With their improved Langendorff heart, the researchers from Technische Universitaet Muenchen and Helmholtz Zentrum Muenchen have now for the first time developed a measurement setup that can be used to analyze the effects of nanoparticles on a complete, intact organ without being influenced by the reactions of other organs. Credit: Andreas Stampfl, courtesy of ACS |
In
light of the increasing demand for artificial nanoparticles in medicine
and industry, it is important for manufacturers to understand just how
these particles influence bodily functions and which mechanisms are at
play?questions to which there has been a dearth of knowledge. Studies on
heart patients have shown for decades that particulate matter has a
negative effect on the cardiovascular system. Yet, it remained unclear
whether the nanoparticles do their damage directly or indirectly, for
example through metabolic processes or inflammatory reactions. The
reactions of the body are simply too complex.
Using
a so-called Langendorff heart?an isolated rodent heart flushed with a
nutrient solution in place of blood?scientists from the Helmholtz
Zentrum Muenchen and the TU Muenchen were for the first time able to
show that nanoparticles have a clearly measurable effect on the heart.
When exposed to a series of commonly used artificial nanoparticles, the
heart reacted to certain types of particles with an increased heart
rate, cardiac arrhythmia and modified ECG values that are typical for
heart disease. “We use the heart as a detector,” explains Professor
Reinhard Nießner, Director of the Institute of Hydrochemistry at the TU
Muenchen. “In this way we can test whether specific nanoparticles have
an effect on the heart function. Such an option did not exist hitherto.”
Scientists
can also use this new model heart to shed light on the mechanism by
which the nanoparticles influence the heart rate. In order to do this,
they enhanced Langendorff’s experimental setup to allow the nutrient
solution to be fed back into the loop once it has flown through the
heart. This allows the scientists to enrich substances released by the
heart and understand the heart’s reaction to the nanoparticles.
According
to Stampfl and Nießner, it is very likely that the neurotransmitter
noradrenaline is responsible for the increased heart rate brought on by
nanoparticles. Noradrenaline is released by nerve endings in the inner
wall of the heart. It increases the heart rate and also plays an
important role in the central nervous system – a tip-off that
nanoparticles might also have a damaging effect there.
Stampfl
and his team used their heart model to test carbon black and titanium
dioxide nanoparticles, as well as spark-generated carbon, which serves
as a model for airborne pollutants stemming from diesel combustion. In
addition, silicon dioxide, different Aerosil silicas used e.g. as
thickening agents in cosmetics, and polystyrene were tested. Carbon
black, spark-generated carbon, titanium dioxide and silicon dioxide led
to an increase in the heart rate of up to 15 percent with altered ECG
values that did not normalize, even after the nanoparticle exposure was
ended. The Aerosil silicas and polystyrene did not show any effect on
the heart function.
This
new heart model may prove to be particularly useful in medical
research. Here, artificial nanoparticles are increasingly being deployed
as transportation vehicles. Their intrinsically large surfaces provide
ideal docking grounds for active agents. The nanoparticles then
transport the active agents to their destination in the human body, e.g.
a tumor. Most of the initial prototypes of such “nano containers” are
carbon or silicate based. So far, the effect of these substances on the
human body is largely unknown. The new heart model could thus serve as a
test organ to help select those particles types that do not affect the
heart in a negative way.
Artificial
nanoparticles are also used in many industrial products – some of them
since decades. Their small size and their large surfaces (compared to
their volume) impart these particles with unique characteristics. The
large surface area of titanium dioxide (TiO2), for example, leads to a
large refractive index that makes the substance appear brilliant white.
It is thus often used in white coating paints or as a UV blocker in
sunscreens. So-called carbon black is also a widely used nanoparticle
(mainly in car tires and plastics) with over 8 million tons produced
annually. The small size of these nanoparticles (they measure only 14
nanometers across) makes them well suited as dyes, e.g. in printers and
copying machines.
With
their enhanced Langendorff heart, the researchers have now for the
first time developed a measurement setup that can be used to analyze the
effects of nanoparticles on a complete, intact organ without being
influenced by the reactions of other organs. The heart is a particularly
good test object. “It has its own impulse generator, the sinus node,
enabling it to function outside the body for several hours,” Andreas
Stampfl, first author of the study, explains. “Additionally, changes in
the heart function can be clearly recognized using the heart rate and
ECG chart.”
“We
now have a model for a superior organ that can be used to test the
influence of artificial nanoparticles,” Nießner explains further. “The
next thing we want to do is to find out why some nanoparticles influence
the heart function, while others do not influence the heart at all.”
Both manufacturing process and shape may play an important role. Hence,
the scientists plan further studies to examine the surfaces of different
types of nanoparticles and their interactions with the cells of the
cardiac wall.
A Model System To Study Cardiovascular Effects of Engineered Nanoparticles