Sexual quality of life after the treatment of gynecologic cancer: what women want.

PURPOSE: While the incidence of sexual dysfunction after treatment for gynecologic malignancies is well documented, few studies describe how patients want healthcare providers to address these concerns. The objective of this study was to evaluate changes in sexual function and describe patient preferences regarding healthcare provider roles in addressing and treating sexual dysfunction in gynecologic cancer survivors. METHODS: Patients undergoing gynecologic cancer treatment from 2013 to 2014 at a single University-based Gynecologic Cancer clinic were surveyed using a modified Changes in Sexual Function Questionnaire (CSFQ), along with questions relating to healthcare provider interactions and preferences. RESULTS: Among 277 eligible patients approached to participate, 85 (30.7%) completed the survey. The mean age was 52.2 ± 12.3 years; most were non-Hispanic White (78.8%), partnered (73.2%), had endometrial or ovarian cancer (30.6% and 44.7%, respectively), and were in surveillance (57.3%). Most women (64.7%) reported much or great sexual enjoyment 1 year prior to cancer treatment which decreased to 27.4% currently; 33.3% report only rare sexual activity. There were no statistically significant differences in mean total CSFQ scores by treatment modality. A minority wanted healthcare providers to initiate sexual health discussions (25.3%); the remaining reported not wanting sexual health addressed or preferred raising the issue themselves. The most commonly cited barrier to communication was the feeling that there are more important issues to discuss with their oncology providers (46.2%). CONCLUSIONS: While gynecologic cancer patients report changes in sexual function following cancer therapy, many believe there are other issues more paramount to be addressed. Further studies are warranted to develop better strategies for addressing sexual health in women receiving treatment for gynecologic cancers.

Bradyarrhythmias: clinical significance and management.

Clinicians have long recognized the potentially serious manifestations of extreme bradycardia. However, even marked bradycardia can often be physiologic, and in the presence of impaired ventricular function may offer important compensatory hemodynamic effects. Disorders of the sinoatrial node producing bradycardia include failure of impulse formation, sinoatrial conduction block, concealed sinus-perinodal reentry, carotid sinus hypersensitivity and the constellation of brady- and tachyarrhythmias that compose the "sick sinus syndrome." Bradycardia can also result from intraatrial block, atrioventricular nodal block or infranodal block. In addition, paroxysmal supraventricular tachyarrhythmias may produce concealment into the atrioventricular junction and simultaneous suppression of sinus node rhythmicity, resulting in long pauses. Pseudobradycardias manifesting as slow peripheral pulse rates can result from frequent, nonconducted early atrial premature beats, from ventricular bigeminy or runs of ventricular extrasystoles or from mechanical alternans. Cardiac pacemakers play an important role in the management of patients with severe symptoms attributable to bradyarrhythmias. However, excessive use of pacemakers and the inappropriate selection of physiologically unfavorable pacemaker systems should be avoided. Frequently, patients who are only mildly symptomatic with bradycardia should not receive a cardiac pacemaker because the prognosis is favorable. Patients with the tachy-bradycardia syndrome often require both pharmacologic and pacemaker therapy. In selected patients electrophysiologic testing may be helpful, but the majority of patients are best managed by careful attention to the history, electrocardiogram and ambulatory electrocardiographic recordings.

Extracellular potassium dynamics in the border zone during acute myocardial ischemia in a canine model.

Bifunctional intramyocardial potassium ion (K+)-sensitive and bipolar wire electrodes were used to evaluate extracellular K+ dynamics and electrophysiologic changes during acute myocardial ischemia in the border zone, ischemic zone (5 to 7 mm from the border), central ischemic zone (15 to 25 mm from the border) and normal myocardium in 11 open chest dogs during a 30 min ligation of the left anterior descending coronary artery. At the end of this period, the hearts were injected with rhodamine dye and quickly frozen. Ultraviolet NADH (nicotinamide adenine dinucleotide) rhodamine fluorescence photography was used to localize the border between normally perfused and ischemic tissue and determine the site of electrodes in relation to this border. Before coronary ligation, extracellular K+ ranged from 4.0 +/- 0.3 to 4.3 +/- 0.3 mM in these four zones. After ligation, extracellular K+ accumulated in the ischemic and central ischemic zones in a pattern characterized by an initial rapid increase for approximately 5 min, followed by a slowly rising plateau phase, reaching maximal levels of 9.8 +/- 2.0 and 14.4 +/- 4.4 mM, respectively. In contrast, K+ dynamics in the border zone showed a biphasic response, with an initial rapid increase to a maximal level of 7.5 +/- 2.4 mM at approximately 9 min after coronary ligation, followed by a gradual decrease to a level of 5.3 +/- 1.2 mM by the end of the 30 min ligation period. No significant changes in K+ occurred in the normal zone throughout the ischemic period. The correlation of K+ electrode, electrophysiologic and postmortem NADH-rhodamine fluorescence data indicated the existence of a well defined border zone.(ABSTRACT TRUNCATED AT 250 WORDS)

