Cholesterol-lowering drugs in familial defective apolipoprotein B-100.
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Anticholesteremic Agents↗
Biomedical subjects
J J Gallagher
Publications and source records attributed to J J Gallagher.
Laser photoablation of ventricular tachycardia: correlation of diastolic activation times and photoablation effects on cycle length and termination--observations supporting a macroreentrant mechanism.
Neodymium:yttrium-aluminum-garnet (YAG) photocoagulation during ventricular tachycardia allows the electrophysiologic effects of the temporal and spatial sequence of energy delivery to be correlated with local activation times. A retrospective analysis was performed of the termination of 19 episodes of ventricular tachycardia for which the local diastolic activation time was known for all successful ablation sites and for 95% of all ablation sites. The mode of termination was compared with that of 26 episodes of spontaneously terminating ventricular tachycardias. Spontaneous terminations occurred without a change in cycle length (54%) or with a 7 +/- 15% change in cycle length over one to three terminal beats (46%). In contrast, laser ablation-induced terminations resulted in a 39 +/- 55% increase in cycle length over nine or more cycles. The effect of attempted laser ablation was compared with the local presystolic activation time and the local activation time expressed as a percent of the diastolic interval (end of QRS complex = 0%, onset of next QRS complex = 100%). With one exception, no tachycardia terminated at ablation sites activating less than -50 ms before the QRS complex. All 8 successful first ablation attempts and 13 of all 19 successful ablations occurred in the 35% to 50% interval of diastolic activation. All successful ablations at sites activating at greater than 50% of the diastolic interval required multiple ablation attempts. Successful ablation was performed from the epicardium in 6 and from the endocardium in 13 episodes of ventricular tachycardia. These results are most consistent with a macroreentrant mechanism with a region of high vulnerability represented by the 35% to 50% interval of diastolic activation.(ABSTRACT TRUNCATED AT 250 WORDS)
Diastole↗
Effective reduction of plasma LDL levels by LDL apheresis in familial defective apolipoprotein B-100.
The clinical response to long-term reduction of the plasma LDL cholesterol concentration was studied in a man with severe coronary artery disease associated with familial defective apolipoprotein B-100 (FDB). Plasma exchange repeated at 2-week intervals, combined with lipid-lowering drugs, led to remission of angina and improved exercise test performance. A similar clinical response was achieved after LDL apheresis with dextran sulphate columns repeated once every 2 weeks in combination with drug treatment. The reduction in plasma LDL cholesterol level brought about by LDL apheresis was at least as marked in the FDB patient as in 5 patients with familial hypercholesterolaemia. We conclude that FDB patients with coronary artery disease may derive clinical benefit from prolonged reduction of their plasma cholesterol levels and that LDL containing apo B-100 in which arginine at position 3500 is replaced by glutamine is removed from plasma by dextran sulphate columns as efficiently as is normal LDL.
Apolipoprotein B-100↗
Lipoprotein(a) in subjects with familial defective apolipoprotein B100.
The plasma lipoprotein(a) (Lp(a)) concentration and apolipoprotein(a) (apo(a)) phenotype were determined in the members of two families affected with familial defective apo B100 (FDB), resulting from the Arg3500----Gln mutation in apo B that disrupts binding to LDL receptors. Eleven different phenotypic species of apo A were identified, five of which were present in both families. Although there was a general increase in Lp(a) concentration as the size of the predominant apo(a) component decreased, there was considerable variability and in three clear instances the concentration of an inherited phenotypic species was atypically low. In five cases where a direct comparison could be made, the plasma Lp(a) concentration was significantly higher in heterozygous FDB subjects than in their non-FDB siblings or close relatives with the same phenotype. However, in vitro competition studies using purified Lp(a) that had been reduced with dithiothreitol to remove the apo(a) component, indicated that the Lp(a) from FDB heterozygotes contained a smaller proportion of defective particles than their LDL. Lp(a) particles containing normal and binding-defective apo B were present at approximately the same concentration, suggesting that the increase in Lp(a) concentration observed in FDB subjects could not be explained by the inability of the particles containing the defective apo B100 to be cleared through LDL-receptor mediated processes.
