mistaken diagnosis of acute (‘‘new’’) MI could lead to

initiate an inappropriate thrombolytic therapy.

References

[1] Szilagyi N, Ginsburg M. Acute MI revealed in the presence of right

bundle branch block and ventricular extrasystoles. Am J Cardiol

1962;9:632�/8.

[2] Gambetta M, Childers RW. Rate-dependent right Q waves: ‘‘septal

focal block’’. Am J Cardiol 1973;32:196�/201.

[3] Loperfido F, Fanelli R, Ansalone G, De Matteis D. Transient right

bundle branch block unmasking anteroseptal infarction concealed

by left posterior fascicular block. Acta Cardiol 1980;35:235�/43.

[4] Rosenbaum MB, Girotti L, Lazzari JO, Halpern MS, Elizari MV.

Abnormal Q waves in right sided chest leads provoked by onset of

right bundle-branch block in patients with anteroseptal infarction.

Br Heart J 1982;47:227�/32.

[5] Klein HO, David D. New Q waves do not always a new infarct

spell: right bundle branch block-dependent Q waves simulating

infarct extension. Coron Artery Dis 1998;9:51�/4.

[6] Ortega-Carnicer J, Gomez-Grande ML, Ambros A. Right bundle

branch block-induced Q waves simulating acute anterior myocar-

dial infarction extension. J Electrocardiol 2000;33:387�/91.

[7] Dhala A, Gonzalez-Zuelgaray J, Deshpande S, Blanck Z, Sra J,

Jazayeri M, et al. Unmasking the trifascicular left intraventricular

conduction system by ablation of the right bundle branch. Am J

Cardiol 1996;77:706�/12.

Julian Ortega-Carnicer

Intensive Care Unit,

Hospital Alarcos,

Los Alisos 10,

Av. Pıo XII s/n,

13002 Ciudad Real,

Spain

E-mail address: jortegacar@wanadoo.es

doi:10.1016/S0300-9572(03)00110-2

Fever-induced ST-segment elevation and T-wavealternans in a patient with Brugada syndrome

Brugada syndrome (BRS), which is characterized byapparent right bundle branch block (or prominent J

wave) with ST-segment elevation in V1�/V3, is consid-

ered as a primary electrical disease caused by gene

mutations These lead to a reduction in the fast sodium

channel current and a propensity to malignant tachyar-

rhythmias [1]. Recent experimental studies have demon-

strated that the sodium channel deactivates prematurely

and recovers from deactivation more slowly at hightemperatures [2,3]. This may predispose some Brugada

patients to arrhythmias during a febrile state. We report

a case of BRS who developed coved ST-segment

elevation and macroscopic (visible) T-wave alternans

(TWA) in the right precordial leads during a febrile

episode.

A 35-year-old man was admitted to the Intensive Care

Unit because of fever due to viral upper respiratoryinfection. There was right precordial ST-segment eleva-

tion. Physical examination on admission was unremark-

able. Vital signs were a temperature of 38.9 8C, a blood

pressure of 125/65 mmHg, and a peripheral pulse rate of

95 beats per minute. There was no history of syncope,

ventricular tachyarrhythmias, cocaine use, or adminis-

tration of cardiac membrane active drugs. The electro-

cardiography (ECG) on admission showed normal sinusrhythm at 95 beats/min, a prominent J wave followed by

a coved ST-segment elevation ending in a negative T

wave in leads V1�/V3 (Fig. 1A). There was also a visible

TWA with a 2:1 appearance in the right precordial leads

(Fig. 1B). Initiation of TWA was not associated with

gross changes in the cycle length or development of

ventricular arrhythmias. Two hours later, when the

body temperature had fallen to 36.8 8C with paraceta-mol, the ECG revealed a partial reduction of the ST-

segment elevation and negative T wave in the right

precordial leads (Fig. 1C). It was noted that TWA had

disappeared in the right precordial leads (Fig. 1D).

Sodium, potassium and calcium values, and serial

cardiac enzyme levels were normal. Echocardiographic

findings, including ventricular segmental kinesis, were

normal. Two days later, the ECG recorded at a bodytemperature of 35.8 8C revealed a diminished J wave

followed by a small saddle-back ST-segment elevation in

leads V1 and V2, and a negative T wave in lead V1 (Fig.

1E). Intravenous administration of flecainide (2 mg/kg)

reproduced the right precordial ST-segment elevation.

No ventricular arrhythmias were induced during ven-

tricular programmed electrical stimulation. Cardiac

catheterization revealed normal coronary arteries andleft ventricular function. He was discharged without any

treatment. Dynamic changes in ST-segment elevation

were observed during follow-up.