Cellular electrophysiologic characteristics of chronically infarcted myocardium in dogs susceptible to sustained ventricular tachyarrhythmias.

Standard microelectrode techniques were used to record transmembrane potentials and determine conduction characteristics in regions of mottled infarcts of canine epicardium, 3 to 5 days or 8 to 15 days after left anterior descending coronary artery occlusion and reperfusion. At 3 to 5 days, resting potential, action potential amplitude, maximal rate of depolarization and action potential duration at 30% repolarization were significantly reduced in the infarcted region. Cells on the epicardial surface showed improvement in resting potential, action potential amplitude and rate of depolarization between 3 to 5 days and 8 to 15 days after infarction. In normal noninfarcted tissues, conduction velocity parallel to fiber orientation was 0.54 +/- 0.06 m/s (mean +/- standard deviation). Slow conduction in infarcted regions ranged from 0.015 to 0.2 m/s. Action potentials recorded from slowly conducting regions tended to include cells with more depressed amplitude and rate of depolarization than other cells in infarcted regions; they also had inappropriately depressed overshoot relative to their resting potential. Action potentials in slowly conducting areas where local conduction block occurred were associated with prepotentials and notches on their depolarization and repolarization phases. The prepotentials and notches appeared to be caused by electrotonic interactions resulting from microcircuitous conduction around or across inexcitable areas. These findings demonstrate that areas of slow conduction are heterogenously distributed in the mottled infarct and suggest that disruptions in cell to cell electrical continuity and decreased excitability may contribute to this slow conduction.

Effects of adenosine and adenosine 5'-triphosphate on ventricular escape rhythm in the canine heart.

The effects of adenosine and adenosine 5'-triphosphate (ATP) on ventricular escape rhythms were studied in 16 closed chest dogs after electroablation of the His bundle region. All dogs exhibited complete atrioventricular (AV) block and stable ventricular escape rhythm with a mean cycle length of 1,210 +/- 80 ms and a QRS width of 91 +/- 5 ms. Physiologic AV sequential pacing was operative during experiments and was interrupted for rapid (less than or equal to 1 second) administration of either adenosine or ATP (3 mumol/kg) into the right atrium. Adenosine and ATP effectively depressed ventricular escape rhythms in a similar manner both qualitatively and quantitatively (cycle length from 1,210 +/- 80 to 1,764 +/- 132 ms and from 1,274 +/- 84 to 2,000 +/- 150 ms, respectively; each p less than 0.01). These effects were not significantly altered by either physostigmine (an acetylcholinesterase inhibitor) or atropine (a muscarinic cholinergic blocker), but were slightly attenuated by propranolol (a beta-adrenoceptor blocker). In the presence of autonomic blockade, the adenosine transport blocker dipyridamole markedly enhanced the depressant effects of adenosine and ATP. The adenosine competitive antagonist aminophylline reversed the action of dipyridamole. Thus, both adenosine and ATP depress ventricular escape rhythms in vivo, independent of the autonomic nervous system. Moreover, the effects of ATP can be accounted for in large part by its rapid breakdown to adenosine.

Importance of the pacing mode in the initiation of ventricular tachyarrhythmia in a canine model of chronic myocardial infarction.

