Made in United States of dmerica

Reprinted from MEDICAL ANNAM OF THE; DISTRICT OF COLUMBIA
          Vol. XX, Iio. G, June, 1951

VERATRUM VIRIDE AND HEXAMETHONIUM IN
THE TREATMENT OF SEVERE DIASTOLIC
HYPERTENSION*tl

e URING the past year we have
been studying the effects of an intensive treat-
ment program in a group of severe hyperten-
sive patients who could be followed closely for
prolonged periods. These patients were made
available through the cocperation of Georgetown
University, Mount Alto and Gallinger Municipal
Hospitals, our own outpatient clinic at George-
town University Hospital, and by referral of
private patients by interested practicing physi-
cians. ,411 of the patients in this study have been
selected on the basis of severity and almost all
have been hospitalized for a period of preliminary
observation and for institution of therapy. The
majority of cases exhibited elevations of dias-

*This investigation was suplvxted in part by research
grants from the Kational Heart Institute of the National In-
stitutes of Health, Public Health Service, The Squibb Ins&
tute for Medical Research, and Irwin Neisler and Coml)any.
t Delivered at the Twenty-first Annual Scientific Assembly
of the Medical Society of the District of Columl)ia, Octolxr
4, 1950.

$ The portion of this article on Veratrum viride was sub
mitted for publication, October 31, 1950; that on hexametho-
nium, May 3, 1951.

tolic pressure persistently above 120 mm. of Hg
even at hospital bed rest.

The reasons for making such a selection are
that these severe cases represent the most urgent
treatment problem, whereas patients with the
more benign forms of the disease may and usually
do live for many years without complications,
and that, since in a high percentage of the severe
cases death occurs within 5 years, it is easier to
evaluate not only hypotcnsive responses but also
success in preventing mortality.

VERATRUM VIKIDE

The plan of management has been as follows:
The patients who did not respond after a pre-
liminary period of observation with conservative
treatment such as rest, reassurance and seda-
tion, were given either Anatensol or Veriloid
(purified extracts of Veratrum viride in tablet
form) or a low sodium diet or both. If this therapy
was successful it was further evaluated by the use
of alternating placebo and treatment periods. If
unsuccessful, sympathectomy has been carried

297


298      Veratrunz Viride and Hexavaethoniunz for Hypertcnsiofz-Freis

JUNE, 19.51

out in a few instances. In short, every effort has
been made, using all the practical procedures at
our disposal, to reduce the blood pressure to a
more benign range.

I shall summarize several cases of scvcrc hy-
pertension so treated in order to indicate the
manner in which therapy has been carried out
and some of the results obtained thus far. The
first is a 60-year-old man who entered the hospital
because of increasing fatigue and mental con-
fusion. The blood pressure averaged 220/140
during 5 days of rest in bed in the hospital
(figure 1). The fundi revealed hemorrhages, exu-
dates and definite papilledema of over 1 diopter.

     180,
LVERAQE

DISCNAAQED        HOSPITAL
FROM HOSPITAL      READMISSION

0 I2 3 4 S 6? S 9
          MONTHS

FIG. 1. Chart of the average arterial ~~rcssurc (supine) and
dosage of Anatcnsol of patient, L. IX., a man aged 61 years.
The recorded levels of arterial ~~rcssure represent averages of
many individual readings for each Imid. See text for further
details.

Renal function was impaired and the blood non-
protein nitrogen was 50 mg. per cent. The patient
was placed on a regular diet without salt shaker
andwas given Anatensol," an extract of Veratrum
viridc in rapidly increasing doses, which was fol-
lowed by a fall in arterial pressure to 190/120.
Nausea and vomiting clue to the Anatensol were
frequent, and the dosage had to be juggled con-
siderably. Differences in doses of as little as 2 of

* A product of The Squibb Institute for Medical Kcsearch,
New York. N. V.

a tablet at times resulted in the difference be-
tween toxic vomiting and therapeutic effects.
However, despite the frequency of nausea and
vomiting the patient slowly improved, and within
a month the papilledema had cleared and the
l~loocl nonprotein nitrogen was reduced to 40 mg.
per cent.

