Parasympathetic and sympathetic alterations of Mobitz type II heart block.

This study examined the effects of changes in parasympathetic and sympathetic tone on the cycle length at which Mobitz type II second degree atrioventricular (AV) block occurred. Four patients who had electrocardiographic evidence of type II AV block and confirmation of block in the His-Purkinje system during electrophysiologic study were evaluated. These patients received intravenous atropine (1.0 to 2.4 mg), propranolol (0.15 mg/kg body weight) or isoproterenol (1 and 2 micrograms/min) alone or in combination. In two of three patients receiving propranolol, the atrial pacing cycle length at which 1:1 His-Purkinje conduction occurred was prolonged relative to control (from 360 to 470 ms and 440 to 590 ms, respectively). In contrast, atropine in the presence of beta-adrenergic blockade shortened the cycle length at which 1:1 His-Purkinje conduction occurred in three of four patients receiving the drug (470 to 390, 630 to 570 and 590 to 560 ms, respectively). Isoproterenol also improved His-Purkinje conduction in the one patient receiving this drug. No agent affected the duration of the HV interval during spontaneous sinus rhythm or right atrial pacing. Thus, drugs that alter autonomic tone influence abnormal His-Purkinje conduction minimally during sinus rhythm but, importantly, may modulate the atrial pacing cycle length at which type II AV block occurs.

Mechanism of antiarrhythmic drug-induced changes in defibrillation threshold: role of potassium and sodium channel conductance.

OBJECTIVES: We sought to determine which ion current predominantly affects defibrillation outcomes by using specific pharmacologic probes (lidocaine [a sodium channel blocking agent] and cesium [an outward potassium channel blocking agent]) in 26 swine. BACKGROUND: The effect of a drug on sodium or potassium channel conductance, or both, may affect defibrillation threshold values. However, it is unknown which ion channel predominates. METHODS: Each pig was randomly assigned to one of four treatment groups with two treatment phases: group 1 = placebo (D5W) in treatment phase I followed by placebo plus cesium in treatment phase II (n = 6); group 2 = lidocaine followed by lidocaine plus placebo (n = 7); group 3 = lidocaine followed by lidocaine plus cesium (n = 7); group 4 = placebo followed by placebo plus placebo (n = 6). Defibrillation threshold values and electrocardiographic measurements were obtained at baseline and at treatment phases I and II. RESULTS: Lidocaine increased defibrillation threshold values from baseline by 71% in group 2 (p = 0.02) and by 92% in group 3 (p < 0.01). There were no changes in defibrillation threshold values from baseline to D5W in groups 1 and 4. When D5W was added to lidocaine in group 2 and D5W in group 4, there were no significant changes in defibrillation threshold values. However, when cesium was added to lidocaine in group 3, the elevated defibrillation threshold values (mean +/- SD) returned to baseline values (from 15.7 +/- 3.46 to 7.55 +/- 3.19 J, p < 0.01). Cesium added to D5W in group 1 also significantly reduced defibrillation threshold values from 7.10 +/- 1.27 to 4.14 +/- 1.75 J (p < 0.01). The effect of cesium on defibrillation threshold values was similar between groups 1 and 3, regardless of lidocaine, such that these values were reduced by 40 +/- 14% and 51 +/- 18%, respectively (p = 0.28). CONCLUSIONS: Cesium, through potassium blockade, reverses lidocaine-induced elevation in defibrillation threshold values. The magnitude of defibrillation threshold reduction when cesium was added to lidocaine was similar to the defibrillation threshold reduction when cesium was added to placebo. Thus, inhibiting outward potassium conductance and prolonging repolarization decreases defibrillation threshold values independent of sodium channel blockade.

Aging effects on the organic base transporter and stereoselective renal clearance.