Fever-induced ECG changes in patients with BRS

have been limited to exceptional cases of recurrent

ventricular fibrillation reverted by an implanted cardi-

overter defibrillator [4], and further ST-segment eleva-

tion associated with malignant ventricular tachyarrhy-thmias [5,6] and TWA [6]. An additional case of ECG

findings resembling BRS in relation with fever, but

which could not be reproduced at normal temperature

on administration of flecainide, has been published

recently by Saura et al. [7]. This patient had a coved

ST-segment elevation and TWA during a febrile state.

Later, when the patient became afebrile, the ECG only

showed minor saddle-back ST-segment elevation.Although transient normalization of the ECG for a

period of time have been described in patients with BRS,

we believe that these ECG findings were induced by

fever because the macroscopic TWA was only observed

Letters to the Editor 315

at high temperatures. A similar case of augmentation of

the ST-segment elevation associated with TWA and

premature ventricular contractions during a febrile

illness has been described by Morita et al. [6] in a

patient with BRS.

Visible TWA is a rare electrocardiographic abnorm-

ality that has been associated with increased vulner-

ability to ventricular arrhythmias under diverse

pathophysiologic conditions such as myocardial ischae-

mia, Prinzmetal’s angina, altered autonomic tone,

electrolyte abnormalities and the long QT syndrome

[8]. In patients with BRS, visible TWA has been

observed during a febrile state [6], and following

intravenous administration of sodium channel blockers

such as cibenzoline [9] or procainamide [10]. In this

Brugada patient, the TWA was probably due to the 2:1

loss of the action potential dome in the epicardium but

not the endocardium resulting in the development of a

marked transmural dispersion of repolarization. This

might cause a predisposition to reentrant arrhythmias

[9].

In conclusion, a febrile episode may induce ST-

segment elevation and TWA in some patients with

BRS. The significance of this finding requires more

clinical investigation.

References

[1] Brugada P, Brugada J. Right bundle branch block, persistent ST

segment elevation and sudden cardiac death: a distinct clinical and

electrocardiographic syndrome. J Am Coll Cardiol 1992;20:1391�/

6.

[2] Dumaine R, Towbin JA, Brugada P, Vatta M, Nesterenko DV,

Nesterenko VV, et al. Ionic mechanisms responsible for the

electrocardiographic phenotype of the Brugada syndrome are

temperature dependent. Circ Res 1999;85:803�/9.

[3] Wang DW, Makita N, Kitabatake A, Balser JR, George AL.

Enhanced Na (�/) channel intermediate inactivation in Brugada

syndrome. Circ Res 2000;87:e37�/43.

[4] Gonzalez Rebollo JM, Hernandez Madrid A, Garcıa A, Garcıa

de Castro A, Mejıas A, Moro C. Recurrent ventricular fibrillation

during a febrile illness in a patient with the Brugada syndrome.

Rev Esp Cardiol 2000;53:755�/7.

Fig. 1. (A�/E) Serial ECGs. (A) The ECG on admission, recorded when the patient had a febrile state of 38.9 8C, showing a prominent J wave

followed by a coved ST-segment elevation ending in a negative T wave in leads V1�/V3. (B) Note TWA in leads V2 (arrows). (C) The ECG recorded

with a body temperature of 36.8 8C revealing partial reduction of the ST-segment elevation and negative T wave in the right precordial leads. (D)

Note complete disappearance of the TWA. (E) The ECG registered with a body temperature of 35.8 8C revealing a small saddle-back ST-segment

elevation in leads V1 and V2, and a negative T wave in lead V1.

Letters to the Editor316

[5] Porres JM, Brugada J, Urbistondo V, Garcıa F, Reviejo K,

Marco P. Fever unmasking the Brugada syndrome. Pacing Clin

Electrophysiol 2002;25:1646�/8.

[6] Morita H, Nagase S, Kusano K, Ohe T. Spontaneous T wave

alternans and premature contractions during febrile illness in a

patient with Brugada syndrome. J Cardiovasc Electrophysiol

2002;13:816�/8.

[7] Saura D, Garcıa-Alberola A, Carrillo P, Pascual D, Martınez-

Sanchez J, Valdes M. Brugada-like electrocardiographic

pattern induced by fever. Pacing Clin Electrophysiol

2002;25:856�/9.

[8] Armoundas AA, Tomaselli GF, Esperer HD. Pathophysiological

basis and clinical application of T-wave alternans. J Am Coll

Cardiol 2002;40:207�/17.