Apolipoprotein B-100↗
New observations on atrial fibrillation before and after surgical treatment in patients with the Wolff-Parkinson-White syndrome.
The records of 342 patients who received surgical treatment for the Wolff-Parkinson-White syndrome between 1968 and 1986 were reviewed to evaluate the characteristics of atrial fibrillation. The patients were classified into two groups according to the presence (n = 166) or absence (n = 176) of documented episodes of atrial fibrillation preoperatively. The mean follow-up duration was 6 years (range 2 to 20). As compared with reports based on smaller patient groups and shorter follow-up, the study revealed several new findings. 1) During follow-up, nine patients in the atrial fibrillation group developed recurrent atrial fibrillation after a successful operation; five of these nine patients did not have associated heart disease. 2) All three patients with a history of atrial fibrillation and an accessory pathway conducting in the anterograde direction only had a successful surgical procedure and no postoperative atrial fibrillation. 3) The cycle length of atrioventricular (AV) reciprocating tachycardia was significantly shorter in the atrial fibrillation group (304 +/- 42 ms, mean +/- SD) than in the no-atrial fibrillation group (321 +/- 54 ms, p less than 0.005), and the cycle length of AV reciprocating tachycardia that degenerated into atrial fibrillation (289 +/- 26 ms) was shorter than that for the AV reciprocating tachycardia without subsequent atrial fibrillation (316 +/- 51 ms, p less than 0.005). 4) Sustained atrial fibrillation was induced in 30% of patients without a history of atrial fibrillation. 5) Atrial fibrillation occurred in four patients with an accessory pathway that conducted only in the retrograde direction.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Does the EcoRI polymorphism in the human apolipoprotein B gene affect the binding of low density lipoprotein to the low density lipoprotein receptor?
In human populations, there is an association between coronary artery disease and a polymorphism in the apolipoprotein B (apo B) gene detected with the enzyme EcoRI. This polymorphism gives rise to two apo B alleles, one (E+) encoding glutamic acid and the other (E-) encoding lysine at position 4,154 in apo B-100, the protein of low density lipoprotein (LDL). We have tested the hypothesis that this amino acid substitution indirectly influences proneness to coronary artery disease by affecting the binding of LDL to LDL receptors. The receptor-binding affinities of LDLs from eight pairs of subjects with genotypes E+/+ and E-/- who were matched for other apo B genotypes were determined in vitro. There was no significant difference between the binding affinities of LDLs from the two groups of subjects. Our results strongly suggest that the amino acid at position 4,154 does not influence the function of the receptor-binding domain in apo B-100 and that the association between coronary artery disease and the EcoRI polymorphism is not mediated by an effect of the polymorphism on serum LDL concentration. In view of our findings, it would be of interest to examine the effect of the amino acid substitution on the binding of LDL to arterial proteoglycans and on the oxidizability of LDL by cells in culture.
Apolipoproteins B↗
Physiological substrate for antidromic reciprocating tachycardia. Prerequisite characteristics of the accessory pathway and atrioventricular conduction system.
