Heart Rate Fragmentation in Rats with Streptozotocin‐induced Diabetes

Abstract

Heart rate fragmentation (HRF) is a recently proposed approach to evaluate sino‐atrial instability characterized by the presence of numerous inflections points in a series of successive values of RR intervals (RRi). HRF has been shown to be increased in aging and coronary diseases and seems to be linked to the risk of life‐threatening cardiovascular events and death. We recently demonstrated that cardiac autonomic modulation in involved in HRF in rats. Moreover, HRF is increased in a rat model of heart failure. Diabetes mellitus (DM) markedly alters HRV indices and might affect HRF as well. Therefore, we hypothesize that HRF is altered in streptozotocin‐ (STZ) induced diabetic rats. Male Sprague‐Dawley rats were injected with STZ (50 mg/kg), or vehicle (citrate buffer) into penile vein. Development of diabetes was confirmed 72h after STZ by the presence of hyperglycemia (> 350 mg/dL). Electrocardiographic (ECG) recordings were performed in conscious rats, 7 days (acute) or 4 weeks (chronic) after STZ or vehicle administration. Series of RR intervals were generated and processed by the customized software PyBios as follows: RRi values were symbolized as “‐1”, “0,” or “1” when the differences between successive RRi were negative, null, or positive, respectively. Transitions between symbols “‐1” and “1” were labeled as “hard” (H) inflection points, while those between “‐1” (or “1”) and “0” were labeled as “soft” (S) inflection points. The percentage of inflection points (PIP) was quantified, as well as sequences of 4 consecutive symbols, so‐called “words”, computing the occurrence of words with zero (W0), one (W1), two (W2), or three (W3) inflections points. The occurrence of words with only hard (WH) or only soft transitions (WS) were also quantified. Both groups of diabetic rats were bradycardic as compared to their control counterparts. Data of HRF are shown in the table below. Occurrences (%, mean ± SEM) of PIP, words with 0 to 3 inflection points, and words with only soft or hard transitions of symbols. As hypothesized, diabetes affects HRF, increasing fragmented indices (PIP, W3 and WH) and decreasing fluent ones (W1 and WS). Moreover, our results showed that changes in HRF due to diabetes in this model is time‐dependent. In addition to traditional methods of analyzing heart rate variability, HRF is a new method that can contribute to the diagnosis and prognosis of cardiovascular diseases in diabetic patients. Further studies are necessary to understand better the mechanisms involved in our findings.