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Biomedical subjects

Bruce D Nearing

Publications and source records attributed to Bruce D Nearing.

14 recordsLinked to original sources
PubMed2006

Suppression of calcium-induced repolarization heterogeneity as a mechanism of nitroglycerin's antiarrhythmic action.

This study examined whether the antifibrillatory action of nitroglycerin (NTG) is attributable to reduction in calcium-induced heterogeneity of repolarization independent of autonomic and coronary vasodilatory influences. The effects of intrapericardial (IPC) NTG on coronary blood flow, contractility, repolarization, and arrhythmia susceptibility were measured in anesthetized pigs (N = 43). Autonomic influences were minimized by vagotomy and beta-adrenergic blockade (metoprolol, 1.25 mg/kg, intravenous). Electrophysiological parameters were tested at 30 min, a time when coronary hemodynamics had returned to baseline. Intracoronary calcium chloride (CaCl2, 50-mg bolus) injection augmented contractility (dP/dt(max), 1760 +/- 144 to 2769 +/- 274 mmHg/s, and following NTG, 1531 +/- 384 to 2138 +/- 242 mmHg/s, P < 0.0002), reflecting increased myocardial intracellular calcium. Calcium increased repolarization heterogeneity (interlead precordial T-wave heterogeneity, 95 +/- 15 to 264 +/- 33 microV, P < 0.006; T(peak)-T(end), an index of transmural dispersion of repolarization, 37 +/- 3 to 76 +/- 6 ms, P < 0.05) and lowered repetitive extrasystole threshold (RET; 24 +/- 2 to 13 +/- 1 mA, and following NTG, 32 +/- 4 to 18 +/- 1 mA, P < 0.0001). IPC NTG raised the RET from baseline by 33% and blunted calcium-induced contractility (dP/dt(max) by 23%, P < 0.05), repolarization changes (T-wave heterogeneity by 24%, P < 0.006; T(peak)-T(end) by 18%, P = 0.04), and arrhythmia vulnerability (RET by 39%, P < 0.003). Thus, the capacity of NTG to suppress calcium-induced repolarization heterogeneity is an important mechanism of its antiarrhythmic action, which is independent of autonomic and vasodilatory actions.

Animals↗
PubMed2006

Personal coronary risk profiles modify autonomic nervous system responses to air pollution.

OBJECTIVE: We investigated whether PM2.5-mediated autonomic modulation depends on individual coronary risk profiles. METHODS: Five-minute average heart rate (HR) and heart rate variability (HRV, including standard deviation of normal-to-normal intervals [SDNN], square root of the mean squared differences of successive NN intervals [rMSSD], high frequency [HF]) were measured from 24-hour ambulatory electrocardiograms, and personal PM(2.5) exposures were monitored in a prospective study of 10 male boilermakers (aged 34.3 +/- 8.1 years). We used the Framingham score to classify individuals into low (score = 1-3) and high (score = 5-6) risk categories. Mixed-effect models were used for statistical analyses. RESULTS: Each 1-mg/m(3) increase in the preceding 4-hour moving average PM(2.5) was associated with HR increase (5.3 beats/min) and HRV reduction (11.7%, confidence interval [CI] = 6.2-17.1% for SDNN; 11.1%, CI = 3.1-19.1% for rMSSD; 16.6%, CI = 1.5-31.7% for HF). Greater responses (2- to 4-fold differences) were observed in high-risk subjects than in low-risk subjects. CONCLUSIONS: Our study suggests that adverse autonomic responses to metal particulate are aggravated in workers with higher coronary risk profiles.

Adult↗
PubMed2005

Noninvasive sudden death risk stratification by ambulatory ECG-based T-wave alternans analysis: evidence and methodological guidelines.