BACKGROUND: Although the anatomic "substrate" for the occurrence of antidromic reciprocating tachycardia (ART) has been previously examined, the underlying physiological substrate for this unusual arrhythmia in patients with the Wolff-Parkinson-White syndrome has not been thoroughly characterized. METHODS AND RESULTS: The electrophysiological properties of the accessory pathway and normal ventriculoatrial conduction system in 30 patients with ART and a single accessory pathway were compared with those observed in a control group of 36 patients without this arrhythmia to elucidate the critical physiological substrate essential for the development and maintenance of ART. Inducible ART had a mean cycle length of 286 +/- 31 msec. The average retrograde ventriculoatrial conduction system effective refractory period in ART patients was significantly less than that in the control group (244 +/- 32 versus 291 +/- 46 msec, p = 0.0002). All of the ART patients showed retrograde conduction over the normal conduction system at cycle lengths of less than or equal to 360 msec; 23 had 1:1 conduction to less than or equal to 300 msec, and 16 showed 1:1 propagation at cycle lengths of less than or equal to 260 msec. The shortest cycle length accompanied by 1:1 retrograde propagation over the normal conduction system in patients with ART was also significantly less than that observed in the control group (274 +/- 39 versus 347 +/- 73 msec, p less than 0.001). The accessory pathway anterograde ERP in ART patients with 1:1 retrograde conduction over the normal ventriculoatrial conduction system at cycle lengths of less than or equal to 360 was significantly less than that seen in comparable control patients (247 +/- 23 versus 284 +/- 56 msec, p = 0.001), and the accessory pathway location was significantly further from the atrioventricular node in 21 patients with ART undergoing surgery than that in 22 operated control patients (3.8 +/- 0.8 versus 2.9 +/- 0.8 mapping units, p = 0.0025) who also had retrograde ventriculoatrial conduction to cycle lengths of less than or equal to 360 msec. No significant differences in anterograde atrioventricular conduction system properties, retrograde accessory pathway refractoriness, or shortest ventricular pacing cycle lengths maintaining 1:1 conduction via the accessory pathway were observed between groups. CONCLUSIONS: This quantitative characterization of the properties of conduction and refractoriness of both the accessory pathway and ventriculoatrial conduction system and the relation between these characteristics and the accessory pathway location in ART patients provides additional insight into the prerequisites for the initiation and maintenance of this rhythm disturbance.
Adult↗
Effect of Ebstein's anomaly on short- and long-term outcome of surgically treated patients with Wolff-Parkinson-White syndrome.
BACKGROUND: Ebstein's anomaly is the most commonly occurring congenital abnormality associated with the Wolff-Parkinson-White (WPW) syndrome. However, the effects of Ebstein's anomaly on the risks and benefits of surgical ablation of accessory pathways in patients with WPW syndrome are unknown. METHODS AND RESULTS: This study compared the long-term outcome of 38 WPW patients with Ebstein's anomaly undergoing accessory pathway ablation to a reference population of 384 similarly treated patients without the anomaly. Ebstein's anomaly was mild in 21 patients (55%) and moderate-to-severe in 17 patients (45%). Sixteen patients (42%) required tricuspid valve surgery, and 23 (61%) had an atrial septal defect or patent foramen ovale repaired. Baseline clinical characteristics and preoperative clinical arrhythmias were similar in both groups. Ten-year survival was 92.4% and 91.2% for patients with and without Ebstein's anomaly, respectively (p = NS). During a mean follow-up of 6.2 +/- 3.8 and 5.3 +/- 3.6 years, 82% of patients with and 90% without Ebstein's anomaly had either clinically insignificant or no arrhythmias, and 18% versus 10% reported symptoms suggesting arrhythmias lasting longer than 1 minute, respectively. Atrial fibrillation was reduced postoperatively to 9% (p less than 0.001) in patients with and to 4% (p less than 0.001) in those without the anomaly. Fewer hospitalizations were reported postoperatively by 90% versus 96% of patients with and without Ebstein's anomaly; 9.4% versus 6.0% of patients were disabled at follow-up, respectively (p = NS). CONCLUSIONS: Patients with Ebstein's anomaly are improved significantly after accessory pathway ablation. The presence of this anomaly should not preclude accessory pathway ablation in these patients.
Adolescent↗
Surgical treatment of ventricular tachycardia with Nd:YAG laser photocoagulation.