OBJECTIVE: The organic base transporter is responsible for stereoselective renal excretion. Changes in activity of this system secondary to aging may affect the disposition of an organic base in a stereoselective manner. METHODS: Eight young men (age range, 22 to 33 years) and seven elderly men (age range, 62 to 79 years) were given 10 mg pindolol twice daily, pindolol with 200 mg trimethoprim once daily (a known inhibitor of organic base secretion) and pindolol with 1.5 gm ammonium chloride (NH4Cl) four times daily for 3 days on three occasions. On day 4, urine and plasma were collected over 24 hours to determine renal clearance (CLR) values of pindolol isomers. RESULTS: R(+)-Pindolol CLR values in young versus elderly men were 203 +/- 82 versus 150 +/- 87 ml/min, 128 +/- 51 versus 113 +/- 35 ml/min, and 480 +/- 248 versus 247 +/- 59 ml/min during the control, trimethoprim, and NH4Cl study phases, respectively. S(-)-Pindolol CLR values in young versus elderly were 279 +/- 81 versus 207 +/- 105 ml/min, 178 +/- 70 versus 136 +/- 42 ml/min, and 593 +/- 294 versus 276 +/- 49 ml/min during control, trimethoprim, and NH4Cl phases, respectively. NH4Cl increased R(+)-pindolol CLR by 138% (p < 0.05 versus pindolol alone) in young men, which was significantly greater than that observed in elderly subjects (66%; p < 0.05 versus pindolol alone; p = 0.016 young versus old). NH4Cl affected S(-)-pindolol CLR in a similar manner. Trimethoprim decreased R(+)-pindolol CLR in the young subjects by 37% (p < 0.05 versus pindolol alone), which was similar to that observed in the elderly subjects (26%; p < 0.05 versus pindolol alone; p = 0.94 young versus elderly). Trimethoprim affected S(-)-pindolol CLR in a similar manner. Stereoselective renal excretion of pindolol was unaffected by NH4Cl and trimethoprim, where the R(+)/S(-)-pindolol CLR ratio was unchanged (p = NS) from control in the young and elderly subjects. Comparison of the pindolol CLR isomer ratio between young and elderly groups showed no significant differences. Changes in pindolol clearance values resulted in significant changes in beta-blocking activity, assessed by isoproterenol (INN, isoprenaline) testing. CONCLUSIONS: Trimethoprim and NH4Cl significantly affect pindolol renal and total clearance values. Aging does not alter renal excretion of pindolol except for the magnitude by which renal excretion can be stimulated.

Cardiac myxoma. A review.

Cardiac myxoma is a true intracardiac neoplasm, which is histologically benign but which on occasion may exhibit behavior suggestive of a true malignancy. It is the most common form of primary cardiac tumor, accounting for 50% of such neoplasms. Seventy-five percent of myxomas are found in the left atrium, typically arising from a stalk attached to the area of the foramen ovale. Cardiac myxomas typically present as a triad of obstructive, embolic, and constitutional symptoms and thus mimic many more common systemic illnesses. This report summarizes 9 cases of cardiac myxoma seen at this institution since a previous report in 1972. Four cases with unusual manifestations are high-lighted in the text to illustrate the protean manifestations of this potentially curable illness. Non-invasive cardiac imaging is essential to establish the diagnosis and differentiate myxoma from the other more common illnesses it imitates. Echocardiography is highly accurate for its diagnosis, has proved invaluable for the management of these patients, and is the imaging technique of choice for initial evaluation of patients in whom the diagnosis of cardiac myxoma is suspected.

Termination of sustained ventricular tachycardia by external noninvasive pacing.

Cardiac pacing has proven useful in the termination of sustained ventricular tachycardia (VT). In this study, the effectiveness of external noninvasive temporary pacing was compared with traditional endocardial burst ventricular pacing for the termination of sustained and hemodynamically stable VT. In 14 patients, 16 VT morphologies induced by programmed right ventricular extrastimulation were reproducibly terminated by endocardial burst pacing (3 to 9 complexes). VT cycle lengths averaged 392 +/- 97 ms (standard deviation) and ranged from 300 to 690 ms. The endocardial burst pacing cycle length used to terminate VT averaged 298 +/- 93 ms (range 220 to 600 ms). External burst pacing terminated 14 of 16 VT morphologies (88%). The pacing cycle length used to terminate these 14 VTs averaged 282 +/- 44 ms. The number of ventricular captures ranged from 5 to 20 beats. Failure to terminate 2 VT morphologies probably represented a failure of the device to capture the ventricle. Acceleration of VT occurred in 1 patient with burst external noninvasive pacing. These observations suggest that external burst pacing may be an effective means of terminating sustained VT in some patients.

