Interaction between ion transporters and the mucociliary transport system in dog and baboon.

To gain insight into the role of epithelial ion channels, pumps, and cotransporters in regulating airway water and mucociliary transport, we administered inhibitors of the Na+ channel (amiloride), 3Na-2K-adenosinetriphosphatase (acetylstrophanthidin), and Na-K-2Cl cotransporter (furosemide) to anesthetized dogs and/or baboons. Tracheal ciliary beat frequency was measured by using heterodyne laser light scattering. Tracheal mucus velocity (TMV) and bronchial mucociliary clearance (BMC) or lung mucociliary clearance were measured by using radioaerosols and nuclear imaging. Respiratory tract fluid output was collected by using a secretion-collecting endotracheal tube. In six dogs, amiloride aerosol -lung deposition, 96 +/- 11 microg (means +/- SE)- had minimal effect, whereas acetylstrophanthidin aerosol (lung deposition, 71 +/- 9 microg) increased BMC, and furosemide (40 mg iv) markedly increased TMV. In five baboons, TMV increased after iv furosemide administration (2 mg/kg) as well as by aerosol (lung deposition, 20 +/- 3 mg), coincident with increases in ciliary-mucus coupling from 11.5 +/- 0. 1 to 29.5 +/- 0.4 and 46.5 +/- 0.7 microm/beat, respectively. Furosemide also increased lung mucociliary clearance in baboons. In dogs, respiratory tract fluid output increased after intravenous furosemide from 2.2 +/- 0.5 to 6.8 +/- 1.7 mg/min. When combined with dry-air inhalation, furosemide failed to stimulate TMV and reversed the inhibition of BMC by dry air. Thus pharmacological manipulation of the Na-K-2Cl cotransporter and the 3Na-2K-adenosinetriphosphatase pump may provide increases of clinical relevance in airway hydration and mucociliary transport.

Roles of hydration, sodium, and chloride in regulation of canine mucociliary transport system.

To gain insight into the homeostatic mechanisms regulating airway ion/water fluxes and mucociliary transport, the canine tracheobronchial airway fluid was perturbed by deposition of hypo- and hyperosmotic aerosols for >1 h. Tracheal ciliary beat frequency (CBF) was measured by using heterodyne laser light scattering. Tracheal mucus velocity (TMV) and bronchial mucociliary clearance (BMC) were measured by using radioaerosols and nuclear imaging. Respiratory tract fluid output (RTFO) was collected by using a secretion-collecting endotracheal tube. In six dogs, CBF increased during water deposition in the airways to 180 +/- 30 mg/min and RTFO increased from 2.2 +/- 0.5 to 18.3 +/- 1.6 mg/min, accounting for <10% of the fluid deposition. TMV and BMC were unchanged. CBF, TMV, and BMC were markedly increased by inhalation of aerosolized 3.4 M NaCl. Aerosolized 0.85 M NaCl, in contrast, decreased BMC. In this case, RTFO represented 24% of aerosol deposition. Aerosolized 0.85 M choline chloride and 0.85 M sodium gluconate enhanced BMC and TMV concurrent with a decrease in CBF. RTFO of sodium gluconate studies exceeded 50% of aerosol deposition. Thus the airways appear to have transepithelial compensatory mechanisms that reduce the impact of a moderate increases in NaCl and hydration load, but when these responses cannot adequately respond because of the delivery of impermeable ions or very high tonicity, removal of the challenges are affected by a stimulation of mucociliary transport.

Nonsustained polymorphous ventricular tachycardia during amiodarone therapy for atrial fibrillation complicating cardiomyopathy. Management with intravenous magnesium sulfate.

A case is presented in which amiodarone was administered to suppress paroxysmal atrial fibrillation in a patient with an idiopathic cardiomyopathy. Eleven days after initiation of therapy with amiodarone, the patient experienced syncope and was noted to have recurrent episodes of polymorphous ventricular tachycardia. The patient was hospitalized and treated with a bolus as well as continuous infusion of intravenous magnesium sulfate. When the infusion was transiently discontinued, recurrences of polymorphous ventricular tachycardia were noted. The probable proarrhythmic action of amiodarone, although rare, is reviewed along with a discussion of the novel use of intravenous magnesium sulfate therapy.

Syncope: the diagnostic value of head-up tilt testing.

