Biomedical subjects

A H Kadish

Publications and source records attributed to A H Kadish.

At least 37 records · Page 2Linked to original sources

PubMed1999

Differential effects of parasympathetic blockade and parasympathetic withdrawal on heart rate variability.

INTRODUCTION: Low heart rate variability (HRV) has been shown to have important prognostic significance in multiple settings. Although this is believed to reflect reduced parasympathetic tone, the physiology of reduced parasympathetic tone has not been elucidated. METHODS AND RESULTS: To evaluate whether parasympathetic withdrawal and partial parasympathetic blockade result in similar changes in HRV, 27 normal volunteers underwent complete beta-adrenergic blockade and then were given (1) graded doses of nitroprusside to achieve baroreflex-mediated parasympathetic withdrawal and (2) low-dose atropine (0.01 mg/kg) to achieve partial parasympathetic blockade. Five-minute ECG recordings were obtained for HRV analysis. In 19 subjects, paired 5-minute recordings from each condition were available with mean RR intervals that differed by < 50 msec (low-dose atropine: 869 +/- 96 msec and nitroprusside 875 +/- 99 msec). The root mean square of the successive RR interval differences was lower following low-dose atropine than following parasympathetic withdrawal with nitroprusside (16 +/- 11 msec vs 22 +/- 15 msec; P < 0.02). During parasympathetic withdrawal, the low-frequency (LF) power was 0.917 +/- 0.602 bpm2 and the high-frequency (HF) power was 0.501 +/- 0.521 bpm2. During partial parasympathetic blockade, the LF and HF powers were significantly lower (0.443 +/- 0.474 bpm2, P < 0.005; and 0.198 +/- 0.207 bpm2, P < 0.02). CONCLUSION: These data confirm that HRV reflects the character of parasympathetic modulation of the heart rate rather than parasympathetic tone per se. Furthermore, this study identifies two distinct physiologic explanations for the finding of low HRV, namely, diminished vagal discharge and resistance of cardiac muscarinic receptors to vagal discharge. Further delineation of the relationships between parasympathetic tone and HRV will allow for better understanding of the pathophysiologic derangements associated with low HRV.

Adult↗

PubMed1998

Nonsustained ventricular tachycardia in the setting of acute myocardial infarction: tachycardia characteristics and their prognostic implications.

BACKGROUND: Nonsustained ventricular tachycardia (NSVT) has significant prognostic implications in the setting of healing and healed myocardial infarction (MI), but only limited information is available on its importance in the setting of acute MI. We evaluated the prognostic significance of NSVT characteristics in the setting of acute MI. METHODS AND RESULTS: A prospective database was used to identify 112 patients with NSVT within 72 hours of acute MI. A control group was identified matched for age, sex, type of MI, and thrombolytic treatment. Mean age was 64 to 65 years in the 2 groups with 71% to 72% men. Q-wave MI was noted in 52% to 53%, and thrombolytic therapy was administered to 31% to 32% of patients in each group. In-hospital ventricular fibrillation occurred more frequently in the NSVT group (9% versus 0% in the control group; P<0. 001), but total in-hospital (10% versus 4%) and follow-up mortality (10% versus 17%) did not differ between the 2 groups. With a Cox regression model, specific NSVT characteristics were predictive of mortality. The strongest predictor was time from presentation to occurrence of NSVT. Shortest RR interval during NSVT was also a univariate predictor of mortality. Multivariate analysis identified time from presentation to occurrence of NSVT as the strongest predictor of mortality (P<0.0001). The increased relative risk of NSVT was first significant when it occurred 13 hours from presentation and continued to increase as the time from presentation to occurrence of NSVT increased, plateauing at approximately 24 hours with a relative risk of 7.5. CONCLUSIONS: Contrary to prevailing clinical opinion, NSVT that occurs in the setting of acute MI does have important prognostic significance. Specifically, the currently accepted notion that NSVT that occurs within 48 hours of acute MI has no prognostic significance needs to be adjusted. Although NSVT that occurs within the first several hours of presentation does not have an associated adverse prognosis, NSVT that occurs beyond the first several hours after presentation is associated with significant increases in relative risk.

Aged↗

PubMed1998

Effects of hormone replacement therapy on QT interval.