BACKGROUND: Directed surgery for the definitive treatment of drug resistant ventricular tachycardia (VT) due to coronary artery disease carries a significant operative mortality. Surgical failure to cure VT remains a problem, especially in patients without anterior left ventricular myocardial infarcts and aneurysms. A method has been developed in which Nd:YAG laser is used to photocoagulate myocardium responsible for the initiation of VT using a "sequential" approach intended to improve operative results and gain insight into the variable substrates causing VT. METHODS: Under normothermic cardiopulmonary bypass, VT is induced and then extensive endocardial and epicardial mapping performed to localize and characterize that form of VT. Nd:YAG is applied to the areas of myocardium from which that form of VT originates until it disappears and is no longer inducible. Next attempts are made to induce other forms of VT and when successful, mapping and lasing repeated until finally VT is no longer inducible. RESULTS: Fifty-one patients were operated on and have been followed for at least 1 year. Operative mortality in 12 patients with preoperative ejection fractions less than 20% was 41%; in 39 patients with ejection fractions greater than 20% operative mortality was 8%. Eighty-eight percent of the 43 operative survivors are free of recurrent sustained VT at 1 year. There have been no arrhythmic mortalities. In a group of 30 patients evaluated for epicardial VT, 9 of 14 patients with inferior infarcts without left ventricular aneurysms had at least one form of epicardial VT. CONCLUSIONS: Nd:YAG laser photocoagulation of myocardial VT using a sequential approach is a viable method that permits an ongoing study of this entity. Operative mortality remains high in patients with diffusely poor left ventricular function. Epicardial VT is frequent in patients with inferior infarcts and may account for inferior results in these patients when conventional endocardial approaches are used alone.
Adult↗
Modification of atrioventricular node transmission properties by intraoperative neodymium-YAG laser photocoagulation in dogs.
The purpose of this study was to test the feasibility of neodymium-yttrium-aluminum-garnet (Nd-YAG) laser photocoagulation of the atrioventricular (AV) node to control the ventricular rate during rapid atrial rhythms without creating AV block. In 12 dogs on normothermic cardiopulmonary bypass, short laser pulses were delivered to an area between the coronary sinus orifice and the site of the most proximally recorded His deflection until second degree AV block occurred at a paced atrial rate of 200 beats/min. Long-term effects on AV node function were followed up for 3 months. Three animals developed chronic high grade AV block. In nine animals with preserved 1:1 conduction, the mean (+/- SEM) critical atrial cycle length resulting in AV node Wenckebach periodicity increased from 183 +/- 6 to 261 +/- 24 ms (+43%), the mean RR interval during induced atrial fibrillation increased from 248 +/- 14 to 330 +/- 27 ms (+32%) and the shortest RR interval during atrial fibrillation increased from 215 +/- 11 to 275 +/- 20 ms (+28%). Laser effects were not reversed by isoproterenol infusion. Histologic examination of the irradiated area showed fibrotic changes in the AV node and fatty metamorphosis. This study suggests that 1) graded Nd-YAG laser photocoagulation of the AV node region in dogs results in long-term modification of anterograde AV node transmission properties; 2) 1:1 conduction during sinus rhythm usually remains preserved, but ventricular rate during rapid atrial rhythms is chronically reduced; and 3) progression to high grade AV block occurs in a minority of animals.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Use of adenosine during hypotension in the Wolff-Parkinson-White syndrome with supraventricular tachycardia.
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Adenosine↗
Response to cholesterol-lowering drugs in familial defective apolipoprotein B-100.
The effect of cholestyramine and simvastatin, given separately or in combination, on serum lipid concentrations in 11 patients with heterozygous familial defective apolipoprotein B-100 was compared with that in 11 matched patients with heterozygous familial hypercholesterolaemia. In both groups of patients there was a substantial fall in serum lipid levels in response to treatment. There were no significant differences between the reductions in serum total or low-density lipoprotein cholesterol levels in the two groups.
Adult↗
Surgical division of posterior septal accessory pathways in the Wolff-Parkinson-White syndrome: a new modified approach.