Encainide for atrial fibrillation associated with Wolff-Parkinson-White syndrome.

Thirty-six patients with a history of atrial fibrillation and Wolff-Parkinson-White syndrome were treated with oral encainide, 175 +/- 44 mg/day, after undergoing baseline drug-free electrophysiologic studies. The mean age was 38 +/- 15 years, with structural heart disease present in only 3 patients. Nine patients had only paroxysmal atrial fibrillation and 27 patients had both atrial fibrillation and atrioventricular reciprocating tachycardia (AVRT). Symptoms were present for a mean of 195 +/- 168 months and were treated with an average of 2.7 +/- 1.6 drugs before encainide. Anterograde block in the accessory pathway occurred in 12 of 30 patients (40%) and retrograde block accessory pathway occurred in 10 of 24 patients in whom comparison could be made. AVRT was initiated in 29 of 36 patients during the control study and could be initiated in 19 of 29 patients while receiving encainide. Drug efficacy was determined by the clinical response judged completely effective, partially effective or ineffective. During a mean follow-up of 30.1 +/- 25 months, 24 patients (67%) continued to take encainide. Encainide was completely effective in 14 of 24 patients and partially effective in another 7 patients. Noncardiac side effects were mild and generally resolved, and required discontinuance in only 1 patient. More frequent AVRT occurred in 2 patients, but was managed with dose reduction and the addition of a beta blocker. Three patients had ventricular tachycardia requiring discontinuance; however 2 of 3 patients had a history of ventricular tachycardia before receiving encainide. Encainide is an effective and safe agent for treating atrial fibrillation in patients with Wolff-Parkinson-White syndrome.

Encainide for treatment of atrioventricular reciprocating tachycardia in the Wolff-Parkinson-White syndrome.

Oral encainide, varying from 75 to 300 mg/day (mean 174 mg/day), was administered to 52 patients with drug-resistant atrioventricular reciprocating tachycardia (AVRT) associated with the Wolff-Parkinson-White syndrome. Electrophysiologic studies were performed before and during drug treatment. Encainide resulted in anterograde accessory pathway block in 15 of 37 (41%) and retrograde accessory pathway block in 11 of 46 (24%) patients. In patients with residual accessory pathway conduction, encainide significantly prolonged the shortest pacing cycle length maintaining anterograde (261 +/- 26 to 404 +/- 85 ms) and retrograde (279 +/- 46 to 436 +/- 87 ms) accessory pathway conduction, as well as the anterograde accessory pathway effective refractory period (271 +/- 32 to 329 +/- 73 ms). AVRT could not be induced during encainide therapy in 20 of 49 patients (41%). In the remaining patients, AVRT cycle length increased (319 +/- 44 to 426 +/- 90 ms, p less than 0.001) due to prolongation of HV and ventriculoatrial intervals. During follow-up (mean 38.5 months), 30 patients continued to take the drug and 7 patients with favorable drug response subsequently elected to undergo surgical accessory pathway ablation (71% overall favorable response). Encainide was ineffective in 11 patients, was discontinued because of drug intolerance in 2 patients and exacerbated ventricular tachycardia in 2 patients. Lack of AVRT inducibility at encainide electrophysiologic study did not always predict recurrence-free follow-up. Encainide is an effective and well-tolerated drug to prevent recurrence of AVRT in patients with Wolff-Parkinson-White syndrome.

Encainide for treatment of supraventricular tachycardias associated with the Wolff-Parkinson-White syndrome.

