Biomedical subjects

B R Choi

Publications and source records attributed to B R Choi.

4 recordsLinked to original sources

PubMed2000

Enhanced dispersion of repolarization and refractoriness in transgenic mouse hearts promotes reentrant ventricular tachycardia.

The heterogeneous distribution of ion channels in ventricular muscle gives rise to spatial variations in action potential (AP) duration (APD) and contributes to the repolarization sequence in healthy hearts. It has been proposed that enhanced dispersion of repolarization may underlie arrhythmias in diseases with markedly different causes. We engineered dominant negative transgenic mice that have prolonged QT intervals and arrhythmias due to the loss of a slowly inactivating K(+) current. Optical techniques are now applied to map APs and investigate the mechanisms underlying these arrhythmias. Hearts from transgenic and control mice were isolated, perfused, stained with di-4-ANEPPS, and paced at multiple sites to optically map APs, activation, and repolarization sequences at baseline and during arrhythmias. Transgenic hearts exhibited a 2-fold prolongation of APD, less shortening (8% versus 40%) of APDs with decreasing cycle length, altered restitution kinetics, and greater gradients of refractoriness from apex to base compared with control hearts. A premature impulse applied at the apex of transgenic hearts produced sustained reentrant ventricular tachycardia (n=14 of 15 hearts) that did not occur with stimulation at the base (n=8) or at any location in control hearts (n=12). In transgenic hearts, premature impulses initiated reentry by encountering functional lines of conduction block caused by enhanced dispersion of refractoriness. Reentrant VT had stable (>30 minutes) alternating long/short APDs associated with long/short cycle lengths and T wave alternans. Thus, optical mapping of genetically engineered mice may help elucidate some electrophysiological mechanisms that underlie arrhythmias and sudden death in human cardiac disorders.

Action Potentials↗

PubMed1998

Optical mapping of atrioventricular node reveals a conduction barrier between atrial and nodal cells.

The mechanisms responsible for atrioventricular (AV) delay remain unclear, in part due to the inability to map electrical activity by conventional microelectrode techniques. In this study, voltage-sensitive dyes and imaging techniques were refined to detect action potentials (APs) from the small cells comprising the AV node and to map activation from the "compact" node. Optical APs (124) were recorded from 5 x 5 mm (approximately 0.5-mm depth) AV zones of perfused rabbit hearts stained with a voltage-sensitive dye. Signals from the node exhibited a set of three spikes; the first and third (peaks I and III) were coincident with atrial (A) and ventricular (V) electrograms, respectively. The second spike (peak II) represented the firing of midnodal (N) and/or lower nodal (NH) cell APs as indicated by their small amplitude, propagation pattern, location determined from superimposition of activation maps and histological sections of the node region, dependence on depth of focus, and insensitivity to tetrodotoxin (TTX). AV delays consisted of tau 1 (49.5 +/- 6.59 ms, 300-ms cycle length), the interval between peaks I and II (perhaps AN to N cells), and tau 2 (57.57 +/- 5.15 ms), the interval between peaks II and III (N to V cells). The conductance time across the node was 10.33 +/- 3.21 ms, indicating an apparent conduction velocity (theta N) of 0.162 +/- 0.02 m/s (n = 9) that was insensitive to TTX. In contrast, tau 1 correlated with changes in AV node delays (measured with surface electrodes) caused by changes in heart rate or perfusion with acetylcholine. The data provide the first maps of activation across the AV node and demonstrate that theta N is faster than previously presumed. These findings are inconsistent with theories of decremental conduction and prove the existence of a conduction barrier between the atrium and the AV node that is an important determinant of AV node delay.

Acetylcholine↗

PubMed1997

Sodium mercaptoacetate is not a useful probe to study the role of fat in regulation of feed intake in dairy cattle.

Inhibition of fatty acid oxidation by mercaptoacetate stimulates food intake of rats fed dietary fat. To study regulation of feed intake of ruminants fed fat, dry matter intake and plasma concentrations of insulin and metabolites were determined in eight nonpregnant Holstein heifers in a cross-over design with two 14-d feeding periods by using a 2 x 2 factorial arrangement of treatments. Treatments were combinations of diet (27 or 103 g fatty acids/kg food dry matter) and injection (mercaptoacetate or saline). Half the heifers were fed each diet in Period 1, and diets were reversed in Period 2. On d 10 of each period, two animals per treatment were injected intravenously with either mercaptoacetate (300 mumol/kg body weight 0.75) or saline at 2 h postfeeding. Injections were reversed on d 12. Dry matter intake was suppressed by the high fat diet. Intravenous injection of mercaptoacetate decreased dry matter intake to 25% that of the control during 4 h postinjection. Both the high fat diet and mercaptoacetate injection increased plasma non-esterified fatty acid concentration, whereas plasma beta-hydroxybutyrate concentration was lowered by the high fat diet and by mercaptoacetate injection. Plasma triglyceride concentration was increased by the high fat diet, but was decreased by mercaptoacetate injection. Mercaptoacetate elevated plasma glucose concentrations at 2 and 3 h postinjection, possibly because plasma insulin concentration was lower. Effects of mercaptoacetate on plasma insulin and metabolite concentrations may have been confounded by the effects of decreased feed intake. Therefore, direct effects of mercaptoacetate injection were not separated from effects of feed intake on plasma insulin and metabolite concentration. Because mercaptoacetate injection decreased dry matter intake it was not a useful probe to study mechanisms of feed intake regulation in dairy cattle fed fat.

Animals↗

PubMed1996

High fat diets increase plasma cholecystokinin and pancreatic polypeptide, and decrease plasma insulin and feed intake in lactating cows.

High fat diets often decrease feed intake in dairy cows; however, mechanisms underlying fat-induced depression of feed intake are yet to be established. The postulate that high fat diets decrease feed intake by increasing concentrations of lipid metabolites or satiety hormones in blood was tested by using eight multiparous Holstein cows in a simultaneously replicated 4 x 4 Latin-square design. Treatments were control diet with 1) no fat added, 2) 30 g/kg calcium salts of long-chain fatty acids, 3) 60 g/kg calcium salts of long-chain fatty acids, and 4) 90 g/kg calcium salts of long-chain fatty acids. Cows were fed once daily a diet of concentrate, corn silage, alfalfa haylage and alfalfa hay (50:25:14:11 on a dry matter basis). Dry matter and energy intakes were decreased by inclusion of calcium salts of long-chain fatty acids >30 g/kg of total diet dry matter (P = 0.0001). Plasma nonesterified fatty acids and triglyceride concentrations were increased linearly by feeding increasing amounts of fat (P < 0.003 and P = 0.0001, respectively), whereas plasma beta-hydroxybutyrate and glucose concentrations were not influenced by supplemental fat. Fat supplementation increased postfeeding plasma cholecystokinin concentrations and linearly increased plasma pancreatic polypeptide concentrations. Highest concentrations of plasma cholecystokinin (P < 0.001) and pancreatic polypeptide (P < 0.05) were observed in cows fed the 90 g/kg fat supplement. Plasma insulin was lowered linearly by feeding fat (P = 0.0001). Increased concentrations of cholecystokinin and pancreatic polypeptide were associated with decreased intakes of feed and energy, whereas insulin may not be involved in the control of feed intake in cows fed fat.

Animals↗