We evaluated the electrocardiograms of 208 postmenopausal women (ages 40 to > or = 70 years) without heart disease, medications that could alter the QT interval, use of vaginal estrogens, unknown hormone replacement therapy, or electrocardiographic abnormalities both with (n = 76) and without (n = 132) hormone replacement therapy, and found no significant effects of hormone replacement therapy status on heart rate, QT interval, or the corrected QT interval. Thus, estrogen and/or progesterone effect does not explain the gender differences in myocardial repolarization.

Adult↗

PubMed1998

Effects of gender on cardiac arrhythmias.

The purpose of this study is to review published data regarding gender differences in cardiac electrophysiology and in the occurrence of clinical arrhythmias. ECG differences between men and women include a faster resting heart rate in women, a longer corrected QT interval, and a lower QT dispersion than in men. The faster resting heart rate in women appears to be primarily related to differences in physical conditioning. The mechanism for the longer corrected QT interval in women is not completely known, but does not appear to be related to acute effects of estrogen or progesterone or differences in autonomic innervation. Women also appear to have a lower incidence of atrial fibrillation, a difference in the age distribution of supraventricular tachycardia, and a lower incidence of sudden death than men. Much of the lower incidence of sudden death in women may relate to a difference in the prevalence of coronary artery disease, but other factors such as inherent differences in repolarization, which may be reflected by a gender difference in the corrected QT interval, also may be operative. The paradox of a longer corrected QT interval and higher incidence of torsades de pointes, but lower population-based incidence of sudden death in women, has not been completely resolved. Further studies will be required to help better understand the basic mechanisms involved in gender differences in electrophysiology and arrhythmias and determine the extent to which these differences have implications for clinical management of cardiac arrhythmias.

Arrhythmias, Cardiac↗

PubMed1998

Detection of ventricular fibrillation by transvenous defibrillating leads: integrated versus dedicated bipolar sensing.

INTRODUCTION: Dedicated bipolar sensing has been suggested to be safer than integrated bipolar sensing due to an increased incidence of failure to redetect ventricular fibrillation after an unsuccessful shock with leads that use integrated bipolar sensing. We compared sensing characteristics during ventricular fibrillation of simultaneously recorded dedicated and integrated bipolar electrograms. METHODS AND RESULTS: Thirty patients undergoing transvenous defibrillator implantation with a Transvene lead were studied. Simultaneous recordings were made from the dedicated bipole and the integrated bipole from the distal tip to the coil (interelectrode distance 18.3 mm). The mean detection time and number of undetected beats for the initial episode of ventricular fibrillation were 2804 +/- 569 msec and 0.9 +/- 0.8 using the dedicated recordings and 2938 +/- 546 msec and 1.4 +/- 1.1 (P = 0.026) using the integrated recordings. The mean redetection times and number of undetected beats following a failed first shock (n = 13) were 2468 +/- 225 msec and 0.8 +/- 1.1 for the dedicated recordings and 3042 +/- 498 msec (P < 0.0003) and 4.2 +/- 4.2 (P < 0.005) for the integrated recordings. Frequency analysis of the ventricular fibrillation electrograms demonstrated that the signal energy in the dedicated electrograms was significantly greater than the energy in the integrated electrograms (P < 0.0001). There was a significant negative relationship between detection times and the ventricular fibrillation signal energy. There was no independent effect of recording type (dedicated versus integrated). CONCLUSION: There are only minor differences in detection/redetection of ventricular fibrillation between dedicated and integrated (with tip to coil spacing of 18.3 mm) recording configurations. Detection times during ventricular fibrillation are related to the signal variance or energy recorded. Differences in the sensing performance of the two recording configurations can be explained by the differences in signal energy between the dedicated and integrated recordings that occur during ventricular fibrillation.

Defibrillators, Implantable↗

PubMed1998

Effects of intravenous propranolol on human ventricular strength interval curves.

BACKGROUND: Prior studies on the effects of propranolol on human ventricular refractoriness have yielded occasionally inconsistent results. Most prior studies have examined refractory periods at a single stimulus intensity and without using continuous pacing; thus, the effects of propranolol on repolarization may have not been completely defined. The purpose of the present study was to reevaluate the effects of beta blockade on the human ventricular effective refractory period. METHODS: Strength-interval curves were performed in duplicate in a group of 10 patients to demonstrate their reproducibility. Strength-interval curves were performed before and after intravenous propranolol administration in a second group of 10 patients who had no evidence of structural heart disease. RESULTS: Propranolol increased the absolute refractory period from 208 +/- 9 milliseconds to 212 +/- 10 milliseconds (p = 0.01). However, propranolol decreased the coupling interval at which the strength-interval curve began to show an increase in the stimulus intensity required for capture from 236 +/- 8 milliseconds to 232 +/- 9 milliseconds. This resulted in a decrease of the width of the strength-interval curve from 28.0 +/- 5.1 milliseconds to 20.4 +/- 5.5 milliseconds (p < 0.005). Propranolol also significantly increased the slope of a logarithmic fit of the strength-interval curves. CONCLUSION: Propranolol exerts complex effects on human ventricular refractoriness. Propranolol decreases the width and increases the slope of human strength-interval curve, rather than increasing or decreasing the refractory period. These results have potential implications for antiarrhythmic effects of propranolol.

