Didier Mesangeau

Early detection of cardiovascular autonomic neuropathy in diabetic pigs using blood pressure and heart rate variability

Cardiac autonomic neuropathy is a common complication in insulin dependent diabetes mellitus. Nevertheless, little is known about when this impairment occurs during the time course of the disease. Analysis of blood pressure (BP) and heart rate (HR) variability could be used to detect early signs of autonomic alteration. To test this proposal, twelve sexually mature male Yucatan miniature pigs were equipped with an arterial catheter for telemetric BP analysis, and with a venous access. BP and HR were recorded together with respiratory movements while the animals were resting in a sling. After the first recording session performed when the pigs were 5 months old, streptozotocin (STZ) was used to induce diabetes in seven pigs, while the five others were controls. BP and HR were measured 3 and 6 months after the onset of diabetes and at a similar age in the controls. BP and HR oscillated at the respiratory range (0.19 Hz). Spectral analysis showed this respiratory component was the main determinant of the short-term variability of BP and HR. Atropine increased HR and BP and markedly diminished the respiratory sinus arrhythmia. Propranolol diminished HR and the respiratory peak of HR. A reduced respiratory oscillation of BP paralleled the diminution of the respiratory peak of HR. Baroreceptor-HR reflex was estimated using injections of phenylephrine and nitroprusside, and by cross-spectral analysis between BP and HR. Atropine shifted the curve to higher HR values, while propranolol reduced the level of the upper plateau. Atropine decreased both the coherence and gain of the cross-spectral analysis. STZ injection resulted in a type 1 diabetes. At 3 months, diabetic pigs exhibited low levels of BP and a reduced overall variability of HR and BP. Spectral analysis indicated the respiratory sinus arrhythmia was markedly reduced. In addition, the sensitivity of the baroreceptor-HR reflex was reduced. At a latter stage of diabetes these alterations were marked and the level of the resting HR was increased. These data demonstrate the dual (vagal and sympathetic) control of HR in pigs and the dominant role of respiration in the genesis of HR and BP fluctuations. The spectral and cross-spectral analysis of BP and HR were altered after 3 months of diabetes and could be proposed as early detectors of cardiac autonomic neuropathy.

Arterial stiffness and the autonomic nervous system during the development of Zucker diabetic fatty rats

AIM This study aimed to investigate the role played by sympathovagal balance in arterial stiffness, a common feature of insulin resistance and type 2 diabetes. METHODS We investigated the relationship between autonomic nervous system activity and arterial stiffness in Zucker diabetic fatty rats (ZDF: Gmi-fa/fa) and their age-matched controls (lean: ?/fa). Using simultaneous catheterization of the proximal and distal aorta, we measured intra-arterial blood pressure (BP), heart rate (HR), their variability (spectral analysis) and aortic pulse wave velocity (PWV) in a series of at least six conscious rats aged 6, 12, 18 and 24 weeks. RESULTS BP and PWV increased with age (P<0.001) in both strains with no differences between strains, despite the insulin resistance already present at 6 weeks in ZDF rats. HR was significantly lower (P<0.001) in ZDF than in lean rats. In ZDF compared with lean rats, the low-frequency (LF) component of the systolic BP variations and the LF/high-frequency (HF) component of the pulse interval (PI) variation ratio were reduced (P<0.01 and P<0.05, respectively), while the HF component of the PI (HF-PI) variation was raised (P<0.05). PWV was negatively correlated with HF-PI (r=-0.37, P<0.01), but not with biochemical parameters. HF-PI was an independent variable explaining the variation in PWV. CONCLUSION During the development of disease of ZDF rats, sympathovagal balance might account for the lack of increase in PWV.