Extensive experimental and clinical evidence supports the utility of T-wave alternans (TWA) as a marker of risk for ventricular fibrillation. This entity appears to reflect the fundamental arrhythmogenic property of enhanced dispersion of repolarization. This relationship probably accounts for its relative ubiquity in patients with diverse types of cardiac disease, as has been recognized with the development of analytical tools. A basic premise of this review is that ambulatory ECG monitoring of TWA as patients experience the provocative stimuli of daily activities can expose latent electrical instability in individuals at heightened risk for arrhythmias. We will discuss the literature that supports this concept and summarize the current state of knowledge regarding the use of routine ambulatory ECGs to evaluate TWA for arrhythmia risk stratification. The dynamic, nonspectral modified moving average analysis method for assessing TWA, which is compatible with ambulatory ECG monitoring, is described along with methodological guidelines for its implementation. Finally, the rationale for combined monitoring of autonomic markers along with TWA will be presented.

Arrhythmias, Cardiac↗
PubMed2005

Air pollution and ST-segment depression in elderly subjects.

Increased levels of daily ambient particle pollution have been associated with increased risk of cardiovascular morbidity. Black carbon (BC) is a measure of the traffic-related component of particles. We investigated associations between ambient pollution and ST-segment levels in a repeated-measures study including 269 observations on 24 active Boston residents 61-88 years of age, each observed up to 12 times from June through September 1999. The protocol involved continuous Holter electrocardiogram monitoring including 5 min of rest, 5 min of standing, 5 min of exercise outdoors, 5 min of recovery, and 20 cycles of paced breathing. Pollution-associated ST-depression was estimated for a 10th- to 90th-percentile change in BC. We calculated the average ST-segment level, referenced to the P-R isoelectric values, for each portion of the protocol. The mean BC level in the previous 12 hr, and the BC level 5 hr before testing, predicted ST-segment depression in most portions of the protocol, but the effect was strongest in the postexercise periods. During postexercise rest, an elevated BC level was associated with -0.1 mm ST-segment depression (p = 0.02 for 12-hr mean BC; p = 0.001 for 5-hr BC) in continuous models. Elevated BC also predicted increased risk of ST-segment depression > or = 0.5 mm among those with at least one episode of that level of ST-segment depression. Carbon monoxide was not a confounder of this association. ST-segment depression, possibly representing myocardial ischemia or inflammation, is associated with increased exposure to particles whose predominant source is traffic.

Aged↗
PubMed2004

Effects of acute mental stress and exercise on T-wave alternans in patients with implantable cardioverter defibrillators and controls.

BACKGROUND: Malignant cardiac arrhythmias can be triggered by exercise and by mental stress in vulnerable patients. Exercise-induced T-wave alternans (TWA) is an established marker of cardiac electrical instability. However, the effects of acute mental stress on TWA have not been investigated as a vulnerability marker in humans. METHODS AND RESULTS: TWA responses to mental stress (anger recall and mental arithmetic) and bicycle ergometry were evaluated in patients with implantable cardioverter defibrillators (ICDs) and documented coronary artery disease (n=23, age 62.1+/-12.3 years) and controls (n=17, age 54.2+/-12.1 years). TWA was assessed from digitized ECGs by modified moving average analysis. Dual-isotope single photon emission computed tomography was used to assess myocardial ischemia. TWA increased during mental stress and exercise (P values <0.001), and TWA responses were higher in ICD patients than in controls (arithmetic Delta=8.9+/-1.4 versus 4.3+/-2.2 microV, P=0.043; exercise Delta=21.4+/-2.8 versus 13.8+/-3.2 microV, P=0.038). TWA increases with mental stress occurred at substantially lower heart rates (anger recall Delta=9.7+/-7.7 bpm, arithmetic Delta=14.3+/-13.3 bpm) versus exercise (Delta=53.7+/-22.7 bpm; P values <0.001). After adjustment for heart rate increases, mental stress and exercise provoked increased TWA in ICD patients (P values <0.05), but not in controls (P values >0.2). Ejection fraction and stress-induced myocardial ischemia were not associated with TWA. CONCLUSIONS: Mental stress can induce cardiac electrical instability, as assessed via TWA, among patients with arrhythmic vulnerability and occurs at lower heart rates than with exercise. Pathophysiological mechanisms of mental stress-induced arrhythmias may therefore involve central and autonomic nervous system pathways that differ from exercise-induced arrhythmias.

Acute Disease↗
PubMed2003

Tracking cardiac electrical instability by computing interlead heterogeneity of T-wave morphology.