There are several points worthy of note in this
case. One is the long period of hospitalization
lasting 3 months. This was necessitated by the
continuously changing dosage rccluirements as
judged by blood pressure changes and toxic re-
actions. These blood pressure recordings are aver-
ages of many readings. The actual pressures
taken on the ward showed great fluctuation, hence
requiring constantly changing minor dosage ad-
justments. The other point is the response to
placebos. It is only by giving placebos under
hospital observation that one can accurately
judge the effect of the drug, and it is only in
such severe cases that one can observe such a
prompt and definite rise when placebos arc given.
After discharge from the hospital the patient has
continued to improve very slowly. He has been
forced to retire from work but is ambulatory and
symptom-free. In fact, he has just returned from
a month's vacation trip to northern Michigan.
Episodes of nausea and vomiting due to the
Anatensol are now infrequent, occurring about
once or twice per month. 1 am quite certain that
without frequent and close observation of the
patient's response, constant readjustment of dos-
age in the first 3 months, persistence, and a ccr-
tain degree of confidence in the treatment
therapy with Anatensol would have long since
been given up as a failure.

The next case (figure 2) is an example of the
effectiveness of combining the 200 mg. sodium
diet and vcratrum extracts. This is a 32-year-old
Negro taxi driver who entered the hospital be-
cause oi headache, blurred vision, and easy fati-
gability. The blood pressure on admission was
2SO/lSO mm. Hg but fell after admission to 180/
120 mm. Hg under the influence of hospital bed
rest. The optic fundi exhibited marked arteriolar


VOL. XX, NO. 6      Medical Annals of the District of Columbia

299

spasm with hemorrhages and exudates, but no
papilledema. The heart size was normal, and
renal function was good. The patient was given
Veriloid," and when the dosage was increased to
3 mg. 4 times per day the blood pressure fell
promptly to 140/90. He was discharged from the

       i 4 ;2 3 4 5 6 7 8   9
        WEEKS              MCNTHS  "i
Fx. 2. Chart of arterial pressure (supine) and treatment
of patient, R. C.. a 31-year-old Negro. N. & V. signifies
nausea and vomiting. See text for details.

hospital and returned to work but was seen daily
in order to check his blood pressure and to ques-
tion him concerning the development of toxic
side-effects. He continued to do well despite re-
turn to full-time active employment as a taxi
driver. When a placebo was given, there was a
prompt rise in blood pressure with return of
headache. It is important to point out that treat-
ment with Veriloid would have been called a
failure at the third month when it became im-
possible to regulate dosage without frequent at-
tacks of nausea and vomiting. On the other hand,
when diet was added the veratrum appeared to
contribute to the effectiveness of the diet as can
be noted by the moderate rise that occurred
when the placebo was again substituted. He has
been followed now for a total of 14 months, and
his last blood pressure was 110/80. He has had
no toxic reactions for the past 6 months.

This synergism of diet plus drug treatment
seems to be an important general principle in the
management of severe hypertension. In the un-

* -4 product of liiker Latmratclries, Los Angeles, Calif.

usual case, such as the first case described, vera-
trum alone appeared to maintain the patient's
blood pressure in the benign range. In a greater
percentage diet plus veratrum is essential to
achieve this purpose, and in still others sympa-
thectomy plus diet plus all that various types
of drug treatment have to offer must be used
together.

The next case illustrates the latter type of
case in which every type of treatment was ap-
plied in combination (figure 3). The patient is a
2%year-old Negro government clerk. Renal and
cardiac function were still good, and the fundi
were only grade II. The blood pressure was re-
markably fixed at a high level of 240,/140 mm.
Hg despite hospital rest and a rice diet followed
by the low sodium diet. There was no response

I     I. ,  2  3  4  s  6  7  s ". s IO  II  12  13
                      MONTHS

FIG. 3. Chart of the average arterial pressure (supine) and
treatment of patient, H. F., a Negro aged 28 years. In each
period the recorded level of arterial pressure represents the
average of many readings. See text for further details.

to a trial of Veriloid, but an unusual and striking
response to Priscoline by mouth 50 mg. 4 times
per day. However, the response did not continue,
and after a month tolerance to the drug became
almost complete. A transthoracic sympathec-
tomy was then performed with a good reduction
in blood pressure, which again was not sustained.
We again tried a low sodium diet and Veriloid
with a good fall in arterial pressure, which also
was only temporary.


300

Vera,trum Viride and Hexamethonium for Hypertension-Fveis    JUNE, 19.51

It then occurred to us that, since this patient
exhibited satisfactory responses to both Veriloid
and Priscoline for short periods and then ex-
hibited tolerance to these drugs, we might fore-
stall the development of tolerance by alternating
the drugs at weekly intervals. Instead of Pris-
coline, we used a very similar drug called Regi-
tine or C-7337. With this regimen tolerance did
not develop and the average blood pressure dur-
ing this period remained reduced. The patient
has returned to work and is completely asymp-
tomatic. The diet was discontinued for several
weeks with moderate elevation of blood pressure
levels, but more striking was the disappearance
of postural hypotension. I have noted in several
instances that patients who have had sympa-
thectomies in years past frequently will exhibit a
return of postural hypotension when salt is
adequately restricted. When placebos were given
in this case the general level of diastolic pressure
returned to the original values but fell again to
the treatment levels on resuming the alternating
drug therapy.

