The role of the accessory pathway in the onset of atrial fibrillation in Wolff-Parkinson-White syndrome--electrophysiological examination before and after surgical ablation.

To determine the role of the accessory pathway in the pathogenesis of atrial fibrillation, we compared electrophysiological findings in 17 patients (44.7 +/- 10.2 years) with a history of atrial fibrillation before and after surgical ablation of the accessory pathway. The PA interval was shortened, and the atrial refractory periods and the potential minimal wavelength of an atrial impulse (FRPA/PA) were significantly increased, after surgery. Fragmented atrial activity (an increase of 150% or more in the duration of the high right atrial electrogram) was observed in 80% of the patients before surgery and in 25% after surgery. Its zone was significantly decreased after surgery. Repetitive atrial firing was defined as the occurrence of 3 or more successive atrial electrograms induced by a premature stimulation. This was observed in 60% of the patients before surgery, but in none after surgery. Atrial fibrillation was induced in 16 patients during the preoperative study, but in only 1 patient postoperatively. In conclusion, these results suggest that accessory pathways affect atrial vulnerability and play an important role in the onset of atrial fibrillation in WPW syndrome.

Differential effect of pharmacological autonomic blockade on some electrophysiological properties of the human ventricle and atrium.

OBJECTIVE: This study investigated the dominance of each limb of the autonomic nervous system and tested sympathetic-vagal interactions in the human ventricle and atrium after administration of propranolol and atropine. PATIENTS AND METHODS: The 90% monophasic action potential duration (MAPD90) and the effective refractory period (ERP) at the right ventricular apex (RV) and the right lateral atrium (RA) were measured in 14 patients. The MAPD90 was measured during constant RV and RA pacing (cycle length 600 ms) and the ERP was measured at a driven cycle length of 600 ms. Electrophysiological variables were measured during a control period, after propranolol (0.15 mg/kg loading dose followed by 0.1 mg/min infusion), and after autonomic blockade (atropine 0.04 mg/kg). RESULTS: Both RV MAPD90 and RV ERP increased after propranolol (RV MAPD90 from 268 (26) ms to 275 (26) ms, p < 0.005; RV ERP from 252 (25) ms to 258 (26) ms, p < 0.0005) and then decreased to below the control values after autonomic blockade (RV MAPD90 256 (24) ms; RV ERP 239 (25) ms, p < 0.0005 v propranolol, p < 0.0005 v control). In contrast, both RA MAPD90 and RA ERP increased after propranolol (RA MAPD90 from 242 (19) ms to 260 (19) ms; RA ERP from 216 (21) ms to 230 (18) ms, p < 0.0005), and then increased slightly more after autonomic blockade (RA MAPD90 265 (16) ms, p = 0.09; RA ERP 235 (16) ms, p = 0.07), thus remaining above control values (p < 0.0005). CONCLUSIONS: The results indicate (a) that in the human ventricle vagal stimulation and sympathetic beta stimulation are antagonistic and that direct vagal stimulation predominates over beta stimulation, with sympathetic-vagal interaction being minimal and (b) that in the human atrium vagal stimulation and beta stimulation are synergistic and beta stimulation predominates over vagal stimulation, with direct vagal stimulation having a minimal effect.

Long-term results of catheter ablation for idiopathic ventricular tachycardia originated from the right ventricular outflow.

We performed catheter ablation in 10 consecutive patients with idiopathic monomorphic right ventricular tachycardia and studied the long-term outcome. All ventricular tachycardias had a left bundle branch block configuration with an inferior axis, and originated from right ventricular outflow. Antiarrhythmic drugs (3-6 drugs) had been ineffective in controlling ventricular tachycardia. The 2 patients who underwent direct-current ablation (2 shocks of 150 J) had no recurrence of ventricular tachycardia and did not require antiarrhythmic drugs during a follow-up of 56 and 51 months, respectively. Of the 8 patients who underwent radiofrequency ablation (30-40 watt, 20-40 sec, 2-15 application, using Inter Nova RA 50, 13.56 MHz), 1 patient had no recurrence of ventricular tachycardias and did not require antiarrhythmic drugs, 4 patients had no recurrence of ventricular tachycardias but did require anti-arrhythmic drugs, and 3 patients experienced recurrence of non-sustained ventricular tachycardia despite the use of antiarrhythmic drugs during a follow-up of 15-40 months. There were no complications except for cardiac perforation which occurred immediately after direct-current ablation in 1 patient. In conclusion, long-term success in preventing ventricular tachycardia was achievable with direct-current ablation, but this success was associated with serious risks, such as cardiac perforation. Radiofrequency ablation was safer than direct-current ablation, but had a lower long-term success rate.