Oscillations in T-wave morphology, particularly T-wave alternans (TWA), have been fundamentally linked to increased susceptibility to ventricular fibrillation (VF). We investigated whether the escalation in complexity of T-wave oscillations before VF is attributable to increased spatial heterogeneity of repolarization. Peak interlead T-wave heterogeneity (TWH) was measured by second central moment analysis of T-wave morphology in epicardial electrograms in dogs during left anterior descending coronary artery occlusion. TWH differentiated cases in which myocardial ischemia provoked VF from those without VF (563 +/- 56 vs. 139 +/- 36 microV, P < 0.01). In the former group, progressive, significant increases in TWH above preocclusion baseline (70 +/- 8 microV) began at 2.25 min after the start of occlusion and were associated successively with TWA (at 155 +/- 19 microV), T-wave multupling (at 386 +/- 100 microV), complex oscillatory T-wave forms (at 560 +/- 76 microV), discordant TWA (at 572 +/- 98 microV), and VF at 4.36 +/- 0.14 min. TWH in precordial ECGs in 12 pigs during angioplasty-balloon-induced myocardial ischemia also discriminated animals that experienced VF (from 90 +/- 14 at baseline to 382 +/- 39 microV, P < 0.05) from those without VF (from 96 +/- 17 at baseline to 199 +/- 61 microV, NS). Ischemia-induced changes in ST segment and T-wave amplitude did not predict VF. Heightened spatial heterogeneity of repolarization, as assessed by second central moment analysis of TWH, underlies TWA and increased risk for ischemia-induced VF. Monitoring spatial TWH from precordial leads could prove useful in stratifying risk for life-threatening arrhythmias.

Algorithms↗
PubMed2003

Potent antifibrillatory effects of intrapericardial nitroglycerin in the ischemic porcine heart.

OBJECTIVES: We investigated the antiarrhythmic effects of intrapericardial nitroglycerin (NTG) during acute myocardial ischemia in the porcine heart. BACKGROUND: Nitroglycerin is a nitric oxide donor that exerts potent effects on the cardiovascular system. Intrapericardial administration allows investigation of pharmacologic actions on cardiac tissue in an in vivo system while minimizing the confounding influences of systemic effects. METHODS: In 29 closed-chest pigs, myocardial ischemia was induced by intraluminal balloon occlusion of the left anterior descending coronary artery. Arrhythmia incidence was monitored during 5-min balloon inflations performed without drug and at 15, 45, 75, and 105 min after NTG (4,000 microg bolus) administered by percutaneous transatrial access into the pericardial space. Electrocardiograms were monitored for ischemia-induced T-wave alternans (TWA), a marker of electrical instability. The antiadrenergic potential of NTG was investigated by examining the drug's suppression of dobutamine-induced increase in myocardial contractility. RESULTS: Control coronary artery occlusion provoked ventricular fibrillation (VF) in all animals. Intrapericardial NTG suppressed VF at 45 min in all six pigs (p < 0.05) and reduced TWA across a parallel time course (from 459.1 +/- 144.4 microV before drug to 42.22 +/- 13.96 microV at 45 min, p = 0.047). The antifibrillatory effect occurred as early as 15 min and persisted for up to 75 min. Augmentation of maximum of the first time derivative of left ventricular pressure by dobutamine was blunted by intrapericardial NTG (from 3,999 +/- 196 mm Hg/s before NTG to 3,543 +/- 220 mm Hg/s at 15 min, p = 0.012). CONCLUSIONS: Intrapericardial NTG exerts a robust antifibrillatory action. Potential mechanisms include reduction in electrical instability and blunting of adrenergic effects.

Adrenergic beta-Antagonists↗
PubMed2003

Ambulatory ECG monitoring of T-wave alternans for arrhythmia risk assessment.

