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Biomedical subjects

J Kupersmith

Publications and source records attributed to J Kupersmith.

At least 19 recordsLinked to original sources

The effect of exercise-induced myocardial ischemia on postischemic left ventricular diastolic filling.

To determine whether exercise-induced ischemia impairs left ventricular diastolic filling in the postischemic period in humans, 101 men (mean age 57 +/- 10 years) were studied before and 2 h after a symptom-limited thallium-201 tomographic treadmill with pulsed Doppler echocardiography of mitral valve inflow. In the postischemic period 2 h after exercise, diastolic filling was significantly impaired in the ischemia group (reversible thallium defect; n = 24) as reflected by a decrease in the peak early filling velocity (44.5 +/- 10.1 to 39.9 +/- 9.9 cm/s, p less than 0.01), peak early to atrial filling velocity ratio (0.91 +/- 0.27 to 0.76 +/- 0.25, p less than 0.001), and deceleration rate of early filling (281 +/- 104 to 245 +/- 86 cm/s2, p less than 0.01). Similar alterations in the postischemic period occurred in the myocardial infarction-ischemia group (partially reversible defect; n = 28) as seen by a decrease in the peak early filling velocity (47.6 +/- 11.6 to 41.8 +/- 12.0 cm/s, p less than 0.001), peak early to atrial filling velocity ratio (0.84 +/- 0.21 to 0.68 +/- 0.18, p less than 0.001), and early time-velocity integral (7.06 +/- 1.78 to 5.64 +/- 2.07 cm, p less than 0.001). In the control group (no defects; n = 33) and myocardial infarction group (fixed defect; n = 16), diastolic filling was unchanged in the postexercise period. Heart rate and blood pressure were unchanged post-exercise in all groups. Exercise-induced ischemia impairs diastolic filling in the postischemic period in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Circulation

The transesophageal echocardiographic diagnosis of left atrial myxoma simulating a left atrial thrombus in the setting of mitral stenosis.

We report a case of left atrial myxoma simulating a thrombus on transthoracic echocardiography, but correctly diagnosed using transesophageal echocardiography. As this tumor is usually fatal unless surgically resected, a correct diagnosis is essential. Myxomas which do not prolapse between the mitral valve leaflets and coexist with mitral stenosis may be difficult to diagnose accurately using transthoracic echocardiography. The advantages of transesophageal compared with transthoracic echocardiography in the diagnosis of nonclassical left atrial myxoma are discussed.

Aged

The influence of obesity on left ventricular filling and systolic function.

Little information on the possible influence of obesity on diastolic function is available. Thus we studied 24 asymptomatic obese volunteers (greater than 120% ideal body weight; mean 153 +/- 30%), aged 34 +/- 11 years. Each obese subject was matched for age, height, and sex, with a healthy normal-weight control subject. Isovolumic relaxation time (IVRT) and diastolic filling indexes were determined by pulsed Doppler echocardiography. The IVRT was significantly prolonged in the obese group (84 +/- 17 msec) as compared with the control group (57 +/- 13 msec; p less than 0.0002). Multiple regression analysis showed that percentage of ideal body weight was the most important predictor of peak early filling velocity (r = 0.59, p less than 0.005) and mean deceleration rate of early filling (r = 0.61, p less than 0.005) in the obese group. However, age as compared with percentage of ideal body weight was a more important determinant of the relative distribution of early and atrial filling, such as peak early-to-atrial filling velocity ratio (r = -0.75, p less than 0.0001). Ejection fraction, heart rate, and blood pressure did not differ between the obese and control groups. In conclusion, obesity is associated with preclinical abnormalities of IVRT, which may reflect impaired relaxation. The IVRT may be useful in the early detection of left ventricular dysfunction in obesity. Last, studies comparing Doppler indexes of diastolic filling among groups must control for potential differences in percentage of ideal body weight.

Adolescent

Left ventricular ejection fraction is increased during transesophageal echocardiography in patients with impaired ventricular function.

