Discussion
Instances of doping, as well as other forms of cheating, have been
documented throughout the history of sports. The utilization of
performance-enhancing drugs in sports is an obvious crisis. The
utilization of substances in professional sports and competitions has
significantly damaged the reputation of numerous athletes worldwide,
while also posing a threat to their health. [7] The pharmaceutical
industry has had significant expansion in the past decade, in tandem
with advancements in technology. This growth has resulted in key
advancements, particularly in the field of cardiac medications. The
recently introduced cardiac medications may enhance sports performance
and therefore may be abused as a form of doping. Therefore, our study
aimed at examining the impact of dapagliflozin and sacubitril/valsartan,
known for their significant symptomatic alleviation and favorable
prognosis, particularly in heart failure, on sports performance. Both
drugs have proved the ability to improve athletic performance, The
impact on improving athletic performance was significantly more
prominent for dapagliflozin.
The effect of exercise on the heart can be observed more quickly in rat.
[8] The change seen in the echo data of the control group regarding
the left ventricle is compatible with the development of an athlete’s
heart. This demonstrates the methodological reliability of the
experiment. In both medical approaches, there was a significant increase
in antegrade flow of the pulmonary artery, compared to baseline. This
may be related to an increase in right ventricular functions. Another
notable feature is the increase of ejection fraction (EF) observed in
the sacubitril/valsartan group. The increase in EF with
sacubitril/valsartan use can also be seen in heart failure patients.
[9] The effect of dapagliflozin on athletic performance was assessed
independently from its impact on EF.
There was a decrease in the weight of the rat in all three groups due to
intense exercise throughout the experiment. But there was no significant
difference between the groups in this decrease. The decrease in weight
is related to both the direct effect of physical activity on energy
expenditure and the increase in metabolic rate during the resting
period. [10] The rat were not under any calorie restriction. They
had unrestricted access to food. If the experimental period was
extended, a plateau in their weight could be observed. [11]
We observed an increase in rotarod results compared to baseline data in
both medication groups. There was no significant difference compared to
the control group. The adaptation of rat should not be ignored. However,
while there is a statistical difference in the medication groups,
although there is an increase in the control group, it is not
statistically significant. These results may be the beginning of more
comprehensive studies. Because the positive effect of dapagliflozin and
sacubitril/valsartan on the rotarod may provide an advantage in skill
sports (golf, table tennis, shooting, curling, bowling etc.). [12]
The primary objective of our investigation was to reveal the improvement
in athletic performance. After similar results were obtained during the
first 9 swimming sessions of exercise, we observed a significant
difference in the athletic performance of rat with both medications.
This effect of sacubitril/valsartan was generally observed parallel to
the control group and slightly better. Sacubitril/valsartan, an
angiotensin receptor-neprilysin inhibitor, enhances the natriuretic
peptide system by suppressing the neprilysin enzyme and inhibits the
renin-angiotensin-aldosterone system by inhibiting the angiotensin II
receptor. Evidence demonstrates that it improves mortality and reduces
hospitalization rates in individuals with heart failure caused by
impaired left ventricular systolic performance. [13] Also
sacubitril/valsartan augments the effects of bradykinin, substance P,
and adrenomedullin, which are other hormones that may contribute to the
cardiac efficacy of the medication. [14] The positive effect of
sacubitril/valsartan on athletic performance may be related to increased
cardiac efficiency and slightly improved left ventricular function.
However, this effect was observed to be limited and there was a relative
increase in athletic performance.
The effect of dapagliflozin was observed remarkably. Sodium-glucose
cotransporter-2 (SGLT) inhibitors reduce the risk of hospitalization for
heart failure in patients with either preserved or reduced ejection
fraction. However, the specific hemodynamic processes responsible for
these advantages are not yet fully understood. [15] A research
conducted on rat has demonstrated that dapagliflozin has a vasodilatory
impact on the thoracic aorta, which is dependent on the voltage of
potassium channels. [16] This demonstrated a direct effect on
vascular cells for both acute and chronic treatment. [17] Therefore,
it is reasonable to observe that the improvement in performance begins
during the initial periods and thereafter advances throughout time.
Another possible mechanism of action may be related to its positive
microvascular and endothelial activity. [18] SGLT-2 inhibitors,
currently the only option in preserved EF heart failure, may have as yet
undisclosed abilities regarding possible cellular myocardial efficiency.
However, our study showed that dapagliflozin has an obvious doping
effect on athletic performance. Future studies on the mechanism of
action may reveal the reasons for this effect more clearly.