Exercise based assessment of cardiac autonomic function in type 1 versus type 2 diabetes mellitus.

BACKGROUND: Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that is associated with increased mortality. Exercise-based assessment of autonomic function has identified diminished parasympathetic reactivation after exercise in type 2 DM. It is postulated herein, that this would be more prominent among those with type 1 DM. METHODS: Sixteen subjects with type 1 DM (age 32.9 ± 10.1 years), 18 subjects with type 2 DM (55.4 ± 8.0 years) and 30 controls (44.0 ± 11.6 years) underwent exercise-based assessment of autonomic function. Two 16-min submaximal bicycle tests were performed followed by 45 min of recovery. On the second test, atropine (0.04 mg/kg) was administered near end-exercise so that all of the recovery occurred under parasympathetic blockade. Plasma epinephrine and norepinephrine levels were measured at rest, during exercise, and during recovery. RESULTS: There were no differences in resting or end-exercise heart rates in the three groups. Parasympathetic effect on RR-intervals during recovery (p < 0.03) and heart rate recovery (p = 0.02) were blunted in type 2 DM. Type 1 DM had higher baseline epinephrine and norepinephrine levels (p < 0.03), and exhibited persistent sympathoexcitation during recovery. CONCLUSIONS: Despite a longer duration of DM in the study patients with type 1 versus type 2 DM, diminished parasympathetic reactivation was not noted in type 1 DM. Instead, elevation in resting plasma catecholamines was noted compared to type 2 DM and controls. The variable pathophysiology for exercise-induced autonomic abnormalities in type 1 versus type 2 DM may impact prognosis.

Detection of cardiovascular autonomic neuropathy using exercise testing in patients with type 2 diabetes mellitus.

AIMS: This study investigated autonomic nervous system function in subjects with diabetes during exercise and recovery. METHODS: Eighteen type 2 diabetics (age 55±2 years) and twenty healthy controls (age 51±1 years) underwent two 16-min bicycle submaximal ECG stress tests followed by 45 min of recovery. During session #2, atropine (0.04 mg/kg) was administered at peak exercise, and the final two minutes of exercise and entire recovery occurred under parasympathetic blockade. Plasma catecholamines were measured throughout. Parasympathetic effect was defined as the difference between a measured parameter at baseline and after parasympathetic blockade. RESULTS: The parasympathetic effect on the RR interval was blunted (P=.004) in diabetic subjects during recovery. Parasympathetic effect on QT-RR slope during early recovery was diminished in the diabetes group (diabetes 0.13±0.02, control 0.21±0.02, P=.03). Subjects with diabetes had a lower heart rate recovery at 1 min (diabetes 18.5±1.9 bpm, control 27.6±1.5 bpm, P<.001). CONCLUSIONS: In subjects with well-controlled type 2 diabetes, even with minimal evidence of CAN using current methodology, altered cardiac autonomic balance is present and can be detected through an exercise-based assessment for CAN. The early post-exercise recovery period in diabetes was characterized by enhanced sympathoexcitation, diminished parasympathetic reactivation and delay in heart rate recovery.

Persistent sympathoexcitation long after submaximal exercise in subjects with and without coronary artery disease.

There is an increased risk of cardiac events after exercise, which may, in part, be mediated by the sympathoexcitation that accompanies exercise. The duration and extent of this sympathoexcitation following moderate exercise is unknown, particularly in those with coronary artery disease (CAD). Twenty control subjects (mean age, 51 years) and 89 subjects with CAD (mean age, 58 years) underwent two 16-min bicycle exercise sessions followed by 30-45 min of recovery. Session 1 was performed under physiological conditions to peak workloads of 50-100 W. In session 2, parasympathetic blockade with atropine (0.04 mg/kg) was achieved at end exercise at the same workload as session 1. RR interval was continually recorded, and plasma catecholamines were measured at rest and selected times during exercise and recovery. Parasympathetic effect, measured as the difference in RR interval with and without atropine, did not differ between controls and CAD subjects in recovery. At 30 and 45 min of recovery, RR intervals were 12% and 9%, respectively, shorter than at rest. At 30 and 45 min of recovery, plasma norepinephrine levels were 15% and 12%, respectively, higher than at rest. A brief period of moderate exercise is associated with a prolonged period of sympathoexcitation extending >45 min into recovery and is quantitatively similar among control subjects and subjects with CAD, with or without left ventricular dysfunction. Parasympathetic reactivation occurs early after exercise and is also surprisingly quantitatively similar in controls and subjects with CAD. The role of these autonomic changes in precipitating cardiac events requires further evaluation.