Experimental and clinical studies indicate a basic linkage between T-wave alternans (TWA) and susceptibility to malignant arrhythmias. In a variety of clinical populations with elevated risk of ventricular tachyarrhythmias, Fast Fourier Transform (FFT)-based assessment of TWA during fixed-rate atrial pacing or bicycle ergometry has shown predictive ability for arrhythmic events. However, after more than a decade since the introduction of TWA testing in human subjects, few studies have explored its utility in ambulatory ECG (AECG) recordings. This gap probably relates to major technical obstacles associated with monitoring of ambulatory subjects, including motion artifact and the requirement of data stationarity, which mandates fixing heart rate. To circumvent these difficulties, we devised a time-domain method, "Modified Moving Average Beat Analysis" (MMA) to determine TWA level accurately in freely moving subjects. Recently, MMA analysis was employed to analyze ambulatory ECG (AECG) records of post-myocardial infarction patients who were were at low risk of arrhythmic death. An increased risk of arrhythmic death was predicted by TWA level above the 75th percentile of controls (p<.05). Thus, the predictive power of TWA obtained with MMA analysis from AECG records obtained appears promising.

Arrhythmias, Cardiac↗
PubMed2003

Analysis of complex T-wave oscillations for prediction of ventricular fibrillation.

Increased attention has been focused on oscillatory behavior of the T wave as a manifestation of heightened electrical instability and risk for ventricular fibrillation (VF). This interest has stemmed from an increasing number of experimental and clinical studies indicating that the relatively simple ABAB oscillation of T-wave alternans (TWA) can be quantified to assess risk for arrhythmias. However, an important unanswered question is whether TWA represents the initial phase of a stepwise progression to higher-order oscillations that culminate in sudden arrhythmic death. Signals were analyzed from epicardial and endocardial ECGs from anesthetized dogs subjected to LAD coronary artery occlusion during fixed-rate atrial pacing. Our study was the first to demonstrate a stepwise increase in complexity of T-wave oscillations from TWA to T-wave tripling and quadrupling and to more complex forms just prior to onset of VF (Circ Res 2002;91:727-732). Discordant T-wave episodes, when T waves alternated out-of-phase, were found to be associated with increases in T-wave complexity and VF. None of the animals that failed to fibrillate exhibited discordant TWA. In these observations, complexity of T-wave oscillations points to a fundamental mechanistic link underlying the ability of TWA to predict lethal arrhythmias.

Animals↗
PubMed2003

Ambulatory electrocardiogram-based tracking of T wave alternans in postmyocardial infarction patients to assess risk of cardiac arrest or arrhythmic death.

INTRODUCTION: This is the first study to assess T wave alternans (TWA) analyzed from routine ambulatory electrocardiograms (AECGs) to identify postmyocardial infarction (post-MI) patients at increased risk for arrhythmic events. METHODS AND RESULTS: The new method of modified moving average (MMA) analysis was used to measure TWA magnitude in 24-hour AECGs from ATRAMI, a prospective study of 1,284 post-MI patients. Using a nested case-control approach, we defined cases as patients who experienced cardiac arrest due to documented ventricular fibrillation or arrhythmic death during the follow-up period of 21 +/- 8 months. We analyzed 15 cases and 29 controls matched for sex, age, site of MI, left ventricular ejection fraction, thrombolysis, and beta-blockade therapy. TWA was reported as the maximum 15-second value at three predetermined times associated with cardiovascular stress: maximum heart rate, 8:00 A.M., and maximum ST segment deviation. TWA increased significantly from baseline in both leads at each time point (P <<0.01) in cases and controls. TWA in V5 increased more in cases than controls during peak heart rate (P = 0.005) and at 8:00 A.M. (P = 0.02). A 4- to 7-fold higher odds of life-threatening arrhythmias was predicted by TWA level above the 75th percentile during maximum heart rate in leads V1 (odds ratio [OR] 4.2, 95% confidence interval [CI]: 1.1-16.3, P = 0.04) and V5 (OR 7.9, 95% CI: 1.9-33.1, P = 0.005). TWA at 8:00 A.M. also predicted risk in leads V1 (OR = 5.0, 95% CI: 1.2-20.5, P = 0.02) and V5 (OR = 4.2, 95% CI: 1.1-16.3, P = 0.04). CONCLUSION: TWA measurement from routine 24-hour AECGs is a promising approach for risk stratification for cardiac arrest and arrhythmic death in relatively low-risk post-MI patients.