In a series such as this it is always impressive
to describe several of the more striking cases, but
such a portrayal fails to give a true picture of the
success of the treatment in the group as a whole.
Since this study has been in progress for only a
year the data are still in the process of being col-
lected. Nevertheless, I am able to indicate in a
rough way the results obtained to date at least
in the patients given Anatensol. one of the es-
tracts of Vcratrum viride.

It should be remembered that these results
pertain only to severe hypertensives. All in this
group had diastolic pressures of 120 mm. Hg or
greater even after 48 hours of rest in bed in the
hospital. X11 had grade II to grade IV hyperten-
sive changes in the fundi and 7 exhibited grade
IV optic funtli, that is, malignant hypertension.
In this entire group approximately half also are
presumed to be taking the 200 mg. low sodium
diet. Of this number, however, only 20 per cent
are following their diet as judged by the excretion
of urine chloride. None are on the rice diet. Two

have had sympathectomies. I have avoided the
use of the classification of excellent result since
in no case has the blood pressure been reduced
to normal and maintained there for a prolonged
period. The duration of observation varies be-
tween 3 and 14 months, with an average duration
of 8 months. A4 good result signifies that the av-
erage diastolic pressure has been reduced 20 mm.
Hg or more as compared to pretreatment hospi-
tal blood pressures and that there has been symp
tomatic relief as well as some objective improve-
ment either in the fundi, the heart size, or renal
function. It also signifies that as judged by the
use of placebo the greater part of this improve-
ment was due to the Anatcnsol.

`There are 32 patients in this group, of which
10 may be classiticd as a good result ant1 1 as a
fair result. In addition there are 6 who had a good
or fair result which was not sustained. However,
1 of these latter patients have exhibited a good
result when Veriloid was substituted for .-\na-
tcnsol. Four patients cannot be classified because
they failed to return for a follow-up, and X arc
judged complete failures. In general, the failures
were due to an inability to regulate dosage with-
out frequent toxic effects.

;\lthough Veriloid seems to be the best of the
veratrum extracts thus far produced, all of the
veratrum derivatives including Veriloid are no-
toriously difficult to regulate over long periods
of time. The reasons for this are as follows:

1. Varying dosage requirements in different
patients necessitating ind'vidual adjustment in
each case. One adjusts the dosage of Veriloid in
much the same fashion as one would adjust the
dose of insulin in a diabetic; that is, he regulates
dosage by observing the response.

2. Varying sensitivity of the patient to a given
dose. I>uring therapy with veratrum there is con-
siderable fluctuation in blood pressure from day
to day although the average may be lower. In
some of our most severe cases it has been neccs-
sary for a member of the family to check the
blood pressure before each dose of the drug and
regulate the dose up or down slightly according
to the reading obtained.


VOL. XX, NO. 6     Medical Annals of the District of Columbia

301

3. Narrow margin between the dose which
lowers blood pressure and that which produces
side-effects. This is the most serious limiting fac-
tor of all. As a result side-effects are to be ex-
pected rather frequently in the adjustment
period and occasionally thereafter. As with any
potent drug which can produce toxic effects, the
physician must decide between the advantages
to be gained by treatment as weighed against
the disadvantages and annoyances of frequent
reactions. It is for this reason that T do not think
the use of veratrum is justified in any but the
most severe types of hypertension.

E'ar better results with fewer severe reactions
have been obtained when the dosage has been
regulated in hospitalized patients, and for this
reason I have just about abandoned the idea of
attempting to begin treatment with Veriloid as
an outpatient or office procedure.

The method of adjusting dosage which has
been found to be most successful is as follows:
The patient is hospitalized for at least 1X hours
prior to beginning therapy. The blood pressure
is recorded 4 times per day in order to obtain a
pretreatment baseline. Quite frecluently in the
hospital the blood pressure will fall to the benign
range prior to treatment. Such patients are
treated preferably symptomatically with seda-
tion, rest periods, and reassurance. However, if
the diastolic pressure remains elevated, treat-
ment is begun with a dose of 2 mg. of Veriloid 1
times per day after each of 3 widely spaced meals
and at midnight. The aim is to keep the interval
between doses as close to 6 hours as possible.
The purpose of this is to permit 1 dose to become
effective as the other is losing its effect. If the
doses are too far apart the blood pressure may
rise between doses, and if they are too close to-
gether severe toxic reactions may occur due to
overlapping of 1 dose on the other.

