Cardiac Muscle Problems 1

Problems

1) Digitalis is an extract of the foxglove plant. Foxglove extract has been used as a drug
for at least 700 years. It is used to counteract the effects of cardiac failure. In heart
failure, one or both ventricles are incapable of developing a normal contractile force
or of producing a normal stroke volume without an increase in end diastolic filling.
In such situations, digitalis type drugs, e.g. digoxin increases the inotropic state
(contractility) of heart muscle. It acts by inhibiting the Na+/K+ ATPase pump.

a) What effect will treatment with digoxin have on the distribution of ions across the
membrane of cardiac muscle cells.

b) The cardiac muscle membrane contains a secondary active transporter, a Na+/Ca+2

exchanger. This countertransporter is one of the mechanisms that maintains a low
cytosolic Ca+2 concentration during diastole. It uses the energy content in the trans-
sarcolemmal Na+ electrochemical gradient to transport 3 Na+ into the cell for each
Ca+2 it extrudes from the cell. Explain how the action of digitalis interacts with the
action of the transporter to increase the force of contraction of the myocardium.
Cardiac Muscle Problems 2

2. The following studies were carried out on two identical isolated rabbit hearts. The
ventricles were made to contract by electrical stimulation of the ventricular
conducting systems. The coronary arteries of heart 1 were perfused with normal,
untreated rabbit blood, thereby maintaining a normal Inotropic State (IS), whereas
those of heart 2 were perfused with blood containing a positive inotropic agent
creating a high Inotropic State (IS). In the description below, subscript "1" refers to
heart 1 and subscript "2" refers to heart 2.

Two experiments were carried out. In the first experiment, the ventricles of heart 1 and
heart 2 were filled to the same low end diastolic volume (low EDV), and stroke
volume (SV1 and SV2) were measured. See the conditions A and B in the table
below.

In the second experiment, the ventricles of both hearts were filled to an equal but greater
EDV (high EDV) than experiment 1. Again the stroke volumes were measured (SV1
and SV2). See conditions C and D in the table below.

Experiment 1 Experiment 2
Low EDV High EDV
Normal IS (heart 1) A C
High IS (heart 2) B D

Predict the following (greater; smaller; same)

a) the size of SV1 compared with SV2 in Experiment 1 (A versus B in the table).
______________

b) the size of SV1 with low EDV compared with SV1 with high EDV (A versus C in the
table). ________________

c) the size of SV2 with low EDV compared with SV2 with high EDV (B versus D in the
table) _________________

d) the change in SV1 when going from low EDV to high EDV (A to C in the table)
compared with the change in SV2 when going from low EDV to high EDV (B to D in
the table) ________________
Cardiac Muscle Problems 3

What is the cause of the difference you predicted in part a (above)?

What is the cause of the difference you predicted in parts b and c (above)?

What is the cause of the difference you predicted in part d (above)?