The use of unipolar anodal or bipolar pacing, as compared with unipolar cathodal pacing, purportedly increases the likelihood of inducing inadvertent ventricular fibrillation in susceptible patients. In this study, the ability to initiate sustained ventricular tachycardia or fibrillation with unipolar cathodal, unipolar anodal and bipolar pacing modes was compared using programmed ventricular stimulation at 82 subendocardial periinfarction sites in 11 dogs with chronic myocardial infarction. The late diastolic excitability threshold was significantly higher and the ventricular refractory period was significantly shorter (p less than 0.001) with anodal pacing (mean 0.62 mA, 156 ms, respectively) than with pacing in either the cathodal (0.12 mA, 174 ms) or the bipolar (0.13 mA, 173 ms) mode. At a current intensity twice that of the excitability threshold, the introduction of one or two extrastimuli induced ventricular tachycardia and ventricular fibrillation comparably among the three pacing modes. However, when three extrastimuli were used, ventricular fibrillation was induced with anodal pacing twice as frequently (50 [61%] of 82 sites) as with either of the other two pacing modes (each 23 [28%] of 82 sites, p less than 0.001), whereas the induction of ventricular tachycardia remained comparable with anodal pacing (15 [18%] of 82 sites) and cathodal and bipolar pacing (each 14 [17%] of 82 sites). Furthermore, a similarly high incidence of inducibility of ventricular fibrillation was observed with both cathodal pacing (56 [68%] of 82 sites) and bipolar pacing (40 [49%] of 82 sites) when an increased current equal to twice the anodal excitability threshold (1.23 mA) was used.(ABSTRACT TRUNCATED AT 250 WORDS)

Extracellular potassium ion dynamics and ventricular arrhythmias in the canine heart.

The relation between extracellular potassium ion activity [( K+]o) and ventricular tachyarrhythmias was studied in an open chest canine model with the use of two protocols. In Protocol I, potassium chloride was administered into the proximal left anterior descending coronary artery at a rate of 0.125 mEq/min for either 20 min or until [K+]o = 20 mEq/liter, whichever came first. In Protocol II, the proximal left anterior descending coronary artery was occluded in one step and was reperfused 20 min later. Fifteen dogs were subjected to Protocol I, nine of which were also subjected to Protocol II. In the latter group, a recovery period of greater than or equal to 1 h separated the two protocols. Local K+ and intramyocardial activities were recorded with use of bifunctional ion-sensitive plunge electrodes at multiple sites located in the region of the left ventricle perfused by the left anterior descending artery and at one site outside of this region. The following variables were recorded and analyzed: Lead II electrocardiogram, heart rate, systemic arterial blood pressure, local [K+]o and its time derivative (dK+/dt), local electrograms and ventricular arrhythmias. Maximal [K+]o and dK+/dt were 23 +/- 3 mEq/liter and 9 +/- 1 mEq/liter per min in Protocol I and 14 +/- 1 mEq/liter and 3 +/- 1 mEq/liter per min in Protocol II, respectively. In both protocols, the occurrence of ventricular arrhythmias correlated with [K+]o (p less than 0.02) as well as with dK+/dt (p less than 0.05). Ventricular arrhythmias were more frequent and more severe in Protocol II than in Protocol I (p less than 0.05). Therefore, whereas K+ dynamics were more pronounced in Protocol I, ventricular arrhythmias were more severe in Protocol II. This occurrence was apparently due, at least in part, to less heterogeneous changes in K+ gradients during constant K+ infusion. It was concluded that, in addition to the magnitude of [K+]o, the rate of change of this variable (that is, dK+/dt) apparently plays an important role in the genesis of ischemic ventricular arrhythmias.

Differential effects of procainamide, lidocaine and acetylstrophanthidin on body surface potentials and epicardial conduction in dogs with chronic myocardial infarction.

Twenty-eight anesthetized mongrel dogs were studied 2 to 74 months after experimental myocardial infarction in order to examine the effects of procainamide, lidocaine and acetylstrophanthidin on conduction within the infarcted region and the way such effects relate to changes in body surface potentials and antiarrhythmic efficacy. In each animal, 100 to 200 QRS complexes in the X, Y, Z leads were signal averaged, vector summed and high pass filtered at 50 Hz. Susceptibility to ventricular arrhythmia was evaluated using routine programmed ventricular extrastimulation in the anesthetized open chest animal. Epicardial electrograms were sequentially recorded at 45 standard sites within the infarcted region and referenced to the beginning of the QRS complex. Of the three agents, only procainamide exhibited antiarrhythmic action whereas lidocaine and acetylstrophanthidin produced inconsistent effects. Procainamide prolonged the time at which activity in the epicardial electrographic recordings ended relative to the beginning of the body surface QRS complex. This effect was significantly greater in electrograms that ended late in the QRS complex in the control state than for those that ended earlier. Such preferential effect on more abnormal sites was reflected on the body surface as a greater effect of procainamide in prolonging the lower energy terminal portion of the signal-averaged QRS complex than the earlier high energy portion. In contrast, lidocaine significantly prolonged the time at which electrograms ended only for those relatively normal electrograms that ended early in the QRS complex in the control state. In the signal-averaged body surface QRS complex, lidocaine produced a small but significant prolongation of the early high energy portion of the QRS complex but no change in the late portion. Acetylstrophanthidin produced a significant prolongation in early-ending electrograms and, surprisingly, significantly shortened the end time of electrograms that ended late in the QRS complex in the control state. Such effects were not reflected, however, on the body surface because acetylstrophanthidin had no significant effect on either the early or the late portion of the QRS complex. It is concluded that procainamide's differential effect between early- and late-ending electrograms is detected on the body surface by a greater prolongation in the terminal portion of the QRS complex. The signal-averaged body surface QRS complex is less sensitive in detecting the more subtle effects on conduction caused by lidocaine and acetylstrophanthidin.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiac arrhythmias. Frequency during fiberoptic bronchoscopy and correlation with hypoxemia.