Adrenergic beta-Antagonists↗

PubMed1997

Acute hemodynamic effects of intravenous ibutilide in patients with or without reduced left ventricular function.

Many antiarrhythmic agents have adverse hemodynamic effects which limit their use in patients with impaired ventricular function or during tachyarrhythmias. Ibutilide is an intravenous, selective class III antiarrhythmic agent that is effective for conversion of atrial fibrillation or flutter. This multicenter, randomized, placebo-controlled, dose-ranging study evaluated the effects of intravenous ibutilide on hemodynamic parameters during invasive monitoring in 47 patients with or without reduced left ventricular ejection fraction (LVEF) > 35% or < or = 35%. Patients received either placebo or ibutilide as a 10-minute loading and a 30-minute maintenance infusion using 1 of the following dosing regimens: placebo then placebo (n = 12); 0.01 then 0.002 mg/kg (n = 12); 0.02 then 0.004 mg/kg (n = 12); or 0.03 then 0.006 mg/kg (n = 11). Ibutilide significantly increased QT and QTc intervals in a dose-related manner with mean increases ranging from 51 to 99 ms, but did not alter the PR interval or QRS duration. During ibutilide infusion, a few small but statistically significant changes from baseline in several hemodynamic variables were present. However, the changes in cardiac output, pulmonary artery or capillary wedge pressures, blood pressure, or heart rate in patients receiving ibutilide were not significantly different from the changes in patients receiving placebo. Thus, ibutilide did not cause clinically important adverse hemodynamic effects, even in patients with depressed ventricular function. One patient developed 2 episodes of nonsustained torsades de pointes during ibutilide. These results demonstrate that with careful monitoring for proarrhythmia, ibutilide can be used safely from a hemodynamic standpoint in the acute treatment of arrhythmias, even in patients with reduced ventricular function.

Adult↗

PubMed1997

Utility of predischarge and one-month transvenous implantable defibrillator tests.

We evaluated the utility of performing predischarge implantable cardioverter-defibrillator (ICD) testing and ICD testing at 1 month in detecting ICD-related problems, identifying 4 patients with an unacceptable increase in defibrillation threshold. Given that ICD testing is noninvasive and has minimal (if any) associated risk, we recommend that predischarge and 1-month follow-up ICD testing should be performed after implantation.

Aged↗

PubMed1997

Gender-specific differences in the QT interval and the effect of autonomic tone and menstrual cycle in healthy adults.

Gender differences in the corrected QT interval have been noted since Bazett's initial description during the 1920s. The mechanism of this gender difference is unknown, and this study was undertaken to evaluate potential autonomic and menstrual cycle effects on the QT interval. The study population consisted of a healthy volunteer sample of 23 women and 20 men. Twelve-lead electrocardiographic determinations were made at rest and following double autonomic blockade (with atropine and propranolol) during the menstrual, follicular, and luteal phases of the menstrual cycle. Men were studied during 3 separate visits as controls. The corrected QT interval at baseline tended to be longer in women than men (421 +/- 16 ms vs 414 +/- 15 ms: p <0.07). Following double autonomic blockade, the corrected QT interval increased to 439 +/- 11 ms: p <0.001). However, the gender difference in corrected QT interval was unchanged (443 +/- 15 ms vs 437 +/- 12 ms). At baseline, there was no significant difference in the corrected QT interval among the 3 phases of the menstrual cycle (421 +/- 10, 423 +/- 18, and 420 +/- 18 in the menstrual, follicular, and luteal phases, respectively) and the corrected QT interval was longer in women than men at each visit. Following double autonomic blockade, the corrected QT interval in women was shorter in the luteal phase (438 +/- 16 ms) versus the menstrual (446 +/- 15 ms) or the follicular phase (444 +/- 13 ms; p <0.05). However, this difference, which was not present at baseline, does not appear to be responsible for the gender difference in the QT interval at rest. In conclusion, our results confirm that the corrected QT interval tends to be longer in women than men. Differences in autonomic tone and menstrual cycle variability in the corrected QT in women at rest do not appear to be responsible for the gender differences in the QT interval. The mechanism responsible for the longer QT interval in women remains to be defined.