A new modified surgical approach for the division of posterior septal accessory pathways is described. This method incorporates some of the desirable components of previously reported techniques, while eliminating difficult and unreliable aspects of those same techniques. Interestingly this procedure was initially illustrated by Sealy and Mikat in 1983, although it has not been used clinically until now. The recognized intent of this dissection is to totally separate atrial and ventricular structures within the posterior septal space so that all accessory pathways encountered are permanently interrupted.
Atrioventricular Node↗
Functional role of the epicardium in postinfarction ventricular tachycardia. Observations derived from computerized epicardial activation mapping, entrainment, and epicardial laser photoablation.
BACKGROUND: Conventionally, monomorphic sustained ventricular tachycardia in patients with remote myocardial infarction is believed to originate from the subendocardium. In a previous study, we demonstrated that electrical activation patterns during ventricular tachycardia occasionally suggest a subepicardial rather than subendocardial reentry. METHODS AND RESULTS: This study prospectively evaluated the functional role of the epicardium in postinfarction ventricular tachycardia with complex intraoperative techniques including computerized electrical activation mapping, entrainment, observation of changes in activation pattern during successful epicardial laser photoblation, and histological study. Five of 10 consecutive patients undergoing intraoperative computerized activation mapping had 10 ventricular tachycardia morphologies displaying epicardial diastolic activation These 10 "epicardial" ventricular tachycardias revealed the following global activation patterns: monoregional spread (two), figure-eight activation (five), and circular macroreentry (three). Entrainment of ventricular tachycardia using epicardial stimulation was successfully performed from an area of slow diastolic conduction in four tachycardia morphologies. During entrainment, global activation remained undisturbed with recordings showing a long stimulus to QRS interval, unchanged QRS morphology, and pacing capture of all components of the reentry circuit. Neodymium:yttrium aluminum garnet laser photocoagulation was delivered during ventricular tachycardia to epicardial sites of presumed reentry. Epicardial photoablation terminated five of five figure-eight tachycardias, two of three circular macroreentry tachycardias but not the monoregional tachycardias. Electrophysiological recordings during epicardial laser photocoagulation demonstrated progressive prolongation of ventricular tachycardia cycle length and apparent interruption of the presumed reentrant circuit. Histological evaluation of the reentrant region (three patients) showed a rim of surviving myocardium under the epicardial surface. CONCLUSIONS: This study suggests that 1) chronic postinfarction ventricular tachycardia may result from subepicardial macroreentry, 2) slow conduction within the reentry circuit can be localized by computerized mapping and epicardial entrainment, and 3) ventricular tachycardia interruption by laser photocoagulation results from conduction delay and block within critical elements of the reentrant pathway. Viable subepicardial muscle fibers may constitute the underlying pathology.
Diagnosis, Computer-Assisted↗
Termination of ventricular tachycardia with epicardial laser photocoagulation: a clinical comparison with patients undergoing successful endocardial photocoagulation alone.
Electrical activation-guided laser photocoagulation was used intraoperatively to terminate ventricular tachycardia in patients with ischemic heart disease. During ventricular tachycardia, laser irradiation was delivered to mapped sites with local diastolic activation. In 30 long-term survivors, 85 ventricular tachycardia configurations were terminated by ablation; 72 (84.7%) were terminated by endocardial photocoagulation. Thirteen (15.3%) required epicardial photocoagulation; however, these 13 ventricular tachycardias occurred in 10 (33%) of the 30 patients. An aneurysm was present in 70% of patients with successful endocardial photocoagulation, but in only 10% of patients requiring epicardial photocoagulation for at least one ventricular tachycardia configuration; 90% of all patients requiring epicardial laser photocoagulation had no aneurysm and had either a right or a left circumflex coronary artery-related infarction. In this group, epicardial activation data were similar to those described for ventricular tachycardia with an "endocardial" origin and included 1) delayed potentials during sinus rhythm, 2) presystolic or pandiastolic activation sequences during ventricular tachycardia, and 3) regions of block near the presumed region of reentry during ventricular tachycardia. This study suggests that the critical anatomic substrates supporting reentry in postinfarction ventricular tachycardia may occur at intramural or epicardial sites, particularly in patients with right or circumflex coronary artery-related infarction and no aneurysm.