The effects of rate-adaptive atrial pacing versus ventricular backup pacing on exercise capacity in patients with left ventricular dysfunction.

BACKGROUND: Atrial rate-adaptive pacing may improve cardiopulmonary reserve in patients with left ventricular dysfunction. METHODS: A randomized, blinded, single-crossover design enrolled dual-chamber implantable defibrillator recipients without pacing indications and an ejection fraction < or =40% to undergo cardiopulmonary exercise treadmill stress testing in both atrial rate-adaptive pacing (AAIR) and ventricular demand pacing (VVI) pacing modes. The primary endpoint was change in peak oxygen consumption (VO(2)). Secondary endpoints were changes in anaerobic threshold, perceived exertion, exercise duration, and peak blood pressure. RESULTS: Ten patients, nine males, eight with New York Heart Association class I, mean ejection fraction 24 +/- 7%, were analyzed. Baseline VO(2) was 3.6 +/- 0.5 mL/kg/min. Heart rate at peak exercise was significantly higher during AAIR versus VVI pacing (142 +/- 18 vs 130 +/- 23 bpm; P = 0.05). However, there was no difference in peak VO(2) (AAIR 23.7 +/- 6.1 vs VVI 23.8 +/- 6.3 mL/kg/min; P = 0.8), anaerobic threshold (AAIR 1.3 +/- 0.3 vs VVI 1.2 +/- 0.2 L/min; P = 0.11), rate of perceived exertion (AAIR 7.3 +/- 1.5 vs VVI 7.8 +/- 1.2; P = 0.46), exercise duration (AAIR 15 minutes, 46 seconds +/- 2 minutes, 54 seconds vs VVI 16 minutes, 3 seconds +/- 2 minutes, 48 seconds; P = 0.38), or peak systolic blood pressure (AAIR 155 +/- 22 vs VVI 153 +/- 21; P = 0.61) between the two pacing modes. CONCLUSION: In this study, AAIR pacing did not improve peak VO(2,) anaerobic threshold, rate of perceived exertion, or exercise duration compared to VVI backup pacing in patients with left ventricular dysfunction and no pacing indications.

Direction-dependent conduction abnormalities in a canine model of atrial fibrillation due to chronic atrial dilatation.

Chronic rapid atrial pacing (RAP) leads to changes that perpetuate atrial fibrillation (AF). Chronic atrial dilatation due to mitral regurgitation (MR) also increases AF inducibility, but it is not clear whether the underlying mechanism is similar. Therefore, we have investigated atrial electrophysiology in a canine MR model (mitral valve avulsion, 1 mo) using high-resolution optical mapping and compared it with control dogs and with the canine RAP model (6-8 wk of atrial pacing at 600 beats/min, atrioventricular block, and ventricular pacing at 100 beats/min). At followup, optical action potentials were recorded using a 16 x 16 photodiode array from 2 x 2-cm left atrial (LA) and right atrial (RA) areas in perfused preparations, with pacing electrodes around the field of view to study direction dependency of conduction. Action potential duration at 80% repolarization (APD(80)) was not different between control and MR but was reduced in RAP atria. Conduction velocities during normal pacing were not different between groups. However, the MR LA showed increased conduction heterogeneity during pacing at short cycle lengths and during premature extrastimuli, which frequently caused pronounced regional conduction slowing. Conduction in the MR LA during extrastimulation also displayed a marked dependence on propagation direction. These phenomena were not observed in the MR RA and in control and RAP atria. Thus both models form distinctly different AF substrates; in RAP dogs, the decrease in APD(80) may stabilize reentry. In MR dogs, regional LA conduction slowing and increased directional dependency, allowing unidirectional conduction block and preferential paths of conduction, may account for increased AF inducibility.