Use of Mexiletin in Ventricular Arrhythmias

The  European College of Veterinary Internal Medicine – Companion Animals.

17 ^th ECVIM-CA Congress & 9 ^th ESVCP Congress.

13 ^th – 15 ^th September 2007 – Budapest – Hungary.

Cited in: Ettinger S.J., Feldman E.C., 2010 –

Textbook  of Veterinary Internal Medicine. Saunders – Elsevier.

USE  OF  MEXILETIN  AT DOGS  WITH  VENTRICULAR  ARRYTHMIAS

Brăslaşu Corneliu Mihail, Brăslaşu E. Daniela, Brădăţan Cătălina,

Budai Mihai.

Faculty of Veterinary Medicine Bucharest. Romania.

Mexiletin is an antiarrhythmic from I b class (Vaughan-Williams) indicated in multiple and multifocal premature ventricular beats and ventricular tachycardia.

A number of 27 dogs from mid and large breed were diagnosed with ventricular arrhythmia: multifocal  premature beats and ventricular tachycardia.

Ventricular tachycardia with a high frequency caused syncope and this case we used first, lidocaina in dose of 2-4 mg/kg in continue rate infusion; then we used Mexiletin in dose of 5-8 mg/kg p.o. bid-tid to prevent ventricular arrhythmias.

After administration of doses 2-5 mg there weren’t  stopped  the ventricular  arrhythmia. High doses of 8 or 10 mg/kg p.o. bid  determined a total disappearance of ventricular arrhythmias.

Biochemical blood exams didn’t show an increase of blood values, creatinine and transaminase levels. There weren’t observed decrease either cardiac frequency  or blood pressure. Also a  adverse reaction wasn’t observed.

In conclusion, Mexiletin administration in dog determined the end of ventricular arrhythmias, the drug being well tolerate by animal.

Mexiletine is used to suppress frequent ventricular ectopy and to reduce the frequency and duration of abrupt self-limiting ventricular tachycardia.

Class IB antiarrhythmics are used only to treat ventricular arrhythmias. These drugs slightly depress depolarization in myocardial cells. Class IB antiarrhythmics are cell membrane stabilizers, but do not affect the automatist of the sinoatrial node or conductivity through the atrioventricular node.

As their major action, class IB antiarrhythmics decrease the action potential duration and to a lesser extent the effective refractory period. The drugs especially affect the Purkinje fibers and myocardial cells in the ventricles. By shortening the effective refractory period, class IB antiarrhythmics eliminate unidirectional block, which can trigger a reentry arrhythmia. The drugs also decrease ventricular ectopy by blocking the slow influx of sodium during plateau (phase 2) and by decreasing the slope of phase 4 depolarization. Class IB antiarrhythmics neither block nor mimic autonomic control of the heart. (Richard K. Gibson and Douglas R. Geraets, 1996).

Usual dosage: 5 – 8 mg/kg PO BID-TID.

  

Table 1. Clinical cases with Mexiletin administration

Nr. crt.	Breed, age, sex	Clinical diagnosis
1.	Schnauzer, male, 9.6 years old	Dilated cardiomyopathy
2.	Boxer, male, 11 years old	Dilated cardiomyopathy
3.	Great dane, male, 6 years old	Dilated cardiomyopathy
4.	Boxer, female, 9.6 years old	Multiple ventricular premature beats, Ventricular parasystolie
5.	German shepard, male, 5.6 years old	Myocarditis
6.	Boxer, male, 8.6 years old	Multiple, multifocal ventricular premature beats
7.	German shepard, male, 6 years old	Tumoral pericarditis
8.	German shepard, male,14 months old	Congenital heart disease (Dilated cardiomyopathy ?)
9.	German shepard, female, 13 years old	Dilated cardiomyopathy
10.	Great dane, female, 10 years old	Pyometra
11.	Boxer, male, 10 years old	Dilated cardiomyopathy
12.	Dog, medium size, male, 10 years old	Cardiac failure, Ventricular tachycardia
13.	Cocker, mascul, 14 ani Cocker, male, 14 years old	Right ventricular hypertrophy-Dirophilariosis
14.	Boxer, female, 11.6 years old	Ventricular tachycardia
15.	Boxer, female, 12 years old	Dilated cardiomyopathy
16.	Basset Hound, male, 9 years old	Dilated cardiomyopathy
17.	Saint Bernard, female, 2.5 years old	Dilated cardiomyopathy
18.	Vijla, female, 3.6 years old	Congenital ventricular arrhythmia
19.	Russian greyhound, female, 12 years                  old	Tumoral pericarditis and pleuresia
20.	Schnauzer, male, 9 yeras old	Myocardial infarction
21.	Doberman, male, 8.6 years old	Dilated cardiomyopathy + Gastric torsion
22.	Doberman, male, 7 years old	Dilated cardiomyopathy
23.	Great dane, male, 5 years old	Dilated cardiomyopathy
24.	Greyhound, mascul, 9 ani	Multiple ventricular premature beats Pleurisy

The conclusions of table 1 are:

-         ventricular premature beats which required specific therapy were diagnosed in large breed dogs;

-         a higher incidence of these ventricular premature beats are recorded in males (70.9%)

-         the diseases with ventricular premature beats in their evolution are: dilated cardiomyopathy (in most of the cases), idiopathic ventricular premature beats and rarely congenital heart disease, myocardial infarction, dirophilariosis (Heartworm disease), malignant congenital  ventricular premature beats

Table 2. ECG changes after Mexiletin administration (a)

 A. Initial ECG

B. ECG after. Mexiletin

Patient		1.	2.	3.	4.	5.
P – T interval	A.	0.32	0.30	0.28	0.34	0.28
	B	0.30	0.30	0.26	0.34	0.28
Q – T interval	A.	0.20	0.20	0.18	0.20	0.20
	B.	0.18	0.20	0.16	0.20	0.20
Heart rate beats/min	A.	150	148.8	176.5	166.6	166.6
	B.	100	125	166.6	150	150

Patient		6.	7.	8.	9.	10.
P – T interval	A.	0.32	0.30	0.32	0.30	0.28
	B	0.34	0.26	0.32	0.30	0.28
Q – T interval	A.	0.16	0.20	0.20	0.16	0.16
	B.	0.18	0.20	0.20	0.16	0.16
Heart rate beats/min	A.	150	166.6	176.4		187.5
	B.	187.5	166.6	150	120	136.36

Observations regarding Mexiletin therapy in dog

-         Mexiletin was administered in multiple ventricular premature beats with different origins (multifocal).

-         Lidocain i.v. (2-4mg/kg) was used until remission of ventricular premature beats in cases with diagnosed multiple ventricular premature beats or ventricular tachycardia, with clinical signs of syncope or heart failure (III Class – ISACHC, 1992).

-         At low doses of Mexiletin, 3-4mg/kg, no clinical signs were observed (persistence of ventricular premature beats).

-         At high doses of Mexiletin (6-8mg/kg), the ventricular premature beats and ventricular tachycardia disappeared and there was an improvement of clinical status (remission of pulmonary edema).

-         Animals receiving Mexiletin were ECG monitored (from 1-2 to 7 days, depending on the diagnosis and clinical status). Mexiletin doses were decreased when the ventricular premature beats were remised and the clinical status was improved. In many cases, after using Mexiletin for 3-4 weeks (together with the therapy for the the principal disease), the interruption in Mexiletin administration wasn’t follow by reappearance of ventricular premature beats.

-         By monitoring hepatic, renal function and glycemia, no increase in creatinine, BUN, SGPT, SGOT were observed. In some cases (Boxer, 10 years, male – Dilatative cardiomyopathy) a decrease in the value of these parameters was observed (creatinine decreased from 1mg/dl to 0.85mg/dl; BUN decreased from 59,15mg/dl to 40.8mg/dl).

-               Except one case, in which during Mexiletin therapy a sinusal bradicardia was diagnosed (Mexiletin administration was interrupted), no other adverse reactions were observed.

Clinical cases

Ventricular tachycardia – paroxysmic attack. Greyhound, male, 9 years

  Ventricular tachycardia - paroxysmic attack. Greyhound, male, 9 years

Remission of ventricular premature beats

 after Mexiletin administration – 7 mg/kg BID (day 4 of treatment)

The case discussed above.

ECG aspect one month after administration of Mexiletin

Ventricular tachycardia - paroxysmic attack, Boxer, female. 11.6 years old

Ventricular tachycardia - paroxysmic attack.

The case discussed above

Control of ventricular tachycardia by i.v. Lidocaine (80 mg)

ECG aspect after the administration of Mexiletin

6 mg/kg P.O. (second day of treatment)

CONCLUSIONS

1. Mexiletin is an IB class anti-arrhythmic used in the treatment of ventricular arrhythmia (ventricular premature beats and ventricular tachycardia). The dosage in dog is 5-8mg/kg BID-TID.
2. After the administration of low doses of Mexiletin there was no improvement of ventricular premature beats, on the contrary, high doses (6-8mg/kg) determined the remission of ventricular premature beats/ventricular tachycardia.

3. No adverse reactions were observed during Mexiletin administration. The creatinine, BUN and glycemia were in normal limits when the biochemical blood exam was performed. In the situations when these parameters were improved, the explanation was due to the decrease of  hemostasis, consecutive to the ventricular arrhythmia.

4.  No significant changes in the length of ventricular and general electric systole were observed on the ECG; instead, a decrease of heart frequency has been shown.

5. The examination of cases in which Mexiletin was administered has shown: most of the clinical cases were large size males (70,90%). Ventricular arrhythmia were diagnosed in most of the cases in dilated cardiomyopathy; other cases were represented by myocardial infarction, congenital ventricular arrhythmia, congenital heart disease, etc. Mexiletin can be called, because of its rapid clinical effects and its low adverse reactions, the oral Lidocaine, which can be given P.O.

Bibliography

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Currently, Mexiletin no longer used in Europe.