Adult↗

PubMed1997

Effect of informed consent on anxiety in patients undergoing diagnostic electrophysiology studies.

The process of informed consent has been suspected to raise patient anxiety, but this supposition has not been well studied or validated. The aim of this study was to evaluate the effect of a detailed informed consent protocol on patient anxiety. Fifty patients (36 men, 14 women, mean age 55 +/- 18 years) undergoing diagnostic cardiac electrophysiologic studies were enrolled. Patients were randomly assigned to receive either a consent that did not detail specific risks regarding the procedure (consent A) or one that detailed the risks (consent B). The Spielberger State-Trait Anxiety Inventory was administered before obtaining consent (state 1), immediately after the consent protocol (state 2), and after the electrophysiologic testing procedure, when the results of the test were known to the patient (state 3). Midazolam was administered during the procedure by staff who were blinded to the state/trait anxiety scores and the type of consent the patient had received. Patients receiving consent A had a significant decrease in state 2 anxiety compared with those who received consent B (adjusted mean difference 3.3; 95% confidence intervals 0.2 to 6.4). In the consent A group, 74% of patients received midazolam as opposed to 96% in the consent B group (p <0.02). Patients without inducible ventricular arrhythmias had a significant decrease in state 3 anxiety compared with those with inducible ventricular arrhythmias (adjusted mean difference 8.9; 95% confidence intervals 2.3 to 15.5). Thus detailed informed consent is associated with increased anxiety relative to a consent that does not detail specific risks. However, the difference in anxiety is mild and its clinical impact requires further exploration.

Anti-Anxiety Agents↗

PubMed1997

Autonomic effects on noise recorded during signal-averaged electrocardiography.

The purpose of this study was to assess the effects of autonomic stimulation and blockade on noise levels and to compare the noise measurements in the ST and TP segments of the signal-averaged ECG. Five-minute electrocardiographic data were recorded in 14 normal volunteers (8 males and 6 females; mean age 28.5 +/- 5.0 years) on two separate days (day 1-baseline, epinephrine infusion, isoproterenol infusion, beta-blockade, and combined adrenergic and parasympathetic blockade; day 2-baseline, phenylephrine infusion, parasympathetic blockade, and during phenylephrine infusion following atropine). Signal averaging was done off-line on 100 beats and noise was measured in both the ST and TP segments as the standard deviation of voltage in the segment of interest. For all conditions tested, the mean noise level measured in the ST segment (0.46 +/- 0.16 microV) was significantly less than that measured in the TP segment (0.52 +/- 0.24 microV; P = 0.0003), but there was good correlation between the noise measured in the ST and the TP segment (R2 = 0.62, P < 0.0001). Noise increased with isoproterenol infusion and decreased following adrenergic blockade. In addition, day 2 baseline noise was less than baseline noise on day 1. Finally, neither parasympathetic stimulation or blockade nor alpha-adrenergic stimulation significantly affected signal-averaged electrocardiography (SAECG) noise levels. Thus, the data support the notion that enhanced sympathetic tone increases noise levels and beta-adrenergic blockade may decrease noise levels, likely due to effects from muscle sympathetic nerve activity. These findings are important since the target population for the SAECG are patients with myocardial infarction and congestive heart failure, conditions associated with increased sympathetic tone, which may in turn impact on the reproducibility or technical aspects of the SAECG. In addition, because noise in the ST and TP segments are highly correlated and the noise measured in the ST segment is less than that in the TP segment, uniform adoption of noise measurement in the ST segment seems most appropriate.

Adrenergic Antagonists↗

PubMed1997

Characterization of the factors that determine the effect of sympathetic stimulation on heart rate variability.