Transesophageal echocardiography (TEE) is increasingly being used to assess left ventricular function (LVF). However, little data exist on the quantitative accuracy of this technique and its influence on LVF. Thus 50 ambulatory adult patients (mean age 62 +/- 15 years) were studied with transthoracic echocardiography (TTE) immediately before, before the end, and 10 minutes after TEE. Left ventricular ejection fraction (LVEF) was calculated using the modified Simpson's method. In subjects (n = 24) with impaired LVF (LVEF less than 55% by TTE), TTE-derived LVEF increased from 37 +/- 13% to 45 +/- 15% (p less than 0.001) during TEE. In 13 of 24 subjects with abnormal LVF, LVEF significantly increased during TEE as defined by an increase in LVEF by at least 5 ejection fraction units. In four of these subjects LVF normalized during TEE. LVEF was unchanged during and after TEE in the subjects (n = 26) with normal LVF (LVEF greater than 55%). An excellent correlation was found between LVEF derived by TEE and that derived by TTE performed during TEE (r = 0.93, SEE = 6.6%, p less than 0.001). LVEF determined by TEE compared well with that derived by TTE and should be a useful measure of global left ventricular function. However, an increase in LVEF during TEE occurs in over 50% of patients with impaired LVF and may be important to consider in individual subjects.

Adult

Conduction of early afterdepolarizations in sheep Purkinje fibers and ventricular muscle. An in vitro arrhythmia model.

To establish an arrhythmia generator model, a double-chambered bath was used in which sheep Purkinje fibers (PF) and ventricular muscle (VM) were placed. The conduction patterns of early afterdepolarization-induced triggered activations (TAs) were examined between normal segments bathed in unmodified Tyrode solution and abnormal segments bathed in ethylenediaminetetraacetate (3.3-5.0 mmol). Three types of preparations were used: PF-PF (n = 10), VM-VM (n = 5), and PF-VM (n = 13). Two types of spontaneous TAs appeared. One type was conducted to normal segments, inducing activations over the entire preparation, while the other type was not conducted. The conducting TAs had significantly more rapid mean dV/dt, larger amplitude, and higher peak transmembrane voltage as compared to nonconducting TAs. While conduction occurred in all PF-PF, VM-VM, and PF-VM preparations, conduction of TAs from abnormal segment VM to normal segment PF was impaired. A low plateau resulting from electrotonic transmission of depolarizing current from abnormal segments was recorded in normal segments near the border. This low plateau probably facilitated the transmission of TAs. In addition to spontaneous TAs, stimulated or spontaneous action potentials from NL were conducted to the not yet fully repolarized ABN and induced activations resembling TAs. These results may be relevant to clinical arrhythmias due to action potential prolongation. The arrhythmia may occur directly as a result of triggered activity or indirectly via slow conducting TAs, creating the possibility for reentry. This type of model may be useful for intervention studies, for example, by identifying agents that block abnormal segment to normal segment conduction.

Action Potentials

Prolongation of isovolumetric relaxation time as assessed by Doppler echocardiography predicts doxorubicin-induced systolic dysfunction in humans.

