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 Yu catan miniature pigs were equipped with an arterial catheter for telemetric BP analysis, and with a venous access. BP and HR were recorded together wi th respiratory movements while the animals were resting in a sling. After t he first recording session performed when the pigs were 5 months old, strep tozotocin (STZ) was used to induce diabetes in seven pigs, while the five o thers 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 si nus arrhythmia. Propranolol diminished KR and the respiratory peak of HR. A reduced respiratory oscillation of BP paralleled the diminution of the res piratory 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 values, while propranolol r educed the level of the upper plateau. Atropine decreased both the coherenc e 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 re duced overall variability of HR and BP. Spectral analysis indicated the res piratory sinus arrhythmia was markedly reduced. In addition, the sensitivit y 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 fluct uations. 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 car diac autonomic neuropathy. (C) 2000 Elsevier Science B.V. All rights reserv ed.