Thirty-three patients with supraventricular tachycardia associated with the Wolff-Parkinson-White syndrome were treated with encainide for 26 months (mean). Encainide at a mean dosage of 187 mg/day abolished or markedly decreased episodes of palpitations in 24 of 33 (73%), and no patient had syncope or required cardioversion while receiving the drug. Encainide was well tolerated and was discontinued in only 2 patients because of side effects (6%). Only 1 patient (3%) had a proarrhythmic effect while taking encainide (ventricular tachycardia). Fourteen of 16 patients (88%) with atrial fibrillation continue receiving encainide. Episodes of palpitations have been abolished or markedly decreased and no patient has had syncope or required cardioversion. All 14 of these patients had either anterograde block in the accessory pathway during atrial fibrillation or greater than or equal to 75 ms increase in the shortest R to R interval formed by 2 preexcited QRS complexes. Encainide prolonged refractory periods of the atrial (p = 0.064) and ventricular (p = 0.061) muscle. It prolonged the cycle length at which 1:1 conduction of the accessory pathway in both the anterograde and retrograde directions occurred (both, p less than 0.001). Induction of atrioventricular-reciprocating tachycardia (AVRT) was prevented in 36% of patients at repeat electrophysiologic study. The AVRT cycle length increased 112 ms (mean, p less than 0.001) in those patients in whom AVRT was still inducible. The loss of delta waves recorded with the 12-lead scalar electrocardiogram during encainide therapy was a significant predictor of anterograde accessory pathway block (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler echocardiographic detection of a ruptured acquired aneurysm of the sinus of Valsalva. Clinical-morphologic correlations.

Two-dimensional, pulsed Doppler echocardiographic and pathologic features of an unusual form of ruptured aneurysm of the sinus of Valsalva are presented. The presence of an aneurysm of the left sinus of Valsalva protruding into the left atrium complicating acute aortic valvular endocarditis was detected by two-dimensional echocardiography. Rupture of the aneurysm of the sinus of Valsalva into the left atrial cavity was suggested by pulsed Doppler echocardiography. The size and location of the site of the rupture precluded recognition by two-dimensional echocardiography or contrast angiography. This report illustrates the unique value of pulsed Doppler echocardiography to define the location and direction of intracardiac flow patterns in evaluating patients with an aneurysm of the sinus of Valsalva and suspected rupture.

Influence of hypertonic saline solution infusion on defibrillation efficacy.

Hypertonic saline solution may enhance cardiac conduction via the fast inward sodium channel and alter transmembrane Ca+2 conductance via the sodium-calcium exchanger. Evidence suggests that both Ca+2 conductance and myocardial conduction velocity may affect ventricular defibrillation. Since hypertonic saline solution solutions (ie, sodium bicarbonate) may be administered to patients who have conditions that often require ventricular defibrillation (ie, cardiac arrest or hypovolemic shock), we studied the effect of hypertonic saline solution on the defibrillation threshold (DFT) in 16 pentobarbital-anesthetized domestic farm swine (20 to 30 kg). Defibrillation was performed using two interfaced epicardial electrode patches. DFTs were determined at baseline and during treatment phase. Pigs were randomly assigned to treatment consisting of either hypertonic saline solution (6 mmol/kg load, 2.0 to 3.0 mmol/kg infusion) to maintain serum sodium concentrations 10 to 15 mmol/L above baseline or control (D5W given in equal volume). DFT values (joules) that predicted 50% success were modeled from a best-fit histogram. Hypertonic saline solution did not change DFT values from baseline values (10.2 +/- 4.3 vs 10.8 +/- 7.0, respectively). Likewise, placebo (D5W) did not change DFT values from baseline values (10.1 +/- 4.5 vs 11.3 +/- 4.3). During treatment phase, DFT values were 99 +/- 28% of baseline values in the hypertonic saline solution group and 116 +/- 23% of baseline values in the D5W groups (p = 0.21). The administration of hypertonic saline solution also did not affect ventricular conduction velocity, right ventricular action potential duration, or right ventricular effective refractory period. These data indicate that hypertonic saline solution does not appreciably affect defibrillation efficacy or electrical treatment of ventricular fibrillation.