Early afterdepolarizations in a patient with idiopathic monomorphic right ventricular tachycardia.

To identify the role of afterdepolarizations in the induction of idiopathic monomorphic right ventricular tachycardia (VT), monophasic action potentials (MAPs) were recorded in a patient with this type of VT. The VT had a left bundle branch block configuration and inferior axis, and originated in the right ventricular outflow tract (RVOT). MAPs were recorded with a contact electrode at the origin of the VT, as well as other ventricular sites. The VT was induced by the intravenous administration of isoproterenol and/or rapid ventricular pacing and was preceded by short-long-short sequences of RR intervals. Early afterdepolarizations (EADs) in MAPs were recorded at the origin of VT (RVOT), but not recorded at other ventricular sites. These data suggest that catecholamine sensitive triggered activity seems to be the mechanism of idiopathic monomorphic right VT and EADs can be recorded in association with the occurrence of this type of VT.

Abnormal systolic blood pressure response during exercise recovery in patients with angina pectoris.

OBJECTIVES: This study was conducted to clarify the mechanisms of the abnormal systolic blood pressure response after exercise in patients with angina pectoris. BACKGROUND: An abnormal systolic blood pressure response in patients with angina pectoris has been observed not only during exercise but also during the recovery period after exercise. However, the mechanisms of this abnormal response during recovery have not been elucidated. METHODS: Thirty-five patients with angina pectoris and 17 control subjects underwent bicycle ergometric studies after insertion of a Swan-Ganz catheter. RESULTS: In control subjects, all hemodynamic variables decreased rapidly after exercise. In 7 of the 35 patients, systolic blood pressure increased after exercise. The patients with angina were classified into two groups. In group I (17 patients), changes in systolic blood pressure during recovery were smaller than those in control subjects. In group II (18 patients) recovery of systolic blood pressure was normal. Changes in stroke index from rest to peak exercise were smaller in group I than in group II. Stroke index in both patient groups increased paradoxically during recovery. The increase in systemic vascular resistance index during recovery and the ratio of plasma norepinephrine concentration to cumulative work load were greater in group I than in group II. CONCLUSIONS: An abnormal systolic blood pressure response after physical exercise in patients with angina pectoris is indicative of severe myocardial ischemia during exercise and may be caused by an increase in stroke volume due to recovery from myocardial ischemia and increased systemic vascular resistance secondary to exaggerated sympathetic nervous activity.

[Percutaneous transvenous mitral commissurotomy in elderly patients with mitral stenosis].

Sixteen elderly patients (age > or = 60 years, elderly group) with mitral stenosis and 20 young patients (age < or = 59 years, young group) underwent percutaneous transvenous mitral commissurotomy (PTMC) by the single balloon technique. Pulmonary arterial and mean left atrial pressures, mitral valvular pressure gradient and left atrial dimension were significantly decrease in both groups after PTMC. Mitral valve areas by Gorlin formula were significantly increased from 1.14 +/- 0.40 to 1.78 +/- 0.66 cm2 in the elderly group and from 1.25 +/- 0.50 to 2.04 +/- 0.81 cm2 in the young group after PTMC. Thirteen elderly and 19 young patients became in NYHA class I or II after PTMC, and three elderly patients with early gastric cancer had the lower risk of the gastrectomies by preoperative PTMC. But, two elderly patients remained in NYHA class III or IV due to increased mitral regurgitation and late tamponade, and one elderly patient died by heart failure after PTMC. PTMC has the advantages of shorter hospitalization and lower invasion for the patients compared with surgery, therefore PTMC is an effective treatment in both elderly and young groups. Elderly patients with severe mitral stenosis have higher risk of PTMC and are needed discrete strategy.

[The effects of pharmacological autonomic blockade on the conduction system in patients with and without sinus node dysfunction].