A reasonably sensitive and specific noninvasive test for doxorubicin cardiotoxicity is needed. In addition, few data exist on the short- and long-term effects of doxorubicin on diastolic filling. To determine if pulsed Doppler indexes of diastolic filling could predict doxorubicin-induced systolic dysfunction, 26 patients (mean age 48 +/- 12 years) were prospectively studied before receiving chemotherapy (control) and 3 weeks after obtaining cumulative doses of doxorubicin. In nine patients developing doxorubicin-induced systolic dysfunction (that is, a decrease in ejection fraction by greater than or equal to 10 ejection fraction units to less than 55%), the isovolumetric relaxation time was prolonged (from 66 +/- 18 to 84 +/- 24 ms, p less than 0.05) after a cumulative doxorubicin dose of 100 to 120 mg/m2. This prolongation preceded a significant decrease in ejection fraction. Other Doppler indexes of filling were impaired after doxorubicin therapy but occurred simultaneously with the decrease in ejection fraction. A greater than 37% increase in isovolumetric relaxation time was 78% (7 of 9) sensitive and 88% (15 of 17) specific for predicting the ultimate development of doxorubicin-induced systolic dysfunction. In 15 patients studied 1 h after the first treatment, doxorubicin enhanced Doppler indexes of filling and shortened isovolumetric relaxation time. In 22 patients, indexes of filling remained impaired and isovolumetric relaxation time was prolonged 3 months after the last doxorubicin dose. In conclusion, doxorubicin-induced systolic dysfunction is reliably predicted by prolongation of Doppler-derived isovolumetric relaxation time. Early after administration, doxorubicin enhances filling and isovolumetric relaxation time. The adverse effects of doxorubicin on both variables persist at least 3 months after cessation of treatment.

Adult

Purkinje fibre-papillary muscle interaction in the genesis of triggered activity in a guinea pig model.

OBJECTIVE: Previous studies have attempted to characterise the genesis of triggered activity related to early afterdepolarisations. Little is known about their conduction behaviour. This study was designed to examine the origin and conduction behaviour of triggered activations to throw light on the pathogenesis of torsade de pointes. METHODS: Electrophysiological interactions related to triggered activations and early afterdepolarisations between papillary muscle and Purkinje fibres were studied in the guinea pig in a single chambered bath. EDTA (5 mM) in Tyrode's solution was used and microelectrodes were placed in both papillary muscle and Purkinje fibres. RESULTS: During early superfusion, marked prolongation of action potential duration and early afterdepolarisations occurred in Purkinje fibres but not in papillary muscle. In addition: (1) with prolongation of action potential duration and early afterdepolarisations in Purkinje fibres, triggered activations arose during phase 2 and were conducted to papillary muscle, where they induced activations; (2) the number of papillary muscle discharges increased with the increase in Purkinje fibre action potential duration in a linear correlation; (3) severing a segment of papillary muscle from Purkinje fibres eliminated these papillary muscle activations; (4) some triggered activations did not conduct to papillary muscle; these had smaller amplitude, slower rate of depolarisation (dV/dt), more positive activation voltage, and similar peak voltages compared to conducted triggered activations; (5) a low plateau resulting from electrotonic interaction was recorded at the Purkinje fibre-papillary muscle junction; this plateau may have facilitated conduction of triggered activations. CONCLUSIONS: In this preparation there was a disparity of effect on Purkinje fibre and papillary muscle. Prolongation of action potential duration and repetitive activations due to early afterdepolarisations originated in Purkinje fibres and were conducted to papillary muscle. Purkinje fibre-papillary muscle interactions are of interest in relation to torsade de pointes arrhythmias which are believed to arise from this mechanism.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

Multicenter evaluation of a new fixed-wire coronary angioplasty catheter system: clinical and angiographic characteristics and results.

Coronary angioplasty is increasingly used as an attempt to revascularize patients with severe coronary artery disease. To determine the efficacy of such treatment, a new fixed wire angioplasty catheter was evaluated by a multicenter group in a non-randomized fashion in 50 patients, average 58 +/- 11 years (+/- 1 SD), 58% men. Forty-four percent had a prior revascularization procedure (28% angioplasty, 16% coronary bypass surgery), 38% had a prior Q-wave myocardial infarction, 43% had grade 4 angina, and 60% multiple vessel disease. Angioplasty was attempted in 63 lesions which were located in a mid to distal location in 69%, with a proximal tortuosity score of 1.8 (2 = 45-60 degrees entrance angle), and lesion angulation of 1.4 (1 = 45 degrees lesion bend). In 88%, the device was the primary catheter used and in 6%, it was chosen when another system failed. The balloon was able to successfully cross 94% of all lesions attempted. Six lesions were crossed and dilated but significant residual stenoses remained. There were no significant device malfunctions, or angiographic or clinical complications. This feasibility evaluation of this new fixed wire system yielded excellent angiographic results. Although not a comparative study, this analysis suggests that this new generation of angioplasty catheter may improve the safety and efficacy of complex coronary angioplasty.