The blood pressure is recorded just before each
dose and 2 hours after each dose except after the
midnight medication. At the end of 48 hours the
blood pressure chart is inspected and the patient
cluestioned about the appearance of side-effects.

The earliest common side-effects are epigastric or
substernal burning sensation, epigastric fullness,
and increased salivation. When these symptoms
occur no further increase in dosage is undertaken
for an additional 48 hours.

If there are no side-effects and no change in
the blood pressure, the dose is increased to 3? 2,
2, and 3 mg. Tf this is ineffective at the end of
an additional 48 hours, all of the doses are in-
creased to 3 mg. In this way one gradually ap-
proaches the therapeutic dose, which usually
varies between 3 and 4 mg. 4 times per day, that
is, a total dose of 12 to 16 mg. per day, which
may be higher or lower in individual cases. By
this gradual increase toxic effects, while not com-
pletely avoided, are at least minimized.

After a therapeutic dose has been reached
there frequently are mild side-effects in addition
to a perceptible drop in blood pressure. I>uring
the ensuing weeks apparently a certain degree of
cumulation occurs! since not infrequently nausea
and vomiting or varying degrees of severe hypo-
tension occur in the second to the fourth weeks of
treatment.

Severe reactions are very alarming to both the
physician and the patient. The nausea comes in
waves for several hours and is accompanied bq
violent retching. A period of extreme hypotension
and hradycardia may accompany this. Occasion-
ally patients have lost consciousness for several
minutes. This violent reaction has been mistaken
for a coronary occlusion by those unfamiliar
with the drug. When such a reaction occurs the
patient should be given atropine 0.9 mg. (1,,`75th
grain) intravenously, and if hypotension con-
tinues he may be given ephedrine 50 mg. intra-
muscularly. It is remarkable that despite these
profound reactions no death or permanent disa-
bility has resulted. However, in advanced uremia
extreme hypotension and vomiting may hasten
the end. T:or this reason I no longer use veratrum
or its derivatives when the blood nonprotein
nitrogen is greater than 70 mg. per cent. The
patient is told that when a reaction occurs he is
to omit the next dose on that day only and on


302      Veratrum Viride and Hexamethonium joy Hypertension-Freis

JUNE, 1951

succeeding days to reduce the offending dose by
no more than a half-tablet amount. Nausea and
vomiting may occur after other doses also, and
in each case the offending dose should be reduced
by a half-tablet amount. Occasionally nausea and
vomiting may be due to the failure to take the
tablets at the specified times and are taken too
closely together. Therefore, it is well to inquire
as to whether the meals are widely spaced and
the tablets taken at the specified times.

-After several months of treatment when the
patient has apparently been satisfactorily regu-
lated, the blood pressure reading may be higher
than previously. It is well to remember that the
blood pressure may fluctuate considerably on
Veriloid therapy, and it is worthwhile to see the
patient several times before changing the dose.
Tf the arterial pressure remains high, one may
cautiously raise the morning or the midnight dose
by 0.5 mg. If there are no toxic effects, another
of the doses may be raised by a similar small in-
crement. This procedure is continued until the
blood pressure falls or the patient develops toxic
effects. If on this second trial nausea and vomit-
ing occur without a fall in blood pressure, only
then is one justified in considering the treatment
a failure. Of course, in malignant hypertensives
periodic reactions seem justified in view of the
serious nature of the illness, if at the same time
the blood pressure is maintained at a lower level.

In case of failure with veratrum alone it has
been my policy to place the patient on a low
sodium diet. This diet contains 200 mg. of so-
dium per day. It is very important either to omit
milk completely since its sodium concentration
is high or to use Lonalac, a salt-free milk powder
which must be flavored with cocoa or powdered
coffee to make it palatable. In addition salt-free
bread which is available in many special food
stores and unsalted butter must be used. Printed
lists of this diet are available to interested phy-
sicians from the Mead Johnson Company. It has
been my experience that the so-called salt-free
diet prescribed in most hospitals is entirely in-
adequate for the purpose, since the sodium con-
tent is not sufficiently restricted.

