A Clinical Study of the Effect of Coenzyme Q on Congestive Heart Failure Taro

ISHIYAMA,

TOYAMA,

M.D.,

M.D.,*

TSUKAMOTO,

Yoshiharu Toru

M.D.,**

Masaaki Yuichi

MORITA,

YAMAGAMI, Noboru

OHKUBO,

WADA,

M.D.,***

YAMAMURA,

M.D.,

M.D.,*

Seiichi

Nozomu M.D.,***

and

M.D.

SUMMARY Expecting activation of myocardial energy liberation, coenzyme Q was applied as a treatment to 55 patients suffering from congestive heart failure. Daily doses of 50 to 100mg of coenzyme Q7 were injected intravenously in 21 cases for 3 to 35 days. Daily doses of 60mg of coenzyme Q7 were administered perorally in 17 cases for 14 to 196 days. Daily doses of 30mg of coenzyme Q10 were administered perorally in 17 cases for 7 to 182 days. Clinical effects were evaluated within 4 weeks by the criteria using a scoring method of severity of congestive heart failure which was devised by the authors. In summary a certain effect was found in 20 cases and a mild effect was observed in 29 cases. No significant changes were observed in heart rate and blood pressure. Exanthema appeared in 2 patients of the group of coenzyme Q7 intravenous injection. In conclusion the therapeutic effect of coenzyme Q was thought to be mild but stable in supplement to digitalis therapy in cases of congestive heart failure. Additional Indexing Words: Activation of myocardial energy liberation Coenzyme Q7 and Q10 Intravenous injection Peroral administration A scoring method to evaluate severity of congestive heart failure

ECENTLY clinical application of substances affecting to myocardial energy metabolism such as vitamin B complexes, adenosine triphosphate or its precursors, cytochrome C, and some metabolites has revealed a certain effect in therapeutics of cardiac diseases. Coenzyme Q was isolated by Crane and his coworkers and it was evidenced to localize mainly in mitochondria of subcellular fraction and to play an important role in oxidative Fromthe Third Department of InternalMedicine,OsakaUniversity MedicalSchool,Osaka. *The CenterforAdultDiseases , Osaka **Departmentof InternalMedicine, Nishinomiya CityCentralHospital , Nishinomiya ***KobeShoseiHospital , Kobe ReceivedforpublicationApril19,1975. 32

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ISHIYAMA, ET AL.

33

phosphorylation in the electron transfer system.1) Therefore it was expected to reveal a same kind of effect in biomedical or clinical field. Although actions of these substances administered exogenously are difficult to prove directly in clinical cases, the effect of these substances on cardiac dysfunctions is able to be evaluated clinically. In congestive heart failure myocardial energy liberation is considered to be impaired secondarily because of continuous relative reduction of coronary blood supply as well as relative increase of oxygen demand. It is expected that exogenous coenzyme Q acts a role of trigger to activate deteriorated mitochondrial energy liberation. This expected action is thought to reveal a different kind of effect when compared with that of digitalis or diuretics. According to the above-mentioned concept, a clinical trial was attempted to apply coenzyme Q to cases of congestive heart failure. SUBJECTS ANDMETHODS Subjects were 21 inpatients and 34 outpatients suffering from congestiveheart failure. Underlying diseaseswere valvular diseases,congenital heart diseases,hypertension, arteriosclerosis,pulmonary diseases, and primary myocardial diseases. Classificationsof cardiac function before the treatment were the second grade of NYHA in almost all cases and the third grade in a few cases. Preceding the start of the treatment, all patients were observedat least 1 week either without medication or continuing the same medication hitherto. Table

I.

A

Proposed

Scoring

Method

of

Severity

of

Congestive

Heart

Failure

34

EFFECT OF COENZYME Q ON CONGESTIVE HEART FAILURE

Jap. Heart J. January, 1976

Subjects were divided into the following 3 groups according to the difference of the treatment: IntravenouscoenzymeQ7 group: included 21 inpatients. The grade of congestive heart failure was more severe in average in this group than the other 2 groups. Daily doses of 50 to 100mg of coenzyme Q7 was injected intravenously for 3 to 35 days. Table

*Prescription sufficiency,

was not changed MI:

mitral

from

insufficiency,

at least AI:

one week

aortic

before

insufficiency.

II.

