102
ACTION OF GIGANTIN ON THE AMPHIBIAN HEART
[Vol. XXI, Part II,
On repeating the dose for the third time the irregularity and the block not only
increased in the intensity but also extended to the sino-auricular conducting fibres,
resulting in the three parts of the heart the sinus, auricle and ventricle taking their
independent rhythms. It recovered gradually but took about 10 minutes to gain
normal rhythm.
It may be inferred from the above experiment that the returning of the normal
rhythm after a dose of gigantin is not an indication of the complete elimination of
the drug from the body. There is a certain amount which is left over in the system
which takes a longer time for complete excretion. When the drug is repeated within
a short interval, though in the same dose, it combines with the drug already existing
in the body and produces a cumulative effect which resembles a toxic dose.
Isolated hearts perfused continuously with 1 in 5 million of gigantin in the
ringer produced a slowing of the rate and increased amplitude. After an hour the
perfusion fluid was changed to normal ringer. The heart however did not return
to normal as expected even after a considerable time. This may probably be due
to the absorption and fixation of the drug in the heart muscle.
Perfusion of isolated frog's heart with 1 cc of ringer containing 1 in 100,000
of gigantin produced no appreciable change, except an increase in the amplitude
of the beats. The use of normal ringer immediately after this took about 9 minutes
to bring back the heart to normal rhythm, showing that the drug got fixed in the
muscle and could be removed only by prolonged perfusion with normal ringer.
After 9 minutes when the heart had apparently returned to normality it was
again perfused with 1 cc of ringer having gigantin in the same concentration as
above and subsequently followed by normal ringer. The heart behaved differently
from the above experiment. The contracture was observed prominently by the
progressive slowness of relaxations, thus resembling the effects of a toxic dose.
The heart returned to normal only after a prolonged perfusion with normal ringer
for an hour.
Perfusion for the third time with 1 cc of ringer having gigantin as in the pre-
vious case and followed by normal ringer subsequently, not only produced more
toxic symptoms as increased contracture but also produced auriculo-ventricular
block and it took about one hour and a half for the heart to return to normal.
A further dose arrested the heart in two minutes, in partial systole.
This only indicates that the drug gets fixed in the heart muscle.
Relation of calcium to gigantin—An isolated heart was perfused with Ringer
containing 0.001 per cent calcium which is less than the normal amount. The
contractions were weaker whereas there taxations were normal. It was subse-
quently perfused with normal ringer and brought back to normal rhythm.
After about two minutes it was perfused with ringer containing 0.001 per cent of
calcium and in. addition 1 in 1 million cencentration of gigantin to make up the
deficiency of the calcium salt. It was found that after some time the strength
of contractions improved as shown by the increase in the systolic level of the
beats,