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Biomedical subjects

Richard L Verrier

Publications and source records attributed to Richard L Verrier.

29 records · Page 2Linked to original sources

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↗

Inhalation of concentrated ambient air particles exacerbates myocardial ischemia in conscious dogs.

Short-term increases in ambient air pollution have been associated with an increased incidence of acute cardiac events. We assessed the effect of inhalation exposure to concentrated ambient particles (CAPs) on myocardial ischemia in a canine model of coronary artery occlusion. Six mongrel dogs underwent thoracotomy for implantation of a vascular occluder around the left anterior descending coronary artery and tracheostomy to facilitate particulate exposure. After recovery (5-13 weeks), pairs of subjects were exposed for 6 hr/day on 3 or 4 consecutive days. Within each pair, one subject was randomly assigned to breathe CAPs on the second exposure day and filtered air at other times. The second subject breathed CAPs on the third exposure day and filtered air at other times. Immediately after each exposure, subjects underwent 5-min coronary artery occlusion. We determined ST-segment elevation, a measure of myocardial ischemia heart rate, and arrhythmia incidence during occlusion from continuous electrocardiograms. Exposure to CAPs (median, 285.7; range, 161.3-957.3 microg/m3) significantly (p = 0.007) enhanced occlusion-induced peak ST-segment elevation in precordial leads V4 (9.4 +/- 1.7 vs. 6.2 +/- 0.9 mm, CAPs vs. filtered air, respectively) and V5 (9.2 +/- 1.3 vs. 7.5 +/- 0.9 mm). ST-segment elevation was significantly correlated with the silicon concentration of the particles and other crustal elements possibly associated with urban street dust (p = 0.003 for Si). No associations were found with CAPs mass or number concentrations. Heart rate was not affected by CAPs exposure. These results suggest that exacerbation of myocardial ischemia during coronary artery occlusion may be an important mechanism of environmentally related acute cardiac events.

Air Pollutants↗

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↗

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↗

Myocardial drug distribution pattern following intrapericardial delivery: an MRI analysis.

OBJECTIVES: The main goal was to gain insights into the pharmacokinetics of intrapericardial drug delivery using magnetic resonance (MR) imaging analysis and the extracellular MR contrast agent gadopentetate dimeglumine (Gd-DTPA) as a model. BACKGROUND: Recent development of catheter-based techniques to access the intact pericardial space has increased interest in intrapericardial delivery for local cardiac therapy. Distribution and myocardial penetration of intrapericardial agents are not well characterized. METHODS: The intact pericardial space was percutaneously accessed through the right atrial appendage in ten anesthetized pigs, following which 5 mL Gd-DTPA (N = 8) or normal saline as control (N = 2) were administered. Animals were sacrificed at 1, 3, 3.5, 5, or 8 hr. The whole heart was excised, washed with normal saline, and the chambers distended with saline-filled bags. Myocardial penetration of Gd-DTPA was analyzed by a series of short-axis T1-weighted turbospin-echo MR images. RESULTS: At 1, 3, and 3.5 hr after Gd-DTPA, a uniform ring of enhancement was found along the epicardium, with a depth density related to time after administration. No contrast ring was visible at 5 or 8 hr or in control animals. Transmural myocardial T1 values obtained 5 hr after Gd-DTPA administration were reduced, suggesting that Gd-DTPA had penetrated uniformly throughout the myocardium. CONCLUSIONS: Intrapericardial administration results in relatively uniform distribution of an agent across the ventricular epicardium. The depth of penetration is consistent with functional evidence that epicardial structures can be targeted by this technique.

Animals↗

Electrocardiographic changes during exposure to residual oil fly ash (ROFA) particles in a rat model of myocardial infarction.

