantation. This was successful in nine of the 11 patients in whom ablation was attempted. Two of these nine patients required two separate ablative procedures. Three patients underwent open surgical ablation. Electrical ablation had failed in two of these patients and had not been undertaken in the remaining patient (inadequate His recording). The mean His amplitude and delivered energy levels were not significantly different between the two groups. Complications occurred in three patients and were minor. Because ventricular arrhythmias and late sudden death are recognised complications in a minority of patients undergoing closed chest ablation of the A-V junction it should be restricted to patients with symptomatic atrial arrhythmias who have failed maximal medical treatment.

Adult↗

Ventricular defibrillation using biphasic waveforms: the importance of phasic duration.

Biphasic waveforms can be used to defibrillate the heart with less energy than that used by monophasic waveforms. In 14 anesthetized open chest dogs with large contoured defibrillation electrodes, the effect on defibrillation efficacy of varying the duration of the two phases of biphasic waveforms was studied. All combinations of 0, 1, 3.5, 6 and 8.5 ms duration were used for both the first and the second phase except for the meaningless case in which both durations were 0 ms. The 3.5-2 waveform (3.5 ms first phase and 2 ms second phase) was also tested. All the hearts were defibrillated with less than or equal to 5 joules using any of the 25 waveforms. However, biphasic waveforms with the second phase shorter than or equal to the first had significantly lower defibrillation thresholds than did those with the second phase longer than the first or than did monophasic waveforms of approximately the same total duration. A plot of defibrillation threshold current strength versus second phase duration for all biphasic waveforms with a 3.5 ms first phase did not produce a hyperbolic strength-duration curve as seen with monophasic waveforms. To verify these findings, defibrillation dose-response curves were obtained for the 3.5-2, 6-6 and 3.5-8.5 biphasic waveforms in another six dogs. The 50 and 80% successful voltage doses of the 3.5-8.5 waveforms were significantly higher than those of the other two waveforms, which were not different from one another.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Four digital algorithms for activation detection from unipolar epicardial electrograms.

The reproducibility of activation detection by each of four algorithms used to calculate maximum derivatives was tested on two sequential paced beats of right ventricular unipolar epicardial electrograms which represented either local activation of the right ventricle alone or synchronous activation of both ventricles. The methods were evaluated by comparing the shape of the two beats aligned on their selected activation times, i.e., the time at which the maximum negative deflection occurred, the differences in activation intervals for the two beats, and the effect on the activation time of superimposing distant events on local activation. The 17-point second-order data fit algorithm performed slightly better than the first-order difference, three-point Lagrange derivative, and five-point second-order data fit algorithms except that activation time selection by the 17-point technique was slightly, but significantly, delayed by the superposition of distant potentials. The 17-point second-order data fit technique is therefore recommended for use in detecting activation unless computation time is a major consideration. In that case, the five-point second-order data fit technique, which uses only four data values for each computation, can be used with only slight decreases in accuracy.

Algorithms↗

Interpolating unipolar epicardial potentials from electrodes separated by increasing distances.

In cardiac mapping, potentials for unexplored areas are estimated by interpolating values from nearest neighbor electrodes regardless of distances between these sites or wave front orientation. The effects of these variables on interpolated unipolar electrograms were analyzed two ways: with a computer model and with electrograms recorded 9.9 and 14.1 mm apart. For the model, wave fronts (n = 39) were generated from electrograms recorded during right ventricular (RV) activation in five dogs following the RV isolation procedure. Each wave front was assumed to propagate radially at 0.5 m/sec from a site 30 mm from the center of a square array with electrodes located at the center and corners. Each wave front crossed the array with its tangent at an angle of 0 degrees, 45 degrees, or 90 degrees to the diagonal line connecting opposite corner electrodes. Potentials for all five sites were generated from each wave front and were interpolated for the center site from the generated corner potentials. Generated and interpolated center site potentials were compared using correlation coefficients (r) and percent root mean square differences (%RMSD). Mean r values fell below 0.90 for interelectrode distances of 15.6 mm, 2.8 mm, and 1.4 mm at 0 degrees, 45 degrees, and 90 degrees wave front orientations, respectively. For experimentally measured potentials recorded 9.9 mm apart, results from interpolated electrograms were similar to results from the model at 0 degrees propagation. Electrograms interpolated from potentials measured 14.1 mm apart had poorer r and %RMS values than those from the computer model. Thus, with linear interpolation unipolar electrograms can be inaccurately interpolated from electrodes less than 3 mm apart or correctly interpolated from electrodes more than 14 mm apart depending upon wave front orientation.