Angiography

Two-dimensional transesophageal echocardiographic determination of aortic valve area in adults with aortic stenosis.

To determine if aortic stenosis severity could be accurately measured by two-dimensional transesophageal echocardiography (TEE), 62 adult subjects (mean age 66 +/- 12 years) with aortic stenosis had their aortic valve area (AVA) determined by direct planimetry using TEE, and with the continuity equation using combined transthoracic Doppler and two-dimensional echocardiography (TTE). Eighteen subjects had AVA calculated by the Gorlin method during catheterization. An excellent correlation (r = 0.93, SEE = 0.17 cm2) was found between AVA determined by TEE (mean 1.24 +/- 0.49 cm2; range 0.40 to 2.26 cm2) and TTE (mean 1.23 +/- 0.46 cm2; range 0.40 to 2.23 cm2). The absolute (0.13 +/- 0.12 cm2) and percent (10.8 +/- 8.9%) differences between AVA determined by TEE versus TTE were small. Excellent correlations between AVA by TEE and TTE were also found in subjects with normal systolic function (r = 0.95, SEE = 0.14 cm2; n = 38) and impaired function (r = 0.91, SEE = 0.21 cm2; n = 24). AVA determined by catheterization correlated better with AVA measured by TEE (r = 0.91, SEE = 0.15 cm2) than AVA measured with TTE (r = 0.84, SEE = 0.19 cm2). These data demonstrate that AVA can be accurately measured by direct planimetry using TEE in subjects with aortic stenosis. TEE may become an important adjunct to transthoracic echocardiography in the assessment of aortic stenosis severity.

Adult

Defibrillation efficacy using two low-profile endocardial electrodes.

The hypothesis that improved energy delivery and defibrillation efficacy can be achieved by using two widely separated endocardial electrodes and a cutaneous patch electrode was explored by positioning two 6.5 F electrodes (NuMed, Hopkinton, New York) with 5 cm platinum-iridium coils in the right ventricular apex (RVA) and the right ventricular outflow (RVO) in eight dogs. In another 12 dogs, an additional electrode was positioned in the RVA. A cutaneous patch (P) was placed at the cardiac apex. Biphasic pulses were delivered, the first pulse (6 ms) positive, the second negative (2 ms). The leading edge of the second was equal to the trailing edge of the first. RVO-/P+ and RVA-RVO-/P+ were compared with RVA-/P+ at a constant voltage setting required to achieve a 60% probability of success (P60) for RVA-/P+. At a constant voltage output, the probability of success for RVA-RVO-/P+ was significantly higher (81%) than RVO-/P+ (60%) or RVA-/P+ (67%) (p less than 0.03). The current delivered was greater for RVA-RVO-/P+ (9.9 +/- 2.3 amps) than for either RVA-RVO-/P+ (8.7 +/- 1.9 amps) or RVO-/P+ (9.0 +/- 2.0 amps) (p less than 0.0001). Similarly, the impedance was significantly lower for RVA-RVO-/P+ (66 +/- 12 omega) than for RVA-/P+ (75 +/- 12 omega) and RVO-/P+ (72 +/- 9.6 omega) (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Is defibrillation testing safe?