To evaluate the occurrence of ECG abnormalities during fiberoptic bronchoscopy in relation to specific stages of the procedure and to hypoxemia, we prospectively studied 50 hospitalized patients aged 53 +/- 18 years (mean +/- SD) who were undergoing bronchoscopy by continuously monitoring cardiac rhythm with a continuous two-channel ECG recorder and oxygen saturation by using ear oximetry. Major disturbances of cardiac rhythm (ie, atrial, ventricular, or both) developed in 20 (40%) patients. Ventricular arrhythmias were recorded in ten patients (20%) and occurred with greatest frequency during passage of the bronchoscope through the vocal cords in five of these patients. Atrial arrhythmias were detected in 16 patients (32%), but their occurrence did not correlate closely with any one stage of the procedure. Arrhythmias were most frequent in association with periods of maximum oxygen desaturation in 12 of these 20 patients. Oxygen desaturation persisted for greater than one hour after bronchoscopy in 34 (68%) of 50 subjects. Notably, no correlation was observed between the frequency of arrhythmias during bronchoscopy and patients' age, sex, prior medications, or preexisting cardiac or pulmonary disorders. In no case was an ECG abnormality associated with adverse clinical sequelae.

Retinal arteriolar changes as an indicator of coronary artery disease.

Funduscopic examination was performed in 70 non diabetic, nonhypertensive patients without valvular heart disease undergoing coronary angiography for evaluation of chest pain syndromes to determine if retinal arteriolar changes could reliably predict presence of coronary artery disease. Retinal arteriolar changes were graded with respect to light reflex, vessel caliber, arteriovenous crossing defects, and vessel tortuosity without knowledge of angiographic findings. Each coronary vessel was graded with respect to its most occlusive lesion by angiography; coronary index was derived for each patient without knowledge of eye findings. Abnormal light reflex changes were the most sensitive indicators of presence and extent of coronary artery disease. Abnormal vessel tortuosity and decreased caliber were less sensitive but more specific; their presence also suggested more extensive coronary lesions. Thus, funduscopic examination demonstrating specific retinal arteriolar lesions may indicate presence of coronary artery disease and may correlate with extent of lesions in selected patients.

Interacting negative chronotropic effects of adenosine and the vagus nerve on the canine sinus node.

The vagus nerve and adenosine exert a negative chronotropic effect on the mammalian sinus node. In addition, adenosine is released from myocardial cells under both physiological and pathophysiological conditions, which are characterised by variable vagal tone. To determine the interaction between adenosine and the vagus nerve, 21 barbiturate anaesthetised mongrel dogs with bilateral cervical vagotomy and stellectomy were studied. In group 1 (n = 16) adenosine (3 mumol.kg-1) was rapidly (less than or equal to 1 s) administered before (control) and during 60 s of repetitive vagal stimulation. Each stimulus (consisting of a burst of 5 square wave pulses, 0.3 mA in amplitude and 1 ms in duration at 0.1 kHz) was given at a fixed point in time in each sinus cycle (that is, one burst per cycle). This protocol was repeated after a 50 ms incremental change in the phase at which vagal stimulation was given until the entire cycle length was scanned. Recovery time of at least 2 min separated any two consecutive adenosine administrations. In four animals the above protocol was performed twice using vagal stimulation amplitude of 0.3 mA and 0.6 mA in the first and second runs respectively. In this group (group 1), the effect of adenosine was altered by the vagus in a phase dependent manner. In each animal, however, there was at least one phase of the sinus cycle during which vagal stimulation significantly enhanced the effect of adenosine.(ABSTRACT TRUNCATED AT 250 WORDS)

Nicardipine and hydrochlorothiazide in essential hypertension.