Action Potentials↗

The assumptions of isochronal cardiac mapping.

Isochronal maps of cardiac activation are commonly used to study the mechanisms and to guide the ablative therapies of arrhythmias. Little has been written about the assumptions implicit in the construction and use of isochronal cardiac maps. These assumptions include the following: (1) the location of the recording electrodes is known with sufficient accuracy to determine the mechanism of an arrhythmia or to guide therapy; (2) a single, discrete activation time can be assigned to each recording electrode location; (3) the presence or absence of activation at an electrode site can be reliable ascertained, and when activation is present, the time of activation can be determined with sufficient accuracy to specify the mechanism of an arrhythmia or to guide therapy; and (4) the recording electrodes are close enough together that the activation sequence can be estimated with sufficient accuracy to determine the mechanism of an arrhythmia or to guide therapy. The manuscript reviews evidence that these assumptions may not always be true, and when they are not, the isochronal map may be misleading.

Arrhythmias, Cardiac↗

Morbidity and mortality in the Systolic Hypertension in the Elderly Program (SHEP) pilot study.

The pilot study of the Systolic Hypertension in the Elderly Program was a randomized, double-blind, placebo-controlled trial of drug therapy for isolated systolic hypertension. It followed 551 elderly participants with untreated blood pressures of greater than 160/less than 90 mm Hg for an average of 34 months. Mean age of the participants was 72 years; 63% were women, and 82% were white. Pretreatment blood pressures averaged 172/75 mm Hg. Participants were randomly assigned to treatment with chlorthalidone or placebo as Step I medication. Blood pressures at annual visits averaged 141/68 and 157/73 mm Hg for the drug-treated and placebo-treated groups, respectively, with 60% and 33% of the survivors on blinded medication having systolic blood pressures of less than 160 mm Hg at their last annual visit. All-cause mortality rates for the drug-treated and placebo-treated groups were 25.4 and 22.7 deaths per 1,000 participant-years of risk, and rates for definite "first stroke" were 8.3 and 12.8 per 1,000 years of risk. Differences between groups were significant for systolic and diastolic blood pressure but not for death or stroke rates. A full-scale study has begun to determine the effects of drug therapy for isolated systolic hypertension on stroke and mortality rates.

Antihypertensive Agents↗

Stimulus-induced critical point. Mechanism for electrical initiation of reentry in normal canine myocardium.

The hypothesis was tested that the field of a premature (S2) stimulus, interacting with relatively refractory tissue, can create unidirectional block and reentry in the absence of nonuniform dispersion of recovery. Simultaneous recordings from a small region of normal right ventricular (RV) myocardium were made from 117 to 120 transmural or epicardial electrodes in 14 dogs. S1 pacing from a row of electrodes on one side of the mapped area generated parallel activation isochrones followed by uniform parallel isorecovery lines. Cathodal S2 shocks of 25 to 250 V lasting 3 ms were delivered from a mesh electrode along one side of the mapped area to scan the recovery period, creating isogradient electric field lines perpendicular to the isorecovery lines. Circus reentry was created following S2 stimulation; initial conduction was distant from the S2 site and spread towards more refractory tissue. Reentry was clockwise for right S1 (near the septum) with top S2 (near the pulmonary valve) and for left S1 with bottom S2; and counterclockwise for right S1 with bottom S2 and left S1 with top S2. The center of the reentrant circuit for all S2 voltages and coupling intervals occurred at potential gradients of 5.1 +/- 0.6 V/cm (mean +/- standard deviation) and at preshock intervals 1 +/- 3 ms longer than refractory periods determined locally for a 2 mA stimulus. Thus, when S2 field strengths and tissue refractoriness are uniformally dispersed at an angle to each other, circus reentry occurs around a "critical point" where an S2 field of approximately 5 V/cm intersects tissue approximately at the end of its refractory period.

