June, 1951]
V.
R.,
J.
O.
D.
AND
V.
I
103
Perfusion of isolated heart with ringer having no calcium produced diastolic
arrest in about a minute. A concentration of 1 in 1 million of gigantin in the ringer
as a substitute to calcium did not revive the heart when applied after the diastolic
arrest. Changing over to normal ringer, having calcium, at this stage however
had the desired effect.
When the heart returned to normal it was again perfused with ringer having
no calcium. As the heart was in half way towards the diastolic arrest the perfusion
fluid was changed over to ringer having 1 in million gigantin in the place of calcium.
The effect of the previous perfusion continued for a few seconds. Then the indivi-
dual beats greatly increased in the amplitude and the heart continued to work with
gigantin in the place of calcium in ringer for about 15 minutes (Plate XII).
Finally it was arrested in systole.
Thus gigantin may be said to synergesise the action of calcium but cannot
replace it in the perfusion fluid.
DISCUSSION
The effect of gigantin on the frog's heart appears to differ diametrically accord-
ing to the dose. The typical action of the drug is a complex of two different factors
namely slowing and increased contracture and is best observed when a minimum
lethal dose is applied to the heart. Most of the changes can be followed in the exposed
intact heart, but the details are best studied in the excised heart perfused with
ringer containing the drug.
The heart rate is often slowed under the action of gigantin in early stages,
more rarely accelerated or unchanged. This change in rate is not inhibitory in
nature and it affects the whole heart, so that it might arise from some change in the
activity of the pace maker. But the occasional intermissions of the ventricle and
the other disturbances in rhythm and the final arrest in diastole must arise from the
failure of efficient stimuli to reach the ventricle, -for the auricles continue to beat
at their previous rate when the ventricle is reduced in its rhythm. Similarly the
sinus preserves its rhythm at a later stage while the auricles beat at a reduced rhythm.
The impulses emitted by the pace maker of the heart in the sinus venosus thus fail
to arouse the auricle to contraction as at a previous stage the impulses which caused
beats in auricle were unable to arouse the ventricle. The auricle or the ventricle
in the absence of impulses to contract remain in the position of rest and intermissions
of the ventricle or of both auricle and ventricle occur and when a number of successive
impulses fail prolonged and final stand still results.
The failure of the conduction is first manifested in the auriculo-ventricular
connecting fibres, but later extends to the sino-auricular fibres, giving rise to auri-
cular intermissions and pauses of the same character as seen more frequently in
the ventricle. Finally the pace maker may be slowed and arrested.
The contracture, which culminates in the arrest in systole, is essentially in its
beginning an imperfect relaxation. Under physiological doses it is manifested by
the slowness of relaxations, in lethal doses by deficient diastole and in very large
toxic doses by the systolic arrest of the ventricle. The exact nature of contracture
is still a matter of question. It has nothing in common with normal contraction.
It has a nearer analogy in the prolonged contracture of voluntary muscle which is