Determination of defibrillation thresholds (DFTs) and implantable cardioverter defibrillator (ICD) testing requires repeated inductions of ventricular fibrillation (VF) and defibrillation attempts using known energy outputs. Little is known about the individual and cumulative effects of repetitive brief episodes of VF and hypoperfusion on cerebral function. The potential clinical utility of quantitative electroencephalographic (QEEG) monitoring during intraoperative ICD testing, by using processed 19-channel EEG (0.5-35 Hz bandwidth), was examined in ten anesthetized patients, five males and five females (mean age 62 +/- 10 years), who underwent ICD implantation and testing. Ischemic QEEG patterns were defined as those with a 3 standard deviation increase (P less than 0.01) in absolute delta (1.5-3.5 Hz) power persisting for greater than or equal to 2.5 minutes. The majority (80%) of the VF episodes (70) were accompanied by QEEG "slowing" (doubling of the pre-VF low frequency delta waves amplitude). All the patients (5/5) experiencing greater than 6 VF episodes showed a statistically significant increase in the low frequency amplitude. In contrast, this EEG abnormality was apparent in only one of five patients experiencing less than 6 VF episodes. These results suggest a cumulative QEEG depression associated with ICD testing. QEEG may provide an objective means for establishing an individualized upper safe limit of DFT testing and the total number of induced VF episodes.

Electric Countershock

The initial clinical experience with an implantable cardioverter defibrillator/antitachycardia pacemaker.

Guardian antitachycardia pacing (ATP) 4210 is a third generation, multi-programmable cardioverter defibrillator undergoing Phase I clinical trials. The tiered response includes ATP, low energy cardioversion or defibrillation, and bradycardia support. Extensive telemetry is available, including an episode log and details of all episode events. Five patients underwent the implantation of Guardian ATP 4210 as part of a Phase I trial at the University of Louisville. Two of the five patients had multiple VT episodes that were reverted successfully using ATP pacing (slow VT) and defibrillation (fast VT) and VF episodes, which resulted in defibrillation therapy over a follow-up period of 6 to 8 months. Four of the five patients required bradycardia support for bradyarrhythmias unassociated with ATP therapy or defibrillation and one patient required bradycardia support postdefibrillation therapy. The device design is microprocessor based and requires continuous interrogation of the microprocessor memory and checks of the validity of programmed parameters to continue its operation. When the safety check fails, the device is designed to shut down its antitachycardia and defibrillator functions. This design feature has a potential for leaving the patient unprotected if the device shuts down. Modification of this feature is required to ensure the device's long-term safety.

Aged

Effects of stress and beta 1 blockade on the ventricular depolarization gradient of the rate modulating pacemaker.

Prism-CLR is a closed loop, rate modulating pacemaker that uses ventricular depolarization gradient (Gd) to continuously adjust heart rate. Heart rate response to a formal mental stress protocol, esmolol (500 mcg/kg bolus, 75-125 mcg/kg/min infusion), and mental stress during esmolol infusion were studied in six patients to investigate if Gd and paced heart rate response are under direct beta-adrenergic control. Paced heart rates increased in response to mental stress in a physiological manner (P less than 0.001). Response to esmolol infusion was paradoxical, with increased paced heart rates during esmolol bolus and infusion (P less than 0.05). There was no significant alteration in either systolic or diastolic blood pressure during mental stress or esmolol infusion (P greater than 0.05). Paradoxical increase in paced heart rates during esmolol administration suggests a primary or secondary effect of esmolol to decrease the ventricular depolarization gradient. This hypothesis was supported in four dog studies in which direct Gd measurements were made during esmolol infusion. Mental stress during esmolol infusion resulted in significantly increased paced heart rates (esmolol effect) with blunted changes in heart rate in response to the mental stress. The results of this study suggest that the physiological rate response during mental stress is attributable to sympathetic autonomic response.

Adrenergic beta-Antagonists

Preliminary results utilizing a new percutaneous transluminal coronary angioplasty balloon catheter.

We report our initial experience with a new percutaneous transluminal coronary angioplasty (PTCA) balloon catheter and compare it to a similar over-the-wire system in a retrospective, nonrandomized fashion. There was no statistical difference in pre-PTCA angiographic indices and post-PTCA angiographic and clinical success rates between the two groups. There was a trend toward a decrease in length of fluoroscopy (P = .08) and a significant decrease in the amount of contrast utilized (P = .007) with the new balloon catheter. Several new construction features of the new catheter account for this improvement and are discussed. The long-term success of this balloon catheter remains to be investigated.

Adult