Animals↗

Cardiac mapping at Duke Medical Center.

CLINICAL PERSPECTIVE: Ventricular fibrillation is a major, but little understood, cause of death. Although defibrillation with electric shock has been in use for several decades, and although many advances have been made in the design of defibrillators (including the development of implantable devices for high-risk patients), this procedure has generally been an empiric one. The mechanisms of the procedures are being intensely studied at Duke University and other institutions in the hope of developing more energy efficient and clinically effective defibrillation equipment.

Action Potentials↗

Epidemiology of hypertension in older patients.

There are few studies devoted specifically to the epidemiology of older hypertensive patients, although some information has been obtained from broader trials in which either the study populations have become older or an older subgroup has been identified. Three areas have been addressed: the changes of blood pressure with age; the prevalence of hypertension in older persons; and the risks of elevated blood pressure in elderly patients. It has been found that blood pressure, especially systolic pressure, increases with age. Consequently, hypertension is extremely prevalent in this age group, affecting 65 percent or more of those over 65 years old, and the phenomenon of isolated systolic hypertension is common. Whereas in the past many physicians treating the elderly have regarded hypertension in these patients as normal and acceptable, or even helpful in ensuring adequate organ perfusion, elevated blood pressure in the elderly is far from benign. Older hypertensive patients' risks of cardiovascular complications and death are from two to five times that of normotensive persons. Treatment of diastolic hypertension in older patients can be expected to delay the onset of cardiovascular disease and improve the quality of life. Hopefully, this will prove to be true for isolated systolic hypertension as well.

Black or African American↗

Pharmacokinetic and pharmacodynamic interactions of propafenone and cimetidine.

The pharmacokinetics and pharmacodynamics of the extensively metabolized antiarrhythmic agent propafenone were assessed alone and during concomitant administration of cimetidine. Twelve healthy subjects were given successively the following treatments: propafenone 225 mg q8h plus cimetidine placebo; cimetidine 400 mg q8h plus propafenone placebo; and propafenone 225 mg plus cimetidine 400 mg q8h. After a minimum of 5 days on each regimen, plasma drug concentrations and electrocardiogram conduction intervals were measured during a drug washout period. The maximum concentration of propafenone in plasma was 993 +/- 532 ng/mL when propafenone was given alone compared with 1230 +/- 591 ng/mL when propafenone was given with cimetidine (P = .0622). Differences in tmax, t1/2, and Cp ss did not approach statistical significance when propafenone alone was compared with propafenone plus cimetidine. When compared with cimetidine, propafenone significantly increased the PR interval from 161 +/- 5 msec to 192 +/- 6 msec (P less than .01) and the QRS duration from 89 +/- 3 msec to 98 +/- 4 msec (P less than .01). Combination therapy caused a modest additional increase in QRS duration to 103 +/- 3 msec (P less than .01). In conclusion, cimetidine caused small changes in propafenone pharmacokinetics and pharmacodynamics; but these changes are unlikely to be clinically important.

Adult↗

Comparison of time domain and frequency domain variables from the signal-averaged electrocardiogram: a multivariable analysis.

