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Biomedical subjects

Valmik Bhargava

Publications and source records attributed to Valmik Bhargava.

10 recordsLinked to original sources

Synchrony between circular and longitudinal muscle contractions during peristalsis in normal subjects.

The current understanding is that longitudinal muscle contraction begins before and outlasts circular muscle contraction during esophageal peristalsis in normal subjects. The goal of our study was to reassess the relationship between the contractility of two muscle layers using novel ways to look at the muscle contraction. We studied normal subjects using synchronized high-frequency ultrasound imaging and manometry. Swallow-induced peristalsis was recorded at 5 and 10 cm above the lower esophageal sphincter (LES). Ultrasound (US) images were analyzed for muscle cross-sectional area (CSA) and circularity index of the esophagus during various phases of esophageal contraction. A plot of the M mode US image, muscle CSA, and esophageal circularity index was developed to assess the temporal correlation between various parameters. The muscle CSA wave began before and lasted longer than the contraction pressure wave at both 5 and 10 cm above the LES. M mode US images revealed that the onset of muscle CSA wave was temporally aligned with the onset of lumen collapse. The peak muscle CSA occurred in close proximity with the peak pressure wave. The esophagus started to become more circular (decrease in circularity index) with the onset of the muscle CSA wave. The circularity index and muscle CSA returned to the baseline at approximately the same time. In conclusion, the onset of lumen collapse and return of circularity index of the esophagus are likely to be the true markers of the onset and end of circular muscle contraction. Circular and longitudinal muscle layers of the esophagus contract in a precise synchronous fashion during peristalsis in normal subjects.

Adult↗

Separating non-isthmus- from isthmus-dependent atrial flutter using wavefront variability.

OBJECTIVES: The aim of this study was to separate isthmus-dependent atrial flutter (IDAFL) from non-isthmus-dependent atrial flutter (NIDAFL) from the electrocardiogram (ECG) based on functional differences. BACKGROUND: The ECG analyses of F-wave shape suboptimally separate NIDAFL from IDAFL. The authors hypothesized that anatomic and functional differences may result in greater wavefront variability in NIDAFL than IDAFL, allowing their separation. The authors tested this hypothesis in patients undergoing ablation for atrial flutter using a novel ECG algorithm to detect subtle F-wave variability, validated by intracardiac measurements. METHODS: In 62 patients (23 NIDAFL, 39 IDAFL) ECG atrial wavefronts were represented as correlations of an F-wave template to the ECG over time. Correlations in orthogonal ECG lead-pairs were plotted at each time point to yield loops reflecting temporal and spatial regularity in each plane. The ECG analyses were compared with intracardiac standard deviations of: 1) atrial electrograms (temporal variability), and 2) bi-atrial activation time differences (spatial variability). RESULTS: Atrial ECG temporospatial loops were reproducible in IDAFL, but varied in NIDAFL (p < 0.01) suggesting greater variability that correctly classified IDAFL (39 of 39 cases) from NIDAFL (22 of 23 cases; p < 0.001). Intra-atrial mapping confirmed greater temporal variability for NIDAFL versus IDAFL, in lateral (p < 0.01) and septal (p = 0.03) right atrium, and proximal (p = 0.02) and distal (p < 0.01) coronary sinus. Spatial variability was greater in NIDAFL than IDAFL (p = 0.02). CONCLUSIONS: Greater cycle-to-cycle atrial wavefront variability separates NIDAFL from IDAFL and is detectable from the ECG using temporospatial analyses. These results have implications for guiding ablation and support the concept that IDAFL and NIDAFL lie along a spectrum of intracardiac organization.

Algorithms↗

Sensory and motor function of the esophagus: lessons from ultrasound imaging.

Catheter-based high-frequency intraluminal ultrasound imaging is a powerful tool to study esophageal sensory and motor function and dysfunction in vivo in humans. It can be combined with manometry, pH, and impedance measurement techniques to determine the relationships between different physiologic parameters. High-frequency intraluminal ultrasound imaging has provided a number of important insights regarding the longitudinal muscle function of the esophagus. On the basis of the ultrasound images and intraluminal pressure recordings, it seems that there is synchrony in the timing and the amplitude of contraction between the circular and longitudinal muscle layers. A sustained contraction of the longitudinal muscle layer is temporally related to esophageal chest pain and heartburn. The biomechanics of the esophageal wall and its relationship to sensory and motor function can be studied in humans in vivo by using high-frequency intraluminal ultrasound much more precisely than has previously been possible. Achalasia, diffuse esophageal spasm, and nutcracker esophagus are associated with hypertrophy of circular and longitudinal muscle layers. Finally, high-frequency intraluminal ultrasound imaging is the only technique that can detect reflux-related distention of the esophagus and its role in esophageal symptoms. Future approaches to display and quantify ultrasound image data are discussed. The principles of high-frequency intraluminal ultrasound described here are also applicable to study of the motor and sensory function of the other regions of the gastrointestinal tract.

Esophageal Sphincter, Upper↗

Asynchrony between the circular and the longitudinal muscle contraction in patients with nutcracker esophagus.