Finally and most important is to determine the
chloride content of the urine at regular intervals.
This value should be at least below 0.6 Gm. of
sodium chloride per liter of urine. If it is above
this, the patient is not following the diet. In this
series more than 7.5 per cent of patients treated
failed to follow the diet as judged by the salt ex-
cretion in the urine, although all avowed they
were living up to it faithfully. When confronted
with the evidence that they were not keeping to
the prescribed regimen a certain number returned
to a fairly satisfactory salt-restricted diet. Be-
cause of this foible of human nature it is oh-
vious that unless the urinary chloride excretion
is followed during treatment with low-salt diets
the physician is truly working in the dark.

If the 200 mg. sodium diet does not produce a
satisfactory response, Veriloid may be tried again
in conjunction with the diet, and it is surprising
how effective these therapeutic regimens are
when used together. During salt restriction many
patients can be maintained on doses of Veriloid
or Anatensol which are below the toxic level. In
short, there appears to be a synergism between
these methods of therapy in many patients.

If this combination treatment fails and if the
patient is below the age of 50 with fairly good
renal function I have resorted to sympathec-
tomy. Csually in such severe cases the operation
is inadequate in itself, but reinstitution of medi-
cal therapy following sympathectomy has in
some instances produced a satisfactory, persist-
ent, hypotensive response.

The so-called hypertensive "crisis" is a sudden
and severe elevation of blood pressure associated
frequently with acute hypertensive encephalop-
athy and can be fatal. It is best treated in the
hospital. A very satisfactory method of treating
this condition has been to administer immedi-
ately 3 mg. of Veriloid followed by 1 mg. every
hour until the blood pressure begins to fall. Csu-
ally a total of 4 to 7 mg. is required to produce a
hypotensive response. This may be repeated as
often as is necessary on succeeding days, or,
better still, the patient may be regulated on a
maintenance dose of the drug.


VOL. XX, NO. 6

Medical Amals of the District of Columbia

303

HEXAMETHONIUM

During the past 6 months we have been study-
ing the effects of the new ganglionic blocking
agent, hexamethonium or C6," in hypertension.
Properly administered, this agent has produced
significant and sustained reductions of arterial
pressure in almost all hypertensive patients
whom we have studied. In a series of 15 patients
with malignant hypertension a remission of the
malignant phase has occurred in 11 cases. The 4
patients who have not responded have all had
advanced renal failure with uremia. Although
hypotension was produced in these cases the
uremia progressed and 3 have died. In less severe
degrees of hypertension results have been almost
uniformly satisfactory in that marked reductions
of blood pressure have been produced.

the levels of blood pressure throughout the 12-
hour period remained lower than pre-treatment
values. However, in the more severe cases the
blood pressure levels fluctuated markedly over
the 12-hour period between doses, from normal
or nearly normal blood pressure values 1 hour
after each dose to markedly hypertensive values
immediately before each dose. Many of these pa-
tients could be controlled by administered L-
hydrazinophthalozine (C-5968)i in doses of 50
to 150 mg. orally midway between doses of C6.
In a few patients it was possible to maintain a
satisfactory reduction of blood pressure by ad-
ministering C6 at X-hour instead of 12-hour in-
tervals.

It must be emphasized, however, that the drug
was given by subcutaneous injection twice per
day. It was also apparent that certain precau-
tions, additions, and modifications in the treat-
ment regimen are essential to obtain satisfactory
results.

It was observed that whereas the hypotensive
response to the initial dose of C6 may be pro-
found, "tolerance" developed rapidly when the
dosages were repeated at such frequent intervals
as every 1 or 6 hours. However, when doses were
separated by 12-hour intervals the development
of tolerance was largely prevented. If under these
circumstances the drug became ineffective, the
hypotensive action could be restored by increas-
ing the dosage. The average initial dose was 10
mg. of the ion, but after several weeks of con-
tinuous therapy the average effective dose was
35 mg. of the ion.

Like all agents which block transmission
through the sympathetic nervous system C6 in-
duces a marked postural hypotcnsion. After the
initial injection of the drug patients may faint
on arising for as long as 3 hours after the drug
has been administered. However, with continued
administration of the drug the postural hypo-
tension, although still marked, becomes no longer
profound. Hence, after the first week of treat-
ment the majority of patients can assume the
upright position without postural giddiness 1
hour after the drug has been given and many can
arise immediately. Since the night dose is given
at bedtime, only the morning injection produces
temporary physical incapacity in some patients.