To determine the usefulness of prolonged head-up tilt in the diagnosis of neurally mediated syncope, 201 patients with history of syncope of unknown cause and 102 age and gender matched control subjects underwent a 40 minute 60 degrees head-up tilt test. Head-up tilt elicited syncope (i.e., was positive) in 74 of the 201 patients (37%) with a history of unexplained syncope and in only 6 of the 102 controls (6%). The specificity of the test was 100% in patients 60 years of age and older. Symptoms during tilt-induced syncope were identified by the patients as similar to those they had suffered during their spontaneous episodes. All 80 subjects who had tilt-induced syncope recovered without sequelae. The positive predictive value of a positive responses to head-up tilt was 93% and the negative predictive value was 43%. The results indicate that the prolonged head-up tilt test is a very specific procedure of high diagnostic value in patients with a history of unexplained syncope. It is particularly useful in the elderly age groups who have a high incidence of syncope.

Predictors of long-term survival in patients with malignant ventricular arrhythmias.

The study consisted of 369 patients (age 62 +/- 13 years) who presented to our institution from April 1984 to April 1994 for malignant ventricular arrhythmias presenting as sustained ventricular tachycardia (VT) in 57% of patients, ventricular fibrillation in 25% of patients, and syncope due to VT in 17% of patients. Coronary artery disease was present in 74% of patients, cardiomyopathy in 19% of patients, and no evident heart disease in 7% of patients. Two hundred twenty-one patients were given drug, therapy, 47 patients underwent arrhythmia surgery, and 75 patients had an implantable cardioverter-defibrillator (ICD). During a mean follow-up of 30 months (range 1 to 101), 66 patients (18%) died from a cardiac death of which 26 (39%) were sudden. Cox regression analysis was conducted utilizing a total of 19 variables (clinical and therapeutic) in the entire population and separately in patients with coronary artery disease and cardiomyopathy. The most significant variables (multivariate analysis) of survival from cardiac mortality in the entire population were: congestive heart failure (CHF) class (p = 0.0003), ejection fraction (p = 0.02), and the use of drug therapy (p = 0.03); in patients with coronary artery disease, CHF class (p = 0.0001) and ejection fraction (p = 0.0006); and in patients with cardiomyopathy, CHF class (p = 0.009) and sustained VT on Holter monitoring (p = 0.007). Kaplan-Meier survival rates from cardiac death were: significantly lower (p = 0.005) in patients with CHF class III and IV compared with CHF class I and II (25% vs 58%, p = 0.005) with drug therapy; marginally significant (47% vs 88%, p = 0.06) from 20 to 40 months in patients with an ICD; and nonsignificant in patients who underwent arrhythmia surgery (63% vs 71%). Patients with an ICD had a better expected survival (82%) than patients who had arrhythmia surgery (69%) and drug therapy (65%). Thus, in patients with malignant ventricular arrhythmias, CHF class was the most significant independent predictor of survival from cardiac mortality over all disease substrates, and therapy influenced survival depending on the CHF class. Patients in CHF class III and IV who underwent arrhythmia surgery or had an ICD had a better expected survival than those taking drug therapy, and the negative impact of antiarrhythmic therapy was most prominent in patients with CHF class III and IV.

Setting of relatively low energy outputs may permit implantation of a nonthoracotomy automatic cardioverter defibrillator system when high energy outputs prove ineffective.

At intraoperative testing of defibrillation thresholds during implantation of internal cardioverter defibrillators, standard step-down approaches of energy outputs are used. If relatively high energy outputs are not successful at defibrillating the heart, the electrodes are frequently reconfigured. When attempting implantation of a nonthoracotomy lead system, high defibrillation thresholds may warrant opening of the chest cavity to place one or more epicardial electrodes. A case is presented where a nonthoracotomy system was able to be implanted using relatively low energy outputs which were reproducibly successful at terminating ventricular fibrillation when higher energy outputs were unsuccessful. Mechanisms for this phenomenon and alternate recommendations for defibrillation testing are presented.

Successful catheter ablation of an inferoseptal accessory pathway within the coronary sinus in a patient with a previously unsuccessful attempt at surgical interruption. Coronary sinus ablation for Wolff-Parkinson-White syndrome.

In a patient with Wolff-Parkinson-White syndrome and a right inferoseptal accessory pathway who had had a previously unsuccessful surgical attempt at accessory pathway ablation, the accessory pathway was found to be adjacent to a branch of the coronary sinus. Radiofrequency energy was delivered within this branch to ablate the pathway successfully. This demonstrates an alternative approach to the more common method of radiofrequency ablation of accessory pathways from a tricuspid or mitral annular location.