Electrophysiological studies were performed in 26 patients with sick sinus syndrome (SSS) and 12 controls before and after pharmacologic autonomic blockade (PAB) with propranolol (0.15 mg/kg) and atropine (0.04 mg/kg). Sinus cycle length (SCL) shortened significantly after PAB in both groups. PA and HV intervals did not change after PAB. AH interval shortened and Wenckebach period increased after PAB in SSS group. Maximum corrected sinus node recovery time shortened in the control group but did not change in the SSS group after PAB. Calculated sinoatrial conduction time shortened after PAB in both groups. Refractory periods of the atrioventricular (AV) node and the ventricle shortened significantly, but those of the atrium did not change after PAB. Linear relations existed between the change of SCL and the change of AH interval and of the Wenckebach period. These results suggested that the autonomic nervous system had the same effects on the sinus and the AV nodes in patients with SSS, and that parasympathetic tone was predominant on the sinus node, the perinodal tissue and the AV node under resting conditions.

Hemodynamic changes due to afterload reduction as a predictor of exercise capacity in patients with dilated cardiomyopathy.

Sixteen patients with dilated cardiomyopathy were examined hemodynamically in order to clarify the relationship between the exercise capacity and the effects of afterload reduction at rest using supine graded bicycle exercise testing before and after sublingual administration of 10 mg nifedipine. 1) The integration of work loads was weakly correlated with the stroke index (r = 0.64), heart rate (r = -0.58) and plasma norepinephrine concentration at rest (r = 0.49), but not with the left ventricular ejection fraction, cardiac index, pulmonary arterial diastolic pressure or the mean arterial pressure at rest. 2) Changes in stroke index and heart rate after administration of nifedipine correlated well with the integration of work loads (r = -0.84, r = 0.81, respectively). Thus, in patients with dilated cardiomyopathy changes in stroke volume and heart rate due to afterload reduction at rest were better predictors of exercise capacity than the baseline left ventricular hemodynamic parameters.

Combination of nifedipine and carteolol compared to nifedipine alone in diurnal blood pressure variation and exercise blood pressure in patients with essential hypertension.

A combination of nifedipine (40 mg twice daily) plus carteolol (10 mg twice daily) was compared with nifedipine monotherapy in ten patients with essential hypertension. Ambulatory blood pressure (BP) monitoring over 24 hours and treadmill exercise testing were performed before treatment with nifedipine (but after the placebo period), after four weeks of nifedipine treatment, and after four weeks of nifedipine+carteolol combination therapy. At the end of nifedipine monotherapy, 24-hour average ambulatory BP, minimum ambulatory BP during sleep, maximum ambulatory BP, and casual BP all decreased significantly (P less than 0.01). However, the standard deviation (SD) of the ambulatory BP was not affected. The change in systolic BP response to treadmill exercise increased. After a four-week period of nifedipine+carteolol combination therapy, average ambulatory BP and maximum ambulatory BP were further decreased (P less than 0.01). The SD of the ambulatory BP and the change in BP response to exercise were significantly decreased (P less than 0.01), but the minimum ambulatory BP was not affected. These findings suggest that nifedipine and carteolol differ in their influence on diurnal BP variation and on exercise-induced BP elevation. Carteolol may mainly attenuate stress-induced BP elevation and have little influence on nocturnal BP decline. In contrast, nifedipine may affect the BP profile uniformly over the entire day. Nifedipine+carteolol combination therapy may be superior to nifedipine monotherapy because carteolol has a minimal effect on nocturnal BP and decreases stress-induced BP elevation.

Effects of volume loading on left atrial systolic time intervals.

The effects of volume loading on the left atrial preejection period (LAPEP) and left atrial ejection time (LAET) were examined in 24 patients with various heart diseases using pulsed Doppler echocardiography. In response to volume loading, the left atrial dimension before atrial contraction significantly increased from 30.6 mm +/- 5.8 mm to 32.4 mm +/- 5.4 mm and the change in the left atrial dimension during atrial contraction tended to increase. The peak velocity in the atrial contraction phase significantly increased from 58 cm/s +/- 14 cm/s to 63 cm/s +/- 13 cm/s, and the integral of the atrial contraction phase tended to increase. LAPEP significantly decreased from 114 ms +/- 16 ms to 104 ms +/- 14 ms and LAET significantly decreased from 128 ms +/- 15 ms to 124 +/- 12 ms. The relation between LAET and left ventricular end-diastolic pressure, and that between LAPEP and mean pulmonary capillary wedge pressure, shifted downward to the right after volume loading. Thus, left atrial ejection is augmented by volume loading according to the Frank-Starling mechanism, while LAPEP decreases due to an increase in preload and LAET decreases due to an increase in afterload.