The relative values of the unprocessed signal-averaged electrocardiogram (ECG) and time domain analysis and frequency domain analysis of the signal-averaged ECG were compared in 36 patients with sustained monomorphic ventricular tachycardia and a remote myocardial infarction, in 29 asymptomatic patients with a remote myocardial infarction and in 23 normal subjects. Area ratios of the energy spectra derived from fast Fourier transform analysis were calculated using six separate 140 ms intervals starting at 0, 40, 50 and 60 ms after QRS onset; 40 and 50 ms before QRS end and a variable length interval starting 40 ms before QRS end and extending to the T wave. Total filtered QRS duration, late potential duration and root mean square voltage of the terminal QRS complex were measured from the filtered vector magnitude signal-averaged ECG. The total QRS duration was also measured from the X, Y, Z leads of the unfiltered signal-averaged ECG. Seven variables were significantly different in univariate tests between myocardial infarction patients with and without ventricular tachycardia: three fast Fourier transform area ratios with the sampling interval starting at 1) QRS onset (p = 0.007), 2) 40 ms after QRS onset (p = 0.02), and 3) 60 ms after QRS onset (p less than 0.0001); and all four time domain variables at 1) total filtered QRS duration (p less than 0.0001), 2) late potential duration (p = 0.0001), 3) root mean square terminal QRS voltage (p = 0.0001), and 4) QRS duration from the unprocessed signal-averaged ECG (p less than 0.0001). Of these seven variables, only the fast Fourier transform area ratio starting at QRS onset was significantly different between patients with myocardial infarction without ventricular tachycardia and normal subjects. In multi-variable analysis, the total filtered vector magnitude QRS duration, a time domain variable that includes the late potential, was the only independent factor that separated patients with myocardial infarction with and without associated ventricular tachycardia.

Analysis of Variance↗

The case for treating hypertension in the elderly.

Not so long ago it was fashionable to ignore a little bit of hypertension in an elderly person. The rationalizations for this position included the limited epidemiological data establishing the risk of elevated blood pressure in the age group over 65, particularly for women; and concern that lowering the blood pressure might not be desirable, from the standpoint of reduced blood flow to vital organs. There was also concern over the known greater responsiveness or sensitivity of older people to customary doses. It was also argued by some that even if the blood pressure could be safely controlled it was hardly worth it, since age itself is the most powerful predictor of mortality in the elderly. Moreover, it seemed unlikely to many that the risk of hypertension could be reduced--that is, that life expectancy could be extended; at the same time it seemed fairly certain that the quality of life would be compromised by therapy. However, since systolic blood pressure continues to be predictive of coronary heart disease mortality well into the ninth decade, and since considerable life expectancy remains for those who have survived to their senior years, it seems logical to attempt to reduce the risk and preserve life expectancy by controlling blood pressure. The question is, is the evidence that treatment helps really convincing, or are we simply extrapolating from studies carried out in younger subjects? Review of the early literature, which focused almost exclusively on stroke survivors and the influence of hypertension on stroke recurrence, provides inconsistent, conflicting, and not persuasive information.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

Effects of treatment for isolated systolic hypertension on cognitive status and depression in the elderly.

The Systolic Hypertension in the Elderly Program (SHEP) was designed as a feasibility study and in part dealt with the effects of the treatment of isolated systolic hypertension on cognitive status and depression. Subjects were 60 years of age or older with a systolic blood pressure of 160 mmHg or greater and diastolic of less than 90 mmHg; free of several specified illnesses or chronic conditions. These volunteers were randomly assigned to treatment (n = 443) and placebo (n = 108) groups. The behavioral assessments at baseline and 1 year later were the SHORT-CARE instrument for depression, cognitive impairment, and disability and other tests of cognitive status (Digit Symbol Substitution and the Trail Making tests). Although the treatment regime was highly successful in controlling the hypertension, it did not have a significant impact on changes in cognitive function or level of depression; a behavioral benefit was not evident but the results are consistent with the view that an effective treatment regime for isolated systolic hypertension in the elderly can be behaviorally safe.

Aged↗