Cardiac Pacing, Artificial↗
Modification of sinus node function by epicardial laser irradiation in dogs.
This study tested the feasibility of neodymium:YAG laser photocoagulation of selected sinus node areas to depress sinus rate responsiveness. In 14 open-chest dogs, origin of the sinus impulse (O point) was electrically mapped from the epicardium before and during isoproterenol infusion. Epicardial laser photocoagulation was applied to the O point observed during isoproterenol infusion and stepwise to remapped new O points until a 30 +/- 5% decrease in heart rate occurred. Long-term effects were assessed by Holter monitoring and electropharmacologic testing preoperatively and up to 10 weeks or 6 months. Mean (+/- SEM) percent decreases were observed at 10 weeks in the following parameters: average 24-hour heart rate, 17.4 +/- 5.0%; maximum heart rate on Holter, 30.5 +/- 3.5%; heart rate during pharmacologic autonomic blockade, 32.7 +/- 3.5%; and maximum heart rate on isoproterenol, 23.1 +/- 4.6% (all p less than 0.01). Curves with pacemaker recovery time plotted against control cycle length remained unchanged. Holter monitoring did not show excessive bradycardic episodes even after administration of propranolol. In three control dogs (sham operation), sinus node function remained unchanged. Histologic study of the irradiated area showed replacement by inflammatory cells, fibrosis, and cartilage formation with surrounding normal cells and occasional cells resembling pacemaker-like cells at the caudal end of the sinoatrial node. This study suggests that 1) map-guided graded laser photocoagulation of sinus node regions showing earliest activation during catecholamine stimulation successfully limits maximum heart rates without causing significant bradycardia, 2) the effects are long lasting, and 3) the remaining pacemaker behaves like the sinus node. Laser modification of sinus node function could become a form of nonpharmacologic heart rate control in patients with coronary artery disease undergoing surgery and in the syndrome of inappropriate sinus tachycardia.
Animals↗
Importance of preexcited QRS morphology during induced atrial fibrillation to the diagnosis and localization of multiple accessory pathways.
The present investigation evaluates the ability of several electrocardiographic (ECG) and electrophysiologic methods to identify multiple accessory pathways in 47 patients in whom the presence and sites of multiple accessory pathways were confirmed intraoperatively. To establish ECG features that suggested the presence of multiple accessory pathways in these patients, we initially studied the 12-lead ECG during maximal preexcitation in 101 patients with single accessory pathways. Distinctive 12-lead ECG patterns were noted for six defined anatomic areas around the right and left atrioventricular groove. Multiple preexcited QRS morphologies, each typical for a separate accessory pathway, and atypical preexcited QRS morphologies were recorded during atrial fibrillation in 31 of 47 (66%) patients with multiple accessory pathways. By comparison, the ECG during sinus rhythm and rapid atrial pacing identified 14 (32%) and 26 (55%) of the patients, respectively. In 12 (26%) patients in whom evidence for multiple accessory pathways was absent from endocardial mapping data, atrial fibrillation provided the diagnosis. In five (11%) patients, atrial fibrillation was the only method that demonstrated the presence of multiple accessory pathways. A combination of ECG findings during atrial fibrillation and rapid atrial pacing plus endocardial mapping data identified 43 (91%) of the patients with multiple accessory pathways. There were two unique fusion patterns on the 12-lead ECG that were characteristic of specific multiple accessory pathway combinations.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
High grade entrance and exit block in an area of healed myocardial infarction associated with ventricular tachycardia with successful laser photoablation of the anatomic substrate.
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Aged↗