Obstructive sleep apnea-induced supraventricular tachycardia.

Obstructive sleep apnea has been associated with various cardiac arrhythmias; however, supraventricular tachycardia has not been reported to occur in this disorder. This case report describes a patient who developed episodes of supraventricular tachycardia during periods of apnea and oxygen desaturation. With the initiation of nasal continuous positive airway pressure during sleep, the arrhythmia was abolished. The etiology and possible mechanisms responsible for the supraventricular tachycardia are discussed.

Complete atrioventricular block with ventricular asystole following infusion of intravenous phenytoin.

A case of complete atrioventricular block with ventricular asystole in a patient receiving intravenous phenytoin is presented. Although the potential for hypotension is generally recognized with the intravenous administration of phenytoin, conduction abnormalities are rarely reported. The differential diagnosis of atrioventricular block and the effects of phenytoin on cardiac conduction are discussed.

Flecainide induced atrial tachycardia with 1:1 ventricular conduction during exercise testing.

Wide complex tachycardias may represent a rare proarrhythmic effect of some antiarrhythmic agents. The authors describe a patient who developed a wide complex tachycardia developing during stress testing while on therapy with flecainide, and the difficulty in interpreting the electrocardiogram. This article reviews potential proarrhythmic effects of flecainide in the treatment of atrial dysrhythmias and the difficulty in differentiating associated wide complex tachycardias.

Determinants of induction of ventricular tachycardia in nonsustained ventricular tachycardia after myocardial infarction and the usefulness of the signal-averaged electrocardiogram.

Assessment of the implications of clinical and noninvasive variables, including the results of signal-averaged electrocardiography, was performed > or = 3 weeks after myocardial infarction in 57 patients with nonsustained ventricular tachycardia (VT) who underwent programmed ventricular stimulation to guide antiarrhythmic therapy. The clinical and noninvasive parameters assessed included ages, left ventricular ejection fractions, sites of infarction, presence of akinetic or dyskinetic left ventricular segments, history of syncope, history of coronary artery bypass surgery, and presence or absence of late potentials from signal-averaged electrocardiography. Other than the presence of late potentials, no clinical or noninvasive parameters identified such persons with a significantly higher likelihood of inducible VT. When assessed as positive if 1 or more variables were abnormal, 16 of 16 (100%) patients with versus 17 of 41 without inducible VT had late potentials (p < 0.002). With more stringent criteria required (defined as prolongation of the QRS vector complex duration and low root-mean-square voltage of the terminal 40 ms of the vector complex) 8 of 16 patients (50%) with and 4 of 41 (10%) without inducible VT had late potentials recorded (p < 0.002). Thus, the signal-averaged electrocardiogram may enable identification of persons with nonsustained VT after myocardial infarction who are most likely to have VT induced at programmed ventricular stimulation.

Effect of oral sotalol on systemic hemodynamics and programmed electrical stimulation in patients with ventricular arrhythmias and structural heart disease.

We explored the central hemodynamic responses to oral sotalol during dose titration in patients with ventricular arrhythmias who underwent programmed ventricular stimulation. Twelve patients were included in the study, 9 with a history of sustained ventricular tachyarrhythmias (6 postmyocardial infarction and 3 with cardiomyopathy) and 3 with a history of nonsustained ventricular tachycardia postmyocardial infarction. Left ventricular ejection fractions were < 45% in 10 patients, and < 35% in 5; the mean ejection fraction was 37% (range 20-51%). Sotalol prevented the induction of ventricular tachycardia in each of 3 patients with nonsustained ventricular tachycardia and in 6 of 9 with sustained ventricular tachycardia at baseline study. At peak action (2 hours) after sotalol loading (mean dose, 167 mg orally twice daily), the hemodynamic effects included bradycardia, decreased cardiac index, increased left ventricular filling pressure and systemic vascular resistance, and no change in stroke volume or stroke work index. One patient was not continued on sotalol, owing to an excessive increase in the pulmonary capillary wedge pressure, despite the lack of symptomatic heart failure. Congestive heart failure in association with marked bradycardia developed in another patient, who had suppression of inducible ventricular tachycardia after sotalol loading; this patient was managed with a reduction in the dose of sotalol and a regimen of digoxin and furosemide, and has been well compensated and without a recurrence of sustained ventricular tachycardia for more than 4 years. Ventricular tachycardia has been controlled with sotalol, without hemodynamic deterioration, in 6 of these patients.(ABSTRACT TRUNCATED AT 250 WORDS)