Clinical applications of external pacing: a renaissance?

It is nearly 40 years since the first reports of noninvasive external pacing for Stokes-Adams syncope. Despite the ease and safety, this method of pacing has yet to flourish despite a recent interest by several authors. At present, external pacing seems best suited for temporary pacing situations that arise as an emergency or for purely prophylactic indications. External pacing is the preferred method of pacing recommended in the advanced cardiac life support guidelines. However, most emergency room and prehospital cardiac arrest trials have not shown any significant benefit from early application of external pacing. The indications have been broadened to include symptomatic bradycardia and termination of some ventricular tachycardias. It may be useful for the termination of AV reciprocating tachycardia and AV nodal reentrant tachycardia. There is a vision that external pacing may be used for serial electrophysiological testing of antiarrhythmic agents. However, there is little data in this regard. More importantly, the external pacing thresholds must be reduced further to allow for sophisticated pacing protocols to be implemented. For practical purposes, external pacing does not capture the atrium. Since the left atrium is easily captured by esophageal pacing, it is likely that noninvasive external pacing will be combined with transesophageal pacing to perform noninvasive electrophysiological testing. The future for external pacing remains in limbo because of the discomfort associated with skeletal muscle contraction. If technical advances can reduce or eliminate this problem, then external pacing may find broader application for bradycardia and tachycardia.

Description of the strength-interval relation with external noninvasive pacing.

The strength-interval relationship obtained by external pacing (EXP) was compared to curves obtained by endocardial pacing from a right ventricular site. There were 17 patients, age 45 +/- 17 years. Effective and functional ventricular refractory periods (ERP, FRP) were determined during a ventricular drive train of 8 stimuli at a cycle length 500 msec. Endocardial pacing threshold current averaged 0.5 +/- 0.3 mA (range 0.2-1.0 mA) and EXP threshold current averaged 64 +/- 14 mA (range 40-80 mA). At twice threshold, endocardial ventricular ERP was 235 +/- 32 msec and FRP was 262 +/- 29 msec. At 10 mA above threshold, EXP ventricular ERP was 276 +/- 29 msec and was significantly longer than endocardial ERP at twice threshold (P less than 0.001). EXP ventricular FRP shortened to 237 +/- 39 msec at twice threshold and was similar to endocardial ERP (P = 0.55). EXP ventricular FRP was significantly longer than endocardial ERP (280 +/- 29 vs 262 +/- 29 msec, P less than 0.001) at twice threshold. EXP strength-interval curves were similar to endocardial curves in 14 of 17 (82%) patients. We conclude, that at twice threshold, similar coupling intervals can be obtained with both endocardial and EXP. Therefore, EXP can provide critically coupled extrastimuli for programmed ventricular stimulation.

Dissimilar right atrial rhythms: a case report.

Dissimilar atrial rhythms are generally defined by the coexistence of atrial fibrillation in one atrium and a more regular rhythm in the other atrium, and are reported with left atrial enlargement and/or digitalis toxicity. We report a unique case of dissimilar atrial rhythms controlling two different parts of the same atrium without interfering with one another. The mechanism of the dissociation of two foci is not clear; however, scarring due to previous surgery remains a possibility.

Differential effects of lidocaine on defibrillation threshold with monophasic versus biphasic shock waveforms.