Determinants of left atrial systolic time intervals--assessment by pulsed Doppler echocardiography.

To evaluate the responsible factors for left atrial ejection, the left atrial preejection period (LAPEP), i.e., the time interval between atrial pacing pulse and onset of atrial ejection, and left atrial ejection time (LAET), i.e., the duration of atrial ejection, were determined from mitral inflow velocity patterns in 35 patients with various heart diseases using pulsed Doppler echocardiography. LAPEP ranged from 75 to 157 (mean 110 +/- 18) msec and LAET from 80 to 169 (mean 124 +/- 19) msec. The left atrial dimension before atrial contraction showed no significant correlation with LAPEP or LAET. Peak velocity during atrial contraction was negatively correlated with LAPEP (r = -0.42, p less than 0.05) and positively with LAET (r = 0.56, p less than 0.01). Left ventricular end-diastolic pressure (LVEDP) indicated a significant negative linear correlation with LAET (r = -0.44, p less than 0.05). LAPEP showed no significant linear correlation with LVEDP, but a significant curvilinear relationship was observed between them (LAPEP = 169 - 9.LVEDP + 0.28.LVEDP2, r = 0.63, p less than 0.001). Mean pulmonary capillary wedge pressure (mPCWP) was curvilinearly related to LAPEP (LAPEP = 168 - 11.mPCWP + 0.42.mPCWP2, r = 0.72, p less than 0.001) and LAET (111 + 4.1.mPCWP - 0.22.mPCWP2, r = 0.63, p less than 0.001). Although LAPEP decreased and LAET increased with increase in mPCWP up to about 15 mmHg, the reverse situation was noted for greater mPCWP. Thus, the major determinants of left atrial systolic time intervals are left atrial and ventricular pressures, and peak velocity during atrial contraction.

WPW syndrome complicated by another cardiac disorder.

During the past 28 months, 16 cases of WPW syndrome were operated on at Hiroshima University Hospital. Two cases were complicated by other cardiac disorders which accelerated tachycardia, making diagnosis difficult. One of these cases showed serious mitral regurgitation, due to infective endocarditis and the patient suffered cardiac failure accompanied by paroxysmal tachycardia not responsive to medical therapy or cardioversion. A complex rhythm with atrial fibrillation and antegrade conduction rhythm through the accessory pathway made diagnosis and therapy quite difficult. The condition of the other patient was associated with myocardial bridging which caused angina pectoris during paroxysmal tachycardia. Myocardial scintigraphy showed myocardial ischemia in the antero-lateral area of the left ventricle. In the former case, mitral valve replacement and interruption of the accessory pathway were undergone simultaneously. In the latter case, myotomy of the muscle on segment 7 was conducted, following interruption of the accessory pathway.

Hemodynamic response to dietary sodium loading in essential hypertension studied with Doppler echocardiography.

The cardiac response to dietary salt loading was assessed by Doppler echocardiography during various sodium intakes (52-345 mEg per day) in 30 patients with essential hypertension. The Mitral flow velocity integral in the rapid filling phase (IntR) and the atrial contraction phase (IntA) was measured from the transmitral flow pattern, and the sum of IntR and IntA (IntR + IntA), the ratio of IntA to IntR (IntA/IntR), cardiac output (CO) and total peripheral resistance (TPR) were calculated. With salt loading, the mitral flow pattern remained almost unchanged in the nonsalt-sensitive (NSS) patients. Fourteen of the 19 salt-sensitive (SS) patients showed significant increases in IntR + IntA and CO with salt loading (IntR + IntA, from 13.9 +/- 2.8 to 17.9 +/- 3.6 cm, p less than 0.01; CO, from 6021 +/- 2130 to 8305 +/- 1699 ml/min, p less than 0.01), and were termed "salt-sensitive CO-dependent" (SS [COdep]), suggesting that the apparent pressor response to sodium loading was mediated by an increased CO. In the remaining five SS patients termed "salt-sensitive CO-independent" (SS [COindep]), IntA/IntR increased significantly with sodium repletion (from 0.66 +/- 0.23 to 0.90 +/- 0.31, p less than 0.01), without a significant change in IntR + IntA. Increments in IntA/IntR observed in the SS [COindep] patients were considered to be due to an elevation of total peripheral resistance (TPR), since changes in IntA/IntR were significantly correlated with those in TPR in all subjects (r = 0.617, p less than 0.01).

