Influence of remote ischemic preconditioning on cardiac function after endurance exercise

Increased levels of cardiac troponins (cTn) are the biochemical gold standard
to diagnose acute myocardial infarction (AMI). However, release of cTn into the
circulation is not restricted to AMI, as cTn elevations are also frequently
observed in athletes during and after endurance exercise. Since it is
well-accepted that regular exercise training is part of a healthy lifestyle, it
seems counterintuitive to ascribe exercise-induced cTn elevations to cardiac
necrosis that characterizes AMI. Several clinical studies challenge the
traditional interpretation of cTn as a *threshold* effect; and propose that cTn
release is rather a physiological continuum from ischemia to infarction. Due to
the rapid rise and fall of cTn in the first hours after exercise, as well as
the possible presence of a cytosolic unbound cTn fraction in the cardiomyocyte
(estimated 5% to 8%), exercise-induced cTn release may be consistent with the
release of the cytosolic cTn pool (reversible damage) rather than the breakdown
of the contractile apparatus (irreversible damage). The hypothesis of
reversible cell damage is supported by the absence of late gadolinium
enhancement on cardiac MRI in endurance athletes, a measurement for cardiac
fibrosis.

Besides biochemical changes observed after endurance-type exercise, acute
impairment in cardiac function has been observed as well. While early studies
showed that intense endurance exercise causes acute left ventricular
dysfunction, recent studies demonstrate an acute temporary alteration in right
ventricular function. This right ventricular impairment is, in contrast to the
left ventricle, strongly associated with post-exercise cTn concentrations. This
suggests that right ventricular functional impairment and biochemical cardiac
alterations seen after endurance exercise may be causally related.

Remote ischemic preconditioning (RIPC) represents a unique technique to gain
more insight into the role of ischemia in exercise-induced functional and
biochemical cardiac changes. RIPC is a non-invasive therapeutic intervention in
which brief ischemia of one tissue or organ protects remote organs from an
extended episode of ischemia-reperfusion. RIPC describes the practice of
applying short cycles of 5 min ischemia in the arm, followed by 5 min
reperfusion and has been shown to provide systemic protection during subsequent
ischemic events. Thus far, RIPC has been shown to reduce cardiac damage in
adults undergoing cardiac and vascular surgery.

Our working hypothesis is that functional and biochemical cardiac alterations
seen after endurance exercise are caused by an oxygen demand-supply imbalance,
which can be reduced by ischemic preconditioning. Therefore, this study aims to
investigate the effect of RIPC (by applying short cycles of ischemia and
reperfusion induced by a blood pressure cuff) on cTn elevations and temporary
alterations in right ventricular function induced by a 30 km run in healthy
trained long distance runners.

To examine the effect of remote ischemic preconditioning on exercise-induced
cTn elevations and indices of cardiac function.

Single blind, cross-over study

Remote ischemic preconditioning, induced by four 5 min cycles of upper limb
ischemia interspaced with 5 min of reperfusion (200 mm Hg) or a control
procedure with low-pressure cuff inflation (10 mm Hg), one hour before a 30 km
run.

The risks involved in participating in this study are minimal. Minor discomfort
may occur during the remote ischemic preconditioning protocol, but this
intervention has been shown to be safe. Furthermore, repeated blood draws will
be taken, with small local haematoma as only possible risk. In addition,
participants will undergo three echocardiograms, which is a safe, non-invasive
imaging technique. Since all participants will be experienced and well-trained
long distance runners, no harmful effects are expected to occur during or after
the 30 km run.