Nicardipine is an investigational dihydropyridine calcium channel blocking agent. One hundred fifty-one patients with hypertension received either 30 mg nicardipine t.i.d. or 25 mg hydrochlorothiazide b.i.d. in a double-blind, randomized, multicenter trial. After 4 weeks of therapy and at the end of the dosing interval, nicardipine reduced arterial pressure by 10/6 mm Hg and 12/6 mm Hg in the supine and standing positions, respectively (all p less than 0.01). In the hydrochlorothiazide group, the reductions were 12/6 mm Hg and 14/6 mm Hg, respectively (all p less than 0.01). The maximum reduction in blood pressure of 16/14 mm Hg supine and 20/15 mm Hg standing occurred within 1 hour after administration of nicardipine. The mean reduction in the hydrochlorothiazide group after 1 hour was 14/11 mm Hg supine and 16/12 mm Hg standing. Neither drug affected autonomic reflexes associated with maximum exercise. Nicardipine increased urinary sodium excretion during the 4-hour period after the first dose. Adverse effects of nicardipine were primarily extensions of its vasodilator effect and included flushing, headache, and edema.

Multiclinic comparison of labetalol to metoprolol in treatment of mild to moderate systemic hypertension.

The antihypertensive effects of oral labetalol, a new alpha- and beta-adrenergic blocking agent, and metoprolol, a relatively beta1 selective adrenergic blocker, were evaluated in 91 patients with mild to moderate hypertension (standing diastolic blood pressure of 90 to 115 mm Hg) in a double-blind parallel group multicenter clinical trial. The effects of the two drugs on plasma lipids and lipoprotein fractions were also assessed. Following a four-week placebo phase, 44 patients were randomized to receive labetalol and 47 metoprolol. During a four-week titration phase, the labetalol dose was increased from 100 mg twice daily to a maximum of 600 mg twice daily to achieve a standing diastolic blood pressure of 90 mm Hg that was decreased by 10 mm Hg or more. Metoprolol was titrated from 50 mg to 200 mg twice daily. An eight-week maintenance period followed during which hydrochlorothiazide could be added. At the end of the maintenance phase, the doses of labetalol and metoprolol were tapered over a two to four day period after which patients received a placebo for one week. Blood pressure in the supine and standing position was measured at each visit. Labetalol and metoprolol both significantly (p less than 0.01) lowered the supine and standing blood pressure from baseline with no significant difference found between the two treatment groups. Both drugs lowered the heart rate; however, the rate-lowering effect was significantly greater with metoprolol (p less than 0.01). There were no significant effects of either drug on plasma lipids or lipoprotein fractions. Fatigue was the most frequently reported complaint with both drugs. Dizziness, dyspepsia, and nausea were more common with labetalol; bradycardia was more common with metoprolol. There was no blood pressure "overshoot" after withdrawing drug treatment; however, a heart rate "overshoot" was seen after metoprolol was tapered off and stopped. Labetalol is as safe and effective as metoprolol in the treatment of patients with mild to moderate hypertension.

Treatment of severe hypertension with labetalol compared with methyldopa and furosemide. Results of a long-term, double-blind, multicenter trial.

Eighty-one severely hypertensive patients were enrolled in a multicenter, double-blind, parallel group study evaluating the efficacy and safety of labetalol alone or in combination with furosemide versus methyldopa in combination with furosemide. A one day to four week placebo lead-in phase was followed by a one- to six-week titration period and a one-year maintenance period. Treatment with labetalol alone or in combination with furosemide, as well as methyldopa plus furosemide, was associated with significant reductions in supine and standing blood pressure levels. Moreover, after six months and one year of treatment, respectively, labetalol caused a significantly (p less than 0.05) greater reduction in the systolic blood pressure than the methyldopa regimen. The antihypertensive effect of labetalol was associated with small, yet significant reductions in heart rate; in contrast, resting tachycardia was observed in methyldopa-treated patients. Side effect profiles of the two treatments were different, with nausea being the most commonly reported side effect during labetalol therapy, and asthenia, somnolence, and dry mouth during methyldopa therapy. Overall, 33 of 65 (53 percent) labetalol-treated and 28 of 60 (47 percent) methyldopa-treated patients had at least a good response (that is, standing diastolic blood pressure 90 to 94 mm Hg) to therapy, including 26 (40 percent) and 22 (37 percent) patients, respectively, who had standing diastolic blood pressure levels of less than 90 mm Hg. Thus, labetalol is a potentially safe and effective agent in the long-term management of the patient with severe hypertension.