The duration of action of each dose varied
between 4 and 12 hours or even longer. In general
the postural hypotension outlasted the reduction
in supine pressure, but in many patients the dis-
ease appeared to be modified while under con-
tinuous therapy in that with return to activity

Since hexamethonium also produces parasym-
pathetic blockade, certain side-effects have arisen
due to this action of the drug. The most common
have been dry mouth due to reduction in the
secretion of the salivary glands and constipation
due to atony of the gastrointestinal tract. The
most serious reactions have been paralytic ileus
and inability to micturate. All of these side-
effects can be overcome by the concurrent ad-
ministration of the urethane of acetyl-methyl-
choline (Urecholine) in doses of 10 mg. under
the tongue 3 times per day, Moderate constipa-
tion may persist in some patients despite the use

* Ristrium obtained from The Squibb Institute for Medical    t .4 product of CIRA Pharmaceutical Products, Inc.,
Research, New York? N. Y.                  Summit, N. J.


304

Veratrum Viride and Hexamethonium for Hypertension-Fveis    JUNE, 1951

of Urecholine, but the constipation can be man-
aged by mild laxatives.

Just as sodium restriction increases the hypo-
tensive effect of other drugs, a diet low in sodium
will increase the patient's responsiveness to C6.
Hence, in occasional resistant cases sodium re-
striction has been used in addition.

Because of the marked hypotension produced
by the initial injection of C6 certain precautions
must be observed in beginning dosage adminis-
tration. Severe hypotensive reactions have been
avoided since we have utilized the following
technic for beginning therapy: With the patient
propped up slightly in bed, C6 is injected intra-
venously at a rate of I to 2 mg. of the ion per
minute. An assistant determines the blood pres-
sure at intervals of 30 seconds in the opposite
arm. As soon as a significant reduction of blood
pressure occurs the injection is halted tempo-
rarily until the blood pressure becomes stabi-
lized. If the degree of hypotension is satisfactory,
the injection is stopped; if not, the slow rate of
administration is begun again and continued un-
til the desired result is obtained. If, despite these
precautions, the reduction of blood pressure is
excessive, it may be easily corrected by raising
the foot of the bed on 6-inch or X-inch blocks and
elevating and passively exercising the lower ex-
tremities. Vasopressor agents, especially epineph-
rine, are unpredictable, and impressed LIS as
being dangerous.

Having determined the initial effective dose,
this amount is administered subcutaneously at
12-hour intervals. A\t the end of 38 hours it is
usually necessary to increase the dosages by 5 to
IO mg. and continue to increase them until the
patient exhibits a sustained response.

`The early results obtained with oral admin-
istration have been disappointing. Large doses
are required, and there has been some evidence
of cumulation as well as of tolerance. In addi-
tion, the bromide and iodide salts of hexa-
methonium are unsuitable for oral use, since the
large doses required lead to toxic levels of these
halides in the circulation. However, it may well
be that a suitable dosage schedule using less toxic

salts of C6 may be evolved with furthe; experi-
mentation. Preliminary evidence suggests that
doses of 0.5 to 1.0 Gm. of C6 ion administered
at bedtime every 24 hours (one dose per day)
may produce satisfactory results. In addition,
the bitartrate, dichloride or citrate salts of C6
may be used instead of the bromide or iodide salts.
In our experience of the past 6 months no form
of treatment of essential hypertension has so
profoundly altered the levels of blood pressure in
such a large percentage of hypertensive patients
as has the use of hexamethonium. Patients have
been taught to administer their own injections
and even record their blood pressures in the
home. Many patients have returned to their
usual occupations and because of the postural
hypotension seem to be protected from blood
pressure elevations due to physical and emo-
tional stress.

It is possible by improper administration of
C6 to obtain poor therapeutic results and dan-
gerous toxic reactions; and, indeed, our early
experiences with this agent wcrc' disappointing
because of improper dosage administration.
ITurthcr experience with this and other similar
agents should bring additional improvements in
the case of administration and circumvention of
side-effects. There is every reason to believe,
however, that the chemotherapy of essential
hypertension has been greatly improved by the
introduction of hexamethonium.

In conclusion, these experiments in therapy
are interesting, but it should be emphasized that
they are not of proven long-term value. The
reduction of blood pressure by any of the
methods employed, whether by surgery, diet or
the presently available hypotensive agents, ap-
parently is nonspecific. Whether or not such non-
specific reduction of blood pressure actually will
prolong life in these severe cases only time and
continued observation can tell. It would be a mis-
take, therefore, to assume on the basis of our
present knowledge that mere reduction of blood
pressure is proof that our treatments actually
delay the progression of the disease.