Heart rate variability analysis has been used to derive indices of sympathetic tone. As different sympathetic stimuli may give rise to divergent changes in heart rate variability, this study was designed to characterize the factors responsible for these divergent responses. Twelve healthy subjects (7 males, age 24.8 +/- 3.1 years) were evaluated. Five-minute electrocardiographic recordings were obtained at baseline, following upright tilt, and during isoproterenol infusion (25 ng/kg per min) under control conditions and following parasympathetic blockade. Data were acquired during spontaneous respiration and when breathing was timed with a metronome (15 breaths/min). Under control conditions, both upright tilt and isoproterenol infusion resulted in significant decreases in the SD and MSSD from baseline values of 69 +/- 3 ms and 64 +/- 5 ms to 48 +/- 4 ms and 21 +/- 5 ms during tilt and 44 +/- 4 ms and 20 +/- 5 ms during isoproterenol infusion, respectively. LF power also significantly increased from 0.47 +/- 0.17 ln (beats/min)2 at baseline to 1.90 +/- 0.20. In (beats/min)2 and 1.34 +/- 0.18. In (beats/min)2 during tilt and isoproterenol infusion, respectively. No change in HF power was noted. Following parasympathetic blockade, all heart rate variability parameters were significantly decreased. No significant change from baseline in the SD, MSSD, or HF power was noted with either tilt or isoproterenol infusion. The LF power increased only with tilt from a baseline value of -3.17 +/- 0.17 in (beats/min)2 to -0.41 +/- 0.19 in (beats/min)2. Similar changes were noted during spontaneous respiration and metronome breathing. These findings demonstrate that the response of the sinus node to beta-adrenergic stimulation depends on the mode of stimulation. In addition, the associated level of parasympathetic tone affects the observed changes in heart rate variability that are associated with sympathetic stimulation.

Adult↗

PubMed1997

Adenosine induced polymorphic ventricular tachycardia in adults without structural heart disease.

Adenosine has been reported to cause polymorphic VT in patients with congenital or acquired prolonged QT intervals and to cause pause dependent VT in a patient with a normal QT interval. There have been no previous reports of adenosine causing nonpause dependent polymorphic VT in patients without structural heart disease. We report two patients, with normal hearts and normal QT intervals, who developed nonsustained polymorphic VT that was not pause dependent. Adenosine induced polymorphic VT does not appear to be a marker of the long QT syndrome, but may be an uncommon yet not unexpected pharmacological response to drug administration.

Adenosine↗

PubMed1997

Late recurrence of atrial flutter following radiofrequency catheter ablation.

The success rate for catheter ablation of atrial flutter has been reported to be approximately 90%, but recurrences are common and can be seen in up to 20% of cases. Most of these recurrences are seen within a few weeks following ablation. We report on a patient who developed a recurrence of type I atrial flutter 2 years after an initially successful radiofrequency catheter ablation procedure. Whether the recurrent atrial flutter is due to a new reentrant circuit resulting from slow progression of atrial disease or due to the changes produced by radiofrequency energy in the nearby myocardium is not clear. Further work to define the electrophysiological changes in the atrial myocardium produced by radiofrequency energy, as well as long-term follow-up of patients undergoing radiofrequency catheter ablation for atrial flutter may help in answering these questions.

Atrial Flutter↗

PubMed1997

Reproducibility of ventricular fibrillation characteristics in patients undergoing implantable cardioverter defibrillator implantation.

INTRODUCTION: The purpose of this study was to evaluate the immediate reproducibility of local electrogram characteristics recorded during repeated episodes of induced ventricular fibrillation (VF) in patients undergoing implantable cardioverter defibrillator (ICD) implantation. METHODS AND RESULTS: Power spectral analysis (using a fast Fourier transform algorithm) of electrograms recorded during 3 seconds of VF were analyzed in 24 patients undergoing ICD implantation using a Medtronic Transvene lead. Patients had 2 to 7 episodes of VF that were induced during defibrillation threshold testing. VF was induced by burst pacing (n = 20) or T wave shock (n = 4). Simultaneous electrograms during VF were recorded from a Medtronic Transvene lead with the following configurations: (1) a narrow spaced (12 mm) dedicated bipole used clinically for sensing; (2) a unipolar electrogram from the right ventricular coil; and (3) a widely spaced (18.3 mm) integrated bipole using the distal tip and the coil. Intraclass correlation coefficients (ICCs) were determined to examine the reproducibility of these VF characteristics among VF episodes in each patient. Recordings from both bipolar configurations had ICCs from 0.40 to 0.55, whereas unipolar recordings ICCs were below 0.40. Reproducibility was similar for dedicated and integrated recordings. CONCLUSIONS: Frequency characteristics of repeated episodes of VF induced in the same subjects show fair-to-good but not excellent reproducibility. Bipolar recordings were far more reproducible than unipolar recordings, but both bipolar configurations had similar reproducibility. These findings have implications for both the pathophysiology of induced VF and the design of VF detection algorithms.