[Percutaneous transvenous mitral commissurotomy in managing rheumatic mitral stenosis].

From April 1987 to October 1989, 32 patients with mitral stenosis (MS) were treated, of whom percutaneous transvenous mitral commissurotomy (PTMC) was performed in 14. PTMC was indicated by the surgeons in 5 patients including 1) 2 patients who refused reoperation, 2) one with early gastric cancer, 3) one with severe hyperthyroidism and cardiac cachexia, and 4) one with acute renal failure and aortic stenosis. In the other 9 patients, PTMC was indicated by the cardiologists, because it is less invasive. Thirteen patients underwent open mitral commissurotomy (OMC) and 5 patients were treated with mitral valve replacement (MVR). PTMC group: Symptoms were alleviated in 10 of 14. The mitral valve areas (MVA) changed from 1.03 +/- 0.47 cm2 to 1.90 +/- 0.67 cm2 (p < 0.001), and the mean pressure gradient between the left atrium and left ventricle decreased from 10.2 +/- 3.6 mmHg to 4.9 +/- 1.7 mmHg (p < 0.001). No significant mitral valve regurgitation (MR) was induced by PTMC. OMC group: Symptomatic improvement was observed in all patients. The MVA changed from 1.54 +/- 0.46 cm2 to 3.06 +/- 1.34 cm2 (p < 0.001) and the mean left atrial pressures were reduced from 17.6 +/- 7.8 mmHg to 10.5 +/- 4.2 mmHg (p < 0.001). MVR group: There was one hospital death, and the other 4 patients were discharged with satisfactory results. It is concluded that although PTMC has been routinely performed for mild cases, this method is also very helpful in treating patients having various complications which impede open heart surgery.

[Familial complete atrioventricular block of adult onset].

A family of complete atrioventricular block (FCAVB) of adult onset was reported. A 36-year-old-female had 1 degree AH block, atrial and ventricular premature beats and mild sinus node dysfunction. Her father had complete AV block and died of it. A 57-year-old uncle and a 52 years-old uncle had bradycardia from 44, 5 years of age and 51 years of age, respectively, and their ECG showed complete AV block with narrow QRS waves. They were implanted with permanent pacemakers. Her grandmother died a sudden death of Adams-Stokes attack. Acquired heart diseases were not seen in any of the family Thus, this family was thought a FCAVB of adult onset.

Efficacy and safety of catheter electrical ablation for ventricular tachycardia--experimental and clinical studies.

We studied the factors determining the extent of myocardial damage induced by catheter electrical ablation in 23 mongrel dogs and evaluated the efficacy and safety of catheter electrical ablation in 6 patients with medically refractory ventricular tachycardias (VT). Electrical shocks were delivered on the epicardium (EPI) and endocardium (END) of the ventricular wall of open-chest anesthetized dogs through a 6F USCI electrode catheter. Effect of the extent of electrode contact pressure was examined by the presence or absence of monophasic action potential using the contact electrode technique. The former was defined as the hard touch condition and the latter was defined as the soft touch condition. The myocardial lesion induced by EPI fulguration was larger than that by END fulguration (EPI-100 J soft touch: 10.2 +/- 2.9 mm in diameter, 6.6 +/- 1.6 mm in depth vs END-100 J soft touch: 7.7 +/- 1.7 mm in diameter, 5.0 +/- 1.2 mm in depth; p less than 0.05, p less than 0.05). The lesion diameter and lesion depth were enlarged by increasing the amount of delivered energy. The lesion depth by the hard touch condition was significantly greater than by the soft touch condition. The transmural perforation was observed in all EPI fulguration in the hard touch condition of the right ventricular wall. In the clinical study, one to three shocks (mean 1.8 +/- 0.7) of 60 to 200 J (mean 151 +/- 48 J) were delivered per session in 6 patients with medically refractory VT.(ABSTRACT TRUNCATED AT 250 WORDS)

[A study on tolerance to denopamine, oral beta 1-agonist].