BACKGROUND & AIMS: The increases in intraluminal pressure and muscle cross-sectional area (CSA) during esophageal contraction are markers of circular and longitudinal muscle contractions. The goal of our study was to determine temporal synchrony between circular and longitudinal muscle contraction in healthy subjects and patients with nutcracker esophagus. METHODS: Pressure and high-frequency intraluminal ultrasound (HFIUS) images were recorded simultaneously in healthy subjects and patients with nutcracker esophagus at 2 and 10 cm above the lower esophageal sphincter during wet swallow. HFIUS images were digitized and analyzed for the muscle CSA. The time interval (delta-t) between the peak muscle CSA and the peak pressure was determined. RESULTS: In healthy subjects, a close temporal correlation existed between the peak contraction pressure and the peak muscle CSA with a maximum delta-t of 0.5 seconds at the 2- and 10-cm levels (0-0.5 seconds). On the other hand, the patient group had a median delta-t of 1.25 seconds (0.75-3.5 seconds) at the 2-cm level and 0.75 seconds (0-2.0 seconds) at the 10-cm level. Ninety-eight of 103 contractions in patients showed a delta-t >0.5 seconds. There was a significant correlation between delta-t and the amplitude of pressure wave, the duration of pressure wave, and the peak muscle CSA. The duration of pressure wave but not the duration of CSA wave was longer in patients with nutcracker esophagus as compared with healthy subjects. CONCLUSIONS: Patients with nutcracker esophagus show temporal asynchrony between the contractions of circular and longitudinal muscle layers.

Adult↗

Temporal and spatial phase analyses of the electrocardiogram stratify intra-atrial and intra-ventricular organization.

We hypothesized that electrocardiogram (ECG) spatial phase analysis would define a spectrum of intracardiac organization from atrial fibrillation (AF), nonisthmus-dependent and isthmus-dependent atrial flutter (AFL) to supraventricular tachycardias (SVT), and similarly for ventricular arrhythmias. We analyzed arrhythmia ECGs of 33 patients with isthmus (n = 9) and nonisthmus (n = 5) dependent AFL and SVT: atrial (n = 3), atrioventricular nodal (n = 3), and orthodromic reciprocating (n = 3) tachycardias, as well as AF (n = 5), ventricular tachycardia (monomorphic, VT-MM; n = 7), and fibrillation (VF; n = 3). ECG spatial phase was considered coherent when the correlation coefficient of an atrial (or ventricular) template to its ECG over time maintained a constant relationship in XY, XZ, and YZ planes. Regularity was quantified spectrally from ECG and correlation series. Spatial coherence occurred in 9/9 cases of isthmus--but only 1/5 of cases of nonisthmus-dependent AFL (p < 0.01; chi2). All showed one dominant spectral peak (temporal coherence). In AF, spatial phase was inconsistent in all planes and spectra were broad band. Temporal and spatial coherence occurred in other SVT. VT-MM maintained spatial phase and a single spectral peak, while VF displayed neither. Our conclusions are that temporal and spatial phase analysis from the ECG stratifies intra-atrial and intra-ventricular organization and reveals subtle variability lost on visual inspection.

Adult↗

Cardiac-directed expression of adenylyl cyclase and heart rate regulation.

Mice with cardiac-directed overexpression of AC(VI) show increased cardiac responsiveness to beta-adrenergic receptor stimulation but regulation of heart rate is unknown. Telemetry was used to test the hypothesis that mice overexpressing cardiac adenylyl cyclase type VI (AC(VI)) would have normal heart rate regulation. Mice overexpressing cardiac AC(VI) were generated using the alphaMHC promoter and studied 10 days after implantation of telemetry devices. Cardiac transgene AC(VI) presence and expression was verified using PCR, RT-PCR and immunoblotting. Ambulatory heart rates were assessed using time and frequency domain analysis over two 24 hour light-dark cycles. Heart rates then were assessed following pharmacological blockade. Time domain analyses showed ambulatory heart rates were unchanged (AC(VI): 597 +/- 15 (SEM) bpm, Control: 595 +/- 12 bpm; p = 0.92). Circadian heart rate variability was preserved and not different from control mice (ANOVA, p = 0.52). Frequency domain analysis of heart rate variability also was unchanged. No difference in heart rate response to pharmacological autonomic blockade was found (intrinsic heart rate: AC(VI) 622 +/- 17 bpm, control 616 +/- 16 bpm, p = 0.79). In conclusion, mice overexpressing cardiac AC(VI) have normal conscious ambulatory heart rates and normal heart rate variability. Overexpression of cardiac AC(VI) does not result in altered heart rate regulation in contrast to cardiac overexpression of other elements of the beta-adrenergic signaling pathway.

Adenylyl Cyclases↗

Quantifying intracardiac organization of atrial arrhythmias using temporospatial phase of the electrocardiogram.

