Phill Rasnick

Nathan Garvin
Section 008
3/27/2013
The Inotropic and Chronotropic Effect of Various Substances on the Heart
Method
Class protocol was followed to administer various substances on the heart and observe the
resulting inotropic and chronotropic effects.
Results
Table 1: The Inotropic and Chronotropic Effect of Various Substances on the Heart
Drug Inotropic Effect Chronotropic Effect
Caffeine + none
Epinephrine + none
Nicotine - -
Table 1 shows the inotropic and chronotropic effect of caffeine, epinephrine, and nicotine on the heart.
According to the data, both caffeine and epinephrine showed a positive inotropic effect with no
chronotropic effect, while nicotine showed both a negative inotropic and chronotropic effect.

As can be seen in the table above, both caffeine and epinephrine had a positive inotropic effect on
the heart without any noticeable chronotropic effect. However, it was observed that the inotropic effect of
epinephrine was slightly greater in comparison to the effect observed with testing caffeine. Additionally
nicotine showed to have a negative inotropic and chronotropic effect.
Discussion
Cardiac output, which is dependent on both the rate and strength of contraction, is controlled in
part by autonomic innervation. Factors affecting the rate of contraction are said to have a chronotropic
effect, while factors affecting the contractility of the heart have an inotropic effect. The heart rate is
initiated by autorhythmic cells in the SA node, however, these pacemaker cells are influenced under
antagonistic control between the parasympathetic and sympathetic autonomic nervous systems.
The sympathetic system, responsible for the fight or flight response, increases heart rate by
releasing catecholamines onto 1- androgenic receptors on the SA node. As a response to this androgen
binding, a cAMP second messenger cascade results, which alters the conformation of Ca
2+
and If channels
allowing for increased Ca
2+
and Na
+
permeability. Increasing permeability of these cations depolarizes
the cells of the SA node enabling them to reach threshold quicker resulting in more rapid contractions.
The influx of Ca
2+
ions is also important for the contraction of heart muscle because it binds to troponin
which alters the conformation of tropomyosin. This reveals the active sites on G-actin filaments thus
enabling cross bridge formation between actin filaments and myosin heads. In addition to the opening of
ion channels, the resulting cAMP cascade from activated androgen receptors results in the activation of
protein kinase A and phosphorylation of the protein phospholamban. Phospholamban enhances Ca
2+
-
ATPase activity which concentrates more Ca
2+
into the sarcoplasmic reticulum increasing the Ca
2+
levels
availably for calcium dependent calcium release. Because force of contraction is proportional to the
number of cross bridges formed, and the number of cross bridges formed is proportional to the amount of
Ca
2+
released into the cytoplasm, the result of this there is an increase in contraction strength in addition
to the increase in heart rate associated with sympathetic innervation on the SA node.
Because epinephrine is a catecholamine and the 1- androgenic receptor is equally sensitive to
both epinephrine and norepinephrine, it is expected that introduction of this neurotransmitter onto the
heart should result in a positive chronotropic and inotropic effect. The collected data, however, was weak,
showing only a slight positive inotropic effect without any effect on chronotropic activity. The weak
results could be due to weakening of the heart taking place over the course of the experiment. Prior to the
testing of epinephrine, acetylcholine was also tested, resulting in complete shutdown of the heart. While
use of atropine and epinephrine eventually brought the heart back to normal rhythm, the stress caused by
this situation may have weakened the heart enough to cause the weak results observed. Additionally, the
use of epinephrine to bring the heart rate up to resting rate prior to epinephrine testing could have
desensitized the 1 receptors also causing weakened results. Like epinephrine, caffeine increases the
levels of cAMP in the autorhythmic cells of the SA node. Instead of causing a cAMP second messenger
cascade, however, caffeine acts as a competitive inhibitor to the enzyme cAMP phosphodiesterase which
breaks down cAMP. As a result caffeine should have a similar but lessened effect compared to
epinephrine. Because the heart rate is under tonic control by the parasympathetic system and because
there was no sympathetic innervation occurring, there could have been low levels of cAMP in the SA
node cells at the beginning of the experiment. As a result, the addition of the cAMP phosphodiesterase
inhibitor would not have as strong an effect on cAMP levels as the addition of catecholamines would
have which could result in the weak results observed during the experiment.
Opposing the effect of the sympathetic system, the parasympathetic system is responsible for
slowing heart rate. The sympathetic system affects the heart by releasing acetylcholine onto muscarinic
receptors within the SA node. These G protein-coupled receptors initiate a second messenger cascade
which affects the opening of K
+
and Ca
2+
ion channels. As a result, K
+
influx increases and hyperpolarizes
the cell while Ca
2+
influx decreases. This results in longer times for the pacemaker cells to reach threshold
and also decreases the calcium available in the intracellular fluid causing negative chronotropic and
inotropic effects.
Because nicotine affects the nicotinic cholinergic receptors in the ganglia of both sympathetic and
parasympathetic autonomic systems, the addition of nicotine could have either a positive or negative
effect on chronotropic and inotropic activity depending on the location of nicotine introduction. While
ganglia of the sympathetic nervous system are located closer to the central nervous system, ganglia of the
parasympathetic system are located close to the affected organs. As a result, introducing nicotine to only
the heart would impact the nicotinic receptors of the parasympathetic system only, resulting in the
negative chronotropic and inotropic effects observed.
While the experimental results did show the general effect of various substances on the
contractility and rate of contraction of the heart, the results were not as strong as they could have been due
to possible issues previously stated. To better test the effects of these substances on cardiac output, it may
be beneficial to test them individually using multiple organisms rather than applying the drugs one after
another.

References
Factors Influencing Cardiac Activity Lab Manual, PSU, Biol 473 Laboratory Sp 2013
Silverthorn, Dee. Human Physiology an Integrated Approach. 6 ed. Glenview, IL: Pearson,
2013. Print.