Certain physical activities engaged by humans have been found to result in a ‘cardiac adaptive response’ called THE ATHLETE HEART. Responses to these activities usually have more effect on the Right ventricle than it does on the Left ventricle, leading to increased stroke volumes or right or left ventricular hypertrophy.
The right ventricular has been identified to be most weakened, easily fatigued and most prone to damages the most in endurance exercises or physical activities than Left ventricle. The leading factor to this could be tied to the Right ventricle having diminished contractile reserve and a limited pulmonary vascular response, resulting in the right chamber walls being stressed 10 times above the usual.
Long term over work and over load of this ventricular walls can result in structural, electrical and functional changes which may lead to certain exercised induced cardiomyopathies likes arrthymogenic Right ventricular cardiomyopathy and increase incidence of Ventricular arrhythmias both in the right or left ventricles.
Nitric oxide place an important role being an endogenous cardiovascular regulator, its major role is to act as a Vasodilator. Endothelial Nitric oxide synthase (NOS3) is the main source of Nitric oxide in the heart. The different variations of the NOS3 gene affect the availability of Nitric oxide bioavailability which in turns affect the heart functionality.
A further study on the genetic variants of the NOS3 gene displayed a different effect. The three polymorphism of the NOS3 gene which include:
1. G894CT (Glu298Asp) in exon 7.
2. 4a/5b 27-basepair variable number of tandem repeats in intron 4.
3. T-786C variant in the promoter region.
A substitution mutation of Glutamine to Aspartic amino acid at the codon 298 in NOS3 gene, results in the increases susceptibility of NOS3 gene to enzymatic cleavage in vitro these affect Nitric Oxide production (decrease production). On the other hand, athletes with the NOS3 289 Glu/Glu genotype were discovered to have a better athletic performance and low finishing times, due to high Nitic oxide production by the endothelial NO synthase. Nevertheless no differences was shown between elite Athlete endurance and sedentary control among genotype distribution of NOS3 gene Polymorphism.
Suggestions were made that linked physiological or pathological cardiac remodeling to the association of NOS3 polymorphism and cardiac function, emphasis was laid specifically on Athlete adaptation. A hypothesis was drawn that an altered NOS3 function and endogenous Nitric oxide production may influence myocardial hypertrophy in elite Athlete. Athlete cardiac adaptation was investigated in a selected population of world class athletes using a Cardiac Magnetic Resonance Imaging (cMRI).
MATERIAL AND METHOD: SELECTION OF CANDIDATE INDIVIDUALS AND STUDY CONTROL
Elite Athletes numbering about one hundred and twenty six from different athletic disciplines (water polo players, kayakers, canoeists, rowers, swimmers) were chosen and compared with non- athlete individuals. Water polo players (n = 48), kayakers (n = 21), Canoeists (n = 19), Rowers (n = 22) and Swimmers (n = 16). Selections of athletes was also based on sports discipline with mixed exertion load which included criteria like SPEED, STRENGHT and ENDURANCE component.
Athletes were selected on a criteria of at least 10years of National and 3 years of international qualifications (World champions or Olympic games). Athletes with VO2 maximum greater than 50ml/kg/min during cardiopulmonary stress test using a bicycle ergometer were referred to cardiac magnetic resonance (cMRI) out of which
* Eight Athletes (8) were excluded due to low VO2 maximum (<50ml/kg/min)
* Eleven Athletes (11) did not complete the cardiac magnetic resonance examination (cMRI) due to intolerance.
For the Control group, one hundred and sixty two Age and Sex matched were screened. Under this group lower VO2 maximum consumption level (<50ml/kg/min) was accepted unlike those in the Elite Athlete groups. Those with higher than 50ml/kg/min VO2 maximum numbering about three (3) were dropped, four (4) volunteers however did not complete the cardiac magnetic resonance examination (cMRI) due to intolerance.