To investigate whether effects of denopamine become weaker or not. Initial single dose (10 mg) effects, single dose effects after long-term treatment (30 mg per day, about 40 days), and chronic effects were studied by Doppler and echocardiography in 23 patients with heart failure (NYHA II-III). 1) Chronic effects: Blood pressure and heart rates didn't change significantly whether they were measured before or after long-term treatment. But left ventricular end-diastolic dimension decreased from 54.6 +/- 10.2 to 53.3 +/- 10.1 mm (p less than 0.01). Percent fractional shortening (%FS) increased from 22.6 +/- 7.8 to 25.3 +/- 8.6% (p less than 0.05). Mean velocity of circumferential fiber shortening (mVCF) tended to increase, and cardiac index (CI) increased from 2.71 +/- 0.47 to 2.98 +/- 0.57 l/min/m2 (p less than 0.01). 2) Initial single dose effects: Blood pressure and heart rates increased significantly. %FS increased from 25.0 +/- 7.7 to 25.9 +/- 7.8% (p less than 0.05), mVCF increased from 0.94 +/- 0.26 to 1.03 +/- 0.28 cir/sec (p less than 0.01), and CI increased from 2.81 +/- 0.49 to 3.09 +/- 0.49 l/min/m2 (p less than 0.01). 3) Single dose effects after long-term treatment: Blood pressure and heart rates increased significantly. %FS tended to increase, mVCF increased from 1.02 +/- 0.27 to 1.09 +/- 0.30 cir/sec (p less than 0.05), and CI increased from 3.05 +/- 0.62 to 3.37 +/- 0.54 l/min/m2 (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical electrophysiological effects of nicorandil on the conduction system in humans].

The electrophysiological effects of nicorandil on the conduction system in humans were examined. Twelve patients with sick sinus syndrome (SSS), 3 patients with AV block and 3 subjects with normal conduction system were studied. The clinical electrophysiological effects were examined before, and 5 min after intravenous administration of nicorandil 2 mg over 3 min. Nicorandil increased heart rate in 6 patients and decreased it in 4. Wenckebach point was increased in 5 patients and decreased in 4. Maximum sinus node recovery time was prolonged in 4 of 12 patients with SSS, and shortened in 3 of them. It was unchanged in 6 patients without SSS. These changes were not statistically significant. There were no changes in PA, AH and HV intervals and refractory periods the atrium, the AV node and ventricle. Nicorandil had no depressant effects on the conduction system of humans. Thus, this drug can be used easily for the treatment of ischemic heart disease in patients with some conduction disturbances.

[Effects of verapamil and disopyramide phosphate on the termination, reinduction and long-term prevention of paroxysmal supraventricular tachycardia].

The efficacy of verapamil and disopyramide phosphate for the termination and prevention of paroxysmal supraventricular tachycardia (PSVT) were studied electrophysiologically in 32 patients with inducible sustained PSVT (17 patients received verapamil, 15 patients received disopyramide). Twelve patients had atrioventricular nodal tachycardia, 7 had concealed and 13 had overt Wolff-Parkinson-White syndrome. Intravenous verapamil (0.15 mg/kg) terminated the sustained PSVT in 15 of the 17 patients (88%) by production of AV block in 13 patients, VA block in one, and a ventricular premature beat in one. PSVT could not be induced in any of these 15 patients after they had received verapamil. In the remaining 2 patients, PSVT could not be terminated by the use of verapamil, but the cycle lengths of PSVT were lengthened. Long-term oral dosages of verapamil of 120-240 mg/day were administered in 13 of the 17 patients. All patients except two, whose PSVT was unable to be effected by intravenous verapamil, were well controlled: PSVT disappeared in 7 patients and decreased in 4. Intravenous disopyramide (1.5 mg/kg) terminated induced PSVT in 10 of the 15 patients (67%) by production of VA block. Although PSVT could not be reinitiated in 5 of these 10 patients, non-sustained PSVT was induced in 2 and sustained PSVT was induced in 3 after having received disopyramide. PSVT was induced in all of the 5 patients who failed to respond to disopyramide. The cycle lengths of PSVT after administration of disopyramide remained unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)