Algorithms↗
PubMed2002

Progressive increases in complexity of T-wave oscillations herald ischemia-induced ventricular fibrillation.

T-wave alternans (TWA), an ABAB oscillation, has been postulated as the initial pattern in a stepwise progression to higher-order oscillations, culminating in sudden arrhythmic death. The present study is the first to provide experimental evidence to support this intriguing concept. Epicardial and endocardial ECGs from 12 dogs were monitored during 8-minute left anterior descending coronary artery occlusion with right atrial pacing at 150 bpm. TWA magnitude was measured by modified moving average beat analysis, and the complexity of T-wave oscillations was assessed by complex demodulation. In 6 animals with subsequent ventricular fibrillation (VF), TWA achieved a threshold of 5.00+/-1.30 mV in epicardial ischemic-zone electrograms, which then exhibited a stepwise increase in T-wave oscillation complexity to quadrupling (ABCDABCD, 3 cases) or tripling (ABCABC, 2 cases) and to more complex forms (5 cases) preceding VF (6 cases). In dogs without VF, peak TWA levels did not increase from baseline, measuring a maximum of 0.35+/-0.10 mV (P=NS), or only 7% the value of those with VF, and T-wave multupling was not observed (0 of 6 versus 5 of 6, P<0.005). Discordant TWA episodes, with T waves alternating out of phase, were associated with increased T-wave complexity and fibrillation in 4 of 6 dogs with VF but in none of the 6 dogs without VF (P<0.025). TWA appears to be the first step in an orderly progression of T-wave complexity, episodes of discordant TWA, and VF. This demonstrated increase in T-wave complexity points to a fundamental mechanistic link underlying the ability of TWA to predict lethal arrhythmias.

Animals↗
PubMed2002

Optimizing ambulatory ECG monitoring of T-wave alternans for arrhythmia risk assessment.

Considerable scientific data support the potential value of T-wave alternans (TWA) as an index of vulnerability to ventricular fibrillation. This chapter summarizes our state of knowledge regarding the use of routine ambulatory ECGs to evaluate TWA and discusses recent methodologic approaches designed to optimize AECG-based TWA analysis for arrhythmia risk stratification. Newer methods, including the nonspectral technique of Modified Moving Average analysis, appear promising in detecting TWA during the changing conditions associated with daily activities. The Modified Moving Average approach does not require specialized electrodes and is not encumbered by the need to achieve target heart rates, as is the case for conventional spectral-based methods. Guidelines are provided for evaluating latent cardiac electrical instability using AECG-based TWA testing. These recent developments make possible the TWA analysis of ambulatory ECGs not only in prospective trials but also in vast stores of archival data.

Arrhythmias, Cardiac↗
PubMed2002

Modified moving average analysis of T-wave alternans to predict ventricular fibrillation with high accuracy.

T-wave alternans is a marker of cardiac electrical instability with the potential for arrhythmia risk stratification. The modified moving average method was developed to measure alternans in settings with artifacts, noise, and nonstationary data. Algorithms were developed and performance characteristics were validated with simulated electrocardiograms (ECGs). Experimental laboratory ECGs with dynamically changing alternans values were analyzed. Alternans values estimated by modified moving average analysis correlated strongly with input alternans values (r(2) = 0.9999). Rapidly changing alternans levels and phase reversals did not perturb the measurement. When heart rate was increased from 60 to 180 beats/min, with T-wave alternans apex moving from 237 to 103 ms after the R wave, the measured alternans peak varied <5% from input value. Simulated 50- to 1,000-microV motion artifact spikes typical of treadmill ECGs produced inaccuracies <2%. Alternans values in experimental laboratory study using standard electrodes tracked vulnerability to myocardial ischemia-induced ventricular fibrillation with 100% sensitivity and specificity at a cut point of 0.75 mV. Modified moving average analysis is a robust method that precisely measures T-wave alternans in settings with artifacts, noise, and nonstationary data typical of clinical ECGs and yields an accurate estimate of risk for ventricular fibrillation.

Algorithms↗