BACKGROUND: Defibrillation waveforms and antiarrhythmic drugs have disparate effects on myocardial excitability and refractoriness, making it likely that antiarrhythmic drugs will interact with one waveform differently than with another. The aim of the present study was to determine if the increase in defibrillation threshold (DFT) induced by lidocaine is similar for electrical shocks with monophasic and biphasic waveforms. METHODS AND RESULTS: Twenty-six pentobarbital-anesthetized farm-raised pigs were instrumented with pacing catheters and epicardial defibrillation electrodes. Each pig was assigned to one of four groups: (1) monophasic shock waveform and placebo (5% dextrose in water [D5W]) (n = 7), (2) monophasic shock waveform and lidocaine (n = 7), (3) biphasic shock waveform and placebo (D5W) (n = 5), or (4) biphasic shock waveform and lidocaine (n = 7). DFT was measured at baseline and subsequently during treatment (D5W or lidocaine). In the monophasic waveform groups, DFT increased from baseline in response to lidocaine by 92% (P < .0001), whereas DFT values in response to D5W did not change. In the biphasic waveform groups, DFT values did not change from baseline in response to lidocaine (P = NS), whereas DFT values from baseline in response to D5W significantly decreased by 29% (P = .04). In the monophasic waveform groups, the change in DFT from baseline in response to lidocaine was significantly different than the change from baseline in response to D5W (92 +/- 29% versus -0.5 +/- 29%, respectively) (P < .0002). In the biphasic waveform groups, however, the change in DFT from baseline in response to lidocaine was similar to the change from baseline in response to D5W (-5.66 +/- 15% versus -29 +/- 17%, respectively) (P = .48). Furthermore, the change in DFT from baseline in response to lidocaine differed significantly between monophasic and biphasic waveform groups (92 +/- 29% versus -5.66 +/- 15%) (P < .0002), whereas the change from baseline in response to D5W did not differ between monophasic and biphasic waveforms (-0.5 +/- 29% versus -29 +/- 17%) (P = .34). CONCLUSIONS: Compared with placebo groups, DFT values increased during lidocaine treatment to a much greater degree in the monophasic waveform group than in the biphasic waveform group receiving lidocaine. These data support our hypothesis that antiarrhythmic drugs can affect the defibrillation efficacy of monophasic waveforms differently than that of biphasic waveforms.

Observations on induction and termination of paroxysmal supraventricular tachycardia by external pacing.

Paroxysmal supraventricular tachycardia (PSVT) can be reproducibly induced and terminated by critically timed atrial or ventricular depolarizations. In this study, noninvasive transcutaneous (external) cardiac pacing (NTCP) was compared to endocardial ventricular pacing for the termination and induction of PSVT. In 24 patients, either atrioventricular (AV) nodal reentrant tachycardia or AV reciprocating tachycardia was reproducibly terminated with either critically timed ventricular depolarizations or overdrive ventricular pacing from an endocardial right ventricular site. There were 32 trials of NTCP attempts to interrupt PSVT in the 24 patients. External pacing was successful at terminating PSVT in 23 patients and in 30 of 32 (94%) trials. In 20 patients, there were 26 trials of external pacing attempts to induce PSVT. External pacing initiated PSVT in 21 of 26 trials (81%). The pacing sequences used to induce and terminate PSVT with external pacing were copied from the endocardial sequences. The external pacing threshold averaged 77 +/- 22 mA but the current needed to terminate PSVT was about 1.5 greater than threshold at 117 +/- 27 mA. Serial external pacing studies were performed in seven patients. The thresholds for external pacing were similar from trial to trial as were the mode of termination and induction between the endocardial and external methods. External pacing can terminate most AV reciprocating tachycardias and many AV nodal reentrant tachycardias. It appears promising as a means of inducing PSVT. However, the high stimulation amplitudes needed will prohibit wide acceptance of external pacing for induction and termination of PSVT.

Hypertonic saline does not reverse the sodium channel blocking actions of lidocaine: evidence from electrophysiologic and defibrillation studies.