Intravenous labetalol in the treatment of severe hypertension and hypertensive emergencies.

The antihypertensive effects of intravenous labetalol were evaluated in 59 patients with hypertensive crises or severe hypertension in need of rapid lowering of blood pressure in a multicenter study. Patients appearing with a supine diastolic blood pressure 125 mm Hg or greater, or a supine systolic blood pressure of more than 200 mm Hg received an initial mini-bolus injection (20 mg) of labetalol. This was followed by repeated incremental doses of 20 to 80 mg given at 10 minute intervals to achieve a supine diastolic blood pressure of less than 95 mm Hg or decrease 30 mm Hg or greater, or a satisfactory decrease in systolic blood pressure. Patients were stratified into those who had taken antihypertensive medication within 24 hours and those who had not. The initial mini-bolus injection caused rapid but not abrupt reduction in blood pressure; the baseline mean blood pressure decreased 23/14 mm Hg. Further injections were needed in the majority of patients (mean: 197 mg). The blood pressure reduction after the last dose of labetalol was 55/33 mm Hg. In pretreated patients and in those who had no medication for 24 hours prior to the intravenous labetalol, the response was similar. Heart rate decreased 10 beats per minute in the total population. In patients pretreated with beta-adrenergic blockers, blood pressure response was similar to that in the total group (59/35 versus 55/33 mm Hg), but heart rate remained essentially unchanged. The dose required to achieve the therapeutic effect was less in pretreated patients than in untreated patients, but the duration of action was shorter. No serious adverse effects were encountered even in patients with concomitant diagnoses of acute left ventricular failure, myocardial infarction, stable congestive heart failure, atrial fibrillation, angina pectoris, acute stroke, transient ischemic attack or encephalopathy. Labetalol is a safe and effective treatment for a rapid blood pressure reduction in hypertensive emergencies.

Multicenter clinical evaluation of long-term efficacy and safety of labetalol in treatment of hypertension.

The long-term efficacy and safety of labetalol, an antihypertensive agent with combined beta- and alpha-blocking activity, were evaluated alone (number = 193) and in combination with a diuretic (number = 144) in an open-label multicenter trial of 337 hypertensive patients aged 21 to 75 years, including initially 205 (61 percent) men and 219 (65 percent) Caucasians. There were 219 (65 percent) mild, 85 (25 percent) moderate, and 33 (10 percent) severe hypertensive patients. Labetalol (100 to 1,200 mg twice a day) alone or in combination with a diuretic reduced the mean standing blood pressure by 13/11 and 25/16 mm Hg to 135/88 and 130/91 mm Hg, respectively (p less than 0.01), and supine blood pressure by 6/7 and 18/13 mm Hg to 141/86 and 138/90 mm Hg (p less than 0.01), respectively. Blood pressure reductions observed at one month were maintained after one year; 206 (62 percent) patients had 10 mm Hg or greater reductions and 184 (56 percent) patients were maintained at diastolic blood pressures less than 90 mm Hg. Most frequently reported drug-related side effects included fatigue (14 percent), dizziness (12 percent), nausea (11 percent), nasal stuffiness (8 percent), headache (4 percent), and male sexual dysfunction (14 percent). Side effects were generally of mild to moderate intensity and often transient. In addition, in 27 (8 percent) patients reversible asymptomatic transaminase elevations to greater than twice normal developed at some time during the study. In 13 (4 percent) patients these alterations resolved during continued labetalol therapy, but in five (2 percent) patients these marked elevations led to discontinuation of the drug. A total of 32 (9.5 percent) patients were terminated prematurely due to side effects (most commonly genitourinary or gastrointestinal) possibly attributable to the drug. These findings indicate that labetalol with or without a diuretic is a potentially effective, safe, and relatively well-tolerated long-term antihypertensive therapy.

Polymorphous ventricular tachycardia associated with normal and long Q-T intervals.