All Athletes in the study were carefully selected from the same ethnic group and subjected to similar environmental factors, smoking status, and dietary habits, duration of Elite athletic status and timing and seasons.
SCREENING PROTOCOL
Stress test was firstly carried out using a bicycle Ergometer with an ‘all out’ protocol. Athletes with a VO2 maximum greater than 50ml/kg/min and control Group with VO2 maximum lower than 50ml/kg/min were referred for cardiac magnetic resonance imaging (cMRI) and thereafter Blood samples were collected for DNA extraction from their very first visit. DNA extraction was voluntary and also part of the prospective athletic screening program.
CARDIOPULMONARY STRESS TEST
A continuous routine of test till exhaustion was performed using an electromagnetically braked bicycle ergometer. The exercise was started with an initial load of 50W and this is increased every one minutes by 25W. Gas exchange parameters, ventilator variables were recorded breath-by-breath along with vital parameters and blood lactate levels were measured before and after the stress test.
CARDIAC MAGNETIC RESONANCE IMAGING (CMRI):
Cardiac MRI scans were performed using a five element cardiac coil was used for signal reception. Endocardial and epicardial contours were traced manually for both the left and the right ventricles and volumetric measures (including papillary muscles),other parameter of measurements included ejection fractions, maximal end-diastolic wall thickness and maximal end-diastolic wall thickness, left ventricular end diastolic volume index ratios. Body height and weight were also measured. Body surface area was calculated using the MOSTELLER FORMULA.
DNA EXTRACTION AND GENOTYPING:
The Protease based techniques was used to isolate Genomic DNA, Lysis buffer was added to sample mixed thoroughly and centrifuged. Samples were denaturized but only after discarding supernatant. DNA sample was precipitated using ethanol and reconstituted into the Lysis buffer. Samples was stored at a temperature of -80 Celsius. Genetic analysis was undertaken blinded to patient data, with the provided software.
STATISTICAL ANALYSIS:
Results findings and data were presented using standards method like
*mean ” SD for continuous variables,
*n (%) for categorical variables.
Comparisons between two groups were performed using:
*Student’s t-test for continuous variables (MR parameters)
*Chi-square test for categorical data (genotype, gender and athletic status)
Analysis of variance (ANOVA) concluded that genotype and athletic status may play a role in right ventricular indices. Linear regression was engaged to confirm whether gender and genotype are independent predictors or combined predictors for changes in right ventricular stroke volume index (RVSVi) and right ventricular mass index (RVMi).
RESULTS OF STUDIES
Characteristics of athletes and control individuals:
‘ Elite athletes group: Men (n = 94) and women (n = 32) and
‘ Non-athletic controls Group: Men (n = 109) and Women (n = 46) were screened.
‘ Age distribution and gender ratio (25.4% and 29.7% female in athletes and non-athletes, respectively) were not different between the study groups.
‘ Height, weight and body mass index was found to be higher in men versus women and in athletes versus non-athletes.
‘ Body surface area, which is very important value in the interpretation of cardiac magnetic resonance imaging results, was also higher in athletes when compared to the body surface area of non-athletic controls.
CARDIAC MORPHOLOGY AND FUNCTION IN ATHLETES AND CONTROLS
‘ Left ventricular end diastolic ((LVEDVi), RV end-diastolic (RVEDVi) and end systolic volumes (LVESVi), end-systolic volume indexes (RVESVi) and left ventricular myocardial mass indexed ((LVMi) and RV mass index (RVMi), respectively were considerately higher in athletes than in the non-athletic group, which suggested eccentric hypertrophy.
‘ Resting LV ejection fraction (LVEF %) was not different between athletes and non-athletes (58.5”6.3% versus 59.4”4.3%, respectively.
‘ Resting RV stroke volume index (RVSVi) and) were both higher in athletes compared to non-athletes
‘ LV stroke volume index (LVSVi) was higher in athletes than in untrained controls (67.6”8.3 versus 54.8”7.8 ml/m2, p<0.0001).