Epidemiological studies have reported a positive association of short-term increases in ambient particulate matter (PM) with daily mortality and hospital admissions for cardiovascular disease. Although patients with cardiopulmonary disease appear to be most at risk, particulate-related cardiac effects following myocardial infarction (MI) have not been examined. To improve understanding of mechanisms, we developed and tested a model for investigating the effects of inhaled PM on arrhythmias and heart rate variability (HRV), a measure of autonomic nervous system activity, in rats with acute MI. Left-ventricular MI was induced in 31 Sprague-Dawley rats by thermocoagulation of the left coronary artery; 32 additional rats served as sham-operated controls. Diazepam-sedated rats were exposed (1 h) to residual oil fly ash (ROFA), carbon black, or room air at 12-18 h after surgery. Each exposure was immediately preceded and followed by a 1-h exposure to room air (baseline and recovery periods, respectively). Lead-II electrocardiograms were recorded. In the MI group, 41% of rats exhibited one or more premature ventricular complexes (PVCs) during the baseline period. Exposure to ROFA, but not to carbon black or room air, increased arrhythmia frequency in animals with preexisting PVCs. Furthermore, MI rats exposed to ROFA, but not to carbon black or room air, decreased HRV. There was no difference in arrhythmia frequency or HRV among sham-operated animals. These results underscore the usefulness of this model for elucidating the physiologic mechanisms of pollution-induced cardiovascular arrhythmias and contribute to defining the specific constituents of ambient particles responsible for arrhythmias.

Administration, Inhalation↗

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↗

Technique for implantation of chronic indwelling aortic access catheters.

INTRODUCTION: For chronic, repeated cardiovascular studies in trained, conscious dogs, we describe a technique for implantation of an arterial vascular access catheter in the aorta. In comparison to previous techniques, our technique enables arterial catheter implantation without interrupting the systemic circulation or compromising peripheral arterial flow, requires only a single penetration of the aortic wall, and results in a catheter facing downstream in the aorta. The catheter is usable for both arterial blood sampling and intra-arterial injection of pharmacologic agents. METHODS: After thoracotomy, two purse-string sutures were set in the aortic wall at the catheter entry-site. A Debakey-Satinsky vena cava clamp was used to partially clamp and isolate a 3-cm portion of aorta surrounding the pursestring sutures. The catheter was prepared by inserting a 0.35 mm guide wire, curve tip end first, into a 7 French silicone Access Technologies catheter. This caused a slight bend at the tip of the catheter, which later facilitated entry into the aorta and prevented damage to the intima of the aortic wall. Catheters were tunneled from the thorax to the nape of the neck, attached to a subcutaneous vascular access port (VAP), and buried in the fascia. Catheters were locked with 2 mL heparinized saline (20 IU/mL). With this technique, we implanted 16 aortic vascular access catheters in 16 dogs. RESULTS: Of the 16 animals, 8 are being maintained for long-term study, 7 were sacrificed for histopathological examination, and 1 died due to improper catheter implantation without the aid of the curved-tip guide-wire technique. VAPs have remained bidirectionally patent in all long-term animals (n = 8) ongoing for 7.5 +/- 1.4 months (mean +/- SEM), with an ongoing maximum of 14 months. In these long-term animals, VAPs were used 5.88 +/- 1.34 times. Postmortem examinations were performed on short-term animals (n = 8) sacrificed at 2.85 +/- 1.29 months. The catheters have remained bidirectionally patent in all but the one animal that died. In the short-term animals, the 7 patent VAPs were used 12.71 +/- 1.64 times. Histopathological examination of hematoxylin and eosin (H&E) slides from the catheter entry site revealed only minimal chronic inflammation. No evidence of tissue overgrowth around any of the intravascular segments of these silicone catheters was noted in any animal. CONCLUSIONS: Thus, this dependable subcutaneous arterial access system provides a means for examining acute and long-term effects of environmental and pathophysiological influences in conscious dogs. These catheters have remained bidirectionally patent ongoing for more than 1 year and allowed infusion of agents and withdrawal of central arterial blood samples.

Animals↗