Studies have shown that increasing extracellular sodium concentration can partially reverse sodium channel blockade. However, there is conflicting in vitro evidence in this regard for lidocaine. The effects of lidocaine on cardiac electrophysiology and defibrillation were studied in a basal and hypernatremic state to determine reversibility of sodium channel blockade. Electrophysiologic studies measured right ventricular effective refractory period at 350 ms pacing cycle length and QRS interval, JT interval, and monophasic action potential duration during sinus rhythm and right ventricular pacing (350 ms cycle length) in 14 pentobarbital-anesthetized swine (25-30 kg). Defibrillation threshold (DFT) was measured by quantitating successful conversion of sustained ventricular fibrillation to normal sinus rhythm. Each pig was randomly assigned to a treatment group with three study phases; group 1 = baseline, lidocaine (20 mg/kg/h), and lidocaine plus placebo (D5W; n = 7); and group 2 = baseline, lidocaine, and lidocaine plus hypertonic saline (2-3 mM/kg/h; n = 7). In groups 1 and 2, lidocaine infused alone significantly (p < 0.01) increased DFT values from baseline (9.8 +/- 3.9 to 15.7 +/- 5.8 J and 8.9 +/- 2.9 to 14.7 +/- 5.4 J, respectively) and increased QRS duration from baseline during right ventricular pacing (89 +/- 6 to 109 +/- 10 ms; p < 0.01; and 87 +/- 6 to 103 +/- 12 ms; p < 0.01). Lidocaine alone reduced right ventricular action potential duration (APD) in groups 1 and 2 (214 +/- 18 to 206 +/- 20 ms; p < 0.10; and 228 +/- 8 to 212 +/- 8 ms; p < 0.05), respectively, and it reduced paced JT interval in both groups (194 +/- 20 to 184 +/- 18 ms; p < 0.10; and 200 +/- 12 to 183 +/- 16 ms; p < 0.05), respectively. When hypertonic saline was added to lidocaine, DFT and QRS duration values were unaffected (14.7 +/- 5.4 to 16.1 +/- 3.7 J and 103 +/- 12 to 100 +/- 11 ms, respectively). However, APD and JT intervals returned to basal values when hypertonic saline was added to lidocaine (212 +/- 8 to 225 +/- 13; p < 0.05; and 183 +/- 16 to 192 +/- 18; p < 0.05, respectively). When D5W was added in the control group, no changes occurred in DFT or electrophysiologic values. Lidocaine slowed ventricular conduction velocity and reduced APD. The administration of hypertonic saline to increase extracellular sodium concentrations failed to reverse the effect of lidocaine on conduction-velocity slowing or elevated DFT values. Hypertonic saline did reverse the effects of lidocaine on repolarization parameters. These data suggest that shortening of repolarization is not a mechanism by which lidocaine makes it more difficult to defibrillate the heart.

Urine acidification affects the activity of the organic base transporter in a nonstereoselective manner.

This investigation determined 1) the effect of urine acidification on renal clearance (Clrenal), total systemic clearance (Cltotal) and nonrenal clearance (Clnonrenal) of pindolol, 2) whether urine acidification affected the stereoselectivity of pindolol excretion and 3) the pharmacodynamic effects that may result from changes in the activity of the organic base transporter. The Clrenal, Cltotal and Clnonrenal values of pindolol isomers were determined during pindolol administration (10 mg twice daily; control phase) and during pindolol administration (10 mg twice daily) with NH4Cl, a systemic and urinary acidifier, (1.5 g every 6 hr). Eight healthy males (22-33 yr) randomly received this therapy for 3 days on two occasions. On day 4, urine and plasma were collected over 24 hr. R-(+) pindolol Clrenal values during control and NH4Cl were 203 +/- 82 and 480 +/- 248 ml/min, respectively (P = .03). S-(-) pindolol Clrenal values during control and NH4Cl were 279 +/- 81 and 593 +/- 294 ml/min, respectively (P = .005). NH4Cl increased R-(+) pindolol Clrenal by 173% +/- 136% (P = .003) and S-(-) pindolol Clrenal by 127% +/- 105% (P = .03). Stereoselective renal excretion of pindolol was unaffected by NH4Cl; the R(+)/S(-) pindolol Clrenal ratio was unchanged from control to NH4Cl (0.74 +/- 0.23 to 0.81 +/- 0.10, P = NS, respectively). NH4Cl, however, affected pindolol Clnonrenal in a stereoselective fashion; R-(+) pindolol Clnonrenal values increased (641 +/- 241 to 851 +/- 251 ml/min; P = .02), whereas S-(-) pindolol Clnonrenal values remained constant (354 +/- 116 vs. 370 +/- 213 ml/min). Changes in pindolol clearance values resulted in a significant reduction in beta-blocking activity assessed by isoproterenol testing. We conclude that increasing the urine proton gradient can increase the Clrenal value of organic bases by 2-fold in a manner that is not stereoselective. NH4Cl, however, did increase the Clnonrenal value of pindolol in a stereoselective manner. These data, therefore, indicate that the administration of a urine-acidifying agent can greatly enhance the elimination of organic bases and ultimately reduce the pharmacologic activity of the organic base.