[9] Tada H, Nogami A, Shimizu W, Naito S, Nakatsugawa M,

Oshima S, et al. ST segment and T wave alternans in a patient

with Brugada syndrome. Pacing Clin Electrophysiol 2000;23:413�/

5.

[10] Chinushi M, Washizumura H, Aizawa Y. Intravenous adminis-

tration of class I antiarrhythmic drugs induced T wave alternans

in a patient with Brugada syndrome. J Cardiovasc Electrophysiol

2001;12:493�/5.

Julian Ortega-Carnicer ,Juan Benezet,

Filomena Ceres

Intensive Care Unit,

Hospital Alarcos.,

Av. Pio XII s/n., 13002

Ciudad Real,

Spain

E-mail address: jortegacar@wanadoo.es

doi:10.1016/S0300-9572(03)00957-1

Endothelin-1 elevates regional cerebral perfusion during

prolonged ventricular fibrillation cardiac arrest in pigs

The role of endothelin-1 in regional cerebral perfusion

during prolonged ventricular fibrillation.

We read with great interest the article by Holzer et al.

[1] published in the December 2002 issue of Resuscita-

tion . The authors report that iv. application of en-

dothelin-1 (ET-1) during resuscitation from prolonged

ventricular fibrillation cardiac arrest elevated regional

cerebral perfusion superior to adrenaline (epinephrine)in pigs. Furthermore, resuscitation success increased

when ET-1 was given in moderate doses (50/100 mg).

These findings are in accordance, in part, with pre-

viously published reports in which ET-1 improved

cerebral blood flow (CBF) during CPR [2], but not

restoration of spontaneous circulation (ROSC) [3].

However, despite the positive effects of ET-1 on CBF

during CPR, we believe that these results must beinterpreted with great caution and might even be

misleading because of possibly detrimental effects of

ET-1 on delayed postischaemic cerebral hypoperfusion

after cardiac arrest.

Successful resuscitation from cardiac arrest frequently

is complicated by severe brain injury. About 50% of

short-term survivors die in permanent coma, and 10�/

30% of long-term survivors suffer permanent braindamage [4]. One of the limiting factors of brain

resuscitation is the postischaemic brain hypoperfusion

syndrome [5]. The delayed hypoperfusion syndrome

develops after a transient phase of reactive hyperaemia

and is associated with a disturbed coupling between

blood flow and metabolism. After short periods of

cerebral ischaemia postischaemic hypoperfusion is pre-

sent after 10 min of recirculation [6], and after pro-longed global ischaemia the disturbances may last

several days [7]. There is considerable evidence that

activation of ET-1 is involved detrimentally in this

hemodynamic disturbance and the associated tissue

injury [8,9]. Spatz et al. first demonstrated that applica-

tion of a selective endothelin receptor (ETA) antagonist

(BQ123) reverses post-ischaemic hypoperfusion after

global cerebral ischaemia induced in gerbils by carotidartery occlusion [10]. We could demonstrate that post-

ischaemic application of BQ123 improved cerebral

hemodynamic as well as functional recovery and long-

term neurological recovery after cardiac arrest in rats

[11,12]. Moreover, it has been suggested that ET-1

enhances the permeability of the blood brain barrier

via ETA [13], and infusion of a selective ETA-antagonist

(S-0139) reduced plasma extravasation and brain injuryafter transient middle-artery occlusion in rats [14].

However, there are no experimental data to date on

the effects of ET-1 applied during CPR on postischae-

mic CBF. Unfortunately, Holzer et al. [1] measured

CBF only during CPR but not during the following

period of cerebral recirculation despite using a protocol

in which the animals were sacrificed 30 min after ROSC.

Therefore, the authors missed the opportunity to assessthe effects of ET-1 on early postischaemic cerebral

recirculation, which may even have a greater impact

on neurological recovery after cardiac arrest than CBF

during CPR. This information would have been an

important contribution, especially since Hilwig et al.

demonstrated dramatically increased postresuscitation

mortality after CPR with ET-1 in pigs [15]. In the study

of Hilwig et al., CBF was not measured but wehypothesize that the increased mortality was the result

of severe brain injury and oedema due to postischaemic

cerebral reperfusion disturbances induced by the long-

lasting cerebral vasoconstriction after ET-1 application.

We agree with the authors that further studies should

be performed to evaluate the effects of ET-1 on CBF

completely during, and in particular, after, resuscitation

from cardiac arrest. However, we expect that theincrease in CBF during CPR will not outweigh the

possible harmful effects of ET-1 on postischaemic CBF

and that the detrimental effects on neurological outcome

rather than improved neurological recovery will be the

Letters to the Editor 317