Polymorphous ventricular tachycardia may occur in the setting of either a normal or a prolonged Q-T interval. Torsade de pointes is a form of polymorphous ventricular tachycardia in which the polarity of the QRS complex exhibits phasic alterations in both axis and rate. Traditionally, torsade de pointes has been described in association with a variety of congenital and acquired (including drug and metabolic) causes of Q-T prolongation. The distinction between torsade de pointes and those polymorphous ventricular tachycardias occurring in patients with a normal Q-T interval has important therapeutic implications. The former requires strict avoidance of all drugs that may potentially further delay repolarization, including class I antiarrhythmic agents; immediately, the initiation of cardiac pacing is often necessary for control of arrhythmia, and on a long-term basis, sympathetic nervous blockade is often efficacious. In contrast, the polymorphous ventricular tachycardias with a normal Q-T interval usually respond to conventional therapy, including administration of class I antiarrhythmic agents. Thus, the management of polymorphous ventricular tachycardia should be based on the presence of absence of associated repolarization rather than on the morphologic features of the tachycardia. Unfortunately, recent advances in basic and clinical electrophysiology have not yet elucidated the pathophysiologic basis for these arrhythmias, although this is an area of active investigative interest.

Esmolol versus verapamil in the acute treatment of atrial fibrillation or atrial flutter.

The effects of esmolol, an ultrashort-acting beta blocker, and verapamil were compared in controlling ventricular response in 45 patients with atrial fibrillation or atrial flutter, in a randomized, parallel, open-label study. Patients with either new onset (less than 48 hours, n = 31) or old onset (greater than 48 hours, n = 14) of atrial fibrillation or flutter with rapid ventricular rate were stratified to receive esmolol (n = 21) or verapamil (n = 24). Drug efficacy was measured by ventricular rate reduction and conversion to sinus rhythm. The heart rate declined with esmolol from 139 to 100 beats/min (p less than 0.001) and with verapamil from 142 to 97 beats/min (p less than 0.001). Fifty percent of esmolol-treated patients with new onset of arrhythmias converted to sinus rhythm, whereas only 12% of those who received verapamil converted (p less than 0.03). Mild hypotension was observed in both treatment groups. Esmolol compares favorably with verapamil with respect to both efficacy and safety in acutely decreasing ventricular response during atrial fibrillation or flutter. Moreover, conversion to sinus rhythm is significantly more likely with esmolol.

Influence of the site of stimulation on atrioventricular nodal refractory periods and the effect of verapamil.

The refractory periods of the atrioventricular (AV) node appear dependent on the pattern of AV nodal input. In 21 superfused AV rabbit heart preparations stimulated from each of the 2 principal input regions, crista terminalis or atrial septum, the effect of changing the site of stimulation of the AV nodal refractoriness and the relative effect of verapamil on AV nodal refractoriness was determined. In 6 of 21 preparations the functional AV refractory curve became discontinuous only when stimulation was applied at the atrial septum and suggested dual AV nodal pathways (dual pathways group). In the 15 other preparations no interruption of the curve occurred with either crista terminalis or atrial septal stimulation (normal conduction group). In the normal conduction group, the difference in the effective refractory period of the AV node obtained by crista terminalis vs atrial septal stimulation was not significant (154 +/- 25 vs 150 +/- 28 ms). However, the functional refractory period was significantly longer with crista terminalis vs atrial septal stimulation (232 +/- 19 vs 239 +/- 19 ms, p less than 0.001). After verapamil administration, the effective and functional refractory periods during crista terminalis vs atrial septal stimulation were prolonged to 270 +/- 49 vs 285 +/- 55 ms (p less than 0.01) and 335 +/- 43 vs 351 +/- 41 ms (p less than 0.001), respectively. Thus, the difference in refractory periods associated with changing the stimulation site was exaggerated with verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial alternans: experimental echocardiographic and hemodynamic demonstration during programmed pacing.

Simultaneous hemodynamic and echocardiographic recordings were used to demonstrate mechanical atrial alternans during programmed atrioventricular (A-V) pacing in five open chest dogs. Each animal was studied in two stages, first with the A-V conduction system intact (phase I) and later after the experimental induction of complete A-V block (phase II). Atrial alternans was demonstrated during rapid atrial stimulation at cycle lengths ranging from 250 to 120 ms. During phase I, rapid atrial pacing resulted in complex combinations of variable A-V conduction disturbances with superimposed atrial and ventricular alternans. During phase II, atrial alternans could be observed during a programmed prolonged pause in ventricular activity. It is anticipated that this method will facilitate recognition of atrial alternans in various clinical situations and shed further light on its possible hemodynamic significance.