‘ There were significant gender-related differences with higher end-diastolic and end-systolic LV volumes and larger LV mass in men versus women, irrespective of athletic activity.
‘ Both, RVSVi and RVMi were higher in men than in women.
‘ At exhaustion both VO2 maximum, (60”7 versus 40”7 ml/kg/min, p<0.0001) and minute ventilation (VE, 150”15 versus 84”39 l/min, p<0.0001) were significantly higher in athletes than in non-athletic controls.
GENOTYPE DISTRIBUTION
Allelic distributions was found to be similar among both groups being studied with aminor allelic frequency values of 0.27 in athletes vs. 0.26 in controls. 64 athletes were Glu homozygous genotype, and 56 were heterozygous while a total of 6 out of 126 athletes carried the Asp homozygous genotype. The genotype distribution was similar in the non-athletic control group (84/ G/G, 62/ G/A, and 9/ A/A, chi-square = 0.62; p = 0.73)
ASSOCIATION OF CARDIAC STRUCTURE AND FUNCTION WITH THE NOS3 298 GENOTYPE
‘ Results showed that resting RV stroke volume index (RVSVi) and RV mass index (RVMi) and right ventricular mass were both higher in Aspartate carriers (athletes and non-athletes, n = 133) compared to Glutamate homozygous participants (athletes and non-athletes, n = 148).
‘ RVMi represents right ventricular hypertrophy and was associated with higher right ventricular stroke volume index (RVSVi) in the Asp allele carrier versus the Glu homozygous athlete group.
‘ In non-athletic individuals no association was observed between genotype and right ventricular function and mass. Similarly, left ventricular function and anatomy was not associated with the genotype in any of the study groups
‘ Oxygen consumption at exhaustion (VO2 maximum) was not different between the Asp allelic variant carriers and the Glu homozygous individuals, irrespective of the athletic.
‘ There was, however, a trend towards higher maximal minute ventilation in Asp allelic variant carrier versus Glu homozygous athletes (152”13 versus 146”11 l/min, p = 0.08). The genotype was not associated with ventilation in non-athletes.
CONCLUSIONS:
The findings of the research corresponded with previously released finding associating sport-related right ventricular adaptation and the Glu298Asp genetic variant of the endothelial nitric oxide synthase 3 gene (NOS3 gene) among elite athletes. However, our research discovered that physical preconditioning evokes genotype-influenced right ventricular adaptation.
Although the adaptation of the left ventricle and its possible functional consequences on athletic performance is still a major and ongoing sport physiology research, there is resounding evidences that right ventricular adaptation may improve or boost athletic performance.
Alongside chamber hypertrophy athletic adaptation decreased resting RV ejection fraction and ventricular-arterial coupling alterations were seen to go hand in hand which may be an early sign for contractile impairment of the heart. Although distinguishing physiologic- from pathologic adaptation remains an important and challenging task.
Nitirc Oxide is known to have an anti-hypertrophic myocardial effects and this could affect athletic performance via several mechanisms:
1. Improved coupling of cardiac oxygen consumption to physical performance
2. Enhanced LV relaxation and decreased LV end-diastolic pressure
3. Increased NO-dependent myocardial Ca2+ influx and contractile force.
NOS3 gene in the cardiovascular system is the primary source of NO. Therefore, substitution mutation of Glu to Asp amino acid at codon 298 in the NOS3 enzyme causes a reduced NO production and altered biological effects, including impaired vasodilation and increased myocardial hypertrophy.
The influence of the NOS3 Glu298Asp polymorphism on enzymatic cleavage and thus NO availability has been shown to reduce treatment efficacy in heart failure patients.
No correlation was found between the NOS3 genotype and left ventricular parameters neither in athletes, nor in untrained-individuals but however interestingly, without a significant effect on maximal oxygen uptake, there was a trend towards higher minute ventilation during peak exercise in persons with Asp allelic carrier compared to those with Glu homozygous athletes.