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Biomedical subjects

M N Langan

Publications and source records attributed to M N Langan.

8 recordsLinked to original sources
PubMed2001

Pacemakers and defibrillators for congestive heart failure.

Although medical therapy is the primary therapy for patients with heart failure, the use of pacemakers to improve cardiac hemodynamics is under investigation. Despite promising initial results, controlled studies have not verified the benefit of application of VDD or DDD pacing to a nonselected population of severely symptomatic congestive heart failure (CHF) patients to simply shorten their atrioventricular (AV) delay. There is increasing interest in pacing the left side of the heart or simultaneously pacing the right and left ventricles. Early studies suggest that these techniques may produce favorable hemodynamic effects in patients with CHF. Controlled, randomized studies are now underway. Further, it has been shown that sudden cardiac death accounts for 50% of deaths in patients with CHF. The value of an implantable cardioverter defibrillator (ICD) in secondary prevention of sudden cardiac death is well established. The use of ICD for primary prevention of sudden cardiac death in patients with CHF is being actively evaluated. Several large multicenter trials are underway, some combined with biventricular pacing, and should provide useful data in the coming years.

Death, Sudden↗
PubMed1999

The impact of recent ion channel science on the development and use of antiarrhythmic drugs.

In the past 20 years in the basic laboratory, tools have been developed to further our understanding of the mechanism of arrhythmias and of the effect of compounds on these or their substrates. Patch clamp studies have better defined the cardiac channels. A new classification of antiarrhythmic drugs was devised, coined the Sicilian Gambit. Drugs, aimed at blocking specific channels, are now being developed. With the cloning of channels, information about their molecular structure became available. One can begin to understand the molecular determinants of antiarrhythmic drug action on specific ion channels, and how this is modulated by effectors. Molecular and electrophysiologic techniques also have been used to collect information about the way disease states affect the cardiac channels, and how this can alter the response to ion channel blockers. This has proceeded utilizing a few technologies. Diseased heart cells from patients, from animal models of disease, or from transgenic mice are studied to examine the change in current expression and channel protein quantity in different stages of disease. Hopefully this new information will make drug therapy more target-oriented.

Animals↗
PubMed1998

Variable effects of adenosine on retrograde conduction in patients with atrioventricular nodal reentry tachycardia.

Adenosine has been demonstrated to reliably produce transient block of atrioventricular nodal (AVN) conduction, and has been advocated as a method of differentiating retrograde conduction via the atrioventricular node from accessory pathway conduction. However, the response of retrograde AVN to adenosine in patients with typical atrioventricular nodal reentry tachycardia (AVNRT) remains unclear. We evaluated 13 patients (mean age 45 +/- 20 years) with typical AVNRT prior to AVN modification. During right ventricular pacing, a rapid bolus of adenosine (0.2 mg/kg; maximum 18 mg) was administered. Adenosine sensitivity, defined by transient ventriculoatrial block, was observed in six patients, while in seven patients ventriculoatrial conduction was unaffected. An adenosine bolus administered during sinus rhythm or atrial pacing resulted in antegrade atrioventricular block in all the adenosine resistant patients in whom this was performed (n = 6). Comparisons of AVN electrophysiological characteristics between the adenosine sensitive and adenosine resistant patients were performed. There was no difference with respect to ventriculoatrial effective refractory period, ventriculoatrial Wenckebach, AVNRT cycle length, and His to atrial echo interval in AVNRT. However, there was a trend toward a longer antegrade fast pathway ERP in the adenosine sensitive group (P = 0.07). Electrophysiological properties do not predict retrograde AVN adenosine sensitivity. Adenosine does not cause retrograde AVN block in all patients with AVNRT, and therefore cannot reliably distinguish between retrograde conduction via the AVN or an accessory pathway.

Adenosine↗
PubMed1997

The acute treatment of supraventricular tachycardia.

The diagnosis of supraventricular tachycardia has become much more important with the advent of radiofrequency ablation. This is usually best done at presentation in an acute setting. A 12-lead electrocardiogram should be a routine aid in making the diagnosis. A continuous rhythm strip must be obtained during administration of adenosine and at the termination of tachycardia. Most recent treatment guidelines would include adenosine as first-line therapy. If adenosine fails to restore normal sinus rhythm, diltiazem or a beta blocker should then be considered. If there is significant heart failure, digoxin may be useful. In the presence of wide complexes, agents that produce atrioventricular nodal block should be avoided.

Acute Disease↗
PubMed1996

A recombinant inwardly rectifying potassium channel coupled to GTP-binding proteins.

GTP-binding (G) proteins have been shown to mediate activation of inwardly rectifying potassium (K+) channels in cardiac, neuronal and neuroendocrine cells. Here, we report functional expression of a recombinant inwardly rectifying channel which we call KGP (or hpKir3.4), to signify that it is K+ selective, G-protein-gated and isolated from human pancreas. KGP expression in Xenopus oocytes resulted in sizeable basal (or agonist-independent) currents while coexpression with a G-protein-linked receptor, yielded additional agonist-induced currents. Coexpression of KGP and hGIRK1 (a human brain homolog of GIRK1/Kir3.1) produced much larger basal currents than those observed with KGP or hGIRK1 alone, and upon coexpression with receptor, similarly large agonist-induced currents could be obtained. Pertussis toxin treatment significantly diminished agonist-dependent currents due to either KGP or KGP/hGIRK1 expression. Interestingly, PTX also significantly reduced basal KGP or KGP/hGIRK1 currents, suggesting that basal activity is largely the result of G-protein gating as well. When the two channels were coexpressed with receptor, the relative increase in current elicited by agonist was similar whether KGP and hGIRK1 were expressed alone or together. When in vitro translated or when expressed in Xenopus oocytes or CHO mammalian cells, KGP gave rise to a nonglycosylated 45-kD protein. Antibodies directed against either KGP or hGIRK1 coprecipitated both proteins coexpressed in oocytes, providing evidence for the heteromeric assembly of the two channels and suggesting that the current potentiation seen with coexpression of the two channel subunits is due to specific interactions between them. An endogenous oocyte protein similar in size to KGP was also coprecipitated with hGIRK1.

Acetylcholine↗
PubMed1995

Sinus node reentrant tachycardia.

This review article discusses the electrophysiological basis of sinus node reentry, clinical features of sinus node reentry, and the management of this uncommon tachycardia with drugs and ablative therapy. It also proposes the use of the term "sinoatrial reentrant tachycardia" for this form of tachycardia.

Animals↗