Adult↗

PubMed1997

Cardiac memory: a mechanical and electrical phenomenon.

Alterations in repolarization following prolonged periods of ventricular pacing, termed "cardiac memory," have been well documented. Postpacing changes in cardiac function have also been noted in hypertrophic cardiomyopathy. This study was designed to evaluate the effects of ventricular pacing on postpacing diastolic function and its relationship to repolarization changes. Eight subjects (mean age, 76 yr) with permanent pacemakers were enrolled in this study. Each subject was evaluated at a fixed pacing rate with recording of electrocardiographic and echocardiographic data. Seven sets of measurements were performed in the same sequential pattern: 1) after 1 wk of atrial pacing, 2) within 10 min after initiation of atrioventricular sequential pacing (ventricular pacing), 3) within 10 min after termination of 1 h of ventricular pacing, 4) after 1 wk of ventricular pacing, and 5) within 10 min, at 1 h, and at 24 h after termination of ventricular pacing. All subjects had repolarization changes characteristic of cardiac memory only after 1 wk of ventricular pacing. Changes in repolarization parameters were accompanied by changes in peak left ventricular filling rate (dD/dt/D; P = 0.02) and isovolumic relaxation time (IVRT; P = 0.03) that at 24 h approached baseline values. Correlations existed between changes in the Q-T interval and IVRT (r = 0.53, P = 0.007) and between changes in T wave amplitude and dD/dt/D (r = 0.48, P = 0.018) after long-term ventricular pacing. Thus changes in both repolarization and diastolic function persist after cessation of ventricular pacing and lend support to the concept of electrical and mechanical cardiac memory.

Aged↗

PubMed1996

Challenges of device therapy for ventricular tachycardia in the rate range of sinus rhythm.

A method is described for patient-activated detection of ventricular tachycardia, under circumstances in which automatic algorithms fail. We present a case of a patient with an implanted defibrillator (Jewel PCD) who presented with symptomatic exercise-induced ventricular tachycardia that was only marginally faster than the preceding sinus tachycardia. Programming the sudden onset criterion avoided delivery of therapy into sinus tachycardia, but failed to detect ventricular tachycardia. Brief application of a magnet resulted in successful detection and therapy. This method is device-specific and requires a co-operative, insightful patient. The benefits and risks of such an approach are discussed.

Defibrillators, Implantable↗

PubMed1996

Gender differences in heart rate before and after autonomic blockade: evidence against an intrinsic gender effect.

OBJECTIVES: To document gender differences in heart rate in healthy young adult men and women, and examine the degree to which autonomic tone and other variables may be associated with the gender differences in heart rate. DESIGNS: Cohort study. SETTINGS: Clinical Research Center of a tertiary care medical center. PATIENTS: A volunteer sample of 20 healthy men and 23 healthy women between ages 21 and 39 years. INTERVENTIONS: Subjects were each studied three times: during the menstrual, follicular, and luteal phases of the menstrual cycle in women; and 5 to 10 days apart in men. Electrocardiograms (ECGs) were obtained at baseline and following double autonomic blockade with propranolol 0.2 mg/kg and atropine 0.04 mg/kg. Maximum exercise capacity was determined by bicycle ergometry. MAIN OUTCOME MEASURES: Sinus cycle length at baseline and following double autonomic blockade, before and after correction for confounding variables. RESULTS: Men had longer sinus cycle length both at baseline and after double autonomic blockade (971 +/- 88 ms versus 918 +/- 115 ms, P < 0.02, and 645 +/- 41 ms versus 594 +/- 57 ms, P < 0.0001). Sinus cycle length in women was longer than during the menstrual than luteal phase but this difference could not account for the gender difference in sinus cycle length. Men also had a greater maximum exercise capacity than women (1295 +/- 167 kpm/min versus 857 +/- 227 kpm/min; P < 0.0001). By analysis of covariance, maximum exercise capacity was the most significant predictor of sinus cycle length (P < 0.0003 at baseline, and P < 0.001 post blockade) and gender did not have a significant effect. The relationship of maximum exercise capacity to sinus cycle length was blunted but not abolished by autonomic blockade. CONCLUSIONS: Sinus cycle length is longer in men than women. This difference appears to be associated with a gender difference in exercise capacity rather than intrinsic gender related properties of the sinus node or differences in autonomic tone. In addition, exercise induced bradycardia is mediated by both autonomic and nonautonomic factors in both genders.

Adrenergic beta-Antagonists↗