Results

of Treatment:

the start of the treatment

until

Vol.17 No.1

ISHIYAMA, ET AL.

35

Peroral coenzymeQ7 group: included 17 outpatients. Coenzyme Q7 was administered perorally 50 to 100mg daily to all cases except 1 case for 14 to 196 days. Peroral coenzymeQ10 group: included 17 outpatients. Coenzyme Q10 was administered perorally 30mg daily to all cases for 7 to 182 days. Subjects were classified randomly into the 2 peroral groups. Although combined use of other drugs was not restricted, alternation of prescripIntravenous Coenzyme Q7 Group

the judgment of effects, **fb: finger breadth,

MS: mitral

stenosis ,

MSI: mitral stenoin-

36 tion

was

date

of

start

of

reveal

prohibited

strictly

evaluation the

of

A

as

the was

substances

slowly

were

devised and

shown

of

ment

effect

than

start

as

other

of

judged

the

treatment

within

coenzyme

4

Q

prevalent

drugs

weeks

were

until

the

after

the

considered

which

had

to

a certain

action.

in

expressed

ferences

before

The such

more

method

Symptoms

scores

1 week

effect.

because

action

scoring

effect.

since

the

treatment,

metabolic

pharmacological

was

Jap. Heart J. January, 1976

EFFECT OF COENZYME Q ON CONGESTIVE HEART FAILURE

by

signs

Table

of

I.

Severity

quantitatively the

total

evaluated

(TOTAL

by

scores as

the

authors

congestive

the

before

the

of total

was

adopted

heart congestive of

each

and

the

order

were

heart

scores

treatment

in

failure

failure

in

symptoms total

to

graded

evaluate and

individual and

scores

after

the

assigned cases

signs.

Dif-

the

treat-

follows:

SCOREbefore

treatment)-(TOTAL

SCOREafter

treatment)•†4

as

"ef-

fective", "mildly

3•†(TOTAL effective"

SCOREbefore

treatment)-(TOTAL

SCOREafter

treatment)•†1

as

, and (TOTAL

SCOREbefore

treatment)-(TOTAL

SCOREafter

treatment)•…0

as

"in-

effective". Heart ment.

Daily

rate

and amount

blood of

pressure urine

was

were

also

recorded

checked on

the

before all

and

after

the

treat-

inpatients.

RESULTS 1. Intravenous Coenzyme Q7 Group Results were summarized in Table II.

Fig.1.

Changes

of heart

rate

before

"Effectives"

and

after

the

treatment.

were found in 10

Vol.17 No.1

ISHIYAMA, ET AL.

cases.

"Mildly

effectives"

were

cases.

As shown

in Fig.1,

changes

ency

after

the

treatment.

in

7 cases,

and"

of heart

Changes

37

rate

of blood

ineffectives"

showed

pressure

no were

were

consistent not

remarkable.

Fig.2. Changes of daily amount of urine before and after the treatment in cases of the inpatients (intravenous coenzyme Q7 group).

Fig.3. before mean

and total

Changes after scores

the

of

total

scores

treatment.

before

and

The after

of severity thick

treatments.

lines

of

congestive represent

heart changes

failure of

in tend-

the

4

38

EFFECT OF COENZYME Q ON CONGESTIVE HEART FAILURE

Jap. Heart J. January, 1976

Vol.17 No.1

ISHIYAMA, ET AL.

39

40

EFFECT OF COENZYME Q ON CONGESTIVE HEART FAILURE

Fig.2

shows

ment.

changes

More

Changes

of

the of

observed

easily

by

Results cases, As

shown

in

the

1.7)

were

as

a whole

lower

dominant

signs.

was

"mildly

but

were

not

all

dominant of

than

those

side

severe.

treat-

of

urine. Fig.3.

exanthema

It

disappeared

heart

rate

subjects

the

in

the

all

7

2 cases. treatof

the

outpatients

deviation=3.6•} coenzyme

Q7

improvement

of

disappearance

peroral from

after

were

intravenous

showed

that

in

Changes

(mean•}standard of

found

were

remarkable.

(p

A clinical study of the effect of coenzyme Q on congestive heart failure.

A Clinical Study of the Effect of Coenzyme Q on Congestive Heart Failure Taro ISHIYAMA, TOYAMA, M.D., M.D.,* TSUKAMOTO, Yoshiharu Toru M.D.,**...
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