INTRODUCTION: Separating nonisthmus-dependent atrial flutter (AFL) from "organized" atrial fibrillation (AF), or isthmus-dependent AFL, may be difficult using ECG characteristics alone. We hypothesized that temporal and spatial phase analysis of ECG atrial waveforms could effectively separate these rhythms by quantifying subtle variations in ECG atrial activation during supraventricular tachycardias (SVT). METHODS AND RESULTS: We studied 52 patients at electrophysiologic study (EPS) who demonstrated isthmus-dependent (n = 15) and nonisthmus-dependent (n = 9) AFL, atrial tachycardia (n = 6), AV nodal reentry (n = 9), orthodromic reciprocating tachycardia (n = 6), and AF (n = 7). Atrial activity was represented as a series of correlations of an atrial template to successive time samples of the arrhythmia ECG. Spatial phase was analyzed as a reproducible relationship of this atrial activity between leads over time; temporal regularity was measured from power spectra. Spatial phase was maintained (coherent) in lead planes V5/aVF (XY), V5/V1 (XZ), and aVF/V1 (YZ) in 15 of 15 cases of isthmus-dependent AFL, but in only 1 of 9 cases of nonisthmus-dependent AFL (P < 0.01; chi2). Temporally, all cases of AFL showed one dominant peak on correlation spectra (magnitude >6 dB), suggesting one activation wavefront, although this was smeared in nonisthmus-dependent cases. In contrast, AF showed inconsistent spatial phase in all planes and broad band spectra, consistent with multiple and/or variable activation paths. All other SVTs showed spatial coherence and one dominant spectral peak. CONCLUSION: Coherence of temporal and spatial phase is a powerful approach to measure the spatial organization of intracardiac activation from the ECG that reveals a spectrum from SVT to isthmus-dependent and nonisthmus-dependent AFL, to AF.

Adult↗

Hemodialysis access assessment with intravascular ultrasound.

Reliable identification and treatment of specific hemodialysis access complications may improve access patency and result in significant cost reduction. Angiography is the gold standard for the evaluation of vascular access; however, it has significant limitations. Intravascular ultrasound (IVUS) is a relatively new technique capable of detecting subtle vascular abnormalities. To investigate the safety, feasibility, and accuracy of IVUS imaging to detect hemodialysis access complications, including stenoses, graft deterioration, and thrombus, we performed 31 IVUS imaging studies in 22 hemodialysis patients. Nineteen studies were performed in the dialysis unit, and 12 studies in the angiography suite. The IVUS catheter was inserted into the graft through the access used for hemodialysis. Findings of 21 studies (17 patients) imaged on the same day by both angiography and IVUS were compared. Grafts and vessels were successfully imaged using IVUS in 29 of 31 studies. There were no adverse effects caused by IVUS. Angiography assessed 17 of 54 vessel segments as normal versus 9 of 54 segments by IVUS (P < 0.001). Angiography detected lesions in 25 segments as opposed to 33 segments by IVUS (P < 0.001). A thrombus was detected in 32 of 54 vessel segments by IVUS, but in only 1 of 54 segments by angiography (P < 0.001). In conclusion, IVUS imaging is feasible and safe to assess hemodialysis access in the angiographic suite and dialysis unit. IVUS detected more vascular abnormalities than angiography. IVUS may be a useful independent imaging and screening modality in the assessment of dialysis access complications, which may help increase graft patency and reduce cost.

Angiography↗

Centered versus noncentered source for intracoronary artery radiation therapy: a model based on the Scripps Trial.

BACKGROUND: The Scripps Trial was a randomized study of intracoronary artery radiation therapy with iridium 192 used to treat restenotic vessels. We used the intravascular ultrasound data from the Scripps Trial to investigate whether a lumen-centered gamma or beta radiation source would reduce radiation dose heterogeneity compared with the noncentered source position used. METHODS: Analysis included 28 patients with stent placement in 20 native vessels and 8 saphenous vein grafts enrolled in this trial. Radiation dosimetry for gamma radiation was calculated to deliver 800 cGy to the far field target, provided the maximum dose to the near field target did not exceed 3000 cGy. Prescribed dosimetry for beta radiation by use of yttrium 90 was 1600 cGy at 2 mm distance from the source. RESULTS: The calculated average minimum source to target distance by use of a lumen-centered source increased by 0.18 mm from 1.70 +/- 0.25 to 1.88 +/- 0.36 mm, whereas the maximum distance decreased by 0.17 mm from 3.64 +/- 0.60 to 3.47 +/- 0.43 mm (P <.05). On the basis of these distances, the maximum radiation dose, as well as radiation dose heterogeneity (ratio of maximum to minimum), would have been reduced in 22 of 28 patients by use of a lumen-centered gamma or beta source (P <.005). The reduction in dose heterogeneity was substantially greater with a beta source compared with a gamma source (48% vs 16% reduction). CONCLUSIONS: Centering of the intracoronary artery radiation therapy delivery catheter within the vessel lumen can significantly reduce radiation dose heterogeneity when compared with a noncentered source position. This dose reduction is substantially greater for a beta compared with a gamma source.

Beta Particles↗