Differential effects of isoproterenol on sustained ventricular tachycardia before and during procainamide and quinidine antiarrhythmic drug therapy.

BACKGROUND: Autonomic modulation, especially increased sympathetic activity may play a role in the genesis of ventricular arrhythmias. The purpose of this study was to determine whether beta-sympathetic stimulation with isoproterenol would alter sustained ventricular tachycardia (VT) circuits similarly during the drug-free and antiarrhythmic drug-treated states. METHODS AND RESULTS: Twenty-five patients with repeatedly inducible, hemodynamically stable, sustained VT were evaluated by programmed ventricular stimulation. In the antiarrhythmic drug-free state, isoproterenol (0.03 microgram/kg per minute) shortened the following intervals (in milliseconds; mean +/- SEM; 25 patients; paired t test): sinus cycle length (792 +/- 37 to 568 +/- 18; (p < 0.001), ventricular paced QT interval (386 +/- 8 to 348 +/- 6; p < 0.001), ventricular paced QRS duration (185 +/- 4 to 182 +/- 4; p = 0.014), ventricular effective (238 +/- 5 to 208 +/- 4; p < 0.001) and functional (261 +/- 6 to 227 +/- 5; p < 0.001) refractory periods, and the VT cycle length (VTCL) (311 +/- 9 to 291 +/- 9; p < 0.001). Isoproterenol (0.03 microgram/kg per minute) was administered during 31 antiarrhythmic drug trials (procainamide, n = 18; quinidine, n = 13) in 22 patients. Isoproterenol shortened the sinus cycle length, QT interval during ventricular pacing, and ventricular effective and functional refractory periods before and during procainamide and quinidine therapy (ANOVA; isoproterenol effect, p < or = 0.0002 for all). The amount of decrease in these intervals with isoproterenol was the same before and during procainamide and quinidine therapy (ANOVA interaction, p = NS for all). The QRS duration during ventricular pacing and VTCL were also shortened by isoproterenol before and during procainamide (baseline, n = 17; QRS, 182 +/- 4 to 178 +/- 4 msec; VTCL, n = 18, 314 +/- 11 to 291 +/- 11 msec; during procainamide, QRS, 218 +/- 7 to 197 +/- 6 msec; VTCL, 422 +/- 15 to 359 +/- 11 msec) and quinidine (baseline, n = 13; QRS, 190 +/- 6 to 185 +/- 5 msec; VTCL, n = 12, 298 +/- 10 to 280 +/- 9 msec; during quinidine, QRS, 223 +/- 9 to 208 +/- 8 msec; VTCL, 415 +/- 14 to 355 +/- 10 msec) (isoproterenol effect p < or = 0.0003 for all). However, the amount of decrease in QRS duration and VTCL with isoproterenol was greater during procainamide and quinidine than in the drug-free state (ANOVA interaction, p < or = 0.02 for all). These changes continued to be significant when normalized for the initial QRS duration and VTCL (p < or = 0.03 for all). CONCLUSIONS: Isoproterenol affects presumed reentrant sustained VT circuits less in the absence of antiarrhythmic drugs but markedly attenuates the antiarrhythmic drug-induced slowing of sustained VT. To the extent that the change in QRS duration reflects a change in conduction within the VT circuit, these data imply that the attenuation of drug-induced slowing of VT by isoproterenol is due to a greater change in conduction rather than refractoriness.