Alterations in Heart Rate Fragmentation After Myocardial Infarction in Rats: A Novel Approach in Heart Rate Variability Analysis

Abstract

Heart rate variability (HRV) has been largely studied by linear and nonlinear approaches, in a variety of clinical scenarios and animal models of diseases. Recently, a new pattern of ultra‐rapid heart rate variation has been proposed and named heart rate fragmentation (HRF). This approach showed that aging and coronary disease, increase the fragmentation of heart rate fluctuations. Since HRF was only evaluated in humans, we aimed to investigate this new HRV index in a rat model of myocardial infarction (MI). For this purpose, Wistar rats (250 a 300g) were submitted to MI by permanent ligation of the left anterior descending coronary artery, or sham‐operation (control animals). At the 4th or 12th weeks after MI, or sham‐operation, animals were instrumented with a polyethylene arterial catheter for arterial pressure recordings which were carried out in freely moving rats. At the end of the protocol, cardiac function was evaluated by echocardiography using a 21 MHZ transducer (VisualSonics‐VEVO2100®). For HRF analysis, the pulse interval (PI) series was transformed into a sequence of symbols named "−1”, “0” or “1", when the difference between successive values (transitions) was negative, zero, or positive, respectively. Next, sequences of 4 consecutive symbols were classified according to the numbers of transitions. The percentage of inflection points (PIP) of PI series were also quantified. As expected, cardiac function was found reduced in rats subjected to MI. Ejection fraction was smaller 4 (28±3 vs 68±2%) and 12 weeks after MI (38±3 vs 70±3%). Similarly, fractional shortening was also smaller 4 (13±2 vs 41±2%) and 12 weeks after MI (20±2 vs 41±3%). On the other hand, PIP values were increased in rats subjected to MI at the 4th (74±2 vs 69±1%) and 12th weeks after surgery (70±2 vs 63±1%), revealing a more fragmented pattern compared to control counterparts. We also found a significant correlation between cardiac functional parameters (ejection fraction and fractional shortening) and HRF (PIP) at both 4 and 12 weeks after MI. These findings reveal that in rats, cardiac ischemia also increases HRF, reinforcing the importance of this new HRV approach as a promising tool to explore physiological and pathophysiological conditions at clinical and experimental levels.Support or Funding InformationFinancial support: CNPq (870308/1997‐1) and FAPESP (2013/20549‐7).